PER3 polymorphisms and their association with prostate cancer risk in Japanese men

Introduction: Prostate cancer (PCa) is one of the most common cancers affecting men globally. Although PER3 has been suggested as a risk factor for cancer development, there are few reports elucidating the relationship between PER3 and PCa. We investigated the association between PER3 polymorphisms (rs2640908 and VNTR) and susceptibility to PCa in the Japanese population. Methods: Eighty three patients with PCa and 122 controls participated in this study. We analyzed rs2640908 and VNTR polymorphisms by using PCR–Restriction Fragment Length Polymorphism (PCR–RFLP). Results: Compared to the C/C genotype with the rs2640908 polymorphism, the T/T (OR: 0.35, 95% CI: 0.15–0.81, P = 0.02) and C/T + T/T (OR: 0.46, 95% CI: 0.24–0.88, P = 0.02) genotypes had a significantly lower risk of PCa. TT (OR: 0.29, 95% CI: 0.10–0.77, P = 0.02) and CT + TT (OR: 0.47, 95% CI: 0.23–0.97, P = 0.04) also had significant protection against PCa in the smoker group. Significantly, we observed an association between smoking and rs2640908 polymorphism in this study. However, no association between the VNTR polymorphisms and PCa was detected. Conclusions: Our results suggest that PER3 rs2640908 polymorphisms influence an individual’s susceptibility to PCa

Combined Gastrectomy with Adjacent Organs in T4 Gastric Cancer : Therapeutic Results and Indication

The postoperative morbidity, mortality and survival of 244 T4 gastric cancer patients were examined to assess the therapeutic results and to clarify the indication for combined gastrectomy with adjacent (T4) organs. A total of 190 combined and 54 simple gastrectomies were performed during the 25-year period between 1969 and 1994. Fourteen (7.4%) and 7 (13.0%) patients died of the complications after combined and simple gastrectomies respectively. No statistical significant difference was found in the mortality rates between the gastrectomies. The histological examination of 190 resected specimens by the combined gastrectomy with T4 organs revealed that gastric resections with conclusive curability A, B and C were performed in 33 (17.4%), 84 (44.2%) and 73 (38.4%) cases respectively. Significant differences (P < 0.01) among 3 survival curves of the patients with curability A, B and C were found, and the 5-year survival rates were 65.5%, 35.4% and 9.2% respectively. The survival curve of 176 patients with combined gastrectomy was significantly (P < 0.01) higher than that of 47 patients with simple gastrectomy, and the 5-year survival rates were 31.3% and 4.3%. However, the survival curve and the 5-year survival rate of the patients with simple gastrectomy were not statistically different from those of the patients with curability C. These results suggest that combined gastrectomy with T4 organs in T4 gastric cancer may be indicated for the patients with surgical curability B, but not surgical curability C

Comprehensive analysis of liver and blood miRNA in precancerous conditions

Streptozotocin administration to mice (STZ-mice) induces type I diabetes and hepatocellular carcinoma (HCC). We attempted to elucidate the carcinogenic mechanism and the miRNA expression status in the liver and blood during the precancerous state. Serum and liver tissues were collected from STZ-mice and non-treated mice (CTL-mice) at 6, 10, and 12 W. The exosome enriched fraction extracted from serum was used. Hepatic histological examination and hepatic and exosomal miRNA expression analysis were serially performed using next-generation sequencing (NGS). Human miRNA expression analysis of chronic hepatitis liver tissue and exosomes, which were collected before starting the antiviral treatment, were also performed. No inflammation or fibrosis was found in the liver of CTL-mice during the observation period. In STZ-mice, regeneration and inflammation of hepatocytes was found at 6 W and nodules of atypical hepatocytes were found at 10 and 12 W. In the liver tissue, during 6–12 W, the expression levels of let-7f-5p, miR-143-3p, 148a-3p, 191-5p, 192-5p, 21a-5p, 22-3p, 26a-5p, and 92a-3p was significantly increased in STZ-mice, and anti-oncogenes of their target gene candidates were down-regulated. miR-122-5p was also significantly down-regulated in STZ-mice. Fifteen exosomal miRNAs were upregulated in STZ-mice. Six miRNAs (let-7f-5p, miR-10b-5p, 143-3p, 191-5p, 21a-5p, and 26a-5p) were upregulated, similarly to human HCC cases. From the precancerous state, aberrant expression of hepatic miRNAs has already occurred, and then, it can promote carcinogenesis. In exosomes, the expression pattern of common miRNAs between mice and humans before carcinogenesis was observed and can be expected to be developed as a cancer predictive marker