# ScreenCell | CTC Isolation Kits For CTC Enumeration

Discover ScreenCell CTC isolation kits for the size-based enumeration and characterization of circulating tumor cells (CTCs) in solid tumors.

## Pages

- [ScreenCell | CTC Isolation Kits For CTC Enumeration](https://www.screencell.com/en/): Discover ScreenCell CTC isolation kits for the size-based enumeration and characterization of circulating tumor cells \(CTCs\) in solid tumors.
- [About ScreenCell | Circulating Tumor Cell Tests Company](https://www.screencell.com/en/about-screencell/): Discover ScreenCell, a pioneer company in circulating tumor cell tests.
- [What Is A Circulating Tumor Cell \(CTC\)? Definition, Detection And Cancer Research](https://www.screencell.com/en/blog-en/science-en/what-is-circulating-tumor-cell-ctc/): Circulating tumor cells: definition, role in cancer and impact on diagnosis. A comprehensive review of these key biomarkers.
- [Evaluation Of Circulating Tumor Cells \(CTC\) Relevance In Breast Cancer Follow-up Using The ScreenCell Device \(PROBE-CTC\) | ScreenCell](https://www.screencell.com/en/clinical-trial/breast-cancer-trial/evaluation-of-circulating-tumor-cells-ctc-relevance-in-breast-cancer-follow-up-using-the-screencell-device-probe-ctc-2/): No description available.
- [Evaluation Of Circulating Tumor Cells \(CTCs\) By The ScreenCell® Device In Breast Cancer: Validation Of Biomarkers | ScreenCell](https://www.screencell.com/en/clinical-trial/breast-cancer-trial/evaluation-of-circulating-tumor-cells-ctcs-by-the-screencell-device-in-breast-cancer-validation-of-biomarkers/): No description available.
- [Analysis Of Circulating Tumor Cells \(CTCs\) In Patients With Metastatic Melanoma Before And During Systemic Treatment | ScreenCell](https://www.screencell.com/en/clinical-trial/melanoma-trial/analysis-of-circulating-tumor-cells-ctcs-in-patients-with-metastatic-melanoma-before-and-during-systemic-treatment/): No description available.
- [Ex Vivo Expansion Of Circulating Tumor Cells As A Model For Cancer Predictive Pharmacology \(EXPEVIVO-CTC\) | ScreenCell](https://www.screencell.com/en/clinical-trial/melanoma-trial/ex-vivo-expansion-of-circulating-tumor-cells-as-a-model-for-cancer-predictive-pharmacology-expevivo-ctc-2/): No description available.
- [Clinical Trials | ScreenCell](https://www.screencell.com/en/clinical-trials/): Discover our ongoing and completed clinical trials on circulating tumor cells \(CTCs\) using liquid biopsy.
- [ScreenCell | Looking For A CTC Enrichment Kit? Contact Us!](https://www.screencell.com/en/contact-us/): To learn more about the use of CTCs and liquid biopsy in your research projects or in clinical routine, contact us!
- [Cookie Policy | ScreenCell](https://www.screencell.com/en/cookie-policy/): No description available.
- [2nd IBC-IC In Africa: Discover The Power Of ScreenCell® Technology | ScreenCell](https://www.screencell.com/en/events/2nd-ibc-ic-2025/): Come Discover ScreenCell® Technology at the 2nd IBC-IC in Africa and the 8th Ariana's OncoDay. These events will take place on May 9th and 10th, 2025, at the Carthage Thalasso Resort Hotel in Tunis, Tunisia.
- [PSCC Innovation Forum 2026 | ScreenCell | Biopsie Liquide](https://www.screencell.com/en/events/3rd-pscc-innovation-forum-2026/): ScreenCell will be attending the 3rd PSCC Innovation Forum 2026 on February 4th in Villejuif. Meet our expert Emile Lakis, Ph.D., to discover our CTC isolation method.
- [ACTC 2025 | Meet ScreenCell® From September 24–27](https://www.screencell.com/en/events/actc-2025/): ScreenCell® will attend the 7th Advances in Circulating Tumor Cells Meeting \(ACTC 2025\) in Thessaloniki, Greece. Join us from September 24–27.
- [ISMRC 2025 | Discover Your New CTCs Isolation Methods](https://www.screencell.com/en/events/ismrc-2025-join-screencell/): ScreenCell will be exhibiting at ISMRC 2025 from May 7 to 9 in Nice. Come and visit us at booth #9 to discover your new CTC isolation method.
- [ScreenCell® Participates In ISLB 2025 | Liquid Biopsy](https://www.screencell.com/en/events/screencell-at-islb-2025/): From November 1st to 3rd, 2025, ScreenCell® will be crossing the Atlantic to Orlando, Florida, for the 7th Annual Liquid Biopsy Conference \(ISLB 2025\). Dr. Sina Naserian, our Chief Technology Officer, will represent the company at this unmissable international gathering that brings together global excellence in liquid biopsy.
- [GA ELBS 2025 | ScreenCell® Will Be Present On November 3 And 4, 2025](https://www.screencell.com/en/events/screencell-to-attend-eslb-2025-general-assembly-in-madrid/): ScreenCell® will be present from November 3rd to 4th at the 2025 General Assembly of the European Liquid Biopsy Society \(ELBS\) in Madrid.
- [ScreenCell At SIMEM 2025: Meet Us On The Genethical® Stand | ScreenCell](https://www.screencell.com/en/events/simem-2025-join-screencell-genethical/): ScreenCell will be present at SIMEM 2025 in Oran from April 9 to 12 at the Genethical stand. Come discover our innovative solutions for the analysis of circulating tumor cells and interact with our experts!
- [Stand Up To Cancer \(SU2C\) Scientific Summit 2026 | ScreenCell](https://www.screencell.com/en/events/stand-up-to-cancer-scientific-summit-2026/): ScreenCell® will be attending the SU2C Scientific Summit 2026 in Pasadena, California, from January 29 to February 1, 2026. Our Chief Technical Officer, Sina NASERIAN, Ph.D., will present our medical devices for the isolation of circulating tumor cells during a dedicated session on January 31. This is a unique opportunity to discover how our liquid biopsy technology is revolutionizing precision medicine in modern oncology.
- [Media Kit | ScreenCell](https://www.screencell.com/en/media-kit-032026/): Journalists, press teams, media partners…
- [ScreenCell® Joins ELBS \(European Liquid Biopsy Society\)](https://www.screencell.com/en/news/company/screencell-joins-elbs-european-liquid-biopsy-society/): ScreenCell® is proud to announce its membership in the European Liquid Biopsy Society \(ELBS\) as an industry member.
- [ScreenCell Joins PMT Santé In Besançon](https://www.screencell.com/en/news/company/screencell-joins-pmt-sante/): ScreenCell® is proud to announce its membership in PMT Santé, the regional health technology cluster led by PMT \(Pôle des Microtechniques\) in Besançon. By joining this dynamic network, ScreenCell® becomes part of the 145 other Medtech and Biotech players in the "Health Technologies" sector in Bourgogne-Franche-Comté.
- [Standardization Of ScreenCell® CTC Isolation Kits In 2026](https://www.screencell.com/en/news/products/standardization-screencell-ctc-isolation-kits/): Starting January 1, 2026, ScreenCell® CTC isolation kits will be standardized to a single format: 2 filtration units and 1 dilution buffer.
- [Newsroom | ScreenCell](https://www.screencell.com/en/newsroom/): Never miss any more ScreenCell news and events with our blog posts on circulating tumor cells \(CTCs\) and liquid biopsy.
- [Events | ScreenCell](https://www.screencell.com/en/newsroom/events/): Events Upcoming events Latest events
- [News | ScreenCell](https://www.screencell.com/en/newsroom/news/): Never miss any more ScreenCell news and events with our blog posts on circulating tumor cells \(CTCs\) and liquid biopsy.
- [Press Releases | ScreenCell](https://www.screencell.com/en/newsroom/press-releases/): Discover all ScreenCell press releases: news, innovations, and advancements in oncology and liquid biopsy. Stay updated with our latest official announcements.
- [ScreenCell Ships 50,000 Units For Circulating Tumor Cells Characterization](https://www.screencell.com/en/press-release/screencell-50000-units-circulating-tumor-cells-characterization/): ScreenCell reaches 50,000 units shipped worldwide, supporting cancer research with innovative Circulating Tumor Cells separation and characterization technology.
- [ScreenCell Advances Breast Cancer CTC Enrichment](https://www.screencell.com/en/press-release/screencell-breast-cancer-ctc-enrichment/): ScreenCell partners with Jefferson Breast Care Center to enhance enrichment and characterization of CTC in breast cancer research.
- [ScreenCell And CTC Detection In Colorectal Cancer](https://www.screencell.com/en/press-release/screencell-colorectal-cancer-ctc/): Researchers highlight ScreenCell’s efficiency in capturing and characterizing circulating tumor cells \(CTCs\) from colorectal cancer patients.
- [Privacy Policy | ScreenCell](https://www.screencell.com/en/privacy-policy/): This Privacy Policy governs the manner in which ScreenCell collects, uses, and maintains information collected from users of the screencell.com website.
- [ScreenCell | Request A Quote | CTC Enrichment Kits](https://www.screencell.com/en/request-a-quote/): Request a personalized quote to integrate circulating tumor cell \(CTC\) counting and liquid biopsy into your projects.
- [Resources | ScreenCell](https://www.screencell.com/en/resources/): Resources Explore our resources Scientific publications Read all Webinars and Videos Watch all Newsroom Learn more Stay informed about our resources
- [Blog | ScreenCell](https://www.screencell.com/en/resources/blog/): Resources
- [Videos | ScreenCell](https://www.screencell.com/en/resources/our-videos/): Découvrez nos articles scientifiques sur l'isolement des CTC et la biopsie liquide rédigés par nos clients et partenaires.
- [Publications | ScreenCell](https://www.screencell.com/en/resources/publications/): Discover our scientific articles on CTCs isolation and liquid biopsy written by our customers and partners.
- [Cytomorphologic Visualization Of Circulating Tumor Cells In Urinary Bladder Cancer Patients Using ScreenCell™ Technology: Potential As A Simple Cytology Test | ScreenCell](https://www.screencell.com/en/scientific-articles/bladder-cancer-publication/cytomorphologic-visualization-of-circulating-tumor-cells-in-urinary-bladder-cancer-patients-using-screencell-technology-potential-as-a-simple-cytology-test-2/): Circulating tumor cells \(CTC\) are a recent technique which is a potentially important prognostic factor in many solid tumors. There are many techniques of detecting CTCs, but they usually implement costly techniques like EpCAM targeted detection, fluorescence-based diagnosis, or magnetic bead based positive or negative selection. The diagnostic utility of simple cytomorphological diagnosis after routine staining of CTCs have been rarely studied. We aimed to detect CTCs in 24 patients clinically suspected to have Urinary Bladder Cancer using a simple but efficient patented filtration technology \(ScreenCell™\), followed by optical microscopic visualization after routine May-Grunwald-Giemsa \(MGG\) staining. The detected CTCs were then tested for association with the histologic type, lamina propria invasion, deep muscle invasion and the T-stage. Out of the 24 patients tested, one was found to have papilloma, nine had low grade urothelial carcinoma, 13 had high grade urothelial carcinoma and one had poorly differentiated adenocarcinoma. Of these, two LGUC, eight HGUC and one adenocarcinoma had detectable CTC. Presence of CTCs had a statistically significant association with Lamina propria invasion \(P = .006\) and T-stage \(P = .02\), and a trend toward significance for differentiating LGUC from HGUC \(P = .10\). These results suggest that cytomorphological detection of CTC is likely to be clinically useful in diagnosis and prognostication of urinary blader cancers. These findings need to be confirmed on studies with larger sample sizes.
- [The Prognostic Value Of The Circulating Tumor Cell-Based Four MRNA Scoring System: A New Non-Invasive Setting For The Management Of Bladder Cancer | ScreenCell](https://www.screencell.com/en/scientific-articles/bladder-cancer-publication/the-prognostic-value-of-the-circulating-tumor-cell-based-four-mrna-scoring-system-a-new-non-invasive-setting-for-the-management-of-bladder-cancer-2/): Simple Summary: Bladder cancer with similar diagnosis based on traditional classification exhibits different behaviors and therapeutic outcomes. Thus, circulating tumor cells \(CTCs\) represent a more accurate approach to investigate bladder cancer features. Our results demonstrate that risk score based on EGFR, TRPM4, TWIST1, and ZEB1 four-gene signature in CTCs is markedly and undoubtedly associated with recurrence, suggesting an innovative and non-invasive strategy to manage both non muscle invasive and muscle invasive bladder cancer progression without the necessity of repetitive and onerous cystoscopies. Abstract: Bladder cancer \(BC\) is one of the most expensive lifetime cancers to treat because of the high recurrence rate, repeated surgeries, and long-term cystoscopy monitoring and treatment. The lack of an accurate classification system predicting the risk of recurrence or progression leads to the search for new biomarkers and strategies. Our pilot study aimed to identify a prognostic gene signature in circulating tumor cells \(CTCs\) isolated by ScreenCell devices from muscle invasive and non-muscle invasive BC patients. Through the PubMed database and Cancer Genome Atlas dataset, a panel of 15 genes modulated in BC with respect to normal tissues was selected. Their expression was evaluated in CTCs and thanks to the univariate and multivariate Cox regression analysis, EGFR, TRPM4, TWIST1, and ZEB1 were recognized as prognostic biomarkers. Thereafter, by using the risk score model, we demonstrated that this 4-gene signature significantly grouped patients into high- and low-risk in terms of recurrence free survival \(HR = 2.704, 95% CI = 1.010–7.313, Log-rank p < 0.050\). Overall, we identified a new prognostic signature that directly impacted the prediction of recurrence, improving the choice of the best treatment for BC patients.
- [Circulating Tumor Cell Clusters Are Frequently Detected In Women With Early-Stage Breast Cancer | ScreenCell](https://www.screencell.com/en/scientific-articles/breast-cancer-publication/circulating-tumor-cell-clusters-are-frequently-detected-in-women-with-early-stage-breast-cancer-2/): The clinical relevance of circulating tumor cell clusters \(CTC-clusters\) in breast cancer \(BC\) has been mostly studied using the CellSearch®, a marker-dependent method detecting only epithelial-enriched clusters. However, due to epithelial-to-mesenchymal transition, resorting to marker-independent approaches can improve CTC-cluster detection. Blood samples collected from healthy donors and spiked-in with tumor mammospheres, or from BC patients, were processed for CTC-cluster detection with 3 technologies: CellSearch®, CellSieve™ filters, and ScreenCell® filters. In spiked-in samples, the 3 technologies showed similar recovery capability, whereas, in 19 clinical samples processed in parallel with CellSearch® and CellSieve™ filters, filtration allowed us to detect more CTC-clusters than CellSearch® \(median number = 7 versus 1, p = 0.0038\). Next, samples from 37 early BC \(EBC\) and 23 metastatic BC \(MBC\) patients were processed using ScreenCell® filters for attaining both unbiased enrichment and marker-independent identification \(based on cytomorphological criteria\). At baseline, CTC-clusters were detected in 70% of EBC cases and in 20% of MBC patients \(median number = 2, range 0–20, versus 0, range 0–15, p = 0.0015\). Marker-independent approaches for CTC-cluster assessment improve detection and show that CTC-clusters are more frequent in EBC than in MBC patients, a novel finding suggesting that dissemination of CTC-clusters is an early event in BC natural history.
- [Circulating Tumour Cell Enumeration Does Not Correlate With Miller-Payne Grade In A Cohort Of Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy | ScreenCell](https://www.screencell.com/en/scientific-articles/breast-cancer-publication/circulating-tumour-cell-enumeration-does-not-correlate-with-miller-payne-grade-in-a-cohort-of-breast-cancer-patients-undergoing-neoadjuvant-chemotherapy-2/): Purpose The association between pathological complete response \(pCR\) in patients receiving neoadjuvant chemotherapy \(NAC\) for breast cancer and Circulating Tumour Cells \(CTCs\) is not clear. The aim of this study was to assess whether CTC enumeration could be used to predict pathological response to NAC in breast cancer as measured by the Miller–Payne grading system. Methods Twenty-six patients were recruited, and blood samples were taken pre- and post-NAC. CTCs were isolated using the ScreenCell device and stained using a modified Giemsa stain. CTCs were enumerated by 2 pathologists and classified as single CTCs, doublets, clusters/microemboli and correlated with the pathological response as measured by the Miller–Payne grading system. χ2 or ANOVA was performed in SPSS 24.0 statistics software for associations. Results 89% of patients had invasive ductal carcinoma \(IDC\) and 11% invasive lobular carcinoma \(ILC\). At baseline 85% of patients had CTCs present, median 7 \(0–161\) CTCs per 3 ml of whole blood. Post-chemotherapy, 58% had an increase in CTCs. This did not correlate with the Miller–Payne grade of response. No significant association was identified between the number of CTCs and clinical characteristics; however, we did observe a correlation between pre-treatment CTC counts and body mass index, p
- [Comparative Performance Of Different Methods For Circulating Tumor Cell Enrichment In Metastatic Breast Cancer Patients | ScreenCell](https://www.screencell.com/en/scientific-articles/breast-cancer-publication/comparative-performance-of-different-methods-for-circulating-tumor-cell-enrichment-in-metastatic-breast-cancer-patients-2/): The isolation and analysis of circulating tumor cells \(CTC\) has the potential to provide minimally invasive diagnostic, prognostic and predictive information. Widespread clinical implementation of CTC analysis has been hampered by a lack of comparative investigation between different analytic methodologies in clinically relevant settings. The objective of this study was to evaluate four different CTC isolation techniques–those that rely on surface antigen expression \(EpCAM or CD45 using DynaBeads® or EasySep™ systems\) or the biophysical properties \(RosetteSep™ or ScreenCell®\) of CTCs. These were evaluated using cultured cells in order to calculate isolation efficiency at various levels including; inter-assay and inter-operator variability, protocol complexity and turn-around time. All four techniques were adequate at levels above 100 cells/mL which is commonly used for the evaluation of new isolation techniques. Only the RosetteSep™ and ScreenCell® techniques were found to provide adequate sensitivity at a level of 10 cells/mL. These techniques were then applied to the isolation and analysis of circulating tumor cells blood drawn from metastatic breast cancer patients where CTCs were detected in 54% \(15/28\) of MBC patients using the RosetteSep™ and 75% \(6/8\) with ScreenCell®. Overall, the ScreenCell® method had better sensitivity.
- [Detection And Characterization Of Circulating Tumor Associated Cells In Metastatic Breast Cancer | ScreenCell](https://www.screencell.com/en/scientific-articles/breast-cancer-publication/detection-and-characterization-of-circulating-tumor-associated-cells-in-metastatic-breast-cancer-2/): The availability of blood-based diagnostic testing using a non-invasive technique holds promise for real-time monitoring of disease progression and treatment selection. Circulating tumor cells \(CTCs\) have been used as a prognostic biomarker for the metastatic breast cancer \(MBC\). The molecular characterization of CTCs is fundamental to the phenotypic identification of malignant cells and description of the relevant genetic alterations that may change according to disease progression and therapy resistance. However, the molecular characterization of CTCs remains a challenge because of the rarity and heterogeneity of CTCs and technological difficulties in the enrichment, isolation and molecular characterization of CTCs. In this pilot study, we evaluated circulating tumor associated cells in one blood draw by size exclusion technology and cytological analysis. Among 30 prospectively enrolled MBC patients, CTCs, circulating tumor cell clusters \(CTC clusters\), CTCs of epithelial–mesenchymal transition \(EMT\) and cancer associated macrophage-like cells \(CAMLs\) were detected and analyzed. For molecular characterization of CTCs, size-exclusion method for CTC enrichment was tested in combination with DEPArray™ technology, which allows the recovery of single CTCs or pools of CTCs as a pure CTC sample for mutation analysis. Genomic mutations of TP53 and ESR1 were analyzed by targeted sequencing on isolated 7 CTCs from a patient with MBC. The results of genomic analysis showed heterozygous TP53 R248W mutation from one single CTC and pools of three CTCs, and homozygous TP53 R248W mutation from one single CTC and pools of two CTCs. Wild-type ESR1 was detected in the same isolated CTCs. The results of this study reveal that size-exclusion method can be used to enrich and identify circulating tumor associated cells, and enriched CTCs were characterized for genetic alterations in MBC patients, respectively.
- [Did Circulating Tumor Cells Tell Us All They Could? The Missed Circulating Tumor Cell Message In Breast Cancer | ScreenCell](https://www.screencell.com/en/scientific-articles/breast-cancer-publication/did-circulating-tumor-cells-tell-us-all-they-could-the-missed-circulating-tumor-cell-message-in-breast-cancer-2/): Purpose To compare circulating tumor cell \(CTC\) detection rates in patients with early \(M0\) and metastatic \(M+\) breast cancer using 2 positive-selection methods or size-based unbiased enrichment. Methods Blood collected at baseline and at different times during treatment from M0 patients undergoing neoadjuvant therapy and from M+ women starting a new line of treatment was processed in parallel using AdnaTest EMT-1/ and EMT-2/Stem CellSelect/Detect kits or ScreenCell Cyto devices. CTC positivity was defined according to the suggested cutoffs and cytological parameters, respectively. Results Higher CTC detection rates were obtained with the AdnaTest approach when using for CTC-enrichment antibodies against ERBB2 and EGFR in addition to MUC1 and the classical epithelial surface marker EPCAM \(13% vs. 48%\). In M0 patients mainly, CTC positivity rates further increased when EMT- and stemness-related marker expression \(PIK3CA, AKT2 and ALDH1\) was evaluated in addition to EPCAM, MUC1 and ERBB2. When the physical properties of tumor cells were exploited, CTCs were detected at higher percentages than with positive-selection-based methods, without any difference between clinical stages \(78% in M0 vs. 72% in M+ cases at baseline\). Circulating tumor microemboli \(CTMs\) were detected in addition to single CTCs with significantly higher frequency in M0 than M+ samples \(78% vs. 27%, p = 0.0002\). Conclusions Different approaches for CTC detection probably identify distinct tumor cell subpopulations, but need technical standardization before their clinical validity and biological specificity may be adequately investigated. The distinct role of CTMs compared with CTCs as prognostic and predictive biomarkers represents a further challenge.
- [Ex Vivo Expansion Of Circulating Tumour Cells \(CTCs\) | ScreenCell](https://www.screencell.com/en/scientific-articles/breast-cancer-publication/ex-vivo-expansion-of-circulating-tumour-cells-ctcs-2/): Circulating tumour cells \(CTCs\) are a critical intermediate step in the process of cancer metastasis. The reliability of CTC isolation/purification has limited both the potential to report on metastatic progression and the development of CTCs as targets for therapeutic intervention. Here we report a new methodology, which optimises the culture conditions for CTCs using primary cancer cells as a model system. We exploited the known biology that CTCs thrive in hypoxic conditions, with their survival and proliferation being reliant on the activation of hypoxia-inducible factor 1 alpha \(HIF-1α\). We isolated epithelial-like and quasi-mesenchymal CTC phenotypes from the blood of a cancer patient and successfully cultured these cells for more than 8 weeks. The presence of CTC clusters was required to establish and maintain long-term cultures. This novel methodology for the long-term culture of CTCs will aid in the development of downstream applications, including CTC theranostics.
- [Fast And Efficient Isolation Of Murine Circulating Tumor Cells Using Screencell Technology For Pre-clinical Analyzes | ScreenCell](https://www.screencell.com/en/scientific-articles/breast-cancer-publication/fast-and-efficient-isolation-of-murine-circulating-tumor-cells-using-screencell-technology-for-pre-clinical-analyzes-2/): Circulating tumor cells \(CTCs\) represent a rare and heterogeneous population of cancer cells that are detached from the tumor site and entered blood or lymphatic circulation. Once disseminated in distant tissues, CTCs could remain dormant or create a tumor mass causing serious danger for patients. Many technologies exist to isolate CTCs from patients’ blood samples, mostly based on microfluidic systems or by sorting them according to their surface antigens, notably EpCAM, and/or cytokeratins for carcinoma. ScreenCell has developed an easy-to-use, antigen-independent, rapid, cost-effective, and efficient technology that isolates CTCs according to their bigger size compared to the blood cells. This study provides the technical information necessary to isolate and characterize CTCs from mouse blood. By using blood samples from transgenic mice with breast cancer or from WT mice in which we spiked cancer cells, we showed that ScreenCell technology is compatible with standard EDTA blood collection tubes. Furthermore, the ScreenCell Cyto kit could treat up to 500 µl and the ScreenCell MB kit up to 200 µl of mouse blood. As the ScreenCell MB kit captures unaltered live CTCs, we have shown that their DNA could be efficiently extracted, and the isolated cells could be grown in culture. In conclusion, ScreenCell provides a rapid, easy, antigen-independent, cost-effective, and efficient technology to isolate and characterize CTCs from the blood samples of cancer patients and murine models. Thanks to this technology CTCs could be captured fixed or alive. Murine cancer models are extensively used in pre-clinical studies. Therefore, this study demonstrates the crucial technical points necessary while manipulating mouse blood samples using ScreenCell technology.
- [Gene Signatures Of Circulating Breast Cancer Cell Models Are A Source Of Novel Molecular Determinants Of Metastasis And Improve Circulating Tumor Cell Detection In Patients | ScreenCell](https://www.screencell.com/en/scientific-articles/breast-cancer-publication/gene-signatures-of-circulating-breast-cancer-cell-models-are-a-source-of-novel-molecular-determinants-of-metastasis-and-improve-circulating-tumor-cell-detection-in-patients-2/): Background Progression to stage IV disease remains the main cause of breast cancer-related deaths. Increasing knowledge on the hematogenous phase of metastasis is key for exploiting the entire window of opportunity to interfere with early dissemination and to achieve a more effective disease control. Recent evidence suggests that circulating tumor cells \(CTCs\) possess diverse adaptive mechanisms to survive in blood and eventually metastasize, encouraging research into CTC-directed therapies. Methods On the hypothesis that the distinguishing molecular features of CTCs reveal useful information on metastasis biology and disease outcome, we compared the transcriptome of CTCs, primary tumors, lymph-node and lung metastases of the MDA-MB-231 xenograft model, and assessed the biological role of a panel of selected genes, by in vitro and in vivo functional assays, and their clinical significance in M0 and M+ breast cancer patients. Results We found that hematogenous dissemination is governed by a transcriptional program and identified a CTC signature that includes 192 up-regulated genes, mainly related to cell plasticity and adaptation, and 282 down-regulated genes, involved in chromatin remodeling and transcription. Among genes up-regulated in CTCs, FADS3 was found to increases cell membrane fluidity and promote hematogenous diffusion and lung metastasis formation. TFF3 was observed to be associated with a subset of CTCs with epithelial-like features in the experimental model and in a cohort of 44 breast cancer patients, and to play a role in cell migration, invasion and blood-borne dissemination. The analysis of clinical samples with a panel of CTC-specific genes \(ADPRHL1, ELF3, FCF1, TFF1 and TFF3\) considerably improved CTC detection as compared with epithelial and tumor-associated markers both in M0 and stage IV patients, and CTC kinetics informed disease relapse in the neoadjuvant setting. Conclusions Our findings provide evidence on the potential of a CTC-specific molecular profile as source of metastasis-relevant genes in breast cancer experimental models and in patients. Thanks to transcriptome analysis we generated a novel CTC signature in the MDA-MB-231 xenograft model, adding a new piece to the current knowledge on the key players that orchestrate tumor cell hematogenous dissemination and breast cancer metastasis, and expanding the list of CTC-related biomarkers for future validation studies.
- [Identification Of Atypical Circulating Tumor Cells With Prognostic Value In Metastatic Breast Cancer Patients | ScreenCell](https://www.screencell.com/en/scientific-articles/breast-cancer-publication/identification-of-atypical-circulating-tumor-cells-with-prognostic-value-in-metastatic-breast-cancer-patients-2/): Circulating tumor cells have a strong potential as a quasi-non-invasive tool for setting up a precision medicine strategy for cancer patients. Using a second-generation “filtration-based” technology to isolate CTCs, the Screencell™ technology \(Sarcelles, France\), we performed a large and simultaneous analysis of all atypical circulating tumor cells \(aCTCs\) isolated from the blood of metastatic breast cancer \(mBC\) patients. We correlated their presence with clinicopathological and survival data. We included 91 mBC patients from the PERMED-01 study. The median number of aCTCs was 8.3 per mL of blood. Three subsets of aCTCs, absent from controls, were observed in patients: single \(s-aCTCs\), circulating tumor micro-emboli \(CTM\), and giant-aCTCs \(g-aCTCs\). The presence of g-aCTCs was associated with shorter progression free survival and overall survival. This study highlights the heterogeneity of aCTCs in mBC patients both at the cytomorphological and molecular levels. In addition, it suggests the usefulness of the g-aCTC subset as a prognostic factor and a potential stratification tool to treat late-stage mBC patients and improve their chances of benefiting from early clinical trials.
- [Immunomodulatory Activity Of A Colony-stimulating Factor-1 Receptor Inhibitor In Patients With Advanced Refractory Breast Or Prostate Cancer: A Phase I Study | ScreenCell](https://www.screencell.com/en/scientific-articles/breast-cancer-publication/immunomodulatory-activity-of-a-colony-stimulating-factor-1-receptor-inhibitor-in-patients-with-advanced-refractory-breast-or-prostate-cancer-a-phase-i-study-2/): Purpose: Tumor-associated macrophages correlate with increased invasiveness, growth, and immunosuppression. Activation of the colony-stimulating factor-1 receptor \(CSF-1R\) results in proliferation, differentiation, and migration of monocytes/macrophages. This phase I study evaluated the immunologic and clinical activity, and safety profile of CSF-1R inhibition with the mAb LY3022855. Patients and Methods: Patients with advanced refractory metastatic breast cancer \(MBC\) or metastatic castration-resistant prostate cancer \(mCRPC\) were treated with LY3022855 intravenously in 6-week cycles in cohorts: \(A\) 1.25 mg/kg every 2 weeks \(Q2W\); \(B\) 1.0 mg/kg on weeks 1, 2, 4, and 5; \(C\) 100 mg once weekly; \(D\)100 mg Q2W. mCRPC patients were enrolled in cohorts A and B; patients with MBC were enrolled in all cohorts. Efficacy was assessed by RECIST and Prostate Cancer Clinical Trials Working Group 2 criteria. Results: Thirty-four patients \(22 MBC; 12 mCRPC\) received ≥1 dose of LY3022855. At day 8, circulating CSF-1 levels increased and proinflammatory monocytes CD14DIMCD16BRIGHT decreased. Best RECIST response was stable disease in five patients with MBC \(23%; duration, 82–302 days\) and three patients with mCRPC \(25%; duration, 50–124 days\). Two patients with MBC \(cohort A\) had durable stable disease >9 months and a third patient with MBC had palpable reduction in a nontarget neck mass. Immune-related gene activation in tumor biopsies posttreatment was observed. Common any grade treatment-related adverse events were fatigue, decreased appetite, nausea, asymptomatic increased lipase, and creatine phosphokinase. Conclusions: LY3022855 was well tolerated and showed evidence of immune modulation. Clinically meaningful stable disease >9 months was observed in two patients with MBC.
- [Liquid Biopsy In Breast Cancer: Redefining Precision Medicine | ScreenCell](https://www.screencell.com/en/scientific-articles/breast-cancer-publication/liquid-biopsy-in-breast-cancer-redefining-precision-medicine-2/): Breast cancer \(BC\) is the most frequent cancer and the leading cause of cancer-related death among women worldwide. It represents a heterogeneous group of diseases with distinct morphological, immunophenotypic, and molecular profiles, which significantly impact clinical behavior and therapeutic response. Moreover, under treatment pressure, tumor cells may undergo molecular changes and phenotypic plasticity, leading to resistance and therapeutic failure. Although tissue biopsy remains the gold standard for diagnosis and molecular characterization, it has several limitations, including invasiveness, sampling bias, and the inability to dynamically capture tumor evolution over time. Hence, a non-invasive and repeatable approach capable of real-time monitoring is increasingly needed. Liquid biopsy \(LB\), through the analysis of circulating tumor cells \(CTCs\) and circulating tumor DNA \(ctDNA\), has emerged as a powerful tool to complement tissue biopsy. It allows for longitudinal assessment of tumor burden, detection of minimal residual disease, and identification of molecular alterations relevant to targeted therapies. Despite promising results, the integration of LB into clinical practice is still limited by methodological heterogeneity, standardization gaps, and regulatory issues. Nonetheless, LB represents a key advancement toward precision oncology and may become essential in the personalized management of BC patients. In this review, we explore the current applications, benefits, and technical limitations of LB in different BC settings. We provide a comprehensive overview of the biological and clinical significance of CTCs and ctDNA, emphasizing their diagnostic, prognostic, and predictive roles. Finally, we present an updated summary of ongoing clinical trials that incorporate LB for clinical decision-making.
- [Optimizing Detection Of Circulating Tumor Cells In Breast Cancer: Unveiling New Markers For Clinical Applications | ScreenCell](https://www.screencell.com/en/scientific-articles/breast-cancer-publication/optimizing-detection-of-circulating-tumor-cells-in-breast-cancer-unveiling-new-markers-for-clinical-applications-en/): Breast cancer \(BC\) is a heterogeneous disease with high metastasis potential, especially in the bones, liver, and lungs. Circulating tumor cells \(CTCs\), which emerge from active tumors, represent an early step toward metastasis and are associated with poor prognosis. CTCs of carcinoma origin are believed to express EpCAM and cytokeratins \(CKs\), common epithelial markers that are frequently used to identify them. However, in practice, the most aggressive CTCs lose the expression of those markers, leading to the partial loss of important information. Thus, finding some novel markers that identify CTCs regardless of their heterogeneity is crucial. A specific bioinformatics workflow integrating primary tumor and diverse BC cell lines transcriptomic expression analysis was developed and compared with single CTC transcriptomic analyses. We have identified a set of genes that are overexpressed in primary BC cells and are commonly upregulated among BC cell lines. Fifty of them were also found to be expressed in BC CTCs by single-cell transcriptomic analysis. Further in silico sorting narrowed this list to 12 genes. Using ScreenCell technology to isolate cancer cells spiked into normal blood, we tested the protein expression of all corresponding genes in vitro using the double immunocytochemistry method and validated MARCKSL1, SLC9A3R1, and RHOD as the most expressed markers. We then isolated the CTCs of 40 LN-invaded BC patients and 18 healthy donors using ScreenCell technology and showed that the combination of these three markers resulted in significantly better recognition of CTCs compared to EpCAM and CK conventional markers. Employing these novel markers, we found a clear distinction between blood samples from patients and healthy donors. In conclusion, through a specific bioinformatics workflow, in addition to in vitro and further clinical validations, we found three novel markers to precisely identify CTCs. These markers, when used together, enable a significantly more efficient identification of CTCs compared to conventional epithelial markers.
