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- W2024065711 abstract "Purpose: To explore whether antitumor immunoadjuvant OM-174 can stimulate immune cells to produce interferon-γ (IFN-γ) and thereby radiosensitize tumor cells.Methods and Materials: Splenocytes from BALB/c mice were stimulated by OM-174 at plasma-achievable concentrations (0.03–3 μg/mL), and afterward analyzed for the expression and secretion of IFN-γ by reverse transcriptase–polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Stimulated splenocytes were used as a source of IFN-γ to radiosensitize hypoxic EMT-6 tumor cells through the cytokine-inducible isoform of nitric oxide synthase (iNOS).Results: OM-174 activated the production of IFN-γ at high levels that reached 70 ng/mL in normoxia (21% oxygen) and 27 ng/mL in tumor-relevant hypoxia (1% oxygen). This caused up to 2.1-fold radiosensitization of EMT-6 tumor cells, which was associated with the iNOS-mediated production of the radiosensitizing molecule nitric oxide, as confirmed by accumulation of its oxidative metabolite nitrite, Western blot analysis, and reverse transcriptase–polymerase chain reaction. Both iNOS activation and radiosensitization were counteracted by neutralizing antibodies against IFN-γ. The same mechanism of radiosensitization through the IFN-γ secretion pathway was identified for IL-12 + IL-18, which are known to mediate IFN-γ responses. Hypoxia displayed a dual effect on the immune-tumor cell interaction, by downregulating the expression of the IFN-γ gene while upregulating iNOS at transcriptional level.Conclusion: Immunoadjuvant OM-174 is an efficient radiosensitizer of tumor cells through activation of the IFN-γ secretion pathway in immune cells. This finding indicates a rationale for combining immunostimulatory and radiosensitizing strategies and extends the potential therapeutic applications of OM-174." @default.
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- W2024065711 date "2007-11-01" @default.
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- W2024065711 title "P38 Radioimmunotherapy (RIT) of refractory or relapsed Hodgkin's lymphoma (HL) with 90Yttrium-labelled antiferritin antibody" @default.
- W2024065711 doi "https://doi.org/10.1016/s1359-6349(08)70053-3" @default.
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