ONCOLOGY & IMMUNE ONCOLOGY & IMMUNE DISORDERSDISORDERS

Introduction to Unit OneIntroduction to Unit OneChapter 16 Text Chapter 16 Text

Today’s Class:Today’s Class:

Immune system and cancerImmune system and cancer Cancer cell characteristicsCancer cell characteristics Tumor classificationTumor classification Phases of the cell cyclePhases of the cell cycle Grading and staging cancerGrading and staging cancer Cancer statistics & risk factorsCancer statistics & risk factors Warning signs of cancerWarning signs of cancer

Class ObjectivesClass Objectives::

Compare the structure and function of the normal cell Compare the structure and function of the normal cell and the cancer cell.and the cancer cell.

Discuss the connection between cancer and the Discuss the connection between cancer and the immune system.immune system.

Differentiate between benign and malignant tumors.Differentiate between benign and malignant tumors. Describe the classification of cancers according to Describe the classification of cancers according to

tissue of origin, Grading and staging.tissue of origin, Grading and staging. Discuss the current trends of cancer in relation to Discuss the current trends of cancer in relation to

incidence, prevalence and mortality of different types incidence, prevalence and mortality of different types of cancer.of cancer.

Describe the warning signs of cancer.Describe the warning signs of cancer. Discuss risk factors associated with cancer.Discuss risk factors associated with cancer. Discuss the 7 steps to health.Discuss the 7 steps to health.

Terms:Terms: OncologyOncology : is the study of cancer : is the study of cancer

The words The words cancer, neoplasm, malignant neoplasm and tumorcancer, neoplasm, malignant neoplasm and tumor are often used are often used interchangeably, however tumor simply refers to a lump, mass, or swellinginterchangeably, however tumor simply refers to a lump, mass, or swelling

Definitions: Definitions: Neoplasm Neoplasm derived from Greek word neos (new) & plasis (molding) is defined as an derived from Greek word neos (new) & plasis (molding) is defined as an

abnormal mass of tissue that serves no useful purpose and maybe harmful to host abnormal mass of tissue that serves no useful purpose and maybe harmful to host organism.organism.

NeoplasmsNeoplasms can be either benign or malignant can be either benign or malignant

Cancer:Cancer: is used to refer to is used to refer to malignant neoplasmsmalignant neoplasms. .

Cancer Cancer is a disease of the cell in which the normal mechanisms of the control of is a disease of the cell in which the normal mechanisms of the control of growth and proliferation have been altered. It is invasive, spreading directly to growth and proliferation have been altered. It is invasive, spreading directly to surrounding tissue or to new sites in the body.surrounding tissue or to new sites in the body.

Proliferation : to : to grow or multiply by rapidly producing new tissue, parts, cells, or grow or multiply by rapidly producing new tissue, parts, cells, or offspring offspring

Just a Disease?Just a Disease? Many people think diseases such as Cancer,

Diabetes, or COPD are just diseases. They are much more than that. A disease is something that happens to your body. Cancer affects every aspect of your whole life. Its much more than a medical problem, it takes over your mind too. It’s more than a simple adjustment of medication,nutrition, therapy or other treatment. It requires a complete retraining of your lifestyle. Nothing is spared, no part of your life is left unscathed (King, 1994).

Normal CellsNormal CellsThe Body’s Primary Defense SystemThe Body’s Primary Defense SystemProvide natural resistance & innate immunityProvide natural resistance & innate immunity

Specific Function Ordered Rate of

Proliferation Limited Mobility Controlled by DNA &

RNA Need oxygen, water &

nutrients Produce energy Eliminate waste

Cancer Cells:Cancer Cells:

Breast Brain Breast Brain

Immune System…Immune System…CancerCancer

The Immune System & Cancer

What is the connection between cancer and the immune system?

•Cancer cells arise continually as a result of mutations.

•The immune system (T-cell lymphocytes, macrophages, & antigens) recognize these cells as non-self and destroys them.

