Glioblastoma(GBM)is the most common and aggressive malignant brain tumor in adults and is poorly controlled.Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression,...Glioblastoma(GBM)is the most common and aggressive malignant brain tumor in adults and is poorly controlled.Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression,and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment.Therefore,this study developed a novel and selective inhibitor of CSFIR and VEGFR,SYHA1813,possessing potent antitumor activity against GBM.SYHA1813 inhibited VEGFR and CSFIR kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo.SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models,including temozolomide(TMZ)insensitive tumors.Notably,SYHA1813 could penetrate the blood-brain barrier(BBB)and prolong the survival time of mice bearing intracranial GBM xenografts.Moreover,SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody.As a clinical proof of concept,SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial.The data of this study support the rationale for an ongoing phase I clinical study(ChiCTR2100045380).展开更多
A reliable and accurate liquid chromatography with evaporative light scattering detection(LC-ELSD)method was developed for simultaneous determination of five constituents in Xue-Fu-Zhu-Yu capsule,a widely used prescri...A reliable and accurate liquid chromatography with evaporative light scattering detection(LC-ELSD)method was developed for simultaneous determination of five constituents in Xue-Fu-Zhu-Yu capsule,a widely used prescription of traditional Chinese medicine(TCM).The chromatographic separation was performed on a Symmetry C_(18)column(150 mm×4.6 mm,5.0μm)using gradient elution of acetonitrile and water(containing 1.0%acetic acid).The flow rate was 0.6 mL/min and the temperature of column was 30℃.A good linearity correlation was obtained over the investigated concentration ranges.Recoveries of the five components varied from 97.31%to 99.84%(RSD<4.0%).The validated method was successfully applied to the quality assessment of Xue-Fu-Zhu-Yu capsule.展开更多
基金supported by grants from the Natural Science Foundation of China for Innovation Research Group(81821005)the National Natural Science Foundation of China(82273948 and 81573271)+2 种基金the"Personalized Medicines,Molecular Signaturebased Drug Discovery and Development",Strategic Priority Research Program of the Chinese Academy of Sciences(XDA12020203 and XDA12020228,China)the National Science&Technology Major Project"Key New Drug Creation and Manufacturing Program",China(2018ZX09711002-011-016)the Youth Innovation Promotion Association of CAS(2018324,China).
文摘Glioblastoma(GBM)is the most common and aggressive malignant brain tumor in adults and is poorly controlled.Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression,and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment.Therefore,this study developed a novel and selective inhibitor of CSFIR and VEGFR,SYHA1813,possessing potent antitumor activity against GBM.SYHA1813 inhibited VEGFR and CSFIR kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo.SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models,including temozolomide(TMZ)insensitive tumors.Notably,SYHA1813 could penetrate the blood-brain barrier(BBB)and prolong the survival time of mice bearing intracranial GBM xenografts.Moreover,SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody.As a clinical proof of concept,SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial.The data of this study support the rationale for an ongoing phase I clinical study(ChiCTR2100045380).
基金financially supported by the Scientific and Technological Innovation Project Foundation of Tianjin(No.06FZZDSH00404).
文摘A reliable and accurate liquid chromatography with evaporative light scattering detection(LC-ELSD)method was developed for simultaneous determination of five constituents in Xue-Fu-Zhu-Yu capsule,a widely used prescription of traditional Chinese medicine(TCM).The chromatographic separation was performed on a Symmetry C_(18)column(150 mm×4.6 mm,5.0μm)using gradient elution of acetonitrile and water(containing 1.0%acetic acid).The flow rate was 0.6 mL/min and the temperature of column was 30℃.A good linearity correlation was obtained over the investigated concentration ranges.Recoveries of the five components varied from 97.31%to 99.84%(RSD<4.0%).The validated method was successfully applied to the quality assessment of Xue-Fu-Zhu-Yu capsule.
