Discovery of gene will likely lead to new treatments for inflammatory diseases, cancer

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Discovery of gene will likely lead to new treatments for inflammatory

diseases, cancer

(Boston) -- In a paper featured today in Proceedings of the National

Academy of Science (PNAS), researchers from Boston University School of

Dental Medicine report the discovery of a new gene, STAT6(, that

helps regulate production of the potentially deadly tumor necrosis

factor alpha (TNF-alpha) cytokine. TNF-alpha is involved in

inflammatory disorders such as Crohn's disease, rheumatoid arthritis,

and irritable bowel syndrome. The paper is the first by a dental school

researcher to be chosen as a featured article in PNAS.

The new gene also regulates vascular endothelial growth factor (VEGF),

which is responsible for new blood vessels. Blocking excess amounts of

VEGF has already led to the cancer therapeutic Avastin; STAT6( works

through a different mechanism and thus will offer new opportunities for

treating cancer. The researchers are publishing this finding in a

separate paper.

STAT6(, which is similar to the previously known STAT6 gene, works

closely with a gene known as LITAF, discovered by the same Boston

University researchers in 1999. The STAT6( and LITAF proteins (which

are coded for by their respective genes) bind to form a complex that

moves into the cell's nucleus to regulate the transcription of

cytokines. The recent Boston University findings will offer new ways to

regulate TNF-alpha, whose overexpression causes inflammatory and

immunological problems.

Drugs regulating TNF-alpha such as Remicade, Embrel, and Humira are a

multibillion dollar market. " Because STAT6( and LITAF affect

TNF-alpha through a different pathway, we expect to develop more

efficient therapeutics to help people with rheumatoid arthritis,

Crohn's disease, and inflammatory bowel syndrome, " says Boston

University School of Dental Medicine Professor Salomon Amar, the

leading author of the paper.

The Boston University researchers are now working on animal models to

control LITAF and thus TNF-alpha overproduction in inflammatory

syndromes.

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The paper, " LPS induces the interaction of a transcription factor,

LPS-induced TNF-{alpha} factor, and STAT6( with effects on multiple

cytokines, " by Xiaoren Tang, Deborah Levy Marciano, E. Leeman,

and Salomon Amar, may be found at

http://www.pnas.org/cgi/content/abstract/0501159102v1?etoc

http://www.eurekalert.org/pub_releases/2005-03/bu-dog032805.php

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