Pathophysiology of Cancer – Flashcards
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What is cancer?
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disease process that begins when a cell is transformed by genetic mutations of the cellular DNA. They can result from inherited or acquired mutations that lead to abnormal cell behavior. The genetically altered cell forms a clone and begins to proliferate abnormally and evades normal growth regulating processes or signals and other body defenses. They eventually invade into surrounding tissues and gain access to lymph and blood cells.
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The incidence of cancer is higher in?
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1. People above 65 2. Industrialized nations 3. Men 4. Less education x2 more likely 5. Death by cancer high in African American Men
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What is hyperplasia?
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Increase in the number of new cells in an organ or tissue.
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What is dysplasia?
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Bizarre cell growth resulting in cells that differ in size, shape or arrangement from other cells. Have a tendency to become malignant.
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What is metaplasia?
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Cell transformation in which there is conversion of one type of mature cell into another type of cell, abnormal but not always bad. Serves as a protective function (in some circumstances). Replacement of one type of epithelium with another that is more likely to be able to withstand the stresses it faces.
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What is neoplasia?
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uncontrolled cell growth of malignant neoplasms that follows no physiologic demand.
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What is Anaplasia?
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A pattern of growth in which cells lack normal characteristics and differ in shape and organization with respect to their cells of origin.
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How is benign/ malignant growths classified?
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Based on the tissue of origin.
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What things do all cancer cells have in common?
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1. Uncontrolled proliferation 2. evasion of growth suppression signals 3. replicative immortality 4. invasion and metastasis 5. resistance to cell death 6. uncontrolled angiogenesis 7. Reprogrammed cellular metabolism 8. Evasion of the immune system
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What are tumor-specifc antigens (TSAs)
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proteins found in malignant cell membrane which develop overtime as the cells become differentiated. **Distinguishes between benign and malignant cells. Aids in assessing the extent of the illness in a person and in tracking the course of illness during treatment or relapse. Contain less fribonectin (cellular cement that makes them less likely to adhere and less cohesive).
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Nuclei of cancer cells
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Large and irregular shaped (phleomorphism).
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What is the warburg effect?
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When cancer cells utilize an increased amount of glucose even in the presence of oxygen. Cancer cells rewire their metabolism to promote growth, survival, proliferation and long-term maintenance. These cancer cells produce energy by a high rate of glycolysis followed by lactic acid fermentation.
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Mitosis in cancer cells happens at what kind of rate?
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Cellular division occurs more rapidly in malignant cells than in normal cells. As the cells growth and divide, more glucose and oxygen are needed.
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What happens if glucose and oxygen are no longer available to use for cell division?
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Malignant cells use anaerobic metabolic channels for cell proliferation.
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2 ways malignant diseases are spread/ transfer cancerous cells?
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1. Invasion 2. Metastasis
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What is invasion?
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Growth of the primary tumor into surrounding host tissues.
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How does invasion work?
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-Works by mechanical pressure that is exerted by rapidly proliferating neoplasms that may force fingerlike projections of tumor cells into surrounding tissue and interstitial spaces. - Malignant cells are less adherent and may break off from the primary tumor and invade adjacent structures. - Malignant cells are thought to possess or produce specific destructive enzymes (proteinases, collagenases, plasminogen activators, lysosomal hydrolyses) in which these enzymes destroy surrounding tissue including the basement membrane which facilitates invasion of malignant cells into the blood and lymphatic vessels.
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What is metastasis?
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The dissemination (act of spreading) of malignant cells from the primary tumor to distant sites by direct spread of tumor cells to body cavities through lymphatic and blood circulation. Seperation from primary tumor, entry into blood vessels. Reaching of distant organs. For example breast cancer mets to bone cancer.... still considered breast cancer stage IV because that is the primary site of tumor.
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Tumors that grow in or penetrate certain body cavities can do what to other organs?
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These tumors may shed cells or emboli that will travel within that body cavity and 'seeds' the surfaces of other organs.
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Example of cancer that 'seeds' nearby organs?
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Ovarian cancer. when malignant cells enter the peritoneal cavity and seed the peritoneal cavity or surfaces of abdominal organs such as the liver of pancreas.
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Most common mechanism of metastasis?
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Lymphatic system
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How is cancer spread through the lymphatic system?
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-Tumor emboli enter the lymph channels by interstitial fluid which communicates with lymphatic fluid. -Malignant cells penetrate lymphatic vessels by invasion.
