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 two microRNAs to be of particular interest after confirming with RT-PCR. Through in silico analysis, important downstream targets have been found and are being tested. Since these targets seem to be modulated by their respective microRNA's, in vitro analysis to prove their causal relationship are underway. 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.
|Simone 2nd, Charles B; Ly, David; Dan, Tu D et al. (2011) Comparison of intensity-modulated radiotherapy, adaptive radiotherapy, proton radiotherapy, and adaptive proton radiotherapy for treatment of locally advanced head and neck cancer. Radiother Oncol 101:376-82|
|Simone 2nd, Charles B; Lonser, Russell R; Ondos, John et al. (2011) Infratentorial craniospinal irradiation for von Hippel-Lindau: a retrospective study supporting a new treatment for patients with CNS hemangioblastomas. Neuro Oncol 13:1030-6|
|Argiris, Athanassios; Duffy, Austin G; Kummar, Shivaani et al. (2011) Early tumor progression associated with enhanced EGFR signaling with bortezomib, cetuximab, and radiotherapy for head and neck cancer. Clin Cancer Res 17:5755-64|