MiR-374b Promotes Proliferation and Inhibits Apoptosis of Human GIST Cells by Inhibiting PTEN through Activation of the PI3K/Akt Pathway.

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. In order to investigate a new treatment fot GIST, we hypothesized the effect of miR-374b targeting PTEN gene-mediated PI3K/Akt signal transduction pathway on proliferation and apoptosis of human gastrointestinal stromal tumor (GIST) cells. We obtained GIST tissues and adjacent normal tissues from 143 patients with GIST to measure the levels of miR-374b, PTEN, PI3K, Akt, caspase9, Bax, MMP2, MMP9, ki67, PCNA, P53 and cyclinD1. Finally, cell viability, cell cycle and apoptosis were detected. According to the KFGG analysis of DEGs, PTEN was involved in a variety of signaling pathways and miRs were associated with cancer development. The results showed that MiR-374b was highly expressed, while PTEN was downregulated in the GIST tissues. The levels of miR-374b, PI3K, AKT and PTEN were related to tumor diameter and pathological stage. Additionally, miR-374b increased the mRNA and protein levels of PI3K, Akt, MMP2, MMP9, P53 and cyclinD1, suggesting that miR-374b activates PI3K/Akt signaling pathway in GIST-T1 cells. Moreover, MiR-374b promoted cell viability, migration, invasion, and cell cycle entry, and inhibited apoptosis in GIST cells. Taken together, the results indicated that miR-374b promotes viability and inhibits apoptosis of human GIST cells by targeting PTEN gene through the PI3K/Akt signaling pathway. Thus, this study provides a new potential target for GIST treatment.

Adjuvant chemoradiotherapy versus adjuvant chemotherapy for R1 resected gastric cancer: a retrospective cohort study.

OBJECTIVE: The aim of this study was to compare the effects of adjuvant chemoradiotherapy (CRT) and adjuvant chemotherapy (ChT) on the survival of locally advanced gastric cancer (LAGC) patients treated with R1 resection. METHODS: The patients with LAGC and microscopically positive margins after a potentially curative gastrectomy in Fudan University Shanghai Cancer Centre were retrospectively identified. The patients who were referred to our hospital for adjuvant CRT after an R1 resection elsewhere were also included. The patients were divided into either the CRT group or ChT group according to the treatment strategy. We, then, examined the patient survival results and patterns of recurrence for each group. RESULTS: There were 114 LAGC patients treated with an R1 resection identified (CRT, n = 33; ChT, n = 81). The baseline characteristics between the two groups were not different. The estimated 3 year recurrence-free survival and overall survival in the CRT and ChT groups were 45.1% vs 31.8% (p = 0.09) and 49.6% vs 39.4% (p = 0.20), respectively. The results indicated that only nodal status was an independent prognostic factor (hazard ratio 4.04, 95% confidence interval 2.06-7.93). The risk of locoregional recurrence was increased in the ChT group. The subgroup analysis revealed that patients with pN0-2 GC showed a better recurrence-free survival due to adjuvant CRT (hazard ratio 0.19, 95% confidence interval 0.04-0.90; p = 0.022). CONCLUSION: Adjuvant CRT improves locoregional control and may benefit patients with pN0-2 GC after R1 resection. The nodal status may be the most important predictor for patient selection. Advances in knowledge: Nodal status may be the most important predictor for patient selection. Compared with adjuvant ChT, LAGC patients with pN0-2 disease may further benefit from additional radiotherapy after R1 resection.

A mixed treatment comparison of toxicity of gemcitabine combined with different targeted drugs in the treatment of advanced or metastatic pancreatic cancer.

