PI3K inhibitor ZSTK474 enhancing the antitumor of vesicular stomatitis virus A51 against osteosarcoma / 解剖学报

Objective To explore whether PI3K inhibitor combined with oncolytic virus can play an effective oncolytic effect on osteosarcoma. Methods The cytotoxicity to tumor cells was detected by MTT method, and the mechanism of enhancing the anti-tumor activity was explored by observation of the swelling of endoplasmic reticulum using electron microscope and the expression of apoptosis-related proteins using Western blotting. The tumor clearance ability of the combination of the PI3k inhibitor ZSTK474 and vesicular stomatitis virus A51 (VSVA51) was verified by anti-tumor experiment in vivo. The apoptosis of tumor cells was verified by immunohistochemistry. Results PI3K inhibitor could be used as sensitizers of oncolytic VSVA51, and confirmed that the)' promoted the strong apoptosis of osteosarcoma cells by aggravating the stress of endoplasmic reticulum in tumor cells (P < 0 . 01). In vivo experiments also showed that PI3K inhibitors combined with VSVA51 could significantly promote the oncolytic effect of osteosarcoma (P<0.001), and this combination therapy enhanced the infiltration of immune cells in the tumor (P<0.001). Conclusion PI3K inhibitors combined with oncolytic virus is a potential therapy for osteosarcoma.

Relationship of c-kit and platelet-derived growth factor receptor alpha gene mutation features with prognosis of patients with gastrointestinal stromal tumor / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the relationship between c-kit and platelet-derived growth factor receptor alpha(PDGFRA) gene mutation features and the prognosis of gastrointestinal stromal tumor(GIST).</p><p><b>METHODS</b>Clinicopathological, genetic testing and follow-up informations of patients admitted to the Shanxi Tumor Hospital from June 2000 to January 2009 were collected. The survival was calculated and univariate analysis was conducted using the Kaplan-Meier method. Multivariate analysis was conducted by the Cox regression method.</p><p><b>RESULTS</b>The 5-year disease-free survival rate was 61.5% and the 5-year overall survival rate was 67.4%. The 5-year disease-free survival rates of patients without disease among those with c-kit exon 11 mutation (n=77), c-kit exon 9 mutation(n=4), and PDGFRA exon 18 mutation (n=2) were 63.4%, 14.3% and 100%, and the 5-year overall survival rates were 70.8%, 50.0% and 100%, respectively. In the patients with c-kit exon 11 mutation, the 5-year disease-free survival rates among those with point mutations(n=26), deletion mutations(n=44), and duplication mutations(n=7) were 87.1%, 44.9% and 80.0%, and the 5-year overall survival rates were 88.1%, 57.0% and 100%, respectively. There were significant differences in overall survival among different factors. Multivariate analysis showed that gene mutation was not the independent factor of prognosis(P=0.492).</p><p><b>CONCLUSIONS</b>In GIST patients undergoing surgery without imatinib treatment, mutated genotype is better than wild type in terms of prognosis. Gene mutation is not the independent factor of prognosis in GIST patients.</p>