"Principle Test" for Isolation and Characterization of Circulating Cancer Cells (CTC)-CXCR4+.
Ontology highlight
ABSTRACT:
DISEASE(S): Neoplasm Malignant,Neoplasms
PROVIDER: 46798 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:This pilot study will aim to determine whether circulating tumor cells (CTCs) can be captured using the novel cMET based ferrofluid. The primary objective of this pilot study will be to describe the numbers of c-MET expressing cells that can be detected by the c-MET CTC capture technique. These data will be separated by disease site. The investigator will also describe the detection rates of both the c-MET CTC capture and the EpCAM CTC capture techniques in each patient, also separated by disease site.
| 2162178 | ecrin-mdr-crc
Project description:Head and neck cancer is the seventh most common cancer in Australia and globally. Despite the current improved treatment modalities, there is still up to 50?60% local regional recurrence and or distant metastasis. High-resolution medical imaging technologies such as PET/CT and MRI do not currently detect the early spread of tumour cells, thus limiting the potential for effective minimal residual detection and early diagnosis. Circulating tumour cells (CTCs) are a rare subset of cells that escape from the primary tumour and enter into the bloodstream to form metastatic deposits or even re-establish themselves in the primary site of the cancer. These cells are more aggressive and accumulate gene alterations by somatic mutations that are the same or even greater than the primary tumour because of additional features acquired in the circulation. The potential application of CTC in clinical use is to acquire a liquid biopsy, by taking a reliable minimally invasive venous blood sample, for cell genotyping during radiotherapy treatment to monitor the decline in CTC detectability, and mutational changes in response to radiation resistance and radiation sensitivity. Currently, very little has been published on radiation therapy, CTC, and circulating cancer stem cells (CCSCs). The prognostic value of CTC in cancer management and personalised medicine for head and neck cancer radiotherapy patients requires a deeper understanding at the cellular level, along with other advanced technologies. With this goal, this review summarises the current research of head and neck cancer CTC, CCSC and the molecular targets for personalised radiotherapy response.
| S-EPMC6468366 | biostudies-literature
Project description:Circulating tumour cell (CTC) behaviours are distinct from those of bulk tissues. Thus, treatments to eliminate CTCs differ from the regimens followed to reduce the primary tumour and its metastases. Accordingly, comprehensively deciphering the single nucleotide variant (SNV) profiles in CTCs, which partially determine CTC behaviours, is a priority. Using viable CTCs isolated with the oHSV1?hTERT?GFP virus coupled with fluorescence?activated cell sorting (FACS), the whole genome was amplified using the multiple annealing and looping?based amplification cycle (MALBAC) method. CTC behaviours were evaluated using the SNVs found to be recurrently mutated in different cells (termed CTC?shared SNVs). Analysis of the sequencing data of 11 CTCs from 8 patients demonstrated that SNVs accumulated sporadically among CTCs and their matched primary tumours (22 co?occurring mutated genes were identified in the exomes of CTCs and their matched primary tissues and metastases), and 394 SNVs were shared by at least two CTCs. Mutated APC and LRP1B genes co?occurred in CTC?shared and bulk?tissue SNVs. Additionally, the breast?originating identity of the CTC?shared SNVs was verified, and they demonstrated the following CTC behaviours: i) intravasation competency; ii) increased migration or motility; iii) enhanced cell?cell interactions; iv) variation in energy metabolism; v) an activated platelet or coagulation system; and vi) dysfunctional mitosis. These results demonstrated that it is feasible to capture and amplify the genomes of single CTCs using the described pipeline. CTC?shared SNVs are a potential signature for identifying the origin of the primary tumour in a liquid biopsy. Furthermore, CTCs demonstrated some behaviours that are unique from those of bulk tissues. Therefore, therapies to eradicate these precursors of metastasis may differ from the existing traditional regimens.
