By screening members of Finnish families displaying hereditary nonpolyposis colorectal cancer (HNPCC) for predisposing germline mutations in MSH2 and MLH1, we show that two mutations in MLH1 together account for 63% (19/30) of kindreds meeting international diagnostic criteria. Mutation 1, originally detected as a 165-base pair deletion in MLH1 cDNA comprising exon 16, was shown to consist of a 3.5-kilobase genomic deletion most likely resulting from Alu-mediated recombination. Mutation 2 destroys the splice acceptor site of exon 6. A simple diagnostic test based on polymerase chain reaction was designed for both mutations. Our results show that these two ancestral founding mutations account for a majority of Finnish HNPCC kindreds and represent the first report of Alu-mediated recombination causing a prevalent, dominantly inherited predisposition to cancer.

Major causes of head and neck squamous cell carcinoma (HNSCC)-related deaths are cervical node and distant metastasis. We previously demonstrated that overexpression of the DNA double-strand break repair protein Nijmegen breakage syndrome 1 (NBS1) is a prognostic marker of advanced HNSCCs. Epithelial-mesenchymal transition (EMT) was demonstrated to be the major mechanism responsible for mediating invasiveness and metastasis of late-stage cancers. We therefore investigated the role of NBS1 overexpression in mediating EMT and metastasis. NBS1 overexpression was associated with metastasis of HNSCC patients using tissue microarray-immunohistochemistry approach. Induction of EMT was observed in an NBS1-overexpressing HNSCC cell line (FADUNBS), whereas short-interference RNA (siRNA)-mediated repression of endogenous NBS1 reversed the shift of EMT markers. Increased migration/invasiveness of FADUNBS was shown by in vitro and in vivo assays. NBS1 overexpression upregulated the expression of an EMT regulator Snail and its downstream target matrix metalloproteinase-2. EMT phenotypes and increased migration/invasiveness of FADUNBS cells were reversed by siRNA-mediated repression of Snail expression or a phosphatidylinositol 3-kinase-specific inhibitor. In HNSCC samples, co-expression of NBS1/Snail in primary tumors correlated with metastasis and the worst prognosis. These results indicate that NBS1 overexpression induces EMT through the upregulation of Snail expression, and co-expression of NBS1/Snail predicts metastasis in HNSCCs.

Compared with placebo, Diascorea alata improves symptoms, particularly the psychological parameters in menopausal women. Safety monitoring indicated that standardized extracts of Diascorea alata were safe during daily administration over a period of 12 months.

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To investigate whether the pre- and postoperative International Prostate Symptom Score (IPSS) change predicts the outcome of transurethral prostatectomy in a Taiwanese population, 99 patients (transurethral prostatectomy candidates) were assessed with the IPSS before and 6-12 months after surgery. All symptoms improved significantly postoperatively. Patients with a greater preoperative IPSS benefited the most. Improvements in preoperative obstructive symptoms (incomplete emptying, intermittency, straining, and weak stream) were greater than those in irritable symptoms (urgency, frequency, and nocturia). A significant correlation was found between IPSS and quality of life (QOL) before and after transurethral prostatectomy. A change of 1 unit on the IPSS scale was found to decrease the QOL score 0.282 units. The positive predictive value of a >or=7-IPSS point decrease depended on the predictive IPSS criteria applied. When the preoperative IPSS was more than 17, the sensitivity was 83.5% and specificity was 30%. Postoperative improvement did not differ significantly between acute urinary retention (AUR) and non-AUR patients. Change in IPSS of more than 7 points predicted symptomatic improvement with high sensitivity. The predictive value depends on the definition of significant improvement (magnitude of IPSS change) and on the level of IPSS symptoms (sufficient to warrant transurethral prostatectomy).