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张继虹

发布时间:2015-03-13

 

张继虹教授、博士、硕士生导师

云南省中青年学术和技术带头人后备人才,昆明市中青年学术和技术带头人后备人选云南省医师协会药物临床评价与研究专业委员会委员、常委、副主任委员,《美国肿瘤治疗和药理》杂志编委。1996年毕业于沈阳药科大学,20103月获英国诺丁汉大学药学博士学位。1996年至2004年工作于云南省第一人民医院药剂科,2004-2006年工作于英国诺丁汉大学药学院,20072010年工作于英国抗肿瘤药物研发公司(Pharminox Ltd)。20104月全职引进到昆明理工大学工作。从事分子药理学研究。主要的研究方向为抗肿瘤药物的筛选及药理机制的研究:在英国工作期间发现了替莫唑胺的耐药机理,并构建了筛选替莫唑胺衍生物的筛药模型,及抗神经胶质瘤的机理研究。目前构建了突变p53、抗血管的靶向筛选模型,并与云南大学、中科院昆明植物所等多家单位合作开发抗肿瘤药物。主持国家自然科学基金3项,参与NSFC-云南联合基金2项(负责药理学研究部分),主持昆明理工大学抗肿瘤药物学科方向团队的建设。发表文章40余篇。主编专著《实用药物学》,获权专利6件。负责本科生《药理学》和研究生《专业外语》的教学工作。

                  

所学专业:

药学

 

所属教研室:

药理教研室

 

研究方向:

主要为抗肿瘤药物的筛选及药理机制的研究

 

主持及参与的科研项目:  

主持国家基金:天然黄杨生物碱降解突变p53的抗肿瘤机理研究81560601),2016.01-2019.12

主持国家基金:抗甲基转移酶耐药的替莫唑胺衍生物的药理机制的研究(81260501),2013.01-2016.12

主持国家自然科学基金项目:δμκ阿片受体三重激动剂的作用机制研究(81173029),2012.01-2012.12

主持云南省面上项目:替莫唑胺衍生物的药理机制研究(KKSA201126061),2011.10-2014.10

参与NSFC-云南联合基金项目:抗血管生成酪氨酸激酶抑制剂的设计合成及抗肿瘤活性研究(U1202221),2013.01-2016.12

参与国家自然科学基金项目:抗肿瘤赤霉素结构衍生物的设计、合成及构效关系研究(21062029),2011.01-2013.12

参与云南省面上项目:补肾活血中药对膝骨关节炎软骨下骨重塑作用机理研究(2011FB149),2011.10-2014.10

参与NSFC-云南联合基金项目:抗肿瘤升麻三萜的构效优化、作用机制和成效性研究(U11926042012.01-2015.12

参与技术开发项目:基于直盲肠抗癌的青蒿素类前药的实验研究2012.9.10-2013.9.10 12万元,昆明制药集团股份有限公司

参与技术合同项目:普洱茶辅助肿瘤化疗的临床预试验研究,中国普洱茶研究院2013.05-2014.12

参与云南省应用基础研究计划重大项目:激活端粒酶及抑制肿瘤的云南特色中药筛选及其药理研究,2013.10-2016.09,(2013FC006)云南省科技厅

参与英国癌症研究基金资助课题: quinol类抗癌药物的研发2002.06-2006.06

参与英国医疗行动计划Medical Research Action (MRC)and the Biotecchnology and Biological Sciences Research Council(BBSRC)资助课题:人体内花生四烯酸代谢物对子宫肌层兴奋性的影响,2004.06-2006.09

参与美国先灵葆雅与英国抗肿瘤药物研发公司Pharminox.Ltd课题:二代替莫唑胺衍生物的研发2006.10-2012.01

 

研究内容:

抗肿瘤药物的筛选及药理机制的研究:

1DNA损伤与修复和抗肿瘤药物的耐药研究;

2)抗血管生成药物的研发和机制研究;

3)针对突变p53的靶向药物研究;

4)作用热休克转录因子的药物研究;

5)体内抗肿瘤药物的评价(异种移植瘤和自发肿瘤动物模型)。

 

主要学习和业务工作经历:

1992. 09 -- 1996.07沈阳药科大学,药学系,获理学学士学位;

2007.01 -- 2010.03英国诺丁汉大学药学院,获药学博士学位

1996. 07-- 2004. 05云南省第一人民医院药剂科,主管药师;

