弥漫性脑桥内生型胶质瘤中功能定义的治疗靶点。
Functionally defined therapeutic targets in diffuse intrinsic pontine glioma.
作者信息
Grasso Catherine S, Tang Yujie, Truffaux Nathalene, Berlow Noah E, Liu Lining, Debily Marie-Anne, Quist Michael J, Davis Lara E, Huang Elaine C, Woo Pamelyn J, Ponnuswami Anitha, Chen Spenser, Johung Tessa B, Sun Wenchao, Kogiso Mari, Du Yuchen, Qi Lin, Huang Yulun, Hütt-Cabezas Marianne, Warren Katherine E, Le Dret Ludivine, Meltzer Paul S, Mao Hua, Quezado Martha, van Vuurden Dannis G, Abraham Jinu, Fouladi Maryam, Svalina Matthew N, Wang Nicholas, Hawkins Cynthia, Nazarian Javad, Alonso Marta M, Raabe Eric H, Hulleman Esther, Spellman Paul T, Li Xiao-Nan, Keller Charles, Pal Ranadip, Grill Jacques, Monje Michelle
机构信息
Center for Spatial Systems Biomedicine, Department of Molecular and Medical Genetics, Oregon Health &Science University (OHSU), Portland, Oregon, USA.
1] Department of Neurology, Stanford University, Stanford, California, USA. [2] Department of Neurosurgery, Stanford University, Stanford, California, USA. [3] Department of Pediatrics, Stanford University, Stanford, California, USA. [4] Department of Pathology, Stanford University, Stanford, California, USA. [5] Present addresses: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Y.T.) and Department of Neurosurgery, The First Affiliated Hospital of Suzhou University, Suzhou, China (Y.H.).
出版信息
Nat Med. 2015 Jun;21(6):555-9. doi: 10.1038/nm.3855. Epub 2015 May 4.
Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood cancer. We performed a chemical screen in patient-derived DIPG cultures along with RNA-seq analyses and integrated computational modeling to identify potentially effective therapeutic strategies. The multi-histone deacetylase inhibitor panobinostat demonstrated therapeutic efficacy both in vitro and in DIPG orthotopic xenograft models. Combination testing of panobinostat and the histone demethylase inhibitor GSK-J4 revealed that the two had synergistic effects. Together, these data suggest a promising therapeutic strategy for DIPG.
弥漫性脑桥内在型胶质瘤（DIPG）是一种致命的儿童癌症。我们在源自患者的DIPG培养物中进行了化学筛选，并结合RNA测序分析和综合计算建模，以确定潜在有效的治疗策略。多组蛋白脱乙酰酶抑制剂帕比司他在体外和DIPG原位异种移植模型中均显示出治疗效果。帕比司他与组蛋白去甲基化酶抑制剂GSK-J4的联合测试表明，二者具有协同作用。这些数据共同表明了一种针对DIPG的有前景的治疗策略。
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