Tumor Necrosis Factor-alpha-308G/A Promoter Polymorphism is Associated with the Severity of Gastric Carcinomas

PURPOSE: The pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), is a central mediator of the immune response involved in a wide range of immuno-inflammatory and infectious diseases. There is increasing evidence that TNF-alpha may promote the development and spread of the cancer. Polymorphisms in the TNF-alpha promoter have been related to TNF-alpha production. Therefore, we investigated the potential association of TNF-alpha genotypes with gastric cancer in the Korean population. METHODS: The study included 66 patients with gastric adenoma, 75 patients with gastric carcinoma, and 551 healthy controls. The -308 and -238 polymorphisms in the TNF-alpha promoter were analyzed by PCR- restriction fragment length polymorphism (RFLP). Distributions of TNF-alpha promoter polymorphisms were compared between groups by chi2 test. P values smaller than 0.05 were considered to be significant. RESULTS: The proportion of individuals carrying the TNF-alpha -308A allele was higher in the carcinoma group compared to controls and adenomas, but the differences were not significant (P=0.124). However, the TNF-alpha -308A allele was significantly associated with advanced gastric carcinoma (P=0.026), serosa invasion (P=0.004), neural invasion (P= 0.021), and lymph node metastasis (P=0.005). On the other hand, the TNF-alpha -238G/A polymorphism was not associated with the development of gastric adenoma and carcinoma and the severity of gastric carcinoma. CONCLUSION: These results suggest that the TNF-alpha -308A allele is associated with the severity of gastric carcinoma in terms of invasion and metastasis in the Korean population. Therefore, TNF-alpha promoter polymorphism could be used as a predictive marker of the severity of gastric carcinoma.

Changes in expression of cell cycle regulators and their hepatic lobular distribution in partial hepatectomy-induced regenerating rat liver

Partial hepatectomy (PH) endorses quiescent hepatocytes to reenter the cell cycle. The regenerating liver returns to its preresection weight after 7 days, following one or two cell division and maintains nearly its original volume after then. We focused on the inhibition of further hepatocyte proliferation, hypothesizing possible involvement of cell cycle upregulators and inhibitors. We studied protein levels in expression of cyclins, cyclin dependent kinases (CDKs) and CDK inhibitors (CKIs), and their in situ hepatic lobular distributions in partial hepatectomized rat liver. Cyclin E was expressed in the same levels in normal liver and after PH. Expression of cyclin A, not detected in normal liver, increased in following times after PH and reached a maximum at 7 day. CDK2 and 4 showed increased expression toward terminal period. Contradictory findings of cyclin A and these CDKs might play an important role in the inhibition of further cell division, although still unclear. Constitutively expressed CDK6 decreased after 1 day. p18 showed peak expression within 1 day, and p16, p21, p27 and p57 were stronger at terminal periods. During the expected period of their activity, intranuclear translocations were observed in cyclin E, p18 and p16. There was no evidence of regional distribution in hepatic lobular architecture, instead, diffuse in situ expression, corroborating synchronous event, was found.