@misc{10481/97004,
year = {2024},
month = {10},
url = {https://hdl.handle.net/10481/97004},
abstract = {umor hypoxia is a dynamic phenomenon marked by fluctuations in oxygen levels across both rapid (seconds to minutes) and slow (hours to days) time scales. While short hypoxia cycles are relatively well understood, the mechanisms behind longer cycles remain largely unclear. In this paper, we present a novel mechanistic mathematical model that explains slow hypoxia cycles through feedback loops involving vascular expansion and regression, oxygen-regulated tumor growth, and toxic cytokine production. Our study reveals that, for the emergence of slow hypoxia cycles, endothelial cells must adapt by decreasing receptor activation as ligand concentration increases. Additionally, the interaction between tumor cells and toxic cytokines influences frequency and intensity of these cycles. By examining the effects of pharmacological interventions, specifically poly (ADP-ribose) polymerase inhibitors, we also demonstrate how targeting cell proliferation can help regulate oxygen levels. Our findings enhance the understanding of hypoxia regulation and suggest PARP proteins as promising therapeutic targets.},
organization = {StateResearchAgency of theSpanishMinistry of Science and Innovation and
European Regional Development Fund through the project (PID2022-
137228OB-I00 MICIU/AEI/10.13039/501100011033) and by ERDF, EU (JS,
MC)},
organization = {the Modeling Nature Research Unit, Grant
QUAL21-011 (JS, MC, FJO) funded by Consejería de Universidad, Investigación
e Innovación (Junta de Andalucía)},
organization = {State Research Agency of
the Spanish Ministry of Science and Innovation and European Regional
Development Fund, project RTI2018-098968-B-I00 (FJO)},
organization = {Junta de
AndalucíaP20_01179 (FJO)},
organization = {FundaciónDomingoMartínez (call 2019) (FJO)},
organization = {grant PID2021-127896OB-I00,
funded by MCIN/AEI/ 10.13039/ 501100011033 ‘ERDF A way of making
Europe’ (TA),by theSpanishResearchAgency through theSeveroOchoa and
Maria deMaeztu Program forCenters andUnits of Excellence inR& D
awarded to the Centre de RecercaMatemàtica (CEX2020-001084-M) (TA)},
organization = {ItalianMinistry of Education,Universities and Research, through theMIUR
grant Dipartimento di Eccellenza 2018-2022, project E11G18000350001
(MC)},
organization = {National Group of Mathematical Physics (GNFM-INdAM)
through the INdAM-GNFMProject (CUPE53C22001930001) “Fromkinetic to
macroscopicmodels for tumor-immune systemcompetition”},
organization = {Project PRIN 2022 PNRR Mathematical
Modelling for a Sustainable Circular Economy in Ecosystems
(P2022PSMT7, CUP D53D23018960001) funded by the European Union -
NextGenerationEU and byMUR-ItalianMinistry of Universities and Research
(MC)},
organization = {Isaac Newton Institute for Mathematical
Sciences for support and hospitality during the program Mathematics of
movement: an interdisciplinary approach to mutual challenges in animal
ecology and cell biology under EP-SRC grant numbr EP/R014604/1 (TA) and
CERCA Program/Generalitat de Catalunya for institutional support (TA).},
publisher = {Springer Nature},
title = {Emergence of cyclic hypoxia and the impact of PARP inhibitors on tumor progression},
doi = {10.1038/s41540-024-00453-2},
author = {Conte, Martina and Cabeza Fernández, Vanesa and Oliver, F. Javier and Alarcón, Tomás and Soler Vizcaino, Juan Segundo},
}