The mixed treatment comparison study was performed in order to compare the toxicities of Gemcitabine and different targeted drug combinations in the treatment of advanced/metastatic pancreatic cancer (PC). Searches were performed from the inception of PubMed and Cochrane Library databases to February 2017. This study included randomized controlled trials (RCTs) of Gemcitabine and different targeted drug combinations in the treatment of advanced/metastatic PC. Odds ratio (OR) values were calculated by direct and indirect comparisons, and the surface under the cumulative ranking curves (SUCRA) were drawn. A total of six RCTs were finally incorporated into the study. These studies included six therapy regimens: Gemcitabine + Axitinib, Gemcitabine + Trametinib, Gemcitabine + Sorafenib, Gemcitabine + Bevacizumab, Gemcitabine + Erlotinib and Gemcitabine + Tipifarnib. The results showed that Gemcitabine + Axitinib combinations showed lower incidence rates of rashes (all grades) in comparison to Gemcitabine + Trametinib and Gemcitabine + Erlotinib combinations. Compared with Gemcitabine+ Trametinib combinations, Gemcitabine + Axitinib combinations showed lower incidence rates of diarrhea (grade ≥ 3). Moreover, the cluster analyses results revealed that Gemcitabine + Axitinib combinations and Gemcitabine + Sorafenib combinations showed lower incidence rates of hematotoxicity, while Gemcitabine + Axitinib combinations showed lower incidence rates of non-hematotoxicity. Collectively, the data provided strong evidence of Gemcitabine + Axitinib combinations showing lower incidence rates of non-hematotoxicity, and Gemcitabine + Axitinib and Gemcitabine + Sorafenib combinations may have lower incidence rates of hematotoxicity in the treatment of advanced/metastatic PC.

Correlations of IGF-1R and COX-2 Expressions with Ras and BRAF Genetic Mutations, Clinicopathological Features and Prognosis of Colorectal Cancer Patients.

This case-control study aims to investigate the correlations of insulin-like growth factor receptor 1 (IGF-1R) and cyclooxygenase 2 (COX-2) expressions with Ras and BRAF genetic mutations, clinicopathological features and prognosis of colorectal cancer (CRC) patients. A total of 213 CRC patients (case group) and 200 healthy individuals (control group) were selected from our hospital. Ras (K-Ras/N-Ras) and BRAF genetic mutations were detected by direct sequencing. The positive expression rates of IGF-IR and COX-2 in CRC and normal tissues were detected using immunohistochemistry. RT-qPCR and Western blotting were applied to detect the mRNA and protein expressions of IGF-IR and COX-2 in CRC tissues and normal tissues. Total mutation rate of N-Ras, BRAF and K-Ras in case group were 5.2%, 12.2% and 47.4%, respectively. The expressions of IGF-IR and COX-2 were higher in CRC tissues with Ras and BRAF mutations than in those without. CRC tissues with Ras mutation showed higher COX-2 expression than those with BRAF mutation. IGF-IR and COX-2 expressions were correlated to infiltration degree, lymphatic metastasis (in CRC tissues with and without Ras and BRAF mutations), and Dukes stages (only in CRC tissues with Ras and BRAF mutations). CRC patients with negative expressions of IGF-IR and COX-2 had significantly higher accumulative survival rate and longer mean survival duration than those with positive expressions of IGF-IR and COX-2. These findings indicate that IGF-1R and COX-2 expressions may be associated with Ras and BRAF genetic mutations, clinicopathological feature and prognosis of CRC patients.

Involvement of Bmi-1 gene in the development of gastrointestinal stromal tumor by regulating p16Ink4A/p14ARF gene expressions: An in vivo and in vitro study.

OBJECTIVE: This study was conducted in order to explore the role that Bmi-1 plays during the development of a gastrointestinal stromal tumor (GIST) by regulation of the p16Ink4A and p14ARF expressions. METHODS: Eighty-six patients diagnosed with GIST were selected to take part in this experiment. The Bmi-1 protein expressions in GIST and adjacent normal tissues were detected using immunohistochemistry and further analyzed by using photodensitometry. To monitor and track the progression of the GIST, a 3-year follow-up was conducted for all affected patients. After cell transfection, the GIST cells were assigned into the control group (without transfection), the negative control (NC) group (transfected with Bmi-1-Scramble plasmid), and the Bmi-1 shRNA group (transfected with the pcDNA3.1-Bmi-1 shRNA plasmid). Protein and mRNA expressions collected from Bmi-1, p16lnk4A, P14ARF, cyclin D1, and CDK4 were measured using both the RT-qPCR and western blotting methods Cell senescence was assessed and obtained by using the ß-Galactosidase (ß-Gal) activity assay. The use of a Soft agar colony formation assay and CCK-8 assay were performed in order to detect the cell growth and subsequent proliferation. Cell invasion and migration were analyzed using the Transwell assay and scratch test. RESULTS: Bmi-1 in the GIST tissues was found to be significantly higher and the p16lnk4A and P14ARF expressions were lower than those in the adjacent normal tissues. Bmi-1 was negatively correlated with p16lnk4A and P14ARF expressions according to the correlation analysis. Bmi-1 expression was associated with the TNM stage, postoperative recurrence, metastasis, tumor size, and the 5-year survival rate. Area under ROC curve was calculated at 0.884, and sensitivity, specificity, and accuracy of Bmi-1 predicting the GIST were 67.44%, 97.67%, and 65.12%, respectively. Patients exhibiting a high Bmi-1 expression in the GIST tissues had lower survival rates than those with low Bmi-1 expression. In comparison with the control group, P14ARF, and p16lnk4A were up-regulated, while cyclinD 1 and CDK4 were down-regulated, cell senescence was promoted, and cell proliferation, invasion, and migration also showed some regression in the Bmi-1 shRNA group. CONCLUSIONS: These collection of data indicated that the down-regulated Bmi-1 might inhibit the proliferation, invasion, and migration of GIST cells and can be subsequently linked to the incidence and developing a prognosis of GIST.

