RESUMO
In this paper elaborate mathematical models and investigative computer simulations for the chemotherapy of haematological and gynaecological cancers are presented. The pharmacodynamics of the actions of the antineoplastic drugs are described by multicompartmental models with the associated model equations taking into account the drug dosage, type of delivery, route of delivery, the intercompartmental drug-transition constants, degradation parameters, and leakage coefficients. The cell-cycle phase-specific six-compartmental cytokinetic tumour growth model presented here incorporates the cell-cycle phase residence time, time lags associated with drug-induced cell-kill, or progression delays due to repair of cell damage. Investigative computer simulations are performed depicting the effects of cell-cycle phase-specific antineoplastic drugs on haematological and gynaecological cancer cells. The computer simulations are performed under various clinically plausible parametric configurations to elucidate the effects of certain critical variables such as tumour cell burden, mode of antineoplastic drug delivery, tumour cell loss and cell-cycle cytokinetic parameters.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias Hematológicas/tratamento farmacológico , Modelos Biológicos , Antineoplásicos/administração & dosagem , Ciclo Celular/efeitos dos fármacos , Simulação por Computador , Feminino , Neoplasias dos Genitais Femininos/patologia , Neoplasias Hematológicas/patologia , Humanos , MatemáticaRESUMO
A mathematical model is developed to describe the process of adoptive cellular immunotherapy (ACI) using the scheme of Rosenberg and other investigators. The model exhibits the dynamics of tumour cells as well as the time evolution of the tumoricidal immunocytes, such as ex vivo interleukin-2 (IL-2) expanded natural killer (NK) cells, lymphokine activated killer (LAK) cells, tumour derived activated cells (TDAC), and interferon-gamma (IFN-gamma) activated killer monocytes (AKM). The model is described mathematically by a system of nonlinear functional-differential equations. Computer simulations based on the model equations are performed using parametric configurations analogous to the protocols used in the clinical trials. The model elucidates explicitly the effects of time delays, effector immunocyte-to-tumour cell ratio, tumour growth parameters, and other critical variables on the prognosis, and the therapeutic efficacy of adoptive cellular immunotherapy.