Maybe good idea: Immune System Review

Available evidence indicates, then, that the immune system responds to cancer cells. Some immunologists believe that it does so on a regular basis. They theorize that the body produces cancer cells fairly regularly, but eliminates most of them before they can spread or form a tumor. They believe that cancer has an opportunity to take hold only when the immune system performs below par. Although they are making progress, scientists still do not completely understand precisely how the immune system works.

Even more convincing are clinical results showing that stimulation of the immune system with bacterial products or components of the immune system itself can lead to tumor regression in some patients. The link between cancer and the immune system is also suggested by the fact that people with an impaired immune system, such as AIDS patients, are more likely to develop certain cancers, including Kaposi's sarcoma, rectal cancer and some types of lymphomas.

Attack:Attack:

-Cancer Cell (Grey)-Immune Cells (Green)-Red Blood Cell (Red)

CARCINOGENSCARCINOGENS

Carcinogens are factors that are associatedCarcinogens are factors that are associatedwith cancer causation: (agents that initiate or with cancer causation: (agents that initiate or

promote cellular transformation)promote cellular transformation)1.1. VirusesViruses2.2. RadiationRadiation3.3. ChemicalsChemicals4.4. Genetic susceptibility (10% of all cancers have Genetic susceptibility (10% of all cancers have

a strong genetic link)a strong genetic link)5.5. Host susceptibility also affected by gender, Host susceptibility also affected by gender,

ethnicity, age, exercise and diet.ethnicity, age, exercise and diet.

Viruses and Bacteria Viruses and Bacteria CARCINOGENS CARCINOGENS

Viruses:Viruses: hard to determine, difficult to isolate, hard to determine, difficult to isolate, incorporate themselves into the genetic structure of incorporate themselves into the genetic structure of cells and alter tem cells and alter tem

• Epstein-Barr virus: Burkitt’s lymphoma, nasopharyngeal Epstein-Barr virus: Burkitt’s lymphoma, nasopharyngeal cancers, non-Hodgkins and Hodgkinscancers, non-Hodgkins and Hodgkins

• HSVII: liverHSVII: liver• Hepatitis B: liver cancerHepatitis B: liver cancer• HPV 16, 18, 33 dysplasia and cervical cancer HPV 16, 18, 33 dysplasia and cervical cancer • Human t-lymphotropic virus: lymphocytic leukemia and Human t-lymphotropic virus: lymphocytic leukemia and

lymphomalymphoma• HIV virus: Karposi’s sarcoma HIV virus: Karposi’s sarcoma

BacteriaBacteria: associated with an increased incidence of : associated with an increased incidence of gastric malignancy, perhaps secondary to gastric malignancy, perhaps secondary to inflammation and injury of gastric cells inflammation and injury of gastric cells

Chemical CarcinogensChemical Carcinogens

Cellular Dysfunctions in CancerCellular Dysfunctions in Cancer

1.1. Defect in cellular proliferationDefect in cellular proliferationa- a- defect indefect in normal balance between normal balance between

cellular proliferation and cell death.cellular proliferation and cell death.

b- b- loss ofloss of Contact inhibition & doubling Contact inhibition & doubling timetime

2.2. Defect in cellular differentiationDefect in cellular differentiationa- a- (defect in cancer )(defect in cancer ) normally an orderly normally an orderly process that progresses from immaturity to process that progresses from immaturity to maturity.maturity.b- b- (defect in cancer)(defect in cancer) as as normal normal cells cells differentiate they become capable of differentiate they become capable of carrying out specific functionscarrying out specific functions

Cellular DifferentiationCellular Differentiation

CancerCancer

Cancer has an opportunity to take hold only when the immune system performs below par (immature, old, or weak).

Chronic illness, malnutrition, use of immunosuppressive drugs contribute to failure of the immune system

Apoptosis: “cell suicide”. In the process of carcinogenesis genetic damage to mutated cells may result in a mutated cell not self-destructing.