MicroRNA-27a Promotes the Proliferation and Invasiveness of Colon Cancer Cells by Targeting SFRP1 through the Wnt/ß-Catenin Signaling Pathway.

OBJECTIVE: This study aims to explore the effects of microRNA-27a (miR-27a) on the proliferation and invasiveness of colon cancer cells through the Secreted Frizzled-related protein 1 (SFRP1) and the Wnt/ß-catenin signaling pathway. METHODS: Colon cancer tissues and adjacent normal tissues from 125 colon cancer patients, together with the HCEpic, HCT-116, HT-29, SW480 and SW620 cell lines, were prepared for this study. The transfected HCT-116 cells were divided into the miR-27a mimics, miR-27a-NC, anti-miR-27a, blank, Lv-SFRP1, Lv-NC, and miR-27a mimics + Lv-SFRP1 groups. RT-qPCR was performed to detect the expressions of miR-27a and SFRP1 mRNA. A dual-luciferase reporter assay was conducted to examine the effect of miR-27a on SFRP1. Western blotting was used to measure the expressions of the SFRP1, ß-catenin, GSK-3ß, p-ß-catenin, p-GSK-3ß, c-Myc and cyclin D1 proteins. MTT, soft agar clone formation and Transwell chamber assays were performed to detect cell proliferation and invasion. RESULTS: Compared with normal tissues and cells, colon cancer tissues and cells demonstrated significantly higher expression of miR-27a, but lower expressions of SFRP1 mRNA and protein. MiR-27a negatively regulated the expression of SFRP1 mRNA. SFRP1 was also found to be a target gene of miR-27a. In the miR-27a mimic group, the proliferation and invasiveness of colon cancer cells were significantly increased, while the expressions of GSK-3 ß and p-ß-catenin were remarkably down-regulated; in contrast, the expressions of p-GSK-3ß, -catenin, c-Myc and cyclin D1 were up-regulated. While the proliferation and invasiveness of colon cancer cells in the anti-miR-27a and Lv-SFRP1 groups were decreased, the expressions of GSK-3ß and p-ß-catenin were elevated, and the expressions of p-GSK-3ß, ß-catenin, c-Myc and cyclin D1 were decreased. CONCLUSION: These findings indicated that miR-27a could promote the proliferation and invasiveness of colon cancer cells by targeting SFRP1 through the Wnt/ß-catenin signaling pathway.

Effect of SOCS1 silencing on proliferation and apoptosis of melanoma cells: An in vivo and in vitro study.