2001.01 -- 2001.06中山医科大学临床药理基地进修药代与药动学

2004. 06 -- 2005.06英国诺丁汉大学药学院,访问学者;

2005.09 -- 2006.09英国诺丁汉大学药学院药物分析中心,助理研究员;

2007.01 -- 2010.01英国Pharminox Ltd药理学科研人员;

2010.04 --至今昆明理工大学医学院,教授

 

所获奖项:

12012年红云园丁奖;

2、第十四届伍达观教育基金先进教师奖;

32013年三育人工作先进个人;

42010-2012年度先进女职工。

 

发表文章及专利:

1.          Zhikuan Yang, Danping Wei,?Xiaoli Dai, Malcolm FG Stevens,Tracey D Bradshaw,?Ying Luo and Jihong Zhang. C8-Substituted Temozolomide Analogs Overcome O6-Methylguanine-DNA Methyltransferase and Mismatch Repair Precipitating Apoptotic Cancer Cell Death. Neuro-Oncology 2017. Vol. 2 No. 1: 2DOI: 10.21767/2572-0376.100018IF 7.37

2.          Xiaoli Dai, Jing Liu, Yin Nian, Ming-HuaQiu, Ying Luo, Jihong Zhang*.A novel cycloartanetriterpenoid from Cimicifuga induces apoptotic and autophagic cell death in human colon cancer HT-29 cells.Oncol Rep.2017 Apr;37(4):2079-2086. doi: 10.3892/or.2017.5444. Epub 2017 Feb 14. IF 2.49

3.         Jing Liu, Tongyang Liu, HancunMou, Chao Huang, Shengjiao Yan, Jun Lin, Ying Luo and Jihong Zhang. An Isoquinolin-1(2H)-Imine Derivative Induces Cell Death via Generation of Reactive Oxygen Species and Activation of JNK in Human A549 Cancer Cells. Journal of Cellular Biochemistry.

4.          Fu-Chao Yu, Xin-Rong Lin, Zhi-Cheng Liu, Ji-Hong Zhang,*Fei-Fei Liu, Wei Wu, Yu-Lu Ma, Wen-Wen Qu, Sheng-Jiao Yan,* and Jun Lin*Beyond the Antagonism: Self-Labeled Xanthone Inhibitors as Modeled “Two-in-One” Drugs in Cancer Therapy. ACS Omega 2017, 2, 873?889. DOI: 10.1021/acsomega.6b00545

5.          YafeiGuo, Yushun Zhang, Jiuling Li, Fen Zhao, Yang Liu, Min Su, Yubo Jiang, Yuqi Liu,Jihong Zhang,* Bo Yang,* and Rui Yang*Inclusion Complex of Podophyllotoxin with γ-Cyclodextrin: Preparation, Characterization, Anticancer Activity, Water-Solubility and Toxicity  Chin. J. Chem. 2016, 34, 425—431

6.          YufengRen, Ying Liu, RaomeiNiu, XialiLiao ,Jihong Zhang*, Bo Yang. Host-guest inclusion system of oleanolic acid with methyl-b- cyclodextrin: Preparation, characterization and anticancer activity.Journal of Molecular Structure 1117 (2016) 1-7.

7.          YufengRen, Ying Liu, Zhikuan Yang, RaomeiNiu, Kai Gao, Bo Yang, Xiali Liao, Jihong Zhang. Solid Inclusion Complexes of Oleanolic Acid with Amino-appended β- Cyclodextrins (ACDs): Preparation, Characterization, Water Solubility and Anticancer Activity. Materials Science & Engineering C[J], 2016, 05(022)

8.          Zhu MLiu TZhang JJia STang WLuo Y. Association between rs1344706 of ZNF804A and schizophrenia: a meta-analysisGenomics Proteomics Bioinformatics. 2014 Dec;12(6):292-6

9.          Jing Liu, Wenhui Huang, Ruoyu Zhou, ShutingJia, Wenru Tang, Ying Luo, and Jihong Zhang*. Bisphosphonates in the Treatment of Patients With Metastatic Breast, Lung, and Prostate Cancer.MedicineVolume 94, Number 46, November 2015.1-5.

10.     Liu JTang WSang LDai XWei DLuo YZhang J. Milk, Yogurt, and Lactose Intake and Ovarian Cancer Risk: A Meta-Analysis.Nutr Cancer. 2015; 67(1):68-72

11.      Yin NianJing YangTong-Yang LiuYing LuoJi-Hong Zhang*, Ming-HuaQiu. New Anti-angiogenic Leading StructureDiscovered in the Fruit of Cimicifugayunnanensis. Scientific Reports 20155:9026,1-7.

