Antioxidant Enzymes and Related Mechanisms in Malignant Pleural Mesothelioma

..................................................................................................................................................................6 LIST OF ORIGINAL PUBLICATIONS .....................................................................................................................8 ABBREVIATIONS........................................................................................................................................................9 INTRODUCTION.......................................................................................................................................................11 REVIEW OF THE LITERATURE............................................................................................................................13 MALIGNANT PLEURAL MESOTHELIOMA ..........................................................................................13 History ...............................................................................................................................................13 Epidemiology .....................................................................................................................................13 Etiology..............................................................................................................................................13 Pathogenesis and pathology ..............................................................................................................15 Clinical features and diagnosis .........................................................................................................16 Treatment and prognosis ...................................................................................................................17 LUNG CANCER ................................................................................................................................18 REACTIVE OXYGEN AND NITROGEN SPECIES ...................................................................................19 ANTIOXIDANTS...............................................................................................................................20 Superoxide dismutases.......................................................................................................................21 Glutathione ........................................................................................................................................23 Enzymes in the glutathione redox cycle: Glutathione peroxidase (GPx) and glutathione reductase (GR) ...................................................................................................................................................24 Enzymes in glutathione biosynthesis .................................................................................................25 Glutathione S-transferases (GSTs) ....................................................................................................27 Catalase .............................................................................................................................................27 OTHER PROTEINS WITH ANTIOXIDANT CAPACITY............................................................................27 ATP-DEPENDENT MULTIDRUG TRANSPORTERS...............................................................................28 P-glycoprotein ...................................................................................................................................28 MRP family ........................................................................................................................................29 OTHER MECHANISMS OF CYTOTOXIC DRUG RESISTANCE ................................................................31 AIMS OF THE STUDY ..............................................................................................................................................33