Nhibition in hypoxic cells, suggesting p38alpha Pathway that the re-establishment chemosensitization NO cGMP signaling cascade in hypoxic cells k Nnte to other mechanisms such as the effect on the enzymes of DNA repair, modulation of transporters efflux of drugs or inhibition of transcription factors such as HIF 1 key. Doxorubicin in these experiments was that, despite some modest activity t in clinical studies of prostate cancer cells have a high intrinsic resistance to the drug class used. Our previous studies have one Hnlichen chemosensitizing effect of restoring NO signaling in other classes of drugs, including normal taxanes shown. Zus Tzlich to the development of resistance, has been shown that hypoxia, the reduction of MICA ligands in the surface cause surface of cancer cells. Previously, Wu et al. indicated that these long hi UNG erh ht in advanced prostate cancer and probably represents an escape mechanism of tumor lysis by immune effectors.
In addition, several studies have obtained a relation between Shown Hten excretion MICA with tumor stage and metastatic potential. Our observations can to prevent the inhibition of PDE hypoxia-induced degradation of MICA k Are important because there is evidence that these drugs k Can other therapeutic benefits, including have the re-entry immune recognition of cancer cells provides prostate, which is also an important part of many cytotoxic therapies. These observations are shown by in vivo animal studies, the growth ged Mpft tumors in a mouse model of xenogeneic NK verst competent RKT, however, these observations further investigation must, including normal depletion studies to best term That the proposed mechanism of inhibition of the tumor by the inhibition of PDE is thanks an improved immune surveillance. Our results differ from those out of Qian et al, suggest that mice had no significant effect on the metastasis with sildenafil in a limited number of M In an orthotopic model of it. This difference can that be Differences in the pattern, in particular the timing of the inhibition of PDE used expression of ligands and the stimulation of cell lines. The results with the PDE inhibitor, zaprinast, in these studies are demonstrated in accordance with our previous observations in vivo with transdermal nitroglycerin. To our knowledge this is the first study, the cGMP and cAMP-dependent Independent PDE activity t characterize in cell lines of prostate cancer.
PDE-specific inhibition attenuated cht Chemoresistance mediated by hypoxia, best CONFIRMS the potential clinical benefit to improve the NO-cGMP signaling in chemosensitize cancer cells. The D Attenuation of the stimulatory ligand MICA elimination of hypoxic cells, and the effect on tumor Bcl-2 pathway growth in mouse studies, schl Gt a m Possible applications for the immunotherapy PDE inhibitors. Although these preliminary studies further term plaintiff ben tion in relation to the specific mechanism of action and translatability of human neoplastic disease, These data provide further evidence for R The intracellular Ren signaling of cGMP in NO hypoxia adaptive Ver Changes in cancer cells. by isolation and identification of metabolites in the urine, doxorubicin metabolites specific fluorescence properties.15 Therefore, retained in this report, we used fluorescence detection c.