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Carcinogenesis . Patricia Jakel, RN,MN,OCN. What Is Cancer?. What is cancer?. A series of cellular, genetic aberrations that cause abnormal cell proliferation. Unchecked local growth (tumor formation) and invasion of surrounding tissue.

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carcinogenesis

Carcinogenesis

Patricia Jakel, RN,MN,OCN

what is cancer
What is cancer?
  • A series of cellular, genetic aberrations that cause abnormal cell proliferation.
  • Unchecked local growth (tumor formation) and invasion of surrounding tissue.
  • Ability to metastasize (e.g. spread in a contiguous fashion to form secondary sites).
changing approach and outcomes
Changing Approach and Outcomes
  • Cancer as disease change from acute to chronic
  • 20th Century Model: “Seek and Destroy”
  • 21st Century Model : “Target and Control”
essential aberrations of malignancy
Essential Aberrations of Malignancy
  • Proliferation
  • Evading Apoptosis-avoiding programmed cell death
  • Cellular Differentiation
  • Motility and Invasion
  • Recruitment of Blood Vessels and Angiogenesis
  • Metastatic Spread
  • Cancer cells must compete successfully at each event to go forward.
mechanism of cancer
Mechanism of Cancer
  • Apoptosis- is programmed cell death-that is, it is an active process controlled by cellular signaling. It may be triggered by the absence of a required growth factor:intercellular signals that indicate DNA damage or other injury to the cell; harmful external agents; or other intra- and extracellular events.
mechanism of cancer1
Mechanism of Cancer
  • Angiogenesis- or the formation of new blood vessels, critical step in tumor growth. Without tumors must obtain oxygen and nutrients by diffusion and therefore cannot grow larger.
  • The tumor remains dormant until it can stimulate blood vessel growth from nearby capillaries.
  • Malignant cells can release growth factors and enzymes that stimulate rapid formation of blood vessels. These chemical include VEGF- Targeted therapy.
carcinogenesis1
Carcinogenesis
  • Refers to the process by which cancer arises. Likely involves a series of multiple steps or cellular changes over time. This three-stage theory is the most widely used explanation of the process by which a normal cell is transformed into a cancer cell.
pathology cancer arsies due to cumulative alteration in a cell s genes

Pathology-cancer arsies due to cumulative alteration in a cell’s genes

1. Proto-oncogenes- the genetic portion of the DNA that regulates normal cell growth and repair: mutation may allow cell to proliferate beyond normal body needs.

pathology
Pathology
  • 2.Tumor suppressor gene- the genetic portion of the DNA that stops cell division; mutation may allow cells to proliferate beyond normal body needs.
  • 3. Oncogenes- abnormal, mutated genes responsible for the transformation of a normal cell into a cancer cell. May arise from mutations in proto-oncogenes, tumor suppressor genes, or other genes.
3 oncogenes continued
3. Oncogenes continued-
  • Different types of oncogenes may act together to induce cancers.
    • 1.p53 tumor suppressor gene-normally functions to stop cell proliferation, which allows DNA damage to be repaired.
      • When mutated, p53 restraint on cell proliferation is lost.
      • p53 mutations occur in about half of all human cancers: most common in colorectal, lung, and breast cancer.
3 oncogene continued
3. Oncogene continued
  • 2. Ras family of proto-oncogens-normally function to promote cellular growth
    • When mutated ras oncognes may allow cells to proliferate unrestrainted.
    • Ras oncogene are the most frequently detected oncogenes in human cancers; most common in pancreatic, colorectal, and thyroid cancers
clinical implications
Clinical Implications
  • Presence of certain oncogenes may have diagnostic and prognostic value.
  • Prevention of gene mutation is one focus of chemoprevention clinical trails.
  • Understanding of genetic changes may result in new targets for treatment
genes and cancer
Genes and Cancer
  • Proto-Oncogenes- normal genes that participate in in normal tissue repair. Molecular “bucket brigade.”
  • Oncogenes- mutated proto-oncogenes. Excessively active
        • Secreted growth factor
        • Cell-surface growth-factor receptors
        • Membrane associated G protein
  • Tumor-Suppressor Genes- normal tell the cell to stop growing, role in cell cycle activity, helps with apoptosis
relationship between genes and cancer
Relationship between genes and cancer
  • Cancer is a disease if genes gone awry. Genes that control the orderly replication of cells become damaged, allowing the cell to reproduce without restraint and eventually to spread into neighboring tissues and set up growths throughout the body.
slide16

