检索范围:
排序: 展示方式:
null
《医学前沿(英文)》 2015年 第9卷 第2期 页码 134-138 doi: 10.1007/s11684-015-0396-9
Drug resistance is a major factor that limits the efficacy of targeted cancer therapies. In this review, we discuss the main known mechanisms of resistance to receptor tyrosine kinase inhibitors, which are the most prevalent class of targeted therapeutic agent in current clinical use. Here we focus on bypass track resistance, which involves the activation of alternate signaling molecules by tumor cells to bypass inhibition and maintain signaling output, and consider the problems of signaling pathway redundancy and how the activation of different receptor tyrosine kinases translates into intracellular signal transduction in different cancer types. This information is presented in the context of research strategies for the discovery of new targets for pharmacological intervention, with the goal of overcoming resistance in order to improve patient outcomes.
关键词: targeted therapy drug resistance receptor tyrosine kinases cancer
Mechanisms of resistance to third-generation EGFR tyrosine kinase inhibitors
null
《医学前沿(英文)》 2016年 第10卷 第4期 页码 383-388 doi: 10.1007/s11684-016-0488-1
The tyrosine kinase inhibitors (TKI) of the epidermal growth factor receptor (EGFR) are becoming the first line of therapy for advanced non-small cell lung cancer (NSCLC). Acquired mutations in EGFR account for one of the major mechanisms of resistance to the TKIs. Three generations of EGFR TKIs have been used in clinical applications. AZD9291 (osimertinib; Tagrisso) is the first and only FDA approved third-generation EGFR TKI for T790M-positive advanced NSCLC patients. However, resistance to AZD9291 arises after 9–13 months of therapy. The mechanisms of resistance to third-generation inhibitors reported to date include the EGFR C797S mutation, EGFR L718Q mutation, and amplifications of HER-2, MET, or ERBB2. To overcome the acquired resistance to AZD9291, EAI045 was discovered and recently reported to be an allosteric EGFR inhibitor that overcomes T790M- and C797S-mediated resistance. This review summarizes recent investigations on the mechanisms of resistance to the EGFR TKIs, as well as the latest development of EAI045 as a fourth-generation EGFR inhibitor.
Dual faces of SH2-containing protein-tyrosine phosphatase
null
《医学前沿(英文)》 2012年 第6卷 第3期 页码 275-279 doi: 10.1007/s11684-012-0216-4
PTPN11, which encodes tyrosine phosphatase Shp2, is a critical gene mediating cellular responses to hormones and cytokines. Against original prediction as tumor suppressor for tyrosine phosphatases, PTPN11 was first identified as a proto-oncogene because activating mutations of this gene are associated with leukemogenesis. However, most recent experimental data suggest PTPN11/Shp2 acting as a tumor suppressor in hepatocarcinogenesis. This review focuses on the tumor-promoting or suppressing roles of the gene PTPN11/Shp2 in different cell types.
LIU Rong, ZENG Ji, ZHOU Xinwen, WANG Jianzhi, PEI Jinjing
《医学前沿(英文)》 2008年 第2卷 第3期 页码 235-238 doi: 10.1007/s11684-008-0044-8
关键词: hyperphosphorylation PP2A activity cellular regulation siRNA siRNA transfection
Nicotinic acetylcholine receptor α7 subunit: a novel therapeutic target for cardiovascular diseases
null
《医学前沿(英文)》 2012年 第6卷 第1期 页码 35-40 doi: 10.1007/s11684-012-0171-0
Inflammation is important in the pathogenesis and development of cardiovascular diseases. Recent studies show that vagus nerve stimulation inhibits pro-inflammatory cytokine production through “the cholinergic anti-inflammatory pathway,” more specifically via the α7 nicotinic acetylcholine receptor (α7nAChR). In the current study, the role of the cholinergic anti-inflammatory pathway during septic shock, hypertension, and myocardial infarction is reviewed, and its possible clinical implications in cardiovascular diseases are discussed.
关键词: α7 nicotinic acetylcholine receptor cardiovascular diseases baroreflex sensitivity
Wenjie Zhu, Binghe Xu
《医学前沿(英文)》 2021年 第15卷 第2期 页码 208-220 doi: 10.1007/s11684-020-0795-4
关键词: endocrine-resistant HR+/HER2- advanced breast cancer randomized clinical trials meta-analysis targeted therapy
《医学前沿(英文)》 2023年 第17卷 第4期 页码 699-713 doi: 10.1007/s11684-022-0972-8
关键词: anti-CD19 chimeric antigen receptor T immunotherapy diffuse large B cell lymphoma tumor microenvironment tumor-associated macrophage metabolism
Chimeric antigen receptor T cell therapies for acute myeloid leukemia
Bin Gu, Jianhong Chu, Depei Wu
《医学前沿(英文)》 2020年 第14卷 第6期 页码 701-710 doi: 10.1007/s11684-020-0763-z
Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy
Zhao Zhang, Jun Jiang, Xiaodong Wu, Mengyao Zhang, Dan Luo, Renyu Zhang, Shiyou Li, Youwen He, Huijie Bian, Zhinan Chen
《医学前沿(英文)》 2019年 第13卷 第1期 页码 57-68 doi: 10.1007/s11684-019-0683-y
Lung cancer is the most common incident cancer and the leading cause of cancer death. In recent years, the development of tumor immunotherapy especially chimeric antigen receptor T (CAR-T) cell has shown a promising future. Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation expressed in various types of tumors and has been detected in non-small cell lung cancer with a mutation rate of 10%. Thus, EGFRvIII is a potential antigen for targeted lung cancer therapy. In this study, CAR vectors were constructed and transfected into virus-packaging cells. Then, activated T cells were infected with retrovirus harvested from stable virus-producing single clone cell lines. CAR expression on the surfaces of the T cells was detected by flow cytometry and Western blot. The function of CAR-T targeting EGFRvIII was then evaluated. The EGFRvIII-CAR vector was successfully constructed and confirmed by DNA sequencing. A stable virus-producing cell line was produced from a single clone by limited dilution. The culture conditions for the cell line, including cell density, temperature, and culture medium were optimized. After infection with retrovirus, CAR was expressed on more than 90% of the T cells. The proliferation of CAR-T cells were induced by cytokine and specific antigen in vitro. More importantly, EGFRvIII-CART specifically and efficiently recognized and killed A549-EGFRvIII cells with an effector/target ratio of 10:1 by expressing and releasing cytokines, including perforin, granzyme B, IFN-g, and TNF-α. The in vivo study indicated that the metastasis of A549-EGFRvIII cells in mice were inhibited by EGFRvIII-CART cells, and the survival of the mice was significantly prolonged with no serious side effects. EGFRvIII-CART showed significantly efficient antitumor activity against lung cancer cells expressing EGFRvIII in vivo and in vitro. Therefore, CAR-T targeting EGFRvIII is a potential therapeutic strategy in preventing recurrence and metastasis of lung cancer after surgery.