This study aimed to investigate the effect of SOCS1 silencing on the proliferation and apoptosis of melanoma cells by in vivo and in vitro studies. Immunohistochemical staining was used to detect SOCS1 expression in melanoma tissues and pigmented nevi. Quantitative real-time polymerase chain reaction and western blotting were applied to detect the messenger RNA and protein expressions of SOCS1 in primary human melanocytes and malignant melanoma cell lines (A375, SK-MEL-5, M14, and MV3). Melanoma cells were assigned into mock, negative small interfering RNA, and SOCS1-small interfering RNA groups. The proliferation, cell cycle and apoptosis, and messenger RNA expression of SOCS1 in MV3 and A375 cells were detected using MTT assay, flow cytometry, and quantitative real-time polymerase chain reaction, respectively. The expressions of SOCS1 protein, extracellular signal-regulated kinase, and janus kinase signal transduction and activators of transcription signaling pathways-related proteins were detected using western blotting. After the establishment of subcutaneous xenograft tumor models in nude mice, the latent period, size, volume and growth speed of xenograft tumors in the mock, negative small interfering RNA, and SOCS1-small interfering RNA groups were examined and compared. The results indicated that positive expression rate of SOCS1 was higher in malignant melanoma tissues than in pigmented nevi. MV3 cells had the highest messenger RNA and protein expressions of SOCS1, followed by A357 cells. Compared with the mock and negative small interfering RNA groups, SOCS1-small interfering RNA group showed lower cell viability, elevated cell apoptosis, more cells in G0/G1 phase and less cells in S and G2/M phases, and decreased messenger RNA and protein expressions of SOCS1, p-ERK1/2, p-JAK2, p-STAT1, and p-STAT3. Compared with the mock and negative small interfering RNA groups, the SOCS1-small interfering RNA group showed longer latent period of tumor, smaller tumor size and volume, and smoother tumor growth curve. To conclude, SOCS1 silencing can inhibit proliferation and induce apoptosis of MV3 and A357 melanoma cells in vivo and in vitro by inhibiting extracellular signal-regulated kinase and janus kinase signal transduction and activators of transcription signaling pathways.

Efficacy and Safety of Single- or Double-Drug Antidiabetic Regimens in the Treatment of Type 2 Diabetes Mellitus: A Network Meta-Analysis.

A network meta-analysis was performed in order to compare the efficacy and safety of single- or double-drug antidiabetic regimens in the treatment of type 2 diabetes mellitus (T2DM). PubMed and Cochrane Library searches were conducted since inception to February 2017. Randomized controlled trials (RCTs) of different antidiabetic regimens in the treatment of T2DM were included in this study. Direct and indirect evidences were combined to calculate the odds ratio (OR) or weighted mean difference (WMD) and its 95% confidence interval (95%CI), and in order to draw the surface under the cumulative ranking curves (SUCRA). A total of 19 RCTs meeting our inclusion criteria were finally incorporated into our network meta-analysis, including 19 single- or double-drug antidiabetic regimens. The network meta-analysis showed that the anti-hyperglycemic effects of Sitagliptin + Metformin, Empagliflozin + Metformin, Exenatide + Metformin, Vildagliptin + Metformin, Taspoglutide + Metformin, and Pioglitazone + Metformin were better than individual Metformin regimens. Dulaglutide + Metformin and Taspoglutide + Metformin regimens were comparatively less safe than individual Metformin regimens. The cluster ranking analysis based on SUCRA values suggested that Taspoglutide + Metformin regimens had best efficacy and worst safety among the different therapy regimens. Our data confirmed previous observations and suggested that Taspoglutide + Metformin regimen may have better efficacy for the treatment of T2DM among 19 therapy regimens, while its incidence of adverse events was relatively higher. J. Cell. Biochem. 118: 4536-4547, 2017. © 2017 Wiley Periodicals, Inc.

CXCR6 predicts poor prognosis in gastric cancer and promotes tumor metastasis through epithelial-mesenchymal transition.

Chemokines and their receptors have been confirmed to be involved in several types of cancer. However, little is known concerning the role of CXCL16 and its receptor CXCR6 in gastric cancer (GC) progression and metastasis. In the present study, expression of CXCL16 and CXCR6 in GC tumor and peritumoral tissues was detected by immunohistochemistry (IHC) in a cohort of 352 GC patients who underwent gastrectomy, and the correlation between CXCL16/CXCR6 expression and clinicopathological characteristics was further analyzed. To evaluate the function of CXCR6, we overexpressed and knocked down CXCR6 in GC cell lines. Results showed that expression of CXCR6, but not CXCL16, was significantly upregulated in GC tumor tissues, and was significantly correlated with lymph node and distant metastases, and advanced clinical stage in the GC patients. Survival analysis showed that large tumor size (>5 cm), elevated preoperative serum carcinoembryonic antigen (CEA) level, advanced TNM stage and high CXCR6 expression indicated worse overall survival (OS) and disease-free survival (DFS) in GC, and CXCR6 was an independent predictor for both OS and DFS in GC. In vitro experiments showed that CXCR6 overexpression induced cell migration and invasion ability, and promoted epithelial-mesenchymal transition of GC cells by upregulation of mesenchymal markers and inhibition of epithelial markers. In contrast, knockdown of CXCR6 in GC cells resulted in inhibition of cell proliferation, migration and invasion ability, and reversal of epithelial-mesenchymal transition (EMT) phenomenon. Our results demonstrated that CXCR6 is an independent prognostic factor for poor survival in GC patients, and may promote GC metastasis through EMT.

