52 research outputs found

    Downregulation of SPARC expression decreases gastric cancer cellular invasion and survival

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    <p>Abstract</p> <p>Background</p> <p>Secreted protein acidic and rich in cysteine (SPARC) plays a key role in the development of many tissues and organ types. Aberrant SPARC expression was found in a wide variety of human cancers, contributes to tumor development. Because SPARC was found to be overexpressed in human gastric cancer tissue, we therefore to explore the expression of SPARC in gastric cancer lines and the carcinogenic mechanisms.</p> <p>Methods</p> <p>SPARC expression was evaluated in a panel of human gastric cancer cell lines. MGC803 and HGC 27 gastric cancer cell lines expressing high level of SPARC were transiently transfected with SPARC-specific small interfering RNAs and subsequently evaluated for effects on invasion and proliferation.</p> <p>Results</p> <p>Small interfering RNA-mediated knockdown of SPARC in MGC803 and HGC 27 gastric cancer cells dramatically decreased their invasion. Knockdown of SPARC was also observed to significantly increase the apoptosis of MGC803 and HGC 27 gastric cancer cells compared with control transfected group.</p> <p>Conclusions</p> <p>Our data showed that downregulating of SPARC inhibits invasion and growth of human gastric cancer cells. Thus, targeting of SPARC could be an effective therapeutic approach against gastric cancer.</p

    Autophagy-related IFNG is a prognostic and immunochemotherapeutic biomarker of COAD patients

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    BackgroundNumerous studies have shown autophagy affects cellular immune responses. This study aims to explore prognosis and immunotherapeutic biomarkers related to autophagy in colon adenocarcinoma (COAD).MethodsBased on R software, we performed the ssGSEA, differential expression analysis, Kaplan-Meier survival analysis, correlation analysis, and enrichment analysis. For wet experiment, we did qRT-PCR, immunohistochemistry and CCK-8 experiments.ResultsUsing autophagy-related genes (ARGs) and the ssGSEA, COAD patients were divided into low and high autophagy groups. For immune score, stromal score, tumor purity, tumor infiltrating immune cells, co-signaling molecules, tumor mutational burden, microsatellite instability, mismatch repair, immune-related pathways, immune signatures, somatic mutations and subtype analysis, high autophagy group might benefit more from immunotherapy. Among 232 ARGs, IFNG was generally significantly correlated with tumor immunotherapy biomarkers (PD-L1, CD8A and cytotoxic T lymphocytes (CTL)). The disease-free survival of high IFNG group was significantly longer than that of low group. On above-mentioned immune-related research, the high IFNG group reached the same conclusion. The qRT-PCR and IHC analysis confirmed that IFNG was significantly higher expressed in dMMR samples compared to pMMR samples. For chemotherapy, the autophagy and IFNG were significantly negatively related to the chemosensitivity to cisplatin; IFNG inhibitor glucosamine increased cisplatin chemoresistance while IFNG increased cisplatin chemosensitivity; IFNG could reverse glucosamine induced chemoresistance. The functional enrichment analysis of IFNG, PD-L1, CD8A and 20 similar proteins were related to the activation of the immune system. The GSEA and ceRNA network partly described interaction mechanisms of IFNG with PD-L1 and CD8A.ConclusionAutophagy score and IFNG expression were novel immunotherapy predictive biomarkers, which might play predictive effects through the JAK-STAT signaling pathway. IFNG might be a potential targeted therapy for cisplatin resistant colon cancer. Besides, IFNG was also a prognostic indicator

    Mangiferin Decreases Plasma Free Fatty Acids through Promoting Its Catabolism in Liver by Activation of AMPK

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    Mangiferin has been shown to have the effect of improving dyslipidemia. Plasma free fatty acids (FFA) are closely associated with blood lipid metabolism as well as many diseases including metabolic syndrome. This study is to investigate whether mangiferin has effects on FFA metabolism in hyperlipidemic rats. Wistar rats were fed a high-fat diet and administered mangiferin simultaneously for 6 weeks. Mangiferin (50, 100, 150 mg/kg BW) decreased dose-dependently FFA and triglycerides (TG) levels in plasma, and their accumulations in liver, but increased the β-hydroxybutyrate levels in both plasma and liver of hyperlipidemic rats. HepG2 cells were treated with oleic acid (OA, 0.2 mmol/L) to simulate the condition of high level of plasma FFA in vitro, and were treated with different concentrations of mangiferin simultaneously for 24 h. We found that mangiferin significantly increased FFA uptake, significantly decreased intracellular FFA and TG accumulations in HepG2 cells. Mangiferin significantly increased AMP-activated protein kinase (AMPK) phosphorylation and its downstream proteins involved in fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT1), but significantly decreased acyl-CoA: diacylgycerol acyltransferase 2 (DGAT2) expression and acetyl-CoA carboxylase (ACC) activity by increasing its phosphorylation level in both in vivo and in vitro studies. Furthermore, these effects were reversed by Compound C, an AMPK inhibitor in HepG2 cells. For upstream of AMPK, mangiferin increased AMP/ATP ratio, but had no effect on LKB1 phosphorylation. In conclusion, mangiferin decreased plasma FFA levels through promoting FFA uptake and oxidation, inhibiting FFA and TG accumulations by regulating the key enzymes expression in liver through AMPK pathway. Therefore, mangiferin is a possible beneficial natural compound for metabolic syndrome by improving FFA metabolism

    Prognostic Utility of Coronary Computed Tomographic Angiography: A 5-Year Follow-Up in Type 2 Diabetes Patients with Suspected Coronary Artery Disease

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    Objectives. To analyze the predictive value of coronary computed tomography angiography on acute coronary artery events in patients with type 2 diabetes. Methods. Coronary computed tomography angiography was performed in 250 type 2 diabetic patients. After a follow-up for 5 years, 145 patients were excluded as they did not have any coronary events. The remaining 95 patients were divided into study group and control group. According to their density and shape, the coronary artery plaques were classified into 3 types and 4 types, respectively. Results. There is no statistically significant difference in the degree of stenosis between two groups. The proportion of calcified plaques in the study group was lower than in the control group. The proportion of mixed-calcified plaques in the study group was higher than in the other. Type III plaques have a 76.2% sensitivity and negative predictive value was 64.5% for acute coronary events; type IV plaques have a sensitivity of 52.6% and positive predictive value of 63% for chronic coronary events. Conclusions. CCTA may be used as a non-invasive modality for evaluating and predicting vulnerable coronary atherosclerosis plaques in patients with type 2 diabetes

    Facile Synthesis of a Polycatenane Compound Based on Ag-triazole Complexes and Phosphomolybdic Acid for the Catalytic Epoxidation of Olefins with Molecular Oxygen

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    A simple and efficient approach was developed for synthesizing a metal-organic polycatenated compound composed of Ag-triazole complexes and phosphomolybdic acid (PMA) clusters. The hybrid compound, namely {[Ag2(trz)2] [Ag24(trz)18]}[PMo12O40]2 (1) (trz = 1,2,4-triazole), showed high catalytic activity, selectivity and recyclability for the epoxidation of olefins with molecular oxygen as the oxidant and isobutyraldehyde as the co-reagent, and could even work well under ambient conditions. The special polycatenane framework, formed by interlocking [Ag24(trz)18]6+ nanocages, provides suitable space for filling the PMA clusters. The existence of multi-interactions, including &pi;-&pi; stacking, Ag-Ag interactions, and electrostatic interactions, should play a determinative role in fabricating the catalytically active and stable PMA-based polycatenane catalyst for aerobic epoxidation of olefins
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