Accession Number : ADA476159


Title :   Killing Prostate Cancer Cells and Endothelial Cells with a VEGF-Triggered Cell Death Receptor


Descriptive Note : Final rept. 14 Jan 2002-13 May 2005


Corporate Author : CALIFORNIA UNIV SAN FRANCISCO


Personal Author(s) : Quinn, Timothy P.


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=ADA476159


Report Date : JUN 2005


Pagination or Media Count : 135


Abstract : The goal of this project was to test a novel chimeric cell death receptor (termed R2Fas) that is triggered by vascular endothelial growth factor (VEGF), as a means to kill prostate cancer cells and vascular endothelial cells. The scope of this project involved: (i) creating adenoviral reagents to express the R2Fas receptor in prostate cancer cells and endothelial cells; (ii) determining if the R2Fas receptor kills cells in a VEGF-dependent manner; and (iii) identifying methods for increasing the killing activity of R2Fas. The major findings were: (i) we generated replication-defective adenoviral reagents to express R2Fas as well as control adenoviruses; (ii) we demonstrated that adenoviral-mediated expression of R2Fas in prostate cancer cells that overexpress VEGF activates apoptotic signaling and induces cell death; (iii) we demonstrated that adenoviral-mediated expression of R2Fas in human endothelial cell is non-toxic, but rendered the cells sensitive to killing when treated with VEGF; and (iv) we demonstrated that R2Fas-mediated apoptosis can be potentiated by addition of several pharmacologic agents, including camptothecin, etoposide, taxol, doxorubicin, cisplatin, and BisVIII.


Descriptors :   *DEATH , *CELLS(BIOLOGY) , *RECEPTOR SITES(PHYSIOLOGY) , *ENDOTHELIUM , *APOPTOSIS , *PROSTATE CANCER , CONTROL , KILL PROBABILITIES , GROWTH(PHYSIOLOGY) , ADENOVIRUSES , CARDIOVASCULAR SYSTEM , HUMANS , CHEMICAL AGENTS , DRUGS


Subject Categories : ANATOMY AND PHYSIOLOGY
      MEDICINE AND MEDICAL RESEARCH


Distribution Statement : APPROVED FOR PUBLIC RELEASE