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BACKGROUND. JC virus (JCV) is a polyomavirus that commonly infects humans and is the causative agent of progressive multifocal leukoencephalopathy in immune‐compromised patients. An association between JCV and human cancers long has been suspected, because this virus induces brain tumors in several animal models. The oncogenic potential of JCV is mediated by a transforming protein, the T‐antigen (T‐Ag), which is a multifunctional protein that transforms cells through interactions with various growth‐regulatory genes, including p53 and pRb, and by stabilizing β‐catenin. Previously, the laboratory at the authors' institution demonstrated that JCV is present frequently in the human gastrointestinal tract and may play a role in colorectal carcinogenesis. However, to date, no studies have determined whether JCV sequences are present specifically in gastric cancers. The current study was designed to investigate whether JCV sequences and expression are found in human gastric cancers. METHODS. DNA was extracted from 23 paraffin embedded and 14 frozen gastric cancer specimens. For the detection of JCV gene sequences, polymerase chain reaction amplifications were performed using gene‐specific primers for T‐Ag, VP‐1 (a JCV capsid gene), and the viral regulatory region (or transcriptional control region). Immunohistochemical staining was performed with an anti‐T‐Ag monoclonal antibody to detect protein expression. RESULTS. Twenty‐one of 37 gastric cancers (57%) harbored JCV T‐Ag sequences, and 13 of 37 gastric cancers (30%) contained VP‐1 sequences. T‐Ag sequences also were found in adjacent nonneoplastic mucosa. In addition, JCV regulatory region sequences were present frequently in gastric cancers and adjacent nonneoplastic mucosa. T‐Ag protein expression was found in 9 of 23 gastric cancers (39%), whereas no expression was observed in any of the nonneoplastic tissues. CONCLUSIONS. To the authors' knowledge, this is the first demonstration of the presence of JCV T‐Ag expression in human gastric cancers. These findings suggest a possible role for this polyomavirus in gastric carcinogenesis. Cancer 2006. © 2006 American Cancer Society.

The results of the present single-center study show that, following distal radial fracture fixation, wrist arthritis may affect the patient's subjective well-being, as documented with the Short Form-36, without influencing the functional outcome. Well-designed longitudinal clinical trials are needed to confirm the findings of the present investigation in terms of quality of life after surgical treatment of intra-articular distal radial fractures.

While there is an increasing interest in selenium chemoprevention against human colon polyp recurrence and other cancers, the mechanism(s) by which these agents inhibit carcinogenesis are uncertain. Some of the proposed mechanisms include the inhibition of cytosine methyltransferases, carcinogen bioactivation, and inhibition of cyclooxygenase (COX). More recently, it has been suggested that selenium may exert growth inhibitory effects by activating p53. However, the molecular mechanisms of action of selenomethionine, an organoselenium compound present in selenized yeast and currently being investigated in human clinical trials for colon polyp prevention, are unclear. In the present study we tested the hypothesis that selenomethionine might affect colon cancer cell growth by p53 mediated apoptosis and/or cell cycle regulation. Four human colon cancer cell lines including HCT116 and RKO (wild type p53), HCT116-p53KO (isogenic control of HCT116 cells with p53 knocked out) and Caco-2 (mutant p53) were treated with 0-100 microM of selenomethionine for 24, 48 and 72 h. Cell viability rates were determined by the MTT assay. Cell cycle analysis was performed by flow cytometry and apoptosis measured by Annexin V-Cy5 staining. Expression of p53 protein was determined by Western blotting and immunofluorescence assays. All cell lines showed concentration and time dependent growth inhibition with selenomethionine, although HCT116 and RKO cells were the most sensitive to such treatments. Interestingly, although HCT116 and HCT116-p53KO are isogenic cell lines, selenomethionine caused a G2/M cell cycle arrest in HCT116 and RKO cells, but not in HCT116-p53KO cells. Similarly, both HCT116 and RKO demonstrated a significant increase in apoptosis (100-170%; p < 0.01) with 50-100 microM selenomethionine. Cell cycle arrest and apoptosis observed in HCT116 and RKO cell lines were accompanied by a marked increase in p53 protein expression following selenium treatment. These results clearly suggest that selenomethionine exerts p53 dependent growth inhibitory effects in colon cancer cells by inducing G2/M cell cycle arrest as well as apoptosis.