- [Rapid And Sensitive Detection Of Breast Cancer Cells In Patient Blood With Nuclease-Activated Probe Technology | ScreenCell](https://www.screencell.com/en/scientific-articles/breast-cancer-publication/rapid-and-sensitive-detection-of-breast-cancer-cells-in-patient-blood-with-nuclease-activated-probe-technology-2/): A challenge for circulating tumor cell \(CTC\)-based diagnostics is the development of simple and inexpensive methods that reliably detect the diverse cells that make up CTCs. CTC-derived nucleases are one category of proteins that could be exploited to meet this challenge. Advantages of nucleases as CTC biomarkers include: \(1\) their elevated expression in many cancer cells, including cells implicated in metastasis that have undergone epithelial-to-mesenchymal transition; and \(2\) their enzymatic activity, which can be exploited for signal amplification in detection methods. Here, we describe a diagnostic assay based on quenched fluorescent nucleic acid probes that detect breast cancer CTCs via their nuclease activity. This assay exhibited robust performance in distinguishing breast cancer patients from healthy controls, and it is rapid, inexpensive, and easy to implement in most clinical labs. Given its broad applicability, this technology has the potential to have a substantive impact on the diagnosis and treatment of many cancers.
- [Circulating Tumor Cells In Right- And Left-Sided Colorectal Cancer | ScreenCell](https://www.screencell.com/en/scientific-articles/colorectal-cancer-publication/circulating-tumor-cells-in-right-and-left-sided-colorectal-cancer-2/): Molecular alterations are not randomly distributed in colorectal cancer \(CRC\), but rather clustered on the basis of primary tumor location underlying the importance of colorectal cancer sidedness. We aimed to investigate whether circulating tumor cells \(CTC\) characterization might help clarify how different the patterns of dissemination might be relative to the behavior of left- \(LCC\) compared to right-sided \(RCC\) cancers. We retrospectively analyzed patients with metastatic CRC who had undergone standard baseline CTC evaluation before starting any first-line systemic treatment. Enumeration of CTC in left- and right-sided tumors were compared. The highest prognostic impact was exerted by CTC in left-sided primary cancer patients, even though the lowest median number of cells was detected in this subgroup of patients. CTC exhibit phenotypic heterogeneity, with a predominant mesenchymal phenotype found in CTC from distal compared to proximal primary tumors. Most CTC in RCC patients exhibited an apoptotic pattern. CTC in left-sided colon cancer patients exhibit a predominant mesenchymal phenotype. This might imply a substantial difference in the biology of proximal and distal cancers, associated with different patterns of tumor cells dissemination. The poor prognosis of right-sided CRC is not determined by the hematogenous dissemination of tumor cells, which appears to be predominantly a passive shedding of non-viable cells. Conversely, the subgroup of poor-prognosis left-sided CRC is reliably identified by the presence of mesenchymal CTC.
- [Colorectal Carcinomas In 2013: The Search For Powerful Prognostic Markers Is Still On The Go! | ScreenCell](https://www.screencell.com/en/scientific-articles/colorectal-cancer-publication/colorectal-carcinomas-in-2013-the-search-for-powerful-prognostic-markers-is-still-on-the-go-2/): Colorectal cancer \(CRC\) is the third cause of cancer worldwide after prostate cancer and breast cancer. Patients have a survival rate of 5 years, which varies between 10 and 95% depending on CRC stage. Today, the management of patients with CRC is based on parameters such as TNM and classic histologic parameters, but new molecular and cell markers have been created to improve treatment and survival. Determining the expression of a characteristic set of genes either from formalin-fixed paraffin-embedded tissue \(Onco type DX test™\) or from fresh tissues \(AGENDIA© ColoPrint®\) has led to encouraging results, but there is a need for clinical validation on a large number of patients. Also, next-generation sequencing \(NGS\) technologies may be the next step in the molecular approach of CRC tumor samples, allowing tumor characterization by gene signature arrays. In addition to molecular markers, evaluation of the presence of cellular markers such as circulating tumor cells \(CTC\) in the blood of patients with CRC can optimize prognostic evaluation and response to treatment. CTC isolation methods used today have different sensitivities and specificities, due not only to the very small number of these cells but also to the epithelial-mesenchymal transitional process \(EMT\). This paper presents the preliminary results of our study conducted on CTC isolation in patients with CRC by filtration method \(Screencells Cyto®\). This fast and efficient method identifies CTCs and also isolates cells in EMT, which explains its high efficiency compared to technologies based on immunomagnetic and microfluidic separation reliant on EpCAM presence on the cell surface.
- [Détection Des Mutations RAS Dans Les Cellules Tumorales Circulantes : Applications Au Cancer Colorectal Et Perspectives | ScreenCell](https://www.screencell.com/en/scientific-articles/colorectal-cancer-publication/detection-des-mutations-ras-dans-les-cellules-tumorales-circulantes-applications-au-cancer-colorectal-et-perspectives-2/): Les mutations somatiques présentes dans les gènes RAS \(KRAS et NRAS\) sont largement associées à l’absence de réponse aux traitements par immunothérapie ciblant le récepteur du facteur de croissance épidermique dans le cancer colorectal métastatique. La recherche de ces mutations est devenue obligatoire pour pouvoir prescrire ces traitements et cette détection est réalisée à partir de biopsies tissulaires. Dans environ 25 % des cas, cette analyse n’est pas possible pour des raisons à la fois analytique et médicale et par conséquent le développement de stratégies alternatives est donc nécessaire. Parmi les solutions envisagées, la recherche de mutations directement dans le sang des patients est une approche prometteuse. Parmi les sources d’ADN tumoral présent dans la circulation sanguine, les cellules tumorales circulantes \(CTC\) représentent une approche particulièrement pertinente. Ces cellules, dont certaines sont à l’origine des métastases, sont parvenues à se détacher de la tumeur primitive, puis à migrer et enfin à entrer dans le système vasculaire. En ce sens, elles sont particulièrement résistantes aux contraintes physico-chimiques et immunologiques mises en œuvre par l’organisme pour empêcher leur dissémination et représentent par conséquent une source d’informations particulièrement précieuse sur la génétique des cellules tumorales les plus agressives. Le corollaire est que ces cellules sont très rares et nécessitent des technologies particulièrement performantes pour les détecter et les caractériser. Dans cette présentation, nous nous focaliserons principalement sur les méthodes moléculaires permettant de détecter les mutations des gènes RAS sur les CTC en analysant les performances d’une solution basée sur une méthode d’enrichissement par filtration suivi d’une détection par PCR digitale. Enfin, nous nous interrogerons sur leur signification biologique avant d’évoquer leurs perspectives dans le cancer colorectal ainsi que dans d’autres types de cancers.
- [Droplet Digital PCR Of Circulating Tumor Cells From Colorectal Cancer Patients Can Predict KRAS Mutations Before Surgery | ScreenCell](https://www.screencell.com/en/scientific-articles/colorectal-cancer-publication/droplet-digital-pcr-of-circulating-tumor-cells-from-colorectal-cancer-patients-can-predict-kras-mutations-before-surgery-2/): In colorectal cancer \(CRC\), KRAS mutations are a strong negative predictor for treatment with the EGFR-targeted antibodies cetuximab and panitumumab. Since it can be difficult to obtain appropriate tumor tissues for KRAS genotyping, alternative methods are required. Circulating tumor cells \(CTCs\) are believed to be representative of the tumor in real time. In this study we explored the capacity of a size-based device for capturing CTCs coupled with a multiplex KRAS screening assay using droplet digital PCR \(ddPCR\). We showed that it is possible to detect a mutant ratio of 0.05% and less than one KRAS mutant cell per mL total blood with ddPCR compared to about 0.5% and 50–75 cells for TaqMeltPCR and HRM. Next, CTCs were isolated from the blood of 35 patients with CRC at various stage of the disease. KRAS genotyping was successful for 86% \(30/35\) of samples with a KRAS codon 12/13 mutant ratio of 57% \(17/30\). In contrast, only one patient was identified as KRAS mutant when size-based isolation was combined with HRM or TaqMeltPCR. KRAS status was then determined for the 26 available formalin-fixed paraffin-embedded tumors using standard procedures. The concordance between the CTCs and the corresponding tumor tissues was 77% with a sensitivity of 83%. Taken together, the data presented here suggest that is feasible to detect KRAS mutations in CTCs from blood samples of CRC patients which are predictive for those found in the tumor. The minimal invasive nature of this procedure in combination with the high sensitivity of ddPCR might provide in the future an opportunity to monitor patients throughout the course of disease on multiple levels including early detection, prognosis, treatment and relapse as well as to obtain mechanistic insight with respect to tumor invasion and metastasis.
- [EpCAM-expressing Circulating Tumor Cells In Colorectal Cancer | ScreenCell](https://www.screencell.com/en/scientific-articles/colorectal-cancer-publication/epcam-expressing-circulating-tumor-cells-in-colorectal-cancer-2/): Background Several studies have raised the issue of the inadequacy of CellSearch® to detect the entire pool of circulating tumor cells \(CTCs\) from blood of cancer patients, suggesting that cells expressing low levels of epithelial cell adhesion molecule \(EpCAM\) are not recognized by the capture reagent. In this exploratory study, we aimed to evaluate the status of EpCAM in CTCs isolated from a group of metastatic colorectal cancer patients, in 40% of whom, CTC had been found to be undetected by the CellSearch® system. Methods CTCs were analyzed using both a microfiltration method \(ScreenCell\) and CellSearch® in parallel. Furthermore, since EpCAM exists in 2 different variants, we investigated the presence of both its intracellular domain \(EpICD\) and extracellular domain \(EpEX\) through immunofluorescence staining of CTCs on filters. Results Results from immunofluorescence experiments demonstrated that, overall, EpICD and/or EpEX was expressed in 176 CTCs detected by ScreenCell, while the CellSearch® system was able to capture only 10 CTCs. Conclusions This is the first demonstration that the low sensitivity of CellSearch® to detect CTCs in colorectal cancer patients is not due to the lack of EpCAM.
- [Isolation And Enumeration Of CTC In Colorectal Cancer Patients: Introduction Of A Novel Cell Imaging Approach And Comparison To Cellular And Molecular Detection Techniques | ScreenCell](https://www.screencell.com/en/scientific-articles/colorectal-cancer-publication/isolation-and-enumeration-of-ctc-in-colorectal-cancer-patients-introduction-of-a-novel-cell-imaging-approach-and-comparison-to-cellular-and-molecular-detection-techniques-2/): Circulating tumour cells \(CTC\) were proven to be prognostically relevant in cancer treatment, e.g., in colorectal cancer \(CRC\). This study validates a molecular detection technique through using a novel cell imaging approach for CTC detection and enumeration, in comparison to a size-based cellular and correlated the data to clinico-pathological characteristics. Overall, 57 CRC patients were recruited for this prospective study. Blood samples were analysed for CTCs by three methods: \(1\) Epithelial marker immunofluorescence staining combined with automated microscopy using the NYONE® cell imager; \(2\) isolation by size using membrane filtration with the ScreenCell® Cyto IS device and immunofluorescence staining; \(3\) detection by semi-quantitative Cytokeratin-20 RT-qPCR. Enumeration data were compared and correlated with clinic-pathological parameters. CTC were detected by either approach; however, with varying positivity rates: NYONE® 36.4%, ScreenCell® 100%, and PCR 80.5%. All methods revealed a positive correlation of CTC presence and higher tumour burden, which was most striking using the ScreenCell® device. Generally, no intercorrelation of CTC presence emerged amongst the applied techniques. Overall, enumeration of CTC after isolation by size demonstrated to be the most reliable strategy for the detection of CTC in CRC patients. Ongoing studies will have to unravel the prognostic value of this finding, and validate this approach in a larger cohort.
- [Sequential Isolation And Characterization Of Single CTCs And Large CTC Clusters In Metastatic Colorectal Cancer Patients | ScreenCell](https://www.screencell.com/en/scientific-articles/colorectal-cancer-publication/sequential-isolation-and-characterization-of-single-ctcs-and-large-ctc-clusters-in-metastatic-colorectal-cancer-patients-2/): Circulating tumor cells \(CTCs\) detach from a primary tumor or its metastases and circulate in the bloodstream. The vast majority of CTCs are deemed to die into the bloodstream, with only few cells representing viable metastatic precursors. Particularly, single epithelial CTCs do not survive long in the circulation due to the loss of adhesion-dependent survival signals. In metastatic colorectal cancer, the generation of large CTC clusters is a very frequent occurrence, able to increase the aptitude of CTCs to survive in the bloodstream. Although a deepened analysis of large-sized CTC clusters might certainly offer new insights into the complexity of the metastatic cascade, most CTC isolation techniques are unfortunately not compatible with large-sized CTC clusters isolation. The inappropriateness of standard CTC isolation devices for large clusters isolation and the scarce availability of detection methods able to specifically isolate and characterize both single CTCs and CTC clusters finally prevented in-depth studies on the prognostic and predictive value of clusters in clinical practice, unlike that which has been described for single CTCs. In the present study, we validated a new sequential filtration method for the simultaneous isolation of large CTC clusters and single CTCs in patients with metastatic colorectal cancer at failure of first-line treatments. The new method might allow differential downstream analyses for single and clustered CTCs starting from a single blood draw, opening new scenarios for an ever more precise characterization of colorectal cancer metastatic cascade.
- [Weighted Correlation Network Analysis Revealed Novel Long Non-coding RNAs For Colorectal Cancer | ScreenCell](https://www.screencell.com/en/scientific-articles/colorectal-cancer-publication/weighted-correlation-network-analysis-revealed-novel-long-non-coding-rnas-for-colorectal-cancer-2/): Colorectal cancer \(CRC\) is one of the most prevalent cancers worldwide, which after breast, lung and, prostate cancers, is the fourth prevalent cancer in the United States. Long non-coding RNAs \(lncRNAs\) have an essential role in the pathogenesis of CRC. Therefore, bioinformatics studies on lncRNAs and their target genes have potential importance as novel biomarkers. In the current study, publicly available microarray gene expression data of colorectal cancer \(GSE106582\) was analyzed with the Limma, Geoquery, Biobase package. Afterward, identified differentially expressed lncRNAs and their target genes were inserted into Weighted correlation network analysis \(WGCNA\) to obtain modules and hub genes. A total of nine differentially expressed lncRNAs \(LINC01018, ITCH-IT, ITPK1-AS1, FOXP1-IT1, FAM238B, PAXIP1-AS1, ATP2B1-AS1, MIR29B2CHG, and SNHG32\) were identified using microarray data analysis. The WGCNA has identified several hub genes for black \(LMOD3, CDKN2AIPNL, EXO5, ZNF69, BMS1P5, METTL21A, IL17RD, MIGA1, CEP19, FKBP14\), blue \(CLCA1, GUCA2A, UGT2B17, DSC2, CA1, AQP8, ITLN1, BEST4, KLF4, IQCF6\) and turquoise \(PAFAH1B1, LMNB1, CACYBP, GLO1, PUM3, POC1A, ASF1B, SDCCAG3, ASNS, PDCD2L\) modules. The findings of the current study will help to improve our understanding of CRC. Moreover, the hub genes that we have identified could be considered as possible prognostic/diagnostic biomarkers. This study led to the determination of nine lncRNAs with no previous association with CRC development.
- [Evaluating Circulating Tumour Cell Enrichment Techniques To Establish An Appropriate Method For Clinical Application In Glioblastomas | ScreenCell](https://www.screencell.com/en/scientific-articles/glioblastoma-publication/evaluating-circulating-tumour-cell-enrichment-techniques-to-establish-an-appropriate-method-for-clinical-application-in-glioblastomas-2/): Brain tumours reduce life expectancy for an average of 20 years per patient, the highest of any cancer. A third of brain tumour patients visit their GP at least five times before diagnosis and many of those are diagnosed late through emergency departments. A possible solution to this challenge is to utilise a ""liquid biopsy"" blood test designed for circulating tumour cells \(CTCs\). Such a test could be applied at a primary healthcare centre, contributing to informed decision making for diagnostic imaging referrals. Furthermore, it could also be applied at secondary health care centres for the ongoing monitoring of disease recurrence. There is increased interest in CTC enrichment methods as a potential approach for faster diagnosis and monitoring of disease progression. The aim of this review to compare four CTC enrichment methods - OncoQuick®, Screen Cell®, pluriBead® and Cell Search® - with the objective of identifying a suitable method for application in the clinical setting for the isolation of CTCs from glioblastomas.
- [Impact Of Label-free Technologies In Head And Neck Cancer Circulating Tumour Cells | ScreenCell](https://www.screencell.com/en/scientific-articles/head-neck-publication/impact-of-label-free-technologies-in-head-and-neck-cancer-circulating-tumour-cells-2/): Background: The ability to identify high risk head and neck cancer \(HNC\) patients with disseminated disease prior to presenting with clinically detectable metastases holds remarkable potential. A fraction of circulating tumour cells \(CTCs\) are invasive cancer cells which mediate metastasis by intravasation, survival and extravasation from the blood stream to metastatic sites. CTCs have been cleared by the FDA for use as surrogate markers of overall survival and progression free survival for breast, prostate and colorectal cancers using the CellSearch® system. However, the clinical significance of CTCs in head and neck cancer patients has yet to be determined. There has been a significant shift in CTC enrichment platforms, away from exclusively single marker selection, to epitope-independent systems. Methods: The aim of this study was to screen advanced stage HNC patients by the CellSearch® platform and utilise two other epitope-independent approaches, ScreenCell® \(microfiltration device\) and RosetteSep™ \(negative enrichment\), to determine how a shift to such methodologies would enable CTC enrichment and detection. Results: In advanced stage HNC patients, single CTCs were detected in 8/43 \(18.6%\) on CellSearch®, 13/28 \(46.4%\) on ScreenCell® and 16/25 \(64.0%\) by RosetteSep™ \(the latter could also detect CTC clusters\). Notably, in patients with suspicious lung nodules, too small to biopsy, CTCs were found upon presentation. Moreover, CTCs were readily detected in advanced stage HNC patients. Conclusion: The epitope-independent platforms detected higher CTC numbers and clusters. Further studies are needed to ascertain whether CTCs can be used as independent prognostic markers for HNCs.
- [Detection Of Circulating Tumor Cells In Patients With Laryngeal Cancer Using ScreenCell: Comparative Pre- And Post-operative Analysis And Association With Prognosis | ScreenCell](https://www.screencell.com/en/scientific-articles/laryngeal-cancer-publication/detection-of-circulating-tumor-cells-in-patients-with-laryngeal-cancer-using-screencell-comparative-pre-and-post-operative-analysis-and-association-with-prognosis-2/): The presence of circulating tumor cells \(CTCs\) in the blood of patients with metastatic breast, colorectal and prostate cancer have been widely investigated; however, few studies have examined CTCs in patients with laryngeal cancer. The present pilot study aimed to detect pre‑ and postoperative CTCs in the blood of patients with laryngeal cancer and evaluate the association with prognosis. Eight patients with laryngeal squamous cell carcinoma \(LSCC\) at stage III were included in the present study and underwent total or subtotal laryngectomy and radical bilateral neck lymph node dissection. Blood samples were collected from all patients before and after surgery at different time‑points. The following processing steps were followed; preoperative blood sampling, surgery, postoperative blood sampling at 3, 6 and 12 month follow‑ups, and prognostic association analysis. CTCs were retained on ScreenCell filters for cytological characterization. The presence of CTCs was associated with a less favorable prognosis, whereas a decrease of CTCs in the postoperative sampling was observed in patients who exhibited an improved therapeutic response. The results of the present pilot study revealed a possible association between the presence of CTCs and a less favorable prognosis in patients with LSCC; therefore, these preliminary findings may encourage further research into the incorporation of a liquid biopsy in the management of LSCC, as this may help identify patients with occult metastatic disease earlier and in a non‑invasive manner. In addition, this approach may represent novel independent prognostic factor for use in the clinical evaluation of patients with LSCC.
- [A Fast And Furious Liquid Biopsy Assay To Monitor Targeted Therapy Resistance. | ScreenCell](https://www.screencell.com/en/scientific-articles/liquid-biopsy-publication/a-fast-and-furious-liquid-biopsy-assay-to-monitor-targeted-therapy-resistance-2/): Liquid biopsies represent a valid alternative to conventional tissue biopsies, offering a real time molecular picture of tumors in a minimally invasive manner. Of the various circulating biomarkers available for liquid biopsy, circulating tumor cells \(CTC\) and circulating tumor DNA \(ctDNA\) are the most intensively studied to date. However, CTC and ctDNA represent different tumor components, therefore, complementary information from both sources might be beneficial. This protocol focuses on the description of a sample processing workflow that allowed for concurrent isolation of CTC and ctDNA from the same source sample. This single tube approach enables simultaneous analysis of multiple biomarkers to better monitor cancer drug resistance.
- [A Novel Combined Methodology For Isolation And Detection Of Circulating Tumor Cells Based On Flow Cytometry And Cellular Filtration Technologies | ScreenCell](https://www.screencell.com/en/scientific-articles/liquid-biopsy-publication/a-novel-combined-methodology-for-isolation-and-detection-of-circulating-tumor-cells-based-on-flow-cytometry-and-cellular-filtration-technologies-2/): Cancer cell presents a dynamic nature that evolves over time in its microenvironment through a complicating molecular and cellular interaction network. Despite the progress already achieved in the imaging technologies and the molecular tools used for tumor cell diagnosis and treatment approaches, metastasis still remains a major hindering factor that limits the clinical outcomes. Circulating tumor cells \(CTCs\) present the potential in providing critical information to understand the metastasis process, the tumor cell and genome heterogeneity, in a way to overcome cancer therapy bottlenecks and improve the efficacy and safety therapeutic profiles. The experience already gained shows that CTCs as tools possess a predictive biomarker capacity by aiming the understanding of most of the known cancer cell hallmarks at the molecular level, as well as the translation of the extracted relevant knowledge in clinical practice. The efficient isolation and characterization of CTCs might reveal the intratumoral heterogeneity present in tumors while providing critical insights into cancer metastasis. Moreover, by combining the emerging single cell omics technologies, CTCs can be valuable biological source material to unveil the existed intratumoral cellular and genomic heterogeneity, as well as to pharmacologically exploit critical knowledge for the validation of prognostic and diagnostic biomarkers within the concept of precision and personalized cancer therapy. In this article, a novel combined methodology for the isolation and detection of CTCs based on flow cytometry and cellular filtration technologies is presented.
- [An Assessment Of Diagnostic Performance Of A Filter-based Antibody-independent Peripheral Blood Circulating Tumour Cell Capture Paired With Cytomorphologic Criteria For The Diagnosis Of Cancer | ScreenCell](https://www.screencell.com/en/scientific-articles/lung-cancer-publication/an-assessment-of-diagnostic-performance-of-a-filter-based-antibody-independent-peripheral-blood-circulating-tumour-cell-capture-paired-with-cytomorphologic-criteria-for-the-diagnosis-of-cancer-2/): Objectives Circulating tumour cells \(CTCs\) are reported to be predictive for prognosis and response to treatment in advanced lung cancer. However, the clinical utility of the CTCs detection remains unknown for early stage lung cancer as the number of CTCs is reported as low, providing challenges in identification. We have evaluated diagnostic performance of filtration-based technology using cytomorphologic criteria in patients undergoing surgery for lung cancer. Material and methods We processed blood from 76 patients undergoing surgery for known or suspected lung cancer using ScreenCell® Cyto filter devices. Captured cells were stained using haematoxylin and eosin and independently assessed by two pathologists for the presence of atypical cells suspicious for cancer. Diagnostic performance was evaluated against pathologist reported diagnoses of cancer from surgically obtained specimens. Results Cancer was diagnosed in 57 patients \(77.0%\), including 32 with primary lung cancer \(56.1%\). The proportion of patients with early stage primary lung cancer in which CTCs were identified was 18 and 21 \(56.3% and 65.6%, respectively\) as reported by two pathologists. The agreement between the pathologists was 77.0% corresponding to a kappa-statistic of 53.7% indicating moderate agreement. No significant differences were found for the percentage of CTCs for primary and metastatic cancer as well as for cancer stages. On sensitivity weighted analysis, a sensitivity and specificity were 71.9% \(95% CI 60.5–83.0\) and 52.9% \(95% CI 31.1–77.0\), respectively. On specificity weighted analysis, a sensitivity and specificity were 50.9% \(95% CI 39.3–64.4\) and 82.4% \(60.4–96.2\), respectively. Conclusion The performance of the tested filter-based antibody-independent technology to capture CTCs using standard cytomorphologic criteria provides the potential of a diagnostic blood test for lung cancer.
- [Circulating Cell-Free DNA And Circulating Tumor Cells As Prognostic And Predictive Biomarkers In Advanced Non-Small Cell Lung Cancer Patients Treated With First-Line Chemotherapy | ScreenCell](https://www.screencell.com/en/scientific-articles/lung-cancer-publication/circulating-cell-free-dna-and-circulating-tumor-cells-as-prognostic-and-predictive-biomarkers-in-advanced-non-small-cell-lung-cancer-patients-treated-with-first-line-chemotherapy-2/): Cell-free DNA \(cfDNA\) and circulating tumor cells \(CTCs\) are promising prognostic and predictive biomarkers in non-small cell lung cancer \(NSCLC\). In this study, we examined the prognostic role of cfDNA and CTCs, in separate and joint analyses, in NSCLC patients receiving first line chemotherapy. Seventy-three patients with advanced NSCLC were enrolled in this study. CfDNA and CTC were analyzed at baseline and after two cycles of chemotherapy. Plasma cfDNA quantification was performed by quantitative PCR \(qPCR\) whereas CTCs were isolated by the ScreenCell Cyto \(ScreenCell, Paris, France\) device and enumerated according to malignant features. Patients with baseline cfDNA higher than the median value \(96.3 hTERT copy number\) had a significantly worse overall survival \(OS\) and double the risk of death \(hazard ratio \(HR\): 2.14; 95% confidence limits \(CL\) = 1.24–3.68; p-value = 0.006\). Conversely, an inverse relationship between CTC median baseline number \(6 CTC/3 mL of blood\) and OS was observed. In addition, we found that in patients reporting stable disease \(SD\), the baseline cfDNA and CTCs were able to discriminate patients at high risk of poor survival. cfDNA demonstrated a more reliable biomarker than CTCs in the overall population. In the subgroup of SD patients, both biomarkers identified patients at high risk of poor prognosis who might deserve additional/alternative therapeutic interventions.
- [Circulating Tumor Cells And Microemboli Can Differentiate Malignant And Benign Pulmonary Lesions | ScreenCell](https://www.screencell.com/en/scientific-articles/lung-cancer-publication/circulating-tumor-cells-and-microemboli-can-differentiate-malignant-and-benign-pulmonary-lesions-2/): The presence of circulating tumor cells \(CTC\) or microemboli \(CTM\) in the peripheral blood can theoretically anticipate malignancy of solid lesions in a variety of organs. We aimed to preliminarily assess this capability in patients with pulmonary lesions of suspected malignant nature. We used a cell-size filtration method \(ScreenCell\) and cytomorphometric criteria to detect CTC/CTM in a 3 mL sample of peripheral blood that was taken just before diagnostic percutaneous CT-guided fine needle aspiration \(FNA\) or core biopsy of the suspicious lung lesion. At least one CTC/CTM was found in 47 of 67 \(70%\) patients with final diagnoses of lung malignancy and in none of 8 patients with benign pulmonary nodules. In particular they were detected in 38 \(69%\) of 55 primary lung cancers and in 9 \(75%\) of 12 lung metastases from extra-pulmonary cancers. Sensitivity of CTC/CTM presence for malignancy was 70.1% \(95%CI: 56.9-83.1%\), specificity 100%, positive predictive value 100% and negative predictive value 28.6% \(95%CI: 11.9-45.3%\). Remarkably, the presence of CTC/CTM anticipated the diagnosis of primary lung cancer in 3 of 5 patients with non-diagnostic or inconclusive results of FNA or core biopsy, whereas CTC/CTM were not observed in 1 patient with sarcoidosis and 1 with amarthocondroma. These results suggest that presently, due to the low sensitivity, the search of CTC/CTM cannot replace CT guided percutaneous FNA or core biopsy in the diagnostic work-up of patients with suspicious malignant lung lesions. However, the high specificity may as yet indicate a role in cases with non-diagnostic or inconclusive FNA or core biopsy results that warrants to be further investigated.
- [Circulating Tumor Cells From Surgical Manipulation Predict Recurrence And Poor Prognosis In Non-Small Cell Lung Cancer | ScreenCell](https://www.screencell.com/en/scientific-articles/lung-cancer-publication/circulating-tumor-cells-from-surgical-manipulation-predict-recurrence-and-poor-prognosis-in-non-small-cell-lung-cancer/): Background/Objectives: In our previous multicenter prospective controlled study \(UMIN000018602\), we investigated the impact of surgical manipulation on circulating tumor cells \(CTCs\) in patients with non-small cell lung cancer \(NSCLC\). CTCs were detected after surgery in four patients \(4/29, 13.8%\), although CTCs were not present before surgery. These four patients had tumor cells leaked into their bloodstream by surgeons' manipulation. We aimed to clarify long-term outcomes according to the presence of CTCs. Methods: Patients with cT1b-2N0M0 NSCLC scheduled for lobectomy were enrolled, based on the selection criteria of a consolidation-to-ground-glass opacity ratio \(over 50%\). Peripheral blood samples \(≥3 mL\) were collected before surgery \(for pre-CTCs\), during surgery, and immediately after pulmonary vein dissection \(for post-CTCs\). CTCs were isolated from these samples using ScreenCell®'s size-selective method. Results: From July 2015 to January 2016, 29 patients were enrolled, yielding paired pre- and post-CTC samples for all patients. Thirteen patients were pre-CTC positive, and post-CTCs were detected in 17 patients. Survival analysis revealed a statistically significant difference in recurrence-free survival between patients with and without post-CTCs \(p = 0.043\), while pre-CTCs status had no significant impact on recurrence \(p = 0.226\). Patients with post-CTCs had a significantly higher recurrence rate than those without \(p = 0.043\). Half of patients with post-CTCs but without pre-CTCs had recurrence within 5 years after surgery. Conclusions: Post-CTCs emerged as a significant predictor of recurrence following lobectomy; however, it could be possible for thoracic surgeons to prevent recurrence by improving surgical techniques for NSCLC patients with post-CTCs but without pre-CTCs.
- [Circulating Tumor Cells In Diagnosing Lung Cancer: Clinical And Morphologic Analysis | ScreenCell](https://www.screencell.com/en/scientific-articles/lung-cancer-publication/circulating-tumor-cells-in-diagnosing-lung-cancer-clinical-and-morphologic-analysis-2/): Background The purpose of this study was to evaluate the value of circulating non-hematologic cells to differentiate benign from malignant lung lesions and their comparison with clinico-histologic features of corresponding primary lesions. Methods Circulating cells were isolated by size method from peripheral blood of 77 patients with malignant \(n = 60\) and benign \(n = 17\) lung lesions. They were morphologically classified as cells with malignant feature; cells with uncertain malignant feature; and cells with benign feature; then statistically correlated with clinico-cytopathologic characteristics of corresponding lung lesion. Results Malignant circulating cells were detected in 54 of 60 \(90%\) malignant patients, and in 1 of 17 \(5%\) benign patients; benign circulating cells in 1 of 60 \(1%\) malignant patients and in 15 of 17 \(88%\) benign patients; and circulating cells with uncertain malignant aspect in 5 of 60 \(8%\) malignant patients and 1 of 17 \(5%\) benign patients. For a malignant circulating cells count greater than 25, sensitivity and specificity were 89% and 100%, respectively. The count was significantly correlated with stage, size, and standard uptake value of primary tumor. In 39 of 54 \(72%\) cases, the malignant circulating cells allowed a specific histologic diagnosis of the corresponding primary tumor after immunohistochemical analysis. Conclusions Malignant circulating cells may be a valid marker in the diagnostic workup of lung lesions. However, our resuts should be corroborated by larger future studies especially for patients having small nodules.
