IMMUNOLOGIC ANALYSIS--MULTIDRUG RESISTANT GENE FAMILY

免疫学分析--多重耐药基因家族

基本信息

批准号：
3192181
负责人：
James M Croop
金额：
$ 26.75万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-09-01 至 1993-06-30
项目状态：
已结题

项目摘要

Resistance to multiple chemotherapeutic agents remains a major obstacle in successful management of human malignancies. Recently a specific gene, termed mdr p-glycoprotein, has been demonstrated to be amplified and overexpressed in multidrug resistant cell lines. This gene which is a member of a multigene family has been shown to convey resistance to multiple drugs in vitro. This proposal is focused on the development of antibodies to specific epitopes of the polypeptides which make up the mdr p- glycoprotein family in the mouse and man. The characterization of these antibodies with respect to specificity for each family member and the interaction with specific functional sites on the polypeptide chain will provide essential information for studies on normal and neoplastic tissues. These antibodies will be essential in determining the distribution and expression of the mdr p- glycoprotein in normal tissues and clinically in neoplasms during chemotherapy. As the role of the mdr p-glycoprotein in the development of drug resistance is clarified then the potential application of appropriate monoclonal antibodies for the reversal of multidrug resistance in vivo will be considered. The specific goals of this project are: 1) generation of antibodies to the 3 members of the mdr p-glycoprotein gene family, 2) generate antibodies to specific domains within the different family members, 3) map the structure of the mdr p-glycoproteins 4) determine the tissue distrimdrn of each of the mdr p- glycoproteins, 5) determine the role each member of the gene family in the generation of drug resistance, 6) evaluate functional domains of the mdr p-glycoprotein family members, 7) screen human tumors with these antibodies to determine the role of this gene family in the clinical development of drug resistance.

对多种化疗药物的耐药性仍然是一个主要因素成功管理人类恶性肿瘤的障碍。最近，一种称为 mdr p-糖蛋白的特定基因已被被证明在多种药物中被扩增和过度表达耐药细胞系。该基因是多基因的成员家庭已被证明对多种药物具有耐药性体外。该提案的重点是抗体的开发构成 mdr p-的多肽的特定表位小鼠和人的糖蛋白家族。表征这些抗体对每个家族的特异性会员以及与特定功能站点的交互多肽链将为研究提供重要信息正常组织和肿瘤组织。这些抗体是必不可少的确定 MDR p 的分布和表达正常组织和临床肿瘤中的糖蛋白化疗。由于 mdr p-糖蛋白在耐药性的发展得到澄清，那么潜在的应用适当的单克隆抗体进行逆转将考虑体内多重耐药性。该项目的具体目标是：1）抗体的产生耐多药 p 糖蛋白基因家族的 3 个成员，2) 产生针对不同区域内特定结构域的抗体家族成员，3) 绘制 MDR p-糖蛋白的结构图 4) 确定每个 MDR p 的组织分布糖蛋白，5）决定基因各成员的作用家族在耐药性的产生中，6）评估功能多重耐药 p-糖蛋白家族成员的结构域，7) 筛选人类肿瘤用这些抗体来确定这种作用耐药性临床发展中的基因家族。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

P-glycoprotein mediates profound resistance to bisantrene.

P-糖蛋白介导对比生群的深度耐药性。

DOI：
发表时间：
1994
期刊：
Oncology research
影响因子：
3.1
作者：
Zhang,XP;Ritke,MK;Yalowich,JC;Slovak,ML;Ho,JP;Collins,KI;Annable,T;Arceci,RJ;Durr,FE;Greenberger,LM
通讯作者：
Greenberger,LM

Functional imaging of multidrug-resistant P-glycoprotein with an organotechnetium complex.