CtBP2 overexpression promotes tumor cell proliferation and invasion in gastric cancer and is associated with poor prognosis.

C-terminal binding protein-2 (CtBP2), a transcriptional corepressor, has been reported to correlate with tumorigenesis and progression and predict a poor prognosis in several human cancers. However, few studies on CtBP2 in gastric cancer (GC) have been performed. In this research, we evaluated the correlations between CtBP2 expression and the clinicopathological characteristics, as well as prognosis of GC patients. The effects of silencing CtBP2 expression on GC cells biology activity were also assessed. The results showed that CtBP2 was overexpressed in GC tissues and closely correlated with poor differentiation, advanced tumor stage and poor prognosis in GC patients. CtBP2 induced epithelial-to-mesenchymal transition (EMT) and repressed PTEN to increase proliferation rate, migration, and invasion in GC cells. Silencing CtBP2 inhibited GC growth in nude mice model. In conclusion, CtBP2 is overexpressed in GC and may accelerate GC tumorigenesis and metastasis, which could represent an independent prognostic marker and promising therapeutic target for GC.

Mechanism of MicroRNA-146a/Notch2 Signaling Regulating IL-6 in Graves Ophthalmopathy.

BACKGROUND/AIMS: We intended to investigate the significance of microRNA-146a, Notch2 and IL-6 on Graves ophthalmopathy (GO) and the relationships among them. METHODS: About 27 GO patients were incorporated in this study, including 13 patients with inactive GO and14 patients with active GO. Another 15 patients who had previously received strabismus orthopedics or ophthalmectomy due to trauma were selected as the control population. QRT-PCR assay was used to detect microRNA-146a and Notch2 expression levels in plasma. MTT assay and flow cytometry were respectively used to assess the viability and mitosis of the fibroblasts isolated from orbital connective tissue. Double antibody sandwich enzyme-linked immunosorbent assay (ELISA) was employed to detect serum IL-6 levels. The dual luciferase reporter gene assay was used to verify the targeting relationship between microRNA-146a and Notch2. RESULTS: Compared with the control group, the relative expression of miR-146a was significantly increased whereas the relative expression of Notch2 was significantly decreased (all P < 0.05) in GO patients compare with the control. Notch2 can be directly targeted by microRNA-146a. The over-expression of miR-146a markedly facilitated Orbital Fibroblasts (OFs) viability and mitosis whereas markedly suppressed cell apoptosis (all P < 0.05). Exogenous microRNA-146a mimics could down-regulat the expression of Notch2 and up-regulate IL-6 (P < 0.05). The inhibition of microRNA-146 resulted in the elevated expression of Notch2 and decreased expression of IL-6 (P < 0.05). CONCLUSION: MicroRNA-146a may increase the IL-6 levels and exacerbate GO by directly targeting Notch2.

Correlations of EGF G1380A, bFGF C754G and VEGF T460C polymorphisms with malignant melanoma susceptibility and prognosis: A case-control study.

This case-control study aims to investigate the correlations of EGF G1380A, bFGF C754G and VEGF T460C polymorphisms with the susceptibility and prognosis of malignant melanoma. A total of 153 patients with multiple primary melanomas were collected as the case group and another 170 healthy individuals were selected as the control group. ELISA and PCR-RFLP were performed to test the serum level of VEGF and to analyze the genotype as well as allele frequencies of VEGF T460C, EGF G1380A, and bFGF C754G, respectively. The patients were assigned into complete remission (CR), partial remission (PR) and non-remission groups after treatment. HE and CD34 staining were conducted in tissue samples of CR and PR patients. Event-free survival (EFS) and overall survival (OS) were measured. AA genotype of EGF G1380A and GG genotype of bFGF C754G had higher frequency distribution in the case group than the control group. Patients with AA genotype of EGF G1380 and GG genotype of bFGF C754G had an elevated VEGF level in comparison to other genotypes. Patients with GA+GG genotypes of EGF G1380A and CG+CC genotypes of bFGF C754G had higher EFS and OS than those with AA genotype and those with GG genotype, respectively. According to the haplotype analysis, the case group had a notably higher frequency of TAG and CAG along with while lower frequency of TGG and CGC compared with the control group. Logistic regression analysis revealed that the polymorphisms of EGF G1380A and bFGF C754G as well as the haploid TAG increased the susceptibility of malignant melanoma. The results indicated that EGF G1380A and bFGF C754G gene polymorphisms were associated with the susceptibility and prognosis of malignant melanoma, and that the polymorphisms of EGF G1380A and bFGF C754G as well as the haploid TAG increased the susceptibility of malignant melanoma.