| S-EPMC5928770 | biostudies-literature
Project description:In many patients with solid tumors circulating tumor cells (CTCs), that form metastases, can be identified in peripheral blood. Detection and characterization of CTCs in cancer patients provide a unique opportunity to predict patient survival, select and monitor the efficacy of treatment as well as to gain insights into the cascade of metastatic events. Here, we describe a novel approach to identify CTC-specific molecular markers. Using an integrated platform for immunomagnetic enrichment and immunofluorescent identification of CTCs, blood samples with large numbers of CTCs were identified from patients with colorectal, prostate and breast cancers. Despite enrichment, CTCs are still outnumbered by "nonspecifically" captured leukocytes. In order to determine gene expression profile for CTCs, "background" gene expression signature of white blood cells must be taken into account. To this end, following enrichment for CTCs, RNA was also extracted from the remaining CTC-depleted blood samples. The following samples were used to generate the global expression profiles for CTCs: 1a) SAMPLE170711SUB735: CTC-enriched blood sample from a patient with breast cancer). 3700 CTCs were identified per 7.5 ml of peripheral blood in this patient. 1b) SAMPLE170712SUB735: Corresponding CTC-depleted blood sample for the above patient with breast cancer. 2a) SAMPLE170829SUB750: CTC-enriched blood sample from a patient with prostate cancer. 647 CTCs were identified per 7.5 ml of peripheral blood in this patient. 2b) SAMPLE170830SUB750: Corresponding CTC-depleted blood sample for the above patient with prostate cancer. 3a) SAMPLE170831SUB751: CTC-enriched sample from a patient with colorectal cancer. 180 CTCs were identified per 7.5 ml of peripheral blood in this patient. 3b) SAMPLE170832SUB751: Corresponding CTC-depleted blood sample for the above patient with colorectal cancer.
| S-ECPF-MEXP-136 | biostudies-other
Project description:A large, prospective, non-interventional study was designed to study gene expression changes in peripheral blood mononuclear cells (PBMCs) associated with asthma exacerbations over the course of a year. PBMC samples were collected from subjects at the time of the study visits defined as 1) Quiet: during stable disease at 3 month intervals, 2) Exacerbation: during a 14 day period of deteriorating asthma and 3) Follow-up: within 14 days after cessation of an exacerbation. Gene expression levels during stable asthma, exacerbation, and two weeks after an exacerbation were compared.
2011-07-14 | GSE19301 | GEO
Project description:Attempts have been made to use CTC values for interpretation of treatment response and to guide change of chemotherapy by using a static cut-off of 5 CTC to stratify patients in favourable or unfavourable responders. We propose a new approach to interpret treatment effect using significant changes in CTC values (SCV-limits(1)) as grouping parameter for responders and non-responders to chemotherapy among metastatic breast cancer (mBC) patients.CTC were analysed using the CellSearch System in blood from 47 mBC patients before the start of new chemotherapy and before the third cycle of therapy. The new and old approach to interpret changes in CTC values were compared in relation to progression free survival (PFS).The new approach using significant CTC change (P = .032) and the old approach using static cut-off (P > .001) correlated significantly with PFS using a cohort of 47 patients.We propose a new approach to interpret significant changes between baseline and follow-up CTC values as a tool for assessing treatment effect in mBC. Our approach stratified patients in new risk groups that were stratified significantly with respect to PFS. More patients are needed to balance the size of the risk groups for better comparison to the existing approach based on a 5 CTC cut-off.
| S-EPMC4311024 | biostudies-other
Project description: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.
