作者机构:
[Tao W.; Jian H.; Yongdong L.; Yonghong D.; Yuanding J.; Peng X.; Richu L.] Department of Neurosurgery, Second Hospital Affiliated to University of South China, Hengyang, 421001, China;[Yongmei Y.] Department of Anatomy, Medical School, University of South China, Hengyang, 421001, China
通讯机构:
[Yongmei, Y.] D;Department of Anatomy, China
通讯作者:
Yujuan Jin<&wdkj&>Liang Hu<&wdkj&>Hongbin Ji
作者机构:
[Zhao, Qiqi; Yue, Meiting; Xue, Yun; Li, Xuefeng; Huang, Hsin-Yi; Jin, Yujuan; Ji, Hongbin; Guo, Chenchen; Hu, Liang] Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China.;[Zhao, Qiqi; Yue, Meiting; Xue, Yun; Cao, Jiayu; Li, Xuefeng; Ji, Hongbin; Guo, Chenchen] Univ Chinese Acad Sci, Beijing 100049, Peoples R China.;[Li, Cheng; Li, Xuefeng] Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Dept Med Oncol, Hengyang 421001, Hunan, Peoples R China.;[Zhao, Qiqi; Ji, Hongbin] Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200120, Peoples R China.;[Cao, Jiayu] Chinese Acad Sci, CAS MPG Partner Inst Computat Biol, Shanghai Inst Nutr & Hlth, Shanghai Inst Biol Sci,CAS Key Lab Computat Biol, Shanghai 200031, Peoples R China.
通讯机构:
[Yujuan Jin; Liang Hu; Hongbin Ji] S;State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China<&wdkj&>University of Chinese Academy of Sciences, Beijing 100049, China<&wdkj&>School of Life Science and Technology, Shanghai Tech University, Shanghai 200120, China<&wdkj&>School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China<&wdkj&>State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China
摘要:
Small cell lung cancer (SCLC) is a phenotypically heterogeneous disease with an extremely poor prognosis, which is mainly attributed to the rapid development of resistance to chemotherapy. However, the relation between the growth phenotypes and chemo-resistance of SCLC remains largely unclear. Through comprehensive bioinformatic analyses, we found that the heterogeneity of SCLC phenotype was significantly associated with different sensitivity to chemotherapy. Adherent or semiadherent SCLC cells were enriched with activation of the PI3K/Akt/mTOR pathway and were highly chemoresistant. Mechanistically, activation of the PI3K/Akt/mTOR pathway promotes the phenotypic transition from suspension to adhesion growth pattern and confers SCLC cells with chemo-resistance. Such chemo-resistance could be largely overcome by combining chemotherapy with PI3K/Akt/mTOR pathway inhibitors. Our findings support that the PI3K/Akt/mTOR pathway plays an important role in SCLC phenotype transition and chemo-resistance, which holds important clinical implications for improving SCLC treatment.
作者机构:
[何洁; 张圆; 林祎] Cancer Research Institute, Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial, Hengyang Medical College, University of South China, Hengyang, 421001, China;[李彩; 刘政海] Clinical Anatomy & Reproductive Medicine Application Institute, School of Medicine, University of South China, Hengyang, 421001, China;[吴琼] Key Laboratory of Brain Science Research & Transformation in Tropical Environment of Hainan Province, Hainan Medical University, Haikou, 571199, China
通讯机构:
[Li, C.; He, J.] C;Clinical Anatomy & Reproductive Medicine Application Institute, China;Cancer Research Institute, China
关键词:
辐照;小鼠;海马;认知障碍;小胶质细胞
摘要:
探讨小胶质细胞在头部X射线照射所致认知障碍过程中的作用。18只ICR(Institute of Cancer Research)小鼠随机分为对照组和头部辐照组,头部辐照组小鼠接受X射线单次头部辐照至吸收剂量10 Gy。辐照56 d后分别采用新旧事物识别实验和新旧位置识别实验检测小鼠认知功能;免疫组织化学法检测小鼠海马小胶质细胞标记物IBA-1阳性细胞数目变化;Sholl Analysis定量分析小胶质细胞形态变化;RT-PCR检测海马M1/M2型小胶质细胞标记物(CD16、INOS、CD68、CXCL10、Arg1、CD206)mRNA水平表达变化。结果显示:与对照组相比,头部辐照组小鼠新事物时间辨别指数(p<0.01)和新位置时间辨别指数(p <0.05)均明显降低;小鼠海马齿状回区(Dentate gyrus,DG)IBA-1阳性细胞数明显增加(p<0.05);小胶质细胞体变大,突起回缩,树突分支数与同心圆交点数目减少(p<0.05);小鼠海马M1型小胶质细胞标记物CD68表达上调(p<0.05),M2型小胶质细胞标记物Arg1表达下调(p<0.001)。头部X射线照射致认知障碍可能与小鼠海马小胶质细胞形态变化及小胶质细胞向M1型极化相关。
作者机构:
[蒋静; 王丽; 李佳; 胡政; 贺荣章; 屈佳肴; 段丽丽; 罗迪贤; 李香凝] Translational Medicine Institute, Chenzhou Hospital Affiliated to University of South China, Chenzhou 423000;[蒋静; 李佳; 贺荣章; 段丽丽; 李香凝] National & Local Joint Engineering Laboratory for High-Through Molecular Diagnosis Technology, Chenzhou Municipal First People's Hospital, Chenzhou 423000, China;[屈佳肴] First School of Clinical Medicine, Southern Medical University, Guangzhou 510000;[屈佳肴] Department of Laboratory Medicine, Shenzhen Third People's Hospital, Shenzhen 518000, China;[王丽; 罗迪贤] First School of Clinical Medicine, Southern Medical University, Guangzhou 510000, China
作者机构:
[王紫涵; Lyu H.-J.; 凌宏艳; 罗金定; 何剑琴] Dept of Physiology, Hengyang Medical College, University of South China, Hunan, Hengyang, 421001, China;[田英入] Clinical Class 21, Grade 2017, Hengyang Medical College, University of South China, Hunan, Hengyang, 421001, China;[奉水东] Dept of Social Medicine and Health Management, Public Health College, University of South China, Hunan, Hengyang, 421001, China
作者机构:
[米海燕] Department of Nephrology, Nanhua Hospital Affiliated to South China University, Hunan, Hengyang, 421002, China;[沈阳; 刘稀金; 刘诗洋; 陈勇军; 漆仕林; 李敏] Department of Neurology, Nanhua Hospital Affiliated to South China University, Hunan, Hengyang, 421002, China
通讯机构:
[Mi, Haiyan] D;Department of Nephrology, Nanhua Hospital Affiliated to South China University, Hengyang, Hunan 421002, China.