Integrative analysis of the inverse expression patterns in pancreas development and cancer progression.

BACKGROUND: As the malignant tumor, pancreatic cancer with a meager 5-years survival rate has been widely concerning. However, the molecular mechanisms that result in malignant transformation of pancreatic cells remain elusive. AIM: To investigate the gene expression profiles in normal or malignant transformed pancreas development. METHODS: MaSigPro and ANOVA were performed on two pancreas development datasets downloaded from the Gene Expression Omnibus database. Six pancreatic cancer datasets collected from TCGA database were used to establish differentially expressed genes related to pancreas development and pancreatic cancer. Moreover, gene clusters with highly similar interpretation patterns between pancreas development and pancreatic cancer progression were established by self-organizing map and singular value decomposition. Additionally, the hypergeometric test was performed to compare the corresponding interpretation patterns. Abnormal regions of metabolic pathway were analyzed using the Sub-pathway-GM method. RESULTS: This study established the continuously upregulated and downregulated genes at different stages in pancreas development and progression of pancreatic cancer. Through analysis of the differentially expressed genes, we established the inverse and consistent direction development-cancer pattern associations. Based on the application of the Subpathway-GM analysis, we established 17 significant metabolic sub-pathways that were closely associated with pancreatic cancer. Of note, the most significant metabolites sub-pathway was related to glycerophospholipid metabolism. CONCLUSION: The inverse and consistent direction development-cancer pattern associations were established. There was a significant correlation in the inverse patterns, but not consistent direction patterns.

PACE4 regulates apoptosis in human pancreatic cancer Panc­1 cells via the mitochondrial signaling pathway.

Previous studies have demonstrated the overexpression of paired basic amino acid cleaving enzyme 4 (PACE4) mRNA in prostate cancer tissues. This overexpression is correlated with higher circulating protein levels in certain patients, however, the role of PACE4 in apoptosis and the potential molecular mechanisms of pancreatic cancer remain to be elucidated. The aim of the present study was to investigate the effect and potential molecular mechanisms of PACE4 on apoptosis in the Panc­1 pancreatic cancer cell line. Cell proliferation was assessed using a Cell Counting Kit­8 assay. Apoptotic nuclear shrinkage was monitored using Hoechst 33258 staining. Caspase­3/7 activities were measured using a colorimetric caspase­glo 3/7 assay. Alterations in protein expression were monitored using Western blot analysis. The results indicated that PACE4 small interfering (si)RNA inhibited cell proliferation and activated caspase­3/7 activities. In addition, PACE4 siRNA significantly increased apoptosis via the activation of caspase­3 and the downregulation of anti­apoptotic proteins, X­linked inhibitor of apoptosis protein and phosphorylated­Akt. In addition, the results showed deregulation of the B cell lymphoma­2 (Bcl­2)-associated X protein/Bcl­2 ratio which led to the release of cytochrome c following PACE4 siRNA transfection. In conclusion, PACE4 siRNA may exert antitumor activity through the mitochondrial pathway and is expected to be a promising therapeutic strategy for the treatment of pancreatic cancer.

Med19 promotes gastric cancer progression and cellular growth.

Med19 was a member of the Mediator complex which forms the bridge between transcriptional activators and RNA polymerase II. We aim to investigate the functional role of Med19 in the progression of human gastric carcinoma. The correlation between Med19 expression and clinicopathologic features in 60 gastric carcinoma specimens was analyzed by using immunohistochemistry. Recombinant lentivirus expressing Med19 short hairpin RNA (shRNA) was constructed and infected into human gastric carcinoma SGC7901 and MGC803 cells. MTT, colony formation and cell cycle analysis were used to study the effect of Med19 shRNA on gastric cancer cell proliferation. Expression of Med19 was associated with tumor size, cancer cell differentiation, and TNM stages (P<0.05). Downregulation of Med19 significantly inhibited cell proliferation and colony-formation capacity, and induced G1 phase cell-cycle arrest. Collectively, Med19 functions in promoting cellular growth and may be a useful therapeutic target in malignant gastric carcinoma.

[Clinical analysis of the treatment:transcatheter arterial chemoembolization combined with sorafenib in advanced hepatocellular carcinoma].

OBJECTIVE: To provide more evidence sources to the standard treatment for patients with advanced hepatocellular carcinoma, the writer analyze patients' time to progression (TTP) and overall survival (OS) after patients receiving transcatheter arterial chemoembolization (TACE) combined with sorafenib as a treatment of advanced hepatocellular carcinoma (HCC); observe the healing effect embolization combined with anti-angiogenic treatment for advanced hepatocellular carcinoma; and also analyze treatment of security. METHODS: There are 36 patients, 33 male and 3 female had been Pathologically or clinical diagnosis. After receiving Transcatheter Arterial Chemoembolization (TACE) therapy, in the following 3 to 7 days, this group of patients continuously take sorafenib (brand name: Nexavar) (per tablet 200 mg), 2 tablets each time, 2 times a day. Every 4 to 8 weeks is called as one period of treatment. Referring to RECIST Evaluation, the writers mainly observe patients' tumor progression (TTP) and overall survival (OS), record adverse events. Using life table method to analyze survival rate, using Kaplan-Meier method to analyze all the survival curves. RESULTS: Till March, 2010, 14 of 36 evaluable patients died and 22 survive; the median time to tumor progression (mTTP) to 8.62 months (95%CI: 6.51-10.24 months); the median survival time (mOS) of 12.41 months (95%CI: 9.57-14.80 months). The overall survival rate to observation period is 61.1%; 36 patients had been studied, 22 survive. Among the survivals, there is no CR cases, and 1 case PR, 15 patients SD, 6 patients PD; disease control rate (DCR) (CR + PR + SD) is 44.4%. The side effects of taking Sorafenib mainly are hand-foot skin reaction, diarrhea, fatigue and loss of appetite. These side effects can be markedly eased after symptomatic treatment. CONCLUSION: Combined with sorafenib treatment may give patients with advanced hepatocellular carcinoma a longer longevity and keep the disease in a steady state. This therapy can be added into the treatments to patients with advanced hepatocellular carcinoma. The side effects of taking Sorafenib (Nexavar) could be stand.