Causes of Cancer

1
Causes of Cancer

• Defective cellular growth
• Stem cells
• Generation time
• Contact Inhibitor
• Defective cellular differentiation
• Exposure to carcinogens
• Moves to less mature form
• Leads to invasion and metastasis

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Characteristics of Normal Cells

• Limited Cell Division
• Specific Morphology
• Small Nuclear-Cytoplasmic Ratio
• Perform Specific Differentiated Functions
• Adhere tightly together
• Are nonmigratory
• Grow in an orderly and well differentiated manner
• Are contact inhibited

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Characteristics of Early Embryonic Cells

• Demonstrate rapid and continuous cell division
• Show anaplastic morphology
• Have a large nuclear-cytoplasmic ratio
• Perform no differentiated functions
• Adhere loosely together
• Are able to migrate
• Are not contact inhibited.

4
Characteristics of Benign Cells

• Demonstrate continuous or inappropriate cell
  growth.
• Show specific morphology
• Have a small nuclear-cytoplasmic ratio
• Perform differentiated functions
• Adhere tightly together
• Are nonmigratory
• Grow in an orderly and well regulated fashion.

5
Characteristics of Malignant Cells

• Demonstrate rapid or continuous cellular
  division.
• Show anaplastic morphology
• Have a large nuclear-cytoplasmic ratio
• Lose some or all differentiated functions
• Adhere loosely together
• Are able to migrate
• Grow by invasion
• Are not contact-inhibited

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Definitions

• Anaplasia
• Anaplastic
• Carcinogen
• Carcinoma

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• Hyperplasia
• Hypertrophy
• Metastasis
• Neoplasia
• Neoplasm

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Stages of Carcinogenesis(Oncogenesis)

• Initiation
• Promotion
• Progression
• Metastasis

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Common Steps in Metastasis

• Extension into Surrounding Tissues
• Penetration into Blood Vessels
• Release of Tumor Cells
• Invasion of Tissue at the Site of Arrest

10
Immune Response

• Attempts to destroy abnormal cells
• Surface Antigens
• Used as tracers to indicate success of treatment
• CEA (carcinoembrionic antigen) - GI tract
• AFP (alphafetoprotein) - liver
• CA 125 - ovarian
• PSA prostate

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Cancer Grade and Stage

• Grading Classifies cellular aspects of a cancer.
• Staging Classifies clinical aspects of the
  cancer.

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Histologic Class

• I - Well differentiated
• II - Moderate differentiation
• III - Poor differentiation
• IV - Immature Undifferentiated

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Clinical Staging

• O - Ca in situ
• I (A) - Localized growth
• II (B) - Limited local growth
• III (C) - Extensive local and regional growth
• IV (D) - Metastasis

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TNM Classification

• T - Primary tumor
• N - Regional lymph nodes
• M - Distant metastasis
• Tis No Mo
• T4 N3 M1

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Goal

• Education and early detection
• C
• A
• U
• T
• I
• O
• N

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Surgical Interventions

• Biopsy
• Cure
• Control - Debulking
• Palliative
• Staging
• Reconstructive
• Prophylaxis

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Radiation

• Destroys cells, causes inflammatory response
• Side Effects
• Goals
• Cure
• Control
• Palliative
• Radiation Recall
• External
• Implants
• Isotopes

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Chemotherapy

• Cell Cycle Non-specific
• Alkylating Cytoxan, Leukeran, N.Mustard
• Antitumor antibiotics - Adriamycin
• Nitrosoureas Carmustine, Hydrourea
• Corticosteroids Prednisone, Decadron
• Hormones Estrogen, Provera, Androgen
• Cell Cycle Specific
• Antimetabolities Methotrexate, 5-FU
• Plant Alkaloids (Miotic Inhibitors) Vinblastine,
  Vincristine
• Cisplatin
• Tamoxifen

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Synergistic Effect

• The total is greater than the individual parts
• Each agent has
• action against cancer
• different site of action
• different organ toxicity or time of toxicity

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MOPP Protocol
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Side Effects

• Cluster the common ones
• bone marrow suppression
• alopecia
• nausea and vomiting
• Adriamycin - Cardiac
• Cisplatin Renal

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Complications

• Pain Control
• Bone Marrow Suppression
• Infection - Neutropenia
• Hemorrhage
• Anemia
• Infarction
• Superior Vena Cava Syndrome
• Spinal Cord Compression
• Tumor Lysis Syndrome

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Common Problems/Complications Associated With
Cancer

• Tumor Lysis Syndrome (TLS)
• Destruction of cells (lysis)
• Release of Purine and Potassium (K) into
  Bloodstream
• Purines converted to uric acid (in liver)
  K into Bloodstream
• Hyperuricemia Hyperkalemia
• Obstruction of Kidney Tubules
• ARF

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Paraneoplastic Syndromes

• Secretion of Insulin
• Secretion of ACTH
• Hypercalcemia
• SIADH

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SIADH - Syndrome of Inappropriate ADH

• ADH release
• Water Reabsorption into circulation -Renal
  Tubules
• Extravascular Fluid
• Plasma Osmolality
• Glomerular Filtration Rate
• Serum Sodium Levels
  CEREBRAL EDEMA

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Leukemia

• AML - Acute Myelogenous
• Age of Onset (15-39 yrs), usually affects adults
• Prognosis is generally poor, best with bone
  marrow transplant
• Most common type of leukemia
• Equal incidence in males and females
• ALL - Acute Lymphocytic
• Age of Onset (lt15 yrs), usually affects
  children, accounts for approx 10 of adult
  leukemia's
• Prognosis is poorer for adults than for children
• Fever Bleeding
• Increased incidence in males

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Leukemia

• CML - Chronic Myelogenous
• Age of Onset (gt50 yrs)
• Involves liver spleen
• Blastic Crisis
• CLL - Chronic Lymphocytic
• Older patients over 50
• Lymph node involvement

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Lymphoma

• Lymph system
• Lymphocytes histiocytes (macrophages)
• Hodgkins
• 15-35 and over 50 yrs.
• Non-Hodgkins
• Outside of lymph nodes
• Wide spread before Dx
• Multiple Myeloma
• Infiltrates marrow
• destroys bone

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Breast

• Early detection - Education
• Treatment options
• Mastectomy care
• Referrals

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Gynecological

• Cervical
• Endometrial
• Ovarian

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Genetics and Cancer

• BRCA