1.Diagnostic value of methylation of p16 genes in patients with non-small cell lung cancer
Qing XUE ; Shaoli XUE ; Yongtang JIN ; Zaicheng YU ; Yasong WANG ; Wenhu TAO
Clinical Medicine of China 2008;24(6):521-523
Objective To detect methylation of p16 gene in lung cancer tissues of non-small cell lung cancer patients,and to approach its clinical diagnostic value.Methods The methylation of p16 gene in DNA from 47 non-small cell lung cancer tissues and corresponding nomalignant tissues were tested with methylation-specific PCR(MSP).Results The total frequency of p16 methylation was significantly higher in lung cancer tissues than that in the corresponding malignant tissue(44.7%vs 17%)(P<0.01).But there was no significant difference in detectiveness,clinical staging,clinical pathology type and clinical classification(P>0.05).Conclusion The detection of methylation of p16 gene may be helpful to clinical diagnosis for non-small cell lung cancer,but its specify,sensitivity and feasibility need to be further studied.
2.Preclinical and early clinical studies of a novel compound SYHA1813 that efficiently crosses the blood-brain barrier and exhibits potent activity against glioblastoma.
Yingqiang LIU ; Zhengsheng ZHAN ; Zhuang KANG ; Mengyuan LI ; Yongcong LV ; Shenglan LI ; Linjiang TONG ; Fang FENG ; Yan LI ; Mengge ZHANG ; Yaping XUE ; Yi CHEN ; Tao ZHANG ; Peiran SONG ; Yi SU ; Yanyan SHEN ; Yiming SUN ; Xinying YANG ; Yi CHEN ; Shanyan YAO ; Hanyu YANG ; Caixia WANG ; Meiyu GENG ; Wenbin LI ; Wenhu DUAN ; Hua XIE ; Jian DING
Acta Pharmaceutica Sinica B 2023;13(12):4748-4764
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 CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R 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).