Fertilized ova

endoderm mesoderm ectoderm

Mature cells of•Trachea•Lungs

•epithelium

Mature cells of•Muscles•Bones

•Connective tissue

Mature cells of the•Brain•Skin

•glands

Normal Cellular Differentiation Normal Cellular Differentiation (specialization & maturity of cells)(specialization & maturity of cells)

Cancer CellsCancer Cells

Less dependent on oxygen (anaerobic)

Variable shapes & sizes Loose contact inhibition (don’t respect boundaries)

Are less adherent and more mobile Less differentiated (no specialization, no specific

function) leads to loss of normal function Abnormal growth (rapid cell growth)

Broad Phases of the Cell Cycle

•Go• G1•S

• G2•M

Cell CycleCell Cycle

G0 resting phaseG0 resting phase G1 cellular contents including RNA and protein G1 cellular contents including RNA and protein

are synthesizedare synthesized S synthesis phase each of the 46 S synthesis phase each of the 46

chromosomes is duplicated by the cell chromosomes is duplicated by the cell G2 the cell “double checks” the duplicated G2 the cell “double checks” the duplicated

chromosomes for error, making any needed chromosomes for error, making any needed repairsrepairs

Mitosis cellular division and production of 2 new Mitosis cellular division and production of 2 new cells cells

Gene expression & protein synthesis

Growth & protein synthesis

G1 / G0G1 / G0

G0 G0 is the resting phase of the cell, cells are not in the is the resting phase of the cell, cells are not in the phase of cellular divisionphase of cellular division

The The G1G1 (Gap 1)(Gap 1) phase is characterized by phase is characterized by RNA and protein synthesis. This enables RNA and protein synthesis. This enables the cell to grow and to produce all the the cell to grow and to produce all the necessary proteins for DNA synthesis. necessary proteins for DNA synthesis.

Period of time cell is in G1 varies, Period of time cell is in G1 varies, depending on cell type and proliferation depending on cell type and proliferation activity. activity.

? Answer? AnswerIt primes the cell to It primes the cell to enter the next phase: enter the next phase: SS

S PhaseS Phase Synthesis phase (S phase)Synthesis phase (S phase) the cell the cell

replicates its DNA...so it now has replicates its DNA...so it now has 2 complete sets of DNA.2 complete sets of DNA.

Lasts 6-8 hoursLasts 6-8 hours Cell proliferation can be measured Cell proliferation can be measured

in a lab, i.e. patho report refers to in a lab, i.e. patho report refers to % of cells in S phase.% of cells in S phase.

Why would the cell want 2 Why would the cell want 2 complete sets of DNA?complete sets of DNA?

AnswerAnswer This allows the cell to divide into This allows the cell to divide into

two daughter cells, each with a two daughter cells, each with a complete copy of DNA. But, complete copy of DNA. But, before the cell can do this, it before the cell can do this, it needs to enter the third phase of needs to enter the third phase of the cell cycle: the G2 (Gap 2) the cell cycle: the G2 (Gap 2) phase.phase.

G2G2 During the During the G2 G2 phase, the cell again phase, the cell again

undergoes growth and protein undergoes growth and protein synthesis (it needs enough proteins synthesis (it needs enough proteins for 2 cells!)...priming it to be able for 2 cells!)...priming it to be able to divide. to divide.

Once this is complete the cell Once this is complete the cell finally enters the fourth and final finally enters the fourth and final phase of the cell cycle: the phase of the cell cycle: the M M (Mitosis) phase.(Mitosis) phase.

M (Mitosis) PhaseM (Mitosis) Phase During the During the MM phase, the cell phase, the cell

splits apart (called splits apart (called cytokinesis) into two cytokinesis) into two daughter cells. Now, the daughter cells. Now, the cycle has been completed!cycle has been completed!

What do the cells do What do the cells do now?now?

