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
Molecular target-based therapy of pancreatic cancer Lebedeva IV; Sarkar D; Su ZZ; Gopalkrishnan RV; Athar M; Randolph A; Valerie K; Dent P; Fisher PBCancer Res 2006[Feb]; 66 (4): 2403-13Pancreatic cancer is genetically complex, and without effective therapy. Mutations in the Kirsten-ras (K-ras) oncogene occur early and frequently (approximately 90%) during pancreatic cancer development and progression. In this context, K-ras represents a potential molecular target for the therapy of this highly aggressive cancer. We now show that a bipartite adenovirus expressing a novel cancer-specific apoptosis-inducing cytokine gene, mda-7/interleukin-24 (IL-24), and a K-ras AS gene, but not either gene alone, promotes growth suppression, induction of apoptosis, and suppression of tumor development mediated by K-ras mutant pancreatic cancer cells. Equally, the combination of an adenovirus expressing mda-7/IL-24 and pharmacologic and genetic agents simultaneously blocking K-ras or downstream extracellular regulated kinase 1/2 signaling also promotes similar inhibitory effects on the growth and survival of K-ras mutant pancreatic carcinoma cells. This activity correlates with the reversal of a translational block in mda-7/IL-24 mRNA in pancreatic cancer cells that limits message association with polysomes, thereby impeding translation into protein. Our study provides support for a "dual molecular targeted therapy" involving oncogene inhibition and selective cancer apoptosis-inducing gene expression with potential for effectively treating an invariably fatal cancer.|*Genes, ras[MESH]|Adenoviridae/genetics[MESH]|Animals[MESH]|Apoptosis/genetics[MESH]|Cell Growth Processes/genetics[MESH]|Cell Line, Tumor[MESH]|Genetic Therapy/*methods[MESH]|Humans[MESH]|Interleukins/*genetics[MESH]|Mice[MESH]|Mice, Nude[MESH]|Mitogen-Activated Protein Kinases/metabolism[MESH]|Pancreatic Neoplasms/*genetics/pathology/*therapy[MESH]|RNA, Messenger/biosynthesis/genetics[MESH]|Signal Transduction/genetics[MESH]|Xenograft Model Antitumor Assays[MESH] |
