1.Development strategy and clinical research progress of universal chimeric antigen receptor T-cell drugs
Chen WANG ; ZHANG ZHANG ; Yinchun LI
Journal of China Pharmaceutical University 2023;54(2):141-149
Chimeric antigen receptor T-cell (CAR-T) immunotherapy has made a breakthrough in the clinical treatment of a variety of hematological tumors.However, the CAR-T cell products listed at China and abroad are all autologous CAR-T.Compared with autologous CAR-T treatment, universal CAR-T exhibits significant advantages, which could fulfill the treatment demand of more patients, but also displays high technical barriers.This paper reviews the universal CAR-T, clearly points out the two major challenges faced by the development of universal CAR-T, and then summarizes and analyzes the feasible solutions according to the mechanism causing the two major problems.This paper also summarizes domestic and foreign companies producing universal CAR-T and the latest clinical progress of their superior products, and then discusses the feasibility of the development strategy from another aspect, in order to provide ideas for developing a new generation of universal CAR-T cell therapy products.
2.Clinical and angiographic characteristics of patients underwent PCI in the era before and after drug-eluting stents
Junping KANG ; Qing LV ; Shaoping NIE ; Xin DU ; Rong HU ; Yin ZHANG ; Liqun HE ; Yinchun GAO ; Xinmin LIU ; Jianzeng DONG ; Xueshi WU ; Xiaohui LIU ; Changshen MA
Journal of Chinese Physician 2000;0(11):-
Objective To elucidate the clinical characteristics and coronary angiographic findings of patients underwent PCI before and after drug-eluting stents(DES).Methods DESIRE(Drug-Eluting Stent Impact on revascularization) was a retrospective registry of patients who received revascularization therapy during July,2001 through June,2002(non-DES era) and July,2003 through February,2004(DES era).In this analysis,we used the DISIRE data to examine the clinical and angiographic features of patients who received PCI in the different era.Results Among 3763 patients in the registry,2180 patients were analyzed(763 were in the non-DES era and 1417 were in the DES era).In the DES era,more diseased vessels(1.31?0.54 vs 1.39?0.61,P
3.Real-time dynamic navigation assisted endodontic microsurgery:A case report
Yinchun ZHANG ; Xiaoxia YANG ; Xuan CHEN ; Lei HUANG ; Xiaoling QIU
Journal of Practical Stomatology 2024;40(5):720-722
With the demand for precise and efficient endodontic microsurgery,dynamic navigation technology has been reported for endo-dontic microsurgery in recent years,which is a digital navigation technology combining 3D reconstruction and spatial position alignment,pro-viding a new treatment model for minimally invasive endodontic microsurgery.In this paper,a case of endodontic microsurgery assisted by re-al-time dynamic navigation is reported.
4.Study on polymorphism of peritoneal microbial community after laparoscopic exploration in New Zealand rabbits based on 16S rDNA sequencing
Pingping ZHANG ; Wenbin WU ; Qi CAO ; Zhuo QU ; Pei WANG
Journal of Pharmaceutical Practice and Service 2022;40(6):494-498
Objective To explore the polymorphism of microbial community after laparoscopic abdominal exploration by using bacterial 16s ribosomal DNA (16S rDNA) sequencing technology. Methods New Zealand rabbits were divided into model group and control group. The rabbits in the model group were operated by portable laparoscopy, and the rabbits in the control group were not treated. One week later, the peritoneal effusions of the model group and the control group were taken for 16S rDNA sequencing to analyze the microbial community polymorphism. To explore the changes of microbial community in peritoneal effusion in the model group compared with the control group. Results After 16S rDNA sequencing, bioinformatics was used to determine the microbial communities. Inter group difference analysis showed a good similarity of microbial communities between the two groups. OTU taxonomic analysis and species composition analysis (Rank-Abundance curve and Venn diagram) found that the microbial community level of the model group was significantly higher than that of the control group. Alpha diversity analysis (Sobs, Ace, Shannon, Simpson) showed that the richness and diversity of microbial community in the model group were higher than those in the control group. Microbial composition analysis showed that the number of miscellaneous bacteria in the model group increased by about 30% compared with the control group. The species differences between the two groups were tested for significance. It was found that Pasteurellales, Neisseria and Tsukamurella increased significantly. Conclusion The diversity of microbial communities in peritoneal effusion increases after laparoscopic abdominal exploration in New Zealand rabbits, and the most significant increases are Pasteurella, Neisseria and Tsukamura.
5.Structure-based drug discovery of novel fused-pyrazolone carboxamide derivatives as potent and selective AXL inhibitors.
Feifei FANG ; Yang DAI ; Hao WANG ; Yinchun JI ; Xuewu LIANG ; Xia PENG ; Jiyuan LI ; Yangrong ZHAO ; Chunpu LI ; Danyi WANG ; Yazhou LI ; Dong ZHANG ; Dan ZHANG ; Meiyu GENG ; Hong LIU ; Jing AI ; Yu ZHOU
Acta Pharmaceutica Sinica B 2023;13(12):4918-4933
As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC50: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC50: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.