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Human Bio Iii Oncology I
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  • 1. Human Biology III Oncology I Ken Bauer [email_address]
  • 2. Objectives
    • Following the lecture the student should be able to:
    • 1. Differentiate between the characteristics of benign and malignant tumors.
    • 2. List the 5 broad categories of cancer etiology
    • 3. Describe the effect cigarette smoking has had on cancer incidence and death rates from 1930 to present.
  • 3. Objectives
    • 4. Explain the roles of oncogenes proro-oncogenes, and tumor suppressor genes in the malignant transformation .
    • 5. List the 3 most common tumor types in men and women by gender
  • 4. Cancer Terminology
    • Cancer is a disorder that occurs at a cellular level
    • Cancer occurs when genetic alterations result in the unregulated proliferation of cells
  • 5. Cancer Terminology
    • Cancer - A group of diseases
    • Anaplasia - Lack of differentiation
    • Dysplasia - Abnormal size, shape
    • Hyperplasia - Increase in number of cells
  • 6. Benign Tumor
    • Characteristics typical of tissue of origin
    • Slow rate of growth
    • Slowly progressive; Not fatal if untreated
    • Encapsulated growth
    • No tissue destruction
    • Rare recurrence
    • Poor prognosis only if unable to remove
  • 7. Malignant Tumor
    • Characteristics atypical of tissue of origin
    • Slow or rapid rate of growth
    • Usually progressive; Fatal if untreated
    • Growth by infiltration or metastasis
    • Tissue destruction is common
    • Recurrence is common
    • Fatal prognosis if uncontrolled
  • 8. 2000 Estimated Cancer Statistics
    • 1,220,100 : Estimated number of new cancer cases.
      • Over 100 types of cancer most common ->
      • Women: Breast, Lung, Colon
      • Men: Prostate, Lung , Colon
    • 552,200 : Estimated number of cancer deaths.
      • Lung cancer is leading cause of cancer deaths.
            • Source: American Cancer Society, www.cancer.org
  • 9. Cancer Statistics
    • From 1930 until 1989 there was a steady overall rise in the age-adjusted death rate due to cancer
    • Since 1989 the mortality trend is downward
    • Major cause of increase over 60 years was increasing tobacco use and lung cancer
    • The current trend down is due at least in part to decreased tobacco use
  • 10. Leading Sites of New Cancer Cases and Deaths—2000 Estimates
  • 11. Age-Adjusted Cancer Death Rates,* Females by Site, US, 1930-1996
  • 12. Age-Adjusted Cancer Death Rates,* Males by Site, US, 1930-1996
  • 13. Etiology of Cancer
    • The most common way of treating cancer today is to treat after detection
    • Ideal strategy is prevention:
      • eliminate/reduce controllable risk factors
        • smoking, diet, alcohol
      • chemoprevention
        • tamoxifen {breast}
        • finasteride {prostate} -investigational
        • retinoids {head and neck} -investigational
  • 14. Etiology of Cancer
    • Environmental factors
    • Viruses
    • Lifestyle factors
    • Medical - Drugs and Hormones
    • Hereditary
  • 15. Environmental Factors
    • Industrial/Occupational
      • Coal miners, factory workers, asbestos
    • Ultraviolet Light
      •  risk of skin cancers
    • Ionizing Radiation (Lifestyle Factor?)
      • X-rays, nuclear weapons or accidents
        • evidence from Japan & Chernobyl
          •  risk of breast cancer and leukemias
        • Thyroid irradiation (for hyperthyroid)
          •  risk thyroid cancer
  • 16. Viruses
    • Epstein-Barr virus - Hodgkin’s lymphoma
    • Human Immuno-deficiency virus - NHL and Kaposi’s sarcoma
    • Human Papilloma virus - Cervical cancer
    • Hepatitis A, B - Hepatocellular cancer
    • HTLV-1 - T-cell leukemia
  • 17. Lifestyle Factors
    • Tobacco - Cigarette Smoking
      • lung, oropharygeal, and bladder cancers
      • “If cigarettes did not exist lung cancer would be an rarity”
    • Radon
      • lung cancer
    • Electromagnetic fields
      • cell phones and high tension power lines
      • causal relationship ?
  • 18. Lifestyle Factors
    • Alcohol
      • associated with several cancers including esophogeal, liver, oropharynx, breast and larynx
      • usually associated with another carcinogen
    • Diet
      • implicated in colorectal cancer
      • Decrease Fat, Increase Fruits and Vegetables
  • 19. Drugs and Hormones
    • Alkylating Agents
      • Cyclophosphamide - bladder
      • melphalan - leukemia
    • Antimetabolites
      • Azathioprine - NHL, skin
    • Corticosteroids
      • Prednisone - NHL
  • 20. Drugs and Hormones
    • Estrogens
      • Diethylstilbestrol - vaginal Ca in offspring
    • Combined Modalities
      • Chemo + Radiation - leukemia
    • Others
      • Phenacetin - renal
      • Phenytoin - liver (rats)
      • Chloramphenicol - leukemia
  • 21. Hereditary/Genetic
    • Cancer as Primary Manifestation
      • Retinoblastoma, neuroblastoma, pheochromocytoma
    • Inherited Condition
      • Familial polyposis, Fanconi’s anemia, xeroderma pigmentosum
    • Inherited Disease of Immune System
      • Wiskott-Aldrich Syndrome
    • Chromosomal Aberrations
      • Down’s Syndrome, Fanconi’s anemia
  • 22. Hereditary/Genetic
    • Breast cancer
      • If first degree relative has(d) breast cancer greatly increases the risk
      • BRCA1 mutation
    • Retinoblastoma
      • Rb
  • 23. Genetic Regulation
    • Oncogenes/Proto-Oncogenes
      • normal exons which when mutated promote oncogenesis
        • wt = proto-oncogene (no tumor promoting effect)
        • mutant = oncogene
    • Tumor Suppressor Genes
      • Genes which regulate cell proliferation and prevent cell from dividing ‘out of control’
        • wt = ‘prevent’ cell from becoming a tumor
        • mutant = unable to prevent tumor-genesis
  • 24. Proto-Oncogenes and Malignant Transformation
    • N-myc {transcription factor}
      • Neuroblastoma
    • Erb-B(her2neu) {cell surface receptor}
      • Breast cancer
    • RAS {intracellular messenger}
      • Acute Myeloid Leukemia
    • BCL {transcription factor/apoptosis}
      • Chronic Myeloid Leukemia
  • 25. Tumor Supressor Genes
    • Rb (cell cycle)
      • retinoblastoma, osteosarcoma
    • p53 (growth arrest/apoptosis)
      • sarcomas, breast, and brain tumors
    • BRCA1 and BRCA2 (DNA repair)
      • breast and ovarian tumors
    • E-Cadherin (cell adhesion regulator)
      • breast, colon, skin, and lung
  • 26. Cell Cycle Entry to Death: Regulation Growth Factor Receptor Activation Intracellular Kinase Cascade Early Nuclear Proteins (myc, fos, jun etc.) Cell Cycle Activators (cyclins) Regulators (Rb) Genome Checkers (p53) Apoptosis: Cell Cycle Balancers (bcl-2 family)
  • 27. Malignant Transformation
    • Genetic alterations transform normal cells into malignant cells
    • Two (multiple) hit hypothesis
      • predisposition + external factor
      • multiple external factors
  • 28. Questions?