| ObjectiveTo observe the effect of four flavor Xiaoliuyin joint temozolomide therapy in nude glioma,explore four flavor Xiaoliuyin anti-glioma angiogenesis in nude mice and its mechanism.To study the influence and mechanism of four flavor Xiaoliuyin and four flavor Xiaoliuyin joint temozolomide for glioma clinical symptoms,TCM symptoms and immune system.Assess the drug safety of four flavor Xiaoliuyin.MethodsThis study included experimental and clinical studies.1.Experimental Research(1)Establish human glioma cell line U87 tumor model.(2)The research of four flavor Xiaoliuyin anti-nude glioma angiogenesis.Mice were randomized to the saline group,the conventional dose four flavor Xiaoliuyin group,high dose group of four flavor Xiaoliuyin,TMZ group,combination therapy group,Gavage 28 days,From the beginning one day before oral weekly measure and record the tumor volume.28 days later to kill mice,remove eye take blood,stripping tumor tissue completely.Select the part of the tumor tissue in formalin-fixed paraffin sections.(3)The research of four flavor Xiaoliuyin anti-nude glioma angiogenesis.?Immunohistochemical staining nude mice tumor tissue biopsies,Using the method of Weidner counted the microvessel density.?ELISA enzyme-linked adsorption method to detect the content of nude mice serum VEGF and ES.2.Clinical Research(1)The research of Four flavor Xiaoliuyin anti-glioma efficacy and safety of drugs.We met the inclusion criteria of 60 patients randomly assigned to the experimental group and the control group.Experimental group received conventional treatment plus four flavor Xiaoliuyin treatment.The control group received conventional therapy.Observed before and after treatment group and control group in patients with TCM symptom integral,KPS score,bloodroutine,liver and kidney function,lymphocyte subgroup.(2)The research of four flavor Xiaoliuyin anti-glioma angiogenesis.ELISA method to detect the content of Patient serum VEGF and ES.Results1.Experimental research result(1)Treatment for 7,14,21 days conventional dose four flavor Xiaoliuyin group in tumor volume less than the control group and the difference was not statistically significant.Treatment for 28 days conventional dose therapy four flavor Xiaoliuyin group in tumor volume less than the control group,the difference was statistically significant(P=0.027<0.0 05).(2)Treatment for 7,14,21 days high dose four flavor Xiaoliuyin group in tumor volume less than the control group and the difference was not statistically significant(P>0.05).Treatment for 28 days high dose therapy four flavor Xiaoliuyin group in tumor volume less than the control group,the difference was statistically significant(P=0.022<0.05).(3)Treatment for 14,21,28days TMZ group in tumor volume less than the control group and the difference was statistically significant(P<0.05).Treatment for 14,21,28days combination therapy group in tumor volume less than the control group and the difference was statistically significant(P<0.05).(4)Conventional-dose group,high dose group,four flavor Xiaoliuyin joint temozolomide group MVD in tumor tissue were less than the control group,the difference was statistically significant(P=0.013,0.009,0.003<0.05).(5)Conventional-dose group,high dose group,four flavor Xiaoliuyin joint temozolomide nude mice serum VEGF levels lower than the control group,the difference was statistically significant(P=0.014,0.001,0.00<0.05).Conventional-dose group,high dose group,four flavor Xiaoliuyin joint temozolomide nude mice serum ES levels higher than the control group,the difference was statistically significant(P=0.04,0.002,0.00<0· 05).2.Clinical findings(1)The test group and the control group of patients before and after treatment in liver and kidney functions were normal,the difference was not statistically significant(P>0.05).(2)Treatment of 7 days in patients with TCM symptoms integral improvement of the experimental group and the control group,the difference was no statistically significant(P>0.05);treatment of 28 days in patients with TCM symptoms integral improvement of the experimental group and the control group,the difference was statistically significant(P=0.026<0.05).(3)7 days of treatment in patients with KPS score the test group and the control group,the difference was statistically significant(P= 0.01<0.05);28 days of treatment in patients with KPS score the test group and the control group,the difference was statistically significant(P<0.05).(4)In the fourth week the CD4+/CD8+ of test group higher control group,the difference was statistically significant(P=0.03<0.05).(5)In the first week test group patients serum VEGF levels lower than the control group,there was no statistically significant difference(P>0.05);In the fourth week test group patients serum VEGF content is lower than the control group,the difference was statistically significant(P= 0.046<0.05).(6)On the 7th day experimental group serum ES content with the control group,the difference was not statistically significant(P>0.05);on the 28th day the test group patients with serum ES content higher than the control group,the difference was statistically significant(P=0.006<0.05).ConclusionThrough this study we showed that four flavor Xiaoliuyin can inhibit glioma angiogenesis,and can improve the clinical symptoms of brain glioma patients and improve the quality of life of patients.Its mechanism of glioma angiogenesis inhibition may be through regulation VEGF and down-regulation of endostatin expression of vascular endothelial growth factor achieved.(1)Four flavor Xiaoliuyin and joint temozolomide can inhibit tumor growth in mouse glioma.(2)Four flavor Xiaoliuyin joint temozolomide anti nude glioma effect than the simple application of four taste Xiaoliuyin and temozolomide strong,four flavor Xiaoliuyin may temozolomide sensitizing effect.(3)Four flavor Xiaoliuyin can inhibit glioma angiogenesis,the mechanism may be implemented through regulation of endostatin and reduced vascular endothelial growth factor.(4)Four flavor Xiaoliuyin joint temozolomide have a synergistic effect in inhibiting angiogenesis of gliomas.(5)Four flavor Xiaoliuyin can improve immune function in patients with glioma.(6)Four flavor Xiaoliuyin In clinical studies,no significant effect on the liver and kidney function,no adverse event occurred.(7)Four flavor Xiaoliuyin can improve the clinical symptoms of brain glioma patients,improve the quality of life of patients. |
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