ZIA BC 010873 (ZIA) | |||
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Title | Underlying Cause of Radiation-induced Fibrosis | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Simone, Nicole | NCI Program Director | N/A |
Cancer Activity | N/A | Division | CCR |
Funded Amount | $136,210 | Project Dates | 10/01/2007 - N/A |
Fiscal Year | 2010 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Cancer (100.0%) Cancer Survivorship (30.0%) |
Breast (100.0%) | ||
Research Type | |||
Interactions of Genes and/or Genetic Polymorphisms with Exogenous and/or Endogenous Factors Resources and Infrastructure Related to Etiology |
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Abstract | |||
In a mouse model, we induced fibrosis in one hind leg of mice using 35Gy of radiation in a single fraction and noted that microRNA's were altered in the radiation induced fibrotic leg as compared with the normal leg. We have done arrays to determine what microRNA changes are seen in various time points to look at the evolution of fibrosis. We have found one microRNA to be of particular interest after confirming with RT-PCR. Through in silico analysis, it is noted that this microRNA species is responsible for the regulation of many targets that are known to play a role in radiation induced fibrosis including TGFB1, RHho-B, RECK, TIMP-3 and TGFBR2. We have gone onto prove this in the laboratory and are currently doing confirmatory studies with either ELISA's or western blots. This has resulted in a potential novel target for radiation induced fibrosis. In the upcoming year we will further investigate this mechanism and will be making a knockout mouse for a microRNA of interest to detemine if late toxicity from radiation may be reversed with a drug against microRNA's. |