Two choices:: 1) 1) Start the cycle again by Start the cycle again by

entering G1entering G1 2) Become quiescent by 2) Become quiescent by

entering G0entering G0

What problems arise with What problems arise with this cyclethis cycle? ?

AnswerAnswer

Once the cell gets going there is not Once the cell gets going there is not stopping it!stopping it!

Cancer cells rapidly divide and quickly Cancer cells rapidly divide and quickly spreadspread

WHY All This Interest in Cell Division?WHY All This Interest in Cell Division?

One of the main clinical interests of cell cycle control is CANCER.

Cancer can be very briefly described as uncontrolled cell growth and proliferation (as well as metastasis, or the invasiveness of cancerous cells into other tissues).

Chemotherapeutic AgentsChemotherapeutic Agents

Drugs that are cell cycle specific and destroy Drugs that are cell cycle specific and destroy cells actively reproducing by means of the cell cells actively reproducing by means of the cell cycle.cycle.

Many agents are specific to certain phases of Many agents are specific to certain phases of the cycle. Most affect cells in the the cycle. Most affect cells in the S phaseS phase by by interfering with DNA & RNA synthesis Others interfering with DNA & RNA synthesis Others are specific to the are specific to the M phaseM phase ( prevent mitosis). ( prevent mitosis).

Classification of CancerClassification of Cancer

Tumors can be classifies according to :

1. Anatomic site

2. Histological analysis (grading)

3. Extent of disease (staging)

Neoplasm Classification: Anatomic SiteNeoplasm Classification: Anatomic Site

1. According to Cell type2. Tissue of originNB Named according to origin of tissue they

arise from generally with oma (means tumor) Epithelial (carcinomas) Connective (sarcoma) lymphatic (lymphoma) CNS (gliomas) Blood forming (leukemias) Carcinoma in situ (pre-invasive epithelial)

3. Whether Benign or Malignant4. Degree of Differentiation

Comparison of Benign and Comparison of Benign and Malignant NeoplasmsMalignant Neoplasms

BENIGNBENIGN Encapsulated Noninvasive Highly Differentiated Mitosis Rare Slow Growth Little/ No Anaplasia No Metastasis Doesn't normally recur Not usually harmful Prognosis good

MALIGNANTMALIGNANT

Nonencapsulated Invasive Poorly Differentiated Mitosis Common Rapid Growth Anaplastic (loss of function &

differentiation) Metastasis Can recur Always harmful Prognosis depends

Tumor Staging and Tumor Staging and GradingGrading

Grading:Grading:

Identification of the type of tissue Identification of the type of tissue

from which the tumor originated and from which the tumor originated and the degree to which the tumor cells the degree to which the tumor cells retain the functional and structural retain the functional and structural characteristics of the tissue or origincharacteristics of the tissue or origin

Thus evaluate cell’s appearance and Thus evaluate cell’s appearance and degree of differentiationdegree of differentiation

CANCERCANCER Grading: refers to the classification of

tumor cells. The appearance of cells and the degree of differentiation are evaluated.

Cancer cells progress from low grade and well differentiated to high grade and poorly differentiated.

Metastasis implies spread, extension and penetration

Terminology: Recognize these Terminology: Recognize these words!words!

Structural changes hyperplasia (increase proliferation) metaplasia (degree of abnormality) dysplasia (abnormal) Anaplasia (malignant) neoplasm (new abnormal growth))

GradingGrading

Grade IGrade I: cells differ slightly from normal : cells differ slightly from normal (mild dysplasia) and are well differentiated.(mild dysplasia) and are well differentiated.

Grade IIGrade II: Cells are more abnormal : Cells are more abnormal (moderate dyplasia) and moderately (moderate dyplasia) and moderately differentiated.differentiated.

Grade IIIGrade III: Cells are very abnormal (severe : Cells are very abnormal (severe dysplasia) and poorly differentiated.dysplasia) and poorly differentiated.

Grade IVGrade IV: Cells are immature and primitive : Cells are immature and primitive (anaplasia) and undifferentiated. (cell of (anaplasia) and undifferentiated. (cell of origin is difficult to determine).origin is difficult to determine).

