1.Effect of anti-transplanted tumor in nude mice by DC induced in vitro
Zibiao HE ; Weiming YANG ; Baoting JIAO ; Hui SONG
Journal of Xi'an Jiaotong University(Medical Sciences) 1982;0(01):-
Objective To study the immune response of dendritic cells(DC)modified with tumor antigen and SEB to transplanted tumor in nude mice.Methods Nude mice models were established with human colon cancer cells inoculated subcutaneously,grouped into control group,therapy group and retherapy group;DC was isolated and purified from PBMC of colon carcinoma patient to activate T lymphocyte with DC modified by tumour antigen and SEB.The T lymphocyte was implanted to the models to inhibit the growth of implanted tumor through tail vein.Tumor formation,growth and size,nude mice feeding and activity status were observed.Results The subcutaneously xenotransplanted tumor model of human colon carcinoma in nude mice was successfully established.After colon cancer cells had been inoculated in nude mice for 60 days,volume of transplanted tumor in the control group was(3 899?22)mm3,therapy group(1 301?16)mm3,and retherapy group(392?18)mm3.Compared with the control group,the tumor in therapy group and retherapy group could grow slowly(P=0.000).Compared with that in the therapy group,the tumor growth in retherapy group became obviously slower(P=0.000).Conclusion The immune response induced by DC can inhibit the growth of transplanted tumor in nudes mice,which may provide a new therapy for tumor.
2.Drug discovery of sclerostin inhibitors.
Sifan YU ; Dijie LI ; Ning ZHANG ; Shuaijian NI ; Meiheng SUN ; Luyao WANG ; Huan XIAO ; Dingdong LIU ; Jin LIU ; Yuanyuan YU ; Zongkang ZHANG ; Samuel Tin Yui YEUNG ; Shu ZHANG ; Aiping LU ; Zhenlin ZHANG ; Baoting ZHANG ; Ge ZHANG
Acta Pharmaceutica Sinica B 2022;12(5):2150-2170
Sclerostin, a protein secreted from osteocytes, negatively regulates the WNT signaling pathway by binding to the LRP5/6 co-receptors and further inhibits bone formation and promotes bone resorption. Sclerostin contributes to musculoskeletal system-related diseases, making it a promising therapeutic target for the treatment of WNT-related bone diseases. Additionally, emerging evidence indicates that sclerostin contributes to the development of cancers, obesity, and diabetes, suggesting that it may be a promising therapeutic target for these diseases. Notably, cardiovascular diseases are related to the protective role of sclerostin. In this review, we summarize three distinct types of inhibitors targeting sclerostin, monoclonal antibodies, aptamers, and small-molecule inhibitors, from which monoclonal antibodies have been developed. As the first-in-class sclerostin inhibitor approved by the U.S. FDA, the monoclonal antibody romosozumab has demonstrated excellent effectiveness in the treatment of postmenopausal osteoporosis; however, it conferred high cardiovascular risk in clinical trials. Furthermore, romosozumab could only be administered by injection, which may cause compliance issues for patients who prefer oral therapy. Considering these above safety and compliance concerns, we therefore present relevant discussion and offer perspectives on the development of next-generation sclerostin inhibitors by following several ways, such as concomitant medication, artificial intelligence-based strategy, druggable modification, and bispecific inhibitors strategy.