Matches in SemOpenAlex for { <https://semopenalex.org/work/W4220798524> ?p ?o ?g. }
- W4220798524 endingPage "111104" @default.
- W4220798524 startingPage "111104" @default.
- W4220798524 abstract "New experimental data have shown how the periodic exposure of cells to low oxygen levels (i.e., cyclic hypoxia) impacts their progress through the cell-cycle. Cyclic hypoxia has been detected in tumours and linked to poor prognosis and treatment failure. While fluctuating oxygen environments can be reproduced in vitro, the range of oxygen cycles that can be tested is limited. By contrast, mathematical models can be used to predict the response to a wide range of cyclic dynamics. Accordingly, in this paper we develop a mechanistic model of the cell-cycle that can be combined with in vitro experiments to better understand the link between cyclic hypoxia and cell-cycle dysregulation. A distinguishing feature of our model is the inclusion of impaired DNA synthesis and cell-cycle arrest due to periodic exposure to severely low oxygen levels. Our model decomposes the cell population into five compartments and a time-dependent delay accounts for the variability in the duration of the S phase which increases in severe hypoxia due to reduced rates of DNA synthesis. We calibrate our model against experimental data and show that it recapitulates the observed cell-cycle dynamics. We use the calibrated model to investigate the response of cells to oxygen cycles not yet tested experimentally. When the re-oxygenation phase is sufficiently long, our model predicts that cyclic hypoxia simply slows cell proliferation since cells spend more time in the S phase. On the contrary, cycles with short periods of re-oxygenation are predicted to lead to inhibition of proliferation, with cells arresting from the cell-cycle in the G2 phase. While model predictions on short time scales (about a day) are fairly accurate (i.e, confidence intervals are small), the predictions become more uncertain over longer periods. Hence, we use our model to inform experimental design that can lead to improved model parameter estimates and validate model predictions." @default.
- W4220798524 created "2022-04-03" @default.
- W4220798524 creator A5018081801 @default.
- W4220798524 creator A5025791169 @default.
- W4220798524 creator A5042849195 @default.
- W4220798524 creator A5053982990 @default.
- W4220798524 creator A5081431968 @default.
- W4220798524 creator A5088374235 @default.
- W4220798524 date "2022-07-01" @default.
- W4220798524 modified "2023-10-16" @default.
- W4220798524 title "A DNA-structured mathematical model of cell-cycle progression in cyclic hypoxia" @default.
- W4220798524 cites W1538419182 @default.
- W4220798524 cites W1760865464 @default.
- W4220798524 cites W1912124796 @default.
- W4220798524 cites W1964279348 @default.
- W4220798524 cites W1965244200 @default.
- W4220798524 cites W1966176927 @default.
- W4220798524 cites W1967880683 @default.
- W4220798524 cites W1972970131 @default.
- W4220798524 cites W2000645646 @default.
- W4220798524 cites W2011006263 @default.
- W4220798524 cites W2012276721 @default.
- W4220798524 cites W2017443272 @default.
- W4220798524 cites W2030072899 @default.
- W4220798524 cites W2031888565 @default.
- W4220798524 cites W2032083230 @default.
- W4220798524 cites W2034269086 @default.
- W4220798524 cites W2040431513 @default.
- W4220798524 cites W2042982699 @default.
- W4220798524 cites W2049982841 @default.
- W4220798524 cites W2059971436 @default.
- W4220798524 cites W2071060299 @default.
- W4220798524 cites W2073063542 @default.
- W4220798524 cites W2074239576 @default.
- W4220798524 cites W2077496900 @default.
- W4220798524 cites W2078757619 @default.
- W4220798524 cites W2081537733 @default.
- W4220798524 cites W2082559623 @default.
- W4220798524 cites W2085967779 @default.
- W4220798524 cites W2086042539 @default.
- W4220798524 cites W2090400615 @default.
- W4220798524 cites W2097439489 @default.
- W4220798524 cites W2097539444 @default.
- W4220798524 cites W2102566266 @default.
- W4220798524 cites W2111609516 @default.
- W4220798524 cites W2122969498 @default.
- W4220798524 cites W2124822779 @default.
- W4220798524 cites W2132935366 @default.
- W4220798524 cites W2138537392 @default.
- W4220798524 cites W2143349422 @default.
- W4220798524 cites W2148739751 @default.
- W4220798524 cites W2154745425 @default.
- W4220798524 cites W2169020257 @default.
- W4220798524 cites W2212249654 @default.
- W4220798524 cites W2469147432 @default.
- W4220798524 cites W2470984080 @default.
- W4220798524 cites W2555458952 @default.
- W4220798524 cites W2595599881 @default.
- W4220798524 cites W2606935752 @default.
- W4220798524 cites W2762502468 @default.
- W4220798524 cites W2767182262 @default.
- W4220798524 cites W2770091082 @default.
- W4220798524 cites W2783302891 @default.
- W4220798524 cites W2884184895 @default.
- W4220798524 cites W2904900566 @default.
- W4220798524 cites W2945754632 @default.
- W4220798524 cites W2964416380 @default.
- W4220798524 cites W2969950545 @default.
- W4220798524 cites W3067067067 @default.
- W4220798524 cites W3135218197 @default.
- W4220798524 cites W3173975756 @default.
- W4220798524 cites W4214940713 @default.
- W4220798524 doi "https://doi.org/10.1016/j.jtbi.2022.111104" @default.
- W4220798524 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35337794" @default.
- W4220798524 hasPublicationYear "2022" @default.
- W4220798524 type Work @default.
- W4220798524 citedByCount "5" @default.
- W4220798524 countsByYear W42207985242022 @default.
- W4220798524 countsByYear W42207985242023 @default.
- W4220798524 crossrefType "journal-article" @default.
- W4220798524 hasAuthorship W4220798524A5018081801 @default.
- W4220798524 hasAuthorship W4220798524A5025791169 @default.
- W4220798524 hasAuthorship W4220798524A5042849195 @default.
- W4220798524 hasAuthorship W4220798524A5053982990 @default.
- W4220798524 hasAuthorship W4220798524A5081431968 @default.
- W4220798524 hasAuthorship W4220798524A5088374235 @default.
- W4220798524 hasBestOaLocation W42207985242 @default.
- W4220798524 hasConcept C12554922 @default.
- W4220798524 hasConcept C1491633281 @default.
- W4220798524 hasConcept C178790620 @default.
- W4220798524 hasConcept C185592680 @default.
- W4220798524 hasConcept C186060115 @default.
- W4220798524 hasConcept C18903297 @default.
- W4220798524 hasConcept C202751555 @default.
- W4220798524 hasConcept C2908647359 @default.
- W4220798524 hasConcept C29537977 @default.
- W4220798524 hasConcept C540031477 @default.
- W4220798524 hasConcept C55493867 @default.