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Explore the basics of neoplasia and nonneoplastic growth disturbances, including molecular aspects, causes, and host-tumor interactions. Learn about DNA diseases, oncogenic viruses, and cell cycle regulators.
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General Pathology Basic Principles of Cellular and Organ Pathology Oncology - I Jaroslava Dušková Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague
General Oncology - 1 • Disorders of the cell proliferation and growth (hypertrophy, hyperplasia, metaplasia) • Neoplasms – disorders of cell proliferation and differentiation • Molecular biology of neoplasia - oncogenesis • Host - neoplasm interactions
Tumour swelling of any kind NEOPLASIA
NEOPLASIA Def.: persistent abnormal relativelyautonomous proliferation of cells
NEOPLASIA – history I. Ramayana – 2000 B.C. • therapy with knife • chemotherapy arsenical compounds
NEOPLASIA – history II. Galen – AD 131–201 TUMOURS • according to nature pregnancy • exceeding nature inflammatory, reparative, callus • against nature true neoplasms
Nonneoplastic Growth Disturbances – I MALFORMATIONS • complete or partial lack of development(aplasia, hypoplasia) • asymmetry • oversize • hamartoma • choristoma • ectopic tissue - +
Hamartia – Hamartoma Def.: A mass of disorganized tissue indigenous to the particular site.
Choristia - Choristoma Def.: A mass of ectopic tissue (cells) with a limmited growth potency
Nonneoplastic Growth Disturbances – II • repair • hypertrophy / atrophy - (incl.pseudohypertrophy) • hyperplasia • metaplasia • dysplasia • anaplasia – undifferentiation
Nonneoplastic Growth Disturbances – II • repair • hypertrophy / atrophy - (incl.pseudohypertrophy) • hyperplasia • metaplasia • dysplasia • anaplasia – undifferentiation
Nonneoplastic Growth Disturbances – II • repair • hypertrophy / atrophy • hyperplasia • metaplasia • dysplasia • anaplasia – undifferentiation
Nonneoplastic Growth Disturbances – II • repair • hypertrophy / atrophy • hyperplasia • metaplasia • dysplasia • anaplasia – undifferentiation
Nonneoplastic Growth Disturbances – II • repair • hypertrophy / atrophy • hyperplasia • metaplasia • dysplasia • anaplasia – undifferentiation
Growth Disturbances to Neoplasms Relation • differential diagnosis pseudotumours • precursors precanceroses (preblastomatoses) • both 1. and 2.
NEOPLASIA Def.: persistent abnormal relativelyautonomous proliferation of cells
Neoplasia (Tumour) • DNA disease • Stepwise accumulation of genetic abnormalities • Escapeof immunological clearing systems
External Irradiation chemical cancerogens oncogenic viruses Internal immunosupression (inborn, acquired) chronic irritation (inflammation) Neoplasia - causes
DNA HPV SV 40 – polyoma Adenoviruses Herpesviruses Epstein– Barr Hepatitis B RNA Rous sarcoma Leukemia HIV Oncogenic Viruses
Cell Cycle Regulators– control of cellular proliferation • polypeptide growth factors EGF, PDGF, FGF, TGFα,β (protooncogenes) • ligand receptor binding • activation via conformation alteration (kinase) • signal transduction – second messengers (tyrosine kinases) • activation of transcription factors • DNA synthesis initiation • cyclins and cyclin dependent kinases cdk • cdk associated inhibitors cki
Polypeptide growth stimulators EGF, PDGF, TGF α(protooncogenes) cytokins IL-1, TNF angiogenesis Polypeptide growth inhibitors T(ransforming)GF β interferon α prostaglandin E-2 Cell Cycle Regulators – growth factors
Cell Cycle Regulation Disorders– uncontroled cellular proliferation • polypeptide growth factors (e.g. EGF, PDGF, FGF,…) acting as oncogenes via overexpression • ligand receptor amplification • signal transducing proteins (e.g. ras oncoproteins) - activation othe mitogenic signaling pathway • nuclear DNA synthesis regulators (myc, jun, fos) • mitochondrial oncogenes (bcl-2) – prevention of apoptosis
Molecular Biological and Morphological Tumour Progression Normal cell dysplasia adenoma infiltrating carcinoma Loss of growth control Loss of apoptosis control Loss of Senescence control genomic instability activation proteases Metastasising tumour cell Molecular biological Morphological Tumour Progression
immune surveillance immune response spontaneous regression local preassure cachexia anaemia immunodepression products of neoplastic cells Host - Neoplasm Interactions
NEOPLASIA – function NEOPLASTIC CELL PRODUCTS: • immunoglobulin • osteiod • keratin • mucus • melanin • hormones
NEOPLASIA – function NEOPLASTIC CELL PRODUCTS: • immunoglobulin • osteiod • keratin • mucus • melanin • HORMONES
ENDOCRINE NEOPLASIAHormone Production and Function • mayor may not be present • unregulated – may be excessive • benign tumours more likely to be active • size of tumour not related to the degree of function • metastases may cause hyperfunction