Cancer: Uncontrolled Cell Division and Differentiation

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• Cancer Uncontrolled Cell Division and
  Differentiation

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Cancer An Introduction

• 100 different types of cancer
• All cancers are diseases of cell division and
  differentiation
• Normal Cells
• Have regulatory mechanisms that maintain an
  appropriate rate of cell division
• Internal clock
• Hormones
• Inhibitory signals from nearby cells
• Remain in one location throughout their lifespan

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Tumors Can Be Benign or Cancerous

• Hyperplasia
• Substantial increase in the rate of cell division
• Tumor
• Also known as a neoplasm
• A discrete mass of cells resulting from
  hyperplasia
• Benign tumors
• Noncancerous
• Remain in one location
• Single, well-defined mass
• May be surrounded by connective tissue
• Often can be readily removed surgically

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Figure 18.1
Benign tumor
Genetically alteredepithelial cell
Hyperplasia
Basement membrane
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Cancerous Cells Lose Control Over Their Functions
and Structures

• Dysplasia
• Abnormal change in cell structure
• Considered a precancerous state
• Cancerous tumors
• Abnormal cell structure
• Loss of regulation of cell growth
• In situ cancer
• Tumor stays in one place

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Cancerous Cells Lose Control Over Their Functions
and Structures

• Malignant tumor
• Tumor invades normal tissue and compromises organ
  function
• Tumor may undergo metastasis
• Spread of the cancer to another organ or body
  region
• Secondary, malignant tumors at other locations
  may develop

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Figure 18.2
Malignant tumor (cancer)
In situ cancer
Dysplasia
Hyperplasia
Geneticallyalteredepithelialcell

• Cell dividesmore rapidlythan normal

• Cells changeform

• Cells stay inone place

• Cancer cells invade surrounding tissueand enter
  blood and lymph
• Metastases may form at distant sites

Metastases
Normal underlying connectiveor muscle tissue
Blood vessel
Invasion
Direction of flow
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Table 18.1
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How Cancer Develops

• Two things must happen simultaneously for cancer
  to develop
• 1. Cell must divide uncontrollably
• 2. Cell must undergo physical changes and break
  away from surrounding cells
• These changes usually correlate with specific
  mutations in the cells genes

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Mutant Forms of Proto-Oncogens, Tumor Suppressor
Genes, and Mutator Genes Contribute to Cancer

• Proto-oncogenes
• Normal regulatory genes that promote cell growth
  and differentiation, division, or adhesion
• Oncogenes
• Mutated or damaged proto-oncogenes
• May cause cells to grow and divide more quickly
  than normal
• May result in a cell failing to respond to
  inhibitory signals
• Cancer develops only when multiple oncogenes are
  present

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Mutant Forms of Proto-Oncogens, Tumor Suppressor
Genes, and Mutator Genes Contribute to Cancer

• Tumor suppressor genes
• Regulatory genes repress cell growth, division,
  differentiation, and adhesion
• May be turned off, damaged, or mutated in cancers
• Example If the p53 tumor suppressor gene is
  mutated, a variety of cancers will develop more
  readily
• p53 mutations have been found in cervical, colon,
  lung, skin, bladder, and breast tumors
• Mutator genes
• Involved in DNA repair during replication
• May be mutated themselves and not function

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Animation Cancer Right-click and select Play
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A Variety of Factors Can Lead to Cancer

• Age single most important factor in development
  of cancer
• The longer we live, the more likely we are to die
  of cancer
• Some genes may be inherited that increase
  susceptibility to cancer
• Multigene basis of cancer
• Carcinogenesis process of transforming a normal
  cell into a cancer cell
• Carcinogen any substance or physical factor that
  causes cancer

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A Variety of Factors Can Lead to Cancer

• Viruses and bacteria (?15 of all cancers)
• Human papillomavirus (HPV) cervical cancer
• Hepatitis B and C viruses liver cancer
• HIV Kaposis sarcoma
• Epstein-Barr virus Hodgkins disease
• Chemicals in the environment
• Asbestos, benzene, some pesticides, dyes
• Tobacco
• Responsible for 30 of all cancer deaths
• Radiation
• Ultraviolet radiation (sun exposure) skin cancer
• Causes ?80 of all skin cancers

