TREATMENT OF EBV LYMPHOMA BY INDUCTION OF EPISOMAL LOSS

通过诱导发作性丢失治疗 EBV 淋巴瘤

• 批准号: 2642945
• 负责人: Karen S Slobod
• 金额: $ 10万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-15 至 1999-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2642945
• 关键词: B lymphocyte; Burkitt's lymphoma; Epstein Barr virus; SCID mouse; clinical research; drug screening /evaluation; human subject; hydroxyurea; lymphoma; neoplasm /cancer chemotherapy; oxidoreductase inhibitor; plasmids; ribonucleotide reductase; virus related neoplasm /cancer; virus replication

The long term objective of this research is to develop new approaches to the therapy of Epstein-Barr virus (EBV)-related lymphomas. In its latent phase, EBV is associated with Burkitt's lymphoma (BL),nasophayngeal carcinoma, Hodgkin's disease, and fatal lymphoproliferative diseases in immunocompromised hosts. Although most are responsive to cytotoxic chemotherapy, relapsed disease or primary malignancies during acquired immunodeficiencies (AIDS, transplantation) often lack effective therapies with acceptable attendant toxicities. Little consideration has been given to EBV-targeted therapeutic strategies, first,because latent herpesviruses are intractable to available antiviral chemotherapy and, second, because of the uncertainty that EBV has any role in long-term maintenance of the malignant cell phenotype. We hypothesize that such an approach may be effective in treatment of EBV lymphomas, based on preliminary data that show successful eradication of EBV episOmes from BL cells treated in vitro with the ribonucleotide reductase inhibitor hydroxyurea, with concurrent loss of the malignant cell phenotype. Specific aims to test this hypothesis are: I. Determine the susceptibility to, and the consequences of; hydroxyurea (HU)-mediated episome loss in a variety of EBV- infected B cells. 2. Determine the mechanism of hydroxyurea (HU)-mediated EBV episome loss: selective interference with episome replication versus physical loss. 3. Evaluate the activity of HU in the treatment of biologically distinct, EBV-associated lymphomas.

这项研究的长期目标是开发新的 EB病毒相关性治疗方法探讨 淋巴瘤。在潜伏期，EB病毒与伯基特病有关 淋巴瘤、鼻咽癌、何杰金氏病和 免疫受损宿主的致命性淋巴增生性疾病。 尽管大多数人对细胞毒性化疗有反应，但复发 获得性疾病或原发恶性肿瘤 免疫缺陷(艾滋病、移植)通常缺乏效果。 伴随毒性可接受的治疗。很少考虑 已经被给予了EBV靶向治疗策略， 首先，因为潜伏的疱疹病毒很难获得 抗病毒化疗，第二，因为不确定 EBV在恶性疾病的长期维持中有任何作用 细胞表型。我们假设这样一种方法可能是 基于初步研究的EBV淋巴瘤的有效治疗 数据显示成功地从BL根除了EBV episOmes 用核糖核苷酸还原酶抑制剂处理体外培养的细胞 羟基脲，恶性细胞同时丢失 表型。检验这一假设的具体目标是： 一、确定疾病的易感性及其后果； 羟基脲(HU)介导的多种EBV-EB病毒的斑点丢失 感染的B细胞。 2.确定羟基脲(HU)介导的EBV的机制 Episome Lost：选择性干扰Episome复制 与身体上的损失相比。 3.评价HU在生物治疗中的活性。 截然不同的EBV相关淋巴瘤。

项目成果

Primary central nervous system lymphoma in a child with acute B-cell lymphoblastic leukaemia: consecutive Epstein-Barr virus-related malignancies.

患有急性 B 细胞淋巴细胞白血病的儿童的原发性中枢神经系统淋巴瘤：连续的 Epstein-Barr 病毒相关恶性肿瘤。

• DOI: 10.1046/j.1365-2141.1998.00709.x
• 发表时间: 1998
• 期刊: British journal of haematology
• 影响因子: 6.5
• 作者: Buckingham,SC;Benaim,E;Sandlund,JT;Gan,YJ;Freiden,PJ;Behm,FG;Ribeiro,RC;Sixbey,JW;Slobod,KS
• 通讯作者: Slobod,KS