Bone morphogenetic protein and activin membrane-bound inhibitor overexpression inhibits gastric tumor cell invasion via the transforming growth factor-ß/epithelial-mesenchymal transition signaling pathway.

Gastric carcinoma is one of the most common human malignancies and remains the second leading cause of cancer-associated mortality worldwide. Gastric carcinoma is characterized by early-stage metastasis and is typically diagnosed in the advanced stage. Previous results have indicated that bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) overexpression has been demonstrated to inhibit growth and metastasis of gastric cancer cells. However, the molecular mechanisms of the BAMBI-mediated signaling pathway in the progression of gastric cancer are poorly understood. In the present study, to assess whether BAMBI overexpression inhibited the growth and aggressiveness of gastric carcinoma cells through regulation of transforming growth factor (TGF)-ß/epithelial-mesenchymal transition (EMT) signaling pathway, the growth and metastasis of gastric carcinoma cells were analyzed following BAMBI overexpression and knockdown in vitro and in vivo. Molecular changes in the TGF-ß/EMT signaling pathway were studied in gastric carcinoma cells following BAMBI overexpression and knockdown. DNA methylation of the gene regions encoding the TGF-ß/EMT signaling pathway was investigated in gastric carcinoma cells. Tumor growth in tumor-bearing mice was analyzed after mice were subjected to endogenous overexpression of BAMBI. Results indicated that BAMBI overexpression significantly inhibited gastric carcinoma cell growth and aggressiveness, whereas knockdown of BAMBI significantly promoted its growth and metastasis compared with the control (P<0.01). The TGF-ß/EMT signaling pathway was downregulated in BAMBI-overexpressed gastric carcinoma cells; however, signaling was promoted following BAMBI knockdown. In addition, it was observed that BAMBI overexpression significantly downregulated the DNA methylation of the gene regions encoding the TGF-ß/EMT signaling pathway (P<0.01). Furthermore, RNA interference-mediated BAMBI overexpression also promoted apoptosis in gastric cancer cells and significantly inhibited growth of gastric tumors in murine xenografts (P<0.01). In conclusion, the present findings suggest that BAMBI overexpression inhibited the TGF-ß/EMT signaling pathway and suppressed the invasiveness of gastric tumors, suggesting BAMBI may be a potential target for the treatment of gastric carcinoma via regulation of the TGF-ß/EMT signaling pathway.

High expression of estrogen-related receptor α is significantly associated with poor prognosis in patients with colorectal cancer.

Colorectal cancer (CRC) is one of the most common types of malignancy with high morbidity and mortality rates worldwide. This biologically heterogeneous disease results in diverse therapeutic responses, thus, novel prognostic biomarkers are required to improve CRC treatment. Estrogen-related receptor α (ERRα) is a nuclear orphan receptor, which is associated with estrogen receptor α. The present study aimed to investigate the expression of ERRα in patients with CRC, and explore the association between ERRα expression and clinicopathological factors, local recurrence and prognosis. In the present study, ERRα expression was detected in 15 fresh CRC tissues using quantitative real-time polymerase chain reaction (RT-qPCR) and in 128 paraffin-embedded CRC tissues using immunohistochemistry. The associations between ERRα expression and prognosis of CRC patients were evaluated by univariate, and multivariate (Cox proportional hazards model) analysis. RT-qPCR demonstrated that the mRNA expression of ERRα in CRC tissues was significantly higher compared with that in matched normal tissues. Immunohistochemistry revealed that ERRα high expression was detected in the nuclei of cancer cells from 39.1% (50/128) of CRC tissues. ERRα expression based on immunohistochemical staining was significantly associated with tumor differentiation, tumor invasion, lymph node status and Dukes stage (all P<0.05). Furthermore, patients with high ERRα expression were significantly associated with an increased risk of recurrence and poor prognosis, compared with patients with low ERRα expression. ERRα expression was identified as an independent prognostic factor for patients with CRC. In conclusion, ERRα serves important roles in the progression of CRC and is a potential prognostic factor for patients with CRC.

GP73 level determines chemotherapeutic resistance in human hepatocellular carcinoma cells.

