GENERAL ETIOLOGY. Definition of health and illness, determining and predisposing etiological factors, pathogenesis, inherited and congenital diseases, teratogenicity, multifactorial diseases. Comprehensive classification of causes of illness: inherited and acquired (environmental or endogenous) causes. Environmental etiology: pathogenesis of local or systemic injury by high or low temperature, exciting and ionizing radiation, electricity, changes of atmospheric pressure.
ONCOLOGY. General features of tumor growth. Monoclonal origin of tumors. Cancer stem cells. Alterations of differentiation: blocking of differentiation (e.g Acute Promyelocytic Leukemia), epithelial-mesenchimal transition, anaplasia, metaplasia (e.g Barrett’s oesophagus), pre-malignant lesions, dysplasia, in situ carcinomas. Classification of tumors: differential characteristics between benign and malignant tumors. Nomenclature. Morphological and metabolic atypia. Molecular basis of neoplastic transformation: proto-oncogenes, oncogenes, and tumor suppressor genes. Mechanisms of oncogene activation and action of oncoproteins (e.g EGF-R, RAS and Ras-related genes), Abl/BCR, MYC, BCL-2); inactivation of tumor suppressor genes and action of tumor suppressor proteins (e.g APC, VHL, TP53 e p53-related genes). Cancerogenesis: chemical, physical and microbiological causes. Hereditary cancer syndromes: mutations in DNA repair genes (e.g Xeroderma Pigmentosus, Lynch-I syndrome, Bloom syndrome, Fanconi’s aplastic anaemia, breast and ovarian carcinoma), mutations in cell cycle genes (e.g Li-Fraumeni syndrome, Atassia telengectasica, Retinoblastoma, Multiple Endocrine Neoplasias (MEN-1 e -2), Familial adenomatous polyposis (FAP)). Multistep carcinogenesis: experimental models, tumor promoting agents in human oncology, role of hormones in neoplastic progression (hints of SERM therapy). Local invasion: changes of cell adhesion and locomotion, extracellular matrix degradation, anchorage-independent growth, role of microenvironment, neo-angiogenesis, metastatic process, routes of cancer dissemination, metastasis tropism. Role of immune system: tumor antigens, immune surveillance and evasion. Hints of paraneoplastic syndromes. Hints of tumor epidemiology and risk factors. Tumor grading and staging. Hints of targeted therapy: monoclonal antibodies and tyrosine kinase inhibitors.
IMMUNOPATHOLOGY. Hypersensitivity: general overview, type I hypersensitivity (local allergic reactions and systemic anaphylaxis), type II hypersensitivity (cytotoxicity, agonist/antagonist antibodies, blood groups, transfusion incompatibility, erythroblastosis fetalis), type III hypersensitivity (serum sickness, Arthus reaction), type IV hypersensitivity (CD4+- e CD8+-mediated reactions). Etiopathogenesis of autoimmunity: predisposing factors and examples of autoimmune diseases (LES, rheumatoid arthritis).