Comparative efficacy and acceptability of endothelin receptor antagonists for pulmonary arterial hypertension: A network meta-analysis.

BACKGROUND: Endothelin receptor antagonists (ERAs) such as ambrisentan, sitaxsentan, bosentan and macitentan are primary drug therapies for pulmonary arterial hypertension (PAH) patients. However, the optimal drugs for PAH remained controversial due to heterogeneous nature of randomized control trials (RCTs). METHODS: Apart from traditional meta-analysis, network meta-analysis (NMA) was performed in this study for multiple comparisons among PAH therapies. The 6 minute walking distance (6MWD) and clinical worsening were efficacy outcomes whereas serious adverse effects (SAE) and all-cause discontinuation were acceptability outcomes. The weighted mean difference (WMD) and odds ratio (OR) along with their 95% confidence interval (95% CI) or 95% credible interval (95% CrI) were used to evaluate the positive and negative effects of these therapies on PAH patients. RESULTS: By synthesizing direct evidence from 10 studies with a total number of 2172 patients, we discovered that all of the four PAH therapies significantly increased the average 6MWD in comparison to the placebo (P-value<0.05). Moreover, bosentan and ambrisentan both showed significant association with a decrease in the risk of clinical worsening compared to placebo. Regarding of all-cause discontinuation, ambrisentan is the only therapy which was significantly associated with a risk decrease compared to placebo. However, there was no sufficient evidence suggesting significant difference in any efficacy or acceptability outcomes between any two of the PAH therapies (P-value>0.05). CONCLUSION: Ambrisentan could be considered as the most appropriate therapy among the four ERAs for PAH patients. Bosentan also behaved well, but it is not as safe as ambrisentan.

Short-term efficacy of different chemotherapy regimens in the treatment of advanced gastric cancer: a network meta-analysis.

OBJECTIVE: A network meta-analysis was performed to compare the short-term efficacy of different chemotherapy regimens in the treatment of advanced gastric cancer. METHODS: Randomized controlled trials of different chemotherapy regimens for advanced gastric cancer were included in this study. Network meta-analysis combined direct evidence and indirect evidence to evaluate the odds ratio and draw surface under the cumulative ranking curves of different chemotherapy regimens in advanced gastric cancer. RESULTS: The results of surface under the cumulative ranking curves showed that S-1 and capecitabine regimens were better than fluorouracil. As for multi-drug combination regimens, the disease control rate of cisplatin + capecitabine, docetaxel + cisplatin + fluorouracil and etoposide + cisplatin + capecitabine regimens were relatively better, while fluorouracil + adriamycin + mitomycin regimen was relatively poorer when compared with cisplatin + fluorouracil regimen. Additionally, the overall response ratio of cisplatin + capecitabine, paclitaxel + fluorouracil, docetaxel + cisplatin + fluorouracil and etoposide + cisplatin + fluorouracil regimens were relatively better, while the disease control rate of fluorouracil + adriamycin + mitomycin regimen was relatively poorer when compared with cisplatin + fluorouracil regimen. Furthermore, the results of cluster analysis demonstrated that cisplatin + capecitabine, etoposide + cisplatin + capecitabine, S-1 + paclitaxel and S-1 + irinotecan chemotherapy regimens had better disease control rate and overall response ratio for advanced gastric cancer patients. CONCLUSION: This network meta-analysis clearly showed that multi-drug combination chemotherapy regimens based on capecitabine and S-1 might be the best chemotherapy regimen for advanced gastric cancer.

A network meta-analysis on the efficacy of sixteen targeted drugs in combination with chemotherapy for treatment of advanced/metastatic colorectal cancer.

