Transcript cancer_teacher

Chapter 23
Cancer
RISK
versus
BENEFIT
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OUTLINE
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Introduction
Normal Cells
Regulation of Cell Division
Tumor Suppressor Genes and Apoptosis
Normal Cell Characteristics
Cancer Cell Characteristics
Angiogenesis
Metastasis
Causes of Cancer
Diagnosis and Treatment of Cancer
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Introduction
The study of cancer is called?
Oncology.
The medical specialist for cancer?
Oncologist.
1/3 Americans will deal with cancer in their
lifetime!
> 50% will survive their cancer.
The critical factor is early detection.
The earlier the cancer is detected, the more
likely it can be effectively treated.
With cancer, FEAR can kill you. . . . .
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Normal Cells
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With few exceptions, cells within a tissue
adhere to one another and are joined by
various junctions.
Chemical signals between cells tell them
whether they should be dividing or not
dividing.
– Stimulatory growth factors.
– Inhibitory growth factors.
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Regulation of Cell Division
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Two sets of genes control cell division.
– Proto-oncogenes.
 Code for transcription factors that control
gene expression.
 When mutated they become Oncogenes.
 “tumor genes”, “lump genes”.
– Tumor suppressor genes.
 Some are transcription factors that control
the expression of proto-oncogenes, while
others prevent molecules in the stimulatory
pathway from working.
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Cell Cycle Regulation
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Tumor Suppressor Genes and Apoptosis
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Certain tumor suppressor genes (TSG) also
control the occurrence of apoptosis.
“Cell death”.
– Enzymes that carry out apoptosis are
always present in a cell, but are held in
check by inhibitors.
 Gene p53 brings about apoptosis when
DNA is damaged.
 Apoptosis protects the body from
cells with abnormal chromosomes or
“run away” cell division.
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Function of p53
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Replicative Potential
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After cells become fully differentiated they
can no longer divide.
– Chromosomes in human cells end with
repetitive DNA sequences, telomeres.
 Telomeres get shorter after each cell
cycle.
 Cells can undergo 60 – 70 divisions.
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Normal Cell Characteristics
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Genetically stable.
Differentiate and adhere to other cells.
Respond appropriately to growth signals.
Undergo apoptosis when DNA repair fails.
Undergo a limited number of cell cycles.
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Cancer Cells
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Carcinogenesis - Development of cancer or
“cancer beginnings”.
– Cancer (“crab”) is a genetic disease
requiring a number of mutations (at least
ten), each propelling cells toward tumor
development  benign, malignant.
 Each tumor is composed of cells that
are experiencing uncontrolled growth.
 Cancer cells are non-specialized and
do not contribute to body functioning.
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Cancer Cell Characteristics
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Genetically unstable.
Not differentiated - Do not adhere to other
cells (no “contact inhibition”).
Insensitive to inhibitory growth signals.
No apoptosis when DNA repair fails.
Unlimited number of cell cycles (immortal).
Induce and sustain angiogenesis.
Invade and metastasize.
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Cancer Cells
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Carcinogenesis
• Takes many years because it requires many
mutations that occur over time.
• 3 Phases (Steps):
• Initiation.
• Promotion.
• Progression.
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Regulation of Cell Cycle
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Approximately 100 oncogenes discovered that can
cause increased cell growth (by producing proteins)
and lead to tumors.
– Genes “turned on” which should be off.
– Form when mutations occur in proto-oncogenes.
– Most frequent are in ras gene family – sequence?
Cancer cells no longer respond to inhibitory growth
factors.
Tumor suppressor genes undergo mutations.
– Approximately half-dozen identified.
– Genes “turned off” which should be on.
– Most common in cancer development is p53.
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Unlimited Replicative Potential
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Cancer cells have unlimited replicative
potential because all division restraints,
including apoptosis and telomere
shortening, have been removed.
In other words, they are essentially
immortal.
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Angiogenesis
Angiogenesis is the formation of new blood
vessels.
– Cancer cells release signals, such as
vascular endothelial growth factor
(VEGF), that bind to receptors on the
epithelial cells of blood vessels.
 New blood vessels branch and send
capillaries into the center of a tumor.
 Occurs when cell mass is ~1 million
cells.
 Essential to provide oxygen/nutrients,
to remove carbon dioxide/wastes. . . . .
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Metastasis
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A benign tumor is a disorganized, usually
encapsulated, mass that does not invade
adjacent tissue.
– Malignancy (malignant tumor) is present
when metastasis establishes new tumors
distant from the primary tumor.
 Due to mutations, cancer cells tend to
be motile because they have a
disorganized internal cytoskeleton and
lack intact actin filament bundles.
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• Based on what we know about cancer and
the processes surrounding it,
• cancer cells might be viewed as normal
cells
• which have reverted to their “embryonic
state”
• by activation of oncogenes and
inactivation of tumor suppressor genes
• and, therefore, demonstrate characteristics
normally seen in cells during the early
stages of embryonic development which . . .
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Causes of Cancer
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Causes of Cancer
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Heredity.
– Certain cancers, such as breast, lung, and
colon cancers, run in families.
– Some childhood cancers are inherited as a
dominant gene.
– Examples: BRCA1, WT1, RB
Environmental Carcinogens.
– “cancer generator”, an environmental agent that
can trigger cancer.
– Mutagen increases chances of DNA mutation.
– Carcinogens contribute to cancer development.
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Causes of Cancer
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Radiation.
 Skin cancers – U.V. radiation in
sunlight and tanning beds.
