A NOVEL CANCER MODEL--VACCINE ASSOCIATED SARCOMA

一种新的癌症模型——疫苗相关肉瘤

• 批准号: 6514863
• 负责人: Elizabeth A McNiel
• 金额: $ 12.43万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6514863
• 关键词: DNA damage; cats; chromosome aberrations; disease /disorder model; feline leukemia /sarcoma virus; fibroblasts; fluorescent in situ hybridization; gene rearrangement; glutathione; hydrogen peroxide; malonaldehyde; neoplasm /cancer genetics; neoplasm /cancer vaccine; rabies vaccines; rabies virus; sarcoma; sulfides; viral carcinogenesis

DESCRIPTION (Applicant's Description): Epidemiologic evidence strongly associates vaccination of cats for rabies and feline leukemia virus with the d e v elopment of soft tissue sarcomas at the vaccine site. Genetic susceptibility, sensitivity to reactive oxygen species (ROS), and chronic low dose environmental exposure to metals may all be significant in the development of this carcinogenesis, as well as in the pathogenesis of human cancer. I propose to carry out studies of vaccine induced tumor genetics and the oxidative status of cats as a potentially informative animal model for solid tumor carcinogenesis. Causative chromosome rearrangement have been i d entified in different human tumors; thus, I will employ classical cytogenetic and such molecular cytogenetic techniques as comparative genomic hybridization (CGH) and Multiplex fluorescence in situ hybridization (M-FISH) t o identify recurrent chromosomal aberrations in feline tumors with significance to carcinogenesis. I am adapting these cytogenetic techniques, designed for human tumors, for use in cats. Sensitivity to ROS in cats with and without vaccine induced tumors will be measured with: 1 ) Blood levels of the antioxidant glutathione in conjunction with indicators of oxidant exposure, oxidized glutathione and malondialdehyde, a product of lipid peroxidation. 2) Oxidative DNA base damage, 8-oxoguanine in particular, quantified by spectrometry of DNA from hydrogen peroxide exposed cat fibroblasts. All of these technologies are in place. Development of pet animal cancer models requires clinical expertise in spontaneous animal tumors combined with laboratory knowledge and skills. I am a veterinary oncologist with abundant clinical experience, currently pursuing a Ph D. I am dedicated to a career in translational cancer research. The Comparative Oncology unit at Colorado State University of which I am a part is dedicated to the development of spontaneous animal tumor models for human cancer and has contributed through the development of experimental therapeutics. I intend to apply the techniques and data acquired from this work to establish a center for animal tumor cytogenetics and genomic to study the role of genetics in the pathogenesis of cancer.

描述（申请人的描述）：广泛的证据很强 伴侣为猫和猫白血病病毒的猫接种疫苗与 在疫苗部位的软组织肉瘤的d e v。 遗传 敏感性，对活性氧（ROS）的敏感性和慢性低 剂量环境暴露于金属中可能都很重要 这种癌变的发展以及人类的发病机理 癌症。 我建议对疫苗诱导的肿瘤遗传学和 猫的氧化状态是作为潜在信息的动物模型 实体瘤致癌。 致病染色体重排 我进入了不同的人类肿瘤； 因此，我将使用古典 细胞遗传学和这种分子细胞遗传学技术作为比较基因组 杂交（CGH）和多重荧光原位杂交（M-FISH） 确定猫肿瘤中的复发性染色体像差 对癌变的意义。 我正在适应这些细胞遗传学技术， 专为人类肿瘤设计，用于猫。 对猫的ROS的敏感性 没有疫苗诱导的肿瘤，将测量以下方法：1）血液水平 抗氧化剂谷胱甘肽与氧化剂的指标结合 暴露，氧化的谷胱甘肽和丙二醛，脂质的产物 过氧化。 2）氧化性DNA碱损伤，特别是8-氧气鸟氨酸， 通过过氧化氢暴露的CAT的DNA光谱法量化 成纤维细胞。 所有这些技术都已经到位。 宠物的发展 动物癌模型需要自发动物肿瘤的临床专业知识 结合实验室知识和技能。 我是兽医肿瘤学家 拥有丰富的临床经验，目前正在追求PHD。我是专门的 从事转化癌研究的职业。 比较肿瘤学单元 在科罗拉多州立大学，我的一员致力于 开发人类癌症自发动物肿瘤模型，并具有 通过开发实验疗法做出了贡献。 我打算 应用从这项工作中获取的技术和数据来建立中心 动物肿瘤细胞遗传学和基因组学以研究遗传学在 癌症的发病机理。