Project description:The main aim of this study is to evaluate how comparable the established colorectal primary tumor cultures are to the original tumor tissues obtained directly from patients in terms of their genomic profile for which they can be eventually utilized to improve in vitro drug assessment and facilitate personalized treatment. Here, we used colorectal cancer patient samples collected after surgery to perform a gene expression comparison study between original tissues and self-established primary cultures. Subsequently, we also investigated the possibility of using primary cells from patients’ tumors as a model for assessing drug response by characterizing the modifications in gene-drug associations of the primary cells which occurred during the establishment of cell cultures. On an auxiliary note, cytogenetic studies are only possible in cultured cells and not in tissue samples, hence, in this study we also evaluated the potential of genome stability analysis on primary cells as an alternative method to improve our understanding of the genomic changes which occur in cancer initiation and progression. Using cRNA microarrays, gene expression of low-passage colorectal tumor primary cultures were compared against colorectal tumor tissues obtained directly from patients.
Project description:The main aim of this study is to evaluate how comparable the established colorectal primary tumor cultures are to the original tumor tissues obtained directly from patients in terms of their genomic profile for which they can be eventually utilized to improve in vitro drug assessment and facilitate personalized treatment. Here, we used colorectal cancer patient samples collected after surgery to perform a gene expression comparison study between original tissues and self-established primary cultures. Subsequently, we also investigated the possibility of using primary cells from patients’ tumors as a model for assessing drug response by characterizing the modifications in gene-drug associations of the primary cells which occurred during the establishment of cell cultures. On an auxiliary note, cytogenetic studies are only possible in cultured cells and not in tissue samples, hence, in this study we also evaluated the potential of genome stability analysis on primary cells as an alternative method to improve our understanding of the genomic changes which occur in cancer initiation and progression.
Project description:To identify the gene expression of early-onset colorectal cancer, we sampled early-onset colorectal cancer patients (age < 50) and late-onset colorectal cancer paitients (age > 70) We then performed gene expression profiling analysis using data obtained from RNA-seq of early-onset colorectal cancer tissues and late-onset colorectal cancer tissues.
Project description:Identification of differentially expressed microRNAs in Colorectal Cancer Distant metastasis is the major determinant of patient outcome in colorectal cancer and microRNAs have emerged as an increasingly important class of molecules which can regulate several steps of the metastatic cascade. By systematically analysing the miR expression profiles of resected metastasis-, corresponding primary tumor- and normal tissues of colorectal cancer patients, we were able to delineate a miR-signature indicative of the metastatically critical microRNA landscape. 9 colorectal cancer patients were profiled comprising 5 patients with tissues from the primary tumor, normal mucosa, secondary metastasis and the background tissue in which the metastasis ocurred. In the remaining 4 patients, one of these four tissue entitities is missing. One patient had two synchronous primary tumors, one in the colon and the other in the rectum.
Project description:Stem cell enriched cultures are generated from primary cultures of colorectal cancer patients. Organoids from normal and tumoral tissue are treated with 1,25(OH)2D3 and vehicle for 96 hours. RNA expression is compared among treatments.
Project description:Cancer is among the major causes of death worldwide, and treatment can be individualized according to a patient’s genotype. Primary cultures of cancer and normal cells provide more accurate information about tumour pathology compared with tumour-derived cell lines, and several methods are available for establishing primary cultures. However, these methods are inefficient, complicated and expensive. Here we describe a method to establish primary cultures of tumour cells, which we designate “isolated tumour-derived Cancer Cells” (iCCs) that retains the phenotypic heterogeneity of primary cancer cells in their in situ niche microenvironments. We used a custom filter, a Matrigel-coated plate, and modified embryonic stem cell (ESC) culture medium to isolate iCCs from tumour tissues of patients with colorectal cancer. All iCCs were viable, and approximately 90% of the cultures were passaged. The morphologies, genotypes and transcription profiles of iCCs were similar to those of their respective tumours of origin. Further, iCCs comprised a specific cell population that expressed Platelet-derived growth factor receptor (PDGFR), which contributes to forming the structure of the original ductal carcinoma. Our results demonstrate that ESC culture medium maintained the heterogeneity of ICCs by supporting the viability of PDGFR-expressing cells. The responses of iCCs to standard anti-cancer drugs differed compared with those of colon cancer cell lines. Moreover, the drug sensitivities of iCCs closely correlated with patients’ clinical outcomes. For example, a clinically significant finding was the reduction of the IC50 of crenolanib, an inhibitor of PDGFR signalling, for iCCs. Therefore, crenolanib may serve as an effective chemotherapeutic agent for managing colorectal cancer.
Project description:The purpose of this study is to identify miRNAs involved in the pathology of colorectal cancer (CRC) liver metastasis and investigate their underlying mechanisms. A total of 39 miRNAs were identified to be differentially expressed between 16 primary CRC tissues with liver metastases and 16 CRC tissues without liver metastases from 32 patients by Affymetric miRNA microarrays. 16 coloretcal cancer tissues with liver metastasis and 16 colorectal cancer tissues without liver metastasis were included in this study for RNA extraction and hybridization on Affymetrix microarrays. We sought to identify the differentially expressed miRNAs between colorectal cancer tissues with and without liver metastasis.