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Preclinical Evaluation of UAB30 in Pediatric Renal and Hepatic Malignancies

机译：UAB30在小儿肾和肝恶性肿瘤中的临床前评估

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Rare tumors of solid organs remain some of the most difficult pediatric cancers to cure. These difficult tumors include rare pediatric renal malignancies, such as malignant rhabdoid kidney tumors (MRKT) and non-osseous renal Ewing sarcoma, and hepatoblastoma, a pediatric liver tumor that arises from immature liver cells. There are data in adult renal and hepatic malignancies demonstrating the efficacy of retinoid therapy. The investigation of retinoic acid therapy in cancer is not a new strategy, but the widespread adoption of this therapy has been hindered by toxicities. Our laboratory has been investigating a novel synthetic rexinoid, UAB30, which exhibits a more favorable side-effect profile. In this study, we hypothesized that UAB30 would diminish the growth of tumor cells from both rare renal and liver tumors in vitro and in vivo. We successfully demonstrated decreased cellular proliferation, invasion and migration, cell-cycle arrest, and increased apoptosis after treatment with UAB30. Additionally, in in vivo murine models of human hepatoblastoma or rare human renal tumors, there were significantly decreased tumor xenograft growth and increased animal survival after UAB30 treatment. UAB30 should be further investigated as a developing therapeutic in these rare and difficult-to-treat pediatric solid organ tumors. (C) 2016 AACR.
机译：罕见的实体器官肿瘤仍然是一些最难治愈的小儿癌症。这些困难的肿瘤包括罕见的小儿肾脏恶性肿瘤，例如恶性横纹肌肾肿瘤（MRKT）和非骨性尤因肉瘤，以及肝母细胞瘤，一种由未成熟肝细胞引起的小儿肝肿瘤。有成人肾和肝恶性肿瘤的数据证明了类维生素A疗法的功效。视黄酸疗法在癌症中的研究并不是一个新的策略，但是这种疗法的广泛使用已受到毒性的阻碍。我们的实验室一直在研究一种新型的合成类维生素UAB30，它具有更有利的副作用。在这项研究中，我们假设UAB30在体外和体内都会减少罕见的肾脏和肝脏肿瘤中肿瘤细胞的生长。我们成功地证明了用UAB30治疗后细胞增殖，侵袭和迁移，细胞周期停滞以及凋亡增加的减少。另外，在人肝母细胞瘤或罕见的人肾肿瘤的体内鼠模型中，UAB30处理后肿瘤异种移植物的生长显着降低，动物存活率提高。在这些罕见且难以治疗的小儿实体器官肿瘤中，应进一步研究UAB30作为发展中的治疗剂。 （C）2016 AACR。

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