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A Variety of Factors Can Lead to Cancer

• Diet and obesity
• Likely involved in approximately 30 of cancers
• Red meat, saturated animal fat increased risk of
  cancer of colon, rectum, prostate
• Alcohol consumption increased risk of breast,
  rectal, colon, and liver cancer
• High salt consumption associated with stomach
  cancer
• Aflatoxin present in raw peanut butter
• Type II diabetics have a much higher risk of
  dying of cancer

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A Variety of Factors Can Lead to Cancer

• Internal factors
• Free radicals produced by metabolism may damage
  DNA
• Antioxidants (vitamins A,C,E) may neutralize free
  radicals
• Antioxidant containing foods blueberries,
  spinach, tomatoes

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The Immune System Plays an Important Role in
Cancer Prevention

• Immune system normally defends the body against
  cancers
• Cancer cells may not be recognized as self and
  may be destroyed by the immune system
• Anything that suppresses the immune system may
  make an individual more susceptible to cancer

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Figure 18.6
Environmental factors
Abnormal cell destroyed
Immune systemresponsive
Normal cell
Abnormal cell
Mutations ofregulatorygenes andgenes
involvedin DNA repair.
Immune systemsuppressed
Internal factors
Inheritance
Tumor
Invasion
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Advances in Diagnosis Enable Early Detection

• Tumor imaging
• X-rays
• Example mammogram
• Positron emission tomography (PET)
• Magnetic resonance imaging (MRI)
• Genetic testing
• Identify mutated genes
• Privacy and treatment issues
• Enzyme tests for cancer markers
• Screening large numbers of people

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Figure 18.8
An X-ray. This is a color-enhanced X-ray of a
breastwith a tumor.
An ultrasound scan. This one shows a
prostatetumor (purple).
A PET scan of the brain.The yellow/red area is
atumor.
An MRI. This is an MRI of a brain, showing a
brain tumor(magenta and red area to the right).
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Cancer Treatments

• Conventional treatments
• Surgery has improved with better imaging
  techniques
• Radiation targets the tumor, but sometimes
  damages healthy cells
• Chemotherapy use of cytotoxic drugs to destroy
  cancer cells
• Side effects nausea, hair loss, anemia
• Often kills normal cells as well
• Often a combination of two or more of the above
  treatments is used

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Cancer Treatments

• Magnetism
• Magnet is placed at the tumor
• Tiny magnetic beads coated with chemotherapy
  drugs are injected and pulled to the tumor
• Photodynamic therapy
• Uses light-sensitive drugs that are taken up by
  cancer cells and lasers, which activate the
  toxicity of the drug

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Cancer Treatments

• Immunotherapy
• Boosts the immune response of patient
• Development of antibodies that specifically
  recognize cancer cells
• Tagging antibodies with radioactive molecules or
  chemotherapeutic drugs
• Development of vaccines against specific cancers
• Starving cancers
• Anti-angiogenic drugs prevent the development of
  a good blood supply to the tumor
• Molecular treatments
• Target oncogenes

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Common Cancers Lung Cancer

• Smoking leading risk factor
• No simple screening test, so the cancer is often
  more advanced when detected
• Early symptoms are nonspecific
• Persistent coughing
• Bronchitis
• Recurrent pneumonia
• Voice change
• Treatment
• Surgery, often combined with radiation and
  chemotherapy

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Common Cancers Colon and Rectal Cancers

• Symptoms
• Blood in stool, rectal bleeding
• Risk factors
• Sedentary lifestyle, obesity, smoking, family
  history, low-fiber diet, high-fat diet
• Start as polyps (benign tumors), which gradually
  become malignant
• Screening tests can detect cancer early
• Detection of blood in stool specimens
• Colonoscopy examining interior of colon with
  flexible fiber-optic scope
• Treatment polyp removal, tumor removal

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Figure 18.10
Polyp
Intestinalfolds
Colonoscope
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Common Cancers Breast Cancer

