Accession Number : ADA501638


Title :   Molecular Modulation of Inhibitors of Apoptosis as a Novel Approach for Radiosensitization of Human Prostate Cancer


Descriptive Note : Annual rept. 15 Oct 2007-14 Oct 2008


Corporate Author : MICHIGAN UNIV ANN ARBOR


Personal Author(s) : Xu, Liang


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a501638.pdf


Report Date : Nov 2008


Pagination or Media Count : 74


Abstract : The major goal of the project is to investigate the radiosensitization activity and mechanism of action of novel IAP-inhibitors in prostate cancer. In the third year of the project, we have investigated the in vivo radiosensitization activity of our lead IAPinhibitors, SH-130 and Embelin, and mechanism of action in human prostate cancer xenograft model. IAP-inhibitors potently enhanced radiation-induced tumor growth inhibition, together with increased induction of apoptosis. In nude mouse xenograft models, IAP-inhibitors Embelin and SH-130 potently sensitized the DU-145 tumors to X-ray radiation. Mechanism studies show that NK-kB pathway activation was also inhibited in the combination therapy. Interestingly, we also observed anti-angiogenic effect of the combination treatment. Due to the lab move in March, 2008, together with our animal room moved and more importantly the move of our X-ray irradiator at the same time, our animal experiments were delayed. We have requested and obtained approval a one year no-cost extension for finish the planned animal and MOA studies.


Descriptors :   *PROSTATE CANCER , APOPTOSIS , HUMANS , MOLECULES , NEOPLASMS , X RAYS , COSTS , THERAPY , ANIMALS , IRRADIATION , INHIBITION , MODULATION , IN VIVO ANALYSIS , RADIATION EFFECTS , GROWTH(PHYSIOLOGY) , RADIATION TOLERANCE , RADIATION , ACTIVATION


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE