Possible new therapeutic target for pancreatic cancer



Bismuth compounds have been used for centuries in medicine. The discovery of H. pylori in 1983 led to renewed interest in bismuth compounds, because these were found to successfully treat the infection in combination with antibiotics. However, in the 1970s bismuth salts, used at high doses for prolonged periods, were found to lead to neurotoxicity.

Full Post: Researchers assess safety of bismuth compounds for treatment peptic ulcer disease

A possible new therapeutic target for pancreatic cancer, the most lethal form of human cancer, has been identified in the proteins whose DNA recipe comes from gene, “Seven-In-Absentia,” according to researchers at the American Society for Cell Biology (ASCB) 48th Annual Meeting, Dec. 13-17, 2008 in San Francisco.

In their studies with the fruit fly, Drosophila melanogaster, at the Mayo Clinic College of Medicine in Minnesota, scientists found a link between the “Seven-In-Absentia” or SINA gene and the aggressive cellular transformation, oncogenesis and metastasis that characterize pancreatic cancer.

Scientists already knew that a mutation in the K-RAS gene underlies the abnormal, excessive cell growth of pancreatic cancer.

Because the mutated form of this growth-promoting gene is hyperactivated, a major signaling pathway that drives cell growth is in over-drive in most patients with this cancer.

The “Seven-In-Absentia-Homolog” (SIAH) protein seems to work as a check and balance mechanism in the K-RAS pathway by chewing up and turning off the excessive growth-promoting proteins produced by the hyperactive, mutated form of the gene, says Amy Tang whose Mayo lab conducted the research.

“By attacking the SIAH-based protein degrading machinery, we block tumor formation in one of the most aggressive human cancers cells known,” she reports.

Because of these results, SIAH may be an attractive new target for novel anti-RAS and anti-cancer therapy in pancreatic cancer, the median survival of which is only six months, and the mortality rate is 95 percent.

By inhibiting SIAH function, Tang and her colleagues were able to completely abolish both tumorigenesis and metastasis of human pancreatic cancer cells that were growing in “nude” mice that have immune system deficits that prevent them from rejecting foreign tissue.

“It is likely to move into the clinical setting for study as an interventional treatment in pancreatic cancer in human patients,” Tang says, referring to the SIAH inhibition.

SINA produces a family of RING domain E3 ubiquitin ligases. In all creatures, ubiquitin ligases turn cell pathways on or off by degrading proteins.

In humans, the SIAH ubiquitin ligases sit smack in the middle of the molecular pathway that leads to pancreatic cancer, Tang explains.

The Tang lab found that SIAH ubiquitin ligases were specifically and markedly “upregulated” in pancreatic cancers.

The increased SIAH expression seemed to correlate with increased grades and aggressiveness of pancreatic cancer. Moreover, SIAH is normally required for mammalian K-RAS signal transduction.

http://www.ascb.org/

Link




Cancer researchers at the Max Delbr?nter for Molecular Medicine (MDC) Berlin-Buch and the Charité - Universit? Medizin Berlin (Germany) have identified a gene which enables them to predict for the first time with high probability if colon cancer is going to metastasize. Assistant Professor Dr. Ulrike Stein, Professor Peter M. Schlag, and Professor Walter Birchmeier

Full Post: Scientists find gene that is a powerful predictor of colon cancer metastasis



A research team from the University of California, San Diego School of Medicine has identified a protein produced by cancerous lung epithelial cells that enhances metastasis by stimulating the activity of inflammatory cells. Their findings, to be published in the January 1 issue of the journal Nature, explain how advanced cancer cells usurp components of

Full Post: Lung cancer cells activate inflammation to induce metastasis



University of Texas Medical Branch at Galveston researchers have identified a promising new target in the battle against colorectal cancer - a biochemical pathway critical to the spread of tumors to new locations in the body. If this “survival pathway” can be successfully blocked under clinical conditions, the result would be a much-needed new therapy

Full Post: Discovery of promising new target in the battle against colorectal cancer



Ovarian cancer cells are “addicted” to a family of proteins produced by the notorious oncogene, MYC. Blocking these Myc proteins halts cell proliferation in the deadliest cancer of the female reproductive system, according to a presentation by University of California, Berkeley scientists at the American Society for Cell Biology (ASCB) 48th Annual Meeting, Dec. 13-17,

Full Post: Blocking Myc proteins stops ovarian cancer cell cycle in its tracks



Ovarian cancer cells are “addicted” to a family of proteins produced by the notorious oncogene, MYC, and blocking these Myc proteins halts cell proliferation in the deadliest cancer of the female reproductive system, according to a presentation by University of California, Berkeley scientists at the American Society for Cell Biology (ASCB) 48th Annual Meeting, Dec.

Full Post: Researchers stop ovarian cancer cell cycle in its tracks