- [Circulating Tumor DNA Reflects Tumor Metabolism Rather Than Tumor Burden In Chemotherapy-Naive Patients With Advanced Non-Small Cell Lung Cancer: 18F-FDG PET/CT Study | ScreenCell](https://www.screencell.com/en/scientific-articles/lung-cancer-publication/circulating-tumor-dna-reflects-tumor-metabolism-rather-than-tumor-burden-in-chemotherapy-naive-patients-with-advanced-non-small-cell-lung-cancer-18f-fdg-pet-ct-study-2/): We aimed to evaluate the relationships between circulating tumor cells \(CTCs\) or plasma cell–free DNA \(cfDNA\) on one side and a comprehensive range of 18F-FDG PET/CT–derived parameters on the other side in chemotherapy-naive patients with advanced non–small cell lung cancer \(NSCLC\). Methods: From a group of 79 patients included in a trial evaluating the role of pretreatment circulating tumor markers as predictors of prognosis in chemotherapy-naive patients with advanced NSCLC, we recruited all those who underwent 18F-FDG PET/CT for clinical reasons at our institution before inclusion in the trial \(and thus just before chemotherapy\). For each patient, a peripheral blood sample was collected at baseline for the evaluation of CTCs and cfDNA. CTCs were isolated by size using a filtration-based device and then morphologically identified and enumerated; cfDNA was isolated from plasma and quantified by a quantitative polymerase chain reaction using human telomerase reverse transcriptase. The following 18F-FDG PET/CT–derived parameters were computed: maximum diameter of the primary lesion \(T\), of the largest lymph node \(N\), and of the largest metastatic lesion \(M\); SUVmax; SUVmean; size-incorporated SUVmax; metabolic tumor volume; and total lesion glycolysis. All parameters were independently measured for T, N, and M. The associations among CTCs, cfDNA, and 18F-FDG PET/CT–derived parameters were evaluated by multivariate-analysis. Patients were divided into 2 groups according to the presence of either limited metastatic involvement \(M1a or M1b due to extrathoracic lymph nodes only\) or disseminated metastatic disease. The presence or absence of metabolically active bone lesions was also recorded for each patient, and patient subgroups were compared. Results: Thirty-seven patients recruited in the trial matched our PET-based criteria \(24 men; age, 64.5 ± 8.1 y\). SUVmax for the largest metastatic lesion was the only variable independently associated with baseline cfDNA levels \(P = 0.016\). Higher levels of cfDNA were detected in the subgroup of patients with metabolically active bone lesions \(P = 0.02\), but no difference was highlighted when patients with more limited metastatic disease were compared with patients with disseminated metastatic disease. Conclusion: The correlation of cfDNA levels with tumor metabolism, but not with metabolic tumor volume at regional or distant levels, suggests that cfDNA may better reflect tumor biologic behavior or aggressiveness rather than tumor burden in metastatic NSCLC.
- [Circulating Tumour Cells In Patients With Lung Cancer Undergoing Endobronchial Cryotherapy | ScreenCell](https://www.screencell.com/en/scientific-articles/lung-cancer-publication/circulating-tumour-cells-in-patients-with-lung-cancer-undergoing-endobronchial-cryotherapy-2/): Early diagnosis of lung cancer still poses a major issue, with a large proportion of patients diagnosed at late stages. Therapeutic options and treatment remain limited in these patients. In most cases only palliative therapies are available to alleviate any severe symptoms. Endobronchial cryotherapy \(EC\) is one form of palliative treatment offered to patients with obstructive airway tumours. Although successful, the impact on circulating tumour cell \(CTCs\) spread has not been investigated in detail. This study recruited 20 patients awaiting EC treatment. Baseline and post EC blood samples were analysed for presence of CTCs. Results showed an increase in CTCs following EC in 75% of patients. Significant increases were noticeable in some cases. Although EC is a well-accepted modality of treatment to alleviate symptoms, it may lead to an increase in CTCs, which in turn may have implications for tumour dissemination and metastatic spread.
- [Circulating Tumour Cells In Patients With Malignant Lung Tumors Undergoing Radio-frequency Ablation | ScreenCell](https://www.screencell.com/en/scientific-articles/lung-cancer-publication/circulating-tumour-cells-in-patients-with-malignant-lung-tumors-undergoing-radio-frequency-ablation-2/): Background/Aim: Radiofrequency ablation \(RFA\) is an increasingly utilised technique in patients with surgically-untreatable lesions. The effect of this therapy on circulating tumor cells \(CTCs\) is unknown. As far as we are aware of, this is the first study to evaluate the effects of RFA on CTCs in patients with malignant lung tumors immediately post-treatment. Patients and Methods: Nine patients with primary or metastatic lung tumors underwent RFA therapy from June to November 2013. Blood samples were taken before and after RFA, and filtered through the ScreenCell CTC capture device. Results: A general increase in CTCs in 7 out of the 9 cases was found, the largest increases were seen in the metastatic group. Conclusion: This study demonstrates that the manipulation and ablative procedure of lung tumors leads to immediate dissemination of tumor cells, the effects of which are unknown and require further investigation.
- [Cluster Circulating Tumor Cells In Surgical Cases Of Lung Cancer | ScreenCell](https://www.screencell.com/en/scientific-articles/lung-cancer-publication/cluster-circulating-tumor-cells-in-surgical-cases-of-lung-cancer-2/): Objectives A cancer lesion sheds tumor cells into the circulating blood as circulating tumor cells \(CTCs\). Since cluster CTCs have been considered as precursor lesions of metastasis, their clinical implication was investigated in this study according to the preoperative status of cluster CTC detection in surgical cases of clinically early-stage lung cancer. Methods Among 104 surgical patients of early-stage lung cancer, CTCs were extracted from the peripheral blood before surgery using a micro-pore size selection method \(ScreenCell®\) and diagnosed microscopically. Implications of detecting cluster CTC were assessed according to the prognosis and clinicopathological characteristics. Results The status of CTC detection was not detected in 77 cases \(74.0%\), single CTC only detection in 7 cases \(6.7%\), and cluster CTC detected in 20 cases \(19.2%\). Patients with cluster CTCs exhibited significantly lower recurrence-free survival and overall survival than did patients of other groups. In addition, in hazard ratio analysis, the hazard ratios were independent of other predictors of poor prognosis, and detection of cluster CTCs was associated with predictors of poor prognosis. Conclusion Cluster CTCs were detected in cases where the original lung cancer lesion had clinical predictors of poor prognosis and were independent negative predictors of survival.
- [Detection Of Circulating Tumour Cells And Survival Of Patients With Non-small Cell Lung Cancer | ScreenCell](https://www.screencell.com/en/scientific-articles/lung-cancer-publication/detection-of-circulating-tumour-cells-and-survival-of-patients-with-non-small-cell-lung-cancer-2/): Background: Detection of circulating tumour cells \(CTCs\) in the peripheral blood of lung cancer patients may predict survival. Various platforms exist that allow capture of these cells for further analysis; little work however, has been done with the ScreenCell device, an antibody-independent CTC platform. The aim of our study was to evaluate the ScreenCell device for detection of CTCs in lung cancer patients and to establish correlations of these findings with survival. Materials and Methods: Twenty-three patients, nine males, and fourteen females, underwent surgical treatment from February to May 2014 for non-small cell lung cancer. Thirteen patients had adenocarcinoma and ten squamous cell carcinoma, while eight were at an early stage \(I-II\) and five at a later stage \(III-IV\). Blood samples were obtained prior to surgery and following filtration through the ScreenCell device, were independently reviewed by 2 consultant pathologists. Results: The pathologists were able to independently identify CTCs in 78.3% \(N=18\) and 73.9% \(N=17\) of the cases examined, with overall 80.6% in early stages compared to 60.0% in late stages. The median survival times of positive vs. negative for CTC patients were 1011 and 711 days respectively, with a survival percentage rate of 77.8% and 60% in positive and negative CTC cohorts respectively. Conclusion: The results of this study suggest that the presence of CTCs analyzed by ScreenCell did not necessarily lead to a poorer prognosis in patients with lung cancer after curative surgery.
- [Lack Of Association Between Screencell-detected Circulating Tumour Cells And Long-term Survival Of Patients Undergoing Surgery For Non-small Cell Lung Cancer: A Pilot Clinical Study. | ScreenCell](https://www.screencell.com/en/scientific-articles/lung-cancer-publication/lack-of-association-between-screencell-detected-circulating-tumour-cells-and-long-term-survival-of-patients-undergoing-surgery-for-non-small-cell-lung-cancer-a-pilot-clinical-study-2/): Circulating tumour cells \(CTCs\) are cancer cells of epithelial origin that are present in peripheral blood samples. ScreenCell detection of CTCs and the association with long term survival in non‑small cell lung cancer \(NSCLC\) patients was evaluated in the present study. A total of 33 patients undergoing surgical resection for NSCLC were recruited. Patients were followed up for 5‑years post‑operatively. Pre‑operative patient bloods samples were processed using ScreenCell. CTCs were detected in 26 \(79%\) patients. In patients who were positive for CTCs, a total of 9 \(35%\) patients succumbed to the disease, whereas in patients negative for CTCs, a total of 4 \(57%\) patients succumbed to the disease \(P=0.29\). No association was identified between positive CTCs and poorer survival \(Chi‑squared 1.47, P=0.23; hazard ratio, 0.42; 95% confidence interval: 0.1‑1.7\). The presence of CTCs detected with ScreenCell does not influence prognosis in patients with NSCLC that was operated on. The high rate of CTC detection is encouraging in supporting this technology to aid early lung cancer diagnosis.
- [Lung Cancer Biopsy Dislodges Tumor Cells Into Circulating Blood. | ScreenCell](https://www.screencell.com/en/scientific-articles/lung-cancer-publication/lung-cancer-biopsy-dislodges-tumor-cells-into-circulating-blood-2/): Aim: A “seed” of lung cancer metastasis is circulating tumor cells \(CTCs\), which may be dislodged from a tumor during biopsy. This possibility was assessed among patients who underwent lung tumor biopsy using flexible fiber-topic bronchoscopy \(FFB\). Methods: The study involved six patients with non-small cell lung cancer who underwent FFB biopsy to diagnose a lesion pathologically \(5 males and 1 female, median age 63 years, 6 adenocarcinomas, of 4 clinical-stage IA, 1 stage IB, and 1 stage IIIA\), CTCs were extracted from the peripheral vein blood at pre-FFB and at post-FFB using a size selection method. Results: No tumor cell was detected at pre- and post-FFB was in three cases \(50%\); no tumor cells were detected pre-FFB while CTCs were detected at post-FFB in two cases \(33.3%\); and CTCs were detected at pre-FFB with numerous CTCs detected at post-FFB in one case \(17.7%\). In addition, similar tendencies were observed in each analysis of single-cell and clustered-cell categories. Conclusion: These results suggest that a FFB biopsy of lung cancer may potentially dislodge CTCs from a tumor into the circulating peripheral blood.
- [Optimum Diagnostic Pathway And Pathologic Confirmation Rate Of Early Stage Lung Cancer: Results From The VIOLET Randomised Controlled Trial | ScreenCell](https://www.screencell.com/en/scientific-articles/lung-cancer-publication/optimum-diagnostic-pathway-and-pathologic-confirmation-rate-of-early-stage-lung-cancer-results-from-the-violet-randomised-controlled-trial/): Background: Pathologic confirmation of lung cancer influences treatment selection for suspected early-stage lung cancer. High pre-treatment tissue confirmation rates are recommended. We sought to define management and outcomes of patients undergoing surgery for primary lung cancer in a UK multi-centre clinical trial. Methods: VIOLET compared minimally invasive video-assisted thoracic surgery versus open surgery for known or suspected lung cancer. Diagnostic patient pathways were identified and methods of tissue confirmation were documented. The outcome of inappropriate lobectomy for benign disease or inappropriate wedge resection for primary lung cancer was compared with respect to the pathologic diagnosis. Findings: From July 2015 to February 2019, 502 patients were randomised and underwent surgery; 262 \(52%\) had a pre-operative pathologic confirmed diagnosis of primary lung cancer, 205 did not have a pre-operative biopsy and 35 had a non-diagnostic pre-operative biopsy. Of the 240 participants without pre-operative pathologic confirmation of primary lung cancer, intraoperative biopsy and frozen section analysis was undertaken in 144 \(60%\). The remaining 96 underwent direct surgical resection without tissue confirmation \(19% of the entire cohort\). Confirmation of histologic diagnosis before surgery was less costly than diagnosis in the operating theatre. The inappropriate surgery rate was 3.6% \(18/502 participants, 7 lobectomy for benign disease, 11 wedge resection for lung cancer\). Interpretation: Low levels of inappropriate resection can be achieved at pre-operative tissue confirmation rates of 50% through a combination of intra-operative confirmatory biopsy and correct risk estimation of lung cancer. Practice needs to be monitored to ensure acceptable levels are consistently achieved.
- [Perioperative Detection Of Circulating Tumour Cells In Patients With Lung Cancer. | ScreenCell](https://www.screencell.com/en/scientific-articles/lung-cancer-publication/perioperative-detection-of-circulating-tumour-cells-in-patients-with-lung-cancer-2/): Lung cancer is a leading cause of mortality and despite surgical resection a proportion of patients may develop metastatic spread. The detection of circulating tumour cells \(CTCs\) may allow for improved prediction of metastatic spread and survival. The current study evaluates the efficacy of the ScreenCell® filtration device, to capture, isolate and propagate CTCs in patients with primary lung cancer. Prior to assessment of CTCs, the present study detected cancer cells in a proof‑of‑principle‑ experiment using A549 human lung carcinoma cells as a model. Ten patients \(five males and five females\) with pathologically diagnosed primary non‑small cell lung cancer undergoing surgical resection, had their blood tested for CTCs. Samples were taken from a peripheral vessel at the baseline, from the pulmonary vein draining the lobe containing the tumour immediately prior to division, a further central sample was taken following completion of the resection, and a final peripheral sample was taken three days post‑resection. A significant increase in CTCs was observed from baseline levels following lung manipulation. No association was able to be made between increased levels of circulating tumour cells and survival or the development of metastatic deposits. Manipulation of the lung during surgical resection for non‑small cell lung carcinoma results in a temporarily increased level of CTCs; however, no clinical impact for this increase was observed. Overall, the study suggests the ScreenCell® device has the potential to be used as a CTC isolation tool, following further work, adaptations and improvements to the technology and validation of results.
- [Prevalence And Number Of Circulating Tumour Cells And Microemboli At Diagnosis Of Advanced NSCLC | ScreenCell](https://www.screencell.com/en/scientific-articles/lung-cancer-publication/prevalence-and-number-of-circulating-tumour-cells-and-microemboli-at-diagnosis-of-advanced-nsclc-2/): Purpose Timing and magnitude of blood release of circulating tumour cells \(CTC\) and circulating tumour microemboli \(CTM\) from primary solid cancers are uncertain. We investigated prevalence and number of CTC and CTM at diagnosis of advanced non-small cell lung cancer \(NSCLC\). Methods Twenty-eight consecutive patients with suspected stage III–IV lung cancer gave consent to provide 15 mL of peripheral blood soon before diagnostic CT-guided fine-needle aspiration biopsy \(FNAB\). CTC and CTM \(clusters of ≥3 CTC\) were isolated by cell size filtration \(ScreenCell\), identified and counted by cytopathologists using morphometric criteria and \(in 6 cases\) immunostained for vimentin. Results FNAB demonstrated NSCLC in 26 cases. At least one CTC/3 mL blood \(mean 6.8 ± 3.7\) was detected in 17 \(65 %\) and one CTM \(mean 4.5 ± 3.3\) in 15 \(58 %\) of 26 NSCLC cases. No correlation between number of CTC or CTM and tumour type or stage was observed. Neoplastic cells from both FNA and CTC/CTM were positive for vimentin but heterogeneously. Conclusions CTC can be detected in two-thirds and CTM in more than half of patients with advanced NSCLC at diagnosis. Reasons underlying lack of CTC and CTM in some advanced lung cancers deserve further investigations.
- [Prognostic Relevance Of Circulating Tumor Cells And Circulating Cell-Free DNA Association In Metastatic Non-Small Cell Lung Cancer Treated With Nivolumab | ScreenCell](https://www.screencell.com/en/scientific-articles/lung-cancer-publication/prognostic-relevance-of-circulating-tumor-cells-and-circulating-cell-free-dna-association-in-metastatic-non-small-cell-lung-cancer-treated-with-nivolumab-2/): The treatment of advanced non-small cell lung cancer \(NSCLC\) has been revolutionized by immune checkpoint inhibitors \(ICIs\). The identification of prognostic and predictive factors in ICIs-treated patients is presently challenging. Circulating tumor cells \(CTCs\) and cell-free DNA \(cfDNA\) were evaluated in 89 previously treated NSCLC patients receiving nivolumab. Blood samples were collected before therapy and at the first and second radiological response assessments. CTCs were isolated by a filtration-based method. cfDNA was extracted from plasma and estimated by quantitative PCR. Patients with baseline CTC number and cfDNA below their median values \(2 and 836.5 ng from 3 mL of blood and plasma, respectively\) survived significantly longer than those with higher values \(p = 0.05 and p = 0.04, respectively\). The two biomarkers were then used separately and jointly as time-dependent covariates in a regression model confirming their prognostic role. Additionally, a four-fold risk of death for the subgroup presenting both circulating biomarkers above the median values was observed \(p < 0.001\). No significant differences were found between circulating biomarkers and best response. However, progressing patients with concomitant lower CTCs and cfDNA performed clinically well \(p = 0.007\), suggesting that jointed CTCs and cfDNA might help discriminate a low-risk population which might benefit from continuing ICIs beyond progression.
- [Y Disruption, Autosomal Hypomethylation And Poor Male Lung Cancer Survival. | ScreenCell](https://www.screencell.com/en/scientific-articles/lung-cancer-publication/y-disruption-autosomal-hypomethylation-and-poor-male-lung-cancer-survival-2/): Lung cancer is the most frequent cause of cancer death worldwide. It affects more men than women, and men generally have worse survival outcomes. We compared gene co-expression networks in affected and unaffected lung tissue from 126 consecutive patients with Stage IA–IV lung cancer undergoing surgery with curative intent. We observed marked degradation of a sex-associated transcription network in tumour tissue. This disturbance, detected in 27.7% of male tumours in the discovery dataset and 27.3% of male tumours in a further 123-sample replication dataset, was coincident with partial losses of the Y chromosome and extensive autosomal DNA hypomethylation. Central to this network was the epigenetic modifier and regulator of sexually dimorphic gene expression, KDM5D. After accounting for prognostic and epidemiological covariates including stage and histology, male patients with tumour KDM5D deficiency showed a significantly increased risk of death \(Hazard Ratio \[HR\] 3.80, 95% CI 1.40–10.3, P = 0.009\). KDM5D deficiency was confirmed as a negative prognostic indicator in a further 1100 male lung tumours \(HR 1.67, 95% CI 1.4–2.0, P = 1.2 × 10–10\). Our findings identify tumour deficiency of KDM5D as a prognostic marker and credible mechanism underlying sex disparity in lung cancer.
- [Isolation And Characterization Of Circulating Melanoma Cells By Size Filtration And Fluorescent In-situ Hybridization. | ScreenCell](https://www.screencell.com/en/scientific-articles/melanoma-publication/isolation-and-characterization-of-circulating-melanoma-cells-by-size-filtration-and-fluorescent-in-situ-hybridization-2/): Isolation of circulating tumor cells \(CTCs\) from blood of melanoma patients has been difficult owing to inconsistent expression of surface antigens. Here we report on the isolation, detection, and characterization of CTCs from blood of melanoma patients using microfiltration and fluorescent in-situ hybridization \(FISH\). Two tubes of blood from 15 patients with advanced melanoma were collected. These two tubes subsequently underwent filtration through a membrane with pore sizes of 7.5 μm. Isolated cells from one tube were analyzed by FISH for RREB1 \(6p24\), MYB \(6q32\), SE6 \(D6Z1\), and CCND1 \(11q13\) and the other paired specimen was analyzed by immunofluorescence for HMB45, melanoma-associated antigen recognized by T cells-1, tyrosinase and melanogenesis associated transcription factor. We identified CTCs in 10 out of 13 melanoma samples by immunofluorescence \(2.5–99 CTCs/3 ml of blood\) and in 13 specimens by FISH \(7.2–76 CTCs/3 ml of blood\) with more CTCs identified by FISH in 10 out 13 samples. Two filters failed. Our results show that CTCs are detectable in the majority of patients with advanced melanoma. These tools will be useful in characterizing treatment related changes of melanoma in CTCs.
- [Detection Of Circulating Tumor Cells In Patients With Adrenocortical Carcinoma: A Monocentric Preliminary Study | ScreenCell](https://www.screencell.com/en/scientific-articles/miscellaneous-publication/adrenocortical-carcinoma-publication/detection-of-circulating-tumor-cells-in-patients-with-adrenocortical-carcinoma-a-monocentric-preliminary-study-2/): Context: Adrenocortical carcinoma \(ACC\) is a rare malignancy, the prognosis of which is mainly dependent on stage at diagnosis. The identification of disease-associated markers for early diagnosis and drug monitoring is mandatory. Circulating tumor cells \(CTCs\) are released into the bloodstream from primary tumor/metastasis. CTC detection in blood samples may have enormous potential for assisting in the diagnosis of malignancy, estimating prognosis, and monitoring the disease. Objective: The aim of the study was to investigate the presence of CTCs in blood samples of patients with ACC or benign adrenocortical adenoma \(ACA\). Setting: We conducted the study at a university hospital. Intervention: CTC analysis was performed in blood samples from 14 ACC patients and 10 ACA patients. CTCs were isolated on the basis of cell size by filtration through ScreenCell devices, followed by identification according to validated morphometric criteria and immunocytochemistry. Main Outcome Measure: We measured the difference in CTC detection between ACC and ACA. Results: CTCs were detected in all ACC samples, but not in ACA samples. Immunocytochemistry confirmed the adrenocortical origin. When ACC patients were stratified according to the median value of tumor diameter and metastatic condition, a statistically significant difference was found in the number of CTCs detected after surgery. A significant correlation between the number of CTCs in postsurgical samples and clinical parameters was found for tumor diameter alone. Conclusions: Our findings provide the first evidence for adrenocortical tumors that CTCs may represent a useful marker to support differential diagnosis between ACC and ACA. The correlation with some clinical parameters suggests a possible relevance of CTC analysis for prognosis and noninvasive monitoring of disease progression and drug response.
- [Cancer-associated Macrophage-like Cells In Patients With Non-metastatic Adenocarcinoma Of The Esophagus - Cytomorphological Heterogeneity | ScreenCell](https://www.screencell.com/en/scientific-articles/miscellaneous-publication/esophageal-adenocarcinoma-publication/cancer-associated-macrophage-like-cells-in-patients-with-non-metastatic-adenocarcinoma-of-the-esophagus-cytomorphological-heterogeneity-2/): Introduction: Esophageal adenocarcinoma \(EAC\) often recurs systemically despite therapy with a curative aim. New diagnostic and therapeutic approaches are urgently needed. A promising field is liquid biopsy, meaning the investigation of tumor-associated cells in the peripheral blood, for example cancer-associated macrophage-like cells \(CAML\). The aim of this multicentric study was to investigate the presence and cytomorphological appearance of CAML in patients with non-metastatic and operable esophageal cancer. Methods: Blood samples from 252 patients with locally advanced EAC were obtained before starting curative treatment including surgery, and then processed using ScreenCell® filtration devices. Cytological analysis was performed via May-Grünwald-Giemsa staining. CAML were defined by their morphological characteristics. We also performed immunofluorescence staining with the mesenchymal marker vimentin on a subset of our study cohort. Results: We detected cytomorphologically heterogeneous CAML in 31.8% \(n=80\) patients. Their presence and cell count did not correlate significantly with pretherapeutic cTNM. Even in patients with small tumors and no lymph-node infiltration, cell counts were high. CAML showed heterogenous staining patterns for vimentin. Conclusion: This is one of the first studies demonstrating the presence and phenotype of CAML in a uniquely broad cohort of EAC patients. As they are believed to be representatives of the inflammatory tumor microenvironment shed into the bloodstream, their presence in non-metastatic EAC is a promising finding.
- [Cytopathological Heterogeneity Of Circulating Tumor Cells In Non-metastatic Esophageal Adenocarcinoma | ScreenCell](https://www.screencell.com/en/scientific-articles/miscellaneous-publication/esophageal-adenocarcinoma-publication/cytopathological-heterogeneity-of-circulating-tumor-cells-in-non-metastatic-esophageal-adenocarcinoma-2/): Background/Aim: The presence of circulating tumor cells \(CTC\) has been reported to have an impact on prognosis in different tumor entities. Little is known about CTC morphology and heterogeneity. Patients and Methods: In a multicenter setting, pre-therapeutic peripheral blood specimens were drawn from patients with non-metastatic esophageal adenocarcinoma \(EAC\). CTCs were captured by size-based filtration \(ScreenCell®\), subsequently Giemsa-stained and evaluated by two trained readers. The isolated cells were categorized in groups based on morphologic criteria. Results: Small and large single CTCs, as well as CTC-clusters, were observed in 69.2% \(n=81\) of the 117 specimens; small CTCs were observed most frequently \(59%; n=69\), followed by large CTCs \(40%; n=47\) and circulating cancer-associated macrophage-like cells \(CAMLs; 34.2%, n=40\). Clusters were rather rare \(12%; n=14\). CTC/CAML were heterogeneous in the cohort, but also within one specimen. Neither the presence of the CTC subtypes/CAMLs nor the exact cell count were associated with the primary clinical TNM stage. Conclusion: Morphologically heterogenic CTCs and CAMLs are present in patients with non-metastatic, non-pretreated EAC.
- [Non-Metastatic Esophageal Adenocarcinoma: Circulating Tumor Cells In The Course Of Multimodal Tumor Treatment | ScreenCell](https://www.screencell.com/en/scientific-articles/miscellaneous-publication/esophageal-adenocarcinoma-publication/non-metastatic-esophageal-adenocarcinoma-circulating-tumor-cells-in-the-course-of-multimodal-tumor-treatment-2/): Background: Isolation of circulating tumor cells \(CTC\) holds the promise to improve response-prediction and personalization of cancer treatment. In this study, we test a filtration device for CTC isolation in patients with non-metastatic esophageal adenocarcinoma \(EAC\) within recent multimodal treatment protocols. Methods: Peripheral blood specimens were drawn from EAC patients before and after neoadjuvant chemotherapy \(FLOT\)/chemoradiation \(CROSS\) as well as after surgery. Filtration using ScreenCell® devices captured CTC for cytologic analysis. Giemsa-stained specimens were evaluated by a cytopathologist; the cut-off was 1 CTC/specimen \(6 mL\). Immunohistochemistry with epithelial \(pan-CK\) and mesenchymal markers \(vimentin\) was performed. Results: Morphologically diverse malignant CTCs were found in 12/20 patients in at least one blood specimen. CTCs were positive for both vimentin and pan-CK. More patients were CTC positive after neoadjuvant therapy \(6/20 vs. 9/15\) and CTCs per/ml increased in most of the CTC-positive patients. After surgery, 8/13 patients with available blood specimens were still CTC positive. In clinical follow-up, 5/9 patients who died were CTC-positive. Conclusions: Detection of CTC by filtration within multimodal treatment protocols of non-metastatic EAC is feasible. The rate of CTC positive findings and the quantity of CTCs changes in the course of multimodal neoadjuvant chemoradiation/chemotherapy and surgery.
- [Liquid Biopsy In Rare Cancers: Lessons From Hemangiopericytoma. | ScreenCell](https://www.screencell.com/en/scientific-articles/miscellaneous-publication/hemangiopericytoma-publication/liquid-biopsy-in-rare-cancers-lessons-from-hemangiopericytoma-2/): Hemangiopericytoma \(HPT\) is a rare mesenchymal tumor of fibroblastic type and for its rarity is poorly studied. The most common sites of metastatic disease in patients with intracranial HPT are the bone, liver, and lung, suggestive for an hematogenous dissemination; for this reason, we investigated, for the first time, the presence of circulating tumor cells \(CTCs\) in hemangiopericytoma patient by CellSearch® and SceenCell® devices. Peripheral blood samples were drawn and processed by CellSearch, an EpCAM-dependent device, and ScreenCell®, a device size based. We found nontypical CTCs by CellSearch system and the immunofluorescence analysis performed on CTCs isolate by ScreenCell demonstrated the presence of single CTCs and CTC clusters. The molecular characterization of single CTCs and CTC clusters, using antibodies directed against EpCAM, CD34, cytokeratins \(8, 18, and 19\), and CD45, showed a great heterogeneity in CTC clusters. We believe that the present study may open a new scenario in the rare tumors: the introduction of the liquid biopsy and the molecular characterization of circulating tumor cells could lead to personalized targeted treatments and also for rare tumors.
- [Rapid Separation Of Mononuclear Hodgkin From Multinuclear Reed-sternberg Cells | ScreenCell](https://www.screencell.com/en/scientific-articles/miscellaneous-publication/hodgkins-lymphoma-publication/rapid-separation-of-mononuclear-hodgkin-from-multinuclear-reed-sternberg-cells-2/): We describe a method to isolate small mononucleated Hodgkin \(H\) cells from multinucleated Reed Sternberg \(RS\) cells of Hodgkin lymphoma using the ScreenCell filter device. This filtration-based approach lends itself to future clinical applications in that it enables the separation of H and RS cells from lymph node biopsies, bone marrow aspirates, pleural effusions, and blood, including the isolation of monoclonal Hodgkin precursor cells from the blood.
- [A New Device For Rapid Isolation By Size And Characterization Of Rare Circulating Tumor Cells | ScreenCell](https://www.screencell.com/en/scientific-articles/miscellaneous-publication/proof-of-concept-publication/a-new-device-for-rapid-isolation-by-size-and-characterization-of-rare-circulating-tumor-cells-2/): Background: Circulating tumor cells \(CTCs\) likely derive from clones in the primary tumor, suggesting that they can be used for all biological tests applying to the primary cells. Materials and Methods: The ScreenCell® devices are single-use and low-cost innovative devices that use a filter to isolate and sort tumor cells by size. Results: The ScreenCell® Cyto device is able to isolate rare, fixed, tumor cells, with a high recovery rate. Cells are well preserved morphologically. Immunocytochemistry and FISH assays can be performed directly on the filter. The ScreenCell® CC device allows isolation of live cells able to grow in culture. High quality genetic materials can be obtained directly from tumor cells isolated on the ScreenCell® MB device filter. Conclusion: Due to their reduced size, versatility, and capacity to isolate CTCs within minutes, the ScreenCell® devices may be able to simplify and improve non-invasive access to tumor cells.
- [Thoracic Surgery In The UK | ScreenCell](https://www.screencell.com/en/scientific-articles/miscellaneous-publication/thoracic-surgery-publication/thoracic-surgery-in-the-uk-2/): No description available.
- [Rapid And Simple Isolation Of Circulating Tumor Cells For Clinical And Research Applications Using ScreenCell ® | ScreenCell](https://www.screencell.com/en/scientific-articles/miscellaneous-publication/white-paper-publication/rapid-and-simple-isolation-of-circulating-tumor-cells-for-clinical-and-research-applications-using-screencell-2/): Circulating tumor cells \(CTCs\) are malignant cells shed by the primary tumor or metastases into the peripheral circulation. CTCs give rise to distant metastases that are usually the ultimate cause of cancer-related death. A significant proportion of patients with early stage cancer in whom no metastases are identifiable will ultimately relapse as a result of hematogenous spread of tumor cells that were undetected at initial diagnosis and treatment.
- [Isolation And Profiling Of Single Circulating Tumor Cells In Myeloma: A New Workflow For Liquid Biopsies. | ScreenCell](https://www.screencell.com/en/scientific-articles/myeloma/isolation-and-profiling-of-single-circulating-tumor-cells-in-myeloma-a-new-workflow-for-liquid-biopsies-2/): Minimal residual disease \(MRD\) is a key prognostic marker for progression-free and overall survival in multiple myeloma \(MM\). Existing high sensitivity assays primarily focus on tumor burden assessment, rely on bone marrow sampling, and are limited in their ability to support frequent longitudinal disease monitoring. Here, we describe a proof-of-principle workflow for isolating morphologically preserved circulating tumor cells \(CTCs\) from peripheral blood \(PB\) using size-based filtration. Based on controlled spiking experiments with RPMI 8226 myeloma cells, we demonstrate an analytical limit of detection of approximately 1 tumor cell per 107 white blood cells. Isolated cells retain nuclear integrity and cytomorphology, allowing for downstream immuno­phenotyping, three-dimensional \(3D\) telomere fluorescence in situ hybridization \(FISH\), and single-cell telomere profiling, a known marker of genomic instability and disease progression in multiple myeloma. The proposed workflow demonstrated its feasibility for isolating, profiling, and analyzing plasma cells from PB of MM patients at different disease stages. It revealed distinct nuclear and telomeric features in MM CTCs compared with normal lymphocytes. The established technically robust liquid biopsy workflow enables 3D telomere profiling of MM CTCs that can be adopted for noninvasive MRD monitoring based on genomic instability rather than on the enumeration of MM plasma cells alone.
- [Circulating Epithelial Cells In Patients With Pancreatic Lesions: Clinical And Pathologic Findings | ScreenCell](https://www.screencell.com/en/scientific-articles/pancreatic-cancer-publication/circulating-epithelial-cells-in-patients-with-pancreatic-lesions-clinical-and-pathologic-findings-2/): Background Circulating epithelial cell \(CEC\) isolation has provided diagnostic and prognostic information for a variety of cancers, previously supporting their identity as circulating tumor cells in the literature. However, we report CEC findings in patients with benign, premalignant, and malignant pancreatic lesions using a size-selective filtration device. Study Design Peripheral blood samples were drawn from patients found to have pancreatic lesions on preoperative imaging at a surgical clinic. Blood was filtered using ScreenCell devices, which were evaluated microscopically by a pancreatic cytopathologist. Pathologic data and clinical outcomes of these patients were obtained from medical records during a 1-year follow-up period. Results Nine healthy volunteers formed the control group and were found to be negative for CECs. There were 179 patients with pancreatic lesions that formed the study cohort. Circulating epithelial cells were morphologically similar in patients with a variety of pancreatic lesions. Specifically, CECs were identified in 51 of 105 pancreatic ductal adenocarcinomas \(49%\), 7 of 11 neuroendocrine tumors \(64%\), 13 of 21 intraductal papillary mucinous neoplasms \(62%\), and 6 of 13 patients with chronic pancreatitis. Rates of CEC identification were similar in patients with benign, premalignant, and malignant lesions \(p = 0.41\). In addition, CEC findings in pancreatic ductal adenocarcinoma patients were not associated with poor prognosis. Conclusions Although CECs were not identified in healthy volunteers, they were identified in patients with benign, premalignant, and malignant pancreatic lesions. The presence of CECs in patients presenting with pancreatic lesions is neither diagnostic of malignancy nor prognostic for patients with pancreatic ductal adenocarcinoma.
