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针对爱泼斯坦-巴尔病毒阳性移植后淋巴细胞增生性疾病的新兴治疗策略。

Emerging therapeutic strategies for Epstein-Barr virus+ post-transplant lymphoproliferative disorder.

作者信息

Hatton Olivia, Martinez Olivia M, Esquivel Carlos O

机构信息

Department of Surgery/Division of Abdominal Transplantation, Stanford University School of Medicine, Stanford, CA 94305, USA.

出版信息

Pediatr Transplant. 2012 May;16(3):220-9. doi: 10.1111/j.1399-3046.2012.01656.x. Epub 2012 Feb 21.

Abstract

De novo malignancies represent an increasing concern in the transplant population, particularly as long-term graft and patient survival improves. EBV-associated B-cell lymphoma in the setting of PTLD is the leading malignancy in children following solid organ transplantation. Therapeutic strategies can be categorized as pharmacologic, biologic, and cell-based but the variable efficacy of these approaches and the complexity of PTLD suggest that new treatment options are warranted. Here, we review current therapeutic strategies for treatment of PTLD. We also describe the life cycle of EBV, addressing the viral mechanisms that contribute to the genesis and persistence of EBV+ B-cell lymphomas. Specifically, we focus on the oncogenic signaling pathways activated by the EBV LMP1 and LMP2a to understand the underlying mechanisms and mediators of lymphomagenesis with the goal of identifying novel, rational therapeutic targets for the treatment of EBV-associated malignancies.

摘要

新发恶性肿瘤在移植人群中越来越受到关注,尤其是随着长期移植物和患者生存率的提高。实体器官移植后,PTLD背景下的EBV相关B细胞淋巴瘤是儿童中的主要恶性肿瘤。治疗策略可分为药物治疗、生物治疗和基于细胞的治疗,但这些方法的疗效各异以及PTLD的复杂性表明需要新的治疗选择。在此,我们综述了目前治疗PTLD的策略。我们还描述了EBV的生命周期,探讨了促成EBV+B细胞淋巴瘤发生和持续存在的病毒机制。具体而言,我们聚焦于由EBV LMP1和LMP2a激活的致癌信号通路,以了解淋巴瘤发生的潜在机制和介质,目标是确定用于治疗EBV相关恶性肿瘤的新型合理治疗靶点。

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