Search results for "colonic"

The N-glycan processing in HT-29 cells is a function of their state of enterocytic differentiation. Evidence for an atypical traffic associated with …

1991

International audience; When the human colon cancer cells HT-29 undergo enterocytic differentiation, they correctly process their N-glycans, whereas their undifferentiated counterpart are unable to process Man9-8-GlcNAc2 species, the natural substrate of alpha-mannosidase I. As this enzyme is fully active in both HT-29 cell populations, we hypothesize that N-glycoproteins are unable to reach the cis Golgi, the site where alpha-mannosidase I has been localized. We have demonstrated this point by using 1-deoxymannojirimycin, leupeptin, and monensin. In the presence of 1-deoxymannojirimycin, a specific inhibitor of alpha-mannosidase I, differentiated HT-29 cells, as expected, accumulate Man9-8…

Label-free quantitative proteomic profiling of colon cancer cells identifies acetyl-CoA carboxylase alpha as antitumor target of Citrus limon-derived…

2017

Abstract We have previously isolated exosome-like nanoparticles from Citrus-limon juice, able to inhibit in vitro and in vivo tumor cell growth. In order to deeply understand the mechanism underlying nanovesicle effects, we performed a proteomic profile of treated colorectal cancer cells. Among the proteins differentially expressed after nanovesicle treatment, we found a significant downregulation of the Acetyl-CoA Carboxylase 1 (ACACA) and we demonstrated that silencing ACACA in cancer cells leads to a reduction of cell growth. Our study proved that the anti-tumor effects of Citrus-limon nanovesicles is partly mediated by lipid metabolism inhibition, in particular via ACACA downregulation.…

Exosomes from metastatic cancer cells transfer amoeboid phenotype to non-metastatic cells and increase endothelial permeability: their emerging role …

2017

AbstractThe goal of this study was to understand if exosomes derived from high-metastatic cells may influence the behavior of less aggressive cancer cells and the properties of the endothelium. We found that metastatic colon cancer cells are able to transfer their amoeboid phenotype to isogenic primary cancer cells through exosomes, and that this morphological transition is associated with the acquisition of a more aggressive behavior. Moreover, exosomes from the metastatic line (SW620Exos) exhibited higher ability to cause endothelial hyperpermeability than exosomes from the non metastatic line (SW480Exos). SWATH-based quantitative proteomic analysis highlighted that SW620Exos are signific…

Integrated multi-omics investigations of metalloproteinases in colon cancer: Focus on MMP2 and MMP9

2021

Colorectal cancer (CRC) develops by genetic and epigenetic alterations. However, the molecular mechanisms underlying metastatic dissemination remain unclear and could benefit from multi-omics investigations of specific protein families. Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in ECM remodeling and the processing of bioactive molecules. Increased MMP expression promotes the hallmarks of tumor progression, including angiogenesis, invasion, and metastasis, and is correlated with a shortened survival. Nevertheless, the collective role and the possible coordination of MMP members in CRC are poorly investigated. Here, we performed a multi-omics analysis of MMP expression…

Proteomic Approaches in Colon Cancer: Promising Tools for New Cancer Markers and Drug Target Discovery

2005

Novel technologies are needed from which to identify new and more efficient biomarkers and improved molecular targets for the expedient and accurate diagnosis and treatment of colorectal cancer. Many advances have been made in direct and virtual imaging for detection of polyps and malignant-type lesions. These require tissue verification before definitive intervention. Inclusion of a simple serum test, more accurate than CEA, especially for early cancer detection, would make virtual imaging much more successful. Proteomics, the study of the proteins and protein pathways involved in disease, is a new dimension in preclinical and clinical development. Mass spectrometric analysis of serum prot…

Resectability, conversion, metastasectomy and outcome according to RAS and BRAF status for metastatic colorectal cancer in the prospective RAXO study

2022

Abstract Background Outcomes after metastasectomy for metastatic colorectal cancer (mCRC) vary with RAS and BRAF mutational status, but their effects on resectability and conversion rates have not been extensively studied. Methods This substudy of the prospective RAXO trial included 906 patients recruited between 2011 and 2018. We evaluated repeated centralised resectability assessment, conversion/resection rates and overall survival (OS), according to RAS and BRAF status. Results Patients included 289 with RAS and BRAF wild-type (RAS and BRAFwt), 529 with RAS mutated (RASmt) and 88 with BRAF mutated (BRAFmt) mCRC. Metastatic prevalence varied between the RAS and BRAFwt/RASmt/BRAFmt groups,…

ErbB-3 activation by NRG-1β sustains growth and promotes vemurafenib resistance in BRAF-V600E colon cancer stem cells (CSCs)

2015

Approximately 5-10% of metastatic colorectal cancers harbor a BRAF-V600E mutation, which is correlated with resistance to EGFR-targeted therapies and worse clinical outcome. Vice versa, targeted inhibition of BRAF-V600E with the selective inhibitor PLX 4032 (Vemurafenib) is severely limited due to feedback re-activation of EGFR in these tumors. Mounting evidence indicates that upregulation of the ErbB-3 signaling axis may occur in response to several targeted therapeutics, including Vemurafenib, and NRG-1β-dependent re-activation of the PI3K/AKT survival pathway has been associated with therapy resistance. Here we show that colon CSCs express, next to EGFR and ErbB-2, also significant amoun…

Understanding the clinical behavior of relapsed colon cancers with microsatellite instability relative to BRAF mutations

2019

Background Microsatellite instable/deficient mismatch repair (MSI/dMMR) metastatic colorectal cancers have been reported to have a poor prognosis. Frequent co-occurrence of MSI/dMMR and BRAFV600E complicates the association. Patients and methods Patients with resected stage III colon cancer (CC) from seven adjuvant studies with available data for disease recurrence and MMR and BRAFV600E status were analyzed. The primary end point was survival after recurrence (SAR). Associations of markers with SAR were analyzed using Cox proportional hazards models adjusted for age, gender, performance status, T stage, N stage, primary tumor location, grade, KRAS status, and timing of recurrence. Results A…

A Case of Severe Dyspnea and an Unusual Bronchoscopy: The Chilaiditi Syndrome

2006

Phytochemical Indicaxanthin Inhibits Colon Cancer Cell Growth and Affects the DNA Methylation Status by Influencing Epigenetically Modifying Enzyme E…

2015

<b><i>Background:</i></b> Recently, we have shown anti-proliferative and pro-apoptotic effects of indicaxanthin associated with epigenetic modulation of the onco-suppressor <i>p16</i><sup><i>INK4a</i></sup> in the human colon cancer cell line CACO2. In the present study, the epigenetic activity of indicaxanthin and the mechanisms involved were further investigated in other colorectal cancer cell lines. <b><i>Methods:</i></b> LOVO1, CACO2, HT29, HCT116, and DLD1 cells were used to evaluate the potential influence of consistent dietary concentrations of indicaxanthin on DNA methylation, and the epigenetic mech…