TAS::75 0849::TAS

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$194,797.00
Award Year:
2011
Program:
SBIR
Phase:
Phase I
Contract:
N43CO110036
Agency Tracking Number:
N43CO110036
Solicitation Year:
2011
Solicitation Topic Code:
NCI
Solicitation Number:
n/a
Small Business Information
RXBIO INC
1325 SUNSET DR, JOHNSON CITY, TN, 37604-3619
Hubzone Owned:
N
Socially and Economically Disadvantaged:
N
Woman Owned:
N
Duns:
185698334
Principal Investigator:
WENLIN DENG
(423) 928-3330
WDENG@RXBIO.COM
Business Contact:
WENLIN DENG
(423) 928-3330
WDENG@RXBIO.COM
Research Institution:
Stub




Abstract
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, invitro 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.

* information listed above is at the time of submission.

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