Cancer Tends to Involve Multiple Mutations

Benign tumor cells grow only locally and cannot spread by invasion or metastasis

Malignant cells invade neighboring tissues, enter blood vessels, and metastasize to different sites

Time

Mutation inactivates suppressor gene

Cells proliferate

Mutations inactivate DNA repair genes

Proto-oncogenes mutate to oncogenes

More mutations, more genetic instability, metastatic disease

cancer and genetics
Cancer and Genetics
  • All cancer is genetic, in that it is triggered by altered genes. However, just a small portion of cancer is inherited: a mutation carried in reproductive cells, passed on from one generation to the next, and present in cells throughout the body.
cancer and genetics1
Cancer and Genetics
  • Most cancer is random mutations that develop in body cells division during one’s lifetime- either as a mistake when cells are going through cell division or in response to injuries from environmental agents such as radiation or chemicals.
1 initiation
1. Initiation
  • A cancer causing agent damages the DNA, this gene may then:
    • Undergo repair
    • Become permanently changed (mutated)but not cause cancer unless exposed to threshold levels of cancer promotors.
    • Become mutated and produce a cancer cell line.
slide20
Promotion- a process by which carcinogens are subsequently introduced, resulting in one of the following changes:
  • Reversible damage to the proliferation mechanism of the cell; the effects of the promoting factors may be inhibited:
    • Cancer-reversing agent.
    • Host Characteristics
    • Time and dose limits.
promotion continued
Promotion continued.
  • Irreversible damage to the proliferation mechanism, resulting in cancer cell transformation.
progression
Progression
  • Invasion -cells continue to divide; increase in bulk, pressure, and secretion of enzymes result in local spread and invasion of surrounding structures.
  • Neovascularization-formation of new blood vessels.
metastasis the production of secondary tumors at distant sites
Metastasis-the production of secondary tumors at distant sites.
  • Routes of metastasis
  • Sites
  • Clinical Implication
    • Metastasis is the major cause of death from cancer.
    • Most tumors have begun to metastasize at the time of detection.
slide24

Invasion and Metastasis

1

Cancer cells invade surrounding tissues and blood vessels

2

Cancer cells are transported by the circulatory system to distant sites

3

Cancer cells reinvade and grow at new location

slide25

Carcinoma in Situ

Normal

Hyperplasia

Milddysplasia

Carcinoma in situ (severe dysplasia)

Cancer(invasive)

neoplasm vs tumor
Neoplasm vs Tumor
  • Interchangeable terms
  • Refers to abnormal growth of tissue that serves no function and continues to grow unchecked.
  • Can be benign or malignant
  • Cancer- common term for all malignancies
tumor nomenclature
Tumor Nomenclature
  • Hematologic Malignancies
    • Lymphomas
      • Malignancies of the lymphocyte
      • Subclassified as:
        • Hodgkin\'s
        • Non-Hodgkin\'s
    • Multiple myeloma-arises from the plasma cell (B lymphocyte) line.
tumor nomenclature1
Tumor Nomenclature
  • Hematologic Malignancies
    • Leukemias
      • Arises from hematopoietic cells
      • Classified according to cell type and maturity.
      • Lympho-denotes leukemia of lymphoid origin.
      • Myleo-denotes leukemia of myeloid origin
slide29

Different Kinds of Cancer

Leukemias:

Bloodstream

Some common carcinomas:

Lung

Breast (women)

Colon

Bladder

Prostate (men)

Lymphomas:

Lymph nodes

Some common sarcomas:

Fat

Bone

Muscle

slide30

Naming Cancers

Cancer Prefixes Point to Location

Prefix Meaning

adeno- gland

chondro- cartilage

erythro- red blood cell

hemangio- blood vessels

hepato- liver

lipo- fat

lympho- lymphocyte

melano- pigment cell

myelo- bone marrow

myo- muscle

osteo- bone

slide31

Why Cancer Is Potentially Dangerous

Brain

Melanoma cells travel through bloodstream

Liver

Melanoma(initial tumor)

slide32

Tumor Grading

General Relationship Between Tumor Grade and Prognosis

100%

Low grade

Patient

Survival

Rate

High grade

1

2

3

4

5

Years

slide33

Tumor Staging

Five-Year Survival Rates forPatients with Melanoma (by stage)

100%

50%

I

II

III

Stage at Time of Initial Diagnosis

slide34

What Causes Cancer?

