Background: MicroRNAs (miRNAs) are involved in cancer development and progression, acting as tumor suppressors or oncogenes. Our previous studies have revealed that miR-148a and miR-152 are significantly down-regulated in gastrointestinal cancers. Interestingly, miR-148b has the same "seed sequences" as miR-148a and miR-152. Although aberrant expression of miR-148b has been observed in several types of cancer, its pathophysiologic role and relevance to tumorigenesis are still largely unknown. The purpose of this study was to elucidate the molecular mechanisms by which miR-148b acts as a tumor suppressor in gastric cancer.Results: We showed significant down-regulation of miR-148b in 106 gastric cancer tissues and four gastric cancer cell lines, compared with their non-tumor counterparts by real-time RT-PCR.In situhybridization of ten cases confirmed an overt decrease in the level of miR-148b in gastric cancer tissues. Moreover, the expression of miR-148b was demonstrated to be associated with tumor size (P = 0.027) by a Mann-Whitney U test. We also found that miR-148b could inhibit cell proliferationin vitroby MTT assay, growth curves and an anchorage-independent growth assay in MGC-803, SGC-7901, BGC-823 and AGS cells. An experiment in nude mice revealed that miR-148b could suppress tumorigenicityin vivo. Using a luciferase activity assay and western blot, CCKBR was identified as a target of miR-148b in cells. Moreover, an obvious inverse correlation was observed between the expression of CCKBR protein and miR-148b in 49 pairs of tissues (P = 0.002, Spearman's correlation).Conclusions: These findings provide important evidence that miR-148b targets CCKBR and is significant in suppressing gastric cancer cell growth. Maybe miR-148b would become a potential biomarker and therapeutic target against gastric cancer.
Metabolic reprogramming is an emerging hallmark of cancer cells, in which cancer cells exhibit distinct metabolic phenotypes to fuel their proliferation and progression. The significant advancements made in the area of metabolic reprogramming make possible new strategies for overcoming malignant cancer, including triple-negative breast cancer. Triple-negative breast cancer (TNBC) is associated with high histologic grade, aggressive phenotype, and poor prognosis. Even though triple-negative breast cancer patients benefit from standard chemotherapy, they still face high recurrence rates and are more likely to develop resistance to chemotherapeutic drugs. Therefore, there is an urgent need to explore vulnerabilities of triple-negative breast cancer and develop novel therapeutic drugs to improve clinical outcomes for triple-negative breast cancer patients. Metabolic reprogramming may provide promising therapeutic targets for the treatment of triple-negative breast cancer. In this paper, we primarily discuss how triple-negative breast cancer cells reprogram their metabolic phenotype and that of stromal cells in the microenvironment to survive under nutrient-poor conditions. Considering that metastasis and chemoresistance are the main contributors to mortality in triple-negative breast cancer patients, we also focus on the role of metabolic adaption in mediating metastasis and chemoresistance of triple-negative breast cancer tumors.
Background: Palliative gastrectomy for patients with advanced gastric cancer remains controversial. The objective of the present meta-analysis was to analyze survival outcomes and establish a consensus on whether palliative gastrectomy is suitable for patients with incurable advanced gastric cancer and which type of patients should be selected to receive palliative gastrectomy. Methods: A literature search was conducted in PubMed, EMBASE and the Cochrane Library. The results for overall survival in the meta-analysis are expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Of 1647 articles and abstracts reviewed, 14 studies with 3003 patients were eligible for the final analysis. The meta-analysis revealed that palliative gastrectomy is associated with a significantly improvement in overall survival (HR 0.56; 95%CI 0.39–0.80; p < 0.002) compared that of patients treated without palliative gastrectomy. An improvement in survival was also observed in patients with stage M1 gastric cancer who received palliative gastrectomy (HR 0.62; 95%CI 0.49–0.78; p < 0.0001), especially those with peritoneal dissemination (HR = 0.76, 95%CI 0.63–0.92), liver metastasis (HR = 0.41, 95%CI 0.30–0.55), or distant lymph-node metastasis (HR = 0.36, 95%CI 0.23–0.59). Combined hepatic resection may be beneficial for patients who under palliative gastrectomy (HR 0.30; 95%CI 0.15–0.61; p = 0.0008). The overall survival of patients who underwent palliative gastrectomy combined with chemotherapy was significantly improved (HR 0.63; 95%CI 0.47–0.84; p = 0.002). Conclusions: From the results of the meta-analysis, palliative gastrectomy for patients with incurable advanced gastric cancer may be associated with longer survival, especially for patients with stage M1 gastric cancer. Combined hepatic resection for patients with liver metastasis and chemotherapy may be beneficial factors compared to simple palliative gastrectomy.
Prognostic significance of preoperative prognostic nutritional index in colorectal cancer: results from a retrospective cohort study and a meta-analysis
Background: In this meta-analysis we aimed to determine the effectiveness and safety of hyperthermic intraperitoneal chemotherapy (HIPC) for patients with advanced gastric cancer who underwent gastrectomy. Methods: In accordance with standard meta-analysis procedures, our study included patients who underwent resection for advanced gastric cancer and were randomly allocated to receive either hyperthermic intraperitoneal chemotherapy or control. We searched PubMed (up to November 2011), EMBASE (up to November 2011), Cochrane Database of Systematic Reviews (CDSR), and Cochrane Central Register of Controlled Trials (CCTR) (up to November 2011). Both published and unpublished trials were included in the analysis, and no search restrictions were imposed. There was no language restriction. The results were analyzed using RevMan 5.1 software, which was provided by Cochrane Collaboration. Results: There were ten randomized controlled trials included in the analysis. A total of 1062 patients with gastric cancer in these studies were divided into the HIPC group (n = 518) and control group (n = 544). A significant improvement in survival was observed in the HIPC groups compared to the control group in the mitomycin C (MMC) subgroup (RR = 0.75, 95%CI 0.65-0.86; P < 0.00001) and the 5-FU group (RR = 0.69, 95%CI 0.52-0.90; P < 0.00001); the total RR was 0.73 (95%CI 0.64-0.83; P < 0.00001). Our findings indicated that HIPC potentially exhibited a lower peritoneal recurrence rate in the HIPC group compared to the control group (RR = 0.45, 95%CI 0.28-0.72; P = 0.001). Conclusions: Our meta-analysis demonstrated that HIPC may improve the overall survival rate for patients who receive resection for advance gastric cancer potentially, and help to prevent peritoneal local recurrence among patients with serosal invasion in gastric cancer.