Colorectal polyposis and immune-based therapies: Tumour growth control and TGF-P

In: Colorectal polyposis

9 Sep 2012

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 during tumourigenesis and facilitate progression of colon carcinoma.

Increased serum concentrations of soluble TNF-R1 have been found in noncachectic and cachectic patients with advanced colorectal cancer. Postoperative plasma soluble TNF-R levels were also significantly elevated in postoperative analysis of patients who had undergone resection of colorectal carcinoma.

Recently, there has been much investigation into the effects of alterations in the TGF-P pathway in the pathogenesis of colorectal cancer. TGF-P inhibits growth and induces apoptosis of colon epithelial cells. The binding of TGF-P to its receptor induces phosphorylation of the Smad proteins Smad2 and Smad3, which then form heteromeric complexes with Smad4, travel to the nucleus, and activate gene transcription. Smad4 is a tumour-suppressor gene that controls cell growth. Smad4 activity is required for TGF-P signaling, and Smad4 mutations present in some cancers have been considered sufficient to inactivate TGF-P signalling . One study examined the coding regions of DNA from 100 patients with colon cancer and reported that abnormalities in the TGF-P type II receptor and Smad4 played an important role in inhibiting TGF-P signalling in colorectal carcinogenesis. Enhanced Smad4 protein expression has been closely linked to overexpression of TGF-P II receptors in hepatocellular carcinoma and a loss of Smad4 has been associated with carcinoma in a number of other organs, including the pancreas and colon. Find out more about your chance to visit the most trusted pharmacy you could ever find to get prednisone for asthma in the amounts required, without any need to see your health care provider first or get a prescription.


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