ArticleCancer gene therapy2003
Gene therapy for hepatocellular carcinoma using non-viral vectors composed of bis guanidinium-tren-cholesterol and plasmids encoding the tissue inhibitors of metalloproteinases TIMP-2 and TIMP-3.
Article in Cancer gene therapy, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
8 citing papers in PubMed, 27 citations in OpenAlex.
- Tissue inhibitor of metalloproteinase-3 expression affects clinicopathological features and prognosis of aflatoxin B1-related hepatocellular carcinoma.World journal of hepatology · 2024Article
- Article
- Comparison of hepatic and serum lipid signatures in hepatocellular carcinoma patients leads to the discovery of diagnostic and prognostic biomarkers.Oncotarget · 2018Article
- TIMP-3 -1296 T>C and TIMP-4 -55 T>C gene polymorphisms play a role in the susceptibility of hepatocellular carcinoma among women.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Inhibition of tumor growth and induction of apoptosis in prostate cancer cell lines by overexpression of tissue inhibitor of matrix metalloproteinase-3.Cancer gene therapy · 2010Article
- "Buy one get one free": armed viruses for the treatment of cancer cells and their microenvironment.Current gene therapy · 2009Review
- Management of hepatocellular carcinoma.Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract · 2006Review
- Inhibition of human leukemia xenograft in nude mice by adenovirus-mediated tissue inhibitor of metalloproteinase-3.Leukemia · 2006Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metalloproteinases (MMPs) and their natural inhibitors (TIMPs) contribute to the regulation of tumor microenvironment. Their expressions are deregulated in almost all human cancers. We report a novel approach to gene therapy of hepatocellular carcinoma (HCC), using repeated injections of DNA plasmids encoding the tissue inhibitors of metalloproteinases (TIMPs) TIMP-2 or TIMP-3, and a novel competent formulation of gene transfer based on nontoxic cationic cholesterol derivatives. The new gene delivery system was efficient in demonstrating the antitumor efficiency of TIMP-2 or TIMP-3 in inhibiting tumor growth of human HuH7 HCC cells xenografted into nude mice. We show, for the first time, an in vivo effect of TIMP-3 in delaying HCC tumor growth. No treatment-related toxicity was noted. An inhibition of angiogenesis and tumor necrosis accompanied the inhibitory effects of TIMP-2 or TIMP-3 on tumor expansion and invasion. We also report a bystander effect produced by transfected HuH7 tumor cells mixed with untransfected cells in 1:1 ratio in culture that resulted in killing 98% of cells within 96 h. In addition, the soluble forms of TIMP-2 and TIMP-3 expressed by transfected cells exerted a cytotoxic effect on untransfected HuH7 cell cultures. Taken together, these results demonstrate the potential efficacy of repeated treatment of secreted TIMP-2 and TIMP-3 for the design of nonviral gene therapy for hepatocarcinoma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.