1. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 1 Section IV Biology of Cancer Biology of Cancer

2. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 2 Definition of Cancer The most generally accepted definition of a tumor is: It is a tissue overgrowth which is independent of the laws governing the rest of the body. The tissue serves no useful purpose. It is a tissue overgrowth which is independent of the laws governing the rest of the body. The tissue serves no useful purpose.

3. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 3 Benign  Usually encapsulated  Well differentiated  Do not invade  Do not spread to regional lymph nodes

4. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 4 Normal tissue to invasive Ca.

5. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 5 What are stem cells? Def: Immature or precursor cells They are: Self renewing Multipotent----have the ability to differentiate into multiple different cell types

6. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 6 What is a tumor marker? Substances produced by Ca. cells found in plasma, blood, spinal fluid, urine. Ex. PSA---(Prostate Specific Antigen)

7. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 7 What is apoptosis Programmed cell death Cancer cells are unable to experience the natural cell death process.

8. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 8 ARE YOU GETTING OLD? Cancer is predominately a disease of aging We all acquire genetic hits or mutations over time When sufficient numbers occur, a Ca. develops

9. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 9 Age as it relates to Cancer

10. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 10 What about the cumulative effect of Radiation exposure and the likelihood of cancer?

11. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 11 What is ANGIOGENESIS? Cancer creates it’s own blood supply

12. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 12 What is an ONCOGENE? A gene having the potential to cause a normal cell to become cancerous. (For an oncogene to be created, the tumor suppressor first must be turned off.)

13. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 13 Causes of Cancer Gene Amplification---Creation of Oncogenes

14. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 14 Causes of Cancer Gene Silencing---Heredity can silence tumor suppression genes which can then promote the growth of a cancer

15. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 15 Causes of Cancer Guardians of the Genome---Caretaker genes repair the genome when division has caused an aberration by things like ionization or UV radiation.

16. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 16 Causes of Cancer Inflammation---Chronic inflammation has been recognized for 140 yrs as a contributor to causing cancer. (Ulcerative colitis causes a 30 fold increase in cancer rates)

17. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 17 Causes of Cancer Genetics & cancer families---Cancer families demonstrate the inheritance of genetic mutated genes that cause cancer.

18. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 18 Causes of Cancer  Viruses---HIV, HBV All cervical cancer is caused by infection with human papillimavirus (HPV)

19. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 19 Bacterial causing Cancer Chronic infections can cause cancer. Ex. H. Pylori causes stomach ca., a leading cause of cancer worldwide.

20. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 20 Environmental Carcinogens--- ionizing radiation---atomic bombs small doses have two theories--- No dose considered safe Less than 1 rad inconsequential Radiation induced ca. seems to have a latent period, 10 yrs for leukemia & 30 yrs for solid tumors

21. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 21 Environmental cont. Obesity Smoking---4-5 million people die/ yr from effects of smoking. UV light Alcohol---oral, pharynx, esophagus Ca. Occupational hazards---Asbestos, pollution

22. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 22 Biology of Cancer Cell differentiation---The process of developing specialized functions. Ca. cells loose their ability to differentiate. Neoplasms resemble undifferentiated tissue.

23. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 23 Normal stem cell division  When a stem divides, it creates a stem cell and a cell committed to terminal differentiation. (This means, the differentiated cell commits to a specific function and to cell death at the end of cell life.) With cancer cells, both cells stay undifferentiated & neither commit to end of life.

24. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 24 Characteristics of Cancer Cells Cell type---some ca. cells retain their useful functions, while others are disorganized & are unidentifiable Progression---Cancer cells invade & destroy neighboring tissue.

25. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 25 Characteristics of Cancer Cells, cont. Cell surface changes---Surface changes reduce communication between cells. Altered membrane permeability---Causes increased demand for sugars. Fibroconetin loss---causes cells to loose their connection to adjacent cells & allows for cell migration. (malignancy)

26. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 26 Tumor creation & spreading 1. Malignant changes in cell--- transformation 2. Growth of transformed cell 3. Local invasion 4. Distant metastasis

27. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 27 Local invasion 1. Cells or clumps of cells loose their adhesion. Cancer is an abnormal violation of tissue boundaries 2. Normal cells that detach undergo apoptosis, (cell self destruction) Tumor cells create their own growth factor & become autonomous

28. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 28 Mechanisms of invasion Lytic enzymes---Tumors produce & secrete lytic enzymes that destroy normal tissue

29. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 29 Mechanisms of invasion, cont. Decreased cell adhesion---Fibroconnectin regulates cell attachment, spreading, phagocytosis, cell structure effects, cell movement. Integrin-fibroconnectin acts like an anchoring molecule. Ca. cell create different types of these materials or less of them.

30. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 30 Mechanisms of invasion, cont. Three step theory of invasion---Tissue components have two types: 1.Basement membranes 2.Interstitial connective tissue

31. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 31 Three step theory of invasion 1.Tumor cell attaches to the extracellular matrix. Surface receptors on the tumor cell bind to parts of the basement membrane.

32. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 32 Three step theory of invasion cont. 2.Degradation of the matrix by the tumor cell. (tumor cell secretes proleolytic enzymes that degrade the matrix close to the tumor cell

33. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 33 Three step theory of invasion cont. 3.Migration of the tumor cell through the basement membrane. (Pseudopodia, finger like projections of the tumor cross the membrane enabling the tumor to extravasate from the blood vessel into interstitial tissue, p. 381)

34. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 34 Three stages of cancer spreading 1. Locally invasive 2. Spreads to regional structures such as lymph nodes 3. Spreads to distant sites such as liver

35. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 35 How does it feel? 1.Pain---Strongly influenced by anxiety, sleep loss, fatigue, overall physical health, culture, psychology.

36. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 36 How does it feel? Cont. 2. Fatigue 3. Cachexia---State of constitutional disorder or general ill health

37. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 37 How does it feel? Cont. Anemia---Caused by chronic bleeding, malnutrition, medical therapies, or malignancy of blood forming organs.

38. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 38 How does it feel? Cont. Leukopenia---Bone marrow tumors cause a decreased no. of leukocytes Infection---May cause death in patient because of complications due to loss of lymphocytes & granulocytes

39. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 39 Let’s kill the little buggers RADIATION SURGERY---Sentinel node surgery. (First to receive damage from any given location.) HORMONAL THERAPY

40. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 40 Let’s kill the little buggers Cont. CHEMOTHERAPY---Depending on stage of cell cycle, some cells are insensitive to radiation & chemo. INTERFERONS---Proteins which have antiviral & immune modulating properties

41. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 41 Let’s kill the little buggers Cont. ANTIGENS---Receptors which tag the cancer cell & bring in a killing agent

42. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 42 Side effects of cancer treatment GI tract---ulcers, malabsorption, diarrhea Bone Marrow---chemo & radiation causes bone marrow suppression. Hair loss Skin erythemia

43. Elsevier items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. End of Radiation Health Safety course