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Mathematical modeling for pharmacological approaches directed to metabolic pathways in "diabetic paradox" in prostate cancer

2021-12-09Master thesis Restricted access
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dc.contributor.advisorFernandes, Rúben
dc.contributor.advisorAlves, Marco
dc.contributor.advisorBaylina, Pilar
dc.contributor.authorSantos, Inês Ribeiro da Silva de Lima
dc.date.accessioned2022-02-09T15:05:56Z
dc.date.available2024-12-09T01:30:40Z
dc.date.issued2021-12-09
dc.description.abstractObesity and diabetes are two metabolic risk factos for cancer. However, there is a metabolic paradox in prostate cancer in which diabetes appears to protect the patient form this type of cancer. The current study aims to develop explanatory models of this contradiction utilizing prostate cancer cell lines, PC3 and LNCaP, in contrast to the metabolismo of normal prostate cells, using bioinformatics methods (HPEpiC). Two of the major routes of prostate metabolism, glycolysis and gluconeogensis, were mathematically manipulated in this study. This mathematical model offers unique and revolutionary implications in personalized medicine since it predicts the Effect, therapeutic dose, and efficacy of medications in varied conditions of the tumor microenvironment and the patient’s metabolismo. As na illustration od the model’s usefulness, a novel anti-tumor drug in the clinical trials phase, 3-bromopyruvate, which has the modeled metabolic pathways as a therapeutic target, was employed. The efficacy od 3-bromopyruvate was investigated, and the IC50 was found to be capable of significantly inhibiting tumor cell lines. When compared to basal metabolismo, its IC50 delayed glycolytic metabolismo by 12 minutes. As a result, the diabetic environment has a slowing Effect on glycolytic metabolismo. The obese environment had no significant diferences in this form os cancer as compared to the healthy environment. Tha value of mathematical modeling is clear, as the Effect of anew drug on metabolismo may be computer evaluated and used as a novel tool to provide a tailored approach to each patient.pt_PT
dc.identifier.tid202929787pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.22/19852
dc.language.isoengpt_PT
dc.subjectBioinformaticspt_PT
dc.subjectDiabetespt_PT
dc.subjectModelingpt_PT
dc.subjectObesitypt_PT
dc.subjectProstate cancerpt_PT
dc.titleMathematical modeling for pharmacological approaches directed to metabolic pathways in "diabetic paradox" in prostate cancerpt_PT
dc.typemaster thesis
dspace.entity.typePublication
rcaap.rightsopenAccesspt_PT
rcaap.typemasterThesispt_PT
thesis.degree.nameBioestatística e Bioinformática Aplicadas à Saúdept_PT

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