- [Circulating Tumor Cells Found In Patients With Localized And Advanced Pancreatic Cancer | ScreenCell](https://www.screencell.com/en/scientific-articles/pancreatic-cancer-publication/circulating-tumor-cells-found-in-patients-with-localized-and-advanced-pancreatic-cancer-2/): Objectives Isolation of circulating tumor cells \(CTCs\) holds the promise of diagnosing and molecular profiling cancers from a blood sample. Here, we test a simple new low-cost filtration device for CTC isolation in patients with pancreatic ductal adenocarcinoma \(PDAC\). Methods Peripheral blood samples drawn from healthy donors and PDAC patients were filtered using ScreenCell devices, designed to capture CTCs for cytologic and molecular analysis. Giemsa-stained specimens were evaluated by a pancreatic cytopathologist blinded to the histological diagnosis. Circulating tumor cell DNA was subjected to KRAS mutational analysis. Results Spiking experiments demonstrated a CTC capture efficiency as low as 2 cells/mL of blood. Circulating tumor cells were identified by either malignant cytology or presence of KRAS mutation in 73% of 11 patients \(P = 0.001\). Circulating tumor cells were identified in 3 of 4 patients with early \(≤American Joint Committee on Cancer stage IIB\) and in 5 of 7 patients with advanced \(≥ American Joint Committee on Cancer stage III\) PDAC. No CTCs were detected in blood from 9 health donors. Conclusions Circulating tumor cells can be found in most patients with PDAC of any stage, whether localized, locally advanced, or metastatic. The ability to capture, cytologically identify, and genetically analyze CTCs suggests a possible tool for the diagnosis and characterization of genetic alterations of PDAC.
- [Cytologic Characteristics Of Circulating Epithelioid Cells In Pancreatic Disease | ScreenCell](https://www.screencell.com/en/scientific-articles/pancreatic-cancer-publication/cytologic-characteristics-of-circulating-epithelioid-cells-in-pancreatic-disease-2/): BACKGROUND Circulating epithelioid cells \(CECs\), also known as circulating tumor, circulating cancer, circulating epithelial, or circulating nonhematologic cells, are a prognostic factor in various malignancies that can be isolated via various protocols. In the current study, the authors analyzed the cytomorphologic characteristics of CECs isolated by size in a cohort of patients with benign and malignant pancreatic diseases to determine whether cytomorphological features could predict CEC origin. METHODS Blood samples were collected from 9 healthy controls and 171 patients with pancreatic disease who were presenting for surgical evaluation before treatment. Blood was processed with the ScreenCell size-based filtration device. Evaluable CECs were analyzed in a blinded fashion for cytomorphologic characteristics, including cellularity; nucleoli; nuclear size, irregularity, variability, and hyperchromasia; and nuclear-to-cytoplasmic ratio. Statistical differences between variables were analyzed via the Fisher exact test. RESULTS No CECs were identified among the 9 normal healthy controls. Of the 115 patients with CECs \(positive or suspicious for\), 25 had nonmalignant disease and 90 had malignancy. There were no significant differences in any of the cytologic criteria noted between groups divided by benign versus malignant, neoplastic versus nonneoplastic, or pancreatic ductal adenocarcinoma versus neuroendocrine tumor. CONCLUSIONS CECs were observed in patients with malignant and nonmalignant pancreatic disease, but not in healthy controls. There were no morphologic differences observed between cells from different pancreatic diseases, suggesting that numerous conditions may be associated with CECs in the circulation and that care must be taken not to overinterpret cells identified by cytomorphology as indicative of circulating tumor cells of pancreatic cancer. Additional studies are required to determine the origin and clinical significance of these cells. Cancer Cytopathol 2017;125:332–340. © 2017 American Cancer Society.
- [Expression Profiling Of Circulating Tumor Cells In Pancreatic Ductal Adenocarcinoma Patients: Biomarkers Predicting Overall Survival | ScreenCell](https://www.screencell.com/en/scientific-articles/pancreatic-cancer-publication/expression-profiling-of-circulating-tumor-cells-in-pancreatic-ductal-adenocarcinoma-patients-biomarkers-predicting-overall-survival-2/): The interest in liquid biopsy is growing because it could represent a non-invasive prognostic or predictive tool for clinical outcome in patients with pancreatic ductal adenocarcinoma \(PDAC\), an aggressive and lethal disease. In this pilot study, circulating tumor cells \(CTCs\), CD16 positive atypical CTCs, and CTC clusters were captured and characterized in the blood of patients with PDAC before and after palliative first line chemotherapy by ScreenCell device, immunohistochemistry, and confocal microscopy analysis. Gene profiles were performed by digital droplet PCR in isolated CTCs, five primary PDAC tissues, and three different batches of RNA from normal human pancreatic tissue. Welsh's t-test, Kaplan-Meier survival, and Univariate Cox regression analyses have been performed. Statistical analysis revealed that the presence of high CTC number in blood is a prognostic factor for poor overall survival and progression free survival in advanced PDAC patients, before and after first line chemotherapy. Furthermore, untreated PDAC patients with CTCs, characterized by high ALCAM, POU5F1B, and SMO mRNAs expression, have shorter progression free survival and overall survival compared with patients expressing the same biomarkers at low levels. Finally, high SHH mRNA levels are negatively associated to progression free survival, whereas high vimentin mRNA levels are correlated with the most favorable prognosis. By hierarchical clustering and correlation index analysis, two cluster gene signatures were identified in CTCs: the first, with high expression of VEGFA, NOTCH1, EPCAM, IHH, is the signature of PDAC patients before chemotherapy, whereas the second, with an enrichment in the expression of CD44, ALCAM, and POU5F1B stemness and pluripotency genes, is reported after palliative chemotherapy. Overall our data support the clinic value of the identification of CTC's specific biomarkers to improve the prognosis and the therapy in advanced PDAC patients.
- [KRAS Mutations In Pancreatic Circulating Tumor Cells: A Pilot Study | ScreenCell](https://www.screencell.com/en/scientific-articles/pancreatic-cancer-publication/kras-mutations-in-pancreatic-circulating-tumor-cells-a-pilot-study-2/): Pancreatic ductal adenocarcinoma \(PDAC\) is most often diagnosed in a metastatic stage. Circulating tumor cells \(CTC\) in the blood are hypothesized as the means of systemic dissemination. We aimed to isolate and characterize CTC to evaluate their significance as prognostic markers in PDAC. Blood obtained from healthy donors and patients with PDAC before therapy was filtered with ScreenCell® filtration devices for size-based CTC isolation. Captured cells were analyzed by immunofluorescence for an epithelial to mesenchymal transition \(EMT\) marker \(zinc finger E-box binding homebox 1 \(ZEB1\)\) and an epithelial antigen \(cytokeratin \(CK\)\). Molecular analysis of parallel specimens evaluated the KRAS mutation status of the CTC. The survival of each patient after study was recorded. As demonstrated by either cytology or finding of a KRAS mutation, CTC were detected in 18 of 21 patients \(86 %\) with proven PDAC: 8 out of 10 patients \(80 %\) with early stage \(UICC IIA/IIB\) and 10 out of 11 \(91 %\) with late stage \(UICC III/IV\) disease. CTC were not found in any of the 10 control patients \(p
- [Usefulness Of Circulating Tumor Cell Detection In Pancreatic Adenocarcinoma Diagnosis. | ScreenCell](https://www.screencell.com/en/scientific-articles/pancreatic-cancer-publication/usefulness-of-circulating-tumor-cell-detection-in-pancreatic-adenocarcinoma-diagnosis-2/): No description available.
- [Advancing Risk Assessment Of Intermediate Risk Prostate Cancer Patients | ScreenCell](https://www.screencell.com/en/scientific-articles/prostate-cancer-publication/advancing-risk-assessment-of-intermediate-risk-prostate-cancer-patients-2/): The individual risk to progression is unclear for intermediate risk prostate cancer patients. To assess their risk to progression, we examined the level of genomic instability in circulating tumor cells \(CTCs\) using quantitative three-dimensional \(3D\) telomere analysis. Data of CTCs from 65 treatment-naïve patients with biopsy-confirmed D’Amico-defined intermediate risk prostate cancer were compared to radical prostatectomy pathology results, which provided a clinical endpoint to the study and confirmed pre-operative pathology or demonstrated upgrading. Hierarchical centroid cluster analysis of 3D pre-operative CTC telomere profiling placed the patients into three subgroups with different potential risk of aggressive disease. Logistic regression modeling of the risk of progression estimated odds ratios with 95% confidence interval \(CI\) and separated patients into “stable” vs. “risk of aggressive” disease. The receiver operating characteristic \(ROC\) curve showed an area under the curve \(AUC\) of 0.77, while prostate specific antigen \(PSA\) \(AUC of 0.59\) and Gleason 3 + 4 = 7 vs. 4 + 3 = 7 \(p > 0.6\) were unable to predict progressive or stable disease. The data suggest that quantitative 3D telomere profiling of CTCs may be a potential tool for assessing a patient’s prostate cancer pre-treatment risk.
- [Circulating Tumour Cell Numbers Correlate With Platelet Count And Circulating Lymphocyte Subsets In Men With Advanced Prostate Cancer: Data From The ExPeCT Clinical Trial \(CTRIAL-IE 15-21\). | ScreenCell](https://www.screencell.com/en/scientific-articles/prostate-cancer-publication/circulating-tumour-cell-numbers-correlate-with-platelet-count-and-circulating-lymphocyte-subsets-in-men-with-advanced-prostate-cancer-data-from-the-expect-clinical-trial-ctrial-ie-15-21-2/): Interactions between circulating tumour cells \(CTCs\) and platelets are thought to inhibit natural killer\(NK\)-cell-induced lysis. We attempted to correlate CTC numbers in men with advanced prostate cancer with platelet counts and circulating lymphocyte numbers. Sixty-one ExPeCT trial participants, divided into overweight/obese and normal weight groups on the basis of a BMI ≥ 25 or
- [Development And Validation Of Circulating Tumour Cell Enumeration \(Epic Sciences\) As A Prognostic Biomarker In Men With Metastatic Castration-resistant Prostate Cancer | ScreenCell](https://www.screencell.com/en/scientific-articles/prostate-cancer-publication/development-and-validation-of-circulating-tumour-cell-enumeration-epic-sciences-as-a-prognostic-biomarker-in-men-with-metastatic-castration-resistant-prostate-cancer-2/): Purpose To evaluate the prognostic significance of circulating tumour cell \(CTC\) number determined on the Epic Sciences platform in men with metastatic castration-resistant prostate cancer \(mCRPC\) treated with an androgen receptor signalling inhibitor \(ARSI\). Patients and methods A pre-treatment blood sample was collected from men with progressing mCRPC starting either abiraterone or enzalutamide as a first-, second- or third-line systemic therapy at Memorial Sloan Kettering Cancer Center \(Discovery cohort, N = 171\) or as a first- or second-line therapy as part of the multicenter PROPHECY trial \(NCT02269982\) \(Validation cohort, N = 107\). The measured CTC number was then associated with overall survival \(OS\) in the Discovery cohort, and progression-free survival \(PFS\) and OS in the Validation cohort. CTC enumeration was also performed on a concurrently obtained blood sample using the CellSearch® Circulating Tumor Cell Kit. Results In the MSKCC Discovery cohort, CTC count was a statistically significant prognostic factor of OS as a dichotomous \(
- [Filtration-based Enrichment Of Circulating Tumor Cells From All Prostate Cancer Risk Groups | ScreenCell](https://www.screencell.com/en/scientific-articles/prostate-cancer-publication/filtration-based-enrichment-of-circulating-tumor-cells-from-all-prostate-cancer-risk-groups-2/): Objective To combine circulating tumor cell \(CTC\) isolation by filtration and immunohistochemistry to investigate the presence of CTCs in low, intermediate, and high-risk prostate cancer \(PCa\). CTCs isolated from these risk groups stained positive for both cytokeratin and androgen receptors, but negative for CD45. Patients and methods Blood samples from 41 biopsy confirmed patients with PCa at different clinical stages such as low, intermediate, and high risk were analyzed. The samples were processed with the ScreenCell filtration device and PCa CTCs were captured for all patients. The isolated CTCs were confirmed PCa CTCs by the presence of androgen receptors and cytokeratins 8, 18, and 19 that occurred in the absence of CD45 positivity. PCa CTC nuclear sizes were measured using the TeloView program. Results The filtration-based isolation method used permitted the measurement of the average nuclear size of the captured CTCs. CTCs were identified by immunohistochemistry in low, intermediate, and high-risk groups of patients with PCa. Conclusion CTCs may be found in all stages of PCa. These CTCs can be used to determine the level of genomic instability at any stage of PCa; this will, in the future, enable personalized patient management.
- [Genomic Analysis Of Localized High-Risk Prostate Cancer Circulating Tumor Cells At The Single-Cell Level | ScreenCell](https://www.screencell.com/en/scientific-articles/prostate-cancer-publication/genomic-analysis-of-localized-high-risk-prostate-cancer-circulating-tumor-cells-at-the-single-cell-level-2/): Accurate risk classification of men with localized high-risk prostate cancer directly affects treatment management decisions and patient outcomes. A wide range of risk assessments and classifications are available. However, each one has significant limitations to distinguish between indolent and aggressive prostate cancers. Circulating tumor cells \(CTCs\) may provide an alternate additional source, beyond tissue biopsies, to enable individual patient-specific clinical assessment, simply because CTCs can reveal both tumor-derived and germline-specific genetic information more precisely than that gained from a single diagnostic biopsy. In this study, we combined a filtration-based CTC isolation technology with prostate cancer CTC immunophenotyping to identify prostate cancer CTCs. Next, we performed 3-D telomere profiling prior to laser microdissection and single-cell whole-exome sequencing \(WES\) of 21 CTCs and 4 lymphocytes derived from 10 localized high-risk prostate cancer patient samples. Localized high-risk prostate cancer patient CTCs present a high number of telomere signals with lower signal intensities \(short telomeres\). To capture the genetic diversity/heterogeneity of high-risk prostate cancer CTCs, we carried out whole-exome sequencing. We identified 202,241 single nucleotide variants \(SNVs\) and 137,407 insertion-deletions \(indels\), where less than 10% of these genetic variations were within coding regions. The genetic variation \(SNVs + indels\) and copy number alteration \(CNAs\) profiles were highly heterogeneous and intra-patient CTC variation was observed. The pathway enrichment analysis showed the presence of genetic variation in nine telomere maintenance pathways \(patients 3, 5, 6, and 7\), including an important gene for telomere maintenance called telomeric repeat-binding factor 2 \(TRF2\). Using the PharmGKB database, we identified nine genetic variations associated with response to docetaxel. A total of 48 SNVs can affect drug response for 24 known cancer drugs. Gene Set Enrichment Analysis \(GSEA\) \(patients 1, 3, 6, and 8\) identified the presence of CNAs in 11 different pathways, including the DNA damage repair \(DDR\) pathway. In conclusion, single-cell approaches \(WES and 3-D telomere profiling\) showed to be useful in unmasking CTC heterogeneity. DDR pathway mutations have been well-established as a target pathway for cancer therapy. However, the frequent CNA amplifications found in localized high-risk patients may play critical roles in the therapeutic resistance in prostate cancer.
- [Long-Term Dynamics Of Three Dimensional Telomere Profiles In Circulating Tumor Cells In High-Risk Prostate Cancer Patients Undergoing Androgen-Deprivation And Radiation Therapy | ScreenCell](https://www.screencell.com/en/scientific-articles/prostate-cancer-publication/long-term-dynamics-of-three-dimensional-telomere-profiles-in-circulating-tumor-cells-in-high-risk-prostate-cancer-patients-undergoing-androgen-deprivation-and-radiation-therapy-2/): Patient-specific assessment, disease monitoring, and the development of an accurate early surrogate of the therapeutic efficacy of locally advanced prostate cancer still remain a clinical challenge. Contrary to prostate biopsies, circulating tumor cell \(CTC\) collection from blood is a less-invasive method and has potential as a real-time liquid biopsy and as a surrogate marker for treatment efficacy. In this study, we used size-based filtration to isolate CTCs from the blood of 100 prostate cancer patients with high-risk localized disease. CTCs from five time points: +0, +2, +6, +12 and +24 months were analyzed. Consenting treatment-naïve patients with cT3, Gleason 8-10, or prostate-specific antigen > 20 ng/mL and non-metastatic prostate cancer were included. For all time points, we performed 3D telomere-specific quantitative fluorescence in situ hybridization on a minimum of thirty isolated CTCs. The patients were divided into five groups based on the changes of number of telomeres vs. telomere lengths over time and into three clusters based on all telomere parameters found on diagnosis. Group 2 was classified as non-respondent to treatment and the Cluster 3 presented more aggressive phenotype. Additionally, we compared our telomere results with the PSA levels for each patient at 6 months of ADT, at 6 months of completed RT, and at 36 months post-initial therapy. CTCs of patients with PSA levels above or equal to 0.1 ng/mL presented significant increases of nuclear volume, number of telomeres, and telomere aggregates. The 3D telomere analysis of CTCs identified disease heterogeneity among a clinically homogeneous group of patients, which suggests differences in therapeutic responses. Our finding suggests a new opportunity for better treatment monitoring of patients with localized high-risk prostate cancer.
- [Platinum-Based Chemotherapy In Metastatic Prostate Cancer With DNA Repair Gene Alterations | ScreenCell](https://www.screencell.com/en/scientific-articles/prostate-cancer-publication/platinum-based-chemotherapy-in-metastatic-prostate-cancer-with-dna-repair-gene-alterations-2/): Purpose Alterations in DNA damage repair \(DDR\) genes occur in up to 25% of patients with metastatic castration-resistant prostate cancer \(mCRPC\) and may sensitize to platinum chemotherapy. We aimed to evaluate the efficacy of platinum-based chemotherapy in DDR-mutant \(DDRmut\) mCRPC. Methods We assessed response to platinum chemotherapy based on DDR gene alteration status in men with mCRPC who underwent tumor and germline genomic profiling. Patients with deleterious alterations in a gene panel that included BRCA2, BRCA1, ATM, PALB2, FANCA, and CDK12 were considered DDRmut. Results A total of 109 patients with mCRPC received platinum-based chemotherapy between October 2013 and July 2018. Sixty-four of 109 patients were taxane refractory and poly \(ADP-ribose\) polymerase inhibitor \(PARPi\) naïve. Within this subset, DDRmut was found in 16/64 patients \(25%\) and was associated with an increased likelihood of achieving a prostate-specific antigen \(PSA\) decline of 50% or more from baseline \(PSA50; odds ratio, 7.0; 95% CI, 1.9 to 29.2\). Time on platinum chemotherapy tended to be longer in the DDRmut group \(median, 3.0 v 1.6 months; hazard ratio, 0.55, 95% CI, 0.29 to 1.24\). No difference in survival was detected. Of 8 patients with DDRmut disease who received platinum-based therapy after a PARPi, 3/7 evaluable patients had radiographic partial response or stable disease, and 2/7 had a PSA50 response. None of 4 patients with ATM mutations had platinum responses regardless of prior PARPi exposure. Conclusion Patients with DDRmut disease had better response to platinum-based chemotherapy, suggesting that DDR status warrants prospective validation as a potential biomarker for patient selection. Responses to platinum chemotherapy were observed in BRCA-altered prostate cancer after PARPi progression. Additional studies are needed to determine the predictive role of individual genes on platinum sensitivity in the context of other clinical and genomic factors.
- [Prospective Multicenter Study Of Circulating Tumor Cell AR-V7 And Taxane Versus Hormonal Treatment Outcomes In Metastatic Castration-Resistant Prostate Cancer | ScreenCell](https://www.screencell.com/en/scientific-articles/prostate-cancer-publication/prospective-multicenter-study-of-circulating-tumor-cell-ar-v7-and-taxane-versus-hormonal-treatment-outcomes-in-metastatic-castration-resistant-prostate-cancer-3/): Purpose Androgen receptor splice variant 7 \(AR-V7\) detection in circulating tumor cells \(CTCs\) is associated with a low probability of response and short progression-free \(PFS\) and overall survival \(OS\) in men with metastatic castration-resistant prostate cancer \(mCRPC\) treated with enzalutamide or abiraterone. However, it is unclear whether such men benefit from taxane chemotherapy. Patients and Methods PROPHECY is a multicenter prospective blinded study of patients with poor-risk mCRPC starting abiraterone or enzalutamide and observed through subsequent progression and taxane chemotherapy. We assessed AR-V7 status using the Johns Hopkins modified AdnaTest CTC AR-V7 messenger RNA assay and the Epic Sciences CTC nuclear-localized AR-V7 protein assay before treatment. The primary objective was to validate the independent prognostic value of CTC AR-V7 status based on radiographic/clinical PFS. OS, confirmed prostate-specific antigen \(PSA\), and objective radiologic responses were secondary end points. Results We enrolled 118 men with mCRPC treated with abiraterone or enzalutamide, 51 of whom received subsequent docetaxel or cabazitaxel. Pretreatment CTC AR-V7 status by the Johns Hopkins and Epic Sciences assays was independently associated with worse PFS \(hazard ratio \[HR\], 1.7; 95% CI, 1.0 to 2.9 and HR, 2.1; 95% CI, 1.0 to 4.4, respectively\) and OS \(HR, 3.3; 95% CI, 1.7 to 6.3 and HR, 3.0; 95% CI, 1.4 to 6.3, respectively\) and a low probability of confirmed PSA responses, ranging from 0% to 11%, during treatment with abiraterone or enzalutamide. At progression, subsequent CTC AR-V7 detection was not associated with an inferior PSA or radiographic response or worse PFS or OS with subsequent taxane chemotherapy after adjusting for CellSearch CTC enumeration and clinical prognostic factors. Conclusion Detection of AR-V7 in CTCs by two different blood-based assays is independently associated with shorter PFS and OS with abiraterone or enzalutamide, but such men with AR-V7–positive disease still experience clinical benefits from taxane chemotherapy.
- [Single-cell Analysis Of Circulating Tumor Cells Identifies Cumulative Expression Patterns Of EMT-related Genes In Metastatic Prostate Cancer | ScreenCell](https://www.screencell.com/en/scientific-articles/prostate-cancer-publication/single-cell-analysis-of-circulating-tumor-cells-identifies-cumulative-expression-patterns-of-emt-related-genes-in-metastatic-prostate-cancer-2/): BACKGROUND Prostate tumors shed circulating tumor cells \(CTCs\) into the blood stream. Increased evidence shows that CTCs are often present in metastatic prostate cancer and can be alternative sources for disease profiling and prognostication. Here we postulate that CTCs expressing genes related to epithelial–mesenchymal transition \(EMT\) are strong predictors of metastatic prostate cancer. METHODS A microfiltration system was used to trap CTCs from peripheral blood based on size selection of large epithelial-like cells without CD45 leukocyte marker. These cells individually retrieved with a micromanipulator device were assessed for cell membrane physical properties using atomic force microscopy. Additionally, 38 CTCs from eight prostate cancer patients were used to determine expression profiles of 84 EMT-related and reference genes using a microfluidics-based PCR system. RESULTS Increased cell elasticity and membrane smoothness were found in CTCs compared to noncancerous cells, highlighting their potential invasiveness and mobility in the peripheral circulation. Despite heterogeneous expression patterns of individual CTCs, genes that promote mesenchymal transitioning into a more malignant state, including IGF1, IGF2, EGFR, FOXP3, and TGFB3, were commonly observed in these cells. An additional subset of EMT-related genes \(e.g., PTPRN2, ALDH1, ESR2, and WNT5A\) were expressed in CTCs of castration-resistant cancer, but less frequently in castration-sensitive cancer. CONCLUSIONS The study suggests that an incremental expression of EMT-related genes in CTCs is associated with metastatic castration-resistant cancer. Although CTCs represent a group of highly heterogeneous cells, their unique EMT-related gene signatures provide a new opportunity for personalized treatments with targeted inhibitors in advanced prostate cancer patients. Prostate 73: 813–826, 2013. © 2012 Wiley Periodicals, Inc.
- [Strategies For Isolating And Propagating Circulating Tumor Cells In Men With Metastatic Prostate Cancer | ScreenCell](https://www.screencell.com/en/scientific-articles/prostate-cancer-publication/strategies-for-isolating-and-propagating-circulating-tumor-cells-in-men-with-metastatic-prostate-cancer-2/): Selecting a well-suited method for isolating/characterizing circulating tumor cells \(CTCs\) is challenging. Evaluating sensitive and specific markers for prostate cancer \(PCa\)-specific CTC identification and analysis is crucial. We used the CellCollector EpCAM-functionalized system \(CC-EpCAM\) and evaluated and developed a PCa-functionalized version \(CC-PCa\); we then compared CTC isolation techniques that exploit the physical and biological properties of CTCs. We established two cohorts of metastatic PCa patients \(mPCa; 15 in cohort 1 and 10 in cohort 2\). CTC cultivation experiments were conducted with two capturing methods \(Ficoll and ScreenCell\). The most sensitive detection rates and highest CTC counts were reached with the CC-PCa and ScreenCell system. Patients with ≥5 CTCs isolated with CC-EpCAM had an overall survival \(OS\) of 0.93 years, and patients with ≥5 CTCs isolated with CC-PCa had an OS of 1.5 years in cohort 1. Nevertheless, we observed the highest sensitivity and specificity for 24-month survival by the Ficoll with CD45 depletion and ScreenCell system with May-Grunwald Giemsa \(MGG\) staining. The EpCAM molecule is an essential factor related to OS for CTC isolation based on biological properties in mPCa patients. The best-suited CTC capture system is not limited to one characteristic of cells but adapted to downstream analysis.
- [Three-Dimensional Telomeric Analysis Of Isolated Circulating Tumor Cells \(CTCs\) Defines CTC Subpopulations | ScreenCell](https://www.screencell.com/en/scientific-articles/prostate-cancer-publication/three-dimensional-telomeric-analysis-of-isolated-circulating-tumor-cells-ctcs-defines-ctc-subpopulations-2/): Circulating tumor cells \(CTCs\) have been identified with the potential to serve as suitable biomarkers for tumor stage and progression, but the availability of effective isolation technique\(s\) coupled with detailed molecular characterization have been the challenges encountered in making CTCs clinically relevant. For the first time, we combined isolation of CTCs using the ScreenCell filtration technique with quantitative analysis of CTC telomeres by TeloView. This resulted in the identification and molecular characterization of different subpopulations of CTCs in the same patient. Three-dimensional \(3D\) telomeric analysis was carried out on isolated CTCs of 19 patients that consisted of four different tumor types, namely, prostate, colon, breast, melanoma, and one lung cancer cell line. With telomeric analysis of the filter-isolated CTCs, the level of chromosomal instability \(CIN\) of the CTCs can be determined. Our study shows that subpopulations of CTCs can be identified on the basis of their 3D telomeric properties.
- [Validation Of Cell-Free RNA And Circulating Tumor Cells For Molecular Marker Analysis In Metastatic Prostate Cancer | ScreenCell](https://www.screencell.com/en/scientific-articles/prostate-cancer-publication/validation-of-cell-free-rna-and-circulating-tumor-cells-for-molecular-marker-analysis-in-metastatic-prostate-cancer-2/): Since tissue material is often lacking in metastatic prostate cancer \(mPCa\), there is increasing interest in using liquid biopsies for treatment decision and monitoring therapy responses. The purpose of this study was to validate the usefulness of circulating tumor cells \(CTCs\) and plasma-derived cell-free \(cf\) RNA as starting material for gene expression analysis through qPCR. CTCs were identified upon prostate-specific membrane antigen and/or cytokeratin positivity after enrichment with ScreenCell \(Westford, Massachusetts, USA\) filters or the microfluidic ParsortixTM \(Guildford, Surrey, United Kingdom\) system. Overall, 50% \(28/56\) of the patients had ≥5 CTCs/7.5 mL of blood. However, CTC count did not correlate with Gleason score, serum PSA, or gene expression. Notably, we observed high expression of CD45 in CTC samples after enrichment, which could be successfully eliminated through picking of single cells. Gene expression in picked CTCs was, however, rather low. In cfRNA from plasma, on the other hand, gene expression levels were higher compared to those found in CTCs. Moreover, we found that PSA was significantly increased in plasma-derived cfRNA of mPCa patients compared to healthy controls. High PSA expression was also associated with poor overall survival, indicating that using cfRNA from plasma could be used as a valuable tool for molecular expression analysis.
- [Are Morphological Criteria Sufficient For The Identification Of Circulating Tumor Cells In Renal Cancer? | ScreenCell](https://www.screencell.com/en/scientific-articles/renal-cancer-publication/are-morphological-criteria-sufficient-for-the-identification-of-circulating-tumor-cells-in-renal-cancer-2/): Background Single circulating tumor cells \(CTCs\) or circulating tumor microemboli \(CTMs\) are potential biomarkers of renal cell cancer \(RCC\), however studies of CTCs/CTMs in RCC are limited. In this pilot study we aimed to evaluate a novel blood filtration technique suited for cytomorphological classification, immunocytochemical and molecular characterization of filtered, so called circulating non-hematologic cells \(CNHCs\) - putative CTCs/CTMs - in patients with RCC. Methods Blood of 40 patients with renal tumors was subjected to ScreenCell® filtration. CNHCs were classified according to cytomorphological criteria. Immunocytochemical analysis was performed with antibodies against CD45, CD31 and carbonic anhydrase IX \(CAIX, a RCC marker\). DNA of selected CNHCs and respective primary tumors was analysed by array-CGH. Results CNHC-clusters with malignant or uncertain malignant cytomorphological features - putative CTMs - were negative for CD45, positive for CD31, while only 6% were CAIX positive. Array-CGH revealed that 83% of malignant and uncertain malignant cells did represent with a balanced genome whereas 17% presented genomic DNA imbalances which did not match the aberrations of the primary tumors. Putative single CTCs were negative for CD45, 33% were positive for CD31 and 56% were positive for CAIX. Conclusions The majority of CNHC-clusters, putative CTMs, retrieved by ScreenCell® filtration may be of endothelial origin. Morphological criteria seem to be insufficient to distinguish malignant from non-malignant cells in renal cancer.
- [Detection Of Circulating Tumour Cells In Urothelial Cancers And Clinical Correlations: Comparison Of Two Methods | ScreenCell](https://www.screencell.com/en/scientific-articles/urothelial-cancer-publication/detection-of-circulating-tumour-cells-in-urothelial-cancers-and-clinical-correlations-comparison-of-two-methods-2/): Circulating tumour cells \(CTC\) are identified exploiting their protein/gene expression patterns or distinct size compared to blood cells. Data on CTC in bladder cancer \(BC\) are still scarce. We comparatively analyzed CTC enrichment by AdnaTest ProstateCancerSelect \(AT\) and ScreenCell®Cyto \(SC\) kits, combined with identification by EPCAM, MUC1, and ERBB2 expression and by cytological criteria, respectively, in 19 nonmetastatic \(M0\) and 47 metastatic \(M+\) BC patients, at baseline \(T0\) and during treatment \(T1\). At T0, CTC positivity rates by AT were higher in M+ compared to M0 cases \(57.4% versus 25%, p = 0.041\). EPCAM was detected in 75% of CTC-positive samples by AT, showing increasing expression levels from T0 to T1 \(median \(interquartile range, IQR\): 0.18 \(0.07–0.42\) versus 0.84 \(0.33–1.84\), p = 0.005\) in M+ cases. Overall, CTC positivity by SC was around 80% regardless of clinical setting and time point of analysis, except for a lower occurrence at T1 in M0 cases. At T0, circulating tumour microemboli were more frequently \(25% versus 8%\) detected and more numerous in M+ compared to M0 patients. The approach used for CTC detection impacts the outcome of CTC studies. Further investigations are required to clarify the clinical validity of AT and SC in specific BC clinical contexts.
- [ScreenCell® Technology | Easy & Fast CTC Isolation Method](https://www.screencell.com/en/screencell-ctc-isolation-method/): ScreenCell® Technology: Discover a fast, versatile, single-use CTC isolation method for CTC enumeration and many other downstream analyses.
- [ScreenCell CSB Kit | CTCs Test.](https://www.screencell.com/en/screencell-ctc-isolation-method/csb-kit/): Discover ScreenCell CSB kit, a single-use circulating tumor cells test for your cytological analyses \(ICC, IF, FISH,...\).
- [ScreenCell® CYTO Kit | CTC Isolation Kit](https://www.screencell.com/en/screencell-ctc-isolation-method/cyto-kit/): Discover our ScreenCell® CYTO kit, a single-use CTC isolation kit dedicated to cytological analyses \(MGG, IF, ICC, FISH\)
- [ScreenCell FCD Kit | Isoler Et Caractériser Facilement Les CTC.](https://www.screencell.com/en/screencell-ctc-isolation-method/fcd-kit/): Discover the ScreenCell FCD Kit, a single-use liquid biopsy device dedicated to the capture of Circulating Tumor Cells.
- [ScreenCell FCD-SP Kit | Easily Isolate And Characterize CTCs.](https://www.screencell.com/en/screencell-ctc-isolation-method/fcdsp-kit/): Discover ScreenCell’s FCD-SP kit, a single-use liquid biopsy device dedicated to the capture of Circulating Tumor Cells.
- [ScreenCell LCD Kit | Easily Isolate And Characterize CTCs.](https://www.screencell.com/en/screencell-ctc-isolation-method/lcd-kit/): Discover the ScreenCell LCD Kit, a single-use liquid biopsy device dedicated to the capture of Circulating Tumor Cells.
- [ScreenCell MB Kit | Easily Isolate And Characterize CTCs.](https://www.screencell.com/en/screencell-ctc-isolation-method/mb-kit/): Discover the ScreenCell MB Kit, a single-use liquid biopsy device dedicated to the capture of Circulating Tumor Cells.
- [ScreenCell MBSB Kit | Easily Isolate And Characterize CTCs.](https://www.screencell.com/en/screencell-ctc-isolation-method/mbsb-kit/): Discover ScreenCell’s MBSB kit, a single-use liquid biopsy device dedicated to the capture of Circulating Tumor Cells.