12.      Haiyu Yang, Danping Wei,Kunxian Yang,WenruTang,YingLuo,Jihong Zhang*. The Prognosis of MGMT Promoter Methylation in Glioblastoma Patients of Different Race: A Meta-analysis. Neuroche Res 2014392277-2287.

13.      Jihong Zhang, Marc Hummersone, Charles S Matthews, Malcolm FG Stevensand Tracey D Bradshaw. N3-Substituted temozolomide analogs overcome methylguanine DNA methyltransferase and mismatch repair precipitating apoptotic and autophagic cancer cell death.Oncology2015;88:28–48

14.      Ai Zhipeng, NingXianming, Shou Tao, Tang wenru andZhang Jihong*. Association of interleukin-6 promoter polymorphism with knee osteoarthritis: a meta-analysis.Chin Med J2014;127(13)

15.      Rui Yang, Jing-Bo Chen, Chuan-Fan Xiao, Zhi-Cheng Liu, Zhan-Yong Gao,Sheng-Jiao Yan,Ji-Hong Zhang*, Hong-Bin Zhang, Jun Lin. Inclusion complex of GA-13316 withβ-cyclodextrin: Preparation, characterization, molecular modeling, and in vitro evaluation.Carbohydrate Polymers, 2014, 111655–662.

16.      Lei FengShi-yanNianJihongzhang*.The GG genotype oftelomerase reverse transcriptase at genetic locus rs2736100 is associated with human atherosclerosis risk in the Han Chinese population. PloS One, 2014, 9(1), 85719.

17.      Yi-Chuan Zhang, Zhi-Cheng Liu, Rui Yang,Ji-Hong Zhang, Sheng-Jiao Yan and Jun Lin.Regioselective construction of 1,3-diazaheterocycle fused [1,2-a] [1,8] naphthyridine derivatives via cascade reaction of quinolines with heterocyclic ketene aminals: a joint experimental–computational approach.Org. Biomol. Chem., 2013, 11, 7276–7288

18.      Liang XiJian-Qiang Zhang,Zhi-Cheng Liu,Ji-Hong ZhangJu-Fang Yan,Yi JinJun Lin. Novel 5-anilinoquinazoline-8-nitro derivatives as inhibitors of VEGFR-2 tyrosine kinase: synthesis, biological evaluation and molecular docking.Org. Biomol. Chem., 2013,11, 4367-4378

19.      Sheng-Jiao Yan, Ying Dong, QiongPeng, Yin-Xin Fan,Ji-Hong Zhang*, Jun Lin. Synthesis of polyhalo 2-aryl-4-aminoquinazoline and 3-amino-indazoles as anticancer agents.RSC Advances.2013, 3, 5563-5569

20.      Bo Yang, Yu-Lin Zhao, Xia Yang, Xia-Li Liao, Jian Yang,Ji-Hong Zhang,Chuan-Zhu Gao. Scutellarin-cyclodextrin conjugates: Synthesis, characterization and anticancer activity.Carbohydrate Polymers.2013, 92, 1308– 1314

21.      Zhang J, Stevens MF, Bradshaw TD. Temozolomide: Mechanisms of Action, Repair and Resistance.Curr Mol Pharmacol.2012,5,102-114.

22.      Zhang J, Stevens MF, Hummersone M, Madhusudan S, Charles Laughton, Bradshaw TD. Certain ImidazotetrazinesEscape O6-Methylguanine-DNA-methyltransferase and Mismatch Repair.Oncology.2011;80:195-207.

23.      Zhang J,Stevens MF,Laughton CA,Madhusudan S,Bradshaw TD.Acquired resistance to Temozolomide in glioma cell lines: molecular mechanisms and potential translational applications.Oncology.2010Mar 31;78(2):103-114.

