Gene And Immunotherapy Of Neoplasms Affecting Human Comm

影响人类通讯的肿瘤的基因和免疫治疗

• 批准号: 6690276
• 负责人: CARTER VAN WAES
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
• 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/6690276
• 关键词: cell line; clinical research; cytokine; disease /disorder model; gene therapy; human subject; human tissue; immunologic assay /test; laboratory mouse; metastasis; molecular oncology; mouth neoplasms; neoplasm /cancer genetics; neoplasm /cancer immunology; neoplasm /cancer immunotherapy; neoplastic process; nonhuman therapy evaluation; respiratory neoplasm; squamous cell carcinoma; transcription factor; transfection

The purpose of this project is to elucidate the molecular and immune pathogenesis of squamous cell neoplasms of the upper aerodigestive tract, and to enable the development of approaches for molecular and immune therapy for these disorders. Human and murine squamous cell carcinoma cell line models have been developed and used to identify genes that are differentially expressed with tumor progression using molecular and immune assays. Proinflammatory cytokines, related signal transduction pathway molecules, and immediate early transcription factor genes have been shown to be overexpressed or activated with tumor progression, and are associated with aggressive growth and metastasis. The function of these candidate genes following overexpression or inhibition by transfection of tumors with dominant negative constructs has been the subject of recent investigations to identify potential targets for molecular and immune therapy. During the past year, the role of transcription factors NF-kB and AP-1 in expression of angiogenic factors IL-8 and VEGF has been elucidated. Hepatocyte Growth Factor/ MET receptor, Epidermal Growth Factor Receptor and the IL-1 Receptor have been identified as upstream activators of these signal pathways and cytokines. Identification of the role of NF-kB has led to a clinical study of a proteasome inhibitor which inhibits tumor growth and angiogenesis and sensitizes head and neck cancers to radiation.

本项目的目的是阐明上呼吸消化道鳞状细胞肿瘤的分子和免疫发病机制，并使这些疾病的分子和免疫治疗方法的发展。已经开发了人和鼠鳞状细胞癌细胞系模型，并使用分子和免疫测定来鉴定随着肿瘤进展而差异表达的基因。促炎细胞因子、相关信号转导通路分子和即刻早期转录因子基因已被证明随着肿瘤进展而过表达或激活，并且与侵袭性生长和转移相关。这些候选基因的功能后，过表达或抑制转染的肿瘤与显性负结构已成为最近的调查，以确定潜在的分子和免疫治疗的目标。在过去的一年中，转录因子NF-κ B和AP-1在血管生成因子IL-8和VEGF表达中的作用已被阐明。肝细胞生长因子/ MET受体、表皮生长因子受体和IL-1受体已被鉴定为这些信号通路和细胞因子的上游激活剂。对NF-kB作用的鉴定导致了对蛋白酶体抑制剂的临床研究，该蛋白酶体抑制剂抑制肿瘤生长和血管生成并使头颈癌对辐射敏感。