• Early detection is crucial for survival
• Mammogram low dose X-ray used for early
  detection
• Detection of a lump on breast exam
• Risk factors
• Genetics two different genes increase risk
• BRCA1 and BRCA2
• Age
• Early onset of menstruation, late menopause
• Obesity after menopause
• Oral contraceptives
• Hormone replacement after menopause

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Common Cancers Prostate Cancer

• Most common after age 50
• Biggest risk factor advancing age
• Symptoms
• Urination difficulties, blood in urine, pain in
  pelvic area
• Diagnosis
• Digital rectal exam
• Blood test for PSA (prostate-specific antigen)
• Biopsy
• Treatment
• Surgery, radiation therapy, hormones

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Common Cancers Leukemia

• Cancer of immature white blood cells in the bone
  marrow
• Risk factors Down syndrome, exposure to ionizing
  radiation, benzene, infection with HTLV-1 virus
• Childhood forms of leukemia as well as adult
  forms of leukemia
• Symptoms nonspecific
• Diagnosis blood tests and bone marrow biopsies
• Treatment chemotherapy, or chemotherapy plus
  bone marrow transplant

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Common Cancers Lymphoma

• Cancer of lymphoid tissue
• Includes Hodgkins and non-Hodgkins lymphoma
• Symptoms
• Enlarged lymph nodes, intermittent fever,
  itching, weight loss, night sweats
• Risk factors
• Altered immune function
• Transplant recipients
• HIV infection
• Occupational exposure to herbicides
• Treatment radiation, chemotherapy, bone marrow
  transplant

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Common Cancers Urinary Bladder Cancer

• Symptoms
• Blood in the urine
• Risk factors
• Smoking, urban living, exposure to arsenic in
  water supply, occupational exposure to leather,
  dye, rubber
• Diagnosis
• Microscopic examination of urine for cancer cells
• Cystoscopy direct examination of bladder wall
  with cystoscope (thin flexible tube with lens)
• Treatment
• Surgery with chemotherapy

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Common Cancers Kidney Cancer

• Risk factors
• Genetics, smoking, exposure to certain toxic
  chemicals, age, gender (female)
• No direct screening tests
• Usually detected during examination for a
  renal-related problem
• Diagnosis
• CT scan or ultrasound
• Treatment
• Surgical removal of affected kidney

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Common Cancers Skin Cancer

• Three major types
• Basal cell carcinoma
• Involves basal cells in base layer of epithelium
• Rarely metastasizes, but should be removed
• Squamous cell carcinoma
• Involves epithelial cells
• May metastasize slowly
• Melanoma
• Deadliest, but least common of skin cancers
• Cancer of the melanocytes
• Metastasizes quickly

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Early Signs of Skin CancerABCs

• Observe skin lesions for
• A ? Asymmetry
• Two halves of the affected area dont match
• B ? Border
• Border is irregular in shape
• C ? Color
• Varies or is black
• D ? Diameter
• Greater than 6 mm (size of pea)

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Figure 18.11
The two halvesof the spot orpatch dont match.
The borderis irregular.
A Asymmetry.
B Border.
The colorvaries or isintenselyblack.
The diameter isgreater than 6mm.
C Color.
D Diameter.
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Common Cancers Uterine, Cervical Cancers

• Uterine cancer
• Involves the endometrium
• Symptom abnormal bleeding
• Risk factors
• Early onset of menstruation, late onset of
  menopause, not having children, estrogen use
  after menopause
• Cervical cancer
• Caused by human papilloma virus (HPV) infection
• Detection Pap test
• Prevention Gardasil or Cervarix vaccines
• Treatment surgery, chemotherapy, radiation,
  hormones

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Table 18.3
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Most Cancers Can Be Prevented

• Know family history
• Know your own body
• Learn self-examination techniques
• Get regular medical screenings
• Avoid direct sunlight 10 a.m. to 4 p.m.,
  sunlamps, and tanning salons
• Watch diet and weight
• Dont smoke
• Drink alcohol in moderation, if at all
• Stay informed