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Neoplasia II & III: Understanding the Mechanisms and Impact of Cancer

This article explores the mechanisms of neoplasia, the factors that contribute to its development, the importance and consequences of cancer, and the diagnostic and clinical stages of cancer. It also covers the essential alterations for malignant transformation and the biology of tumor growth.

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Neoplasia II & III: Understanding the Mechanisms and Impact of Cancer

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  1. NEOPLASIA II & III PongsakMahanupab, M.D. Department of Pathology Faculty of Medicine Chiang Mai University connectnigeria.com Path351 – Sept.,2016

  2. วัตถุประสงค์ 1. ทราบกลไกและขั้นตอนการเกิดเนื้องอก 2. ทราบสิ่งที่สามารถก่อให้เกิดเนื้องอก 3. ทราบความสำคัญและผลของเนื้องอกต่อคน 4. ทราบปฏิกิริยาที่คนใช้ต่อต้านเนื้องอก 5. ทราบวิธีวินิจฉัยมะเร็งทางห้องปฏิบัติการ 6. ทราบวิธีการแบ่งขั้นและระยะของมะเร็งทางคลินิก

  3. REFERENCES Standard textbooks of pathology - Robbins - Anderson • Rubin • Websites

  4. NEOPLASIA Benigntumor Malignanttumor(cancer) Crab

  5. CANCER

  6. CANCER The common term for all malignant tumors

  7. Alltumorshavetwobasiccomponents. 1.Parenchyma - parenchymalcells 2. Stroma - connectivetissue - bloodvessels - lymphaticvessels - collagenbundle, etc. Desmoplasia = theformationofanabundantcollagenousstroma

  8. MOLECULAR BASISOF CANCER

  9. Carcinogenesis is a multistep processat both phenotypic and genetic levels

  10. Certain tumor arises from one single cell

  11. Nonlethal genetic damage - Genetic damage = Mutation

  12. In normal cell Four classes of normal regulatory genes

  13. 1. Growth-promoting proto-oncogenes - Promote normal growth and differentiation - Proto-oncogene - RAS, WNT, MYC, ERK, and TRK Oncogene

  14. 2. Growth-inhibiting cancer suppressor genes (anti-oncogenes)- p53, BRCA1, BRCA2, APC and RB1 - Regulate cell growth - Not to prevent tumor formation

  15. 3. Genes that control programmed cell death (apoptosis)

  16. 4. Genes that regulate repair of damaged cells

  17. ESSENTIAL ALTERATIONS FOR MALIGNANT TRANSFORMATION • Self-sufficiency in growth signals • Insensitivity to growth-inhibitory signals • Evasion of apoptosis

  18. ESSENTIAL ALTERATIONS FOR MALIGNANT TRANSFORMATION • Limitless replicative potential • Sustained angiogenesis • Ability to invade and metastasize • Defects in DNA repair

  19. They are the TARGETS of genetic damage

  20. BIOLOGY OF TUMOR GROWTH 1. Transformation 2. Growth of transformed cell 3. Local invasion 4. Distant metastasis

  21. Malignant cell Normal cell

  22. CARCINOGENIC AGENTS 1. CHEMICALS Two stages - INITIATION - cause permanent DNA damage, irreversible, has memory - PROMOTION - promoter (nontumorogenic) - reversible

  23. MAJOR CHEMICAL CARCINOGENS 1. Direct-Acting Carcinogens Alkylating agents - Anticancer drugs etc. Acylating agents

  24. MAJOR CHEMICAL CARCINOGENS 2. Procarcinogens that require metabolic activation - Polycyclic and heterocyclic aromatic hydrocarbons - Aromatic amines, amides, azo dyes - Natural plants and microbial products (Aflatoxin B1, betel nuts) - Others (nitrosamines and amides, vinyl chloride, nickel, chromium, insecticides, fungicides etc.)

  25. 2. RADIATION - UV (A,B,C) - Ionizing radiation and particles

  26. 3. VIRUS - DNA ONCOGENIC VIRUS Adenovirus Human papilloma virus Epstein-Barr virus Hepatitis B virus - RNA ONCOGENIC VIRUS HTLV - 1

  27. PREDISPOSITION FOR NEOPLASIA • GEOGRAPHIC AND RACIAL FACTORS - Sex

  28. 2. AGE - Incidence and age - Childhood < 1 year Neuroblastoma Wilms’ tumor Rhabdomyosarcoma Retinoblastoma

  29. 3. ENVIRONMENTAL AND CULTURAL FACTORS - Asbestos, vinyl chloride, 2-Napthylamine - UV, drugs - ALCOHOL : - cancer of oropharynx (excluding lips, larynx, esophagus) - Alcoholic hepatitis - Hepatocellular carcinoma

  30. - CIGARETTE SMOKING : cancer of lung, lip, pharynx,pancreas, urinary bladder - VIRAL INFECTION: cancer of cervix (HPV)

  31. 4. HEREDITARY - Lung cancer - Breast cancer - Retinoblastoma - Osteogenic sarcoma - Multiple polyposis coli - in general 3 times

  32. Inherited Predisposition to Cancer 1. Inherited cancer syndromes (Autosomal Dominant) Strong family history of uncommon cancer and /or associated marker phenotype - Retinoblastoma (familial) - Familial adenomatous polyps of colon - Multiple endocrine neoplasia syndrome - Neurofibromatosis types 1 and 2 - Von Hippel-Lindau syndrome

  33. Inherited Predisposition to Cancer 2. Familial cancers Evident familial clustering of cancer but role of inherited predisposition may not be clear in an individual case - Breast cancer - Ovarian cancer - Colon cancer

  34. Inherited Predisposition to Cancer 3. Autosomal recessive syndromes of defective DNA repair - Xerodermapigmentosum - Ataxia-telangiectasia - Bloom syndrome - Fanconi syndrome

  35. 5. PREDISPOSING FACTORS PRECANCEROUS LESIONS - Endometrial hyperplasia - Cervical dysplasia - Bronchial mucosal metaplasia and dysplasia

  36. - Cirrhosis - Chronic atrophic gastritis - Solar keratosis - Chromosomal breakage syndrome - Ulcerative colitis - Leukoplakia

  37. BIOLOGY OF TUMOR GROWTH 1. Transformation 2. Growth of transformed cell 3. Local invasion 4. Distant metastasis

  38. KINETICS OF TUMOR CELLS • Proliferative pool • Nonproliferative pool

  39. Cell cycle time of tumor cells are longer than or equal to that of normal cells • Growth fraction

  40. TUMOR ANGIOGENESIS • NEW CAPILLARY FORMATION • Tumor-associated angiogenic factor from tumor cells or macrophages • eg. Basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF)

  41. Chemotactic and mitogenic factors for endothelial cells • Induce production of proteolytic enzyme that allows penetration of the stroma by endothelial cells

  42. BIOLOGY OF TUMOR GROWTH 1. Transformation 2. Growth of transformed cell 3. Local invasion 4. Distant metastasis

  43. MECHANISM OF INVASION AND METASTASIS

  44. Two phases 1. Invasion of extracellular matrix (basement membranes and interstitial tissue) - Detachment of tumor cells (loss of epithelial cadherins) - Attachment of matrix component

  45. - Degradation of ECM (proteolytic enzymes liberate from tumor cells, fibroblasts or macrophages) - Migration of tumor cells

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