Carcinogenesis
Download
1 / 60

Carcinogenesis - PowerPoint PPT Presentation


  • 129 Views
  • Uploaded on

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.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' Carcinogenesis ' - kreeli


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
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 cell’s genes

  • 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- cell’s genes

  • 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 cell’s genes

  • 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 cell’s genes

  • 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 cell’s genes

  • 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 cell’s genes

    • 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.


    Cancer Tends to Involve Multiple Mutations cell’s genes

    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 cell’s genes

    • 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 cell’s genes

    • 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 cell’s genes

    • 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.


    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. introduced, resulting in one of the following changes

    • Irreversible damage to the proliferation mechanism, resulting in cancer cell transformation.


    Progression
    Progression introduced, resulting in one of the following changes

    • 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.


    Invasion and Metastasis sites.

    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


    Carcinoma in Situ sites.

    Normal

    Hyperplasia

    Milddysplasia

    Carcinoma in situ (severe dysplasia)

    Cancer(invasive)


    Neoplasm vs tumor
    Neoplasm vs Tumor sites.

    • 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 sites.

    • 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 sites.

    • 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


    Different Kinds of Cancer sites.

    Leukemias:

    Bloodstream

    Some common carcinomas:

    Lung

    Breast (women)

    Colon

    Bladder

    Prostate (men)

    Lymphomas:

    Lymph nodes

    Some common sarcomas:

    Fat

    Bone

    Muscle


    Naming Cancers sites.

    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


    Why Cancer Is Potentially Dangerous sites.

    Brain

    Melanoma cells travel through bloodstream

    Liver

    Melanoma(initial tumor)


    Tumor Grading sites.

    General Relationship Between Tumor Grade and Prognosis

    100%

    Low grade

    Patient

    Survival

    Rate

    High grade

    1

    2

    3

    4

    5

    Years


    Tumor Staging sites.

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

    100%

    50%

    I

    II

    III

    Stage at Time of Initial Diagnosis


    What Causes Cancer? sites.

    Some viruses or bacteria

    Some chemicals

    Radiation

    Heredity

    Diet

    Hormones


    Population-Based Studies sites.

    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


    Heredity? Behaviors? Other Factors? sites.

    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.


    Tobacco Use and Cancer sites.

    Some Cancer-Causing Chemicals in Tobacco Smoke


    Low-Strength Radiation sites.

    High

    Dallas

    Skin

    Cancer

    Incidence

    Pittsburgh

    Detroit

    Low

    Least

    Most

    Annual Sunshine

    (UV radiation)


    High-Strength Radiation sites.

    High

    Leukemia Incidence

    Low

    Least

    Most

    X-ray Dose(atomic radiation)


    Ultraviolet radiation a complete carcinogen
    Ultraviolet radiation-a complete carcinogen sites.

    • Sources of UVR

      • Sunlight

      • Tanning salons

      • Industrial sources-welding arcs


    Viruses
    Viruses- sites.

    • Infect DNA, resulting in proto-oncogene changes and cell mutation.

    • Effects modified by:

      • Age

      • Immunocompetence


    Viruses sites.

    Virus inserts and changes genes forcell growth

    Cancer-linked virus


    Examples of Human Cancer Viruses sites.

    Some Viruses Associated with Human Cancers


    AIDS and Kaposi’s Sarcoma sites.

    Without

    disease

    HIV infection

    Depressed

    immune

    system

    KSHV infection

    Kaposi’s

    sarcoma


    Bacteria and Stomach Cancer sites.

    Patient’s tissue sample

    H. pylori


    Heredity Can Affect Many Types of Cancer sites.

    Inherited Conditions That Increase Risk for Cancer


    Mutations and Cancer sites.

    Genes Implicated in Cancer


    What causes cancer
    What causes cancer??? sites.

    • 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.


    Cancer Prevention sites.

    Carcinogenic chemicals

    Carcinogenic radiation

    Cancer viruses or bacteria


    Avoid Tobacco sites.

    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 sites.

    • Melanoma

    • Basal cell carcinoma

    • Squamous cell carcinoma


    Avoid Cancer Viruses sites.

    HPV Infection Increases Risk for Cervical Cancer

    High

    Cervical Cancer Risk

    Low

    Noninfected women

    Women infected with HPV


    Chemical carcinogens
    Chemical Carcinogens sites.

    • Chemical substances that alter DNA


    Avoid Carcinogens at Work sites.

    Some Carcinogens in the Workplace


    Examples of ionizing radiation
    Examples of ionizing radiation sites.

    • 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 sites.

    • 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 sites.

    • 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.


    ad