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James O. Park, Carlos A. Lopez, Vinay K. Gupta, Charles K. Brown, Helena J. Mauceri, Thomas E. Darga, Abdullah Manan, Samuel Hellman, Mitchell C. Posner, Donald W. Kufe, Ralph R. Weichselbaum
J Clin Invest. 2002;
110(3):403
doi:10.1172/JCI15548
Abstract |
Full text
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I
onizing radiation (IR) and radical oxygen intermediates (ROIs) activate the early growth response-1 (Egr1) promoter through specific cis-acting sequences termed CArG elements. Ad.Egr.TNF.11D, a replication-deficient adenoviral vector containing CArG elements cloned upstream of the cDNA for human recombinant TNF-α was used to treat human esophageal adenocarcinoma and rat colon adenocarcinoma cells in culture and as xenografts in athymic nude mice. Cisplatin, a commonly used chemotherapeutic agent, causes tumor cell death by producing DNA damage and generating ROIs. The present studies demonstrate induction of TNF-α production in tumor cells and xenografts treated with the combination of Ad.Egr.TNF.11D and cisplatin. The results show that the Egr1 promoter is induced by cisplatin and that this induction is mediated in part through the CArG elements. These studies also demonstrate an enhanced antitumor response without an increase in toxicity following treatment with Ad.Egr.TNF.11D and cisplatin, compared with either agent alone. Chemo-inducible cancer gene therapy thus provides a means to control transgene expression while enhancing the effectiveness of commonly used chemotherapeutic agents.
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(13)
| Title and authors |
Publication |
Year |
Translation of the radio- and chemo-inducible TNFerade vector to the treatment of human cancers
R R Weichselbaum, D Kufe
|
Cancer Gene Ther
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2009 |
Combination of human tumor necrosis factor-alpha (hTNF-α) gene delivery with gemcitabine is effective in models of pancreatic cancer
S R Murugesan, C R King, R Osborn, W R Fairweather, E M O'Reilly, M O Thornton, L L Wei
|
Cancer Gene Ther
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2009 |
Synergistic effect of 15-lipoxygenase 2 and radiation in killing head-and-neck cancer
Q Yang, Y Feng, C J Schultz, X A Li, H Wu, D Wang
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Cancer Gene Ther
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2008 |
Development of a second-generation oncolytic Herpes simplex virus expressing TNFα for cancer therapy
Z. Q. Han, M. Assenberg, B. L. Liu, Y. B. Wang, G. Simpson, S. Thomas, R. S. Coffin
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J. Gene Med.
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2007 |
Local gene delivery of tumor necrosis factor alpha can impact primary tumor growth and metastases through a host-mediated response
Randall S. MacGill, Thomas A. Davis, Jennifer Macko, Helena J. Mauceri, Ralph R. Weichselbaum, C. Richter King
|
Clin Exp Metastasis
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2007 |
Resveratrol is an effective inducer of CArG-driven TNF-α gene therapy
K A Bickenbach, J Veerapong, M Y Shao, H J Mauceri, M C Posner, S J Kron, R R Weichselbaum
|
Cancer Gene Ther
|
2007 |
Gene therapy vectors containing CArG elements from the Egr1 gene are activated by neutron irradiation, cisplatin and doxorubicin
Olga Greco, Tanya M Powell, Brian Marples, Michael C Joiner, Simon D Scott
|
Cancer Gene Ther
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2005 |
Chemoinducible gene therapy
James J. Mezhir, Hank Schmidt, Bakhtiar Yamini, Neil N. Senzer, Mitchell C. Posner, Donald W. Kufe, Ralph R. Weichselbaum
|
Anti-Cancer Drugs
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2005 |
Ionizing radiation: a genetic switch for cancer therapy
J J Mezhir, K D Smith, M C Posner, N Senzer, B Yamini, D W Kufe, R R Weichselbaum
|
Cancer Gene Ther
|
2005 |
c-Abl regulates Early Growth Response Protein (EGR1) in response to oxidative stress
Jeremy R Stuart, Hidehiko Kawai, Kelvin K C Tsai, Eric Y Chuang, Zhi-Min Yuan
|
Oncogene
|
2005 |
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