Regulatory sequences of H19 and IGF2 genes in DNA-based therapy of colorectal rat liver metastases.

Ohana, Patricia and Schachter, Pinhas and Ayesh, Basim and Mizrahi, Aya and Birman, Tatiana and Schneider, Tamar and Matouk, Imad and Ayesh, Suhail and Kuppen, Peter J K and de Groot, Nathan and Czerniak, Abraham and Hochberg, Abraham Regulatory sequences of H19 and IGF2 genes in DNA-based therapy of colorectal rat liver metastases. The Journal of Gene Medicine.

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BACKGROUND Malignant tumors of the liver are among the most common causes of cancer-related death throughout the world. Current therapeutic approaches fail to control the disease in most cases. This study seeks to explore the potential utility of transcriptional regulatory sequences of the H19 and insulin growth factor 2 (IGF2) genes for directing tumor-selective expression of a toxin gene (A fragment of diphtheria toxin), delivered by non-viral vectors. METHODS The therapeutic potential of the toxin vectors driven by the H19 and the IGF2-P3 regulatory sequences was tested in a metastatic model of rat CC531 colon carcinoma in liver. RESULTS Intratumoral injection of these vectors into colon tumors implanted in the liver of rats induced an 88% and a 50% decrease respectively in the median tumor volume as compared with the control groups. This therapeutic action was accompanied by increased necrosis of the tumor. Importantly, no signs of toxicity were detected in healthy animals after their treatment by the toxin expression vectors. CONCLUSIONS DT-A was preferentially expressed in liver metastases after being transfected with H19 or IGF2-P3 promoter-driven DT-A expression plasmids, causing a very significant inhibition of tumor growth as a result of its cytotoxic effect. Our findings strongly support the feasibility of our proposed therapeutic strategy, which may contribute to open new gene therapeutic options for human liver metastases.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Medicine, Health and Life Sciences > School of Biological Sciences
Depositing User: د. باسم محمد حسين عايش
Date Deposited: 25 Mar 2018 16:40
Last Modified: 25 Mar 2018 16:40

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