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- [Can We Isolate Viable #ctcs For Downstream Applications? Emile Lakis Answers Your Question #2 ! | ScreenCell](https://www.screencell.com/en/video-en/short-format/can-we-isolate-viable-ctcs-for-downstream-applications-emile-lakis-answers-your-question-2/): No description available.
- [Can We Perform Mutational Studies On CTCs Enriched By ScreenCell Technology? | ScreenCell](https://www.screencell.com/en/video-en/short-format/can-we-perform-mutational-studies-on-ctcs-enriched-by-screencell-technology/): No description available.
- [CTCs In Clinical Routine: What Concrete Applications? Our CSO Answers Your Question | ScreenCell](https://www.screencell.com/en/video-en/short-format/ctcs-in-clinical-routine-what-concrete-applications-our-cso-answers-your-question/): No description available.
- [Is ScreenCell's Technology Sensitive Enough To Detect Small Amounts Of Circulating Tumor Cells ? | ScreenCell](https://www.screencell.com/en/video-en/short-format/is-screencells-technology-sensitive-enough-to-detect-small-amounts-of-circulating-tumor-cells/): No description available.
- [Learn In Depth How Our CTCs Isolation Support #cancerresearch | ScreenCell](https://www.screencell.com/en/video-en/short-format/learn-in-depth-how-our-ctcs-isolation-support-cancerresearch/): No description available.
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- [What Role Will The Analysis Of Circulating Tumor Cells \(CTCs\) Play In 2024 ? | ScreenCell](https://www.screencell.com/en/video-en/short-format/what-role-will-the-analysis-of-circulating-tumor-cells-ctcs-play-in-2024/): No description available.
- [Which ScreenCell Kit Is Right For My Application? | Liquid Biopsy Test](https://www.screencell.com/en/which-screencell-kit-is-right-for-my-application/): Find the ScreenCell kit that fits your research or clinical routine needs for CTC capture using liquid biopsy.
- [ScreenCell | Dispositif Médical Pour L'isolement Des CTC](https://www.screencell.com/fr/): ScreenCell® - Une méthode simple et rapide dédiée à l'isolement des CTC conçue pour les centres de recherche sur le cancer et les entreprises pharmaceutiques.
- [À Propos De ScreenCell – Pionnière Dans Les Cellules Tumorales Circulantes \(CTC\) Et La Biopsie Liquide](https://www.screencell.com/fr/a-propos-screencell/): Découvrez ScreenCell, société française de biotechnologie pionnière dans l'isolement des cellules tumorales circulantes \(CTC\) et la biopsie liquide.
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- [La Nouvelle Standardisation Des Kits ScreenCell® - ScreenCell® 2026](https://www.screencell.com/fr/actualites/produit/standardisation-kits-screencell-2026/): À partir du 1er janvier 2026, les kits ScreenCell® se standardiseront autour d'un format unique : 2 unités de filtration et 1 tampon de dilution par kit, le tout dans un packaging entièrement repensé. Une évolution à 360° pensée pour l'optimisation et la simplicité.
- [ScreenCell Adhère Au PMT Santé à Besançon](https://www.screencell.com/fr/actualites/societe/screencell-pmt-sante/): ScreenCell® est fière d'annoncer son adhésion au PMT Santé, le cluster régional des technologies de santé porté par le PMT \(Pôle des Microtechniques\) à Besançon. En intégrant ce réseau dynamique, ScreenCell® rejoint les 145 autres acteurs Medtech et Biotech de la filière « Technologies de santé » en Bourgogne-Franche-Comté.
- [ScreenCell® Rejoint L'ELBS \(European Liquid Biopsy Society\)](https://www.screencell.com/fr/actualites/societe/screencell-rejoint-elbs-societe-europeenne-biopsie-liquide/): ScreenCell® est fière d'annoncer son adhésion à l'ELBS \(European Liquid Biopsy Society\) en tant que membre industriel.
- [Les Cellules Tumorales Circulantes \(CTC\) : Qu'est-ce Que C'est ?](https://www.screencell.com/fr/blog-fr/science/definition-cellules-tumorales-circulantes-ctc/): Les cellules tumorales circulantes \(CTC\) : définition, rôle dans le cancer et impact sur le diagnostic. Un point complet sur ces biomarqueurs clés.
- [ScreenCell® - 50 000 Unités Pour La Caractérisation Des Cellules Tumorales Circulantes](https://www.screencell.com/fr/communique-de-presse/screencell-50000-unites-caracterisation-cellules-tumorales-circulantes/): ScreenCell atteint 50 000 unités expédiées dans le monde pour la caractérisation des cellules tumorales circulantes, renforçant la recherche en oncologie.
- [ScreenCell Et La Détection Des CTC Du Cancer Colorectal](https://www.screencell.com/fr/communique-de-presse/screencell-ctc-cancer-colorectal/): Des chercheurs démontrent l’efficacité de ScreenCell pour capturer et caractériser les cellules tumorales circulantes \(CTC\) chez des patients atteints de cancer colorectal.
- [ScreenCell Optimise L’enrichissement Des CTC Du Cancer Du Sein](https://www.screencell.com/fr/communique-de-presse/screencell-enrichissement-ctc-cancer-du-sein/): ScreenCell collabore avec le Jefferson Breast Care Center pour enrichir et caractériser les cellules tumorales circulantes \(CTC\) du cancer du sein.
- [Un Projet Sur La Biopsie Liquide ? Contactez Nous ! | ScreenCell](https://www.screencell.com/fr/contactez-nous/): Pour en savoir plus sur l'utilisation des CTC et de la biopsie liquide dans vos projets de recherche ou en routine clinique, contactez nous !
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- [Essais Cliniques | ScreenCell](https://www.screencell.com/fr/essais-cliniques/): Découvrez nos essais cliniques en cours et terminés sur les cellules tumorales circulantes \(CTC\) utilisant la biopsie liquide.
- [Evaluation Des Cellules Tumorales Circulantes \(CTC\) Par Le Dispositif ScreenCell® Dans Le Cancer Du Sein : Validation De Biomarqueurs | ScreenCell](https://www.screencell.com/fr/etudes-cliniques/cancer-sein-etude/evaluation-des-cellules-tumorales-circulantes-ctc-par-le-dispositif-screencell-dans-le-cancer-du-sein-validation-de-biomarqueurs/): No description available.
- [Evaluation Of Circulating Tumor Cells \(CTC\) Relevance In Breast Cancer Follow-up Using The ScreenCell Device \(PROBE-CTC\) | ScreenCell](https://www.screencell.com/fr/etudes-cliniques/cancer-sein-etude/evaluation-of-circulating-tumor-cells-ctc-relevance-in-breast-cancer-follow-up-using-the-screencell-device-probe-ctc/): No description available.
- [Analyse Des Cellules Tumorales Circulantes \(CTC\) Chez Des Patients Atteints De Mélanome Métastatique Avant Et Au Cours Du Traitement Systémique | ScreenCell](https://www.screencell.com/fr/etudes-cliniques/melanome-etude/analyse-des-cellules-tumorales-circulantes-ctc-chez-des-patients-atteints-de-melanome-metastatique-avant-et-au-cours-du-traitement-systemique/): No description available.
- [Ex Vivo Expansion Of Circulating Tumor Cells As A Model For Cancer Predictive Pharmacology \(EXPEVIVO-CTC\) | ScreenCell](https://www.screencell.com/fr/etudes-cliniques/melanome-etude/ex-vivo-expansion-of-circulating-tumor-cells-as-a-model-for-cancer-predictive-pharmacology-expevivo-ctc/): No description available.
- [PSCC Innovation Forum 2026 | ScreenCell | Biopsie Liquiode](https://www.screencell.com/fr/evenements/3e-pscc-innovation-forum-2026/): ScreenCell assistera au 3e PSCC Innovation Forum 2026 le 4 février à Villejuif. Rencontrez notre expert Emile Lakis, Ph.D. pour découvrir nos solutions d'isolement de CTC.
- [ACTC 2025 | Rencontrez ScreenCell® Du 24 Au 27 Septembre](https://www.screencell.com/fr/evenements/actc-2025-2/): ScreenCell® participera à la 7e édition du congrès « Advances in Circulating Tumor Cells Meeting » \(ACTC 2025\) à Thessalonique, en Grèce.
- [AG ELBS 2025 | ScreenCell® Présente Du 3 Au 4 Novembre 2025](https://www.screencell.com/fr/evenements/elbs-ag-2025/): ScreenCell® sera présent du 3 au 4 novembre à l'assemblée générale 2025 de la société européenne de biopsie liquide \(ELBS\) à Madrid.
- [2nd IBC-IC In Africa : Venez Découvrir ScreenCell® | ScreenCell](https://www.screencell.com/fr/evenements/ibc-ic-2025/): Venez découvrir la technologie ScreenCell® lors du 2nd IBC-IC in Africa et du 8th Ariana's OncoDay. Ces événements se tiendront les 9 et 10 mai 2025 au Carthage Thalasso Resort Hotel à Tunis, en Tunisie.
- [ISMRC 2025 : Rejoignez ScreenCell Pour Découvrir Notre Méthode De Détection Des CTCs | ScreenCell](https://www.screencell.com/fr/evenements/ismrc-2025-rejoignez-screencell/): Nous sommes ravis d'annoncer que ScreenCell sera présent à la prochaine édition de l'International Symposium on Molecular and Cellular Research \(ISMRC\) qui se tiendra du 7 au 9 mai 2025 à Nice en France. Cet événement majeur dans le domaine de la biopsie liquide représente une opportunité unique de partager nos dernières innovations et d'échanger avec les différents acteurs du secteur.
- [ScreenCell® Participe À L'ISLB 2025 | Biopsie Liquide](https://www.screencell.com/fr/evenements/screencell-participe-a-islb-2025/): Du 1er au 3 novembre 2025, ScreenCell® traverse l'Atlantique pour rejoindre Orlando, en Floride, à l'occasion du 7ème Congrès Annuel de Biopsie Liquide \(ISLB 2025\). Le Dr. Sina Naserian, notre Directeur Technique, portera les couleurs de l'entreprise lors de ce rassemblement international incontournable qui mobilise l'excellence mondiale en matière de biopsie liquide.
- [ScreenCell Au SIMEM 2025 : Retrouvez-nous Sur Le Stand Genethical® | ScreenCell](https://www.screencell.com/fr/evenements/simem-2025-rejoignez-screencell-genethical/): ScreenCell sera présent au SIMEM 2025 à Oran du 9 au 12 avril sur le stand Genethical. Venez découvrir nos solutions innovantes pour l’analyse des cellules tumorales circulantes et échanger avec nos experts !
- [Stand Up To Cancer \(SU2C\) Scientific Summit 2026 | ScreenCell](https://www.screencell.com/fr/evenements/su2c-scientific-summit-2026/): ScreenCell® sera présente au SU2C Scientific Summit 2026 à Pasadena, Californie, du 29 janvier au 1er février 2026. Notre Directeur Technique, Sina NASERIAN, Ph.D., y présentera nos dispositifs médicaux d'isolement de cellules tumorales circulantes lors d'une intervention dédiée le 31 janvier. Une occasion unique de découvrir comment notre technologie de biopsie liquide révolutionne la médecine de précision dans l'oncologie moderne.
- [Kit Média | ScreenCell](https://www.screencell.com/fr/kit-media-032026/): Journalistes, équipes de presse, partenaires média…
- [Plan Du Site | ScreenCell](https://www.screencell.com/fr/plan-du-site/): Plan du site
- [Politique De Confidentialité | ScreenCell](https://www.screencell.com/fr/politique-de-confidentialite/): La présente politique de confidentialité régit la manière dont ScreenCell recueille, utilise, conserve les informations recueillies auprès des utilisateurs du
- [A Fast And Furious Liquid Biopsy Assay To Monitor Targeted Therapy Resistance. | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/biopsie-liquide-publication/a-fast-and-furious-liquid-biopsy-assay-to-monitor-targeted-therapy-resistance/): Liquid biopsies represent a valid alternative to conventional tissue biopsies, offering a real time molecular picture of tumors in a minimally invasive manner. Of the various circulating biomarkers available for liquid biopsy, circulating tumor cells \(CTC\) and circulating tumor DNA \(ctDNA\) are the most intensively studied to date. However, CTC and ctDNA represent different tumor components, therefore, complementary information from both sources might be beneficial. This protocol focuses on the description of a sample processing workflow that allowed for concurrent isolation of CTC and ctDNA from the same source sample. This single tube approach enables simultaneous analysis of multiple biomarkers to better monitor cancer drug resistance.
- [A Novel Combined Methodology For Isolation And Detection Of Circulating Tumor Cells Based On Flow Cytometry And Cellular Filtration Technologies | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/biopsie-liquide-publication/a-novel-combined-methodology-for-isolation-and-detection-of-circulating-tumor-cells-based-on-flow-cytometry-and-cellular-filtration-technologies/): Cancer cell presents a dynamic nature that evolves over time in its microenvironment through a complicating molecular and cellular interaction network. Despite the progress already achieved in the imaging technologies and the molecular tools used for tumor cell diagnosis and treatment approaches, metastasis still remains a major hindering factor that limits the clinical outcomes. Circulating tumor cells \(CTCs\) present the potential in providing critical information to understand the metastasis process, the tumor cell and genome heterogeneity, in a way to overcome cancer therapy bottlenecks and improve the efficacy and safety therapeutic profiles. The experience already gained shows that CTCs as tools possess a predictive biomarker capacity by aiming the understanding of most of the known cancer cell hallmarks at the molecular level, as well as the translation of the extracted relevant knowledge in clinical practice. The efficient isolation and characterization of CTCs might reveal the intratumoral heterogeneity present in tumors while providing critical insights into cancer metastasis. Moreover, by combining the emerging single cell omics technologies, CTCs can be valuable biological source material to unveil the existed intratumoral cellular and genomic heterogeneity, as well as to pharmacologically exploit critical knowledge for the validation of prognostic and diagnostic biomarkers within the concept of precision and personalized cancer therapy. In this article, a novel combined methodology for the isolation and detection of CTCs based on flow cytometry and cellular filtration technologies is presented.
- [Circulating Tumor Cells In Right- And Left-Sided Colorectal Cancer | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-colorectal-publication/circulating-tumor-cells-in-right-and-left-sided-colorectal-cancer/): Molecular alterations are not randomly distributed in colorectal cancer \(CRC\), but rather clustered on the basis of primary tumor location underlying the importance of colorectal cancer sidedness. We aimed to investigate whether circulating tumor cells \(CTC\) characterization might help clarify how different the patterns of dissemination might be relative to the behavior of left- \(LCC\) compared to right-sided \(RCC\) cancers. We retrospectively analyzed patients with metastatic CRC who had undergone standard baseline CTC evaluation before starting any first-line systemic treatment. Enumeration of CTC in left- and right-sided tumors were compared. The highest prognostic impact was exerted by CTC in left-sided primary cancer patients, even though the lowest median number of cells was detected in this subgroup of patients. CTC exhibit phenotypic heterogeneity, with a predominant mesenchymal phenotype found in CTC from distal compared to proximal primary tumors. Most CTC in RCC patients exhibited an apoptotic pattern. CTC in left-sided colon cancer patients exhibit a predominant mesenchymal phenotype. This might imply a substantial difference in the biology of proximal and distal cancers, associated with different patterns of tumor cells dissemination. The poor prognosis of right-sided CRC is not determined by the hematogenous dissemination of tumor cells, which appears to be predominantly a passive shedding of non-viable cells. Conversely, the subgroup of poor-prognosis left-sided CRC is reliably identified by the presence of mesenchymal CTC.
- [Colorectal Carcinomas In 2013: The Search For Powerful Prognostic Markers Is Still On The Go! | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-colorectal-publication/colorectal-carcinomas-in-2013-the-search-for-powerful-prognostic-markers-is-still-on-the-go/): Colorectal cancer \(CRC\) is the third cause of cancer worldwide after prostate cancer and breast cancer. Patients have a survival rate of 5 years, which varies between 10 and 95% depending on CRC stage. Today, the management of patients with CRC is based on parameters such as TNM and classic histologic parameters, but new molecular and cell markers have been created to improve treatment and survival. Determining the expression of a characteristic set of genes either from formalin-fixed paraffin-embedded tissue \(Onco type DX test™\) or from fresh tissues \(AGENDIA© ColoPrint®\) has led to encouraging results, but there is a need for clinical validation on a large number of patients. Also, next-generation sequencing \(NGS\) technologies may be the next step in the molecular approach of CRC tumor samples, allowing tumor characterization by gene signature arrays. In addition to molecular markers, evaluation of the presence of cellular markers such as circulating tumor cells \(CTC\) in the blood of patients with CRC can optimize prognostic evaluation and response to treatment. CTC isolation methods used today have different sensitivities and specificities, due not only to the very small number of these cells but also to the epithelial-mesenchymal transitional process \(EMT\). This paper presents the preliminary results of our study conducted on CTC isolation in patients with CRC by filtration method \(Screencells Cyto®\). This fast and efficient method identifies CTCs and also isolates cells in EMT, which explains its high efficiency compared to technologies based on immunomagnetic and microfluidic separation reliant on EpCAM presence on the cell surface.
- [Détection Des Mutations RAS Dans Les Cellules Tumorales Circulantes : Applications Au Cancer Colorectal Et Perspectives | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-colorectal-publication/detection-des-mutations-ras-dans-les-cellules-tumorales-circulantes-applications-au-cancer-colorectal-et-perspectives/): Les mutations somatiques présentes dans les gènes RAS \(KRAS et NRAS\) sont largement associées à l’absence de réponse aux traitements par immunothérapie ciblant le récepteur du facteur de croissance épidermique dans le cancer colorectal métastatique. La recherche de ces mutations est devenue obligatoire pour pouvoir prescrire ces traitements et cette détection est réalisée à partir de biopsies tissulaires. Dans environ 25 % des cas, cette analyse n’est pas possible pour des raisons à la fois analytique et médicale et par conséquent le développement de stratégies alternatives est donc nécessaire. Parmi les solutions envisagées, la recherche de mutations directement dans le sang des patients est une approche prometteuse. Parmi les sources d’ADN tumoral présent dans la circulation sanguine, les cellules tumorales circulantes \(CTC\) représentent une approche particulièrement pertinente. Ces cellules, dont certaines sont à l’origine des métastases, sont parvenues à se détacher de la tumeur primitive, puis à migrer et enfin à entrer dans le système vasculaire. En ce sens, elles sont particulièrement résistantes aux contraintes physico-chimiques et immunologiques mises en œuvre par l’organisme pour empêcher leur dissémination et représentent par conséquent une source d’informations particulièrement précieuse sur la génétique des cellules tumorales les plus agressives. Le corollaire est que ces cellules sont très rares et nécessitent des technologies particulièrement performantes pour les détecter et les caractériser. Dans cette présentation, nous nous focaliserons principalement sur les méthodes moléculaires permettant de détecter les mutations des gènes RAS sur les CTC en analysant les performances d’une solution basée sur une méthode d’enrichissement par filtration suivi d’une détection par PCR digitale. Enfin, nous nous interrogerons sur leur signification biologique avant d’évoquer leurs perspectives dans le cancer colorectal ainsi que dans d’autres types de cancers.
- [Droplet Digital PCR Of Circulating Tumor Cells From Colorectal Cancer Patients Can Predict KRAS Mutations Before Surgery | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-colorectal-publication/droplet-digital-pcr-of-circulating-tumor-cells-from-colorectal-cancer-patients-can-predict-kras-mutations-before-surgery/): In colorectal cancer \(CRC\), KRAS mutations are a strong negative predictor for treatment with the EGFR-targeted antibodies cetuximab and panitumumab. Since it can be difficult to obtain appropriate tumor tissues for KRAS genotyping, alternative methods are required. Circulating tumor cells \(CTCs\) are believed to be representative of the tumor in real time. In this study we explored the capacity of a size-based device for capturing CTCs coupled with a multiplex KRAS screening assay using droplet digital PCR \(ddPCR\). We showed that it is possible to detect a mutant ratio of 0.05% and less than one KRAS mutant cell per mL total blood with ddPCR compared to about 0.5% and 50–75 cells for TaqMeltPCR and HRM. Next, CTCs were isolated from the blood of 35 patients with CRC at various stage of the disease. KRAS genotyping was successful for 86% \(30/35\) of samples with a KRAS codon 12/13 mutant ratio of 57% \(17/30\). In contrast, only one patient was identified as KRAS mutant when size-based isolation was combined with HRM or TaqMeltPCR. KRAS status was then determined for the 26 available formalin-fixed paraffin-embedded tumors using standard procedures. The concordance between the CTCs and the corresponding tumor tissues was 77% with a sensitivity of 83%. Taken together, the data presented here suggest that is feasible to detect KRAS mutations in CTCs from blood samples of CRC patients which are predictive for those found in the tumor. The minimal invasive nature of this procedure in combination with the high sensitivity of ddPCR might provide in the future an opportunity to monitor patients throughout the course of disease on multiple levels including early detection, prognosis, treatment and relapse as well as to obtain mechanistic insight with respect to tumor invasion and metastasis.
- [EpCAM-expressing Circulating Tumor Cells In Colorectal Cancer | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-colorectal-publication/epcam-expressing-circulating-tumor-cells-in-colorectal-cancer/): Background: Several studies have raised the issue of the inadequacy of CellSearch® to detect the entire pool of circulating tumor cells \(CTCs\) from blood of cancer patients, suggesting that cells expressing low levels of epithelial cell adhesion molecule \(EpCAM\) are not recognized by the capture reagent. In this exploratory study, we aimed to evaluate the status of EpCAM in CTCs isolated from a group of metastatic colorectal cancer patients, in 40% of whom, CTC had been found to be undetected by the CellSearch® system. Methods: CTCs were analyzed using both a microfiltration method \(ScreenCell\) and CellSearch® in parallel. Furthermore, since EpCAM exists in 2 different variants, we investigated the presence of both its intracellular domain \(EpICD\) and extracellular domain \(EpEX\) through immunofluorescence staining of CTCs on filters. Results: Results from immunofluorescence experiments demonstrated that, overall, EpICD and/or EpEX was expressed in 176 CTCs detected by ScreenCell, while the CellSearch® system was able to capture only 10 CTCs. Conclusions: This is the first demonstration that the low sensitivity of CellSearch® to detect CTCs in colorectal cancer patients is not due to the lack of EpCAM."
- [Isolation And Enumeration Of CTC In Colorectal Cancer Patients: Introduction Of A Novel Cell Imaging Approach And Comparison To Cellular And Molecular Detection Techniques | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-colorectal-publication/isolation-and-enumeration-of-ctc-in-colorectal-cancer-patients-introduction-of-a-novel-cell-imaging-approach-and-comparison-to-cellular-and-molecular-detection-techniques/): Circulating tumour cells \(CTC\) were proven to be prognostically relevant in cancer treatment, e.g., in colorectal cancer \(CRC\). This study validates a molecular detection technique through using a novel cell imaging approach for CTC detection and enumeration, in comparison to a size-based cellular and correlated the data to clinico-pathological characteristics. Overall, 57 CRC patients were recruited for this prospective study. Blood samples were analysed for CTCs by three methods: \(1\) Epithelial marker immunofluorescence staining combined with automated microscopy using the NYONE® cell imager; \(2\) isolation by size using membrane filtration with the ScreenCell® Cyto IS device and immunofluorescence staining; \(3\) detection by semi-quantitative Cytokeratin-20 RT-qPCR. Enumeration data were compared and correlated with clinic-pathological parameters. CTC were detected by either approach; however, with varying positivity rates: NYONE® 36.4%, ScreenCell® 100%, and PCR 80.5%. All methods revealed a positive correlation of CTC presence and higher tumour burden, which was most striking using the ScreenCell® device. Generally, no intercorrelation of CTC presence emerged amongst the applied techniques. Overall, enumeration of CTC after isolation by size demonstrated to be the most reliable strategy for the detection of CTC in CRC patients. Ongoing studies will have to unravel the prognostic value of this finding, and validate this approach in a larger cohort.
- [Sequential Isolation And Characterization Of Single CTCs And Large CTC Clusters In Metastatic Colorectal Cancer Patients | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-colorectal-publication/sequential-isolation-and-characterization-of-single-ctcs-and-large-ctc-clusters-in-metastatic-colorectal-cancer-patients/): Circulating tumor cells \(CTCs\) detach from a primary tumor or its metastases and circulate in the bloodstream. The vast majority of CTCs are deemed to die into the bloodstream, with only few cells representing viable metastatic precursors. Particularly, single epithelial CTCs do not survive long in the circulation due to the loss of adhesion-dependent survival signals. In metastatic colorectal cancer, the generation of large CTC clusters is a very frequent occurrence, able to increase the aptitude of CTCs to survive in the bloodstream. Although a deepened analysis of large-sized CTC clusters might certainly offer new insights into the complexity of the metastatic cascade, most CTC isolation techniques are unfortunately not compatible with large-sized CTC clusters isolation. The inappropriateness of standard CTC isolation devices for large clusters isolation and the scarce availability of detection methods able to specifically isolate and characterize both single CTCs and CTC clusters finally prevented in-depth studies on the prognostic and predictive value of clusters in clinical practice, unlike that which has been described for single CTCs. In the present study, we validated a new sequential filtration method for the simultaneous isolation of large CTC clusters and single CTCs in patients with metastatic colorectal cancer at failure of first-line treatments. The new method might allow differential downstream analyses for single and clustered CTCs starting from a single blood draw, opening new scenarios for an ever more precise characterization of colorectal cancer metastatic cascade.
- [Weighted Correlation Network Analysis Revealed Novel Long Non-coding RNAs For Colorectal Cancer | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-colorectal-publication/weighted-correlation-network-analysis-revealed-novel-long-non-coding-rnas-for-colorectal-cancer/): Colorectal cancer \(CRC\) is one of the most prevalent cancers worldwide, which after breast, lung and, prostate cancers, is the fourth prevalent cancer in the United States. Long non-coding RNAs \(lncRNAs\) have an essential role in the pathogenesis of CRC. Therefore, bioinformatics studies on lncRNAs and their target genes have potential importance as novel biomarkers. In the current study, publicly available microarray gene expression data of colorectal cancer \(GSE106582\) was analyzed with the Limma, Geoquery, Biobase package. Afterward, identified differentially expressed lncRNAs and their target genes were inserted into Weighted correlation network analysis \(WGCNA\) to obtain modules and hub genes. A total of nine differentially expressed lncRNAs \(LINC01018, ITCH-IT, ITPK1-AS1, FOXP1-IT1, FAM238B, PAXIP1-AS1, ATP2B1-AS1, MIR29B2CHG, and SNHG32\) were identified using microarray data analysis. The WGCNA has identified several hub genes for black \(LMOD3, CDKN2AIPNL, EXO5, ZNF69, BMS1P5, METTL21A, IL17RD, MIGA1, CEP19, FKBP14\), blue \(CLCA1, GUCA2A, UGT2B17, DSC2, CA1, AQP8, ITLN1, BEST4, KLF4, IQCF6\) and turquoise \(PAFAH1B1, LMNB1, CACYBP, GLO1, PUM3, POC1A, ASF1B, SDCCAG3, ASNS, PDCD2L\) modules. The findings of the current study will help to improve our understanding of CRC. Moreover, the hub genes that we have identified could be considered as possible prognostic/diagnostic biomarkers. This study led to the determination of nine lncRNAs with no previous association with CRC development.
- [Detection Of Circulating Tumor Cells In Patients With Laryngeal Cancer Using ScreenCell: Comparative Pre- And Post-operative Analysis And Association With Prognosis | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-larynx-publication/detection-of-circulating-tumor-cells-in-patients-with-laryngeal-cancer-using-screencell-comparative-pre-and-post-operative-analysis-and-association-with-prognosis/): The presence of circulating tumor cells \(CTCs\) in the blood of patients with metastatic breast, colorectal and prostate cancer have been widely investigated; however, few studies have examined CTCs in patients with laryngeal cancer. The present pilot study aimed to detect pre- and postoperative CTCs in the blood of patients with laryngeal cancer and evaluate the association with prognosis. Eight patients with laryngeal squamous cell carcinoma \(LSCC\) at stage III were included in the present study and underwent total or subtotal laryngectomy and radical bilateral neck lymph node dissection. Blood samples were collected from all patients before and after surgery at different time-points. The following processing steps were followed; preoperative blood sampling, surgery, postoperative blood sampling at 3, 6 and 12 month follow-ups, and prognostic association analysis. CTCs were retained on ScreenCell filters for cytological characterization. The presence of CTCs was associated with a less favorable prognosis, whereas a decrease of CTCs in the postoperative sampling was observed in patients who exhibited an improved therapeutic response. The results of the present pilot study revealed a possible association between the presence of CTCs and a less favorable prognosis in patients with LSCC; therefore, these preliminary findings may encourage further research into the incorporation of a liquid biopsy in the management of LSCC, as this may help identify patients with occult metastatic disease earlier and in a non-invasive manner. In addition, this approach may represent novel independent prognostic factor for use in the clinical evaluation of patients with LSCC.
- [Circulating Epithelial Cells In Patients With Pancreatic Lesions: Clinical And Pathologic Findings | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-pancreas-publication/circulating-epithelial-cells-in-patients-with-pancreatic-lesions-clinical-and-pathologic-findings/): Background Circulating epithelial cell \(CEC\) isolation has provided diagnostic and prognostic information for a variety of cancers, previously supporting their identity as circulating tumor cells in the literature. However, we report CEC findings in patients with benign, premalignant, and malignant pancreatic lesions using a size-selective filtration device. Study Design Peripheral blood samples were drawn from patients found to have pancreatic lesions on preoperative imaging at a surgical clinic. Blood was filtered using ScreenCell devices, which were evaluated microscopically by a pancreatic cytopathologist. Pathologic data and clinical outcomes of these patients were obtained from medical records during a 1-year follow-up period. Results Nine healthy volunteers formed the control group and were found to be negative for CECs. There were 179 patients with pancreatic lesions that formed the study cohort. Circulating epithelial cells were morphologically similar in patients with a variety of pancreatic lesions. Specifically, CECs were identified in 51 of 105 pancreatic ductal adenocarcinomas \(49%\), 7 of 11 neuroendocrine tumors \(64%\), 13 of 21 intraductal papillary mucinous neoplasms \(62%\), and 6 of 13 patients with chronic pancreatitis. Rates of CEC identification were similar in patients with benign, premalignant, and malignant lesions \(p = 0.41\). In addition, CEC findings in pancreatic ductal adenocarcinoma patients were not associated with poor prognosis. Conclusions Although CECs were not identified in healthy volunteers, they were identified in patients with benign, premalignant, and malignant pancreatic lesions. The presence of CECs in patients presenting with pancreatic lesions is neither diagnostic of malignancy nor prognostic for patients with pancreatic ductal adenocarcinoma."
- [Circulating Tumor Cells Found In Patients With Localized And Advanced Pancreatic Cancer | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-pancreas-publication/circulating-tumor-cells-found-in-patients-with-localized-and-advanced-pancreatic-cancer/): Objectives Isolation of circulating tumor cells \(CTCs\) holds the promise of diagnosing and molecular profiling cancers from a blood sample. Here, we test a simple new low-cost filtration device for CTC isolation in patients with pancreatic ductal adenocarcinoma \(PDAC\). Methods Peripheral blood samples drawn from healthy donors and PDAC patients were filtered using ScreenCell devices, designed to capture CTCs for cytologic and molecular analysis. Giemsa-stained specimens were evaluated by a pancreatic cytopathologist blinded to the histological diagnosis. Circulating tumor cell DNA was subjected to KRAS mutational analysis. Results Spiking experiments demonstrated a CTC capture efficiency as low as 2 cells/mL of blood. Circulating tumor cells were identified by either malignant cytology or presence of KRAS mutation in 73% of 11 patients \(P = 0.001\). Circulating tumor cells were identified in 3 of 4 patients with early \(≤American Joint Committee on Cancer stage IIB\) and in 5 of 7 patients with advanced \(≥ American Joint Committee on Cancer stage III\) PDAC. No CTCs were detected in blood from 9 health donors. Conclusions Circulating tumor cells can be found in most patients with PDAC of any stage, whether localized, locally advanced, or metastatic. The ability to capture, cytologically identify, and genetically analyze CTCs suggests a possible tool for the diagnosis and characterization of genetic alterations of PDAC.
- [Cytologic Characteristics Of Circulating Epithelioid Cells In Pancreatic Disease | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-pancreas-publication/cytologic-characteristics-of-circulating-epithelioid-cells-in-pancreatic-disease/): BACKGROUND Circulating epithelioid cells \(CECs\), also known as circulating tumor, circulating cancer, circulating epithelial, or circulating nonhematologic cells, are a prognostic factor in various malignancies that can be isolated via various protocols. In the current study, the authors analyzed the cytomorphologic characteristics of CECs isolated by size in a cohort of patients with benign and malignant pancreatic diseases to determine whether cytomorphological features could predict CEC origin. METHODS Blood samples were collected from 9 healthy controls and 171 patients with pancreatic disease who were presenting for surgical evaluation before treatment. Blood was processed with the ScreenCell size-based filtration device. Evaluable CECs were analyzed in a blinded fashion for cytomorphologic characteristics, including cellularity; nucleoli; nuclear size, irregularity, variability, and hyperchromasia; and nuclear-to-cytoplasmic ratio. Statistical differences between variables were analyzed via the Fisher exact test. RESULTS No CECs were identified among the 9 normal healthy controls. Of the 115 patients with CECs \(positive or suspicious for\), 25 had nonmalignant disease and 90 had malignancy. There were no significant differences in any of the cytologic criteria noted between groups divided by benign versus malignant, neoplastic versus nonneoplastic, or pancreatic ductal adenocarcinoma versus neuroendocrine tumor. CONCLUSIONS CECs were observed in patients with malignant and nonmalignant pancreatic disease, but not in healthy controls. There were no morphologic differences observed between cells from different pancreatic diseases, suggesting that numerous conditions may be associated with CECs in the circulation and that care must be taken not to overinterpret cells identified by cytomorphology as indicative of circulating tumor cells of pancreatic cancer. Additional studies are required to determine the origin and clinical significance of these cells."
