Biology, Clinical Manifestations, and Treatment of CancerChapter 9Unit III: Cell Proliferation: CancerCancer EpidemiologyChapter 10

CancerDerived from Greek word for crab, karkinomaMalignant tumorTumorAlso referred to as a neoplasm new growth

Benign vs. Malignant TumorsMitotic index = rate of growth

BenignMalignantGrow slowlyGrow rapidlyWell-defined capsuleNot encapsulatedNot invasiveInvasiveWell differentiatedPoorly differentiatedLow mitotic indexHigh mitotic indexDo not metastasizeCan spread distantly (metastasis)

Classification and NomenclatureBenign tumorsNamed according to the tissues from which they arise, and include the suffix -omaLipoma HemangiomaLeiomyoma Chondroma

Classification and NomenclatureMalignant tumorsNamed according to the tissues from which they ariseMalignant epithelial tumors are referred to as carcinomasAdenocarcinoma (from glandular epithelium)

Malignant CT tumors are referred to as sarcomasRhabdomyosarcomas (from skeletal muscle)

Classification and NomenclatureCancers of lymphatic tissue are lymphomasCancers of blood-forming cells are leukemiasCarcinoma in situ (CIS)Epithelial malignant tumors that have not broken through BM or invaded the surrounding stroma

Classification and Nomenclature

Stages of Cancer SpreadStage 1: Confined to organ of origin

Stage 2: Locally invasive

Stage 3: Spread to lymph nodes

Stage 4: Spread to distant sites

CIS special case

Tumor Staging by TNM SystemTUMORNODESMETASTASIS

Tumor MarkersTumor cell markers (biologic markers) are substances produced by cancer cells or that are found on plasma cell membranes, in the blood, CSF, or urineHormones (Epi in blood, adrenal medullary tumor)EnzymesGenesAntigens (PSA in blood, prostate cancer)Antibodies

Hallmarks of Cancer

Viruses and CancerImplicatedHepatitis B and C viruses

Epstein-Barr virus (EBV)

Kaposis sarcoma herpesvirus (KSHV)

Human papillomavirus (HPV)

Human T cell leukemialymphoma virus (HTLV)

Bacterial Cause of CancerHelicobacter pyloriChronic infections are associated with: Peptic ulcer disease Stomach carcinomaMucosa-associated lymphoid tissue lymphomas

Inflammation and CancerChronic inflammation is an important factor in development of cancerCytokine release from inflammatory cellsFree radicalsMutation promotionDecreased response to DNA damage

Tumor SpreadDirect invasion of contiguous organsKnown as local spread

Metastases to distant organsLymphatics and blood

Metastases by way of implantation

Local SpreadInvasionCellular multiplicationMitotic rate vs. cellular death rateMechanical pressureRelease of lytic enzymesDecreased cell-to-cell adhesionIncreased motilityIntravasationExtravasation

Three-Step Theory of InvasionTumor cell attachmentFibronectin and lamininDegradation or dissolution of the matrixEnzymesLocomotion into the matrixInvadopodia (pseudopodia)

HeLa cell a cell type in an immortal cell line used in research one of the oldest, most commonly used human cell linesderived from cervical cancer cells taken from Henrietta Lacks patient eventually died of her cancer on October 4, 1951 cell line was found to be remarkably durable cells propagated by George Otto Gey first human cell line to prove successful in vitro, which was a scientific achievement for the benefit of science neither Lacks nor her family gave Gey permission (at that time, permission was neither required nor sought)HeLa cells were used by Jonas Salk to test the first polio vaccine in the 1950s

Concept Check1. Neoplasiaa. abnormal proliferating cells w/ higher degree of autonomy

2. Anaplasiab. lack of differentiation, primitive cells

3. Autonomyc. cancer cells independence from normal cell controls

4. Tumor markers d. substances produced by cancer cells

5. Which characterizes cancer cells?A. Poorly differentiatedB. MetastasisC. Infiltrative growthD. Poor cell cohesivenessE. All of the above

6. Which is/are not malignant?A. GliomaB. AdenocarcinomaC. RhabdomyomaD. LeukemiaE. A and C

7. Metastasis is:A. Alteration in normal cell growthB. Growth of benign or or malignant cellsC. MutationalD. Ability to establish a secondary neoplasm at a new site

8. CIS is:A. PreinvasiveB. Glandular or epithelial lesionC. TeratomaD. Carcinoma that has broken through BME. Both a and b are correct

Cancer EpidemiologyChapter 10

Environmental Risk FactorsIncreasedDecreasedTobacco * ExerciseRadiation * Proper DietIonizingUVAlcoholSexual BehaviorDietObesityOccupational HazardsElectromagnetic Fields ?