关键词: chimeric antigen receptor T cells epidermal growth factor receptor lung cancer immunotherapy tumor immunology
Blockage of receptor-interacting protein 2 expression by small interfering RNA in murine macrophages
LIU Hongchun, CAO Zhongwei, JIN Jianjun, WANG Jiyao
《医学前沿(英文)》 2008年 第2卷 第2期 页码 166-170 doi: 10.1007/s11684-008-0030-1
Changlin Cao, Jingxian Gu, Jingyao Zhang
《医学前沿(英文)》 2017年 第11卷 第2期 页码 169-177 doi: 10.1007/s11684-017-0505-z
关键词: soluble triggering receptor expressed on myeloid cells-1 infectious diseases diagnosis and prognosis biomarker
Quan LI MD , Weiming LI MD , Ping ZOU MD , Jian ZHANG BM ,
《医学前沿(英文)》 2009年 第3卷 第3期 页码 309-315 doi: 10.1007/s11684-009-0043-4
关键词: graft vs host disease proteinase-activated receptor murine model hematopoietic stem cell transplantation
A giant step forward: chimeric antigen receptor T-cell therapy for lymphoma
Houli Zhao, Yiyun Wang, Elaine Tan Su Yin, Kui Zhao, Yongxian Hu, He Huang
《医学前沿(英文)》 2020年 第14卷 第6期 页码 711-725 doi: 10.1007/s11684-020-0808-3
关键词: chimeric antigen receptor T (CAR-T) cell lymphoma cytokine release syndrome (CRS) immune effector cell-associated neurotoxicity syndrome (ICANS)
XU Aijun, TIAN Yuke, DUAN Shiming
《医学前沿(英文)》 2007年 第1卷 第2期 页码 207-210 doi: 10.1007/s11684-007-0039-x
Lili Zhou, Ping Li, Shiguang Ye, Xiaochen Tang, Junbang Wang, Jie Liu, Aibin Liang
《医学前沿(英文)》 2020年 第14卷 第6期 页码 786-791 doi: 10.1007/s11684-020-0751-3
关键词: anti-CD19 chimeric antigen receptor T cell soft tissue bone marrow relapsed or refractory non-Hodgkin lymphoma
标题 作者 时间 类型 操作
Resistance to receptor tyrosine kinase inhibition in cancer: molecular mechanisms and therapeutic strategies
null
期刊论文
Effect of inhibiting tyrosine kinase Src expression on protein phosphatase 2A and tau phosphorylation
LIU Rong, ZENG Ji, ZHOU Xinwen, WANG Jianzhi, PEI Jinjing
期刊论文
Nicotinic acetylcholine receptor α7 subunit: a novel therapeutic target for cardiovascular diseases
null
期刊论文
Overcoming resistance to endocrine therapy in hormone receptor-positive human epidermal growth factorreceptor 2-negative (HR
Wenjie Zhu, Binghe Xu
期刊论文
microenvironment contributes to tumor progression in diffuse large B-cell lymphoma upon anti-CD19 chimeric antigen receptor
期刊论文
Chimeric antigen receptor T cell therapies for acute myeloid leukemia
Bin Gu, Jianhong Chu, Depei Wu
期刊论文
Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy
Zhao Zhang, Jun Jiang, Xiaodong Wu, Mengyao Zhang, Dan Luo, Renyu Zhang, Shiyou Li, Youwen He, Huijie Bian, Zhinan Chen
期刊论文
Blockage of receptor-interacting protein 2 expression by small interfering RNA in murine macrophages
LIU Hongchun, CAO Zhongwei, JIN Jianjun, WANG Jiyao
期刊论文
Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1): a potential biomarker for the diagnosis
Changlin Cao, Jingxian Gu, Jingyao Zhang
期刊论文
Gene and protein expression of proteinase-activated receptor-1, 2 in a murine model of acute graft host
Quan LI MD , Weiming LI MD , Ping ZOU MD , Jian ZHANG BM ,
期刊论文
A giant step forward: chimeric antigen receptor T-cell therapy for lymphoma
Houli Zhao, Yiyun Wang, Elaine Tan Su Yin, Kui Zhao, Yongxian Hu, He Huang
期刊论文
Effects of intracerebroventricular NMDA and non-NMDA receptor agonists or antagonists on general anesthesia
XU Aijun, TIAN Yuke, DUAN Shiming
期刊论文