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Human Bio Iii Oncology I
 

Human Bio Iii Oncology I

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    Human Bio Iii Oncology I Human Bio Iii Oncology I Presentation Transcript

    • Human Biology III Oncology I Ken Bauer [email_address]
    • 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.
    • 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
    • Cancer Terminology
      • Cancer is a disorder that occurs at a cellular level
      • Cancer occurs when genetic alterations result in the unregulated proliferation of cells
    • Cancer Terminology
      • Cancer - A group of diseases
      • Anaplasia - Lack of differentiation
      • Dysplasia - Abnormal size, shape
      • Hyperplasia - Increase in number of cells
    • 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
    • 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
    • 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
    • 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
    • Leading Sites of New Cancer Cases and Deaths—2000 Estimates
    • Age-Adjusted Cancer Death Rates,* Females by Site, US, 1930-1996
    • Age-Adjusted Cancer Death Rates,* Males by Site, US, 1930-1996
    • 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
    • Etiology of Cancer
      • Environmental factors
      • Viruses
      • Lifestyle factors
      • Medical - Drugs and Hormones
      • Hereditary
    • 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
    • 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
    • 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 ?
    • 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
    • Drugs and Hormones
      • Alkylating Agents
        • Cyclophosphamide - bladder
        • melphalan - leukemia
      • Antimetabolites
        • Azathioprine - NHL, skin
      • Corticosteroids
        • Prednisone - NHL
    • Drugs and Hormones
      • Estrogens
        • Diethylstilbestrol - vaginal Ca in offspring
      • Combined Modalities
        • Chemo + Radiation - leukemia
      • Others
        • Phenacetin - renal
        • Phenytoin - liver (rats)
        • Chloramphenicol - leukemia
    • 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
    • Hereditary/Genetic
      • Breast cancer
        • If first degree relative has(d) breast cancer greatly increases the risk
        • BRCA1 mutation
      • Retinoblastoma
        • Rb
    • 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
    • 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
    • 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
    • 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)
    • Malignant Transformation
      • Genetic alterations transform normal cells into malignant cells
      • Two (multiple) hit hypothesis
        • predisposition + external factor
        • multiple external factors
    • Questions?