Prognostic value of small mother against decapentaplegic expression in human gastric cancer.

Gastric cancer is the fifth most common malignancy in the world with alow 5-year survival rate. To date, no study has investigated the prognostic role of the small mother against decapentaplegic (SMAD) in gastric cancer. The association of SMADs with overall survival (OS) of gastric cancer was analyzed on the online Kaplan-Meier (KM) plotter database. Clinical data such as stage, differentiation, gender, treatment, and Her2 mutation status of gastric cancer patients were analyzed. The (E)-SIS3 was used to inhibit SMAD3 expression in gastric cancer cells, and the effects of SMAD3 on gastric cancer cells were analyzed via real-time cellular analysis (RTCA), flow cytometry, colony formation, and immunofluorescence assay. The results showed that the high expression of three members of SMADs (SMAD1, SMAD2, SMAD4) was correlated with afavorable OS of gastric cancer patients. Meanwhile, SMAD3 expression level indicated highly differentiated cancer. We also observed that surgical treatment was associated with high expression level of SMAD1 and SMAD2. Besides, the effect of Her2 on gastric cancer was not noticeable. Moreover, (E)-SIS3 pharmacological assay revealed that inhibition of expression of SMAD3 suppressed the proliferation and migration ability of gastric cancer cells via inducing apoptosis. Collectively, these results demonstrate that the high expression level of three members of SMADs (SMAD1, SMAD2, and SMAD4) is significantly correlated with favorable OS of gastric cancer patients, which is opposite to SMAD3. Thus, SMADs regulate the differentiation of cancer and can be used to guide treatment decisions.

A novel genomic-clinicopathologic nomogram to improve prognosis prediction of hepatocellular carcinoma.

There is a lack of precise and clinical accessible model to predict the prognosis of hepatocellular carcinoma (HCC) in clinic practice currently. Here, an inclusive nomogram was developed by integrating genomic markers and clinicopathologic factors for predicting the outcome of patients with HCC. A total of 365 samples of HCC were obtained from the Cancer Genome Atlas (TCGA) database. The LASSO analysis was carried out to identify HCC-related mRNAs, and the multivariate Cox regression analysis was used to construct a genomic-clinicopathologic nomogram. As results, 9 mRNAs were finally identified as prognostic indicators, including RGCC, CDH15, XRN2, RAB3IL1, THEM4, PIF1, MANBA, FKTN and GABARAPL1, and used to establish a 9-mRNA classifier. Additionally, an inclusive nomogram was built up by combining the 9-mRNA classifier (P < 0.001) and clinicopathologic factors including age (P = 0.006) and metastasis (P < 0.001) to predict the mortality of HCC patients. Time-dependent receiver operating characteristic, index of concordance and calibration analyses indicated favorable accuracy of the model. Decision curve analysis suggested that appropriate intervention according to the established nomogram will bring net benefit when threshold probability was above 25%. The genomic-clinicopathologic model could be a reliable tool for predicting the mortality, helping determining the individualized treatment and probably improving HCC survival.

Islet transplantation attenuates cardiac fibrosis in diabetic rats through inhibition of TGF-ß1/Smad3 pathway.

Although islet transplantation has been identified as a promising endocrine replacement treatment for patient with diabetes mellitus (DM), it still remains unclear whether islet transplantation can inhibit the diabetic-induced myocardial injury and subsequent adverse ventricular remodeling. Here, we sought to explore the molecular mechanism underlying the cardioprotective effect of islet transplantation. We established the diabetic rat model by intraperitoneal injection of STZ, which was followed by either islet transplantation or conventional insulin treatment. Compared with insulin treatment, islet transplantation further reduced the elevated blood glucose which was nearly restored to normoglycaemia. In addition, islet transplantation attenuated the increased levels of cTn-I and CK-MB, cleaved-caspase-3 in response to DM, and ameliorated diabetic-induced cardiac hypertrophy and interstitial fibrosis, along with improved extracellular matrix (ECM) deposition. Moreover, diabetic rats that underwent islet transplantation had lower expression of TGF-ß1 and lower phosphorylation levels of Smad3. Therefore, islet transplantation exerted protective effect against diabetic-induced myocardial injury and fibrotic remodeling through deactivation of TGF-ß1/Smad3 signaling pathway.