Adenoviral (full-length) Apo2L/TRAIL gene transfer is an ineffective treatment strategy for malignant glioma.

作者: Ulrike Naumann , Robert Waltereit , Jörg B. Schulz , Michael Weller

DOI: 10.1023/A:1021248329980

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摘要: Death ligand-mediated apoptosis is a promising strategy of gene therapy for human malignant glioma. We here report that the infection glioma cell lines with an adenoviral vector encoding full length Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Ad-Apo2L/TRAIL) results in strong Apo2L/TRAIL transgene expression and release full-length into culture medium. However, Ad-Apo2L/TRAIL poor inducer death, even presence inhibitors protein synthesis, which are sensitive to soluble recombinant His-tagged (amino acids 114-281). Moreover, transfer inhibits Apo2L/TRAIL-induced apoptosis, strongly suggesting adenovirally encoded not suitable molecule cancer therapy. This study has important implications future development therapeutic strategies aiming at death receptor activation refractory cancers such as

参考文章(20)
Hartwig Wolburg, Wolfgang Wick, Gesa Rascher, Mathias Bähr, Ulrike Naumann, Emmanuel Conseiller, Michael Weller, Sebastian Kügler, Jörg B. Schulz, Chimeric tumor suppressor 1, a p53-derived chimeric tumor suppressor gene, kills p53 mutant and p53 wild-type glioma cells in synergy with irradiation and CD95 ligand. Cancer Research. ,vol. 61, pp. 5833- 5842 ,(2001)
Minji Jo, Tae-Hyoung Kim, Dai-Wu Seol, James E. Esplen, Kenneth Dorko, Timothy R. Billiar, Stephen C. Strom, Apoptosis induced in normal human hepatocytes by tumor necrosis factor-related apoptosis-inducing ligand Nature Medicine. ,vol. 6, pp. 564- 567 ,(2000) , 10.1038/75045
M. Simons, S. Beinroth, M. Gleichmann, P. Liston, R. G. Korneluk, A. E. MacKenzie, M. Bähr, T. Klockgether, G. S. Robertson, M. Weller, J. B. Schulz, Adenovirus‐Mediated Gene Transfer of Inhibitors of Apoptosis Proteins Delays Apoptosis in Cerebellar Granule Neurons Journal of Neurochemistry. ,vol. 72, pp. 292- 301 ,(1999) , 10.1046/J.1471-4159.1999.0720292.X
Wilfried Roth, Stefan Isenmann, Ulrike Naumann, Sebastian Kügler, Mathias Bähr, Johannes Dichgans, Avi Ashkenazi, Michael Weller, Locoregional Apo2L/TRAIL eradicates intracranial human malignant glioma xenografts in athymic mice in the absence of neurotoxicity. Biochemical and Biophysical Research Communications. ,vol. 265, pp. 479- 483 ,(1999) , 10.1006/BBRC.1999.1693
Robert Nitsch, Ingo Bechmann, Rudolf A Deisz, Dorit Haas, Thomas N Lehmann, Uwe Wendling, Frauke Zipp, Human brain-cell death induced by tumour-necrosis-factor-related apoptosis-inducing ligand (TRAIL) The Lancet. ,vol. 356, pp. 827- 828 ,(2000) , 10.1016/S0140-6736(00)02659-3
Michael Weller, Ann M. Marini, Steven M. Paul, Niacinamide blocks 3-acetylpyridine toxicity of cerebellar granule cells in vitro Brain Research. ,vol. 594, pp. 160- 164 ,(1992) , 10.1016/0006-8993(92)91043-E
Johannes Rieger, Ulrike Naumann, Tamara Glaser, Avi Ashkenazi, Michael Weller, APO2 ligand: a novel lethal weapon against malignant glioma? FEBS Letters. ,vol. 427, pp. 124- 128 ,(1998) , 10.1016/S0014-5793(98)00409-8
Michael Weller, Paul Kleihues, Johannes Dichgans, Hiroko Ohgaki, CD95 ligand: lethal weapon against malignant glioma? Brain Pathology. ,vol. 8, pp. 285- 293 ,(2006) , 10.1111/J.1750-3639.1998.TB00154.X