{"database":"BioModels","file_versions":[],"scores":null,"additional":{"submitter":["Quentin Thommen"],"curationStatus":["Non-curated"],"modellingApproach":["differential equation model"],"levelVersion":["L3V2"],"full_dataset_link":["https://www.ebi.ac.uk/biomodels/MODEL2608180004"],"isPrivate":["false"],"repository":["BioModels"],"modelFormat":["SBML"],"omics_type":["Models"],"tokenised_name":["Minimal dynamical thermal dose model   Ladjimi et al. 2019"],"publication_year":["2019"],"submissionId":["MODEL2608180004"],"publication_authors":["M T Ladjimi, D Labavić, M Guilbert, François Anquez, A Pruvost, Emmanuel Courtade, B Pfeuty, Thommen Q"],"first_author":["M T Ladjimi"],"publication":["10.1080/02656736.2019.1633478,\n                            <b>Introduction:</b> Models of dose-effect relationships seek systematic and predictive descriptions of how cell survival depends on the level and duration of the stressor. The CEM43 thermal dose model has been empirically derived more than thirty years ago and still serves as a benchmark for hyperthermia protocols despitethe advent of regulatory network models. <b>Objective:</b> In this paper, we propose and realize a simple experimental test to assess whether mechanistic models can prove more reliable indicators for some protocols. We define two time-asymmetric hyperthermia profiles, faster rise than decay or slower rise than decay, for which the CEM43 model predicts the same survival while a regulatory network model predicts significant differences. <b>Materials:</b> Experimental data (both control 37°C and hyperthermia assays) were collected from duplicate HeLa cell cultures. Cells were imaged before and 24, 48 and 72 h after the hyperthermia assay double-stained with fluorescein-5-isothiocyanate (FITC)-labeled annexin V and propidium iodide for detecting cell death. <b>Results:</b> Survival experiments of HeLa cells show that a fast temperature rise followed by a slow decay can be twice more lethal than the opposite, consistently with the prediction of the network model. <b>Conclusions:</b> Using a model reduction approach, we obtained a simple nonlinear dynamic equation that identifies the limited repair capacity as the main factor underlying the dose-asymmetry effect and that could be useful for refining thermal doses for dynamic protocols.. 1, 36.\n                            a Laboratoire de Physique des Lasers, Atomes et Molécules, UMR-CNRS 8523, Université de Lille , France."],"submitter_mail":["quentin.thommen@univ-lille.fr"],"publication_doi":["10.1080/02656736.2019.1633478"],"submitter_affiliation":["Univ. Lille"],"additional_accession":[]},"is_claimable":false,"name":"Minimal dynamical thermal dose model - Ladjimi et al. 2019","description":"The model provides a minimal mechanistic description of cellular survival under hyperthermia. Heat induces the production of misfolded proteins, which are either degraded or repaired by molecular chaperones. The repair process is saturable because chaperone resources are limited, causing misfolded proteins to accumulate when the thermal stress exceeds the cellular repair capacity. Cell survival decreases according to the accumulated misfolded-protein burden. This nonlinear repair limitation allows the model to reproduce thermal dose time-profile effects that cannot be captured by the conventional CEM43 description, including the different survival responses produced by fast-rise/slow-decay and slow-rise/fast-decay temperature profiles.","dates":{"last_modification":"2026-08-18","publication":"2026-09-02","submission":"2026-08-18"},"accession":"MODEL2608180004","cross_references":{"doi":["10.1080/02656736.2019.1633478"]}}