Accession Number : ADB253499


Title :   Radiosensitization of Prostate Tumor Cells by Prenyltransferase Inhibitors


Descriptive Note : Annual rept. 1 Oct 1998-30 Sep 1999


Corporate Author : PENNSYLVANIA UNIV PHILADELPHIA


Personal Author(s) : Bernhard, Eric J.


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=ADB253499


Report Date : OCT 1999


Pagination or Media Count : 19


Abstract : The purpose of this study is to determine whether ras oncogene activation contributes to radiation resistance in prostate tumor cells, and if so, whether this resistance can be reversed through the use of prenyltransferase inhibitors. We have examined both rodent and human prostate tumor cell lines in vitro and determined that radiation resistance is increased in some, but not all lines after expression of activated ras is induced by transfection or transduction with activated ras oncogenes. In cells where expression of activated ras was linked to increased radiation resistance, treatment with farnesyltransferase inhibitors resulted in radiosensitization in vitro. Preliminary in vivo results show that farnesyltransferase inhibitors have the effect of reducing tumor hypoxia in prostate tumors expressing activated ras. Our results imply that prenyltransferase inhibitors may be useful in the treatment of prostate tumors when used in conjunction with radiation therapy. These inhibitors appear to affect both intrinsic cell radiosensitivity (as measured in vitro) as well as altering the tumor micro-environment (as shown in vivo).


Descriptors :   *PROSTATE CANCER , *CELLS(BIOLOGY) , *RADIATION TOLERANCE , *ONCOGENIC VIRUSES , *RADIATION RESISTANCE , *PROSTATE GLAND , RADIOTHERAPY , TRANSFECTION , IN VIVO ANALYSIS , MEDICAL SERVICES , HYPOXIA , IN VITRO ANALYSIS , NEOPLASMS , GENETICS


Subject Categories : ANATOMY AND PHYSIOLOGY
      MEDICINE AND MEDICAL RESEARCH
      RADIOBIOLOGY


Distribution Statement : APPROVED FOR PUBLIC RELEASE