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• W2896514396 abstract "Medulloblastomas are among the most frequently diagnosed pediatric solid tumors, and drug resistance remains as the principal cause of treatment failure. Hypoxia and the subsequent activation of hypoxia‑inducible factor 1α (HIF‑1α) are considered key factors in modulating drug antitumor effectiveness, but the underlying mechanisms in medulloblastomas have not yet been clearly understood. The aim of the present study was to determine whether hypoxia induces resistance to cyclophosphamide (CPA) and ifosfamide (IFA) in DAOY medulloblastoma cells, whether the mechanism is dependent on HIF‑1α, and whether involves the modulation of the expression of cytochromes P450 (CYP)2B6, 3A4 and 3A5 and the control of cell proliferation. Monolayer cultures of DAOY medulloblastoma cells were exposed for 24 h to moderate (1% O2) or severe (0.1% O2) hypoxia, and protein expression was evaluated by immunoblotting. Cytotoxicity was studied with the MTT assay and by Annexin V/PI staining and flow cytometry. Cell proliferation was determined by the trypan‑blue exclusion assay and cell cycle by propidium iodide staining and flow cytometry. Hypoxia decreased CPA and IFA cytotoxicity in medulloblastoma cells, which correlated with a reduction in the protein levels of CYP2B6, CYP3A4 and CYP3A5 and inhibition of cell proliferation. These responses were dependent on hypoxia‑induced HIF‑1α activation, as evidenced by chemical inhibition of its transcriptional activity with 2‑methoxyestradiol (2‑ME), which enhanced the cytotoxic activity of CPA and IFA and increased apoptosis. Our results indicate that by stimulating HIF‑1α activity, hypoxia downregulates the expression of CYP2B6, CYP3A4 and CYP3A5, that in turn leads to decreased conversion of CPA and IFA into their active forms and thus to diminished cytotoxicity. These results support that the combination of HIF‑1α inhibitors and canonical antineoplastic agents provides a potential therapeutic alternative against medulloblastoma." @default.
• W2896514396 created "2018-10-26" @default.
• W2896514396 creator A5013209374 @default.
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• W2896514396 date "2018-10-12" @default.
• W2896514396 modified "2023-10-18" @default.
• W2896514396 title "Hypoxia increases chemoresistance in human medulloblastoma DAOY cells via hypoxia‑inducible factor 1α‑mediated downregulation of the CYP2B6, CYP3A4 and CYP3A5 enzymes and inhibition of cell proliferation" @default.
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• W2896514396 cites W1508632532 @default.
• W2896514396 cites W1858311216 @default.
• W2896514396 cites W1959922605 @default.
• W2896514396 cites W1970248216 @default.
• W2896514396 cites W1971256943 @default.
• W2896514396 cites W1972802699 @default.
• W2896514396 cites W1991181302 @default.
• W2896514396 cites W2000058195 @default.
• W2896514396 cites W2006175671 @default.
• W2896514396 cites W2006774917 @default.
• W2896514396 cites W2007100907 @default.
• W2896514396 cites W2007922385 @default.
• W2896514396 cites W2013735638 @default.
• W2896514396 cites W2017720960 @default.
• W2896514396 cites W2018715542 @default.
• W2896514396 cites W2022501326 @default.
• W2896514396 cites W2038539486 @default.
• W2896514396 cites W2042200862 @default.
• W2896514396 cites W2042255145 @default.
• W2896514396 cites W2043259574 @default.
• W2896514396 cites W2043333048 @default.
• W2896514396 cites W2043875467 @default.
• W2896514396 cites W2044810945 @default.
• W2896514396 cites W2045359719 @default.
• W2896514396 cites W2047297204 @default.
• W2896514396 cites W2054785151 @default.
• W2896514396 cites W2061368752 @default.
• W2896514396 cites W2065296596 @default.
• W2896514396 cites W2069872261 @default.
• W2896514396 cites W2077522929 @default.
• W2896514396 cites W2078699156 @default.
• W2896514396 cites W2079605491 @default.
• W2896514396 cites W2088474340 @default.
• W2896514396 cites W2091662568 @default.
• W2896514396 cites W2098535272 @default.
• W2896514396 cites W2100534366 @default.
• W2896514396 cites W2104068314 @default.
• W2896514396 cites W2104124411 @default.
• W2896514396 cites W2109118524 @default.
• W2896514396 cites W2110711017 @default.
• W2896514396 cites W2114005496 @default.
• W2896514396 cites W2114090713 @default.
• W2896514396 cites W2124828801 @default.
• W2896514396 cites W2128760555 @default.
• W2896514396 cites W2128772465 @default.
• W2896514396 cites W2129497554 @default.
• W2896514396 cites W2132172164 @default.
• W2896514396 cites W2135284064 @default.
• W2896514396 cites W2135594199 @default.
• W2896514396 cites W2159256342 @default.
• W2896514396 cites W2160201665 @default.
• W2896514396 cites W2164679539 @default.
• W2896514396 cites W2165558476 @default.
• W2896514396 cites W2166435019 @default.
• W2896514396 cites W2168323912 @default.
• W2896514396 cites W2171440354 @default.
• W2896514396 cites W2184810122 @default.
• W2896514396 cites W2255357451 @default.
• W2896514396 cites W2256501514 @default.
• W2896514396 cites W2292137207 @default.
• W2896514396 cites W2294022467 @default.
• W2896514396 cites W2336704086 @default.
• W2896514396 cites W2366536035 @default.
• W2896514396 cites W2419279732 @default.
• W2896514396 cites W2564083928 @default.
• W2896514396 cites W2564460377 @default.
• W2896514396 cites W2603940135 @default.
• W2896514396 cites W2604899752 @default.
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• W2896514396 doi "https://doi.org/10.3892/or.2018.6790" @default.
• W2896514396 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6278548" @default.
• W2896514396 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30320358" @default.
• W2896514396 hasPublicationYear "2018" @default.
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