ANTIVIRAL MEDIATED APOPTOSIS OF NON HODGKIN'S LYMPHOMA

描述：(申请者摘要)申请者发现某些高 恶性疱疹病毒相关淋巴瘤对抗病毒介导剂敏感 体外和体内的细胞凋亡。Epstein-Barr病毒阳性Burkitt淋巴瘤 与人类疱疹病毒8型相关的原发渗出性淋巴瘤 在叠氮胸苷(AZT)或AZT存在下培养时的细胞凋亡和 干扰素(干扰素)。他研究了这一现象的机制 治疗会导致这些淋巴瘤亚型的细胞凋亡。他发现 AZT与Burkitt淋巴瘤细胞孵育后CD95表达上调 和细胞凋亡。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，干扰素阿尔法 诱导B细胞淋巴瘤死亡受体配体、TRAIL和Fas配体。 与Burkitt淋巴瘤和原发性渗出性淋巴瘤相比，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和干扰素α具有抗药性。这些初步调查结果表明 一些淋巴瘤可能对抗病毒治疗选择性敏感。在……里面 易感淋巴瘤、AZT和干扰素α不介导细胞凋亡 仅通过Fas/Fas-配体相互作用发生，可能涉及激活 关于细胞凋亡的其他机制。申请者将调查该角色 病毒和细胞内的促凋亡和抗凋亡蛋白在阻断或 AZT和干扰素α诱导原代细胞凋亡的作用 淋巴瘤标本和细胞系是从这些肿瘤发展而来的。一种机制 诱导侵袭性淋巴瘤细胞凋亡将使患有这些疾病的患者受益 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.