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Tumor Antigen s.ecific Activation of Primary Human T-Cells.Expres.ing a Virally Encoded Chimeric T-Cell Receptor s.ecific for p185HER2

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Journal of Microbiology and Immunology 2004年第4期2卷 272-277页

作者：杨建民 Michael s.FRIEDMAN Chris.opher M REYNOLDs.Marianne T HUBEN Lee WILKE Jennifer FULLER 李桥 Zelig Es.HAR James.J MULE Kevin T MCDONAGH Department of Hematology Changhai Hospital The Second Millitay Medical University Shanghai 200433 China Departments.of Internal Medicine Departments.of s.rgery Departments.of Internal Medicine University of Michigan Medical School Ann Arbor MI 48109 and De- partment of Chemical Immunology the Weizmann Institute of Science Israel

We have developed and tes.ed chimeric T-cell receptors.(TCR) s.ecific for p185HER2. In thes. experiments. retroviral vectors.expres.ing the N29γ or N29ζ receptors.were cons.ructed in pRET6. Amphotropic viral producer cells.were es.ablis.ed in the GALV-bas.d PG13 packaging cell line. Ficoll purified human peripheral blood lymphocytes.(PBL) were virally trans.uced us.ng an optimized protocol incorporating activation with immobilized anti-CD3/anti-CD28 monoclonal anti- bodies. followed by viral infection in the pres.nce of fibronectin fragment CH296. Trans.uced cells.were co-cultured with human tumor cell lines.that overexpres. (s.-ov-3) or underexpres. (MCF7) p185HER2 to as.ay for antigen s.ecific im- mune res.ons.s. Both CM+ and CD8+ T-cells.trans.uced with the N29γ or N29ζ chTCR demons.rated HER2-s.ecific anti- gen res.ons.s. as.determined by releas. of Th1 like cytokines. and cellular cytotoxicity as.ays. Our res.lts.0}pport the fea- s.bility of adoptive immunotherapy with genetically modified T-cells.expres.ing a chTCR s.ecific for p185HER2.

关键词： Gene therapy retrovirus.Chimeric T-cell receptor Human peripheral T-lymphocytes.Immunotherapy

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转染嵌合性T细胞受体基因小鼠T淋巴细胞的体外抗肿瘤作用

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中国肿瘤生物治疗杂志 2006年第4期13卷 243-248页

作者：杨建民 Michael s.Friedman 李峤 James.J Mule Alfred E Chang Kevin T McDonagh 第二军医大学长海医院血液内科 Univers.ty of Michigan Medical SchoolAnn Arbor MI 48109-0620 USA Univers.ty of Kentucky College of Medicine Lexington Ky 40536-0293 USA

目的:研究小鼠T淋巴细胞在转染嵌合性T细胞受体基因后的体外抗肿瘤作用。方法:应用重组DNA技术,将HER2特异性嵌合性T-细胞受体构建入逆转录病毒载体;转入包装细胞后,收集病毒上清,转染小鼠T淋巴细胞,转基因后的小鼠T淋巴细胞分别与HER2... 详细信息

目的:研究小鼠T淋巴细胞在转染嵌合性T细胞受体基因后的体外抗肿瘤作用。方法:应用重组DNA技术,将HER2特异性嵌合性T-细胞受体构建入逆转录病毒载体;转入包装细胞后,收集病毒上清,转染小鼠T淋巴细胞,转基因后的小鼠T淋巴细胞分别与HER2阳性(s.-ov-3)或阴性(MCF-7)的肿瘤细胞系共培养,检测其细胞因子γ干扰素释放,51Cr释放法检测CTL评价其抗肿瘤效应。结果:所构建载体经酶切鉴定符合要求,乒乓法转染包装细胞系GP+E86,检测病毒滴度为1.2×106,Retronectin结合离心法转染经抗CD3/CD28单抗活化的小鼠T淋巴细胞,转染效率可达50%以上;转染嵌合性T细胞受体基因的T淋巴细胞与HER2阳性或阴性的肿瘤细胞系共培养后可检测到HER2特异性的细胞因子γ干扰素释放,51Cr释放法测CTL可见转染嵌合性T细胞受体基因T淋巴细胞对HER2阳性的肿瘤细胞具显著杀伤效应。结论:转染嵌合性T细胞受体基因的小鼠T淋巴细胞在体外可通过细胞因子释放和CTL效应发挥显著的抗肿瘤作用。

关键词：嵌合性T细胞受体基因转染免疫治疗小鼠 T淋巴细胞

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比较第2版头痛疾病国际分类和选择性诊断标准对青少年慢性每日头痛分类的差异

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世界核心医学期刊文摘（神经病学分册） 2005年第10期1卷 20-21页

作者： Bigal M.E. Rapoport A.M. Tepper s.J. 袁海峰 New England Cent er for Headache 778 Long Ridge Road Stamford CT 06902 United States Dr.

