Causes of CancerCauses of Cancer Defective cellular growthDefective cellular growth

– Stem cellsStem cells– Generation timeGeneration time– Contact InhibitorContact Inhibitor

Defective cellular differentiationDefective cellular differentiation– Exposure to carcinogensExposure to carcinogens– Moves to less mature formMoves to less mature form– Leads to invasion and metastasisLeads to invasion and metastasis

Characteristics of Characteristics of Normal CellsNormal Cells

Limited Cell DivisionLimited Cell Division Specific MorphologySpecific Morphology SmallSmall Nuclear-Cytoplasmic Ratio Nuclear-Cytoplasmic Ratio Perform Specific Differentiated FunctionsPerform Specific Differentiated Functions Adhere tightly together…Adhere tightly together… Are nonmigratoryAre nonmigratory Grow in an Grow in an orderly and well orderly and well

differentiateddifferentiated manner manner Are contact inhibitedAre contact inhibited

Characteristics of Early Characteristics of Early Embryonic CellsEmbryonic Cells

Demonstrate rapid and continuous cell Demonstrate rapid and continuous cell divisiondivision

Show anaplastic morphologyShow anaplastic morphology Have a Have a largelarge nuclear-cytoplasmic ratio nuclear-cytoplasmic ratio Perform no differentiated functions Perform no differentiated functions Adhere loosely togetherAdhere loosely together Are able to migrateAre able to migrate Are not contact inhibited. Are not contact inhibited.

Characteristics of Characteristics of Benign CellsBenign Cells Demonstrate continuous or Demonstrate continuous or

inappropriateinappropriate cell growth. cell growth. Show specific morphologyShow specific morphology Have a Have a smallsmall nuclear-cytoplasmic rationuclear-cytoplasmic ratio Perform differentiated functionsPerform differentiated functions Adhere tightly togetherAdhere tightly together Are nonmigratoryAre nonmigratory Grow in an orderly and well regulated Grow in an orderly and well regulated

fashion.fashion.

Characteristics of Characteristics of Malignant CellsMalignant Cells Demonstrate rapid or continuous Demonstrate rapid or continuous

cellular division. cellular division. Show Show anaplastic morphologyanaplastic morphology Have aHave a largelarge nuclear-cytoplasmic rationuclear-cytoplasmic ratio Lose some or all differentiated functionsLose some or all differentiated functions Adhere loosely togetherAdhere loosely together Are able to migrateAre able to migrate Grow by invasionGrow by invasion Are Are not contact-inhibitednot contact-inhibited

DefinitionsDefinitionsDefinitionsDefinitions

AnaplasiaAnaplasia

AnaplasticAnaplastic

CarcinogenCarcinogen

CarcinomaCarcinoma

HyperplasiaHyperplasia

HypertrophyHypertrophy

MetastasisMetastasis

NeoplasiaNeoplasia

NeoplasmNeoplasm

Stages of Stages of CarcinogenesisCarcinogenesis(Oncogenesis)(Oncogenesis)

InitiationInitiation

PromotionPromotion

ProgressionProgression

MetastasisMetastasis

Common Steps in Common Steps in MetastasisMetastasis

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

Immune ResponseImmune Response Attempts to destroy abnormal cellsAttempts to destroy abnormal cells Surface AntigensSurface Antigens

– Used as tracers to indicate success of Used as tracers to indicate success of treatmenttreatment

– CEA (carcinoembrionic antigen) - GI CEA (carcinoembrionic antigen) - GI tracttract

– AFP (alphafetoprotein) - liverAFP (alphafetoprotein) - liver– CA 125 - ovarianCA 125 - ovarian– PSA – prostatePSA – prostate

Cancer Grade and Cancer Grade and StageStage

Grading;Grading; Classifies Classifies cellular cellular aspectsaspects of a cancer. of a cancer.

Staging;Staging; Classifies Classifies clinical clinical aspectsaspects of the cancer. of the cancer.

Histologic ClassHistologic Class

I - Well differentiatedI - Well differentiated II - Moderate differentiationII - Moderate differentiation III - Poor differentiationIII - Poor differentiation IV - Immature & UndifferentiatedIV - Immature & Undifferentiated

Clinical StagingClinical Staging

O - Ca in situO - Ca in situ I (A) - Localized growthI (A) - Localized growth II (B) - Limited local growthII (B) - Limited local growth III (C) - Extensive local and III (C) - Extensive local and

regional growthregional growth IV (D) - MetastasisIV (D) - Metastasis

TNM ClassificationTNM Classification

T - Primary tumorT - Primary tumor N - Regional lymph nodesN - Regional lymph nodes M - Distant metastasisM - Distant metastasis

– TTisis N No o MMoo

– TT44 NN33 MM11

GoalGoal Education and early detectionEducation and early detection CC AA UU TT II OO NN

Surgical InterventionsSurgical Interventions

BiopsyBiopsy CureCure Control - DebulkingControl - Debulking PalliativePalliative StagingStaging ReconstructiveReconstructive ProphylaxisProphylaxis

RadiationRadiation Destroys cells, causes inflammatory Destroys cells, causes inflammatory

responseresponse Side EffectsSide Effects Goals:Goals:

– CureCure– ControlControl– PalliativePalliative

Radiation RecallRadiation Recall ExternalExternal ImplantsImplants IsotopesIsotopes

