""""""""DISCONTINUED Last year we hypothesized that late effects of radiation are caused in part by chronically misregulated production of mesenchymal growth factors. We now have pioneering evidence of this in patients and substantial evidence that anti-cytokine therapies can prevent late radiation sequela in animals. That is the purpose of this study. We have shown that early exposure to certain growth factors, especially bFGF, shortly after irradiation can preserve bone marrow, hair follicles, and gut crypt cells. In several cases these growth factors can prevent otherwise lethal doses of radiation from causing significant toxicity. On the other hand, animal strains (C57) with naturally elevated TGFB have an increased propensity to develop fibrosis following radiation, while strains with naturally low levels such as C3H have a low propensity to develop fibrosis. Likewise, we have shown that heterozygous TGFB1 knockout mice on a C57 background have a lower endogenous TGFB than the wild type, and a low propensity to develop fibrosis. The results suggest that patients at risk for fibrosis might be identified in advance, and thus treatment to prevent fibrosis in these patients may be possible. We are currently in the process of testing a number of anticytokine therapies aimed at reducing chronically high bFGF and TGFB after irradiation.""""""""
