非免疫抑制性FTY720衍生物OSU-2S介导犬B细胞淋巴瘤中活性氧介导的细胞毒性。
Non-immunosuppressive FTY720-derivative OSU-2S mediates reactive oxygen species-mediated cytotoxicity in canine B-cell lymphoma.
作者信息
Mani R, Yan R, Mo X, Chen C-S, Phelps M A, Klisovic R, Byrd J C, Kisseberth W C, London C A, Muthusamy N
机构信息
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
出版信息
Vet Comp Oncol. 2017 Sep;15(3):1115-1118. doi: 10.1111/vco.12221. Epub 2016 May 2.
OSU-2S is a FTY720 (Fingolimod) derivative that lacks immunosuppressive properties but exhibits strong anti-tumour activity in several haematological and solid tumour models. We have recently shown OSU-2S to mediate potent cytotoxicity in human mantle cell lymphoma cell lines and primary cells. We report here the pre-clinical activity of OSU-2S in spontaneous B-cell lymphoma of dogs which shares many characteristics of human lymphoma. OSU-2S mediated apoptosis in canine B-cell lines and primary B-cell lymphoma cells obtained from spontaneous lymphoma bearing dogs. OSU-2S induced reactive oxygen species (ROS) in canine lymphoma cells and inhibition of ROS partially rescued OSU-2S-mediated cell death. These studies provide a rational basis for the use of spontaneous lymphoma in pet dogs as a preclinical large animal model for the development of OSU-2S as small molecule for treating people and dogs with lymphoma.
OSU-2S是一种FTY720（芬戈莫德）衍生物，它缺乏免疫抑制特性，但在几种血液学和实体瘤模型中表现出强大的抗肿瘤活性。我们最近发现OSU-2S在人套细胞淋巴瘤细胞系和原代细胞中介导强效细胞毒性。我们在此报告OSU-2S在犬自发性B细胞淋巴瘤中的临床前活性，犬自发性B细胞淋巴瘤与人类淋巴瘤有许多共同特征。OSU-2S介导犬B细胞系和从患有自发性淋巴瘤的犬获得的原代B细胞淋巴瘤细胞凋亡。OSU-2S在犬淋巴瘤细胞中诱导活性氧（ROS），抑制ROS可部分挽救OSU-2S介导的细胞死亡。这些研究为将宠物犬的自发性淋巴瘤作为临床前大动物模型用于开发OSU-2S这种治疗人和犬淋巴瘤的小分子药物提供了合理依据。
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