A study by Dong et al has provided further evidence that attenuation of apoptosis may facilitate tumour progression in colon cells. Dong et al examined the role of cytosolic phospholipase A2 (cPLA2) in TNF-a-induced apop-tosis of cultured mouse colonocytes. The specific cPLA-2 inhibitor, AACOCF-3 (arachidonoyl trifluoromethyl ketone), was able to protect colonocytes from TNF-a-induced apoptosis in vitro. The study supports the idea that down-regulation of cPLA2 may attenuate TNF-a mediated apoptosis […]
Apoptosis is an important regulatory mechanism by which unwanted cells are eliminated in tumourigenesis. Apoptosis is initiated by binding of death receptors such as Fas, TNF-R and TRAIL-R to their ligands. Binding of the receptors results in transmission of apoptotic signals and the activation of enzymatic caspase complexes . IFNs function in […]
Normal colonic epithelial cells are dependent on cell-cell adhesion and survival factors for the inhibition of apoptosis. In colorectal tumourigenesis , cells develop mechanisms to evade control signals and are able to survive despite the loss of cellcell contacts. Overexpression of adhesion molecules and an abnormal enhancement of growth factors may be an indicator of colon tumourigenesis. In a recent study, chronic trinitrobenzene sulfonic acid-induced inflammation of the colon coincided with […]
IL-23, a novel cytokine that is structurally and functionally similar to IL-12, has been found to stimulate the proliferation of memory T cells and induce immune-dependent antitumour effects in murine colon carcinoma cell lines. In addition to the production of cytokines by TH1 cells, tumour cells themselves have been found to secrete […]
Currently, there has been much interest in cytokines as immunological mediators in colon adenoma and colorectal cancer. Many studies have associated inflammation and cancer of the colon with the immune-mediated actions of cytokines, and several studies have linked cytokine production and premalignant polyps. Cytokine involvement in colon cancer may be characterized by four types of biological activities: growth and proliferation of T cells, dysregulation of cell-cell adhesion signals, induction of apoptotic […]
Two receptors for IL-8 have been identified, both of which are members of the G-protein receptor family and are expressed in neutrophils, T cells, monocytes, macrophages, fibroblasts and melanoma cells . IL-13 and IL-4 convert IL-8 into monocyte chemotactic agonists by upregulating receptor expression. IL-8 and related […]
Increases in TGF-P1 stimulate the recruitment of tumour-infiltrating lymphocytes to the neoplastic site and cause a direct inhibitory effect of rat TNF-a and IL-10 on tumour proliferation in vitro. These seemingly contradictory findings on the role of TGF-P may be explained by a clear site dependency and biphasic mechanism of action. TGF-P levels are lowest in the rectum and highest in the ascending colon. Low levels of TGF-P are associated […]
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