Some viruses or bacteria

Some chemicals

Radiation

Heredity

Diet

Hormones

slide35

Population-Based Studies

Regions of Highest Incidence

U.K.:

Lung

cancer

JAPAN:

Stomach

cancer

CANADA:

Leukemia

U.S.:Colon

cancer

CHINA:

Liver

cancer

BRAZIL:

Cervical

cancer

AUSTRALIA:

Skin

cancer

slide36

Heredity? Behaviors? Other Factors?

Colon Cancer(Number of new cases per 100,000 people)

Stomach Cancer

(Number of new cases per 100,000 people)

100

50

5

0

100

70

7

0

Japan

Japanese familiesin U.S.

U.S.

Japan

Japanese familiesin U.S.

U.S.

slide37

Tobacco Use and Cancer

Some Cancer-Causing Chemicals in Tobacco Smoke

slide38

Low-Strength Radiation

High

Dallas

Skin

Cancer

Incidence

Pittsburgh

Detroit

Low

Least

Most

Annual Sunshine

(UV radiation)

slide39

High-Strength Radiation

High

Leukemia Incidence

Low

Least

Most

X-ray Dose(atomic radiation)

ultraviolet radiation a complete carcinogen
Ultraviolet radiation-a complete carcinogen
  • Sources of UVR
    • Sunlight
    • Tanning salons
    • Industrial sources-welding arcs
viruses
Viruses-
  • Infect DNA, resulting in proto-oncogene changes and cell mutation.
  • Effects modified by:
    • Age
    • Immunocompetence
slide42

Viruses

Virus inserts and changes genes forcell growth

Cancer-linked virus

slide43

Examples of Human Cancer Viruses

Some Viruses Associated with Human Cancers

slide44

AIDS and Kaposi’s Sarcoma

Without

disease

HIV infection

Depressed

immune

system

KSHV infection

Kaposi’s

sarcoma

slide45

Bacteria and Stomach Cancer

Patient’s tissue sample

H. pylori

slide46

Heredity Can Affect Many Types of Cancer

Inherited Conditions That Increase Risk for Cancer

slide47

Mutations and Cancer

Genes Implicated in Cancer

what causes cancer
What causes cancer???
  • Exposure to carcinogens-chemical, or viral, or physical or familial
    • Exposure to radiation-cellular DNA damage by physical release of energy.
      • Ionizing radiation
        • Damage to the cell by this source;
          • Is usually repaired and no mutation results.
          • May give rise to a malignancy when damage affects proto-oncogenes or tumor suppressor genes.
          • Depends on numerous factors.
slide49

Cancer Prevention

Carcinogenic chemicals

Carcinogenic radiation

Cancer viruses or bacteria

slide50

Avoid Tobacco

Lung Cancer Risk Increases with Cigarette Consumption

15x

10x

5x

Lung Cancer Risk

0 15 30

Non-smoker

Cigarettes Smoked per Day

skin cancers most common with uvr
Skin cancers most common with UVR
  • Melanoma
  • Basal cell carcinoma
  • Squamous cell carcinoma
slide53

Avoid Cancer Viruses

HPV Infection Increases Risk for Cervical Cancer

High

Cervical Cancer Risk

Low

Noninfected women

Women infected with HPV

chemical carcinogens
Chemical Carcinogens
  • Chemical substances that alter DNA
slide55

Avoid Carcinogens at Work

Some Carcinogens in the Workplace

examples of ionizing radiation
Examples of ionizing radiation
  • Most exposure is natural and unavoidable.
  • Diagnostic radiographs, radiation therapy, radioisotopes used in imaging.
  • Cosmic rays.
  • Radioactive ground minerals and gases-radon, radium, uranium.
  • Cancers linked to ionizing radiation.
compromised immune system
Compromised Immune System
  • Immune surveillance against cancer
  • Surveillance occurs via recognition of tumor-associated antigens
  • Immune response may fail .
    • Age
    • Tumor burden
    • Shed substances
    • Outside factors
staging of cancer
Staging of Cancer
  • TNM
    • T-extent or size of the tumor
    • N-absence or presence and extent of regional lymph node metastasis
    • M-absence or presence of distant metastases.
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