TAS::75 0849::TAS

Information

  • Research Project
  • 8341331
  • ApplicationId
    8341331
  • Core Project Number
    261201100036C-0-0-1
  • Full Project Number
    261201100036C-0-0-1
  • Serial Number
    0
  • FOA Number
  • Sub Project Id
  • Project Start Date
    9/23/2011 - 14 years ago
  • Project End Date
    6/22/2012 - 13 years ago
  • Program Officer Name
  • Budget Start Date
    -
  • Budget End Date
    -
  • Fiscal Year
    2011
  • Support Year
  • Suffix
  • Award Notice Date
    -
Organizations

TAS::75 0849::TAS

No satisfactory medical interventions for radiation enteritis are available yet. We have demonstrated that polyamine inhibition by a-difluoromethylornithine orDFMO, a selective and irreversible inhibitor of ornithine decarboxylase (ODC, the primary rate-limiting enzyme in the production of polyamines) significantly protects the gastrointestinal (GI) tract from whole-body radiation exposure. Here we propose to further develop it into a highly efficient radioprotector/radiomitigator for indications (1) radiotherapy associated enteritis and (2) GI injury due to nuclear accidents or incidents. Aim #1. Evaluate the radioprotecting/mitigating effect of DFMO on GI injury Aim #2. Evaluate the effect of DFMO on cancer radiosensitivity Methods: (1) For efficacy studies under Aim #1, we will use a mouse model of abdomen-pelvis irradiation. Morphological evaluations include crypt survival and crypt-villus recovery. Intestinal barrier integrity will be evaluated by measuring plasma citrulline and serum endotxoin levels. (2) Under Aim #2, we will first evaluate the effect of DFMO on cancer growth and radiosensitivity in HCT116 and HT29 cell lines, and then move to mouse models of colon cancer and simulate abdomen-pelvis radiotherapy. Methods involved are cell culture, in vitro clonogenic assay of tumor cell growth, Xenograft implantation of HCT116 cells and HT29 cells and measuring tumor volume Relevance to public health: The concept proposed in this project, if proved, will lead to a full-scale development program to advance DFMO into a highly efficient drug for managing radiation enteritis in cancer patients as well as GI injury due to unintended radiation exposure.

IC Name
NATIONAL CANCER INSTITUTE
  • Activity
    N43
  • Administering IC
    CA
  • Application Type
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    194797
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    395
  • Ed Inst. Type
  • Funding ICs
    NCI:194797\
  • Funding Mechanism
    Contracts, Extramural
  • Study Section
  • Study Section Name
  • Organization Name
    RXBIO, INC.
  • Organization Department
  • Organization DUNS
    185698334
  • Organization City
    JOHNSON CITY
  • Organization State
    TN
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    376043619
  • Organization District
    UNITED STATES