Objective GP73 is a new hepatocellular carcinoma (HCC) marker, which is highly expressed in hepatocellular carcinoma and closely relates to prognosis. This study was to investigate the effects of GP73 on cellular proliferation, apoptosis, oxaliplatin (OXA) resistance and secretory clusterin (sCLU) of HCC cells. Materials and Methods Western blot and immunofluorescence was used to detect the expression of GP73 in 8 types of commonly used HCC cell lines. Drug resistance was induced by increasing concentration gradient method. The drug-resistant human HCC cell lines underwent GP73 overexpression or inhibition. Flow cytometry were used to detect the proliferation and apoptosis of HCC cell lines. The changes of sCLU were detected by enzyme-linked immunosorbent assay (ELISA). Results The expression of GP73 in MHC-97H cells was the highest and in Hep3B cells the lowest. The expression of GP73 was found further elevated in OXA-resistant MHC-97H cells. After the knockdown of GP73 in OXA-resistant 97H cells, the IC50 of OXA decreased and the ability of cell proliferation decreased significantly. After over-expression of GP73 in OXA-resistant Hep3B cells, the IC50 of OXA increased and the cell proliferation ability increased, showing that GP73 is critical for OXA resistant in HCC cell lines; No significant change of sCLU level in GP73 overexpressed Hep3B and GP73 blocked MHCC-97H were identified. Conclusion The expression level of GP73 is critical for the resistance of OXA in HCC cell lines.

APE1 overexpression is associated with poor survival in patients with solid tumors: a meta-analysis.

APE1 is known as a key mediator of DNA damage repair pathways, and its clinical significance in different types of cancer is well studied. Herein, we performed a meta-analysis to determine the association of APE1 expression and survival in different types of solid cancer. We searched all eligible publications in PubMed, Web of Science and Embase platforms from inception to January 2017 and found 15 relevant manuscripts. Overall survival (OS), 12- and 36-month survival rates, and hazard ratios (HRs) were extracted and analyzed. Heterogeneity and publication bias were also assessed. A subgroup analysis of the different subcellular locations of APE1 was also conducted. Patients with higher APE1 levels demonstrated lower 12- and 36-month survival rates than those with low APE1 levels (HR 2.00, 95% CI 1.33-3.00, P = 0.0009; HR 1.84, 95% CI 1.19-2.84, P = 0.006). Importantly, the pooled analysis showed that high levels of APE1 predict shorter OS (HR 1.44, 95% CI 1.13-1.83, P = 0.003). Subgroup analysis revealed that both nuclear and cytoplasmic expression levels of APE1 are important indicators of poor prognosis in solid tumors.

The clinical significance and biological function of large tumour suppressor 2 in hepatocellular carcinoma.

OBJECTIVES: Present evidence has suggested that large tumour suppressor 2 (LATS2) is abnormally expressed in most human cancer. However, the clinical and prognostic value in hepatocellular carcinoma (HCC) is still unknown. MATERIALS AND METHODS: Large tumour suppressor 2 mRNA and protein expression levels in HCC tissues and cell lines were detected by qRT-PCR, immunohistochemistry or Western blot. The correlation between LATS2 expression and clinicopathological factors was analysed through immunohistochemistry. The function of LATS2 on HCC cell growth and mobility was explored through MTT, colony formation, Transwell migration and invasion assays. The molecular mechanism of LATS2 was screened and confirmed by qRT-PCR and Western blot. RESULTS AND CONCLUSION: In this study, LATS2 mRNA and protein expressions were decreased in HCC tissues and cell lines compared with normal hepatic tissues and hepatic cell line. Low LATS2 expression was oppositely corrected with tumour stage, vascular invasion and metastasis. The univariate and multivariate analyses suggested that low LATS2 expression was an independent poor prognostic factor for HCC patients. The in vitro experiments showed that LATS2 regulated HCC cells migration and invasion, but had no effect on HCC cells proliferation. Meanwhile, LATS2 modulated metastasis-associated genes expression including E-cadherin, vimentin, snail, slug, MMP2 and MMP9. In conclusion, LATS2 is a prognostic biomarker and a tumour metastasis suppressor in HCC.

Intraperitoneal Perfusion Therapy of Endostar Combined with Platinum Chemotherapy for Malignant Serous Effusions: A Meta-analysis.

BACKGROUND: Malignant serous effusions (MSE) are one complication in patients with advanced cancer. Endostar is a new anti-tumor drug targeting vessels which exerts potent inhibition of neovascularization. This study aimed to systematically evaluate the efficacy and safety of intraperitoneal perfusion therapy of Endostar combined with platinum chemotherapy for malignant serous effusions (MSE). MATERIALS AND METHODS: Randomized controlled trials (RCTs) on intraperitoneal perfusion therapy of Endostar combined with platinum chemotherapy for malignant serous effusions were searched in the electronic data of PubMed, EMBASE, Web of Science, CNKI, VIP, CBM and WanFang. The quality of RCTs was evaluated by two independent researchers and a meta-analysis was performed using RevMan 5.3 software. RESULTS: The total of 25 RCTs included in the meta-analysis covered 1,253 patients, and all literature quality was evaluated as "B" grade. The meta-analysis showed that Endostar combined with platinum had an advantage over platinum alone in terms of response rate of effusions (76% vs 48%, RR=1.63, 95%CI: 1.50-1.78, P<0.00001) and improvement rate in quality of life (69% vs 44%, RR=1.57, 95%CI: 1.42-1.74, P<0.00001). As for safety, there was no significant difference between the two groups in the incidences of nausea and vomiting (35% vs 34%, RR=1.01, 95%CI: 0.87-1.18, P=0.88), leucopenia (38% vs 38%, RR=1, 95%CI: 0.87-1.15, P=0.99), and renal impairment (18% vs 20%, RR=0.86, 95%CI: 0.43-1.74, P=0.68). CONCLUSIONS: Endostar combined with platinum by intraperitoneal perfusion is effective for malignant serous effusions, and patient quality of life is significantly improved without the incidence of adverse reactions being obviously increased.

