Colorectal polyposis and immune-based therapies: INDUCTION OF APOPTOTIC PATHWAYS

In: Colorectal polyposis

8 Sep 2012

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 the apoptotic pathway by sensitizing cancer cells to apoptotic factors and inducing production of nitric oxide. The execution phase of apoptosis requires the participation of caspase proteases, which exert their downstream effects through a process of destruction of nuclear lamina, DNA fragmentation, membrane blebbing and cell shrinkage.

Disassembly of the cell results in membrane-enclosed vesicles (apoptotic bodies), which are cleared by phagocytes without inciting an inflammatory response.

To clarify the role of apoptosis in the pathogenesis of colon cancer, apoptotic indices and expression of apoptosis-related antigens in colon tumour cells have been investigated. Fas, a member of the TNF/nerve growth factor receptor superfamily, mediates apoptosis in response to agonistic antibodies or FasL binding. Several studies report that FasL expression is significantly elevated in advanced colon and gastric carcinomas than in early adenomas, and that higher levels of FasL are correlated with increased apoptotic indices . The results indicate a strong role for Fas in the cancer-protective apoptotic activity of the colon.

TNF-a and TRAIL induce apoptosis in tumour cells of the colon but not in normal cells. Culture medium from macrophages of colon cancer patients was found to contain TRAIL at significantly higher levels than normal, indicating the significance of these cytokines in colon tumour cell apop-tosis. You have a great opportunity to discover the pharmacy that will always be sure to live up to your highest expectations, no matter if you would like to get prednisone online or buy any other prescription medicine with no prescription required on very advantageous terms.


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