DTIC ADA594169: Reducing Toxicity of Radiation Treatment pdf

DTIC ADA594169: Reducing Toxicity of Radiation Treatment

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Toxicity is a major impediment to effective radiation therapy of locally advanced prostate cancer. Work under this award focuses on the potential of a novel class of pharmacological radiation protectors to reduce normal tissue toxicity of radiation therapy. During the first year we screened a series of signal transduction modifiers targeting either canonical NF- B activation or GSK3 for their potential to protect mice against lethal doses of ionizing radiation. We identified one compound that performed better than the others in preventing catastrophic damage to the epithelial lining of the GI tract and increasing survival of irradiated mice. Importantly, this compound also showed anti-tumor activity against four human prostate cancer cell lines grown as xenotransplants in mice. The compound in question is an anti-inflammatory mediator that inhibits NF- B activity and other key signaling events of relevance to prostate cancer growth and survival. It exerts these effects by covalently interacting with reactive cysteines on the surface of those proteins.

Ongoing work focuses on the characterization of the molecular target spectrum responsible for the differential effects of this drug on normal and tumor tissues

• Creator/s: Defense Technical Information Center
• Date: 10/1/2013
• Year: 2013
• Book Topics/Themes: DTIC Archive, , THOMAS JEFFERSON UNIV PHILADELPHIA PA, *PROSTATE CANCER, *RADIATION, *RADIOTHERAPY, CATASTROPHIC CONDITIONS, DAMAGE, DRUGS, GROWTH(PHYSIOLOGY), LETHAL DOSAGE, NEOPLASMS, REACTIVITIES, SIGNALS, TISSUES(BIOLOGY), TOXICITY

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