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Causes of Cancer

Defective cellular growth
– Stem cells
– Generation time
– Contact Inhibitor
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Defective cellular differentiation
– Exposure to carcinogens
– Moves to less mature form
– Leads to invasion and metastasis
Characteristics of Normal
Cells
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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
Characteristics of Early
Embryonic Cells
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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.
Characteristics of Benign
Cells
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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.
Characteristics of Malignant
Cells
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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
Definitions
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Anaplasia
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Anaplastic
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Carcinogen
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Carcinoma
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Hyperplasia
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Hypertrophy
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Metastasis
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Neoplasia
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Neoplasm
Stages of Carcinogenesis
(Oncogenesis)
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Initiation
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Promotion
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Progression
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Metastasis
Common Steps in
Metastasis
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Extension into Surrounding Tissues
Penetration into Blood Vessels
Release of Tumor Cells
Invasion of Tissue at the Site of
Arrest
Immune Response
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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
Cancer Grade and Stage
 Grading;
Classifies cellular
aspects of a cancer.
 Staging;
Classifies clinical
aspects of the cancer.
Histologic Class
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I - Well differentiated
II - Moderate differentiation
III - Poor differentiation
IV - Immature & Undifferentiated
Clinical Staging
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O - Ca in situ
I (A) - Localized growth
II (B) - Limited local growth
III (C) - Extensive local and regional
growth
IV (D) - Metastasis
TNM Classification
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T - Primary tumor
N - Regional lymph nodes
M - Distant metastasis
–Tis No Mo
–T4 N3 M1
Goal
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Education and early detection
C
A
U
T
I
O
N
Surgical Interventions
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Biopsy
Cure
Control - Debulking
Palliative
Staging
Reconstructive
Prophylaxis
Radiation
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Destroys cells, causes inflammatory response
Side Effects
Goals:
– Cure
– Control
– Palliative
Radiation Recall
External
Implants
Isotopes
Chemotherapy
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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
Synergistic Effect
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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
MOPP Protocol
Complete
response
Agent
Action
Toxicity
Mustargen
DNA
Marrow – 10
days
 10%
Oncovin
Mitosis
Neurotoxic
 10%
Procarbazine
Marrow – 21
days
 5%
Prednisone
RNA
Synthesis
Cell
membrane
20%
80%
Synergistic Effect
Immune
suppression
Side Effects
Cluster the common ones:
bone marrow suppression
alopecia
nausea and vomiting
Adriamycin - Cardiac
Cisplatin – Renal
Complications
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Pain Control
Bone Marrow Suppression
– Infection - Neutropenia
– Hemorrhage
– Anemia
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Infarction
Superior Vena Cava Syndrome
Spinal Cord Compression
Tumor Lysis Syndrome
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)
Hyperuricemia
Obstruction of Kidney Tubules
ARF
K+ into Bloodstream
Hyperkalemia
Paraneoplastic
Syndromes
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Secretion of Insulin
Secretion of ACTH
Hypercalcemia
SIADH
SIADH - Syndrome of
Inappropriate ADH
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ADH release
Water Reabsorption into circulation -Renal
Tubules
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Extravascular Fluid
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Plasma Osmolality
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Glomerular Filtration Rate
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Serum Sodium Levels
CEREBRAL EDEMA
Leukemia
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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
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ALL - Acute Lymphocytic
– Age of Onset (<15 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
Leukemia
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CML - Chronic Myelogenous
– Age of Onset (>50 yrs)
– Involves liver & spleen
– Blastic Crisis
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CLL - Chronic Lymphocytic
– Older patients – over 50
– Lymph node involvement
Lymphoma
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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
Breast
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Early detection - Education
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Treatment options
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Mastectomy care
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Referrals
Gynecological
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Cervical
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Endometrial
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Ovarian
Genetics and Cancer
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BRCA