Increased VEGF levels induced by anti-VEGF treatment are independent of tumor burden in colorectal carcinomas in mice

Gene Therapy
Volker SchmitzC Qian

Abstract

Inhibition of vascular endothelial growth factor (VEGF) by gene transfer techniques was effectively applied to control experimental tumor growth, whereas effects on systemic VEGF levels had not been investigated. Therefore, we evaluated the effect of VEGF inhibition by adenoviral-mediated gene delivery of a dominant-negative soluble fragment of FLK-1 (sFlk-1) on systemic VEGF levels, organ-specific VEGF-RNA expression and antitumor efficacy in a murine colorectal cancer (CRC) tumor model. Vector function of AdsFlk-1 was shown by Western blot analysis and transgene expression was documented over a time period of 42 days in the serum of treated mice. Although cell supernatant of CT26 cells contained considerable levels of VEGF, systemic VEGF levels in the serum of tumor-bearing mice remained unaffected. Interestingly, mice that were systemically treated with AdsFlk-1 showed a strong upraise of circulating VEGF, whereas VEGF remained at background levels in the control. Vascular endothelial growth factor was increased not only in tumor bearing but also in healthy, tumor-free mice. Vascular endothelial growth factor determination in liver tissue homogenates showed a 16.5-fold upraise in AdsFlk-1-treated animals as compared to the A...Continue Reading

References

Jul 1, 1995·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·C QianJ Prieto
Apr 1, 1993·The American Journal of Physiology·W T MonacciE H Oldfield
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·H H Marti, W Risau
Mar 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·C J KuoR C Mulligan
Jul 5, 2002·Nature·Anton P McCaffreyMark A Kay
Nov 1, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Harold F Dvorak
Dec 24, 2002·Cancer Biology & Therapy·Christian M BeckerBruce R Zetter
Apr 2, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·M Gabriela KramerJesus Prieto
Sep 19, 2003·Trends in Biochemical Sciences·Michael J CrossLena Claesson-Welsh
Mar 12, 2005·The Lancet Oncology·Ed Susman
May 26, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Esther RaskopfVolker Schmitz
Jan 27, 2006·The American Journal of Pathology·Arindel S R MaharajPatricia A D'Amore

❮ Previous
Next ❯

Citations

May 23, 2009·Arteriosclerosis, Thrombosis, and Vascular Biology·Tony E WalshePatricia A D'Amore
Aug 12, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Alexandre BozecGérard Milano
Oct 11, 2008·Journal of Hepatology·Esther RaskopfVolker Schmitz
Jul 22, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ravindra GujarPradip Sen

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.