Regression of solid tumors by engineered overexpression of von Hippel-Lindau tumor suppressor protein and antisense hypoxia-inducible factor-1alpha Sun, X., Kanwar, J.R., Leung, E., Vale, M. and Krissansen, G.W. 2003, Regression of solid tumors by engineered overexpression of von Hippel-Lindau tumor suppressor protein and antisense hypoxia-inducible factor-1alpha, Gene Therapy, vol. 10, no. 25, pp. 2081-2089, doi: 10.1038/sj.gt.3302118. Attached Files Name Description MIMEType Size Downloads Title Regression of solid tumors by engineered overexpression of von Hippel-Lindau tumor suppressor protein and antisense hypoxia-inducible factor-1alpha Author(s) Sun, X. Kanwar, J.R. orcid.org/0000-0003-3728-9568 Leung, E. Vale, M. Krissansen, G.W. Journal name Gene Therapy Volume number 10 Issue number 25 Start page 2081 End page 2089 Publisher Nature Publishing Group Place of publication London, England Publication date 2003-12 ISSN 0969-7128 1476-5462 Summary The von Hippel-Lindau tumor suppressor protein (pVHL) suppresses tumor formation by binding the alpha subunits of hypoxia-inducible factors (HIFs) responsible for stimulating tumor angiogenesis and glycolysis, targeting them for ubiquitination and proteasomal destruction. Loss of pVHL leads to the development of sporadic renal cell carcinomas (RCCs). In the present study, we sought to determine whether engineered overexpression of pVHL in tumors other than RCC can inhibit tumor growth, either as a monotherapy, or in combination with antisense HIF-1alpha therapy. Intratumoral injection of subcutaneous EL-4 thymic lymphomas with an expression plasmid encoding pVHL resulted in the downregulation of HIF-1alpha and vascular endothelial growth factor (VEGF). There was a concomitant reduction in tumor angiogenesis and increased tumor cell apoptosis due in part to downregulation of Bcl-2 expression. VHL therapy resulted in the complete regression of small (0.1 cm diameter) tumors whereas, in contrast, large (0.4 cm diameter) EL-4 tumors were only slowed in their growth. Nevertheless, large tumors completely regressed in response to intratumoral injection of a combination of antisense HIF-1alpha and VHL plasmids. Combination therapy resulted in increased losses of HIF-1alpha, VEGF, and tumor blood vessels, and increased tumor cell apoptosis. These novel results suggest that synergistic therapies that simultaneously block the expression or function of HIF-1alpha, and enhance the expression or function of VHL may be beneficial in the treatment of cancer. Language eng DOI 10.1038/sj.gt.3302118 Field of Research 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies) 111204 Cancer Therapy (excl Chemotherapy and Radiation Therapy) HERDC Research category C1.1 Refereed article in a scholarly journal Copyright notice ©2003, Nature Publishing Group Persistent URL http://hdl.handle.net/10536/DRO/DU:30026570 Document type: Journal Article Collections: Faculty of Science, Engineering and Built Environment Institute of Biotechnology Related Links Link Description Connect to published version Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Versions Version Filter Type Thu, 01 Apr 2010, 14:00:04 EST Tue, 13 Apr 2010, 15:23:02 EST Sun, 18 Apr 2010, 12:25:08 EST Thu, 07 Nov 2019, 13:36:48 EST Mon, 25 Apr 2022, 08:36:50 EST Filtered Full Citation counts:   Cited 25 times in TR Web of Science Cited 33 times in Scopus Search Google Scholar Access Statistics: 868 Abstract Views, 0 File Downloads  -  Detailed Statistics Created: Thu, 01 Apr 2010, 14:00:01 EST by Jagat Kanwar