OBJECTIVE: A network meta-analysis was conducted comparing the short-term efficacies of 16 targeted drugs in combination with chemotherapy for treatment of advanced/metastatic colorectal cancer (CRC). RESULTS: Twenty-seven RCTs were ultimately incorporated into this network meta-analysis. Compared with chemotherapy alone, bevacizumab + chemotherapy, panitumumab + chemotherapy and conatumumab + chemotherapy had higher PR rate. Bevacizumab + chemotherapy, cetuximab + chemotherapy, panitumumab + chemotherapy, trebananib + chemotherapy and conatumumab + chemotherapy had higher ORR rate in comparison to chemotherapy alone. Furthermore, bevacizumab + chemotherapy had higher DCR rate than chemotherapy alone. The results of our cluster analysis showed that chemotherapy combined with bevacizumab, cetuximab, panitumumab, conatumumab, ganitumab, or brivanib + cetuximab had better efficacies for the treatment of advanced/metastatic CRC in comparison to chemotherapy alone. MATERIALS AND METHODS: Electronic databases were comprehensively searched for potential and related randomized controlled trials (RCTs). Direct and indirect evidence were incorporated for evaluation of stable disease (SD), progressive disease (PD), complete response (CR), partial response (PR), disease control rate (DCR) and overall response ratio (ORR) by calculating odds ratio (OR) and 95% confidence intervals (CI), and using the surface under the cumulative ranking curve (SUCRA). CONCLUSIONS: These results indicated that bevacizumab + chemotherapy, panitumumab + chemotherapy, conatumumab + chemotherapy and brivanib + cetuximab + chemotherapy may have better efficacies for the treatment of advanced/metastatic CRC.

Marital status and survival in patients with gastric cancer.

The objective of this study is to examine the impact of marital status on incidence of metastasis at diagnosis, receipt of surgery, and cause-specific survival (CSS) in patients with gastric cancer (GC). Research data is extracted from The Surveillance, Epidemiology, and End Results (SEER) database, and 18,196 patients diagnosed with GC from 2004 to 2010 are involved. Effects of marital status on incidence of metastasis at diagnosis, receipt of surgery, and CSS are determined using multivariable logistic regression and multivariable Cox regression models, as appropriate. Single GC patients have a higher incidence of metastasis at diagnosis than married patients, while the differences between divorced/separated patients or widowed patients and married patients are not significant. Among those without distant metastasis, single patients, divorced/separated patients, and widowed patients are much less likely to accept surgery compared with married patients. Finally, in the whole group of 18,196 GC patients, single patients, divorced/separated patients, and widowed patients have shorter CSS compared with married patients, even in each of the TNM stage. Marriage had a protective effect against undertreatment and cause-specific mortality (CSM) in GC. Spousal support may contribute to higher rate of surgery receipt and better survival in patients with GC.

Association of IL-17 polymorphisms with gastric cancer risk in Asian populations.

AIM: To investigate associations between the IL-17 rs2275913 G>A and rs763780 T>C polymorphisms and susceptibility to gastric cancer in Asian populations. METHODS: We reviewed studies published up to 2014 on IL-17 polymorphisms with gastric cancer susceptibility systematically. Relevant articles were identified in the MEDLINE, Science Citation Index, Cochrane Library, PubMed, EMBASE, CINAHL and Current Contents Index databases. We used version 12.0 STATA statistical software to evaluate the statistical data. Two reviewers abstracted the data independently. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated. RESULTS: Seven independent, case-control studies were chosen for the meta-analysis, which included 3210 gastric cancer patients and 3889 healthy controls. The overall estimation showed a positive association between the IL-17 rs2275913 G>A polymorphism and the occurrence of gastric cancer for five genetic models (all P < 0.05) and similar results were observed for the IL-17 rs763780 T>C variation with four genetic models (all P < 0.05), but not for the dominant model (P > 0.05). Subgroup analysis by country revealed that the rs2275913 G>A and rs763780 T>C polymorphisms may be the main risk factor for gastric cancer in Chinese and Japanese populations. CONCLUSION: The IL-17 gene may be significantly correlated with gastric cancer risk in Asian populations, especially those carrying the rs2275913 G>A and rs763780 T>C polymorphisms.

Association between cadherin-17 expression and pathological characteristics of gastric cancer: a meta-analysis.