- [Expression Profiling Of Circulating Tumor Cells In Pancreatic Ductal Adenocarcinoma Patients: Biomarkers Predicting Overall Survival | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-pancreas-publication/expression-profiling-of-circulating-tumor-cells-in-pancreatic-ductal-adenocarcinoma-patients-biomarkers-predicting-overall-survival/): The interest in liquid biopsy is growing because it could represent a non-invasive prognostic or predictive tool for clinical outcome in patients with pancreatic ductal adenocarcinoma \(PDAC\), an aggressive and lethal disease. In this pilot study, circulating tumor cells \(CTCs\), CD16 positive atypical CTCs, and CTC clusters were captured and characterized in the blood of patients with PDAC before and after palliative first line chemotherapy by ScreenCell device, immunohistochemistry, and confocal microscopy analysis. Gene profiles were performed by digital droplet PCR in isolated CTCs, five primary PDAC tissues, and three different batches of RNA from normal human pancreatic tissue. Welsh's t-test, Kaplan-Meier survival, and Univariate Cox regression analyses have been performed. Statistical analysis revealed that the presence of high CTC number in blood is a prognostic factor for poor overall survival and progression free survival in advanced PDAC patients, before and after first line chemotherapy. Furthermore, untreated PDAC patients with CTCs, characterized by high ALCAM, POU5F1B, and SMO mRNAs expression, have shorter progression free survival and overall survival compared with patients expressing the same biomarkers at low levels. Finally, high SHH mRNA levels are negatively associated to progression free survival, whereas high vimentin mRNA levels are correlated with the most favorable prognosis. By hierarchical clustering and correlation index analysis, two cluster gene signatures were identified in CTCs: the first, with high expression of VEGFA, NOTCH1, EPCAM, IHH, is the signature of PDAC patients before chemotherapy, whereas the second, with an enrichment in the expression of CD44, ALCAM, and POU5F1B stemness and pluripotency genes, is reported after palliative chemotherapy. Overall our data support the clinic value of the identification of CTC's specific biomarkers to improve the prognosis and the therapy in advanced PDAC patients.
- [KRAS Mutations In Pancreatic Circulating Tumor Cells: A Pilot Study | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-pancreas-publication/kras-mutations-in-pancreatic-circulating-tumor-cells-a-pilot-study/): Pancreatic ductal adenocarcinoma \(PDAC\) is most often diagnosed in a metastatic stage. Circulating tumor cells \(CTC\) in the blood are hypothesized as the means of systemic dissemination. We aimed to isolate and characterize CTC to evaluate their significance as prognostic markers in PDAC. Blood obtained from healthy donors and patients with PDAC before therapy was filtered with ScreenCell® filtration devices for size-based CTC isolation. Captured cells were analyzed by immunofluorescence for an epithelial to mesenchymal transition \(EMT\) marker \(zinc finger E-box binding homebox 1 \(ZEB1\)\) and an epithelial antigen \(cytokeratin \(CK\)\). Molecular analysis of parallel specimens evaluated the KRAS mutation status of the CTC. The survival of each patient after study was recorded. As demonstrated by either cytology or finding of a KRAS mutation, CTC were detected in 18 of 21 patients \(86 %\) with proven PDAC: 8 out of 10 patients \(80 %\) with early stage \(UICC IIA/IIB\) and 10 out of 11 \(91 %\) with late stage \(UICC III/IV\) disease. CTC were not found in any of the 10 control patients \(p
- [Usefulness Of Circulating Tumor Cell Detection In Pancreatic Adenocarcinoma Diagnosis. | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-pancreas-publication/usefulness-of-circulating-tumor-cell-detection-in-pancreatic-adenocarcinoma-diagnosis/): No description available.
- [An Assessment Of Diagnostic Performance Of A Filter-based Antibody-independent Peripheral Blood Circulating Tumour Cell Capture Paired With Cytomorphologic Criteria For The Diagnosis Of Cancer | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-poumon-publication/an-assessment-of-diagnostic-performance-of-a-filter-based-antibody-independent-peripheral-blood-circulating-tumour-cell-capture-paired-with-cytomorphologic-criteria-for-the-diagnosis-of-cancer/): Objectives Circulating tumour cells \(CTCs\) are reported to be predictive for prognosis and response to treatment in advanced lung cancer. However, the clinical utility of the CTCs detection remains unknown for early stage lung cancer as the number of CTCs is reported as low, providing challenges in identification. We have evaluated diagnostic performance of filtration-based technology using cytomorphologic criteria in patients undergoing surgery for lung cancer. Material and methods We processed blood from 76 patients undergoing surgery for known or suspected lung cancer using ScreenCell® Cyto filter devices. Captured cells were stained using haematoxylin and eosin and independently assessed by two pathologists for the presence of atypical cells suspicious for cancer. Diagnostic performance was evaluated against pathologist reported diagnoses of cancer from surgically obtained specimens. Results Cancer was diagnosed in 57 patients \(77.0%\), including 32 with primary lung cancer \(56.1%\). The proportion of patients with early stage primary lung cancer in which CTCs were identified was 18 and 21 \(56.3% and 65.6%, respectively\) as reported by two pathologists. The agreement between the pathologists was 77.0% corresponding to a kappa-statistic of 53.7% indicating moderate agreement. No significant differences were found for the percentage of CTCs for primary and metastatic cancer as well as for cancer stages. On sensitivity weighted analysis, a sensitivity and specificity were 71.9% \(95% CI 60.5–83.0\) and 52.9% \(95% CI 31.1–77.0\), respectively. On specificity weighted analysis, a sensitivity and specificity were 50.9% \(95% CI 39.3–64.4\) and 82.4% \(60.4–96.2\), respectively. Conclusion The performance of the tested filter-based antibody-independent technology to capture CTCs using standard cytomorphologic criteria provides the potential of a diagnostic blood test for lung cancer.
- [Circulating Cell-Free DNA And Circulating Tumor Cells As Prognostic And Predictive Biomarkers In Advanced Non-Small Cell Lung Cancer Patients Treated With First-Line Chemotherapy | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-poumon-publication/circulating-cell-free-dna-and-circulating-tumor-cells-as-prognostic-and-predictive-biomarkers-in-advanced-non-small-cell-lung-cancer-patients-treated-with-first-line-chemotherapy/): Cell-free DNA \(cfDNA\) and circulating tumor cells \(CTCs\) are promising prognostic and predictive biomarkers in non-small cell lung cancer \(NSCLC\). In this study, we examined the prognostic role of cfDNA and CTCs, in separate and joint analyses, in NSCLC patients receiving first line chemotherapy. Seventy-three patients with advanced NSCLC were enrolled in this study. CfDNA and CTC were analyzed at baseline and after two cycles of chemotherapy. Plasma cfDNA quantification was performed by quantitative PCR \(qPCR\) whereas CTCs were isolated by the ScreenCell Cyto \(ScreenCell, Paris, France\) device and enumerated according to malignant features. Patients with baseline cfDNA higher than the median value \(96.3 hTERT copy number\) had a significantly worse overall survival \(OS\) and double the risk of death \(hazard ratio \(HR\): 2.14; 95% confidence limits \(CL\) = 1.24–3.68; p-value = 0.006\). Conversely, an inverse relationship between CTC median baseline number \(6 CTC/3 mL of blood\) and OS was observed. In addition, we found that in patients reporting stable disease \(SD\), the baseline cfDNA and CTCs were able to discriminate patients at high risk of poor survival. cfDNA demonstrated a more reliable biomarker than CTCs in the overall population. In the subgroup of SD patients, both biomarkers identified patients at high risk of poor prognosis who might deserve additional/alternative therapeutic interventions.
- [Circulating Tumor Cells And Microemboli Can Differentiate Malignant And Benign Pulmonary Lesions | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-poumon-publication/circulating-tumor-cells-and-microemboli-can-differentiate-malignant-and-benign-pulmonary-lesions/): The presence of circulating tumor cells \(CTC\) or microemboli \(CTM\) in the peripheral blood can theoretically anticipate malignancy of solid lesions in a variety of organs. We aimed to preliminarily assess this capability in patients with pulmonary lesions of suspected malignant nature. We used a cell-size filtration method \(ScreenCell\) and cytomorphometric criteria to detect CTC/CTM in a 3 mL sample of peripheral blood that was taken just before diagnostic percutaneous CT-guided fine needle aspiration \(FNA\) or core biopsy of the suspicious lung lesion. At least one CTC/CTM was found in 47 of 67 \(70%\) patients with final diagnoses of lung malignancy and in none of 8 patients with benign pulmonary nodules. In particular they were detected in 38 \(69%\) of 55 primary lung cancers and in 9 \(75%\) of 12 lung metastases from extra-pulmonary cancers. Sensitivity of CTC/CTM presence for malignancy was 70.1% \(95%CI: 56.9-83.1%\), specificity 100%, positive predictive value 100% and negative predictive value 28.6% \(95%CI: 11.9-45.3%\). Remarkably, the presence of CTC/CTM anticipated the diagnosis of primary lung cancer in 3 of 5 patients with non-diagnostic or inconclusive results of FNA or core biopsy, whereas CTC/CTM were not observed in 1 patient with sarcoidosis and 1 with amarthocondroma. These results suggest that presently, due to the low sensitivity, the search of CTC/CTM cannot replace CT guided percutaneous FNA or core biopsy in the diagnostic work-up of patients with suspicious malignant lung lesions. However, the high specificity may as yet indicate a role in cases with non-diagnostic or inconclusive FNA or core biopsy results that warrants to be further investigated.
- [Circulating Tumor Cells From Surgical Manipulation Predict Recurrence And Poor Prognosis In Non-Small Cell Lung Cancer | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-poumon-publication/circulating-tumor-cells-from-surgical-manipulation-predict-recurrence-and-poor-prognosis-in-non-small-cell-lung-cancer-2/): Background/Objectives: In our previous multicenter prospective controlled study \(UMIN000018602\), we investigated the impact of surgical manipulation on circulating tumor cells \(CTCs\) in patients with non-small cell lung cancer \(NSCLC\). CTCs were detected after surgery in four patients \(4/29, 13.8%\), although CTCs were not present before surgery. These four patients had tumor cells leaked into their bloodstream by surgeons' manipulation. We aimed to clarify long-term outcomes according to the presence of CTCs. Methods: Patients with cT1b-2N0M0 NSCLC scheduled for lobectomy were enrolled, based on the selection criteria of a consolidation-to-ground-glass opacity ratio \(over 50%\). Peripheral blood samples \(≥3 mL\) were collected before surgery \(for pre-CTCs\), during surgery, and immediately after pulmonary vein dissection \(for post-CTCs\). CTCs were isolated from these samples using ScreenCell®'s size-selective method. Results: From July 2015 to January 2016, 29 patients were enrolled, yielding paired pre- and post-CTC samples for all patients. Thirteen patients were pre-CTC positive, and post-CTCs were detected in 17 patients. Survival analysis revealed a statistically significant difference in recurrence-free survival between patients with and without post-CTCs \(p = 0.043\), while pre-CTCs status had no significant impact on recurrence \(p = 0.226\). Patients with post-CTCs had a significantly higher recurrence rate than those without \(p = 0.043\). Half of patients with post-CTCs but without pre-CTCs had recurrence within 5 years after surgery. Conclusions: Post-CTCs emerged as a significant predictor of recurrence following lobectomy; however, it could be possible for thoracic surgeons to prevent recurrence by improving surgical techniques for NSCLC patients with post-CTCs but without pre-CTCs.
- [Circulating Tumor Cells In Diagnosing Lung Cancer: Clinical And Morphologic Analysis | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-poumon-publication/circulating-tumor-cells-in-diagnosing-lung-cancer-clinical-and-morphologic-analysis/): Background: The purpose of this study was to evaluate the value of circulating non-hematologic cells to differentiate benign from malignant lung lesions and their comparison with clinico-histologic features of corresponding primary lesions. Methods: Circulating cells were isolated by size method from peripheral blood of 77 patients with malignant \(n = 60\) and benign \(n = 17\) lung lesions. They were morphologically classified as cells with malignant feature; cells with uncertain malignant feature; and cells with benign feature; then statistically correlated with clinico-cytopathologic characteristics of corresponding lung lesion. Results: Malignant circulating cells were detected in 54 of 60 \(90%\) malignant patients, and in 1 of 17 \(5%\) benign patients; benign circulating cells in 1 of 60 \(1%\) malignant patients and in 15 of 17 \(88%\) benign patients; and circulating cells with uncertain malignant aspect in 5 of 60 \(8%\) malignant patients and 1 of 17 \(5%\) benign patients. For a malignant circulating cells count greater than 25, sensitivity and specificity were 89% and 100%, respectively. The count was significantly correlated with stage, size, and standard uptake value of primary tumor. In 39 of 54 \(72%\) cases, the malignant circulating cells allowed a specific histologic diagnosis of the corresponding primary tumor after immunohistochemical analysis. Conclusions: Malignant circulating cells may be a valid marker in the diagnostic workup of lung lesions. However, our resuts should be corroborated by larger future studies especially for patients having small nodules.
- [Circulating Tumor DNA Reflects Tumor Metabolism Rather Than Tumor Burden In Chemotherapy-Naive Patients With Advanced Non-Small Cell Lung Cancer: 18F-FDG PET/CT Study | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-poumon-publication/circulating-tumor-dna-reflects-tumor-metabolism-rather-than-tumor-burden-in-chemotherapy-naive-patients-with-advanced-non-small-cell-lung-cancer-18f-fdg-pet-ct-study/): We aimed to evaluate the relationships between circulating tumor cells \(CTCs\) or plasma cell–free DNA \(cfDNA\) on one side and a comprehensive range of 18F-FDG PET/CT–derived parameters on the other side in chemotherapy-naive patients with advanced non–small cell lung cancer \(NSCLC\). Methods: From a group of 79 patients included in a trial evaluating the role of pretreatment circulating tumor markers as predictors of prognosis in chemotherapy-naive patients with advanced NSCLC, we recruited all those who underwent 18F-FDG PET/CT for clinical reasons at our institution before inclusion in the trial \(and thus just before chemotherapy\). For each patient, a peripheral blood sample was collected at baseline for the evaluation of CTCs and cfDNA. CTCs were isolated by size using a filtration-based device and then morphologically identified and enumerated; cfDNA was isolated from plasma and quantified by a quantitative polymerase chain reaction using human telomerase reverse transcriptase. The following 18F-FDG PET/CT–derived parameters were computed: maximum diameter of the primary lesion \(T\), of the largest lymph node \(N\), and of the largest metastatic lesion \(M\); SUVmax; SUVmean; size-incorporated SUVmax; metabolic tumor volume; and total lesion glycolysis. All parameters were independently measured for T, N, and M. The associations among CTCs, cfDNA, and 18F-FDG PET/CT–derived parameters were evaluated by multivariate-analysis. Patients were divided into 2 groups according to the presence of either limited metastatic involvement \(M1a or M1b due to extrathoracic lymph nodes only\) or disseminated metastatic disease. The presence or absence of metabolically active bone lesions was also recorded for each patient, and patient subgroups were compared. Results: Thirty-seven patients recruited in the trial matched our PET-based criteria \(24 men; age, 64.5 ± 8.1 y\). SUVmax for the largest metastatic lesion was the only variable independently associated with baseline cfDNA levels \(P = 0.016\). Higher levels of cfDNA were detected in the subgroup of patients with metabolically active bone lesions \(P = 0.02\), but no difference was highlighted when patients with more limited metastatic disease were compared with patients with disseminated metastatic disease. Conclusion: The correlation of cfDNA levels with tumor metabolism, but not with metabolic tumor volume at regional or distant levels, suggests that cfDNA may better reflect tumor biologic behavior or aggressiveness rather than tumor burden in metastatic NSCLC.
- [Circulating Tumour Cells In Patients With Lung Cancer Undergoing Endobronchial Cryotherapy | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-poumon-publication/circulating-tumour-cells-in-patients-with-lung-cancer-undergoing-endobronchial-cryotherapy/): Early diagnosis of lung cancer still poses a major issue, with a large proportion of patients diagnosed at late stages. Therapeutic options and treatment remain limited in these patients. In most cases only palliative therapies are available to alleviate any severe symptoms. Endobronchial cryotherapy \(EC\) is one form of palliative treatment offered to patients with obstructive airway tumours. Although successful, the impact on circulating tumour cell \(CTCs\) spread has not been investigated in detail. This study recruited 20 patients awaiting EC treatment. Baseline and post EC blood samples were analysed for presence of CTCs. Results showed an increase in CTCs following EC in 75% of patients. Significant increases were noticeable in some cases. Although EC is a well-accepted modality of treatment to alleviate symptoms, it may lead to an increase in CTCs, which in turn may have implications for tumour dissemination and metastatic spread.
- [Circulating Tumour Cells In Patients With Malignant Lung Tumors Undergoing Radio-frequency Ablation | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-poumon-publication/circulating-tumour-cells-in-patients-with-malignant-lung-tumors-undergoing-radio-frequency-ablation/): Background/Aim: Radiofrequency ablation \(RFA\) is an increasingly utilised technique in patients with surgically-untreatable lesions. The effect of this therapy on circulating tumor cells \(CTCs\) is unknown. As far as we are aware of, this is the first study to evaluate the effects of RFA on CTCs in patients with malignant lung tumors immediately post-treatment. Patients and Methods: Nine patients with primary or metastatic lung tumors underwent RFA therapy from June to November 2013. Blood samples were taken before and after RFA, and filtered through the ScreenCell CTC capture device. Results: A general increase in CTCs in 7 out of the 9 cases was found, the largest increases were seen in the metastatic group. Conclusion: This study demonstrates that the manipulation and ablative procedure of lung tumors leads to immediate dissemination of tumor cells, the effects of which are unknown and require further investigation.
- [Cluster Circulating Tumor Cells In Surgical Cases Of Lung Cancer | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-poumon-publication/cluster-circulating-tumor-cells-in-surgical-cases-of-lung-cancer/): Objectives A cancer lesion sheds tumor cells into the circulating blood as circulating tumor cells \(CTCs\). Since cluster CTCs have been considered as precursor lesions of metastasis, their clinical implication was investigated in this study according to the preoperative status of cluster CTC detection in surgical cases of clinically early-stage lung cancer. Methods Among 104 surgical patients of early-stage lung cancer, CTCs were extracted from the peripheral blood before surgery using a micro-pore size selection method \(ScreenCell®\) and diagnosed microscopically. Implications of detecting cluster CTC were assessed according to the prognosis and clinicopathological characteristics. Results The status of CTC detection was not detected in 77 cases \(74.0%\), single CTC only detection in 7 cases \(6.7%\), and cluster CTC detected in 20 cases \(19.2%\). Patients with cluster CTCs exhibited significantly lower recurrence-free survival and overall survival than did patients of other groups. In addition, in hazard ratio analysis, the hazard ratios were independent of other predictors of poor prognosis, and detection of cluster CTCs was associated with predictors of poor prognosis. Conclusion Cluster CTCs were detected in cases where the original lung cancer lesion had clinical predictors of poor prognosis and were independent negative predictors of survival.
- [Detection Of Circulating Tumour Cells And Survival Of Patients With Non-small Cell Lung Cancer | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-poumon-publication/detection-of-circulating-tumour-cells-and-survival-of-patients-with-non-small-cell-lung-cancer/): Background: Detection of circulating tumour cells \(CTCs\) in the peripheral blood of lung cancer patients may predict survival. Various platforms exist that allow capture of these cells for further analysis; little work however, has been done with the ScreenCell device, an antibody-independent CTC platform. The aim of our study was to evaluate the ScreenCell device for detection of CTCs in lung cancer patients and to establish correlations of these findings with survival. Materials and Methods: Twenty-three patients, nine males, and fourteen females, underwent surgical treatment from February to May 2014 for non-small cell lung cancer. Thirteen patients had adenocarcinoma and ten squamous cell carcinoma, while eight were at an early stage \(I-II\) and five at a later stage \(III-IV\). Blood samples were obtained prior to surgery and following filtration through the ScreenCell device, were independently reviewed by 2 consultant pathologists. Results: The pathologists were able to independently identify CTCs in 78.3% \(N=18\) and 73.9% \(N=17\) of the cases examined, with overall 80.6% in early stages compared to 60.0% in late stages. The median survival times of positive vs. negative for CTC patients were 1011 and 711 days respectively, with a survival percentage rate of 77.8% and 60% in positive and negative CTC cohorts respectively. Conclusion: The results of this study suggest that the presence of CTCs analyzed by ScreenCell did not necessarily lead to a poorer prognosis in patients with lung cancer after curative surgery.
- [Lack Of Association Between Screencell-detected Circulating Tumour Cells And Long-term Survival Of Patients Undergoing Surgery For Non-small Cell Lung Cancer: A Pilot Clinical Study. | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-poumon-publication/lack-of-association-between-screencell-detected-circulating-tumour-cells-and-long-term-survival-of-patients-undergoing-surgery-for-non-small-cell-lung-cancer-a-pilot-clinical-study/): Circulating tumour cells \(CTCs\) are cancer cells of epithelial origin that are present in peripheral blood samples. ScreenCell detection of CTCs and the association with long term survival in non‑small cell lung cancer \(NSCLC\) patients was evaluated in the present study. A total of 33 patients undergoing surgical resection for NSCLC were recruited. Patients were followed up for 5‑years post‑operatively. Pre‑operative patient bloods samples were processed using ScreenCell. CTCs were detected in 26 \(79%\) patients. In patients who were positive for CTCs, a total of 9 \(35%\) patients succumbed to the disease, whereas in patients negative for CTCs, a total of 4 \(57%\) patients succumbed to the disease \(P=0.29\). No association was identified between positive CTCs and poorer survival \(Chi‑squared 1.47, P=0.23; hazard ratio, 0.42; 95% confidence interval: 0.1‑1.7\). The presence of CTCs detected with ScreenCell does not influence prognosis in patients with NSCLC that was operated on. The high rate of CTC detection is encouraging in supporting this technology to aid early lung cancer diagnosis.
- [Lung Cancer Biopsy Dislodges Tumor Cells Into Circulating Blood. | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-poumon-publication/lung-cancer-biopsy-dislodges-tumor-cells-into-circulating-blood/): Aim: A “seed” of lung cancer metastasis is circulating tumor cells \(CTCs\), which may be dislodged from a tumor during biopsy. This possibility was assessed among patients who underwent lung tumor biopsy using flexible fiber-topic bronchoscopy \(FFB\). Methods: The study involved six patients with non-small cell lung cancer who underwent FFB biopsy to diagnose a lesion pathologically \(5 males and 1 female, median age 63 years, 6 adenocarcinomas, of 4 clinical-stage IA, 1 stage IB, and 1 stage IIIA\), CTCs were extracted from the peripheral vein blood at pre-FFB and at post-FFB using a size selection method. Results: No tumor cell was detected at pre- and post-FFB was in three cases \(50%\); no tumor cells were detected pre-FFB while CTCs were detected at post-FFB in two cases \(33.3%\); and CTCs were detected at pre-FFB with numerous CTCs detected at post-FFB in one case \(17.7%\). In addition, similar tendencies were observed in each analysis of single-cell and clustered-cell categories. Conclusion: These results suggest that a FFB biopsy of lung cancer may potentially dislodge CTCs from a tumor into the circulating peripheral blood.
- [Optimum Diagnostic Pathway And Pathologic Confirmation Rate Of Early Stage Lung Cancer: Results From The VIOLET Randomised Controlled Trial | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-poumon-publication/optimum-diagnostic-pathway-and-pathologic-confirmation-rate-of-early-stage-lung-cancer-results-from-the-violet-randomised-controlled-trial-2/): Background: Pathologic confirmation of lung cancer influences treatment selection for suspected early-stage lung cancer. High pre-treatment tissue confirmation rates are recommended. We sought to define management and outcomes of patients undergoing surgery for primary lung cancer in a UK multi-centre clinical trial. Methods: VIOLET compared minimally invasive video-assisted thoracic surgery versus open surgery for known or suspected lung cancer. Diagnostic patient pathways were identified and methods of tissue confirmation were documented. The outcome of inappropriate lobectomy for benign disease or inappropriate wedge resection for primary lung cancer was compared with respect to the pathologic diagnosis. Findings: From July 2015 to February 2019, 502 patients were randomised and underwent surgery; 262 \(52%\) had a pre-operative pathologic confirmed diagnosis of primary lung cancer, 205 did not have a pre-operative biopsy and 35 had a non-diagnostic pre-operative biopsy. Of the 240 participants without pre-operative pathologic confirmation of primary lung cancer, intraoperative biopsy and frozen section analysis was undertaken in 144 \(60%\). The remaining 96 underwent direct surgical resection without tissue confirmation \(19% of the entire cohort\). Confirmation of histologic diagnosis before surgery was less costly than diagnosis in the operating theatre. The inappropriate surgery rate was 3.6% \(18/502 participants, 7 lobectomy for benign disease, 11 wedge resection for lung cancer\). Interpretation: Low levels of inappropriate resection can be achieved at pre-operative tissue confirmation rates of 50% through a combination of intra-operative confirmatory biopsy and correct risk estimation of lung cancer. Practice needs to be monitored to ensure acceptable levels are consistently achieved.
- [Perioperative Detection Of Circulating Tumour Cells In Patients With Lung Cancer. | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-poumon-publication/perioperative-detection-of-circulating-tumour-cells-in-patients-with-lung-cancer/): Lung cancer is a leading cause of mortality and despite surgical resection a proportion of patients may develop metastatic spread. The detection of circulating tumour cells \(CTCs\) may allow for improved prediction of metastatic spread and survival. The current study evaluates the efficacy of the ScreenCell® filtration device, to capture, isolate and propagate CTCs in patients with primary lung cancer. Prior to assessment of CTCs, the present study detected cancer cells in a proof‑of‑principle‑ experiment using A549 human lung carcinoma cells as a model. Ten patients \(five males and five females\) with pathologically diagnosed primary non‑small cell lung cancer undergoing surgical resection, had their blood tested for CTCs. Samples were taken from a peripheral vessel at the baseline, from the pulmonary vein draining the lobe containing the tumour immediately prior to division, a further central sample was taken following completion of the resection, and a final peripheral sample was taken three days post‑resection. A significant increase in CTCs was observed from baseline levels following lung manipulation. No association was able to be made between increased levels of circulating tumour cells and survival or the development of metastatic deposits. Manipulation of the lung during surgical resection for non‑small cell lung carcinoma results in a temporarily increased level of CTCs; however, no clinical impact for this increase was observed. Overall, the study suggests the ScreenCell® device has the potential to be used as a CTC isolation tool, following further work, adaptations and improvements to the technology and validation of results.
- [Prevalence And Number Of Circulating Tumour Cells And Microemboli At Diagnosis Of Advanced NSCLC | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-poumon-publication/prevalence-and-number-of-circulating-tumour-cells-and-microemboli-at-diagnosis-of-advanced-nsclc/): Purpose Timing and magnitude of blood release of circulating tumour cells \(CTC\) and circulating tumour microemboli \(CTM\) from primary solid cancers are uncertain. We investigated prevalence and number of CTC and CTM at diagnosis of advanced non-small cell lung cancer \(NSCLC\). Methods Twenty-eight consecutive patients with suspected stage III–IV lung cancer gave consent to provide 15 mL of peripheral blood soon before diagnostic CT-guided fine-needle aspiration biopsy \(FNAB\). CTC and CTM \(clusters of ≥3 CTC\) were isolated by cell size filtration \(ScreenCell\), identified and counted by cytopathologists using morphometric criteria and \(in 6 cases\) immunostained for vimentin. Results FNAB demonstrated NSCLC in 26 cases. At least one CTC/3 mL blood \(mean 6.8 ± 3.7\) was detected in 17 \(65 %\) and one CTM \(mean 4.5 ± 3.3\) in 15 \(58 %\) of 26 NSCLC cases. No correlation between number of CTC or CTM and tumour type or stage was observed. Neoplastic cells from both FNA and CTC/CTM were positive for vimentin but heterogeneously. Conclusions CTC can be detected in two-thirds and CTM in more than half of patients with advanced NSCLC at diagnosis. Reasons underlying lack of CTC and CTM in some advanced lung cancers deserve further investigations.
- [Prognostic Relevance Of Circulating Tumor Cells And Circulating Cell-Free DNA Association In Metastatic Non-Small Cell Lung Cancer Treated With Nivolumab | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-poumon-publication/prognostic-relevance-of-circulating-tumor-cells-and-circulating-cell-free-dna-association-in-metastatic-non-small-cell-lung-cancer-treated-with-nivolumab/): The treatment of advanced non-small cell lung cancer \(NSCLC\) has been revolutionized by immune checkpoint inhibitors \(ICIs\). The identification of prognostic and predictive factors in ICIs-treated patients is presently challenging. Circulating tumor cells \(CTCs\) and cell-free DNA \(cfDNA\) were evaluated in 89 previously treated NSCLC patients receiving nivolumab. Blood samples were collected before therapy and at the first and second radiological response assessments. CTCs were isolated by a filtration-based method. cfDNA was extracted from plasma and estimated by quantitative PCR. Patients with baseline CTC number and cfDNA below their median values \(2 and 836.5 ng from 3 mL of blood and plasma, respectively\) survived significantly longer than those with higher values \(p = 0.05 and p = 0.04, respectively\). The two biomarkers were then used separately and jointly as time-dependent covariates in a regression model confirming their prognostic role. Additionally, a four-fold risk of death for the subgroup presenting both circulating biomarkers above the median values was observed \(p < 0.001\). No significant differences were found between circulating biomarkers and best response. However, progressing patients with concomitant lower CTCs and cfDNA performed clinically well \(p = 0.007\), suggesting that jointed CTCs and cfDNA might help discriminate a low-risk population which might benefit from continuing ICIs beyond progression.
- [Y Disruption, Autosomal Hypomethylation And Poor Male Lung Cancer Survival. | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-poumon-publication/y-disruption-autosomal-hypomethylation-and-poor-male-lung-cancer-survival/): Lung cancer is the most frequent cause of cancer death worldwide. It affects more men than women, and men generally have worse survival outcomes. We compared gene co-expression networks in affected and unaffected lung tissue from 126 consecutive patients with Stage IA–IV lung cancer undergoing surgery with curative intent. We observed marked degradation of a sex-associated transcription network in tumour tissue. This disturbance, detected in 27.7% of male tumours in the discovery dataset and 27.3% of male tumours in a further 123-sample replication dataset, was coincident with partial losses of the Y chromosome and extensive autosomal DNA hypomethylation. Central to this network was the epigenetic modifier and regulator of sexually dimorphic gene expression, KDM5D. After accounting for prognostic and epidemiological covariates including stage and histology, male patients with tumour KDM5D deficiency showed a significantly increased risk of death \(Hazard Ratio \[HR\] 3.80, 95% CI 1.40–10.3, P = 0.009\). KDM5D deficiency was confirmed as a negative prognostic indicator in a further 1100 male lung tumours \(HR 1.67, 95% CI 1.4–2.0, P = 1.2 × 10–10\). Our findings identify tumour deficiency of KDM5D as a prognostic marker and credible mechanism underlying sex disparity in lung cancer.
- [Advancing Risk Assessment Of Intermediate Risk Prostate Cancer Patients | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-prostate-publication/advancing-risk-assessment-of-intermediate-risk-prostate-cancer-patients/): The individual risk to progression is unclear for intermediate risk prostate cancer patients. To assess their risk to progression, we examined the level of genomic instability in circulating tumor cells \(CTCs\) using quantitative three-dimensional \(3D\) telomere analysis. Data of CTCs from 65 treatment-naïve patients with biopsy-confirmed D’Amico-defined intermediate risk prostate cancer were compared to radical prostatectomy pathology results, which provided a clinical endpoint to the study and confirmed pre-operative pathology or demonstrated upgrading. Hierarchical centroid cluster analysis of 3D pre-operative CTC telomere profiling placed the patients into three subgroups with different potential risk of aggressive disease. Logistic regression modeling of the risk of progression estimated odds ratios with 95% confidence interval \(CI\) and separated patients into “stable” vs. “risk of aggressive” disease. The receiver operating characteristic \(ROC\) curve showed an area under the curve \(AUC\) of 0.77, while prostate specific antigen \(PSA\) \(AUC of 0.59\) and Gleason 3 + 4 = 7 vs. 4 + 3 = 7 \(p > 0.6\) were unable to predict progressive or stable disease. The data suggest that quantitative 3D telomere profiling of CTCs may be a potential tool for assessing a patient’s prostate cancer pre-treatment risk.
