Search results for "Colorectal Neoplasms."
showing 10 items of 431 documents
Pharmacological targeting of the novel β-catenin chromatin-associated kinase p38α in colorectal cancer stem cell tumorspheres and organoids
2021
AbstractThe prognosis of locally advanced colorectal cancer (CRC) is currently unsatisfactory. This is mainly due to drug resistance, recurrence, and subsequent metastatic dissemination, which are sustained by the cancer stem cell (CSC) population. The main driver of the CSC gene expression program is Wnt signaling, and previous reports indicate that Wnt3a can activate p38 MAPK. Besides, p38 was shown to feed into the canonical Wnt/β-catenin pathway. Here we show that patient-derived locally advanced CRC stem cells (CRC-SCs) are characterized by increased expression of p38α and are “addicted” to its kinase activity. Of note, we found that stage III CRC patients with high p38α levels display…
No evidence of EMAST in whole genome sequencing data from 248 colorectal cancers.
2021
Microsatellite instability (MSI) is caused by defective DNA mismatch repair (MMR), and manifests as accumulation of small insertions and deletions (indels) in short tandem repeats of the genome. Another form of repeat instability, elevated microsatellite alterations at selected tetranucleotide repeats (EMAST), has been suggested to occur in 50% to 60% of colorectal cancer (CRC), of which approximately one quarter are accounted for by MSI. Unlike for MSI, the criteria for defining EMAST is not consensual. EMAST CRCs have been suggested to form a distinct subset of CRCs that has been linked to a higher tumor stage, chronic inflammation, and poor prognosis. EMAST CRCs not exhibiting MSI have b…
Prognostic significance of spatial and density analysis of T lymphocytes in colorectal cancer.
2022
Abstract Background Although high T cell density is a strong favourable prognostic factor in colorectal cancer, the significance of the spatial distribution of T cells is incompletely understood. We aimed to evaluate the prognostic significance of tumour cell-T cell co-localisation and T cell densities. Methods We analysed CD3 and CD8 immunohistochemistry in a study cohort of 983 colorectal cancer patients and a validation cohort (N = 246). Individual immune and tumour cells were identified to calculate T cell densities (to derive T cell density score) and G-cross function values, estimating the likelihood of tumour cells being co-located with T cells within 20 µm radius (to derive T cell p…
DNA methylation profiling to explore colorectal tumor differences according to menopausal hormone therapy use in women
2019
Aim: Use of menopausal hormone therapy (MHT) has been associated with a reduced risk for colorectal cancer, but mechanisms underlying this relationship are not well understood. In the colon, MHT appears to act through estrogen receptor β (ERβ) which may influence DNA methylation by binding to DNA. Using genome-wide methylation profiling data, we aimed to identify genes that may be differentially methylated according to MHT use. Materials & methods: DNA methylation was measured using Illumina HumanMethylation450k arrays in two independent tumor sample sets of colorectal cancer patients. Differential methylation was determined using R/limma. Results: In the discovery analysis, two CpG si…
Diagnostic yield of a one sample immunochemical test at different cut-off values in an organised screening programme for colorectal cancer
2013
Abstract Background Quantitative immunochemical faecal occult blood tests have become the recommended tests for colorectal cancer screening. The aim of this study was to complete our knowledge on the performance of one of the quantitative immunochemical tests available, FOB-Gold, and to propose a possible strategy for an organised screening programme. Patients and methods Within the French organised screening programme, 23,231 average-risk individuals, aged 50–74 performed both a 3-day Hemoccult test and a 1-day FOB-Gold test. Performances of the immunochemical test were evaluated at different cut-off levels. Results The positivity rate for the Hemoccult was 2.1% and for the FOB-Gold varied…
Factors Associated with Prolonged Patient-Attributable Delay in the Diagnosis of Colorectal Cancer
2018
Purpose The delayed diagnosis of colorectal cancer (CRC) may be attributable to sociodemographic characteristics, to aspects of tumour histopathology or to the functioning of the health system. We seek to determine which of these factors most influences prolonged patient-attributable delay (PPAD) in the diagnosis and treatment of CRC. Materials and methods A prospective, multicentre observational study was conducted in 22 Spanish hospitals. In total, 1,785 patients were recruited to the study between 2010 and 2012 and underwent elective or urgent surgery. PPAD is considered to occur when the time elapsed between a patient presenting the symptom and him/her seeking attention from the primary…
Colorectal Cancer in Elderly Patients: From Best Supportive Care to Cure
2013
Colorectal cancer is one of the major causes of cancer mortality in the elderly population (median age at diagnosis of 71 years) in Western Countries. Moreover patients with metastatic disease are often elderly with significant co- morbidities. Unfortunately, elderly patients are often untreated and under-represented in clinical trials, even if most clinical trials that have included this setting of population have shown similar survival rates and toxicities to younger patients. Age itself should not be considered for candidacy to chemotherapy but it should be taken in consideration the great heterogeneity of co-morbidities present in the elderly population. Therefore, the best treatment st…
Hsp60 molecular anatomy and role in colorectal cancer diagnosis and treatment
2011
Quantitative changes in Hsp60 during the development of some tumors suggest that this chaperonin plays a role in carcinogenesis. A description of the specific role(s) of Hsp60 in tumor-cell growth and proliferation is still incomplete, but it is already evident that monitoring its levels and distribution in tissues and fluids has potential for diagnosis and staging, and for assessing prognosis and response to treatment. Although Hsp60 is considered an intramitochondrial protein, it has been demonstrated in the cytosol, cell membrane, vesicles, cell surface, extracellular space, and blood. The knowledge that Hsp60 occurs at all these locations opens new avenues for basic and applied research…
The prognostic value of skeletal muscle index on clinical and survival outcomes after cytoreduction and HIPEC for peritoneal metastases from colorect…
2021
BACKGROUND Cytoreductive surgery (CRS) and hypertermic intraperitoneal chemotherapy (HIPEC) represent the most effective strategy to manage peritoneal metastases (PM). This systematic review and meta-analysis aimed to assess the impact of body composition on clinical outcomes in patients with PM. METHODS A systematic literature search was performed using Medline, Web of Science and EMBASE databases from inception to the 20st August 2020. Data were independently extracted by 3 authors. Newcastle-Ottawa Scale was used to assess quality and risk of bias of studies. Pooled analyses were performed using Mantel-Haenszel method to estimate overall effect size with mean differences or odd ratios (O…
Dynamic regulation of the cancer stem cell compartment by Cripto-1 in colorectal cancer.
2015
Stemness was recently depicted as a dynamic condition in normal and tumor cells. We found that the embryonic protein Cripto-1 (CR1) was expressed by normal stem cells at the bottom of colonic crypts and by cancer stem cells (CSCs) in colorectal tumor tissues. CR1-positive populations isolated from patient-derived tumor spheroids exhibited increased clonogenic capacity and expression of stem-cell-related genes. CR1 expression in tumor spheroids was variable over time, being subject to a complex regulation of the intracellular, surface and secreted protein, which was related to changes of the clonogenic capacity at the population level. CR1 silencing induced CSC growth arrest in vitro with a …