. Transforming growth factor β (TGF- β ) is a multifunctional cytokine that strongly inhibits epithelial cell growth. Disabling of TGF- β signaling is thought to be involved in development of a variety of tumors in...
详细信息
. Transforming growth factor β (TGF- β ) is a multifunctional cytokine that strongly inhibits epithelial cell growth. Disabling of TGF- β signaling is thought to be involved in development of a variety of tumors in which abnormal expression or function of TGF- β receptor plays critical roles. In the present study, we examined aberrant expression and mutation of the gene TGF- β receptor type II (Tβ RII) in endometrial cancers of endometrioid subtype. Methods and results. Real-time PCR analysis using surgical tissue specimens of 27 endometrial cancers and 24 normal endometria revealed that endometrial cancers had significantly decreased levels of Tβ RII mRNA expression (mean level 2.44 ± 2.65), compared to normal endometria (mean level 7.23 ± 6.07) (P < 0.001). Methylation status of Tβ RII promoter containing 30 CpGs was examined by bisulfite sequencing analysis, and 98% (51/52) of the patients were found to have unmethylated Tβ RII promoter, indicating that promoter hypermethylation is not the major cause of decreased expression of Tβ RII in endometrial cancers. Mutational analysis revealed that 15.1% (8/53) of endometrial cancers had frameshift mutations at polyadenine repeats in exon 3 of the Tβ RII gene. Notably, these mutations were preferentially accumulated in patients with MSI- H phenotype (7/19:37% ) (P < 0.001) or with those with methylated MLH1 promoters (6/16:38% ) (P < 0.01). Thus, it appears that the Tβ RII gene is a target of mismatch repair deficiency. Conclusion. Taken together, we found that the decreased expression of Tβ RII as well as frameshift mutation of Tβ RII via mismatch repair deficiency frequently occurs in this tumor type, possibly causing loss of receptor function and unresponsiveness of TGF- β signaling that may lead to endometrial carcinogenesis.
AIM: To examine the long term survival of geriatric patients treated with percutaneous endoscopic gastrostomy (PEG) in Japan. METHODS: We retrospectively included 46 Japanese community and tertiary hospitals to invest...
详细信息
AIM: To examine the long term survival of geriatric patients treated with percutaneous endoscopic gastrostomy (PEG) in Japan. METHODS: We retrospectively included 46 Japanese community and tertiary hospitals to investigate 931 consecutive geriatric patients (≥ 65 years old) with swallowing difficulty and newly performed PEG between Jan 1st 2005 and Dec 31st 2008. We set death as an outcome and explored the associations among patient’s characteristics at PEG using log-rank tests and Cox proportional hazard models. RESULTS: Nine hundred and thirty one patients were followed up for a median of 468 d. A total of 502 deaths were observed (mortality 53%). However, 99%, 95%, 88%, 75% and 66% of 931 patients survived more than 7, 30, 60 d, a half year and one year, respectively. In addition, 50% and 25% of the patients survived 753 and 1647 d, respectively. Eight deaths were considered as PEG-related, and were associated with lower serum albumin levels (P = 0.002). On the other hand, among 28 surviving patients (6.5%), PEG was removed. In a multivariate hazard model, older age [hazard ratio (HR), 1.02; 95% confidence interval (CI), 1.00-1.03; P = 0.009], higher C-reactive protein (HR, 1.04; 95% CI: 1.01-1.07; P = 0.005), and higher blood urea nitrogen (HR, 1.01; 95% CI: 1.00-1.02; P = 0.003) were significant poor prognostic factors, whereas higher albumin (HR, 0.67; 95% CI: 0.52-0.85; P = 0.001), female gender (HR, 0.60; 95% CI: 0.48-0.75; P < 0.001) and no previous history of ischemic heart disease (HR, 0.69; 95% CI: 0.54-0.88, P = 0.003) were markedly better prognostic factors. CONCLUSION: These results suggest that more than half of geriatric patients with PEG may survive longer than 2 years. The analysis elucidated prognostic factors.
暂无评论