This illustration shows Dr Gleason's own This illustration shows Dr Gleason's own simplified drawing of the five Gleason grades simplified drawing of the five Gleason grades of prostate cancer. Grade 1 appears on the of prostate cancer. Grade 1 appears on the far left and grade 5 on the far right. Adapted far left and grade 5 on the far right. Adapted from Gleason DF (1997).from Gleason DF (1997).

Staging (TNM)Staging (TNM)

Staging determines the size of the tumor Staging determines the size of the tumor and the existance of metastases.and the existance of metastases.

Refer to text regarding Staging of CancerRefer to text regarding Staging of Cancer

Tumor (T): TX, T0, Tis, T1-4 Regional Lymph Nodes (N): NX, N0, N1-3 Distant Metastasis (M): MX, M0, M1

TNM STAGING CLASSIFICATIONTNM STAGING CLASSIFICATION

Tumor T0TisT1,T2, T3, T4

No evidence

Tumor in situ

Ascending degrees of tumor size &involvement

Nodes NoN1a,N2aN1b, N2b, N3bNx

No abnormal regional nodes

Regional nodes, no metastasis

Regional nodes, metastasissuspected

Regional nodes can’t be assessedclinically

Metas MoM1,M2,M3

No evidence of distant metastaticAscending degrees of metastaticinvolvement of host includingdistant nodes

Hint, Hint!!Hint, Hint!!

On a test or exam On a test or exam I will ask you to I will ask you to correctly interpret correctly interpret TNM & or TNM & or Grading.Grading.

Sample Question:Sample Question:

A client receives a report from a biopsy with A client receives a report from a biopsy with results TO, NO and MO. This indicates:results TO, NO and MO. This indicates:

A. no evidence of a primary tumor, lymph node A. no evidence of a primary tumor, lymph node involvement and metastasis.involvement and metastasis.

B. no primary tumor, but evidence of a degree of B. no primary tumor, but evidence of a degree of distant metastasis.distant metastasis.

C. a primary tumor and regional nodes C. a primary tumor and regional nodes involvement.involvement.

D. carcinoma in situ.D. carcinoma in situ.

Answer to previous question is: AAnswer to previous question is: A

Leading Cause of Death in Leading Cause of Death in CanadaCanada

Heart Cancer CVA COPD Pneumonia & Flu Diabetes Mellitus Suicide

Highlights: Canadian Cancer Statistics 2010Highlights: Canadian Cancer Statistics 2010

An estimated 6,000 new cases of cancer and 2,700 deaths from An estimated 6,000 new cases of cancer and 2,700 deaths from cancer are expected to occur in Nova Scotia in 2009. (Nationally, cancer are expected to occur in Nova Scotia in 2009. (Nationally, those figures are 171,000 and 72,600 respectively.) those figures are 171,000 and 72,600 respectively.)

In Nova Scotia, the most common cancers among men include In Nova Scotia, the most common cancers among men include prostate, lung and colorectal, and among women, breast, lung and prostate, lung and colorectal, and among women, breast, lung and colorectal. colorectal.

The five-year relative survival rate for all cancers combined is 62 per The five-year relative survival rate for all cancers combined is 62 per cent, an improvement of 4.5 per cent over the past 10 years.* cent, an improvement of 4.5 per cent over the past 10 years.*

In Nova Scotia, the improvement in survival was greatest for non-In Nova Scotia, the improvement in survival was greatest for non-Hodgkin lymphoma in men and lung cancer in women. Hodgkin lymphoma in men and lung cancer in women.

About 40 per cent of Canadian women and 45 per cent of men will About 40 per cent of Canadian women and 45 per cent of men will develop cancer during their lifetimes. develop cancer during their lifetimes.

About 24 per cent of women and 29 per cent of men, or About 24 per cent of women and 29 per cent of men, or approximately one out of four Canadians, is expected to die from approximately one out of four Canadians, is expected to die from cancer.cancer.