24.      Zhang JH, Pearson T, Matharoo-Ball B, Ortori CA, Warren AY, Khan R, Barrett DA.Quantitative profiling of epoxyeicosatrienoic, hydroxyeicosatetraenoic, and dihydroxyeicosatetraenoic acids in human intrauterine tissues using liquid chromatography/electrospray ionization tandem mass spectrometry.Anal Biochem.2007Jun 1; 365(1):40-51. Epub 2007 Mar 7

25.      Pearson T,Zhang J, Arya P, Warren AY, Ortori C, Fakis A, Khan RN, Barrett DA. Measurement of vasoactive metabolites (hydroxyleicosatetraenoic and epoxyeicosatrienoicacids ) in uterine tissues of normal and compromised human pregnancy.J Hypertens.28(12):2429-37,2010

26.     Chew E-H, Matthews CS,Zhang J,McCarroll AJ, Hagen T, Stevens MFG, Westwell AD, Bradshaw TD. Antitumor quinols: role of glutathione in modulating quinol-induced apoptosis and identification of putative cellular protein targets.Biochem Biophys Res Commun.2006Jul 21; 346(1):242-51. Epub 2006 May 26

 

会议论文:

1.     Ji-hong Zhang, Tracey Bradshaw, Malcolm Stevens, Yin-xain Fan. Temozolomide analogs overcome tumor resistance and induce DNA damage. The 12thmeeting of the Asia Pacific Federation of Pharmacologist. S1.73

2.     Zhi-peng AI,Xian-ming NINGJi-hong ZHANG*. Mechanism of traditional Chinese medicine for knee osteoarthritis subchondral bone remodeling.The Proceedings of 12th Meeting of the Asia Pacific Federation of Pharmacologists (ActaPharmacologicaSinica 2013 volume 34 Supplement)

3.      Zhang J,Stevens MFG, Kerschmeier P, Hummersone MG, Laughton CA, Bradshaw TD. Novel temozolomide analog may overcome MGMT and MMR. 21thEORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics2009, abstract No, 432

4.     T.D. Bradshaw,J. Zhang, M.F.G. Stevens, C.A. Laughton, S. Madhusudan, P. Kirschmeier. Acquired resistance to temozolomide in glioma cell lines: molecular mechanisms and potential translational applications. 20thEORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics2008, abstract No, 154.

5.     Westwell AD, Chew EH,Zhang JH, Matthews CS, Hagen T, Bradshaw TD, McCarroll AJ, Wells, G, Stevens MF Thiol-interactive antitumor quinols as modulators of cellular redox homeostasis. AACR/NCI/EORTC international conference on molecular targets and cancer therapeutics, Philadelphis, Nov-14-18,2005

6.     Chew E-H, Cookson JC, Matthews CS,Zhang J-H, Hagen T, Bradshaw TD, Stevens MFG, Westwell AD. Novel antitumor quinols: the role of thioredoxin. 96th AACR Annual Meeting2005, Abstract No: 636.

7.     T.D. BradshawM. Hummersone, J. Hartley, M.F.G. Stevens,J. Zhang.N3-Substituted temozolomide analogs overcome methylguanine DNA methyltransferase and mismatch repair.21thEORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics2010, abstract No, 176

 

中文文章

1.       魏丹萍,代晓丽,罗瑛,张继虹(通讯). O 6 -M G -D N A -甲基转移酶基因表达调控及其与肿瘤耐药性的研究进展,医学分子生物学杂志,2014 115278-282.

2.       桂思倩,张继虹,罗瑛.突变型p53蛋白稳定表达机制的研究进展.肿瘤vol 34. No7 2014673-677.

3.       代晓丽,刘静,罗瑛,张继虹(通讯).靶向作用p53药物的研究进展中国药理学通报2014 Jul;30(7):912-916.

4.       杨海钰,吴晓明,罗瑛,张继虹(通讯).自噬与肿瘤耐受的关系,生命科学研究,2014,18(2):179-183.

5.       艾志鹏,贾舒婷,罗 瑛,张继虹(通讯).靶向DNA修复缺陷的合成致死作用研究进展,肿瘤2013年5月第33卷第5期.

6.       范应仙,张继虹(通讯),张宽仁. 凋亡抑制蛋白及其拮抗剂研发进展,中国新药与临床杂志,2013,4(32),4,257-264.

7.       宁显明,张继虹(通讯),屠文莲,刘红.替莫唑胺的耐药性研究进展,中国新药与临床杂志,2013,4(32),4,251-256.

8.       刘晓玲,唐文如,罗瑛,张继虹(通讯). DNA修复与肿瘤的耐药,生命的化学,2012,32(6),526-532.

9.       张宽仁,张继虹,彭琼,范应仙. 凋亡因子(TRAIL)对癌细胞凋亡的机制研究,昆明理工大学学报(自然科学版, 2012,37(1):53-60.

10.   伊首璞,陈忠明,张继虹,张宽仁.阿片类受体亚型间相互作用研究进展,中国药理学通报20122811):1493-1496.

