Document Detail


Insulin-like growth factor-binding protein-7 (IGFBP7): a promising gene therapeutic for hepatocellular carcinoma (HCC).
MedLine Citation:
PMID:  23319057     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hepatocellular carcinoma (HCC) is a highly fatal disease mandating development of novel, targeted therapies to elicit prolonged survival benefit to the patients. Insulin-like growth factor-binding protein-7 (IGFBP7), a secreted protein belonging to the IGFBP family, functions as a potential tumor suppressor for HCC. In the present study, we evaluated the therapeutic efficacy of a replication-incompetent adenovirus expressing IGFBP7 (Ad.IGFBP7) in human HCC. Ad.IGFBP7 profoundly inhibited viability and induced apoptosis in multiple human HCC cell lines by inducing reactive oxygen species (ROS) and activating a DNA damage response (DDR) and p38 MAPK. In orthotopic xenograft models of human HCC in athymic nude mice, intravenous administration of Ad.IGFBP7 profoundly inhibited primary tumor growth and intrahepatic metastasis. In a nude mice subcutaneous model, xenografts from human HCC cells were established in both flanks and only left-sided tumors received intratumoral injection of Ad.IGFBP7. Growth of both left-sided injected tumors and right-sided uninjected tumors were markedly inhibited by Ad.IGFBP7 with profound suppression of angiogenesis. These findings indicate that Ad.IGFBP7 might be a potent therapeutic eradicating both primary HCC and distant metastasis and might be an effective treatment option for terminal HCC patients.
Authors:
Dong Chen; Ayesha Siddiq; Luni Emdad; Devaraja Rajasekaran; Rachel Gredler; Xue-Ning Shen; Prasanna K Santhekadur; Jyoti Srivastava; Chadia L Robertson; Igor Dmitriev; Elena A Kashentseva; David T Curiel; Paul B Fisher; Devanand Sarkar
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-15
Journal Detail:
Title:  Molecular therapy : the journal of the American Society of Gene Therapy     Volume:  21     ISSN:  1525-0024     ISO Abbreviation:  Mol. Ther.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-01     Completed Date:  2013-11-01     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  100890581     Medline TA:  Mol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  758-66     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics
Animals
Carcinoma, Hepatocellular / genetics,  metabolism*,  therapy*
Humans
Insulin-Like Growth Factor Binding Proteins / genetics,  metabolism*
Liver Neoplasms / genetics,  metabolism*,  therapy*
Male
Mice
Mice, Nude
Reactive Oxygen Species / metabolism
Xenograft Model Antitumor Assays
Grant Support
ID/Acronym/Agency:
P30 CA016059/CA/NCI NIH HHS; R01 CA134721/CA/NCI NIH HHS; R01 CA138540/CA/NCI NIH HHS; R01 CA138540/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Insulin-Like Growth Factor Binding Proteins; 0/Reactive Oxygen Species; 0/insulin-like growth factor binding protein-related protein 1
Comments/Corrections

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