| S-EPMC3573654 | biostudies-literature
Project description:PURPOSE:Liquid biopsies, including circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), can be used to understand disease prognosis, tumor heterogeneity, and dynamic response to treatment in metastatic breast cancer (MBC). We explored a novel, 180-gene ctDNA panel and the association of this platform with CTCs and CTC clusters. METHODS:A total of 40 samples from 22 patients with MBC were included in the study. For the primary analysis, all patients had ctDNA sequencing using the PredicinePLUS™ platform. CTCs and CTC clusters were examined using the CellSearch™ System. Clinical and pathological variables were reported using descriptive analyses. Associations between CTC count and specific genomic alterations were tested using the Mann-Whitney U test. RESULTS:Of 43 sequenced patients, 40 (93%) had at least one detectable genomic alteration with a median of 6 (range 1-22). Fifty-seven different genes were altered, and the landscape of genomic alterations was representative of MBC, including the commonly encountered alterations TP53, PTEN, PIK3CA, ATM, BRCA1, CCND1, ESR1, and MYC. In patients with predominantly hormone-receptor-positive MBC, the number of CTCs was significantly associated with alterations in ESR1 (P <?0.005), GATA3 (P <?0.05), CDH1 (P <?0.0005), and CCND1 (P <?0.05) (Mann-Whitney U test). Thirty-six percent of patients had CTC clusters, which were associated with alterations in CDH1, CCND1, and BRCA1 (all P <?0.05, Mann-Whitney U test). In an independent validation cohort, CTC enumeration confirmed significant associations with ESR1 and GATA3, while CTC clusters were significantly associated with CDH1. CONCLUSIONS:We report on a novel ctDNA platform that detected genomic alterations in the vast majority of tested patients, further indicating potential clinical utility for capturing disease heterogeneity and for disease monitoring. Detection of CTCs and CTC clusters was associated with particular genomic profiles.
| S-EPMC6894208 | biostudies-literature
Project description:BackgroundContemporary cancer diagnostics are becoming increasing reliant upon sophisticated new molecular methods for analyzing genetic information. Limiting the scope of these new technologies is the lack of adequate solid tumor tissue samples. Patients may present with tumors that are not accessible to biopsy or adequate for longitudinal monitoring. One attractive alternate source is cancer cells in the peripheral blood. These rare circulating tumor cells (CTC) require enrichment and isolation before molecular analysis can be performed. Current CTC platforms lack either the throughput or reliability to use in a clinical setting or they provide CTC samples at purities that restrict molecular access by limiting the molecular tools available.Methodology/principal findingsRecent advances in magetophoresis and microfluidics have been employed to produce an automated platform called LiquidBiopsy®. This platform uses high throughput sheath flow microfluidics for the positive selection of CTC populations. Furthermore the platform quantitatively isolates cells useful for molecular methods such as detection of mutations. CTC recovery was characterized and validated with an accuracy (<20% error) and a precision (CV<25%) down to at least 9 CTC/ml. Using anti-EpCAM antibodies as the capture agent, the platform recovers 78% of MCF7 cells within the linear range. Non specific recovery of background cells is independent of target cell density and averages 55 cells/mL. 10% purity can be achieved with as low as 6 CTCs/mL and better than 1% purity can be achieved with 1 CTC/mL.Conclusions/significanceThe LiquidBiopsy platform is an automated validated platform that provides high throughput molecular access to the CTC population. It can be validated and integrated into the lab flow enabling CTC enumeration as well as recovery of consistently high purity samples for molecular analysis such as quantitative PCR and Next Generation Sequencing. This tool opens the way for clinically relevant genetic profiling of CTCs.
| S-EPMC3906064 | biostudies-literature
Project description:Circulating tumour cells (CTCs) serve as valuable biomarkers. However, EpCAM positive CTCs are less frequently detected in NSCLC patients compared to other epithelial tumours. First, EpCAM protein expression was analysed in primary and metastatic lung cancer tissue. In both groups 21% of the samples were EpCAM negative. Second, the CellSearch system identified 15% of patients (n?=?48) as CTC positive whereas a multiplex RT-PCR for PIK3CA, AKT2, TWIST, and ALDH1 following EGFR, HER2 and EpCAM based enrichment detected CTCs in 29% of the patients. Interestingly, 86% of CTC positive patients were found to express ALDH1. Only 11% of the patients were CTC-positive by both techniques. CTC positivity was associated with patient disease state when assessed by the multiplex RT-PCR assay (p?=?0.015). Patients harbouring tumours with an altered EGFR genotype were more frequently CTC-positive compared to patients with EGFR wildtype tumours. In subsets of patients, CTCs were found to express genes involved in resistance to therapy such as HER3 and MET. In conclusion, using multiple targets for CTC capture and identification increases the sensitivity of CTC detection in NSCLC patients, which can be explained by the presence of different CTC subtypes with distinct molecular features.
| S-EPMC4908396 | biostudies-literature