ANTIVIRAL MEDIATED APOPTOSIS OF NON HODGKIN'S LYMPHOMA

本申请人已经发现，某些高分子材料可以用于制备高分子材料。 等级疱疹病毒相关淋巴瘤对抗病毒介导的 细胞凋亡在体外和体内。EB病毒阳性伯基特淋巴瘤 和人类疱疹病毒8型相关的原发性渗出性淋巴瘤经历 当在叠氮胸苷（AZT）或AZT存在下培养时， 干扰素α（IFN α）。他研究了这一过程的机制， 治疗引起这些淋巴瘤亚型的细胞凋亡。他发现 伯基特淋巴瘤细胞与AZT孵育导致CD 95上调 和凋亡。原发性渗出性淋巴瘤需要干扰素α 增强AZT介导的细胞凋亡。他还发现干扰素α 诱导B细胞淋巴瘤中的死亡受体配体、TRAIL和Fas配体。 与Burkitt淋巴瘤和原发性Efflymphoma相比，EBV阳性 大细胞免疫母细胞性淋巴瘤和EB病毒阴性淋巴瘤 对AZT和α干扰素有抵抗力这些初步发现表明 一些淋巴瘤可能对抗病毒治疗选择性敏感。在 易感性淋巴瘤，AZT和干扰素α介导的细胞凋亡不 仅通过Fas/Fas-配体相互作用发生，可能涉及激活 细胞凋亡的其他机制。申请人将调查角色 病毒和细胞促凋亡和抗凋亡蛋白在阻断或 促进AZT和干扰素α诱导原发性肝癌细胞凋亡 淋巴瘤标本和从这些肿瘤发展的细胞系。机制 在侵袭性淋巴瘤中诱导细胞凋亡将使这些患者受益。 疾病

DESCRIPTION: (Applicant's Abstract) The applicant has found that certain high grade Herpes virus associated lymphomas are sensitive to anti-viral mediated apoptosis in vitro and in vivo. Epstein-Barr Virus positive Burkitt's lymphoma and Human Herpes Virus Type 8 related Primary Effusion Lymphomas undergo apoptosis when cultured in the presence of Azidothymidine (AZT) or AZT and Interferon Alpha (IFN Alpha). He has investigated the mechanisms by which this therapy causes apoptosis in these lymphoma subtypes. He has found that incubation of Burkitt's lymphoma cells with AZT results in upregulation of CD95 and apoptosis. Primary Effusion Lymphoma requires Interferon Alpha to potentiate AZT mediated apoptosis. He has also found that Interferon Alpha induces the death receptor ligands, TRAIL and Fas Ligand in B cell lymphomas. In contrast to Burkitt's lymphoma and Primary Effusion Lymphoma, EBV positive large cell immunoblastic lymphomas and Epstein-Barr virus negative lymphomas were resistant to AZT and Interferon Alpha. These initial findings indicate that some lymphomas might be selectively sensitive to anti-viral therapy. In susceptible lymphomas, AZT and Interferon Alpha mediated apoptosis does not occur solely through Fas/Fas-Ligand interaction and likely involves activation of additional mechanisms of apoptosis. The applicant will investigate the role of viral and cellular pro- and anti-apoptotic proteins in blocking or facilitating AZT and Interferon Alpha induction of apoptosis in primary lymphoma specimens and cell lines developed from these tumors. A mechanism of inducing apoptosis in aggressive lymphomas would benefit patients with these diseases.