- [Circulating Tumour Cell Numbers Correlate With Platelet Count And Circulating Lymphocyte Subsets In Men With Advanced Prostate Cancer: Data From The ExPeCT Clinical Trial \(CTRIAL-IE 15-21\). | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-prostate-publication/circulating-tumour-cell-numbers-correlate-with-platelet-count-and-circulating-lymphocyte-subsets-in-men-with-advanced-prostate-cancer-data-from-the-expect-clinical-trial-ctrial-ie-15-21/): Interactions between circulating tumour cells \(CTCs\) and platelets are thought to inhibit natural killer\(NK\)-cell-induced lysis. We attempted to correlate CTC numbers in men with advanced prostate cancer with platelet counts and circulating lymphocyte numbers. Sixty-one ExPeCT trial participants, divided into overweight/obese and normal weight groups on the basis of a BMI ≥ 25 or
- [Development And Validation Of Circulating Tumour Cell Enumeration \(Epic Sciences\) As A Prognostic Biomarker In Men With Metastatic Castration-resistant Prostate Cancer | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-prostate-publication/development-and-validation-of-circulating-tumour-cell-enumeration-epic-sciences-as-a-prognostic-biomarker-in-men-with-metastatic-castration-resistant-prostate-cancer/): Purpose: To evaluate the prognostic significance of circulating tumour cell \(CTC\) number determined on the Epic Sciences platform in men with metastatic castration-resistant prostate cancer \(mCRPC\) treated with an androgen receptor signalling inhibitor \(ARSI\). Patients and methods: A pre-treatment blood sample was collected from men with progressing mCRPC starting either abiraterone or enzalutamide as a first-, second- or third-line systemic therapy at Memorial Sloan Kettering Cancer Center \(Discovery cohort, N = 171\) or as a first- or second-line therapy as part of the multicenter PROPHECY trial \(NCT02269982\) \(Validation cohort, N = 107\). The measured CTC number was then associated with overall survival \(OS\) in the Discovery cohort, and progression-free survival \(PFS\) and OS in the Validation cohort. CTC enumeration was also performed on a concurrently obtained blood sample using the CellSearch® Circulating Tumor Cell Kit. Results: In the MSKCC Discovery cohort, CTC count was a statistically significant prognostic factor of OS as a dichotomous \(
- [Filtration-based Enrichment Of Circulating Tumor Cells From All Prostate Cancer Risk Groups | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-prostate-publication/filtration-based-enrichment-of-circulating-tumor-cells-from-all-prostate-cancer-risk-groups/): Objective: To combine circulating tumor cell \(CTC\) isolation by filtration and immunohistochemistry to investigate the presence of CTCs in low, intermediate, and high-risk prostate cancer \(PCa\). CTCs isolated from these risk groups stained positive for both cytokeratin and androgen receptors, but negative for CD45. Patients and methods: Blood samples from 41 biopsy confirmed patients with PCa at different clinical stages such as low, intermediate, and high risk were analyzed. The samples were processed with the ScreenCell filtration device and PCa CTCs were captured for all patients. The isolated CTCs were confirmed PCa CTCs by the presence of androgen receptors and cytokeratins 8, 18, and 19 that occurred in the absence of CD45 positivity. PCa CTC nuclear sizes were measured using the TeloView program. Results: The filtration-based isolation method used permitted the measurement of the average nuclear size of the captured CTCs. CTCs were identified by immunohistochemistry in low, intermediate, and high-risk groups of patients with PCa. Conclusion: CTCs may be found in all stages of PCa. These CTCs can be used to determine the level of genomic instability at any stage of PCa; this will, in the future, enable personalized patient
- [Genomic Analysis Of Localized High-Risk Prostate Cancer Circulating Tumor Cells At The Single-Cell Level | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-prostate-publication/genomic-analysis-of-localized-high-risk-prostate-cancer-circulating-tumor-cells-at-the-single-cell-level/): Accurate risk classification of men with localized high-risk prostate cancer directly affects treatment management decisions and patient outcomes. A wide range of risk assessments and classifications are available. However, each one has significant limitations to distinguish between indolent and aggressive prostate cancers. Circulating tumor cells \(CTCs\) may provide an alternate additional source, beyond tissue biopsies, to enable individual patient-specific clinical assessment, simply because CTCs can reveal both tumor-derived and germline-specific genetic information more precisely than that gained from a single diagnostic biopsy. In this study, we combined a filtration-based CTC isolation technology with prostate cancer CTC immunophenotyping to identify prostate cancer CTCs. Next, we performed 3-D telomere profiling prior to laser microdissection and single-cell whole-exome sequencing \(WES\) of 21 CTCs and 4 lymphocytes derived from 10 localized high-risk prostate cancer patient samples. Localized high-risk prostate cancer patient CTCs present a high number of telomere signals with lower signal intensities \(short telomeres\). To capture the genetic diversity/heterogeneity of high-risk prostate cancer CTCs, we carried out whole-exome sequencing. We identified 202,241 single nucleotide variants \(SNVs\) and 137,407 insertion-deletions \(indels\), where less than 10% of these genetic variations were within coding regions. The genetic variation \(SNVs + indels\) and copy number alteration \(CNAs\) profiles were highly heterogeneous and intra-patient CTC variation was observed. The pathway enrichment analysis showed the presence of genetic variation in nine telomere maintenance pathways \(patients 3, 5, 6, and 7\), including an important gene for telomere maintenance called telomeric repeat-binding factor 2 \(TRF2\). Using the PharmGKB database, we identified nine genetic variations associated with response to docetaxel. A total of 48 SNVs can affect drug response for 24 known cancer drugs. Gene Set Enrichment Analysis \(GSEA\) \(patients 1, 3, 6, and 8\) identified the presence of CNAs in 11 different pathways, including the DNA damage repair \(DDR\) pathway. In conclusion, single-cell approaches \(WES and 3-D telomere profiling\) showed to be useful in unmasking CTC heterogeneity. DDR pathway mutations have been well-established as a target pathway for cancer therapy. However, the frequent CNA amplifications found in localized high-risk patients may play critical roles in the therapeutic resistance in prostate cancer. Accurate risk classification of men with localized high-risk prostate cancer directly affects treatment management decisions and patient outcomes. A wide range of risk assessments and classifications are available. However, each one has significant limitations to distinguish between indolent and aggressive prostate cancers. Circulating tumor cells \(CTCs\) may provide an alternate additional source, beyond tissue biopsies, to enable individual patient-specific clinical assessment, simply because CTCs can reveal both tumor-derived and germline-specific genetic information more precisely than that gained from a single diagnostic biopsy. In this study, we combined a filtration-based CTC isolation technology with prostate cancer CTC immunophenotyping to identify prostate cancer CTCs. Next, we performed 3-D telomere profiling prior to laser microdissection and single-cell whole-exome sequencing \(WES\) of 21 CTCs and 4 lymphocytes derived from 10 localized high-risk prostate cancer patient samples. Localized high-risk prostate cancer patient CTCs present a high number of telomere signals with lower signal intensities \(short telomeres\). To capture the genetic diversity/heterogeneity of high-risk prostate cancer CTCs, we carried out whole-exome sequencing. We identified 202,241 single nucleotide variants \(SNVs\) and 137,407 insertion-deletions \(indels\), where less than 10% of these genetic variations were within coding regions. The genetic variation \(SNVs + indels\) and copy number alteration \(CNAs\) profiles were highly heterogeneous and intra-patient CTC variation was observed. The pathway enrichment analysis showed the presence of genetic variation in nine telomere maintenance pathways \(patients 3, 5, 6, and 7\), including an important gene for telomere maintenance called telomeric repeat-binding factor 2 \(TRF2\). Using the PharmGKB database, we identified nine genetic variations associated with response to docetaxel. A total of 48 SNVs can affect drug response for 24 known cancer drugs. Gene Set Enrichment Analysis \(GSEA\) \(patients 1, 3, 6, and 8\) identified the presence of CNAs in 11 different pathways, including the DNA damage repair \(DDR\) pathway. In conclusion, single-cell approaches \(WES and 3-D telomere profiling\) showed to be useful in unmasking CTC heterogeneity. DDR pathway mutations have been well-established as a target pathway for cancer therapy. However, the frequent CNA amplifications found in localized high-risk patients may play critical roles in the therapeutic resistance in prostate cancer.
- [Platinum-Based Chemotherapy In Metastatic Prostate Cancer With DNA Repair Gene Alterations | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-prostate-publication/platinum-based-chemotherapy-in-metastatic-prostate-cancer-with-dna-repair-gene-alterations/): Purpose: Alterations in DNA damage repair \(DDR\) genes occur in up to 25% of patients with metastatic castration-resistant prostate cancer \(mCRPC\) and may sensitize to platinum chemotherapy. We aimed to evaluate the efficacy of platinum-based chemotherapy in DDR-mutant \(DDRmut\) mCRPC. Methods: We assessed response to platinum chemotherapy based on DDR gene alteration status in men with mCRPC who underwent tumor and germline genomic profiling. Patients with deleterious alterations in a gene panel that included BRCA2, BRCA1, ATM, PALB2, FANCA, and CDK12 were considered DDRmut. Results: A total of 109 patients with mCRPC received platinum-based chemotherapy between October 2013 and July 2018. Sixty-four of 109 patients were taxane refractory and poly \(ADP-ribose\) polymerase inhibitor \(PARPi\) naïve. Within this subset, DDRmut was found in 16/64 patients \(25%\) and was associated with an increased likelihood of achieving a prostate-specific antigen \(PSA\) decline of 50% or more from baseline \(PSA50; odds ratio, 7.0; 95% CI, 1.9 to 29.2\). Time on platinum chemotherapy tended to be longer in the DDRmut group \(median, 3.0 v 1.6 months; hazard ratio, 0.55, 95% CI, 0.29 to 1.24\). No difference in survival was detected. Of 8 patients with DDRmut disease who received platinum-based therapy after a PARPi, 3/7 evaluable patients had radiographic partial response or stable disease, and 2/7 had a PSA50 response. None of 4 patients with ATM mutations had platinum responses regardless of prior PARPi exposure. Conclusion: Patients with DDRmut disease had better response to platinum-based chemotherapy, suggesting that DDR status warrants prospective validation as a potential biomarker for patient selection. Responses to platinum chemotherapy were observed in BRCA-altered prostate cancer after PARPi progression. Additional studies are needed to determine the predictive role of individual genes on platinum sensitivity in the context of other clinical and genomic factors.
- [Prospective Multicenter Study Of Circulating Tumor Cell AR-V7 And Taxane Versus Hormonal Treatment Outcomes In Metastatic Castration-Resistant Prostate Cancer | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-prostate-publication/prospective-multicenter-study-of-circulating-tumor-cell-ar-v7-and-taxane-versus-hormonal-treatment-outcomes-in-metastatic-castration-resistant-prostate-cancer/): Purpose: Androgen receptor splice variant 7 \(AR-V7\) detection in circulating tumor cells \(CTCs\) is associated with a low probability of response and short progression-free \(PFS\) and overall survival \(OS\) in men with metastatic castration-resistant prostate cancer \(mCRPC\) treated with enzalutamide or abiraterone. However, it is unclear whether such men benefit from taxane chemotherapy. Patients and methods: PROPHECY is a multicenter prospective blinded study of patients with poor-risk mCRPC starting abiraterone or enzalutamide and observed through subsequent progression and taxane chemotherapy. We assessed AR-V7 status using the Johns Hopkins modified AdnaTest CTC AR-V7 messenger RNA assay and the Epic Sciences CTC nuclear-localized AR-V7 protein assay before treatment. The primary objective was to validate the independent prognostic value of CTC AR-V7 status based on radiographic/clinical PFS. OS, confirmed prostate-specific antigen \(PSA\), and objective radiologic responses were secondary end points. Results: We enrolled 118 men with mCRPC treated with abiraterone or enzalutamide, 51 of whom received subsequent docetaxel or cabazitaxel. Pretreatment CTC AR-V7 status by the Johns Hopkins and Epic Sciences assays was independently associated with worse PFS \(hazard ratio \[HR\], 1.7; 95% CI, 1.0 to 2.9 and HR, 2.1; 95% CI, 1.0 to 4.4, respectively\) and OS \(HR, 3.3; 95% CI, 1.7 to 6.3 and HR, 3.0; 95% CI, 1.4 to 6.3, respectively\) and a low probability of confirmed PSA responses, ranging from 0% to 11%, during treatment with abiraterone or enzalutamide. At progression, subsequent CTC AR-V7 detection was not associated with an inferior PSA or radiographic response or worse PFS or OS with subsequent taxane chemotherapy after adjusting for CellSearch CTC enumeration and clinical prognostic factors. Conclusion: Detection of AR-V7 in CTCs by two different blood-based assays is independently associated with shorter PFS and OS with abiraterone or enzalutamide, but such men with AR-V7-positive disease still experience clinical benefits from taxane chemotherapy.
- [Single-cell Analysis Of Circulating Tumor Cells Identifies Cumulative Expression Patterns Of EMT-related Genes In Metastatic Prostate Cancer | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-prostate-publication/single-cell-analysis-of-circulating-tumor-cells-identifies-cumulative-expression-patterns-of-emt-related-genes-in-metastatic-prostate-cancer/): Background: Prostate tumors shed circulating tumor cells \(CTCs\) into the blood stream. Increased evidence shows that CTCs are often present in metastatic prostate cancer and can be alternative sources for disease profiling and prognostication. Here we postulate that CTCs expressing genes related to epithelial-mesenchymal transition \(EMT\) are strong predictors of metastatic prostate cancer. Methods: A microfiltration system was used to trap CTCs from peripheral blood based on size selection of large epithelial-like cells without CD45 leukocyte marker. These cells individually retrieved with a micromanipulator device were assessed for cell membrane physical properties using atomic force microscopy. Additionally, 38 CTCs from eight prostate cancer patients were used to determine expression profiles of 84 EMT-related and reference genes using a microfluidics-based PCR system. Results: Increased cell elasticity and membrane smoothness were found in CTCs compared to noncancerous cells, highlighting their potential invasiveness and mobility in the peripheral circulation. Despite heterogeneous expression patterns of individual CTCs, genes that promote mesenchymal transitioning into a more malignant state, including IGF1, IGF2, EGFR, FOXP3, and TGFB3, were commonly observed in these cells. An additional subset of EMT-related genes \(e.g., PTPRN2, ALDH1, ESR2, and WNT5A\) were expressed in CTCs of castration-resistant cancer, but less frequently in castration-sensitive cancer. Conclusions: The study suggests that an incremental expression of EMT-related genes in CTCs is associated with metastatic castration-resistant cancer. Although CTCs represent a group of highly heterogeneous cells, their unique EMT-related gene signatures provide a new opportunity for personalized treatments with targeted inhibitors in advanced prostate cancer patients.
- [Strategies For Isolating And Propagating Circulating Tumor Cells In Men With Metastatic Prostate Cancer | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-prostate-publication/strategies-for-isolating-and-propagating-circulating-tumor-cells-in-men-with-metastatic-prostate-cancer/): Selecting a well-suited method for isolating/characterizing circulating tumor cells \(CTCs\) is challenging. Evaluating sensitive and specific markers for prostate cancer \(PCa\)-specific CTC identification and analysis is crucial. We used the CellCollector EpCAM-functionalized system \(CC-EpCAM\) and evaluated and developed a PCa-functionalized version \(CC-PCa\); we then compared CTC isolation techniques that exploit the physical and biological properties of CTCs. We established two cohorts of metastatic PCa patients \(mPCa; 15 in cohort 1 and 10 in cohort 2\). CTC cultivation experiments were conducted with two capturing methods \(Ficoll and ScreenCell\). The most sensitive detection rates and highest CTC counts were reached with the CC-PCa and ScreenCell system. Patients with ≥5 CTCs isolated with CC-EpCAM had an overall survival \(OS\) of 0.93 years, and patients with ≥5 CTCs isolated with CC-PCa had an OS of 1.5 years in cohort 1. Nevertheless, we observed the highest sensitivity and specificity for 24-month survival by the Ficoll with CD45 depletion and ScreenCell system with May-Grunwald Giemsa \(MGG\) staining. The EpCAM molecule is an essential factor related to OS for CTC isolation based on biological properties in mPCa patients. The best-suited CTC capture system is not limited to one characteristic of cells but adapted to downstream analysis.
- [Three-Dimensional Telomeric Analysis Of Isolated Circulating Tumor Cells \(CTCs\) Defines CTC Subpopulations | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-prostate-publication/three-dimensional-telomeric-analysis-of-isolated-circulating-tumor-cells-ctcs-defines-ctc-subpopulations/): Circulating tumor cells \(CTCs\) have been identified with the potential to serve as suitable biomarkers for tumor stage and progression, but the availability of effective isolation technique\(s\) coupled with detailed molecular characterization have been the challenges encountered in making CTCs clinically relevant. For the first time, we combined isolation of CTCs using the ScreenCell filtration technique with quantitative analysis of CTC telomeres by TeloView. This resulted in the identification and molecular characterization of different subpopulations of CTCs in the same patient. Three-dimensional \(3D\) telomeric analysis was carried out on isolated CTCs of 19 patients that consisted of four different tumor types, namely, prostate, colon, breast, melanoma, and one lung cancer cell line. With telomeric analysis of the filter-isolated CTCs, the level of chromosomal instability \(CIN\) of the CTCs can be determined. Our study shows that subpopulations of CTCs can be identified on the basis of their 3D telomeric properties.
- [Validation Of Cell-Free RNA And Circulating Tumor Cells For Molecular Marker Analysis In Metastatic Prostate Cancer | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-prostate-publication/validation-of-cell-free-rna-and-circulating-tumor-cells-for-molecular-marker-analysis-in-metastatic-prostate-cancer/): Since tissue material is often lacking in metastatic prostate cancer \(mPCa\), there is increasing interest in using liquid biopsies for treatment decision and monitoring therapy responses. The purpose of this study was to validate the usefulness of circulating tumor cells \(CTCs\) and plasma-derived cell-free \(cf\) RNA as starting material for gene expression analysis through qPCR. CTCs were identified upon prostate-specific membrane antigen and/or cytokeratin positivity after enrichment with ScreenCell \(Westford, Massachusetts, USA\) filters or the microfluidic ParsortixTM \(Guildford, Surrey, United Kingdom\) system. Overall, 50% \(28/56\) of the patients had ≥5 CTCs/7.5 mL of blood. However, CTC count did not correlate with Gleason score, serum PSA, or gene expression. Notably, we observed high expression of CD45 in CTC samples after enrichment, which could be successfully eliminated through picking of single cells. Gene expression in picked CTCs was, however, rather low. In cfRNA from plasma, on the other hand, gene expression levels were higher compared to those found in CTCs. Moreover, we found that PSA was significantly increased in plasma-derived cfRNA of mPCa patients compared to healthy controls. High PSA expression was also associated with poor overall survival, indicating that using cfRNA from plasma could be used as a valuable tool for molecular expression analysis.
- [Are Morphological Criteria Sufficient For The Identification Of Circulating Tumor Cells In Renal Cancer? | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-rein-publication/are-morphological-criteria-sufficient-for-the-identification-of-circulating-tumor-cells-in-renal-cancer/): Background: Single circulating tumor cells \(CTCs\) or circulating tumor microemboli \(CTMs\) are potential biomarkers of renal cell cancer \(RCC\), however studies of CTCs/CTMs in RCC are limited. In this pilot study we aimed to evaluate a novel blood filtration technique suited for cytomorphological classification, immunocytochemical and molecular characterization of filtered, so called circulating non-hematologic cells \(CNHCs\) - putative CTCs/CTMs - in patients with RCC. Methods: Blood of 40 patients with renal tumors was subjected to ScreenCell filtration. CNHCs were classified according to cytomorphological criteria. Immunocytochemical analysis was performed with antibodies against CD45, CD31 and carbonic anhydrase IX \(CAIX, a RCC marker\). DNA of selected CNHCs and respective primary tumors was analysed by array-CGH. Results: CNHC-clusters with malignant or uncertain malignant cytomorphological features - putative CTMs - were negative for CD45, positive for CD31, while only 6% were CAIX positive. Array-CGH revealed that 83% of malignant and uncertain malignant cells did represent with a balanced genome whereas 17% presented genomic DNA imbalances which did not match the aberrations of the primary tumors. Putative single CTCs were negative for CD45, 33% were positive for CD31 and 56% were positive for CAIX. Conclusions: The majority of CNHC-clusters, putative CTMs, retrieved by ScreenCell filtration may be of endothelial origin. Morphological criteria seem to be insufficient to distinguish malignant from non-malignant cells in renal cancer.
- [Circulating Tumor Cell Clusters Are Frequently Detected In Women With Early-Stage Breast Cancer | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-sein-publication/circulating-tumor-cell-clusters-are-frequently-detected-in-women-with-early-stage-breast-cancer/): The clinical relevance of circulating tumor cell clusters \(CTC-clusters\) in breast cancer \(BC\) has been mostly studied using the CellSearch®, a marker-dependent method detecting only epithelial-enriched clusters. However, due to epithelial-to-mesenchymal transition, resorting to marker-independent approaches can improve CTC-cluster detection. Blood samples collected from healthy donors and spiked-in with tumor mammospheres, or from BC patients, were processed for CTC-cluster detection with 3 technologies: CellSearch®, CellSieve™ filters, and ScreenCell® filters. In spiked-in samples, the 3 technologies showed similar recovery capability, whereas, in 19 clinical samples processed in parallel with CellSearch® and CellSieve™ filters, filtration allowed us to detect more CTC-clusters than CellSearch® \(median number = 7 versus 1, p = 0.0038\). Next, samples from 37 early BC \(EBC\) and 23 metastatic BC \(MBC\) patients were processed using ScreenCell® filters for attaining both unbiased enrichment and marker-independent identification \(based on cytomorphological criteria\). At baseline, CTC-clusters were detected in 70% of EBC cases and in 20% of MBC patients \(median number = 2, range 0-20, versus 0, range 0-15, p = 0.0015\). Marker-independent approaches for CTC-cluster assessment improve detection and show that CTC-clusters are more frequent in EBC than in MBC patients, a novel finding suggesting that dissemination of CTC-clusters is an early event in BC natural history.
- [Circulating Tumour Cell Enumeration Does Not Correlate With Miller-Payne Grade In A Cohort Of Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-sein-publication/circulating-tumour-cell-enumeration-does-not-correlate-with-miller-payne-grade-in-a-cohort-of-breast-cancer-patients-undergoing-neoadjuvant-chemotherapy/): Purpose The association between pathological complete response \(pCR\) in patients receiving neoadjuvant chemotherapy \(NAC\) for breast cancer and Circulating Tumour Cells \(CTCs\) is not clear. The aim of this study was to assess whether CTC enumeration could be used to predict pathological response to NAC in breast cancer as measured by the Miller–Payne grading system. Methods Twenty-six patients were recruited, and blood samples were taken pre- and post-NAC. CTCs were isolated using the ScreenCell device and stained using a modified Giemsa stain. CTCs were enumerated by 2 pathologists and classified as single CTCs, doublets, clusters/microemboli and correlated with the pathological response as measured by the Miller–Payne grading system. χ2 or ANOVA was performed in SPSS 24.0 statistics software for associations. Results 89% of patients had invasive ductal carcinoma \(IDC\) and 11% invasive lobular carcinoma \(ILC\). At baseline 85% of patients had CTCs present, median 7 \(0–161\) CTCs per 3 ml of whole blood. Post-chemotherapy, 58% had an increase in CTCs. This did not correlate with the Miller–Payne grade of response. No significant association was identified between the number of CTCs and clinical characteristics; however, we did observe a correlation between pre-treatment CTC counts and body mass index, p
- [Comparative Performance Of Different Methods For Circulating Tumor Cell Enrichment In Metastatic Breast Cancer Patients | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-sein-publication/comparative-performance-of-different-methods-for-circulating-tumor-cell-enrichment-in-metastatic-breast-cancer-patients/): The isolation and analysis of circulating tumor cells \(CTC\) has the potential to provide minimally invasive diagnostic, prognostic and predictive information. Widespread clinical implementation of CTC analysis has been hampered by a lack of comparative investigation between different analytic methodologies in clinically relevant settings. The objective of this study was to evaluate four different CTC isolation techniques-those that rely on surface antigen expression \(EpCAM or CD45 using DynaBeads® or EasySep™ systems\) or the biophysical properties \(RosetteSep™ or ScreenCell®\) of CTCs. These were evaluated using cultured cells in order to calculate isolation efficiency at various levels including; inter-assay and inter-operator variability, protocol complexity and turn-around time. All four techniques were adequate at levels above 100 cells/mL which is commonly used for the evaluation of new isolation techniques. Only the RosetteSep™ and ScreenCell® techniques were found to provide adequate sensitivity at a level of 10 cells/mL. These techniques were then applied to the isolation and analysis of circulating tumor cells blood drawn from metastatic breast cancer patients where CTCs were detected in 54% \(15/28\) of MBC patients using the RosetteSep™ and 75% \(6/8\) with ScreenCell®. Overall, the ScreenCell® method had better sensitivity.
- [Detection And Characterization Of Circulating Tumor Associated Cells In Metastatic Breast Cancer | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-sein-publication/detection-and-characterization-of-circulating-tumor-associated-cells-in-metastatic-breast-cancer/): The availability of blood-based diagnostic testing using a non-invasive technique holds promise for real-time monitoring of disease progression and treatment selection. Circulating tumor cells \(CTCs\) have been used as a prognostic biomarker for the metastatic breast cancer \(MBC\). The molecular characterization of CTCs is fundamental to the phenotypic identification of malignant cells and description of the relevant genetic alterations that may change according to disease progression and therapy resistance. However, the molecular characterization of CTCs remains a challenge because of the rarity and heterogeneity of CTCs and technological difficulties in the enrichment, isolation and molecular characterization of CTCs. In this pilot study, we evaluated circulating tumor associated cells in one blood draw by size exclusion technology and cytological analysis. Among 30 prospectively enrolled MBC patients, CTCs, circulating tumor cell clusters \(CTC clusters\), CTCs of epithelial-mesenchymal transition \(EMT\) and cancer associated macrophage-like cells \(CAMLs\) were detected and analyzed. For molecular characterization of CTCs, size-exclusion method for CTC enrichment was tested in combination with DEPArray™ technology, which allows the recovery of single CTCs or pools of CTCs as a pure CTC sample for mutation analysis. Genomic mutations of TP53 and ESR1 were analyzed by targeted sequencing on isolated 7 CTCs from a patient with MBC. The results of genomic analysis showed heterozygous TP53 R248W mutation from one single CTC and pools of three CTCs, and homozygous TP53 R248W mutation from one single CTC and pools of two CTCs. Wild-type ESR1 was detected in the same isolated CTCs. The results of this study reveal that size-exclusion method can be used to enrich and identify circulating tumor associated cells, and enriched CTCs were characterized for genetic alterations in MBC patients, respectively.
- [Did Circulating Tumor Cells Tell Us All They Could? The Missed Circulating Tumor Cell Message In Breast Cancer | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-sein-publication/did-circulating-tumor-cells-tell-us-all-they-could-the-missed-circulating-tumor-cell-message-in-breast-cancer/): Purpose: To compare circulating tumor cell \(CTC\) detection rates in patients with early \(M0\) and metastatic \(M+\) breast cancer using 2 positive-selection methods or size-based unbiased enrichment. Methods: Blood collected at baseline and at different times during treatment from M0 patients undergoing neoadjuvant therapy and from M+ women starting a new line of treatment was processed in parallel using AdnaTest EMT-1/ and EMT-2/Stem CellSelect/Detect kits or ScreenCell Cyto devices. CTC positivity was defined according to the suggested cutoffs and cytological parameters, respectively. Results: Higher CTC detection rates were obtained with the AdnaTest approach when using for CTC-enrichment antibodies against ERBB2 and EGFR in addition to MUC1 and the classical epithelial surface marker EPCAM \(13% vs. 48%\). In M0 patients mainly, CTC positivity rates further increased when EMT- and stemness-related marker expression \(PIK3CA, AKT2 and ALDH1\) was evaluated in addition to EPCAM, MUC1 and ERBB2. When the physical properties of tumor cells were exploited, CTCs were detected at higher percentages than with positive-selection-based methods, without any difference between clinical stages \(78% in M0 vs. 72% in M+ cases at baseline\). Circulating tumor microemboli \(CTMs\) were detected in addition to single CTCs with significantly higher frequency in M0 than M+ samples \(78% vs. 27%, p = 0.0002\). Conclusions: Different approaches for CTC detection probably identify distinct tumor cell subpopulations, but need technical standardization before their clinical validity and biological specificity may be adequately investigated. The distinct role of CTMs compared with CTCs as prognostic and predictive biomarkers represents a further challenge.
- [Ex Vivo Expansion Of Circulating Tumour Cells \(CTCs\) | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-sein-publication/ex-vivo-expansion-of-circulating-tumour-cells-ctcs/): Circulating tumour cells \(CTCs\) are a critical intermediate step in the process of cancer metastasis. The reliability of CTC isolation/purification has limited both the potential to report on metastatic progression and the development of CTCs as targets for therapeutic intervention. Here we report a new methodology, which optimises the culture conditions for CTCs using primary cancer cells as a model system. We exploited the known biology that CTCs thrive in hypoxic conditions, with their survival and proliferation being reliant on the activation of hypoxia-inducible factor 1 alpha \(HIF-1α\). We isolated epithelial-like and quasi-mesenchymal CTC phenotypes from the blood of a cancer patient and successfully cultured these cells for more than 8 weeks. The presence of CTC clusters was required to establish and maintain long-term cultures. This novel methodology for the long-term culture of CTCs will aid in the development of downstream applications, including CTC theranostics.
- [Fast And Efficient Isolation Of Murine Circulating Tumor Cells Using Screencell Technology For Pre-clinical Analyzes | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-sein-publication/fast-and-efficient-isolation-of-murine-circulating-tumor-cells-using-screencell-technology-for-pre-clinical-analyzes/): Circulating tumor cells \(CTCs\) represent a rare and heterogeneous population of cancer cells that are detached from the tumor site and entered blood or lymphatic circulation. Once disseminated in distant tissues, CTCs could remain dormant or create a tumor mass causing serious danger for patients. Many technologies exist to isolate CTCs from patients' blood samples, mostly based on microfluidic systems or by sorting them according to their surface antigens, notably EpCAM, and/or cytokeratins for carcinoma. ScreenCell has developed an easy-to-use, antigen-independent, rapid, cost-effective, and efficient technology that isolates CTCs according to their bigger size compared to the blood cells. This study provides the technical information necessary to isolate and characterize CTCs from mouse blood. By using blood samples from transgenic mice with breast cancer or from WT mice in which we spiked cancer cells, we showed that ScreenCell technology is compatible with standard EDTA blood collection tubes. Furthermore, the ScreenCell Cyto kit could treat up to 500 µl and the ScreenCell MB kit up to 200 µl of mouse blood. As the ScreenCell MB kit captures unaltered live CTCs, we have shown that their DNA could be efficiently extracted, and the isolated cells could be grown in culture. In conclusion, ScreenCell provides a rapid, easy, antigen-independent, cost-effective, and efficient technology to isolate and characterize CTCs from the blood samples of cancer patients and murine models. Thanks to this technology CTCs could be captured fixed or alive. Murine cancer models are extensively used in pre-clinical studies. Therefore, this study demonstrates the crucial technical points necessary while manipulating mouse blood samples using ScreenCell technology.
- [Gene Signatures Of Circulating Breast Cancer Cell Models Are A Source Of Novel Molecular Determinants Of Metastasis And Improve Circulating Tumor Cell Detection In Patients | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-sein-publication/gene-signatures-of-circulating-breast-cancer-cell-models-are-a-source-of-novel-molecular-determinants-of-metastasis-and-improve-circulating-tumor-cell-detection-in-patients/): Background: Progression to stage IV disease remains the main cause of breast cancer-related deaths. Increasing knowledge on the hematogenous phase of metastasis is key for exploiting the entire window of opportunity to interfere with early dissemination and to achieve a more effective disease control. Recent evidence suggests that circulating tumor cells \(CTCs\) possess diverse adaptive mechanisms to survive in blood and eventually metastasize, encouraging research into CTC-directed therapies. Methods: On the hypothesis that the distinguishing molecular features of CTCs reveal useful information on metastasis biology and disease outcome, we compared the transcriptome of CTCs, primary tumors, lymph-node and lung metastases of the MDA-MB-231 xenograft model, and assessed the biological role of a panel of selected genes, by in vitro and in vivo functional assays, and their clinical significance in M0 and M+ breast cancer patients. Results: We found that hematogenous dissemination is governed by a transcriptional program and identified a CTC signature that includes 192 up-regulated genes, mainly related to cell plasticity and adaptation, and 282 down-regulated genes, involved in chromatin remodeling and transcription. Among genes up-regulated in CTCs, FADS3 was found to increases cell membrane fluidity and promote hematogenous diffusion and lung metastasis formation. TFF3 was observed to be associated with a subset of CTCs with epithelial-like features in the experimental model and in a cohort of 44 breast cancer patients, and to play a role in cell migration, invasion and blood-borne dissemination. The analysis of clinical samples with a panel of CTC-specific genes \(ADPRHL1, ELF3, FCF1, TFF1 and TFF3\) considerably improved CTC detection as compared with epithelial and tumor-associated markers both in M0 and stage IV patients, and CTC kinetics informed disease relapse in the neoadjuvant setting. Conclusions: Our findings provide evidence on the potential of a CTC-specific molecular profile as source of metastasis-relevant genes in breast cancer experimental models and in patients. Thanks to transcriptome analysis we generated a novel CTC signature in the MDA-MB-231 xenograft model, adding a new piece to the current knowledge on the key players that orchestrate tumor cell hematogenous dissemination and breast cancer metastasis, and expanding the list of CTC-related biomarkers for future validation studies.
- [Identification Of Atypical Circulating Tumor Cells With Prognostic Value In Metastatic Breast Cancer Patients | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-sein-publication/identification-of-atypical-circulating-tumor-cells-with-prognostic-value-in-metastatic-breast-cancer-patients/): Circulating tumor cells have a strong potential as a quasi-non-invasive tool for setting up a precision medicine strategy for cancer patients. Using a second-generation ""filtration-based"" technology to isolate CTCs, the Screencell™ technology \(Sarcelles, France\), we performed a large and simultaneous analysis of all atypical circulating tumor cells \(aCTCs\) isolated from the blood of metastatic breast cancer \(mBC\) patients. We correlated their presence with clinicopathological and survival data. We included 91 mBC patients from the PERMED-01 study. The median number of aCTCs was 8.3 per mL of blood. Three subsets of aCTCs, absent from controls, were observed in patients: single \(s-aCTCs\), circulating tumor micro-emboli \(CTM\), and giant-aCTCs \(g-aCTCs\). The presence of g-aCTCs was associated with shorter progression free survival and overall survival. This study highlights the heterogeneity of aCTCs in mBC patients both at the cytomorphological and molecular levels. In addition, it suggests the usefulness of the g-aCTC subset as a prognostic factor and a potential stratification tool to treat late-stage mBC patients and improve their chances of benefiting from early clinical trials.
