MOLECULAR MECHANISMS OF CD30+ LYMPHOMA GROWTH

CD30 淋巴瘤生长的分子机制

• 批准号: 6342143
• 负责人: ECKHARD R PODACK
• 金额: $ 21.05万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6342143
• 关键词: CD antigens; T lymphocyte; biological signal transduction; gene targeting; genetically modified animals; growth factor receptors; immunologic memory; laboratory mouse; leukocyte activation /transformation; lymphoma; molecular oncology; neoplasm /cancer immunology; neoplastic growth; proteolysis; tumor necrosis factor alpha

CD30 has long been recognized as a unique antigen on lymphomas of T or B origin of immature to the fully differentiated state. CD30 moreover has been found to be associated with disease progression in anaplastic large cell lymphoma. CD30 is expressed as a disease marker in allergic conditions and CD30 expression is associated with progression of HIV disease, with Epstein-Bar virus infection and transformation and with HTLV associated lymphomas. Finally, CD30 over-expression is found in Omenn's syndrome, a severe combined immunodeficiency of unknown etiology, characterized by high Il-5 levels, eosinophilia and IgE production. CD30 signaling functions via TRAF proteins have recently been elucidated. Similar to other members of the TNF-R family of receptors, CD30 signals have a dual role for activation, proliferation and anti-apoptosis; or for apoptosis. CD30 expression itself is favored by a TH2 environment and suppressed by Ifn-gamma. It is postulated and will be tested in this application that CD30 expressed on lymphomas provides a selective advantage to lymphomas or other CD30 positive cells through its co- stimulatory activity, by promoting proliferation and increasing resistance to apoptosis. This hypothesis will be examined 1. by analyzing pathways regulating TRAF2 activity which is primarily responsible for anti apoptotic signals through Jun-N-terminal kinase (JNK) and NFkappaB activation; 2. by CD30-L gene ablation to eliminate CD30-L triggered CD30 signals and signaling by CD30 induction on ongoing immune responses to tumors in vivo and in vitro.

长期以来，CD30被认为是T或B的淋巴瘤上的独特抗原 不成熟到完全分化状态的起源。 CD30此外 被发现与大型塑性大的疾病进展有关 细胞淋巴瘤。 CD30在过敏性中表示为疾病标记 条件和CD30表达与HIV的进展有关 疾病，爱泼斯坦 - 巴尔病毒感染和转化以及HTLV 相关的淋巴瘤。最后，在Omenn的CD30过表达 综合征，一种严重的病因的严重合并免疫缺陷， 以高IL-5水平，嗜酸性粒细胞和IgE产生为特征。 CD30 最近已经阐明了通过TRAF蛋白通过TRAF蛋白的信号传导功能。 类似于TNF-R受体家族的其他成员，CD30信号 在激活，增殖和抗凋亡中具有双重作用；或 凋亡。 CD30表达本身受到TH2环境的青睐，并且 被IFN-GAMMA抑制。它是假定的，将在此中进行测试 CD30在淋巴瘤上表达的应用提供了选择性 通过其共同细胞对淋巴瘤或其他CD30阳性细胞的优势 刺激活动，通过促进增殖和增加的抗性 凋亡。该假设将通过分析途径进行检查1。 调节主要负责抗的TRAF2活动 通过Jun-N-N末端激酶（JNK）和NFKappab的凋亡信号 激活; 2。通过CD30-L基因消融以消除CD30-L触发CD30 CD30引起的信号和信号传导持续的免疫反应 体内和体外肿瘤。