Environmental Risk FactorsTobaccoMultipotent carcinogenic mixtureLinked to cancers of the lung, lower urinary tract, aerodigestive tract, liver, kidney, pancreas, cervix Linked to myeloid leukemia

Environmental Risk FactorsIonizing radiationEmission from x-rays, radioisotopes, and other radioactive sourcesExposure causes cell death, gene mutations, and chromosome aberrationsBystander effectsPoor gene repairChanges in gap junction intercellular communication

Environmental Risk FactorsUltraviolet radiationCauses basal cell carcinoma, squamous cell carcinoma, and melanomaPrincipal source is sunlightUltraviolet A (UVA) and ultraviolet B (UVB)Promotes skin inflammation and release of free radicals

Environmental Risk FactorsAlcohol consumptionRisk factor for oral cavity, pharynx, hypopharynx, larynx, esophagus, and liver cancersCigarette/alcohol combination increases a persons risk

Environmental Risk FactorsSexual reproductive behaviorCarcinogenic types of human papilloma virusHigh-risk HPV

Environmental Risk FactorsPhysical activityReduces cancer riskDecreases insulin and insulin-like growth factorsDecreases obesityDecreases inflammatory mediators and free radicalsIncreased gut motility

Environmental Risk FactorsOccupational hazardsSubstantial number of occupational carcinogenic agentsAsbestosDyes, rubber, paint, explosives, rubber cement, heavy metals, air pollution, etc.Radon

Environmental Risk FactorsElectromagnetic fieldsCarcinogenic?Are they, or arent they?

Environmental Risk FactorsDietXenobioticsToxic, mutagenic, and carcinogenic chemicals in foodActivated by phase I activation enzymesDefense mechanismsPhase II detoxification enzymesExamplesCompounds produced in the cooking of fat, meat, or proteinsAlkaloids or mold by-products

Environmental Risk FactorsObesityCorrelates with the body mass index (BMI)

Adipose tissue is active endocrine and metabolic tissue

Environmental Risk FactorsObesityIn response to endocrine and metabolic signaling, adipose tissue releases free fatty acids

Increased free fatty acids gives rise to insulin resistance and causes chronic hyperinsulinemia

Correlates with colon, breast, pancreatic, and endometrial cancers

Clinical Manifestations of CancerPainLittle or no pain is associated with early stages of malignancyInfluenced by fear, anxiety, sleep loss, fatigue, and overall physical deteriorationMechanismsPressure, obstruction, invasion of sensitive structures, stretching of visceral surfaces, tissue destruction, and inflammation

Clinical Manifestations of CancerFatigueSubjective clinical manifestationTiredness, weakness, lack of energy, exhaustion, lethargy, inability to concentrate, depression, sleepiness, boredom, and lack of motivation

Suggested causesSleep disturbance, biochemical changes (cytokines), secondary to disease and treatment, psychosocial factors, level of activity, nutritional status, and environmental factors

Clinical Manifestations of CancerSyndrome of cachexia (Gr. bad condition)Most severe form of malnutritionPresent in 80% of cancer patients at death

Includes: Anorexia, early satiety, weight loss, anemia, asthenia, taste alterations, and altered protein, lipid, and CHO metabolism

Cachexia

Clinical Manifestations of CancerAnemiaA decrease of hemoglobin in the bloodMechanismsChronic bleeding resulting in iron deficiency, severe malnutrition, medical therapies, or malignancy in blood-forming organs

Clinical Manifestations of CancerLeukopenia and thrombocytopeniaDirect tumor invasion to the bone marrow causes leukopenia and thrombocytopeniaChemotherapy drugs are toxic to the bone marrow

InfectionRisk increases when the absolute neutrophil and lymphocyte counts fall

Cancer TreatmentChemotherapyUse of nonselective cytotoxic drugs that target vital cellular machinery or metabolic pathways critical to both malignant and normal cell growth and replication

GoalEliminate enough tumor cells so bodys defense can eradicate any remaining cells