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After malignant cells have entered the lymphatic circulation where do they go next? (one of two places)
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1. They lodge themselves in the lymph nodes 2. Pass between the lymphatic and venous circulations
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If a tumor develops in an area of high lymphatic circulation are at a high risk for what?
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Metastasis through the lymphatic system
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Breast cancer metastasis through which lymphatic channels?
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1. auxillary lymph nodes 2. clavicular lymph nodes 3. Thoracic lymph nodes
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Hematogenous spread of cancer cells is directly related to what factor?
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Dissemination of malignant cells via the bloodstream is directly related to the vascularity of the tumor.
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Why can only a few malignant cells survive hemoteogenously?
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1. Hard to survive turbulent arterial circulation 2. insufficient oxygenation 3. Destruction via immune system ALSO the structure of arteries and arterioles are too secure to permit malignant invasion.
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How to malignant cells survive in the blood?
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They attach to the endothelium and attract fibrin, platelets, and clotting factors to seal themselves from immune surveillance. The endothelium will retract itself and allow the malignant cells to enter the basement membrane and secrete proteolytic enzymes (breakdown of proteins). Degrade ECM and allow for implantation.
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What is angiogenesis?
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Growth of new blood vessels from the host tissue stimulated by the release of growth factors (VEFG). Rapid formation of new blood vessels helps malignant cells obtain the necessary nutrients and oxygen. The vessels that are formed are abnormal and function inefficiently. *A way for tumor emboli to travel to distant sites and enter systemic circulation.
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What is Carcinogenesis?
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malignant transformation or initiation of cancer formation.
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What are carcinogens?
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Agents that intiate or promote cellular transformation.
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Examples of carcinogens include
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1. tobacco and tobacco smoke (chemical/ toxin) 2. pesticides (chemical/ toxin) 3. UV light (radiation) 4. Asbestos (environmental) 5. Formaldehyde (environmental) 7. Arsenic (environmental)
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Three stages of carcinogenesis?
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Initiation, promotion and progression.
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Initiation phase
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During this phase carcinogens cause mutations in the cellular DNA which is irreversible.
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Promotion phase
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Repeated exposure to promoting agents causes proliferation and expansion of initiated cells with increased expression or manifestations of abnormal genetic information. There are latency periods that vary depending depending on the type of agent, dosage of the promotor and the characteristics/ stability of the target cell. This phase leads to to formation of preneoplastic (cancerous) or benign lesion.
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What is a co-carcinogen?
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a chemical the promotes the effects of a carcinogen in the production of cancer.
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Progression phase
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The altered cells exhibit increasingly malignant behavior. They acquire the ability to stimulate angiogenesis, can invade surrounding tissues and metastasize.
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Proto- oncogenes
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A normal gene that have many functions of the cell including coding for proteins that stimulate cell division, prevent cell differentiation and regulate programmed cell death (apoptosis). When it is altered by a mutation, an increase in the amount of these proteins occur leading to unregulated cellular division thus becoming an oncogene... and can lead to cancer. *Act as "turn on" genes for cellular growth..
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Examples of proto-cocogenes
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-Epidermal growth factor receptor (EGFR) -Transcription factors (c-Myc) - Cell signaling proteins (KRAS)
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Cancer suppressor genes
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Turn off or regulate uneeded cellular proliferation.
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What happens when cancer suppressor genes are mutated or silenced?
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They lose their regulatory capabilities and malignant cel reproduction continues uncontrolled.
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TP53 tumor suppressor gene
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this gene determines whether cells will live or die after DNA damage. 50% in non-inherited cancers
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What happens if their is an alteration in p53?
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Decrease in apoptic signals which gives a survival advantage for mutant cell populations. Mutant TP53 is associated with poor prognosis. Once this genetic expression occurs in cells. the cells begin to produce mutant cell populations that are different from their original cellular ancestors.
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what are some factors known to induce carcinogenesis?
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1. Viruses and bacteria 2. Physical agents 3. Chemicals 4. Genetic or familial factors 5. Diet 6. Hormones
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In what ways are viruses/ bacteria a factor in causing cancer?
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DNA viruses insert a part of their own DNA near the infected cell genes causing cell division. The newly formed cells that now carry viral DNA lack normal controls on growth. Other viruses carry a gene that causes the infected cells to degrade tumor supressor genes or over produce proto-oncogenes.
