Cancer

Cancer 150 150 Tony Guo

Cancer

Cancer – Incidence

  • Group of diseases characterized by uncontrolled and unregulated growth of cells
  • Occurs in people of all ages
    • Majority of cases are diagnosed in those over age 55
  • Both the incidence and mortality rate of cancer has been declining
    • Incidences of lung, colorectal, breast, and oral cancer have decreased
    • Other cancers have increased
    • Higher in men than women
    • Second most common cause of death in United States after heart disease
    • Leading cause of death in people 40-79 years of age
  • > 14.5 million Americans are alive today who have a history of cancer
    • Disease free
    • In remission
    • Under treatment

 

Biology of Cancer

  • Two major dysfunctions in the process of cancer development:
    • Defective cell proliferation (growth)
      • Stem cells
        • Undifferentiated cells
        • Ultimately differentiate and become mature, functioning cells of only that tissue
      • All cells are controlled by an intracellular mechanism that determines proliferation
        • Orderly process progressing from a state of immaturity to a state of maturity
        • Stable and will not change
      • Cancer cells grown in culture are characterized by loss of contact inhibition
        • Grow on top of one another and on top of or between normal cells
      • Cancer cells respond differently than normal cells to intracellular signals regulating equilibrium
        • Divide indiscriminately and continuously
  • Pyramid effect
  • Defective cell differentiation
    • Two types of genes that can be affected by mutation are
      • Protooncogenes 
        • Regulate normal cellular processes such as promoting growth
        • Genetic locks that keep cells functioning normally
        • Mutations that alter their expression can activate them to function as oncogenes
      • Tumor suppressor genes 
        • Suppress growth
        • Function to regulate cell growth
  • Prevent cells from going through the cell cycle
  • Mutations make them inactive
  • Result in loss of suppression of tumor growth

Gene mutations: Development of cancer

  • Inherited
    • About 5% to 10% of all cancers or predisposition to cancers are inherited
    • Lead to a very high risk for cancer
  • Acquired 
    • Most cancers are acquired
      • Chemical
        • Many chemicals have been identified as carcinogens over the years
          • Benzene
          • Arsenic
          • Formaldehyde
      • Radiation
        • Radiation can cause cancer in almost any human tissue
        • Damage occurs to DNA
        • Ultraviolet radiation is associated with melanoma and squamous and basal cell carcinoma
          • Sunlight is main source of UV exposure
      • Viral
Virus Associated cancer
Epstein-Barr virus (EBV) Burkitt’s lymphoma
Human immunodeficiency virus (HIV) Kaposi sarcoma
Hepatitis B virus Hepatocellular carcinoma
Human papillomavirus (HPV) Squamous cell carcinomas

 

  • Promotion
    • Characterized by reversible proliferation of altered cells
    • Activities of promotion are reversible
      • Obesity
      • Smoking, alcohol
      • Dietary fat
  • Latent period 
    • May range from 1 to 40 years
    • Length of latent period associated with mitotic rate of tissue of origin and environmental factors
    • For disease to be clinically evident, tumor must reach a critical mass that can be detected
  • Progression
    • Characterized by 
      • Increased growth rate of tumor
      • Invasiveness
      • Metastasis (spread of the cancer to a distant site)
        • The most frequent sites of metastasis are lungs, liver, bone, brain and cerebrospinal, and adrenal gland
        • The pathogenesis of cancer metastasis. 
          • To produce metastases, tumor cells must detach from the primary tumor and enter the circulation, survive in the circulation to rest in the capillary bed, adhere to capillary basement membrane, gain entrance into the organ parenchyma, respond to growth factors, proliferate and induce angiogenesis, and evade host defenses.
        • Detached cells can invade lymph nodes and vascular vessels to travel to distant sites
        • Most mobile tumor cells do not survive
        • Surviving tumor cells must create an environment conducive to growth and development

 

Role of immune system

  • Immune response is to reject or destroy cancer cells
    • May be inadequate as cancer cells arise from normal human cells
  • Some cancer cells have changes on their surface antigens
    • Tumor-associated antigens (TAAs)
  • Cytotoxic  T cells 
    • Kill tumor cells directly
    • Produce cytokines
  • Natural killer cells and activated macrophages can lyse tumor cells
  • B cells produce antibodies that bind to tumor cells

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