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• W4313448654 abstract "Abstract Background HeberFERON is a co-formulation of α2b and γ interferons, based on their synergism, which has shown its clinical superiority over individual interferons in basal cell carcinomas. In glioblastoma (GBM), HeberFERON has displayed promising preclinical and clinical results. This led us to design a microarray experiment aimed at identifying the molecular mechanisms involved in the distinctive effect of HeberFERON compared to the individual interferons. Methods Transcriptional expression profiling including a control (untreated) and three groups receiving α2b-interferon, γ-interferon and HeberFERON was performed using an Illumina HT-12 microarray platform. Unsupervised methods for gene and sample grouping, identification of differentially expressed genes, functional enrichment and network analysis computational biology methods were applied to identify distinctive transcription patterns of HeberFERON. Validation of most representative genes was performed by qPCR. For the cell cycle analysis of cells treated with HeberFERON for 24h, 48h and 72h we used flow cytometry. Results The three treatments show different behavior based on the gene expression profiles. The enrichment analysis identified several mitotic cell cycle related events, in particular from prometaphase to anaphase, which are exclusively targeted by HeberFERON. The FOXM1 transcription factor network that is involved in several cell cycle phases and is highly expressed in GBMs, is significantly down regulated. Flow cytometry experiments corroborated the action of HeberFERON on the cell cycle in a dose and time dependent manner with a clear cellular arrest as of 24h post-treatment. Despite the fact that p53 was not down-regulated, several genes involved in its regulatory activity were functionally enriched. Network analysis also revealed a strong relationship of p53 with genes targeted by HeberFERON. We propose a mechanistic model to explain this distinctive action, based on the simultaneous activation of PKR and ATF3, p53 phosphorylation changes, as well as its reduced MDM2 mediated ubiquitination and export from the nucleus to the cytoplasm. PLK1, AURKB, BIRC5 and CCNB1 genes, all regulated by FOXM1, also play central roles in this model. These and other interactions could explain a G2/M arrest and the effect of HeberFERON on the proliferation of U-87MG. Conclusions We proposed molecular mechanisms underlying the distinctive behavior of HeberFERON compared to the treatments with the individual interferons, where cell cycle related events were highly relevant." @default.
• W4313448654 created "2023-01-06" @default.
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• W4313448654 date "2022-12-20" @default.
• W4313448654 modified "2023-10-12" @default.
• W4313448654 title "A co-formulation of Interferons alpha2b and gamma distinctively targets Cell Cycle in the glioblastoma-derived cell line U-87MG" @default.
• W4313448654 cites W1516095885 @default.
• W4313448654 cites W1817120407 @default.
• W4313448654 cites W1960918491 @default.
• W4313448654 cites W1966680971 @default.
• W4313448654 cites W1975764372 @default.
• W4313448654 cites W1976848613 @default.
• W4313448654 cites W1981414879 @default.
• W4313448654 cites W1989277387 @default.
• W4313448654 cites W1995051337 @default.
• W4313448654 cites W1999605095 @default.
• W4313448654 cites W2001275070 @default.
• W4313448654 cites W2007610766 @default.
• W4313448654 cites W2010358674 @default.
• W4313448654 cites W2011945422 @default.
• W4313448654 cites W2015500590 @default.
• W4313448654 cites W2017205117 @default.
• W4313448654 cites W2020541351 @default.
• W4313448654 cites W2027315326 @default.
• W4313448654 cites W2031163071 @default.
• W4313448654 cites W2038465110 @default.
• W4313448654 cites W2042231416 @default.
• W4313448654 cites W2054260164 @default.
• W4313448654 cites W2057231921 @default.
• W4313448654 cites W2060584880 @default.
• W4313448654 cites W2068229930 @default.
• W4313448654 cites W2069643337 @default.
• W4313448654 cites W2073089988 @default.
• W4313448654 cites W2076292802 @default.
• W4313448654 cites W2078844752 @default.
• W4313448654 cites W2080604015 @default.
• W4313448654 cites W2082259005 @default.
• W4313448654 cites W2082376103 @default.
• W4313448654 cites W2084587700 @default.
• W4313448654 cites W2094536296 @default.
• W4313448654 cites W2096287682 @default.
• W4313448654 cites W2096766502 @default.
• W4313448654 cites W2099249565 @default.
• W4313448654 cites W2103017472 @default.
• W4313448654 cites W2103089522 @default.
• W4313448654 cites W2104488717 @default.
• W4313448654 cites W2105100844 @default.
• W4313448654 cites W2105899429 @default.
• W4313448654 cites W2108244474 @default.
• W4313448654 cites W2110942624 @default.
• W4313448654 cites W2116454541 @default.
• W4313448654 cites W2118373398 @default.
• W4313448654 cites W2122683221 @default.
• W4313448654 cites W2125754609 @default.
• W4313448654 cites W2130410032 @default.
• W4313448654 cites W2133465414 @default.
• W4313448654 cites W2134656216 @default.
• W4313448654 cites W2135630561 @default.
• W4313448654 cites W2140520689 @default.
• W4313448654 cites W2145025818 @default.
• W4313448654 cites W2145690501 @default.
• W4313448654 cites W2146512944 @default.
• W4313448654 cites W2146588049 @default.
• W4313448654 cites W2149055925 @default.
• W4313448654 cites W2152135248 @default.
• W4313448654 cites W2153744866 @default.
• W4313448654 cites W2155225188 @default.
• W4313448654 cites W2155660862 @default.
• W4313448654 cites W2159482845 @default.
• W4313448654 cites W2161959295 @default.
• W4313448654 cites W2415141352 @default.
• W4313448654 cites W2585352231 @default.
• W4313448654 cites W2758489288 @default.
• W4313448654 cites W2772116600 @default.
• W4313448654 cites W2802521290 @default.
• W4313448654 cites W2900536667 @default.
• W4313448654 cites W2940964825 @default.
• W4313448654 cites W2969466581 @default.
• W4313448654 cites W2979950278 @default.
• W4313448654 cites W3017070412 @default.
• W4313448654 cites W3080951954 @default.
• W4313448654 cites W3099018540 @default.
• W4313448654 cites W3124899091 @default.
• W4313448654 cites W3159576913 @default.
• W4313448654 cites W3168098587 @default.
• W4313448654 cites W3200029506 @default.
• W4313448654 cites W4237335579 @default.
• W4313448654 cites W4240488547 @default.
• W4313448654 cites W4256409604 @default.
• W4313448654 cites W45534775 @default.
• W4313448654 doi "https://doi.org/10.21203/rs.3.rs-2369826/v1" @default.
• W4313448654 hasPublicationYear "2022" @default.
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