ROLE OF PAPILLOMAVIRUS IN CERVICAL NEOPLASIA

乳头状病毒在宫颈肿瘤中的作用

• 批准号: 3170540
• 负责人: WAYNE D LANCASTER
• 金额: $ 14.95万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-01-01 至 1992-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3170540
• 关键词: Escherichia coli; Papillomavirus; biopsy; cervix neoplasms; gene expression; genetic manipulation; genetic mapping; genetic recombination; human tissue; immunofluorescence technique; in situ hybridization; laboratory mouse; laboratory rabbit; microorganism immunology; molecular cloning; monoclonal antibody; neoplasm /cancer immunology; nucleic acid hybridization; nucleic acid sequence; oncogenic virus; spectrometry; tumor antigens; virus DNA; virus antigen; virus genetics

Recent molecular virologic and immunologic studies have shown a relationship between human papillomavairus (HPV) infection and dysplasia of the uterine cervix. The significance of these observations is underscored by the fact that dysplasias are considered precursor lesions to cervical carcinoma. The specific aims of this proposal are to characterize HPV sequences from dysplasias by molecular cloning for the purpose of identifying the various HPV types associated with these lesions using molecular hybridization and immunological tests with antibodies directed against virus type-specific poly- or oligopeptides. HPV sequences will be cloned into plasmid or Charon vectors and subsequently characterized by hybridization to DNAs of known HPV types. These cloned DNAs will be used in blot transfer and in situ hybridization experiments with dysplasias and cervical carcinomas. Sequence analysis of the viral DNAs will provide necessary information for the synthesis of virus type-specific structural polypeptides in bacterial expression vector systems or synthesis of oligopeptides by solid-phase chemistry. The resultant antibodies will be used to screen biopsy specimens to determine the HPV type associated with dysplasias which regress and those which progress to more serious disease. Antibodies directed against papillomavirus genus-specific nonstructural (transforming) proteins will be synthesized in bacteria for use in immunocytochemical studies on cervical cancers. From the behavior of cervical dysplasia (regression or progression) it would be of prognostic and/or diagnostic value to be able to predict the outcome of HPV infection of the cervix. Such information could provide a more rational approach to the management of cervical neoplasia.

最近的分子病毒学和免疫学研究表明 人乳头瘤病毒（HPV）感染与发育不良的关系 子宫颈。 强调了这些观察结果的重要性 事实上，发育异常被认为是宫颈癌的先兆病变 癌。 该提案的具体目标是描述 HPV 的特征 通过分子克隆从发育异常中获得序列，目的是 使用以下方法识别与这些病变相关的各种 HPV 类型： 分子杂交和抗体定向免疫学测试 对抗病毒类型特异性的多聚肽或寡肽。 HPV 序列将被克隆到质粒或 Charon 载体中，并 随后通过与已知 HPV 类型的 DNA 杂交来表征。 这些克隆的 DNA 将用于印迹转移和原位杂交 不典型增生和宫颈癌的实验。 序列分析 病毒DNA将为合成提供必要的信息 细菌表达载体中的病毒类型特异性结构多肽 系统或通过固相化学合成寡肽。 这 所得抗体将用于筛选活检标本以确定 与消退的不典型增生相关的 HPV 类型以及与不典型增生相关的 HPV 类型 进展为更严重的疾病。 抗体针对 乳头瘤病毒属特异性非结构（转化）蛋白将 在细菌中合成，用于宫颈免疫细胞化学研究 癌症。 从宫颈发育不良的行为（消退或进展）来看 将具有预后和/或诊断价值，能够预测 子宫颈HPV感染的结果。 此类信息可以提供 更合理的宫颈肿瘤治疗方法。