 Radon gas can lead to lung cancer.
 X rays and nuclear radiation.
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Causes of Cancer
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Organic chemicals.
 Tobacco smoke - contains carcinogens
that can lead to cancers of the lung,
mouth, larynx, bladder, kidney, and
pancreas.
 Foods – rich in saturated fats and low
in fiber are correlated with increased
cancer rates for the colon, rectum, and
prostate.
 Pollutants – industrial chemicals,
pesticides, and herbicides are
mutagenic and can lead to cancer.
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Causes of Cancer
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Viruses.
 Have been linked to liver cancer, cervical
cancer, form of lymphoma, and
nasopharyngeal cancer.
 Only 5 viruses implicated in human
cancer.
 Example: HBV, HPV, EBV, HIV, HTLV.
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Types of Cancer by Origin:
• Carcinomas.
• Arise from epithelial cells.
• Sarcomas.
• Arise from connective / muscle tissue.
• Leukemia and lymphomas.
• Arise from bone marrow (blood cancer) and
from lymphatic tissue.
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The Top 4 Cancers in the United States
Population (by death rate):
• #1 - Lung cancer
• #2 – Colon cancer
• #3 – Breast cancer
• #4 – Prostate cancer
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Diagnosis and Treatment
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Warning Signs.
– Change in bowel or bladder habits.
– A sore that does not heal.
– Unusual bleeding or discharge.
– Thickening or lump.
– Indigestion or difficulty swallowing.
– Obvious change in wart or mole.
– Nagging cough or hoarseness.
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Routine Screening Tests
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Cervical Cancer
– Pap smears
– Used since 1938, one of most
effective screens.
Breast Cancer.
– Monthly self-exam.
– Annual examination by physician.
– Mammography.
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Health Focus
“Shower Check for Cancer”
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Routine Screening Tests
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Colon Cancer.
– Digital rectal examination.
– Flexible sigmoidoscopy.
– Stool occult blood test.
– Colonoscopy.
– (CEA blood test).
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Routine Screening Tests
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Tumor Marker Tests.
– Blood tests for tumor antigens/antibodies
produced against tumors.
– Used to detect first-time cancers and
cancer relapses.
– PSA (prostate specific antigen): prostate
cancer.
– CEA: colon cancer relapse.
– CA-125: ovarian cancer.
– AFP: liver cancer.
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Routine Screening Tests
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Genetic Tests.
– Test for genetic mutations in protooncogenes and tumor suppressor genes.
– When an individual tests positive for the
presence of marker genes.
– Examples: ras gene for colon cancer and
BRCA1 for breast cancer.
– They should be vigilant for signs of
cancer.
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Routine Screening Tests
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Confirming Diagnosis.
– Surgery.
– Needle biopsies.
– Imaging techniques such as CAT scans,
MRI, radioactive scans, ultrasound.
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Prognosis
• The predicted outcome of a disease
(cancer).
• Depends on:
• (1) Whether the tumor has spread to
surrounding tissue.
• (2) Whether there is lymph node
involvement.
• (3) Whether distant tumors have begun.
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Treatment of Cancer
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Traditional (Standard) Therapies.
– Surgery when “in situ” (localized).
– Radiation (localized).
 Radiation should cause cancer cells to
mutate and undergo apoptosis.
 Cancers of the cervix, early prostate,
larynx, Hodgkin’s disease.
– epithelial cells lining systems, hair cells.
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Treatment of Cancer
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Chemotherapy (systemic).
 Used for “metastatic cancers”.
 Most chemotherapeutic drugs kill cells
by damaging their DNA or interfering
with DNA synthesis.
 However, these agents also impact
normal, rapidly dividing cells . . . . . .
 Epithelial cells lining systems, hair cells.
 Example: use of Taxol to treat ovarian
cancer.
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Treatment of Cancer
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Bone Marrow Transplants.
 Are used when the patient is to receive
high doses of chemotherapy and
radiation in combination.
 Is needed to replace the blood-forming
tissues destroyed by the treatment.
 Autotransplantation involves . . . .
 Can also be used treat leukemias.
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Treatment of Cancer
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Treatment of Cancer
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Future Therapies.
– Cancer vaccine therapy.
– Monoclonal antibody therapy.
 A type of Immunotherapy.
 Used to deliver chemotherapeutic drugs
to cancer cells.
– p53 gene therapy.
 Retroviruses and adenoviruses are
used to carry normal genes in
cancerous tissues.
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Treatment of Cancer
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Inhibitory drug therapy.
 Also called Chemoprevention.
 Drugs that deactivate the enzymes that
allow metastasis.
 Turning off angiogenesis using
antiangiogenic drugs.
 Promoting differentiation (promyelocytic
leukemia).
 Preventing carcinogenesis (Tamoxifen
prevents breast cancer).
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Treatment of Cancer
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Complementary therapy.
 Due to the insistence of patients, some
institutions are beginning to investigate
and make use of alternative therapies.
 Homeopathy.
 Biofeedback.
 Acupuncture.
 Exotic foods.
 Nutrition (foods, vitamins A, C).
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Health Focus
“Prevention of Cancer”
• What vitamins are
associated with cancer
prevention?
• A and C
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Bioethical Focus
“Tobacco and Alcohol Use”
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Review
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Introduction
Normal Cells
Regulation of Cell Division
Tumor Suppressor Genes and Apoptosis
Normal Cell Characteristics
Cancer Cell Characteristics
Angiogenesis
Metastasis
Causes of Cancer
Diagnosis and Treatment of Cancer
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