Initial in vivo testing of TPO-receptor agonist eltrombopag in osteosarcoma patient-derived xenograft models by the pediatric preclinical testing consortium.
Initial in vivo testing of TPO-receptor agonist eltrombopag in osteosarcoma patient-derived xenograft models by the pediatric preclinical testing consortium.
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由儿科临床前试验联盟在骨肉瘤患者来源的异种移植模型中进行tpo受体激动剂埃曲巴格的初步体内试验。
DOI：
10.1080/08880018.2020.1802539
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发表时间：
2021-03
影响因子：
1.7
通讯作者：
Gorlick R
中科院分区：
文献类型：
--
作者：
Nevil G;Roth M;Gill J;Zhang W;Teicher B;Erickson SW;Gatto G;Smith M;Kolb EA;Gorlick R
艾曲泊帕是一种小分子血小板生成素受体激动剂，获批用于治疗再生障碍性贫血和慢性免疫性血小板减少症患者。它也是一种多价阳离子螯合剂，通过减少细胞内铁来抑制白血病细胞增殖。在5 mg/kg/天（中等剂量）和50 mg/kg/天（高剂量）剂量下，检测了艾曲泊帕对一组6个儿科临床前试验联盟骨肉瘤异种移植物的体内疗效。在6/6个模型中，中等剂量的艾曲泊帕未能显著改善无事件生存期（EFS）。在高剂量下，艾曲泊帕在2/2模型中显著延长了EFS，但效应量较小。所有测试的模型均表现出进行性疾病。虽然艾曲泊帕没有显著抑制骨肉瘤生长，但它也没有刺激肿瘤生长，这表明它可以安全地作为支持性治疗药物进行研究，以促进化疗后的血小板恢复。
Eltrombopag is a small molecule, thrombopoietin receptor agonist approved for the treatment of patients with aplastic anemia and chronic immune thrombocytopenia. It is also a polyvalent cation chelator and inhibits leukemia cell proliferation via reduction of intracellular iron. The in vivo efficacy of eltrombopag was tested against a panel of six Pediatric Preclinical Testing Consortium osteosarcoma xenografts at doses of 5 mg/kg/day (moderate dose) and 50 mg/kg/day (high dose). Eltrombopag, at moderate doses, failed to significantly improve event-free survival (EFS) in 6/6 models. At high doses, eltrombopag significantly prolonged EFS in 2/2 models, though the effect size was small. All models tested demonstrated progressive disease. While eltrombopag did not meaningfully inhibit osteosarcoma growth, it also did not stimulate tumor growth, suggesting it may be safely investigated as a supportive care agent to enhance platelet recovery post chemotherapy.
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艾曲波帕和改善难治性再生障碍性贫血的造血功能。
DOI：
10.1056/nejmoa1200931
发表时间：
2012-07-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Olnes MJ;Scheinberg P;Calvo KR;Desmond R;Tang Y;Dumitriu B;Parikh AR;Soto S;Biancotto A;Feng X;Lozier J;Wu CO;Young NS;Dunbar CE
通讯作者：
Dunbar CE
影响因子：
2.7
作者：
Mavroudi, Irene;Pyrovolaki, Katerina;Papadaki, Helen A.
通讯作者：
Papadaki, Helen A.
影响因子：
20.3
作者：
Vlachodimitropoulou E;Chen YL;Garbowski M;Koonyosying P;Psaila B;Sola-Visner M;Cooper N;Hider R;Porter J
通讯作者：
Porter J
影响因子：
8.8
作者：
Rokita, Jo Lynne;Rathi, Komal S.;Maris, John M.
通讯作者：
Maris, John M.
影响因子：
24.7
作者：
Frey, Noelle;Jang, Jun Ho;Strickland, Stephen
通讯作者：
Strickland, Stephen