Farnesyltransferase Inhibitor FTI-277 Reduces Mortality of Septic Mice along with Improved Bacterial Clearance

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Farnesyltransferase inhibitor FTI-277 reduces mortality of septic mice along with improved bacterial clearance.

Treatment with statins, inhibitors of HMG-CoA reductase, extends the survival of septic mice. However, the molecular mechanisms underlying the cholesterol-lowering, independent beneficial effects of statins in sepsis are poorly understood. The inhibition of protein isoprenylation, namely farnesylation and geranylgeranylation, has been proposed as a mediator of the pleiotropic protective effects...

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Title : Farnesyltransferase inhibitor , FTI - 277 , reduces mortality of septic mice along with improved bacterial clearance

Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129 (W.Y., M.Y., Y.T., K.C., J.M., L.Z., Y.F., K.K., W.C., F.I., M.K.), Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 (Y-M.Y., R.G.T.), Shriners Hospitals for Children, Boston, MA 02114 (M.Y., Y.T., J.M., Y-M.Y, A...

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The farnesyltransferase inhibitor FTI-277 radiosensitizes H-ras-transformed rat embryo fibroblasts.

Many tumor cells have a greater resistance to ionizing radiation than their normal counterparts, suggesting that the development of drugs that can reduce that radioresistance would potentiate the efficacy of radiation therapy. Because activated H-ras expression has been shown to markedly increase radiation resistance in some transformed cells, the inactivation of H-ras would then be predicted t...

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Bacterial Clearance Is Improved in Septic Mice by Platelet-Activating Factor-Acetylhydrolase (PAF-AH) Administration

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Growth inhibition by the farnesyltransferase inhibitor FTI-277 involves Bcl-2 expression and defective association with Raf-1 in liver cancer cell lines.

Farnesyltransferase inhibitors (FTIs) block the growth of tumor cells in vitro and in vivo with minimal toxicity toward normal cells. In general, inhibition of protein farnesylation results in G0/G1 cell cycle block, G2/M cell cycle arrest, or has no effect on cell cycle progression. One aspect of FTI biology that is poorly understood is the ability of these drugs to induce cancer cell growth a...

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ژورنال

عنوان ژورنال: Journal of Pharmacology and Experimental Therapeutics

سال: 2011

ISSN: 0022-3565,1521-0103

DOI: 10.1124/jpet.111.183558