AIM: To construct a meta-analysis in order to examine the relationship between cadherin-17 (CDH17) and gastric cancer (GC). METHODS: Related articles were selected by searching the following English or Chinese electronic databases: CINAHL, MEDLINE, Science Citation Index, the Chinese Journal Full-Text, and the Weipu Journal. Newcastle-Ottawa Scale (NOS) criteria were used to ensure consistency in reviewing and reporting results. Statistical analyses were conducted with Version 12.0 STATA statistical software. RESULTS: Ultimately, 11 articles, with a total of 2,120 GC patients, were found to be eligible for study inclusion. In comparisons of GC patients by TNM stage (III-IV vs I-II: OR = 2.35, 95%CI: 1.15-4.825, P = 0.019), histologic grade (3-4 vs 1-2: OR = 3.48, 95%CI: 1.36-8.92, P = 0.009), invasion grade (T3-4 vs T1-2: OR = 2.86; 95%CI: 1.69-4.83; P = 0.000), and lymph node metastasis (positive vs negative: OR = 2.64; 95%CI: 1.33-5.27; P = 0.006), it was found that CDH17 showed more positive expressions in each of the more severe cases. Country-stratified analyses from all four experimental subgroups showed that high CDH17 expression levels may be related to GC among Chinese and Korean populations (all P < 0.05), with the exception of the invasion grade T3-4 vs T1-2 comparison, where the relation only held among the Chinese population (OR = 2.86, 95%CI: 1.69-4.83, P = 0.000). CONCLUSION: Collectively, the data reflects the capacity of CDH17 in tumor proliferation and metastasis among GC patients.

Prognostic factors and survival in patients with gastric stump cancer.

AIM: To elucidate the clinicopathological characteristics and prognostic factors of gastric stump cancer (GSC). METHODS: The clinical data for 92 patients with GSC were collected at Fudan University Shanghai Cancer Center. The prognostic factors were analyzed with Cox proportional hazard models. RESULTS: GSC tended to occur within 25 years following the primary surgery, when the initial disease is benign, whereas it primarily occurred within the first 15 years post-operation for gastric cancer. Patients with regular follow-up after primary surgery had a better survival rate. The multivariate Cox regression analysis revealed that Borrmann type I/II (HR = 3.165, 95%CI: 1.055-9.500, P = 0.040) and radical resection (HR = 1.780, 95%CI: 1.061-2.987, P = 0.029) were independent prognostic factors for GSC. The overall 1-, 3-, and 5-year survival rates of the 92 patients were 78.3%, 45.6% and 27.6%, respectively. The 1-, 3-, and 5-year survival rates of those undergoing radical resection were 79.3%, 52.2%, and 37.8%, respectively. The 5-year survival rates for stages I, II, III, and IV were 85.7%, 47.4%, 16.0%, and 13.3%, respectively (P = 0.005). CONCLUSION: The appearance of GSC occurs sooner in patients with primary malignant cancer than in patients with a primary benign disease. Therefore, close follow-up is necessary. The overall survival of patients with GSC is poor, and curative resection can improve their prognosis.

Three-port laparoscopic exploration is not sufficient for patients with T4 gastric cancer.

Gastric cancer continues to be a leading cause of cancer death. The majority of patients with gastric adenocarcinoma in China present with advanced disease. Ruling out unresectable cancers from an unnecessary ''open'' exploration is very important. The aim of this study was to assess the value of five-port anatomical laparoscopic exploration in T4 gastric cancer in comparison with three-port laparoscopic exploration and laparotomy exploration. We conducted a retrospective study on 126 patients with T4 stage scheduled for D2 curative gastrectomy based on computed tomography (CT) staging at Department of Gastric Cancer and Soft Tissue Sarcoma, Fudan University Shanghai Cancer Center, from Apr. 2011 to Apr. 2013. Laparotomy exploration (Group I), three-port laparoscopic exploration (Group II) or five-port anatomical laparoscopic exploration (Group III) were performed prior to radical gastrectomy. Accuracy rate for feasibility of D2 curative gastrectomy in laparotomy exploration and five-port anatomical laparoscopic exploration groups was higher than that in the three-port laparoscopic exploration group. Five-port anatomical laparoscopic exploration group had the highest accuracy resection rate (Group I vs Group II vs Group III,92.6% vs78.6% vs 97.7%; p<0.05) and shorter length of hospitalization (Group I vs Group II vs Group III, 9.58±4.17 vs 6.13±2.85 vs 5.00±1.81; p<0.001). Three-port laparoscopic exploration has low accuracy rate for assessing feasibility of D2 curative gastrectomy and five-port anatomical laparoscopic exploration should be performed on patients with T4 gastric cancer.