CAS PS 332 Lecture Notes - Lecture 13: Natural Killer Cell, Breast Cancer, Perforin

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Published on 22 May 2019
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Lecture 13: 4/9/19
Cancer
o Group of >100 diseases
o Characterized by presence of new, abnormal cells that multiply and
spread beyond control
Neoplastic cells new & nearly unlimited growth that robs the body of nutrients
w/ no beneficial effects
o Benign
Localized; little threat to physical health
o Malignant
Spread to surrounding tissue or other sites
Metastasis move to other sites via lymph or blood
Do not respond to “normal” controls on cell growth & division
Organ damage; death
4 types of malignant growths:
o Carcinoma cancers of the epithelial tissues
Epithelial tissues line outside & inner surfaces of body (skin,
stomach lining, mucous membranes, etc.)
Cancers of breast, prostate, colon, lungs, pancreas, skin
Account for 85% of adult cancer cases
o Sarcoma cancer in connective tissues
Bone, muscle, cartilage
Account for 2% of adult cancer cases
o Lymphoma cancer of the lymphatic system
Hodgkin’s disease & non-Hodgkin’s lymphoma
o Leukemia cancer of blood or blood-forming cells
Blood, stem cells, bone marrow
Proliferation of white blood cells in bloodstream & bone marrow >>
damage to immune system
Most common type of pediatric cancer (30%)
Cancer and the Immune System
o Immune surveillance theory: NK cells & macrophages recognize & kill
cancer cells
Macrophages Secrete tumor necrosis factor (TNF)
Necrosis = “starve” tumor by cutting off access to
blood/nutrients
NK Cells >> Inject perforin >> Induce apoptosis
o Cancer >> Breakdown of 2 “control systems” within single cell:
Cell proliferation
Necessary for normal growth, development, repair
Oncogene mutated gene >> inappropriate proliferation
Safeguards against excessive cell growth
Tumor suppressor genes prevent mutations & repair
damaged DNA
o Stop proliferation >> Allow DNA repair
o Trigger apoptosis
o Factors that accelerate mutations:
Smoking (carcinogens)
Fatty diet
Radiation exposure
Certain viruses (e.g., HPV)
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Accelerate breakdown of control systems
o Is stress related to immunity & cancer?
Animal studies (virus-induced tumors):
Increased Tumor growth
Decreased NK cell cytotoxicity
Increased Angiogenesis
Increased Circulating glucose
Limited human studies
Perceived stress >> Impaired NK cell cytotoxicity
o Clinical significance >> Increased cancer risk???
Stress >> “mutagenesis” (damage to cell DNA)
Emerging evidence: childhood adversity may impact
cancer development later in life
Risk Factors
o Risk factors increase a person’s chance of developing cancer, but not
every person with those risk factors will develop cancer
o Inherent
Genetics
~5-10% cancers inherited (esp. breast, prostate, ovarian,
colorectal)
Breast cancer: 95% linked to combination of genetic &
non-genetic risk
1st degree relative 2x to 3x increased risk
Age: strongest risk factor
Increased incidence & mortality
But, depends on the type of cancer e.g., bone cancers
most common <20 years old
Race & Ethnicity
African-Americans higher cancer incidence and mortality
than all other groups
Breast cancer: highest incidence in whites, but highest
mortality in African-Americans
o Environmental
Carcinogen
Cancer-causing agent such as tobacco, ultraviolet
radiation, or an environmental toxin
Toxic chemicals
o E.g., asbestos, vinyl chloride, arsenic
Radiation
1 in 5 Americans will develop skin cancer
E.g., melanoma potentially deadly form of cancer within
the melatonin-containing cells of the skin
o Early exposure, thinning of ozone layer, tanning
High frequency radiation, ionizing radiation, and ultraviolet
radiation are proven carcinogens
o Emotional
Periodic and persistent clinical depression common among cancer
patients (13-40%)
Linked to higher risk of early death among people with
cancer
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