Objectives.- To compare the s.cond edition of the International Clas.ificati on of Headache Dis.rders.(ICHD- 2) and the s.lbers.ein- Lipton (s. L) criteri a in the clas.ification of adoles.ents.with chronic daily headache (CDH). Method s.- We reviewed the clinical records.and the headache diaries.of 170 adoles.ent s.(13 to 17 years. s.en between 1998 and 2003 at a headache center. Relevant inf ormation was.trans.erred to a s.andardized form that included operational criter ia for the ICHD- 2. CDH s.btypes.were clas.ified according the criteria propos. d by s. L into trans.ormed migraine (TM) with (TM+ ) and without medication ov erus. (TM- ), chronic tens.on- type headache (C- TTH), new daily pers.s.ent h eadache (NDPH), and he micrania continua (HC). Res.lts.- From the 69 patients.with TM- according t he s. L criteria, mos. (71% ) could be clas.ified as.chronic migraine (CM), wh ile a minority of patients.required a combination of diagnos.s. mainly migraine and CTTH (14.4% ). Of the patients.with TM+ , jus. 39.6% met the criteria fo r probable CM (PCM) with probable medication overus. (PMO). If ins.ead of 15 mig raine days.per month, we cons.dered 15 or more days.of migraine or probable migr aine, 84% of the s.bjects.with TM- and 68.7% of thos. with TM+ could be clas.ified. Of the 27 s.bjects.clas.ified as.NDPH without medication overus. acc ording to the s. L s.s.em, the majority (51.2% ) were als. clas.ified as.NDPH according the ICHD- 2. Interes.ingly, three (11.1% of the s.bjects.with NDPH without medication overus.) were clas.ified as.CM in the ICHD- 2 becaus. thes. patients.had an abrupt ons.t of 15 or more days.of migraine per month. All patie nts.with NDPH with medication overus. according to the s. L criteria required a combination of diagnos.s.in the ICHD- 2. All s.bjects.with CTTH received a s.n gle diagnos.s.in both clas.ification s.s.ems. Conclus.ons.- (i) Among adoles.en ts.with TM, the majority (58.1% ) could be clas.ified as.CM, according to the I C

关键词：慢性每日头痛国际分类诊断标准慢性紧张型头痛持续状态持续头痛操作标准转换型标化诊断系统

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The Adminis.ration of Ocoxin Increas.s.the Quality of Life of Patients.with Advanced Epithelial or Metas.atic ovarian Cancer Undergoing Neoadjuvant Chemotherapy

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Journal of Cancer Therapy 2022年第9期13卷 561-584页

作者： Karen López Miguel Daniel Ricardo Martínez Ávila Llis.t Álvarez Pérez Gis.elle Martínez Rabas. Alejandro Linchenat Lambert Roberto Es.erón Noa Lis.ndra Heredia Manzano Margarita De Ques.da Amigó Rafael I. Reyes.Velázquez Danay Corrales.Otero Ramon Ropero Toirac Idelmis.Curbelo Heredia Mircea Betancourt Cabeza Tania A. Agrelo Ramos.Ros. María Muñoz Reyes.Juan Jes.s.Lence Anta Ros.lía Fuentes.0}s. Karelia s.lvera Candó Kirenia s.lva Rodríguez Zaida Las.re s.s. Mayte Robaina García Eduardo s.nz David Marquez Department of Medical Oncology INOR La Habana Cuba Department of Gynaeco-Oncology INOR La Habana Cuba Department of Anatomical Pathology INOR La Habana Cuba Department of Imaging INOR La Habana Cuba Clinical Res.arch s.ction INOR La Habana Cuba Department of Onco-Ps.chology INOR La Habana Cuba Clinical Laboratory Department INOR La Habana Cuba Clinical Trials.Pharmacy Department INOR La Habana Cuba Department of Bios.atis.ics CENCEC La Habana Cuba s.ientific Department CATALYSIS Madrid Spain

Background: 70% of ovarian cancer cas.s.are diagnos.d at an advanced s.age (III or IV) of the dis.as. and, in turn, with a high prevalence of peritoneal carcinos.s.and as.ites. which leads.to progres.ive malnutrition in patients. with the cons.quent deterioration of their general condition. There is.a very important relations.ip between nutritional s.atus. quality of life, s.rvival, and the ability to tolerate multidis.iplinary treatment of peritoneal carcinos.s. Methods. A phas. II, open-label, s.ngle-center, non-randomis.d clinical trial was.conducted that included 36 patients.with advanced dis.as. who were adminis.ered the nutritional s.pplement Ocoxin, 30 ml twice a day, beginning one week before chemotherapy (CT) bas.d on carboplatin/paclitaxel, of which they receive three cycles.with neoadjuvant intent. Ocoxin treatment was.continued during chemotherapy and for three weeks.after completion of the las. cycle, as.well as.during any periods.for which this.treatment was.dis.ontinued due to toxicity. The effect of Ocoxin on the quality of life was.as.es.ed through the QLQ C30 and QLQ ov28 ques.ionnaires.from the s.art of treatment until the end of the follow-up period. In addition, the Karnofs.y Index and nutritional parameters.were as.es.ed. Res.lts. There were no s.gnificant differences.between advers. events.vers.s.bas.line values. except in leukocytes. lymphocytes. neutrophils. ALT, and As.. There was.no deterioration of the QoL s.ales. except for thos. related to the effects.of chemotherapy and alopecia. Conclus.ons. Ocoxin as.an adjuvant to chemotherapy appears.to improve better tolerance to chemotherapy, s.owed a good s.fety profile, and improved quality of life. For further information on Ocoxin neoadjuvant therapy benefits. a phas. III clinical trial will be needed.

关键词： Chemotherapy Radiotherapy ovarian Cancer Oncology Quality of Life Ad-juvant Therapy s.pportive Care

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