1. General Pathology Basic Principles of Cellular and Organ Pathology Oncology - I Jaroslava Dušková Inst. Pathol.,1st Med. Faculty, Charles Univ. Prague

2. General Oncology - 1 u Disorders of the cell proliferation and growth (hypertrophy, hyperplasia, metaplasia) u Neoplasms – disorders of cell proliferation and differentiation u Molecular biology of neoplasia - oncogenesis u Host - neoplasm interactions

3. Tumour swelling of any kind NEOPLASIA

4. Def.: persistent abnormal relatively autonomous proliferation of cells

5. NEOPLASIA – history I. Ramayana – 2000 B.C. v therapy with knife v chemotherapy arsenical compounds

6. NEOPLASIA – history II. Galen – AD 131–201 TUMOURS v according to nature pregnancy v exceeding nature inflammatory, reparative, callus v against nature true neoplasms

7. Growth Disturbances & Their Relation to Neoplasms

8. Nonneoplastic Growth Disturbances – I MALFORMATIONS v complete or partial lack of development (aplasia, hypoplasia) v asymmetry v oversize v hamartoma v choristoma v ectopic tissue - +

9. Hamartia – Hamartoma Def.: A mass of disorganized tissue indigenous to the particular site.

10. Choristia - Choristoma Def.: A mass of ectopic tissue (cells) with a limmited growth potency

11. Nonneoplastic Growth Disturbances – II v repair v hypertrophy / atrophy - (incl.pseudohypertrophy) v hyperplasia v metaplasia v dysplasia v anaplasia – undifferentiation

12. Nonneoplastic Growth Disturbances – II v repair v hypertrophy / atrophy - (incl.pseudohypertrophy) v hyperplasia v metaplasia v dysplasia v anaplasia – undifferentiation

13. Nonneoplastic Growth Disturbances – II v repair v hypertrophy / atrophy v hyperplasia v metaplasia v dysplasia v anaplasia – undifferentiation

14. Nonneoplastic Growth Disturbances – II v repair v hypertrophy / atrophy v hyperplasia v metaplasia v dysplasia v anaplasia – undifferentiation

15. Nonneoplastic Growth Disturbances – II v repair v hypertrophy / atrophy v hyperplasia v metaplasia v dysplasia v anaplasia – undifferentiation

16. Growth Disturbances to Neoplasms Relation 1. differential diagnosis pseudotumours 2. precursorsprecanceroses (preblastomatoses) 3. both 1. and 2.

17. NEOPLASIA Def.: persistent abnormal relatively autonomous proliferation of cells

18. Neoplasia (Tumour) v DNA disease v Stepwise accumulation of genetic abnormalities v Escape of immunological clearing systems

19. Neoplasia - causes External v Irradiation v chemical cancerogens v oncogenic viruses Internal  immunosupression (inborn, acquired)  chronic irritation (inflammation)

20. Oncogenic Viruses DNA u HPV u SV 40 – polyoma u Adenoviruses u Herpesviruses Epstein– Barr u Hepatitis B RNA u Rous sarcoma u Leukemia u HIV

21. Cell Cycle Regulators – control of cellular proliferation u polypeptide growth factors EGF, PDGF, FGF, TGFα, β (protooncogenes) u ligand receptor binding u activation via conformation alteration (kinase) u signal transduction – second messengers (tyrosine kinases) u activation of transcription factors u DNA synthesis initiation u cyclins and cyclin dependent kinases cdk u cdk associated inhibitors cki

22. Cell Cycle Regulators – growth factors Polypeptide growth stimulators u EGF, PDGF, TGF α (protooncogenes) u cytokins – IL-1, – TNF angiogenesis Polypeptide growth inhibitors u T(ransforming)GF β u interferon α u prostaglandin E-2

23. Cell Cycle Regulation Disorders – uncontroled cellular proliferation u polypeptide growth factors (e.g. EGF, PDGF, FGF,…) acting as oncogenes via overexpression u ligand receptor amplification u signal transducing proteins (e.g. ras oncoproteins) - activation othe mitogenic signaling pathway u nuclear DNA synthesis regulators (myc, jun, fos) u mitochondrial oncogenes (bcl-2) – prevention of apoptosis

24. Molecular Biological and Morphological Tumour Progression Normal cell Loss of growth control Loss of apoptosis control Loss of Senescence control Metastasising tumour cell dysplasia adenoma infiltrating carcinoma Molecular biological Morphological Tumour Progression genomic instability activation proteases

25. Host - Neoplasm Interactions  immune surveillance  immune response spontaneous regression  local preassure  cachexia  anaemia  immunodepression  products of neoplastic cells

26. NEOPLASIA – function NEOPLASTIC CELL PRODUCTS: v immunoglobulin v osteiod v keratin v mucus v melanin v hormones

27. NEOPLASIA – function NEOPLASTIC CELL PRODUCTS: v immunoglobulin v osteiod v keratin v mucus v melanin v HORMONES

28. ENDOCRINE NEOPLASIA Hormone Production and Function v may or may not be present v unregulated – may be excessive v benign tumours more likely to be active v size of tumour not related to the degree of function v metastases may cause hyperfunction