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Possible Novel Therapy for Malignant Gliomas with Secretable Trimeric TRAIL 英文参考文献
PossibleNovelTherapyforMalignantGliomaswith
SecretableTrimericTRAIL
MoonsupJeong1,2,Yong-SamKwon1,Soon-HyePark1,Chae-YoungKim1,Sin-SooJeun2 ,Kang-Won
Song3,YongKo3,PaulD.Robbins4,TimothyR.Billiar5,Byong-MoonKim1*,Dai-WuSeol5,6,7*
1Biopharmaceutical Research Laboratories of Dong-A Pharmaceutical Co., Ltd., Kyunggi-Do, Korea, 2Department of Neurosurgery, The Catholic University of Korea,
Seoul, Korea, 3Department of Neurosurgery, Hanyang University Medical Center, Seoul, Korea, 4Department of Molecular Genetics and Biochemistry, University of
Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America, 5Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh,
Pennsylvania, United States of America, 6Department of Life Science, Kyungwon University, Kyunggi-Do, Korea, 7Gachon BioNano Research Institute, Kyungwon
University,Kyunggi-Do,Korea
Abstract
Malignant gliomas are the most common primary brain tumors. Despite intensive clinical investigation and many novel
therapeutic approaches, average survival for the patients with malignant gliomas is only about 1year. Tumor necrosis
factor-related apoptosis-inducing ligand (TRAIL) has shown potent and cancer-selective killing activity and drawn
considerableattentionasapromisingtherapyforcancers,butconcernsoverdeliveryandtoxicityhavelimitedprogress.We
have developed a secretable trimeric TRAIL (stTRAIL) and here evaluated the therapeutic potential of this stTRAIL-based
genetherapyinbraintumors.Anadenovirus(Ad-stTRAIL)deliveringstTRAILwasinjectedintointra-cranialhumanglioma
tumorsestablishedinnudemiceandtumorgrowthmonitoredusingthemagneticresonanceimaging(MRI).Ad-stTRAIL
genetherapyshowedpotenttumorsuppressoractivitywithnotoxicsideeffectsattherapeuticallyeffectivedoses.When
compared with 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a conventional therapy for malignant gliomas, Ad-stTRAIL
suppressed tumor growth more potently. The combination of Ad-stTRAIL and BCNU significantly in
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