Warning: Undefined variable $zfal in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Deprecated: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 530
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 531
 
English Wikipedia
Nephropedia Template TP (
Twit Text
DeepDyve
Pubget Overpricing |  
lüll
Eradication of therapy-resistant human prostate tumors using a cancer terminator virus Sarkar D; Lebedeva IV; Su ZZ; Park ES; Chatman L; Vozhilla N; Dent P; Curiel DT; Fisher PBCancer Res 2007[Jun]; 67 (11): 5434-42Terminal prostate cancer is refractory to conventional anticancer treatments because of frequent overexpression of antiapoptotic proteins Bcl-2 and/or Bcl-x(L). Adenovirus-mediated delivery of melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24), a secreted cytokine having cancer-selective apoptosis-inducing properties, profoundly inhibits prostate cancer cell growth. However, forced overexpression of Bcl-2 or Bcl-x(L) renders prostate cancer cells resistant to Ad.mda-7. We constructed a conditionally replication-competent adenovirus in which expression of the adenoviral E1A gene, necessary for replication, is driven by the cancer-specific promoter of progression elevated gene-3 (PEG-3) and which simultaneously expresses mda-7/IL-24 in the E3 region of the adenovirus (Ad.PEG-E1A-mda-7), a cancer terminator virus (CTV). This CTV generates large quantities of MDA-7/IL-24 as a function of adenovirus replication uniquely in cancer cells. Infection of Ad.PEG-E1A-mda-7 (CTV) in normal prostate epithelial cells and parental and Bcl-2- or Bcl-x(L)-overexpressing prostate cancer cells confirmed cancer cell-selective adenoviral replication, mda-7/IL-24 expression, growth inhibition, and apoptosis induction. Injecting Ad.PEG-E1A-mda-7 (CTV) into xenografts derived from DU-145-Bcl-x(L) cells in athymic nude mice completely eradicated not only primary tumors but also distant tumors (established in the opposite flank), thereby implementing a cure. These provocative findings advocate potential therapeutic applications of this novel virus for advanced prostate cancer patients with metastatic disease.|Adenoviridae/genetics[MESH]|Adenovirus E1A Proteins/biosynthesis/genetics[MESH]|Animals[MESH]|Antigens, Differentiation/genetics[MESH]|Cell Line, Tumor[MESH]|Genetic Therapy/*methods[MESH]|Humans[MESH]|Interleukins/biosynthesis/*genetics[MESH]|Male[MESH]|Mice[MESH]|Mice, Nude[MESH]|Neovascularization, Pathologic/genetics/therapy/virology[MESH]|Oncolytic Virotherapy/methods[MESH]|Promoter Regions, Genetic[MESH]|Prostatic Neoplasms/blood supply/genetics/*therapy/virology[MESH]|Proto-Oncogene Proteins/genetics[MESH]|Xenograft Model Antitumor Assays[MESH]|bcl-X Protein/biosynthesis/genetics[MESH] |
