Biology of Cancer

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Biology of Cancer

• Chapter 11

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Cancer

• Derived from Greek word for crab, karkinoma
• Malignant tumor
• Tumor
• Also referred to as a neoplasmnew growth

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Benign vs. Malignant Tumors
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Classification and Nomenclature

• Benign tumors
• Named according to the tissues from which they
  arise, and include the suffix oma
• Lipoma
• Glioma
• Leiomyoma
• Chondroma

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Classification and Nomenclature

• Malignant tumors
• Named according to the tissues from which they
  arise
• Malignant epithelial tumors are referred to as
  carcinomas
• Adenocarcinoma and basal cell carcinoma
• Malignant connective tissue tumors are referred
  to as sarcomas
• Chondrosarcoma and osteosarcoma

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Classification and Nomenclature

• Cancers of lymphatic tissue are lymphomas
• Cancers of blood-forming cells are leukemias
• Carcinoma in situ (CIS)
• Pre-invasive epithelial malignant tumors of
  glandular or epithelial origin that have not
  broken through the basement membrane or invaded
  the surrounding stroma

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Classification and Nomenclature
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Classification and Nomenclature
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Cancer Cells

• Transformation
• Cancer cells independence from normal cellular
  controls
• Anchorage independent
• Immortal
• Anaplasia
• Pleomorphic

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Cancer Stem Cells

• Stem cells self-renew
• Cell divisions create new stem cells
• Stem cells are multipotent
• Ability to differentiate into multiple different
  cell types

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Cancer Stem Cells
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Cancer Stem Cells
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Tumor Markers

• Tumor cell markers (biological markers) are
  substances produced by cancer cells or that are
  found on plasma cell membranes, in the blood,
  CSF, or urine
• Hormones
• Enzymes
• Genes
• Antigens
• Antibodies

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Tumor Markers

• Tumor markers are used to
• Screen and identify individuals at high risk for
  cancer
• Diagnose specific types of tumors
• Observe clinical course of cancer

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Cancer-Causing Mutations

• Cancer is predominantly a disease of aging
• Clonal proliferation or expansion
• Due to a mutation, a cell acquires
  characteristics that allow it to have selective
  advantage over its neighbors
• Increased growth rate or decreased apoptosis
• Multiple mutations are required before cancer can
  develop

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Cancer-Causing Mutations
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Types of Mutated Genes

• Secretion of growth factors (autocrine
  stimulation)
• Increased growth factor receptors
• Signal from cell-surface receptor is mutated in
  the on position
• Mutation in the ras intracellular signaling
  protein
• Inactivation of Rb tumor suppressor
• Activation of protein kinases that drive the cell
  cycle
• Mutation in the p53 gene

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Types of Mutated Genes
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Angiogenesis

• Growth of new vessels
• Advanced cancers can secrete angiogenic factors

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Hallmarks of Cancer
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Telomeres and Immorality

• Body cells are not immortal and can only divide a
  limited number of times
• Telomeres are protective caps on each chromosome
  and are held in place by telomerase
• Telomeres become smaller and smaller with each
  cell division

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Telomeres and Immorality
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Oncogenes and Tumor-Suppressor Genes

• Oncogenes
• Mutant genes that in their nonmutant state direct
  protein synthesis and cellular growth
• Tumor-suppressor genes
• Encode proteins that in their normal state
  negatively regulate proliferation
• Also referred to as anti-oncogenes
• Proto-oncogene
• A normal, nonmutant gene that codes for cellular
  growth

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Mutation of Normal Genes

• Point mutations
• Changes in one or a few nucleotide base pairs
• Chromosome translocation
• A piece on one chromosome is transferred to
  another
• Gene amplification
• Duplication of a small piece of chromosome over
  and over
• Results in an increased expression of an oncogene

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Mutation of Normal Genes
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Mutation of Normal Genes
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Mutation of Normal Genes

• Mutation of tumor-suppressor genes
• Allows unregulated cellular growth
• Loss of heterozygosity
• Both chromosome copies of a gene are inactivated
• Gene silencing
• Whole regions of chromosomes are shut off while
  the same regions in other cells remain active

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Mutation of Normal Genes
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Mutation of Normal Genes

• Caretaker genes
• Encode for proteins that are involved in
  repairing damaged DNA
• Chromosome instability
• Increased in malignant cells
• Results in chromosome loss, loss of
  heterozygosity, and chromosome amplification

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Inflammation and Cancer

• Chronic inflammation is an important factor in
  the development of cancer
• Cytokine release from inflammatory cells
• Free radicals
• Mutation promotion
• Decreased response to DNA damage

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Genetics and Cancer

• Exposure to mutagens
• If the mutation occurs in somatic cells, it is
  not passed to progeny
• If the mutation occurs in germline cells, it can
  be passed to future generations

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Viruses and Cancer

• Implicated
• Hepatitis B and C viruses
• Epstein-Barr virus (EBV)
• Kaposi sarcoma herpesvirus (KSHV)
• Human papillomavirus (HPV)
• Human T cell leukemialymphoma virus (HTLV)

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Bacterial Cause of Cancer

• Helicobacter pylori
• Chronic infections are associated with
• Peptic ulcer disease
• Stomach carcinoma
• Mucosa-associated lymphoid tissue lymphomas

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Environmental Risk Factors

• Tobacco
• Multipotent carcinogenic mixture
• Linked to cancers of the lung, lower urinary
  tract, aerodigestive tract, liver, kidney,
  pancreas, cervix uteri, and myeloid leukemia

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Environmental Risk Factors

• Ionizing radiation
• Emission from x-rays, radioisotopes, and other
  radioactive sources
• Exposure causes cell death, gene mutations, and
  chromosome aberrations
• Bystander effects
• Poor gene repair
• Changes in gap junction intercellular
  communication

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Ionizing Radiation
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Environmental Risk Factors

• Ultraviolet radiation
• Causes basal cell carcinoma, squamous cell
  carcinoma, and melanoma
• Principal source is sunlight
• Ultraviolet A (UVA) and ultraviolet B (UVB)
• Promotes skin inflammation and release of free
  radicals

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Environmental Risk Factors

• Alcohol consumption
• Risk factor for oral cavity, pharynx,
  hypopharynx, larynx, esophagus, and liver cancers
• Cigarette/alcohol combination increases a
  persons risk

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Environmental Risk Factors

• Sexual reproductive behavior
• Carcinogenic types of human papillomavirus
• High-risk HPV
• Physical activity
• Reduces cancer risk
• Decreases insulin and insulin-like growth factors
• Decreases obesity
• Decreases inflammatory mediators and free
  radicals
• Increased gut motility

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Environmental Risk Factors

• Occupational hazards
• Substantial number of occupational carcinogenic
  agents
• Asbestos
• Dyes, rubber, paint, explosives, rubber cement,
  heavy metals, air pollution, etc.
• Radon

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Environmental Risk Factors

• Electromagnetic fields
• Carcinogenic?
• Are they, or arent they?

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Environmental Risk Factors

• Diet
• Xenobiotics
• Toxic, mutagenic, and carcinogenic chemicals in
  food
• Activated by Phase I activation enzymes
• Defense mechanisms
• Phase II detoxification enzymes
• Examples
• Compounds produced in the cooking of fat, meat,
  or proteins
• Alkaloids or mold by-products

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Environmental Risk Factors

• Obesity
• Correlates with the body mass index (BMI)
• Adipose tissue is active endocrine and metabolic
  tissue
• In response to endocrine and metabolic signaling,
  adipose tissue releases free fatty acids
• Increased free fatty acids gives rise to insulin
  resistance and causes chronic hyperinsulinemia
• Correlates with colon, breast, pancreatic, and
  endometrial cancers