| Autor: |
Moeller BJ; Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA., Dreher MR, Rabbani ZN, Schroeder T, Cao Y, Li CY, Dewhirst MW |
| Jazyk: |
angličtina |
| Zdroj: |
Cancer cell [Cancer Cell] 2005 Aug; Vol. 8 (2), pp. 99-110. |
| DOI: |
10.1016/j.ccr.2005.06.016 |
| Abstrakt: |
We have previously shown that radiation increases HIF-1 activity in tumors, causing significant radioprotection of the tumor vasculature. The impact that HIF-1 activation has on overall tumor radiosensitivity, however, is unknown. We reveal here that HIF-1 plays an important role in determining tumor radioresponsiveness through regulating four distinct processes. By promoting ATP metabolism, proliferation, and p53 activation, HIF-1 has a radiosensitizing effect on tumors. Through stimulating endothelial cell survival, HIF-1 promotes tumor radioresistance. As a result, the net effect of HIF-1 blockade on tumor radioresponsiveness is highly dependent on treatment sequencing, with "radiation first" strategies being significantly more effective than the alternative. These data provide a strong rationale for pursuing sequence-specific combinations of HIF-1 blockade and conventional therapeutics. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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