Cancer TreatmentChemotherapyCompartments1: cells undergoing mitosis and cytokinesis2: cells capable of entering the cell cycle in G1 phase3: cells not dividing or have irreversibly left cell cycleCells in compartment 3 will die a natural death

Chemotherapy

Cancer TreatmentIonizing radiationEradicate cancer without excessive toxicityAvoid damage to normal structuresIonizing radiation damages the cancer cells DNASurgeryBiopsy and lymph node samplingSentinel nodesDebulking surgery remove most of tumorPalliative surgery relief of symptomsHormone therapyReceptor activation or blockageInterferes with cellular growth and signaling

Cancer TreatmentImmunotherapyTheoretically, antitumor responses can selectively eliminate cancer cells while sparing normal cellsImmune memory is long livedNumerous immunologic mechanisms are capable of rejecting different types of cancerBiologic response modifiers (BRMs)

Cancer TreatmentOther forms of immunotherapyInterferon administrationAntigensEffector cell lymphokinesMonoclonal antibodies

Side Effects of Cancer TreatmentGastrointestinal tractBone marrowHair and skinReproductive tract

Concept Check1. Likely cause for fatigue in cancer patients:A. Biochemical changes due to treatmentB. Muscle lossC. Pychologic factorsD. All of the above

2. The pain experience with cancer:A. Affects the patient only in the early stagesB. Occurs in bone metastasisC. Due to tissue necrosisD. Both b and c are correct

*Bio217 F12Fats, glial cells, uterine SMC, cartilage*Bio217 F12Adrenal medulla tumor - pheochromocytoma*Bio217 F12Currently accepted that multiple mutations are nec. for cancer to dev.A number of cell control paths must be altered:1. cancer cells proliferate in absence of growth factors2. antigrowth signals (contact inhibition) inactivated in cancer3. & 4. apoptosis = self destruction path (like excessive growth) is disabled excess growth takes place5. Angiogenesis new blood vessel growth6. VEGF (vascular endothel. GF) is inactivated will fight cancer growth and spread*Bio217 F12Bio217 F12*The cells were later commercialized, although never patented in their original form. Then, as now, there was no requirement to inform a patient, or their relatives, about such matters because discarded material, or material obtained during surgery, diagnosis or therapy, was the property of the physician and/or medical institution. This issue and Mrs. Lacks' situation was brought up in the Supreme Court of California case of Moore v. Regents of the University of California. The court ruled that a person's discarded tissue and cells are not their property and can be commercialized.(As stated in The Immortal Life of Henrietta Lacks by Rebecca Skloot)Initially, the cell line was said to be named after a "Helen Lane" or "Helen Larson", in order to preserve Lacks' anonymity. Despite this attempt, her real name was used by the press within a few years of her death. These cells are treated as cancer cells, as they are descended from a biopsy taken from a visible lesion on the cervix as part of Mrs. Lacks' diagnosis of cancer. A debate still continues on the classification of the cells.[citation needed]HeLa cells are termed "immortal" in that they can divide an unlimited number of times in a laboratory cell culture plate as long as fundamental cell survival conditions are met (i.e. being maintained and sustained in a suitable environment). There are many strains of HeLa cells as they continue to evolve by being grown in cell cultures, but all HeLa cells are descended from the same tumor cells removed from Mrs. Lacks. It has been estimated that the total number of HeLa cells that have been propagated in cell culture far exceeds the total number of cells that were in Henrietta Lacks' body.[5]Since that time HeLa cells have been used for "research into cancer, AIDS, the effects of radiation and toxic substances, gene mapping, and countless other scientific pursuits".[6] According to author Rebecca Skloot, by 2009, "more than 60,000 scientific articles had been published about research done on HeLa, and that number was increasing steadily at a rate of more than 300 papers each month."[7]Rebecca Skloot author of The Immortal Life of Henrietta Lacks 2009http://www.jhu.edu/jhumag/0400web/01.html*Bio217 F121. A2.B3.C4.D*Bio217 F125. E 6. E (a and c)*Bio217 F127. D new growth at new site8. e*Bio217 F12EMR or EMF http://quwave.com/EMF-Pollution.html?gclid=CIyygLqm76kCFRYf3wodghjoYwBio217 F12*Xeno = foreigner, stranger; bios = lifeBio217 F12*1. D2. D*Bio217 F12