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Human Papilloloma Virus leads to?
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leads to cervical, head and neck cancers.
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Hepatitis B leads to?
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Liver cancer
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Epstein-Barr virus leads to?
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Burkitt lymphoma, nasopharyngeal cancer.
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Which bacteria is associated to the incidence of increased gastric malignancy?
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H. Pylori
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What are some physical agents that lead to carcinogenesis?
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Exposure to sunlight, radiation, chronic irritation or inflammation and tobacco use.
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Ways people are exposed to radiation?
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x- rays radiation therapy
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Radiation therapy and exposure to radioactive materials place people at a higher risk for what types of cancers?
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1. Leukemias 2. Multiple myeloma 3. cancers of lung, bone, breast and thyroid.
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Tobacco Smoke
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Most lethal chemical carcinogen. Accounts for at least 30% of cancer deaths. Associated with cancers of the lung, head and neck, esophagus, stomach, pancreas, cervix, kidney and bladder. 4000 individual chemicals, 60 known carcinogens. Chewing tobacco associated with oral cancer, and found most common in men younger than 40. Passive smoke (second hand smoke) has been linked to lung cancer. Nonsmokers whom live with a smoker have a 20-30% greater risk of developing lung cancer. May also be linked to childhood leukemia.
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The hallmarks of families with a hereditary cancer syndrome includes what?
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1. Cancer in 2 or more first degree or second degree relatives 2. Early onset of cancer in family members younger then 50 3. same type of cancer in several family members 4. Individual family members with more than 1 type of cancer 5. A rare cancer in one or more family members
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What should be included in a family history assessment with a patient that has cancer in the family?
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- Obtain information about both maternal and paternal sides of family for 3 generations - Obtain cancer history for at least 3 generations - Look for clustering cancers in one individual, cancer in paired organs, and two or more close relatives with the same type of cancer suggestive of hereditary cancer syndrome.
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Dietary substances that increase the risk for cancer include?
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- fats - alcohol - salt-cured or smoked meats - nitrate and nitrite containing foods - red processed meats
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Alcohol intake should be limited to?
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2 drinks a day for men 1 drink a day for women
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What types of cancers are thought to depend on endogenous hormonal levels?
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Breast, prostate and uterus cancers
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What hormonally can increase the risk for cancers?
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1. Oral contraceptives (the combination of estrogen and progesterone appears safer than estrogen alone) 2. Prolonged estrogen therapy increase especially for liver, endometrial and breast cancer
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DES
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Synthetic estrogen, given to women because it was thought to prevent miscarriages during 1938-1971. Actually causes vaginal carcinomas.
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What hormonal changes in the reproductive cycle are associated with cancer?
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1. Early onset of menses before age 12 2. Delayed onset of menopause after 55 3. nulliparty (never given birth) 4. delayed child birth after age 30 All increase the risk for breast cancer... the increase in # of birth, decreases incidence of breast cancer, endometrial and ovarian cancers.
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People that have an increased risk for cancer include?
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1. Patients who are immunocompromised 2. Renal transplant recipients whom receive immunosuppression therapy to prevent rejection of the transplant organ (lymphoma, Kaposi's sarcoma, cancers of skin and cervix). 3. Patients with immunodeficiency diseases ex: AIDS. (Kaposi's sarcoma, Non-Hodgkin, cervical carcinoma). 4. Patients previously treated with chemo, stem cell transplant, radiation which involve total body irradiation are at an increased risk for secondary primary cancers related to treatment associated immunosuppression. 5. Autoimmune diseases such as RA, Sjogren syndrome 6. Age related changes such as declining organ function, increase risk of chronic diseases.
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Process of survelliance
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Malignant cells are capable of developing on a regular basis. However, through surveillance cells of the immune system can detect the development of transformed cells and destroy them before cel growth becomes uncontrolled. When the immune system fails to identify and stop the growth of transformed cells, cancer develops.
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What is the role of T lymphocytes against foreign antigens?
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They recognize TAAs (tumor associated antigens) as foreign. T lymph release cytokines that illicit various immune system actions 1. Proliferation of cytotoxic (Cell-killing) T lymphocytes capable of direct destruction of cancer calls 2. Induction of cancer cell apoptosis 3. recruitment of additional immune system cells (B-cells, which produce antibodies, NK cells and macrophages) that contribute to the destruction and degradation of cancer cells.
