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e23516Background: For newly diagnosed small intestinal GIST with hepatic metastases, imatinib (IM) resistance is sometimes seen during targeted therapy preoperatively. Subsequent treatment preferri...

11005Background: No standard therapies are available in China for Soft tissues sarcomas (STS)patients who failed to chemotherapies. Anlotinib is a multi-target RTK inhibitor, with VEGFR1/2/3, FGFR1...

77 Background: Although the comprehensive treatment has improved outcomes in most advanced gastric cancers, these protocols have had little effect on advanced gastric signet-ring cell carcinoma (GSRCC). New biomarkers and therapeutic targets are needed to improve its outcomes. MicroRNAs have been closely linked to the carcinogenesis of gastric cancer and have been considered as powerful prognostic markers. The function of miR-935 has never been reported in cancer before. Methods: We used microarrays in six cell lines to explore which miRNAs had dysregulated expression in GSRCC, includingGES-1, SGC-7901, MGC8-03, AGS,MKN-45 and KATO-III. We selected MKN-45 and KATO-III (with down-regulated miR-935) to transfect the miR-935 mimic, and MGC8-03 and HGC-27 (with up-regulated miR-935) to transfect the miR-935 inhibitor. TargetScan 7.0 predicted that Notch1 would have a single conserved binding sequence for miR-935 in the 3′UTR. We also assessed miR-935 expression in clinical gastric carcinoma tissue samples with adjacent normal tissue samples from the same patient. Data were analyzed with SPSS v.17.0 software. Results: Over-expression of miR-935 markedly decreased proliferation, migration and invasion of MKN-45 and KATO-III cells compared with the negative control. In contrast, the inhibitor that was transfected into MGC8-03 and HGC-27 cells significantly increased proliferation, migration and invasion compared the negative control. These results indicate that ectopic miR-935 expression decreases GSRCC proliferation, migration and invasion in vitro, and acted as a tumor suppressor for GSRCC. Expression of Notch1 is negatively regulated by miR-935. Notch1 knock-down significantly inhibited GSRCC proliferation, migration and invasion. MiR-935 was downregulated in GSRCC tissues. Conclusions: The expression of miR-935 in GSRCC cell lines is lower than in non-GSRCC cell lines, and enhanced expression of miR-935 in GSRCC cell-lines inhibit cell proliferation, migration and invasion. Notch1 is a direct target of miR-935 to reduce the proliferation, migration/invasion of GSRCC cells. MiR-935 is a potential marker for GSRCC diagnosis and therapy.

76 Background: Gastric cancer (GC) is a prevalent malignant cancer worldwide and is highly lethal because of its fast growth. Currently, the comprehensive treatment is the combination of surgery, chemotherapy and radiotherapy, which has made progress in the treatment of advanced GC. However, the accuracy of current diagnostic methods is not very satisfactory. To address these limitations and improve the survival rate and reduce mortality it is necessary to identify sensitive early diagnostic markers. MiR-32 has been reported as an oncogenic microRNA in many cancers, but its role in GC is unclear. Methods: We detected miR-32 expression in clinical gastric carcinoma tissue samples and adjacent normal tissue samples from the same patient. The expression of miR-32 was also detected in 40 gastric carcinoma patients’ plasma, as compared with the plasma of 40 healthy individuals. The proliferation ability of cells was monitored by the xCELLigence Real-Time Cell Analyzer (RTCA)-MP system. Transwell insert chambers with an 8 μm diameter porous membrane (Neuro Probe, MD, USA) were used for the migration/invasion assays. Also, the plasmid construction and luciferase reporter assay, western blotting analysis and immunofluorescence cell staining were performed. Data were analyzed with SPSS v.17.0 software. Results: We detected the expression level of miR-32 in two normal gastric tissue, the GES-1 cell line, and eight gastric carcinoma cell lines. The expression of miR-32 was significantly higher in tumor tissues as compared with normal tissues, p = 0.0016. The expression of miR-32 was significantly higher in 40 gastric carcinoma patients’ plasma, as compared with the plasma of 40 healthy individuals, p = 0.004.MiR-32 promotes the proliferation, migration and invasion of GC cells. The expression of KLF4 is negatively regulated by miR-32. Knockdown of KLF4 promotes cell proliferation, migration and invasion in GC cell-lines. Conclusions: In addition to identifying upregulated miR-32 as a diagnosis biomarker in clinical GC tissue and plasma, we have defined the biological functions of miR-32 as an oncogene in GC cells and explored the molecular mechanism of miR-32 in GC cells’ aggressive phenotype.