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- Rosendahl, Ann, et al.
(författare)
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Systemic IGF-I administration stimulates the in vivo growth of early, but not advanced, renal cell carcinoma.
- 2008
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 123, s. 1286-1291
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-like growth factor I (IGF-I) is a potent mitogen and antiapoptotic factor. Although elevated serum IGF-I levels have been associated with increased cancer risk, it is not yet clear whether IGF-I sensitivity is sustained throughout tumor progression. To evaluate the biological effects of IGF-I during renal cell carcinoma (RCC) establishment and progression, we administered recombinant human IGF-I to severe combined immuno-deficient mice bearing early or more established Caki-2 human RCC tumors. IGF-I significantly enhanced the tumor growth 2.4-fold when administered early after tumor inoculation. This IGF-I-induced growth was accompanied with enhanced tumor cell proliferation, tumor vascularization, as well as increased intratumoral insulin-like growth factor binding protein 3 (IGFBP-3) and pSmad2 levels. In contrast, IGF-I administrated to more established RCC tumors showed no effect on tumor growth, with subsequently much lower Ki-67, IGFBP-3 and pSmad2 levels. Taken together, these data suggest that systemic IGF-I has potent actions during early RCC tumor development with a sustained long-term effect on proliferation and neovascularization although with progression, later tumors appear to become desensitized to systemic IGF-I effects. (c) 2008 Wiley-Liss, Inc.
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