11.   宁显明,艾志鹏,张继虹,王海彬,刘红,朱洪民。补肾活血中药对模拟体外骨重塑作用的细胞特征的影响.广州中医药大学学报,2014,31(6)963-973.

12.   刘静桑磊贾舒婷张继虹罗瑛.绿茶对苯并芘致人胚肺成纤维细胞DNA损伤的保护作用.《医学分子生物学杂志》, 2015(5)

13.   刘同阳 ,郭海强 ,朱美妍 ,黄英泽 ,贾舒婷 ,罗瑛 ,张继虹。 突变 p53 与其合成致死基因的研究进展。《遗传》,2015(4):321-326

14.   刘飞飞,刘静,吴谓,刘颖,罗瑛,张继虹。靶向内皮细胞糖酵解限速酶PFKFB3的抗肿瘤血管生成研究进展《肿瘤》,201636103-108.

15.   吴谓,刘飞飞,刘颖,张继虹。靶向HSF1在肿瘤治疗中的作用。《医学分子生物学杂志》, 2016, 13 (1): 52-58

16.   刘颖,张洪英,唐涛,刘飞飞,吴谓,罗瑛,张继虹。以芳香烃受体为药物靶点的肿瘤治疗研究《中国药理学通报》2016 May; 32( 5) : 607 ~ 12

17.   杨志宽,暴亚锋,牟汉川,刘静,张继虹。靶向真核细胞起始因子4F复合体的抗肿瘤药物研究进展。《肿瘤》Vol. 36, September 2016: 1050-1057.

18.   牟汉川,杨志宽,暴亚锋,王玉玲,刘静,张继虹。他汀药物对p53突变肿瘤细胞的作用及机制中国老年学杂志20172月第37卷:788-790.

 

论著

《实用药物学》 主编 吉林科学技术出版社2014.5 ISBN 978-7-5384-7708-5

 

国际专利

1. STEVENS, Malcolm, Francis; Graham COUSIN, David;  JENNINGS , Sharon;  McCARROLL, Andrew, James; WILLIAMS , John, Gareth; HUMMERSONE , Marc, Geoffery;ZHANG,Jihong.3-Substituted-8-Substituted-3H-Imidazo[5,1-D][1,2,3,5-Tetrazin-4-one Compounds and Their Use.U.S. Provisional Patent Application Serial No 61/219,575 filed 23 June 2009.

2STEVENS, Malcolm, Francis; Graham COUSIN, David;  JENNINGS, Sharon;  McCARROLL, Andrew, James; WILLIAMS , John, Gareth; HUMMERSONE , Marc, Geoffery;ZHANG,Jihong.3-Substituted-4-Oxo-3,4-Dihydro-Imidazo[5,1-d][1,2,3,5-Tetrazine-8-Carboxylic Acid Amides and Their Use.International Patent Application No PCT/GB2008/004140 filed 16 December 2008. International Publication Number WO2009/077741

国内专利:

1.     环阿尔廷型三萜化合物及其应用,发明人:张继虹;邱明华;唐文如;年寅;罗瑛;王海燕;朱晖;陆思千;贾舒婷;吴晓明.申请号:CN201310104207

2.     羊毛甾烷三萜类化合物及其应用,发明人:唐文如;邱明华;张继虹;年寅;罗瑛;王海燕;朱晖;吴晓明;贾舒婷.申请号:CN201310104175

3.     一种升麻三萜类化合物及其应用,发明人:贾舒婷;邱明华;唐文如;年寅;罗瑛;王海燕;张继虹;朱晖;陆思千;吴晓明.申请号:CN201310104160

4.     四种黄杨生物碱化合物的医药用途,发明人:罗瑛;邱明华;张继虹;阎玉鑫;苏红;陆思千;贾舒婷;吴晓明.申请号:CN201310104292

5.     一种色酮化合物的医药用途,发明人:吴晓明;邱明华;张继虹;年寅;唐文如;王海燕;罗瑛;陆思千;贾舒婷.申请号:CN201310104300

6.一种黄杨生物碱化合物的医药用途,发明人:罗瑛;邱明华;张继虹;阎玉鑫;苏红;陆思千;贾舒婷;吴晓明. 申请号:CN201410111214.6

7.一种基于普洱茶主要成分的组合物及其应用,发明人:罗瑛;张继虹;唐文如。申请号:2013CN10010855.8

 

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