Sarek Grzegorz, Ojala Päivi M
Genome-Scale Biology Program, Biomedicum Helsinki, Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
Cell Cycle. 2007 Sep 15;6(18):2205-9. doi: 10.4161/cc.6.18.4730. Epub 2007 Jul 10.
KSHV infection is the causative agent in three different tumor types: Kaposi's sarcoma, a plasmablastic variant of multicentric Castelman's disease and an AIDS-related form of B cell lymphoproliferative disorder called primary effusion lymphoma (PEL). PEL manifests as an effusion malignancy in Kaposi's sarcoma patients with advanced AIDS, but also occurs in HIV-negative individuals. PEL is a very aggressive disease, and currently there are no efficient therapies for treating PEL. In our recent paper we report that p53 reactivation by a small molecule inhibitor of p53-MDM2 interaction, Nutlin-3a, induces selective and massive apoptosis in PEL cells, and has striking anti-tumor activity in a mouse xenograft PEL model. In the light of current treatment regimens for PEL, we discuss here the benefits of using reactivation of the p53 pathway as a novel principle for the treatment of this virally induced highly aggressive malignancy.
卡波西肉瘤相关疱疹病毒（KSHV）感染是三种不同肿瘤类型的致病因子：卡波西肉瘤、多中心Castleman病的浆母细胞变异型以及一种与艾滋病相关的B细胞淋巴增殖性疾病，称为原发性渗出性淋巴瘤（PEL）。PEL在晚期艾滋病的卡波西肉瘤患者中表现为渗出性恶性肿瘤，但也发生于HIV阴性个体。PEL是一种极具侵袭性的疾病，目前尚无有效的治疗方法。在我们最近的论文中，我们报道了通过一种p53-MDM2相互作用的小分子抑制剂Nutlin-3a重新激活p53，可诱导PEL细胞发生选择性大量凋亡，并在小鼠异种移植PEL模型中具有显著的抗肿瘤活性。鉴于目前PEL的治疗方案，我们在此讨论将p53途径重新激活作为治疗这种病毒诱导的高度侵袭性恶性肿瘤的新原则的益处。
