ISG15 Promotes Progression and Gemcitabine Resistance of Pancreatic Cancer Cells Through ATG7.

Chemoresistance is an obstacle of improving pancreatic cancer (PC) prognosis. However, the biological function of ISG15 in PC and whether it correlates with the resistance to chemotherapy are still unknown. Here, we aimed to reveal the clinical significance of ISG15 in PC and its regulatory mechanism in cancer progression and resistance to therapy. The level of ISG15, a protein involved in post-translational modifications, is elevated in PC tissues. Clinically, higher ISG15 expression correlates with higher PC grades, stronger resistance to treatment and poorer prognosis. Moreover, ISG15 promotes the proliferation, migration, invasion, colony formation of PC cells and resistance to Gemcitabine, a classic chemotherapeutics for PC, both in vitro and in vivo. ISG15 promotes progression and resistance to therapy in PC cells by binding to ATG7, reducing its degradation, and thereby leading to enhanced autophagy in PC cells. ISG15 may be used as both a potential diagnosis marker and sensitizer for chemotherapeutics such as Gemcitabine during PC intervention.

Establishment and assessment of the hepatic venous pressure gradient using biofluid mechanics (HVPGBFM): protocol for a prospective, randomised, non-controlled, multicentre study.

INTRODUCTION: Portal hypertension (PH) is a severe disease with a poor outcome. Hepatic venous pressure gradient (HVPG), the current gold standard to detect PH, is available only in few hospitals due to its invasiveness and technical difficulty. This study aimed to establish and assess a novel model to calculate HVPG based on biofluid mechanics. METHODS AND ANALYSIS: This is a prospective, randomised, non-controlled, multicentre trial. A total of 248 patients will be recruited in this study, and each patient will undergo CT, blood tests, Doppler ultrasound and HVPG measurement. The study consists of two independent and consecutive cohorts: original cohort (124 patients) and validation cohort (124 patients). The researchers will establish and improve the HVPG using biofluid mechanics (HVPGBFM)model in the original cohort and assess the model in the validation cohort. ETHICS AND DISSEMINATION: The study was approved by the Scientific Research Projects Approval Determination of Independent Ethics Committee of Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (approval number 2017-430 T326). Study findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03470389.

Chemotherapy for patients with gastric cancer after complete resection: a network meta-analysis.

AIM: To conduct a network meta-analysis to evaluate the effectiveness of different chemotherapy regimens for patients with gastric cancer. METHODS: PubMed (1966-2011.12), the Cochrane Library (2011 Issue 2) and EMBASE (1974-2011.12) were searched with the terms "gastric cancer" and "chemotherapy", as well as the medical subject headings. References from relevant articles and conferences were also included. Patients who had previous gastric surgery, radiation before or after surgery or chemotherapy before surgery were excluded. In this study, only randomized controlled trials (RCTs) were considered, and the end-point was the overall mortality. Direct comparisons were performed using traditional meta-analysis whereas indirect comparisons were performed using network meta-analysis. RESULTS: In total, 31 RCTs with 7120 patients were included. Five chemotherapy regimens, fluorouracil (FU) + BCNU, FU + methyl-CCNU (mCCNU), FU + cisplatin, FU + anthracyclines and FU + mitomycin c (MMC) + cytarabine (Ara-c), were found to be less beneficial in terms of overall mortality. In contrast, four chemotherapy regimens were effective for the patients after surgery, including FU + MMC + adriamycin (FMA), FU + MMC (FM), Tegafur and MMC, There was no significant difference in terms of overall mortality among these regimens. The evidence for the FM regimen and MMC regimen was poor. Additionally, the FMA regimen, which includes a variety of chemotherapy drugs and causes many side effects, was not better than the Tegafur regimen. CONCLUSION: Although the four chemotherapy regimens were effective in patients with gastric cancer after surgery and the overall mortality revealed no significant difference among them in the network meta-analysis, thorough analysis of the results recommends Tegafur as the first-line adjuvant chemotherapy regimen for patients after complete resection.

Efficacy of antioxidant vitamins and selenium supplement in prostate cancer prevention: a meta-analysis of randomized controlled trials.

Several studies have evaluated the possible association between antioxidants vitamins or selenium supplement and the risk of prostate cancer, but the evidence is still inconsistent. We systematically searched PubMed, EMBASE, the Cochrane Library, Science Citation Index Expanded, Chinese biomedicine literature database, and bibliographies of retrieved articles up to January 2009. We included 9 randomized controlled trials with 165,056 participants; methodological quality of included trials was generally high. Meta-analysis showed that no significant effects of supplementation with beta-carotene (RR 0.97, 95% CI 0.90-1.05) (3 trials), vitamin C (RR 0.98, 95% CI 0.91-1.06) (2 trials), vitamin E (RR 0.96, 95% CI 0.85-1.08) (5 trials), and selenium (RR 0.78, 95% CI 0.41-1.48) (2 trials)versus placebo on prostate cancer incidence. The mortality of prostate cancer did not differ significantly by supplement of beta-carotene (RR 1.19, 95% CI 0.87 -1.65) (1 trial), vitamin C (RR 1.45, 95%CI 0.92-2.29) (1 trial), vitamin E (RR 0.85, 95%CI 0.58-1.24) (2 trials), and selenium (RR 2.98, 95% CI 0.12-73.16) (1 trial). Our findings indicate that antioxidant vitamins and selenium supplement did not reduce the incidence and mortality of prostate cancer, these data provide no support for the use of these supplements for the prevention of prostate cancer.