ChemotherapyChemotherapy Cell Cycle Non-specificCell Cycle Non-specific

– Alkylating –Cytoxan, Leukeran, N.MustardAlkylating –Cytoxan, Leukeran, N.Mustard– Antitumor antibiotics - AdriamycinAntitumor antibiotics - Adriamycin– Nitrosoureas –Carmustine, HydroureaNitrosoureas –Carmustine, Hydrourea– Corticosteroids –Prednisone, DecadronCorticosteroids –Prednisone, Decadron– Hormones –Estrogen, Provera, AndrogenHormones –Estrogen, Provera, Androgen

Cell Cycle SpecificCell Cycle Specific– Antimetabolities –Methotrexate, 5-FUAntimetabolities –Methotrexate, 5-FU– Plant Alkaloids (Miotic Inhibitors) –Vinblastine, Plant Alkaloids (Miotic Inhibitors) –Vinblastine,

VincristineVincristine CisplatinCisplatin TamoxifenTamoxifen

Synergistic EffectSynergistic Effect

The total is greater than the The total is greater than the individual partsindividual parts

Each agent has:Each agent has:– action against canceraction against cancer– different site of actiondifferent site of action– different organ toxicity or time of different organ toxicity or time of

toxicitytoxicity

MOPP ProtocolMOPP Protocol

Complete response

Agent Action Toxicity

20% Mustargen DNA Marrow – 10 days

10% Oncovin Mitosis Neurotoxic

10% Procarbazine RNA Synthesis

Marrow – 21 days

5% Prednisone Cell membrane

Immune suppression

80% Synergistic Effect

Side EffectsSide Effects

Cluster the common onesCluster the common ones::bone marrow suppressionbone marrow suppression

alopeciaalopecia

nausea and vomitingnausea and vomiting

AdriamycinAdriamycin - Cardiac - Cardiac

CisplatinCisplatin – Renal – Renal

ComplicationsComplications Pain ControlPain Control Bone Marrow SuppressionBone Marrow Suppression

– Infection - NeutropeniaInfection - Neutropenia– HemorrhageHemorrhage– AnemiaAnemia

InfarctionInfarction Superior Vena Cava SyndromeSuperior Vena Cava Syndrome Spinal Cord CompressionSpinal Cord Compression Tumor Lysis SyndromeTumor Lysis Syndrome

Common Common Problems/Complications Problems/Complications Associated With CancerAssociated With Cancer

Tumor Lysis Syndrome (TLS);Tumor Lysis Syndrome (TLS);

Destruction of cells (lysis)Destruction of cells (lysis)

Release of Purine and Potassium (K+) into BloodstreamRelease of Purine and Potassium (K+) into Bloodstream

Purines converted to uric acid (in liver) K+ into BloodstreamPurines converted to uric acid (in liver) K+ into Bloodstream

HyperuricemiaHyperuricemia HyperkalemiaHyperkalemia

Obstruction of Kidney TubulesObstruction of Kidney Tubules

ARFARF

Paraneoplastic Paraneoplastic SyndromesSyndromes

Secretion of InsulinSecretion of Insulin Secretion of ACTHSecretion of ACTH HypercalcemiaHypercalcemia SIADHSIADH

SIADH - Syndrome of SIADH - Syndrome of Inappropriate ADHInappropriate ADH ADH releaseADH release

Water Reabsorption into circulation -Water Reabsorption into circulation -

Renal TubulesRenal Tubules

Extravascular FluidExtravascular Fluid

Plasma OsmolalityPlasma Osmolality

Glomerular Filtration RateGlomerular Filtration Rate

Serum Sodium Levels Serum Sodium Levels

CEREBRAL EDEMACEREBRAL EDEMA

LeukemiaLeukemia AML - Acute MyelogenousAML - Acute Myelogenous

– Age of Onset (15-39 yrs), usually affects adultsAge of Onset (15-39 yrs), usually affects adults– Prognosis is generally poor, best with bone Prognosis is generally poor, best with bone

marrow transplantmarrow transplant– Most common type of leukemiaMost common type of leukemia– Equal incidence in males and femalesEqual incidence in males and females

ALL - Acute LymphocyticALL - Acute Lymphocytic – Age of Onset (<15 yrs), usually affects Age of Onset (<15 yrs), usually affects

children, accounts for approx 10% of adult children, accounts for approx 10% of adult leukemia'sleukemia's

– Prognosis is poorer for adults than for childrenPrognosis is poorer for adults than for children– Fever & BleedingFever & Bleeding– Increased incidence in malesIncreased incidence in males

LeukemiaLeukemia

CML - Chronic MyelogenousCML - Chronic Myelogenous– Age of Onset (>50 yrs)Age of Onset (>50 yrs)– Involves liver & spleenInvolves liver & spleen– Blastic CrisisBlastic Crisis

CLL - Chronic LymphocyticCLL - Chronic Lymphocytic– Older patients – over 50Older patients – over 50– Lymph node involvement Lymph node involvement

LymphomaLymphoma

Lymph systemLymph system Lymphocytes & histiocytes Lymphocytes & histiocytes

(macrophages)(macrophages) HodgkinsHodgkins

– 15-35 and over 50 yrs.15-35 and over 50 yrs. Non-Hodgkins Non-Hodgkins

– Outside of lymph nodesOutside of lymph nodes– Wide spread before DxWide spread before Dx

Multiple MyelomaMultiple Myeloma– Infiltrates marrow Infiltrates marrow – destroys bonedestroys bone

BreastBreast

Early detection - EducationEarly detection - Education

Treatment optionsTreatment options

Mastectomy careMastectomy care

ReferralsReferrals

GynecologicalGynecological

CervicalCervical

EndometrialEndometrial

OvarianOvarian

Genetics and CancerGenetics and Cancer

BRCABRCA