Cellular Susceptibility

细胞敏感性

• 批准号: 7899813
• 负责人: Mary Eileen Dolan
• 金额: $ 22.02万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7899813
• 关键词: 6-Mercaptopurine; Antineoplastic Agents; CYP3A4 gene; Cell Line; Cytarabine; Cytotoxic agent; Data; Drug resistance; Etoposide; Family; Generations; Genes; Genetic; Genetic Determinism; Genotype; In Vitro; Inherited; Letters; Malignant Neoplasms; Pharmaceutical Preparations; Pharmacogenetics; Predisposition; Research; SN-38; Testing; Tissues; Vincristine; Work; cancer cell; cytotoxicity; drug sensitivity; genetic pedigree

Our studies in the CS Project continue our identification of genetic determinants of chemotherapeutic sensitivity of agents that target CRC and ALL. In the ALL Project we obtain primary malignant cells for determining in vitro drug sensitivity and identifying genes associated with drug resistance in primary cancer tissue (46). This is not practical . for CRC. Our second approach for the CS project is to test for inherited determinants of drug sensitivity using LCLs derived from CEPH families. Three-generation pedigrees provide the power to evaluate the genetic contribution to anticancer drug cytotoxicity (41). Drugs that are relevant to the objectives of PAAR include: etoposide (ALL, CRC, CYP3A); vincristine and daunbrubicin (ALL, CYP3A); mercaptopurine and cytarabine (ALL); SN-38 and platinating agents (CRC). Complementary studies are being performed in CREATE (42) and we are working together to share baseline microarray data, genotyping on CEPH cell lines and statistical expertise (see letter from Dr. McLeod). We hypothesize that a significant component of cellular susceptibility to cytotoxic agents is due to heritable factors.

我们在CS项目中的研究继续我们确定化学治疗敏感性的遗传决定因素 针对CRC和所有目标的代理。在所有项目中，我们获得用于确定体外的主要恶性细胞 药物敏感性和鉴定与原发性癌组织中耐药性相关的基因（46）。这是不切实际的。 对于CRC。我们对CS项目的第二种方法是使用LCLS测试药物敏感性的遗传决定因素 源自Ceph家族。三代血统提供了评估遗传贡献的能力 抗癌药细胞毒性（41）。与PAAR目标相关的药物包括：依托泊苷（所有，CRC，， CYP3A）; vincristine和daunbrubicin（ALL，CYP3A）；胃嘌呤和细胞丁滨（全）； SN-38和柏拉图式 代理商（CRC）。正在创建（42）中进行互补研究，我们正在共享 基线微阵列数据，针对CEPH细胞系的基因分型和统计专业知识（请参阅McLeod博士的信）。我们 假设细胞对细胞毒性剂的易感性的重要组成部分是由于可遗传的因素。