Project description:Platelets play a pivotal role in venous thromboembolism (VTE) and in mediating colorectal cancer (CRC) progression. Still, platelets’ role in the hypercoagulability after surgical intervention for metastatic bone diseases (MBD) is ill-defined. Here, we utilised a high-resolution imaging approach to temporally examine platelet procoagulant membrane dynamics (PMD) in four CRC patients with MBD (CRC/MBD), before and after surgical intervention, over a 6-month period. We coupled this investigation with thrombelastography, quantitative plasma shot-gun proteomics and biochemical analysis. The plasma of CRC/MBD patients was enriched in ADAM1a, ADAMTS7 and physiological ligands for platelet glycoprotein-VI (GPVI/Syk) activation. Thromboprophylaxis attenuated procoagulation from post-operative day-1 (POD1), however, all patients experienced rebound procoagulation on POD3 or POD5, which was associated with a VTE event in two patients. Plasma levels of DNA-histone complexes increased steadily after surgery and throughout the study period. Also, we increasingly sighted both homotypic and heterotypic platelet microaggregates after surgery in CRC/MBD but not healthy control participants plasma. Together, our data elucidates the cell biology of a prothrombo-inflammatory state caused by disease and vascular injury, and recalcitrant to thromboprophylaxis. New mechanistic insights into hypercoagulability in CRC/MBD patients may identify novel drug targets for effective thromboprophylaxis type and duration after orthopaedic surgery.
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:Transcriptomes of visceral and subcutaneous adipose tissue from colorectal cancer patients were profiled to investigate differences between depots. Samples were collected at time-point of primary surgery.
Project description:To search for potential miRNAs associated with prognosis in colorectal carcinoma, miRNA expression profiles were analyzed in patients with stage III colorectal carcinoma. miRNA expression levels were compared between long and short time survival after surgery with standard chemotherapy.
Project description:This study investigates the correlation between gene overexpression and resistance to apoptosis and hyper-proliferative phenotype in colorectal cancer. We analyzed the transcriptome of a cohort of xenografted colorectal tumors and primary resected biopsies together with normal tissue datasets and identified a set of genes overexpressed in colon cancer. KEYWORDS: transcription-profile, colon, colon-cancer, xenograft
Project description:To search for potential miRNAs associated with prognosis in colorectal carcinoma, miRNA expression profiles were analyzed in patients with stage III colorectal carcinoma. miRNA expression levels were compared between long and short time survival after surgery with standard chemotherapy. Two groups of colorectal carcinoma tissues for miRNA array. Long time (L) survival (≥5 years) group and short time survival (S) (<5 years) group.