Hyperthermia : a systems approach in analysis of the effects on different organization levels

Abstract

Aim: Hyperthermia is a potent addendum to the existing cancer treatment modalities (surgery, chemotherapy and radiotherapy) that can improve clinical outcome up to 25%, however, the molecular and physiological mechanisms determining cellular fate during hyperthermia are still unclear. The present study is a systematic overview on effects of hyperthermic treatment on different organization levels (biomacromolecules, mitochondria, cells, liver tissue) considering cancer and normal tissues, different temperature ranges, gender, age, drugs and drug metabolites. Methods: Parameters evaluated under the conditions of hyperthermia (37-51ºC) in biomacromolecules: protein denaturation and lipid phase transition; in isolated mitochondria: mitochondrial respiratory rate in different metabolic states, mitochondrial swelling, membrane potential, ROS generation; in normal and cancer cell lines: cell viability, plasma and mitochondrial membrane permeability, Ca2+, adenine and pyridine nucleotides concentration; in liver perfusion and thermoablation experiments: NAD(P)H fluorescence, mitochondrial functions. The combined treatment of hyperthermia with cisplatin was evaluated in cell culture, with acetaminophen and its metabolite NAPQI in mitochondrial model. [...]