- [Immunomodulatory Activity Of A Colony-stimulating Factor-1 Receptor Inhibitor In Patients With Advanced Refractory Breast Or Prostate Cancer: A Phase I Study | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-sein-publication/immunomodulatory-activity-of-a-colony-stimulating-factor-1-receptor-inhibitor-in-patients-with-advanced-refractory-breast-or-prostate-cancer-a-phase-i-study/): Purpose: Tumor-associated macrophages correlate with increased invasiveness, growth, and immunosuppression. Activation of the colony-stimulating factor-1 receptor \(CSF-1R\) results in proliferation, differentiation, and migration of monocytes/macrophages. This phase I study evaluated the immunologic and clinical activity, and safety profile of CSF-1R inhibition with the mAb LY3022855. Patients and methods: Patients with advanced refractory metastatic breast cancer \(MBC\) or metastatic castration-resistant prostate cancer \(mCRPC\) were treated with LY3022855 intravenously in 6-week cycles in cohorts: \(A\) 1.25 mg/kg every 2 weeks \(Q2W\); \(B\) 1.0 mg/kg on weeks 1, 2, 4, and 5; \(C\) 100 mg once weekly; \(D\)100 mg Q2W. mCRPC patients were enrolled in cohorts A and B; patients with MBC were enrolled in all cohorts. Efficacy was assessed by RECIST and Prostate Cancer Clinical Trials Working Group 2 criteria. Results: Thirty-four patients \(22 MBC; 12 mCRPC\) received ≥1 dose of LY3022855. At day 8, circulating CSF-1 levels increased and proinflammatory monocytes CD14DIMCD16BRIGHT decreased. Best RECIST response was stable disease in five patients with MBC \(23%; duration, 82-302 days\) and three patients with mCRPC \(25%; duration, 50-124 days\). Two patients with MBC \(cohort A\) had durable stable disease >9 months and a third patient with MBC had palpable reduction in a nontarget neck mass. Immune-related gene activation in tumor biopsies posttreatment was observed. Common any grade treatment-related adverse events were fatigue, decreased appetite, nausea, asymptomatic increased lipase, and creatine phosphokinase. Conclusions: LY3022855 was well tolerated and showed evidence of immune modulation. Clinically meaningful stable disease >9 months was observed in two patients with MBC.
- [Liquid Biopsy In Breast Cancer: Redefining Precision Medicine | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-sein-publication/liquid-biopsy-in-breast-cancer-redefining-precision-medicine/): Breast cancer \(BC\) is the most frequent cancer and the leading cause of cancer-related death among women worldwide. It represents a heterogeneous group of diseases with distinct morphological, immunophenotypic, and molecular profiles, which significantly impact clinical behavior and therapeutic response. Moreover, under treatment pressure, tumor cells may undergo molecular changes and phenotypic plasticity, leading to resistance and therapeutic failure. Although tissue biopsy remains the gold standard for diagnosis and molecular characterization, it has several limitations, including invasiveness, sampling bias, and the inability to dynamically capture tumor evolution over time. Hence, a non-invasive and repeatable approach capable of real-time monitoring is increasingly needed. Liquid biopsy \(LB\), through the analysis of circulating tumor cells \(CTCs\) and circulating tumor DNA \(ctDNA\), has emerged as a powerful tool to complement tissue biopsy. It allows for longitudinal assessment of tumor burden, detection of minimal residual disease, and identification of molecular alterations relevant to targeted therapies. Despite promising results, the integration of LB into clinical practice is still limited by methodological heterogeneity, standardization gaps, and regulatory issues. Nonetheless, LB represents a key advancement toward precision oncology and may become essential in the personalized management of BC patients. In this review, we explore the current applications, benefits, and technical limitations of LB in different BC settings. We provide a comprehensive overview of the biological and clinical significance of CTCs and ctDNA, emphasizing their diagnostic, prognostic, and predictive roles. Finally, we present an updated summary of ongoing clinical trials that incorporate LB for clinical decision-making.
- [Optimizing Detection Of Circulating Tumor Cells In Breast Cancer: Unveiling New Markers For Clinical Applications | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-sein-publication/optimizing-detection-of-circulating-tumor-cells-in-breast-cancer-unveiling-new-markers-for-clinical-applications-fr/): Breast cancer \(BC\) is a heterogeneous disease with high metastasis potential, especially in the bones, liver, and lungs. Circulating tumor cells \(CTCs\), which emerge from active tumors, represent an early step toward metastasis and are associated with poor prognosis. CTCs of carcinoma origin are believed to express EpCAM and cytokeratins \(CKs\), common epithelial markers that are frequently used to identify them. However, in practice, the most aggressive CTCs lose the expression of those markers, leading to the partial loss of important information. Thus, finding some novel markers that identify CTCs regardless of their heterogeneity is crucial. A specific bioinformatics workflow integrating primary tumor and diverse BC cell lines transcriptomic expression analysis was developed and compared with single CTC transcriptomic analyses. We have identified a set of genes that are overexpressed in primary BC cells and are commonly upregulated among BC cell lines. Fifty of them were also found to be expressed in BC CTCs by single-cell transcriptomic analysis. Further in silico sorting narrowed this list to 12 genes. Using ScreenCell technology to isolate cancer cells spiked into normal blood, we tested the protein expression of all corresponding genes in vitro using the double immunocytochemistry method and validated MARCKSL1, SLC9A3R1, and RHOD as the most expressed markers. We then isolated the CTCs of 40 LN-invaded BC patients and 18 healthy donors using ScreenCell technology and showed that the combination of these three markers resulted in significantly better recognition of CTCs compared to EpCAM and CK conventional markers. Employing these novel markers, we found a clear distinction between blood samples from patients and healthy donors. In conclusion, through a specific bioinformatics workflow, in addition to in vitro and further clinical validations, we found three novel markers to precisely identify CTCs. These markers, when used together, enable a significantly more efficient identification of CTCs compared to conventional epithelial markers.
- [Rapid And Sensitive Detection Of Breast Cancer Cells In Patient Blood With Nuclease-Activated Probe Technology | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-sein-publication/rapid-and-sensitive-detection-of-breast-cancer-cells-in-patient-blood-with-nuclease-activated-probe-technology/): A challenge for circulating tumor cell \(CTC\)-based diagnostics is the development of simple and inexpensive methods that reliably detect the diverse cells that make up CTCs. CTC-derived nucleases are one category of proteins that could be exploited to meet this challenge. Advantages of nucleases as CTC biomarkers include: \(1\) their elevated expression in many cancer cells, including cells implicated in metastasis that have undergone epithelial-to-mesenchymal transition; and \(2\) their enzymatic activity, which can be exploited for signal amplification in detection methods. Here, we describe a diagnostic assay based on quenched fluorescent nucleic acid probes that detect breast cancer CTCs via their nuclease activity. This assay exhibited robust performance in distinguishing breast cancer patients from healthy controls, and it is rapid, inexpensive, and easy to implement in most clinical labs. Given its broad applicability, this technology has the potential to have a substantive impact on the diagnosis and treatment of many cancers.
- [Impact Of Label-free Technologies In Head And Neck Cancer Circulating Tumour Cells | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-tete-et-cou-publication/impact-of-label-free-technologies-in-head-and-neck-cancer-circulating-tumour-cells/): Background: The ability to identify high risk head and neck cancer \(HNC\) patients with disseminated disease prior to presenting with clinically detectable metastases holds remarkable potential. A fraction of circulating tumour cells \(CTCs\) are invasive cancer cells which mediate metastasis by intravasation, survival and extravasation from the blood stream to metastatic sites. CTCs have been cleared by the FDA for use as surrogate markers of overall survival and progression free survival for breast, prostate and colorectal cancers using the CellSearch® system. However, the clinical significance of CTCs in head and neck cancer patients has yet to be determined. There has been a significant shift in CTC enrichment platforms, away from exclusively single marker selection, to epitope-independent systems. Methods: The aim of this study was to screen advanced stage HNC patients by the CellSearch® platform and utilise two other epitope-independent approaches, ScreenCell® \(microfiltration device\) and RosetteSep™ \(negative enrichment\), to determine how a shift to such methodologies would enable CTC enrichment and detection. Results: In advanced stage HNC patients, single CTCs were detected in 8/43 \(18.6%\) on CellSearch®, 13/28 \(46.4%\) on ScreenCell® and 16/25 \(64.0%\) by RosetteSep™ \(the latter could also detect CTC clusters\). Notably, in patients with suspicious lung nodules, too small to biopsy, CTCs were found upon presentation. Moreover, CTCs were readily detected in advanced stage HNC patients. Conclusion: The epitope-independent platforms detected higher CTC numbers and clusters. Further studies are needed to ascertain whether CTCs can be used as independent prognostic markers for HNCs.
- [Detection Of Circulating Tumour Cells In Urothelial Cancers And Clinical Correlations: Comparison Of Two Methods | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-urothelial-publication/detection-of-circulating-tumour-cells-in-urothelial-cancers-and-clinical-correlations-comparison-of-two-methods/): Circulating tumour cells \(CTC\) are identified exploiting their protein/gene expression patterns or distinct size compared to blood cells. Data on CTC in bladder cancer \(BC\) are still scarce. We comparatively analyzed CTC enrichment by AdnaTest ProstateCancerSelect \(AT\) and ScreenCell®Cyto \(SC\) kits, combined with identification by EPCAM, MUC1, and ERBB2 expression and by cytological criteria, respectively, in 19 nonmetastatic \(M0\) and 47 metastatic \(M+\) BC patients, at baseline \(T0\) and during treatment \(T1\). At T0, CTC positivity rates by AT were higher in M+ compared to M0 cases \(57.4% versus 25%, p = 0.041\). EPCAM was detected in 75% of CTC-positive samples by AT, showing increasing expression levels from T0 to T1 \(median \(interquartile range, IQR\): 0.18 \(0.07–0.42\) versus 0.84 \(0.33–1.84\), p = 0.005\) in M+ cases. Overall, CTC positivity by SC was around 80% regardless of clinical setting and time point of analysis, except for a lower occurrence at T1 in M0 cases. At T0, circulating tumour microemboli were more frequently \(25% versus 8%\) detected and more numerous in M+ compared to M0 patients. The approach used for CTC detection impacts the outcome of CTC studies. Further investigations are required to clarify the clinical validity of AT and SC in specific BC clinical contexts.
- [Cytomorphologic Visualization Of Circulating Tumor Cells In Urinary Bladder Cancer Patients Using ScreenCell™ Technology: Potential As A Simple Cytology Test | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-vessie-publication/cytomorphologic-visualization-of-circulating-tumor-cells-in-urinary-bladder-cancer-patients-using-screencell-technology-potential-as-a-simple-cytology-test/): Circulating tumor cells \(CTC\) are a recent technique which is a potentially important prognostic factor in many solid tumors. There are many techniques of detecting CTCs, but they usually implement costly techniques like EpCAM targeted detection, fluorescence-based diagnosis, or magnetic bead based positive or negative selection. The diagnostic utility of simple cytomorphological diagnosis after routine staining of CTCs have been rarely studied. We aimed to detect CTCs in 24 patients clinically suspected to have Urinary Bladder Cancer using a simple but efficient patented filtration technology \(ScreenCell™\), followed by optical microscopic visualization after routine May-Grunwald-Giemsa \(MGG\) staining. The detected CTCs were then tested for association with the histologic type, lamina propria invasion, deep muscle invasion and the T-stage. Out of the 24 patients tested, one was found to have papilloma, nine had low grade urothelial carcinoma, 13 had high grade urothelial carcinoma and one had poorly differentiated adenocarcinoma. Of these, two LGUC, eight HGUC and one adenocarcinoma had detectable CTC. Presence of CTCs had a statistically significant association with Lamina propria invasion \(P = .006\) and T-stage \(P = .02\), and a trend toward significance for differentiating LGUC from HGUC \(P = .10\). These results suggest that cytomorphological detection of CTC is likely to be clinically useful in diagnosis and prognostication of urinary blader cancers. These findings need to be confirmed on studies with larger sample sizes.
- [The Prognostic Value Of The Circulating Tumor Cell-Based Four MRNA Scoring System: A New Non-Invasive Setting For The Management Of Bladder Cancer | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/cancer-vessie-publication/the-prognostic-value-of-the-circulating-tumor-cell-based-four-mrna-scoring-system-a-new-non-invasive-setting-for-the-management-of-bladder-cancer/): Simple Summary: Bladder cancer with similar diagnosis based on traditional classification exhibits different behaviors and therapeutic outcomes. Thus, circulating tumor cells \(CTCs\) represent a more accurate approach to investigate bladder cancer features. Our results demonstrate that risk score based on EGFR, TRPM4, TWIST1, and ZEB1 four-gene signature in CTCs is markedly and undoubtedly associated with recurrence, suggesting an innovative and non-invasive strategy to manage both non muscle invasive and muscle invasive bladder cancer progression without the necessity of repetitive and onerous cystoscopies. Abstract: Bladder cancer \(BC\) is one of the most expensive lifetime cancers to treat because of the high recurrence rate, repeated surgeries, and long-term cystoscopy monitoring and treatment. The lack of an accurate classification system predicting the risk of recurrence or progression leads to the search for new biomarkers and strategies. Our pilot study aimed to identify a prognostic gene signature in circulating tumor cells \(CTCs\) isolated by ScreenCell devices from muscle invasive and non-muscle invasive BC patients. Through the PubMed database and Cancer Genome Atlas dataset, a panel of 15 genes modulated in BC with respect to normal tissues was selected. Their expression was evaluated in CTCs and thanks to the univariate and multivariate Cox regression analysis, EGFR, TRPM4, TWIST1, and ZEB1 were recognized as prognostic biomarkers. Thereafter, by using the risk score model, we demonstrated that this 4-gene signature significantly grouped patients into high- and low-risk in terms of recurrence free survival \(HR = 2.704, 95% CI = 1.010–7.313, Log-rank p < 0.050\). Overall, we identified a new prognostic signature that directly impacted the prediction of recurrence, improving the choice of the best treatment for BC patients.
- [Cancer-associated Macrophage-like Cells In Patients With Non-metastatic Adenocarcinoma Of The Esophagus - Cytomorphological Heterogeneity | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/divers-publication/adenocarcinome-oesophagien-publication/cancer-associated-macrophage-like-cells-in-patients-with-non-metastatic-adenocarcinoma-of-the-esophagus-cytomorphological-heterogeneity/): Introduction: Esophageal adenocarcinoma \(EAC\) often recurs systemically despite therapy with a curative aim. New diagnostic and therapeutic approaches are urgently needed. A promising field is liquid biopsy, meaning the investigation of tumor-associated cells in the peripheral blood, for example cancer-associated macrophage-like cells \(CAML\). The aim of this multicentric study was to investigate the presence and cytomorphological appearance of CAML in patients with non-metastatic and operable esophageal cancer. Methods: Blood samples from 252 patients with locally advanced EAC were obtained before starting curative treatment including surgery, and then processed using ScreenCell® filtration devices. Cytological analysis was performed via May-Grünwald-Giemsa staining. CAML were defined by their morphological characteristics. We also performed immunofluorescence staining with the mesenchymal marker vimentin on a subset of our study cohort. Results: We detected cytomorphologically heterogeneous CAML in 31.8% \(n=80\) patients. Their presence and cell count did not correlate significantly with pretherapeutic cTNM. Even in patients with small tumors and no lymph-node infiltration, cell counts were high. CAML showed heterogenous staining patterns for vimentin. Conclusion: This is one of the first studies demonstrating the presence and phenotype of CAML in a uniquely broad cohort of EAC patients. As they are believed to be representatives of the inflammatory tumor microenvironment shed into the bloodstream, their presence in non-metastatic EAC is a promising finding.
- [Cytopathological Heterogeneity Of Circulating Tumor Cells In Non-metastatic Esophageal Adenocarcinoma | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/divers-publication/adenocarcinome-oesophagien-publication/cytopathological-heterogeneity-of-circulating-tumor-cells-in-non-metastatic-esophageal-adenocarcinoma/): Background/Aim: The presence of circulating tumor cells \(CTC\) has been reported to have an impact on prognosis in different tumor entities. Little is known about CTC morphology and heterogeneity. Patients and Methods: In a multicenter setting, pre-therapeutic peripheral blood specimens were drawn from patients with non-metastatic esophageal adenocarcinoma \(EAC\). CTCs were captured by size-based filtration \(ScreenCell®\), subsequently Giemsa-stained and evaluated by two trained readers. The isolated cells were categorized in groups based on morphologic criteria. Results: Small and large single CTCs, as well as CTC-clusters, were observed in 69.2% \(n=81\) of the 117 specimens; small CTCs were observed most frequently \(59%; n=69\), followed by large CTCs \(40%; n=47\) and circulating cancer-associated macrophage-like cells \(CAMLs; 34.2%, n=40\). Clusters were rather rare \(12%; n=14\). CTC/CAML were heterogeneous in the cohort, but also within one specimen. Neither the presence of the CTC subtypes/CAMLs nor the exact cell count were associated with the primary clinical TNM stage. Conclusion: Morphologically heterogenic CTCs and CAMLs are present in patients with non-metastatic, non-pretreated EAC.
- [Non-Metastatic Esophageal Adenocarcinoma: Circulating Tumor Cells In The Course Of Multimodal Tumor Treatment | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/divers-publication/adenocarcinome-oesophagien-publication/non-metastatic-esophageal-adenocarcinoma-circulating-tumor-cells-in-the-course-of-multimodal-tumor-treatment/): Background: Isolation of circulating tumor cells \(CTC\) holds the promise to improve response-prediction and personalization of cancer treatment. In this study, we test a filtration device for CTC isolation in patients with non-metastatic esophageal adenocarcinoma \(EAC\) within recent multimodal treatment protocols. Methods: Peripheral blood specimens were drawn from EAC patients before and after neoadjuvant chemotherapy \(FLOT\)/chemoradiation \(CROSS\) as well as after surgery. Filtration using ScreenCell® devices captured CTC for cytologic analysis. Giemsa-stained specimens were evaluated by a cytopathologist; the cut-off was 1 CTC/specimen \(6 mL\). Immunohistochemistry with epithelial \(pan-CK\) and mesenchymal markers \(vimentin\) was performed. Results: Morphologically diverse malignant CTCs were found in 12/20 patients in at least one blood specimen. CTCs were positive for both vimentin and pan-CK. More patients were CTC positive after neoadjuvant therapy \(6/20 vs. 9/15\) and CTCs per/ml increased in most of the CTC-positive patients. After surgery, 8/13 patients with available blood specimens were still CTC positive. In clinical follow-up, 5/9 patients who died were CTC-positive. Conclusions: Detection of CTC by filtration within multimodal treatment protocols of non-metastatic EAC is feasible. The rate of CTC positive findings and the quantity of CTCs changes in the course of multimodal neoadjuvant chemoradiation/chemotherapy and surgery.
- [Detection Of Circulating Tumor Cells In Patients With Adrenocortical Carcinoma: A Monocentric Preliminary Study | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/divers-publication/carcinome-adenocortical-publication/detection-of-circulating-tumor-cells-in-patients-with-adrenocortical-carcinoma-a-monocentric-preliminary-study/): Context: Adrenocortical carcinoma \(ACC\) is a rare malignancy, the prognosis of which is mainly dependent on stage at diagnosis. The identification of disease-associated markers for early diagnosis and drug monitoring is mandatory. Circulating tumor cells \(CTCs\) are released into the bloodstream from primary tumor/metastasis. CTC detection in blood samples may have enormous potential for assisting in the diagnosis of malignancy, estimating prognosis, and monitoring the disease. Objective: The aim of the study was to investigate the presence of CTCs in blood samples of patients with ACC or benign adrenocortical adenoma \(ACA\). Setting: We conducted the study at a university hospital. Intervention: CTC analysis was performed in blood samples from 14 ACC patients and 10 ACA patients. CTCs were isolated on the basis of cell size by filtration through ScreenCell devices, followed by identification according to validated morphometric criteria and immunocytochemistry. Main outcome measure: We measured the difference in CTC detection between ACC and ACA. Results: CTCs were detected in all ACC samples, but not in ACA samples. Immunocytochemistry confirmed the adrenocortical origin. When ACC patients were stratified according to the median value of tumor diameter and metastatic condition, a statistically significant difference was found in the number of CTCs detected after surgery. A significant correlation between the number of CTCs in postsurgical samples and clinical parameters was found for tumor diameter alone. Conclusions: Our findings provide the first evidence for adrenocortical tumors that CTCs may represent a useful marker to support differential diagnosis between ACC and ACA. The correlation with some clinical parameters suggests a possible relevance of CTC analysis for prognosis and noninvasive monitoring of disease progression and drug response.
- [Thoracic Surgery In The UK | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/divers-publication/chirurgie-thoracique-publication/thoracic-surgery-in-the-uk/): No description available.
- [Liquid Biopsy In Rare Cancers: Lessons From Hemangiopericytoma. | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/divers-publication/hemangiopericytome-publication/liquid-biopsy-in-rare-cancers-lessons-from-hemangiopericytoma/): Hemangiopericytoma \(HPT\) is a rare mesenchymal tumor of fibroblastic type and for its rarity is poorly studied. The most common sites of metastatic disease in patients with intracranial HPT are the bone, liver, and lung, suggestive for an hematogenous dissemination; for this reason, we investigated, for the first time, the presence of circulating tumor cells \(CTCs\) in hemangiopericytoma patient by CellSearch® and SceenCell® devices. Peripheral blood samples were drawn and processed by CellSearch, an EpCAM-dependent device, and ScreenCell®, a device size based. We found nontypical CTCs by CellSearch system and the immunofluorescence analysis performed on CTCs isolate by ScreenCell demonstrated the presence of single CTCs and CTC clusters. The molecular characterization of single CTCs and CTC clusters, using antibodies directed against EpCAM, CD34, cytokeratins \(8, 18, and 19\), and CD45, showed a great heterogeneity in CTC clusters. We believe that the present study may open a new scenario in the rare tumors: the introduction of the liquid biopsy and the molecular characterization of circulating tumor cells could lead to personalized targeted treatments and also for rare tumors.
- [Rapid And Simple Isolation Of Circulating Tumor Cells For Clinical And Research Applications Using ScreenCell ® | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/divers-publication/livre-blanc-publication/rapid-and-simple-isolation-of-circulating-tumor-cells-for-clinical-and-research-applications-using-screencell/): Circulating tumor cells \(CTCs\) are malignant cells shed by the primary tumor or metastases into the peripheral circulation. CTCs give rise to distant metastases that are usually the ultimate cause of cancer-related death. A significant proportion of patients with early stage cancer in whom no metastases are identifiable will ultimately relapse as a result of hematogenous spread of tumor cells that were undetected at initial diagnosis and treatment.
- [Rapid Separation Of Mononuclear Hodgkin From Multinuclear Reed-sternberg Cells | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/divers-publication/lymphome-de-hodgkin-publication/rapid-separation-of-mononuclear-hodgkin-from-multinuclear-reed-sternberg-cells/): We describe a method to isolate small mononucleated Hodgkin \(H\) cells from multinucleated Reed Sternberg \(RS\) cells of Hodgkin lymphoma using the ScreenCell filter device. This filtration-based approach lends itself to future clinical applications in that it enables the separation of H and RS cells from lymph node biopsies, bone marrow aspirates, pleural effusions, and blood, including the isolation of monoclonal Hodgkin precursor cells from the blood.
- [A New Device For Rapid Isolation By Size And Characterization Of Rare Circulating Tumor Cells | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/divers-publication/preuve-de-concept-publication/a-new-device-for-rapid-isolation-by-size-and-characterization-of-rare-circulating-tumor-cells/): Background: Circulating tumor cells \(CTCs\) likely derive from clones in the primary tumor, suggesting that they can be used for all biological tests applying to the primary cells. Materials and methods: The ScreenCell® devices are single-use and low-cost innovative devices that use a filter to isolate and sort tumor cells by size. Results: The ScreenCell® Cyto device is able to isolate rare, fixed, tumor cells, with a high recovery rate. Cells are well preserved morphologically. Immunocytochemistry and FISH assays can be performed directly on the filter. The ScreenCell® CC device allows isolation of live cells able to grow in culture. High quality genetic materials can be obtained directly from tumor cells isolated on the ScreenCell® MB device filter. Conclusion: Due to their reduced size, versatility, and capacity to isolate CTCs within minutes, the ScreenCell® devices may be able to simplify and improve non-invasive access to tumor cells.
- [Evaluating Circulating Tumour Cell Enrichment Techniques To Establish An Appropriate Method For Clinical Application In Glioblastomas | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/glioblastome-publication/evaluating-circulating-tumour-cell-enrichment-techniques-to-establish-an-appropriate-method-for-clinical-application-in-glioblastomas/): Brain tumours reduce life expectancy for an average of 20 years per patient, the highest of any cancer. A third of brain tumour patients visit their GP at least five times before diagnosis and many of those are diagnosed late through emergency departments. A possible solution to this challenge is to utilise a ""liquid biopsy"" blood test designed for circulating tumour cells \(CTCs\). Such a test could be applied at a primary healthcare centre, contributing to informed decision making for diagnostic imaging referrals. Furthermore, it could also be applied at secondary health care centres for the ongoing monitoring of disease recurrence. There is increased interest in CTC enrichment methods as a potential approach for faster diagnosis and monitoring of disease progression. The aim of this review to compare four CTC enrichment methods - OncoQuick®, Screen Cell®, pluriBead® and Cell Search® - with the objective of identifying a suitable method for application in the clinical setting for the isolation of CTCs from glioblastomas.
- [Isolation And Characterization Of Circulating Melanoma Cells By Size Filtration And Fluorescent In-situ Hybridization. | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/melanome-publication/isolation-and-characterization-of-circulating-melanoma-cells-by-size-filtration-and-fluorescent-in-situ-hybridization/): Isolation of circulating tumor cells \(CTCs\) from blood of melanoma patients has been difficult owing to inconsistent expression of surface antigens. Here we report on the isolation, detection, and characterization of CTCs from blood of melanoma patients using microfiltration and fluorescent in-situ hybridization \(FISH\). Two tubes of blood from 15 patients with advanced melanoma were collected. These two tubes subsequently underwent filtration through a membrane with pore sizes of 7.5 μm. Isolated cells from one tube were analyzed by FISH for RREB1 \(6p24\), MYB \(6q32\), SE6 \(D6Z1\), and CCND1 \(11q13\) and the other paired specimen was analyzed by immunofluorescence for HMB45, melanoma-associated antigen recognized by T cells-1, tyrosinase and melanogenesis associated transcription factor. We identified CTCs in 10 out of 13 melanoma samples by immunofluorescence \(2.5–99 CTCs/3 ml of blood\) and in 13 specimens by FISH \(7.2–76 CTCs/3 ml of blood\) with more CTCs identified by FISH in 10 out 13 samples. Two filters failed. Our results show that CTCs are detectable in the majority of patients with advanced melanoma. These tools will be useful in characterizing treatment related changes of melanoma in CTCs.
- [Isolation And Profiling Of Single Circulating Tumor Cells In Myeloma: A New Workflow For Liquid Biopsies. | ScreenCell](https://www.screencell.com/fr/publications-scientifiques/myelome/isolation-and-profiling-of-single-circulating-tumor-cells-in-myeloma-a-new-workflow-for-liquid-biopsies/): Minimal residual disease \(MRD\) is a key prognostic marker for progression-free and overall survival in multiple myeloma \(MM\). Existing high sensitivity assays primarily focus on tumor burden assessment, rely on bone marrow sampling, and are limited in their ability to support frequent longitudinal disease monitoring. Here, we describe a proof-of-principle workflow for isolating morphologically preserved circulating tumor cells \(CTCs\) from peripheral blood \(PB\) using size-based filtration. Based on controlled spiking experiments with RPMI 8226 myeloma cells, we demonstrate an analytical limit of detection of approximately 1 tumor cell per 107 white blood cells. Isolated cells retain nuclear integrity and cytomorphology, allowing for downstream immuno­phenotyping, three-dimensional \(3D\) telomere fluorescence in situ hybridization \(FISH\), and single-cell telomere profiling, a known marker of genomic instability and disease progression in multiple myeloma. The proposed workflow demonstrated its feasibility for isolating, profiling, and analyzing plasma cells from PB of MM patients at different disease stages. It revealed distinct nuclear and telomeric features in MM CTCs compared with normal lymphocytes. The established technically robust liquid biopsy workflow enables 3D telomere profiling of MM CTCs that can be adopted for noninvasive MRD monitoring based on genomic instability rather than on the enumeration of MM plasma cells alone.
- [Quel Kit ScreenCell Correspond À Mon Application ? | Test Biopsie Liquide](https://www.screencell.com/fr/quel-kit-screencell-correspond-a-mon-application/): Trouvez le kit ScreenCell qui correspond à vos besoins en recherche ou en routine clinique pour la capture des CTC grâce à la biopsie liquide.
- [Ressources | ScreenCell](https://www.screencell.com/fr/ressources/): Ressources Découvrez toutes nos ressources Publications scientifiques Voir tout Webinaires et vidéos Voir tout Regardez les shorts ScreenCell® Voir toutes les
- [Blog | ScreenCell](https://www.screencell.com/fr/ressources/blog-fr/): Notre dernier article de blog Par catégories Actualités Produit Société Blog Science Communiqué de presse Étude clinique Cancer du sein Mélanome Événements
- [Publications Scientifiques | ScreenCell](https://www.screencell.com/fr/ressources/publications-scientifiques/): Découvrez nos articles scientifiques sur l'isolement des CTC et la biopsie liquide rédigés par nos clients et partenaires.
- [Vidéos | ScreenCell](https://www.screencell.com/fr/ressources/videos/): Découvrez nos articles scientifiques sur l'isolement des CTC et la biopsie liquide rédigés par nos clients et partenaires.
- [Technologie ScreenCell® – Isolement Des Cellules Tumorales Circulantes \(CTC\) Par Microfiltration](https://www.screencell.com/fr/technologie-isolement-ctc-microfiltration/): Découvrez la technologie ScreenCell®, une solution innovante d’isolement des cellules tumorales circulantes \(CTC\) par microfiltration.
- [ScreenCell Kit CSB | Isoler Et Caractériser Facilement Les CTC.](https://www.screencell.com/fr/technologie-isolement-ctc-microfiltration/kit-csb/): Découvrez le Kit CSB de ScreenCell, un dispositif à usage unique de biopsie liquide dédié à la capture des Cellules Tumorales Circulantes.
- [ScreenCell Kit CYTO | Isoler Et Caractériser Facilement Les CTC.](https://www.screencell.com/fr/technologie-isolement-ctc-microfiltration/kit-cyto/): Découvrez le kit CYTO de ScreenCell, un dispositif à usage unique dédié à la capture des CTC pour vos analyses cytologiques.
- [ScreenCell Kit FCD | Isoler Et Caractériser Facilement Les CTC.](https://www.screencell.com/fr/technologie-isolement-ctc-microfiltration/kit-fcd/): Découvrez le Kit FCD de ScreenCell, un dispositif à usage unique de biopsie liquide dédié à la capture des Cellules Tumorales Circulantes.
- [ScreenCell Kit FCD-SP | Isoler Et Caractériser Facilement Les CTC.](https://www.screencell.com/fr/technologie-isolement-ctc-microfiltration/kit-fcdsp/): Découvrez le Kit FCD-SP de ScreenCell, un dispositif à usage unique de biopsie liquide dédié à la capture des Cellules Tumorales Circulantes.
- [ScreenCell Kit LCD | Isoler Et Caractériser Facilement Les CTC.](https://www.screencell.com/fr/technologie-isolement-ctc-microfiltration/kit-lcd/): Découvrez le kit LCD de ScreenCell, un dispositif à usage unique de biopsie liquide dédié à la capture des Cellules Tumorales Circulantes.
- [ScreenCell Kit MB | Isoler Et Caractériser Facilement Les CTC.](https://www.screencell.com/fr/technologie-isolement-ctc-microfiltration/kit-mb/): Découvrez le Kit MB de ScreenCell, un dispositif à usage unique de biopsie liquide dédié à la capture des Cellules Tumorales Circulantes.
- [ScreenCell Kit MBSB | Isoler Et Caractériser Facilement Les CTC.](https://www.screencell.com/fr/technologie-isolement-ctc-microfiltration/kit-mbsb/): Découvrez le Kit MBSB de ScreenCell, un dispositif à usage unique de biopsie liquide dédié à la capture des Cellules Tumorales Circulantes.
- [Can We Isolate Viable #ctcs For Downstream Applications? Emile Lakis Answers Your Question #2 ! | ScreenCell](https://www.screencell.com/fr/video-fr/format-short/can-we-isolate-viable-ctcs-for-downstream-applications-emile-lakis-answers-your-question-2-2/): No description available.
- [Can We Perform Mutational Studies On CTCs Enriched By ScreenCell Technology? | ScreenCell](https://www.screencell.com/fr/video-fr/format-short/can-we-perform-mutational-studies-on-ctcs-enriched-by-screencell-technology-2/): No description available.
- [CTCs In Clinical Routine: What Concrete Applications? Our CSO Answers Your Question | ScreenCell](https://www.screencell.com/fr/video-fr/format-short/ctcs-in-clinical-routine-what-concrete-applications-our-cso-answers-your-question-2/): No description available.
- [Is ScreenCell's Technology Sensitive Enough To Detect Small Amounts Of Circulating Tumor Cells ? | ScreenCell](https://www.screencell.com/fr/video-fr/format-short/is-screencells-technology-sensitive-enough-to-detect-small-amounts-of-circulating-tumor-cells-2/): No description available.
- [Learn In Depth How Our CTCs Isolation Support #cancerresearch | ScreenCell](https://www.screencell.com/fr/video-fr/format-short/learn-in-depth-how-our-ctcs-isolation-support-cancerresearch-2/): No description available.
- [Q&A: Emile Lakis Answers Your Question! #1 | ScreenCell](https://www.screencell.com/fr/video-fr/format-short/qa-emile-lakis-answers-your-question-1-2/): No description available.
- [What Role Will The Analysis Of Circulating Tumor Cells \(CTCs\) Play In 2024 ? | ScreenCell](https://www.screencell.com/fr/video-fr/format-short/what-role-will-the-analysis-of-circulating-tumor-cells-ctcs-play-in-2024-2/): No description available.