Clinical efficacy of bevacizumab concomitant with pemetrexed in patients with advanced non-small cell lung cancer.

OBJECTIVE: To observe the clinical efficacy of bevacizumab concomitant with pemetrexed in patients with advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: A total of 72 patients were randomly divided into a combination group (pemetrexed+bevacizumab, n=36) and a pemetrexed group (n=36) and assessed for disease control (CR+PR+SD) after 4-cycles of first-line GP chemotherapy (gemcitabine+cisplatin). Clinical efficacy, progression-free survival time (PFS), overall survival time (OS), overall response rate (ORR), disease control rate (DCR) and rate of adverse responses between two groups were observed and compared. RESULTS: ORR and DCR were 27.8% and 83.4% in combination group, and 16.7% and 69.5% in the pemetrexed group, respectively, but there were no significant differences (P>0.05). PFS in combination group and pemetrexed group were 4.6 months and 3.9 months respectively (P=0.09), whereas OS in the combination group was 14 months, evidently higher than in the pemetrexed group (11 months, P=0.004). Adverse responses in both groups included high blood pressure, bleeding, thrombocytopenia, anemia, elevated transaminase, diarrhea, vomiting and proteinuria, but there were no significant differences (P>0.05). CONCLUSIONS: Bevacizumab concomitant with pemetrexed has better clinical efficacy and safety, giving rise to prolonged survival time in patients with advanced NSCLC.

[Study on preparation of total flavones in Glechoma longituba sustained-release tablets and its in vitro release].

OBJECTIVE: To study the preparation of total flavones in Glechoma longituba sustained-release tablets and evaluate its releasing features in vitro. METHODS: Orthogonal experiment (L(9)3(4)) was used to optimize the process of preparation of total flavones in Glechoma longituba sustained-release tablets. Investigated the release effect in vitro of optimization test result. RESULTS: The optimized prescription was HPMC-K4M and carbopol 934p account for 30% of the total tablet weight, their dosage ratio was 2: 1; Lactose as additives, 20% dosage; 5% PVP ethanol as adhesives, and compressed the wet granule of the materials into the total flavones in Glechoma longituba sustained-release tablets. The released profiles of the sustained-release tablets followed zero-order equation. CONCLUSION: The sustained-release effect of total flavones in Glechoma longituba sustained-release tablets is good, the preparation craft is easy and feasible and worth widely promoting.

[Studies on purification process of total flavones from Glechoma longituba with macroporous adsorption resin].

OBJECTIVE: To study the purification process of total flavones from Glechoma longituba with macroporous adsorption resin. METHODS: The eluting power and purified ratio of total flavones were selected as indices, the adsorbility and eluting parameters of the process were studied. RESULTS: The best result that the purity of total flavones from Glechoma longituba could reach 68. 94% was based on the followings: total flavones content in the liquid-0.383 mg/mL, feeding volume--20 mL, feeding rate--1.0 mL/min, eluting agent-5BV purify water and 10BV 30% ethanol, eluting rate--1.0 mL/min. CONCLUSION: The process is simple and convenient which can be used in the purification of total flavones from Glechoma longituba, it may has a good application foreground.

[Circulated extraction of flavonoids from Glechoma longituba by ultrasonic wave].

OBJECTIVE: To investigate the optimum condition of extraction for the flavonoids in Glechoma longituba by ultrasonic wave. METHOD: Using orthogonal test, the effects of ultrasonic power, ultrasonic time, extraction temperature and solvent concentration were considered, the comprehensive evaluation was guided by the content of the flavonoids determined by ultraviolet spectrophotometer. RESULT: The optimum condition was as follow: ultrasonic power; 800 W, ultrasonic time 90 min, extraction temperature 40 degrees C, solvent concentration 65%. The flavonoids concent is 5.228%. CONCLUSION: Using ethanol as solvent, circulated extraction of the flavonoids from G. longituba with ultrasonic wave is feasible with the optimum conditions in low temperature, short time and high production yield.