Highlights 2010: Cancer in Canadian Highlights 2010: Cancer in Canadian adolescents and young people (15 to 29 years adolescents and young people (15 to 29 years

of age) of age) In the past five years in Nova Scotia, there were 312 young people In the past five years in Nova Scotia, there were 312 young people

diagnosed with some form of cancer, which represents diagnosed with some form of cancer, which represents approximately 62 young people annually.approximately 62 young people annually.

Approximately 2,075 young people in Canada between 15 and 29 Approximately 2,075 young people in Canada between 15 and 29 years of age are diagnosed each year with cancer with about 326 years of age are diagnosed each year with cancer with about 326 deaths per year in this age group. deaths per year in this age group.

The five-year survival for this age group is 85 per cent – a five per The five-year survival for this age group is 85 per cent – a five per cent increase from 1992–1995. cent increase from 1992–1995.

The overall cancer incidence rate has risen since 1996. The death The overall cancer incidence rate has risen since 1996. The death rate has declined since 1992. rate has declined since 1992.

Lymphomas are one of the most commonly diagnosed types of Lymphomas are one of the most commonly diagnosed types of cancer in both sexes, along with thyroid cancer in females and cancer in both sexes, along with thyroid cancer in females and testicular cancer in males. testicular cancer in males.

Leukemia accounts for the most cancer deaths in each sex.Leukemia accounts for the most cancer deaths in each sex.

Canadian Cancer Society 2011Canadian Cancer Society 2011

Lung cancer remains by far the leading cause of death from cancer.

Canada is one of the few nations in the world with a cancer registry system that allows cancer patterns to be monitored and compared across the entire population. Such comparisons can provide valuable information for research, knowledge exchange, planning and decision-making

Nova Scotia Stats:Nova Scotia Stats:

estimated 5200 new cases all types estimated 5200 new cases all types cancerscancers

2500 deaths are expected2500 deaths are expected 720 men Dx Prostrate Ca720 men Dx Prostrate Ca 710 women Dx Breast Ca 710 women Dx Breast Ca Lung Ca leading cause death both Lung Ca leading cause death both

genders 870 new Dxgenders 870 new Dx 690 estimated to die lung Ca690 estimated to die lung Ca

WARNING SIGNSWARNING SIGNSCAUTIONCAUTION

CC Change in bowel or bladder A A sore that does not heal U Unusual bleeding or discharge T Thickening or lump I Indigestion or difficulty swallowing O Obvious change in wart or mole N Nagging cough or hoarseness

Risk Reduction for Developing Cancer:Risk Reduction for Developing Cancer:the 7 Steps to Healththe 7 Steps to Health

Step 1: Step 1: Don’t smokeDon’t smoke Step 2: Step 2: Eat healthy foodEat healthy food Step 3: Step 3: Be activeBe active Step 4: Step 4: Be sensible in the sunBe sensible in the sun Step 5: Step 5: Follow cancer screening guidelinesFollow cancer screening guidelines Step 6: Step 6: Report changes in your healthReport changes in your health Step 7: Step 7: Use caution with hazardous Use caution with hazardous

materialsmaterials

MesotheliomaMesothelioma

Large mesothelioma Large mesothelioma around the right lung around the right lung (left side of image) on (left side of image) on CT scan CT scan

Information:Information:

www.cancer.cawww.cancer.ca

Cancer Care Nova ScotiaCancer Care Nova Scotiawww.cancercare.ns.cawww.cancercare.ns.ca

students should be able to:students should be able to: Discuss the biological processes by which normal cells Discuss the biological processes by which normal cells

become cancerousbecome cancerous

Discuss current research that has consequences for Discuss current research that has consequences for people with cancerpeople with cancer

Understand medical treatment under developmentUnderstand medical treatment under development

Ramifications of support persons & nurses involved in Ramifications of support persons & nurses involved in their caretheir care