Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Topoisomerase I inhibitors have shown positive effects in combination with radiation therapy in some studies. Normally oxygenated and hypoxic human MCF-7 breast carcinoma-cells were exposed to irinotecan (100 mu M or 250 mu M) or to SN-38 (10 mu M or 25 mu M) for 1 h prior to, during and for 3 h after radiation. Irinotecan and SN-38 showed little or no radiation sensitization of normally oxygenated MCF-7 cells but were effective radiation sensitizers of hypoxic cells. Both irinotecan and SN-38 diminished or eliminated the shoulder of the radiation survival curves of both the normally oxygenated and hypoxic cells indicating inhibition of the repair of sublethal radiation damage to DNA. Irinotecan (20 mg/kg or 30 mg/kg) was administered to mice bearing the EMT-6 mammary carcinoma on days 7 through 11 just prior to fractionated radiation (5x3 Gray). The tumor growth delays obtained with the combination regimens were greater than expected for simple additivity of the two treatments. Treatment with irinotecan resulted in decreased expression of topoisomerase I mRNA and increased expression of topoisomerase II mRNA in EMT-6 tumor tissue. Irinotecan treatment did not alter the protein levels for topoisomerase I or II in the tumor tissue; however, the combination of radiation therapy and irinotecan administration resulted in decreased topisomerase I and increased topoisomerase II protein in the tumor tissue. These results suggest that with appropriate scheduling of a topoisomerase I inhibitor and a topoisomerase II inhibitor with fractionated radiation therapy maximal cyto-reduction can be achieved.
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PMID:Irinotecan and radiation in vitro and in vivo. 2152 28

To explore the photo-therapeutic capacity of UV radiation in solid tumors, we herein employed an nLC-MS/MS technology to profile the proteomic landscape of irradiated WM-266-4 human metastatic-melanoma cells. Obtained data resulted in proteomic catalogues of 5982 and 7280 proteins for UVB- and UVC-radiation conditions, respectively, and indicated the ability of UVB/C-radiation forms to eliminate metastatic-melanoma cells through induction of synergistically operating programs of apoptosis and necroptosis. However, it seems that one or more WM-266-4 cell sub-populations may escape from UV-radiation's photo-damaging activity, acquiring, besides apoptosis tolerance, an EMT phenotype that likely offers them the advantage of developing resistance to certain chemotherapeutic drugs. Low levels of autophagy may also critically contribute to the selective survival and growth of UV-irradiated melanoma-cell escapers. These are the cells that must be systemically targeted with novel therapeutic schemes, like the one of UV radiation and Irinotecan herein suggested to be holding strong promise for the effective treatment of metastatic-melanoma patients. Given the dual nature of UV radiation to serve as both anti-tumorigenic and tumorigenic agent, all individuals being subjected to risk factors for melanoma development have to be appropriately informed and educated, in order to integrate the innovative PPPM concept in their healthcare-sector management.
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PMID:Unraveling the human protein atlas of metastatic melanoma in the course of ultraviolet radiation-derived photo-therapy. 2918 45