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):

Report Date:

2008-11-01

Pagination or Media Count:

74.0

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.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE