ONCOLOGY & IMMUNE DISORDERS

1. ONCOLOGY & IMMUNE DISORDERS Introduction to Unit One Chapter 16 Text

2. Today’s Class: • Immune system and cancer • Cancer cell characteristics • Tumor classification • Phases of the cell cycle • Grading and staging cancer • Cancer statistics & risk factors • Warning signs of cancer

3. Class Objectives: • Compare the structure and function of the normal cell and the cancer cell. • Discuss the connection between cancer and the immune system. • Differentiate between benign and malignant tumors. • Describe the classification of cancers according to tissue of origin, Grading and staging. • Discuss the current trends of cancer in relation to incidence, prevalence and mortality of different types of cancer. • Describe the warning signs of cancer. • Discuss risk factors associated with cancer. • Discuss the 7 steps to health.

4. Terms: • Oncology : is the study of cancer • The words cancer, neoplasm, malignant neoplasm and tumor are often used interchangeably, however tumor simply refers to a lump, mass, or swelling Definitions: • Neoplasm 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 organism. • Neoplasms can be either benign or malignant • Cancer:is used to refer to malignant neoplasms. • Cancer 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 surrounding tissue or to new sites in the body. • Proliferation : to grow or multiply by rapidly producing new tissue, parts, cells, or offspring

5. 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).

6. Normal CellsThe Body’s Primary Defense SystemProvide natural resistance & innate immunity • Specific Function • Ordered Rate of Proliferation • Limited Mobility • Controlled by DNA & RNA • Need oxygen, water & nutrients • Produce energy • Eliminate waste

8. Cancer Cells: Breast Brain

10. Immune System…Cancer

11. 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

12. Immune 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.

13. 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.

14. Attack: -Cancer Cell (Grey) -Immune Cells (Green) -Red Blood Cell (Red)

15. CARCINOGENS Carcinogens are factors that are associated with cancer causation: (agents that initiate or promote cellular transformation) • Viruses • Radiation • Chemicals • Genetic susceptibility (10% of all cancers have a strong genetic link) • Host susceptibility also affected by gender, ethnicity, age, exercise and diet.

16. Viruses and Bacteria CARCINOGENS • Viruses: hard to determine, difficult to isolate, incorporate themselves into the genetic structure of cells and alter tem • Epstein-Barr virus: Burkitt’s lymphoma, nasopharyngeal cancers, non-Hodgkins and Hodgkins • HSVII: liver • Hepatitis B: liver cancer • HPV 16, 18, 33 dysplasia and cervical cancer • Human t-lymphotropic virus: lymphocytic leukemia and lymphoma • HIV virus: Karposi’s sarcoma • Bacteria: associated with an increased incidence of gastric malignancy, perhaps secondary to inflammation and injury of gastric cells

17. Chemical Carcinogens

18. Cellular Dysfunctions in Cancer • Defect in cellular proliferation a- defect innormal balance between cellular proliferation and cell death. b- loss ofContact inhibition & doubling time • Defect in cellular differentiation a- (defect in cancer ) normally an orderly process that progresses from immaturity to maturity. b- (defect in cancer) as normal cells differentiate they become capable of carrying out specific functions

19. Cellular Differentiation

20. Cancer • 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.

21. Normal Cellular Differentiation (specialization & maturity of cells) differentiation

22. Cancer 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)

23. Broad Phases of the Cell Cycle • Go • G1 • S • G2 • M

24. Cell Cycle • G0 resting phase • G1 cellular contents including RNA and protein are synthesized • S synthesis phase each of the 46 chromosomes is duplicated by the cell • G2 the cell “double checks” the duplicated chromosomes for error, making any needed repairs • Mitosis cellular division and production of 2 new cells

25. Gene expression & protein synthesis Growth & protein synthesis

26. G1 / G0 • G0 is the resting phase of the cell, cells are not in the phase of cellular division • The G1(Gap 1) phase is characterized by RNA and protein synthesis. This enables the cell to grow and to produce all the necessary proteins for DNA synthesis. • Period of time cell is in G1 varies, depending on cell type and proliferation activity. Why Important?

27. ? Answer • It primes the cell to enter the next phase: S

28. S Phase • Synthesis phase (S phase) the cell replicates its DNA...so it now has 2 complete sets of DNA. • Lasts 6-8 hours • Cell proliferation can be measured in a lab, i.e. patho report refers to % of cells in S phase. • Why would the cell want 2 complete sets of DNA?

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

30. G2 • During the G2 phase, the cell again undergoes growth and protein synthesis (it needs enough proteins for 2 cells!)...priming it to be able to divide. • Once this is complete the cell finally enters the fourth and final phase of the cell cycle: the M (Mitosis) phase.

31. M (Mitosis) Phase • During the M phase, the cell splits apart (called cytokinesis) into two daughter cells. Now, the cycle has been completed!

32. What do the cells do now? Two choices: • 1) Start the cycle again by entering G1 • 2) Become quiescent by entering G0 What problems arise with this cycle?

33. Answer • Once the cell gets going there is not stopping it! • Cancer cells rapidly divide and quickly spread

34. 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 invasivenessof cancerous cells into other tissues).

35. Chemotherapeutic Agents • Drugs that are cell cycle specific and destroy cells actively reproducing by means of the cell cycle. • Many agents are specific to certain phases of the cycle. Most affect cells in the S phase by interfering with DNA & RNA synthesis Others are specific to the M phase ( prevent mitosis).

36. Classification of Cancer Tumors can be classifies according to : • Anatomic site • Histological analysis (grading) • Extent of disease (staging)

37. Neoplasm Classification: Anatomic Site 1. According to Cell type 2. Tissue of origin NB 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 Malignant 4. Degree of Differentiation

38. BENIGN Encapsulated Noninvasive Highly Differentiated Mitosis Rare Slow Growth Little/ No Anaplasia No Metastasis Doesn't normally recur Not usually harmful Prognosis good MALIGNANT Nonencapsulated Invasive Poorly Differentiated Mitosis Common Rapid Growth Anaplastic (loss of function & differentiation) Metastasis Can recur Always harmful Prognosis depends Comparison of Benign and Malignant Neoplasms

40. Tumor Staging and Grading

41. Grading: • Identification of the type of tissue from which the tumor originated and the degree to which the tumor cells retain the functional and structural characteristics of the tissue or origin Thus evaluate cell’s appearance and degree of differentiation

42. CANCER • 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, extensionand penetration

43. Terminology: Recognize these words! • Structural changes • hyperplasia (increase proliferation) • metaplasia(degree of abnormality) • dysplasia (abnormal) • Anaplasia (malignant) • neoplasm (new abnormal growth)

44. Grading • Grade I: cells differ slightly from normal (mild dysplasia) and are well differentiated. • Grade II: Cells are more abnormal (moderate dyplasia) and moderately differentiated. • Grade III: Cells are very abnormal (severe dysplasia) and poorly differentiated. • Grade IV: Cells are immature and primitive (anaplasia) and undifferentiated. (cell of origin is difficult to determine).

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

46. Staging (TNM) Staging determines the size of the tumor and the existance of metastases. Refer 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

47. TNM STAGING CLASSIFICATION

48. Hint, Hint!! • On a test or exam I will ask you to correctly interpret TNM & or Grading.

49. Sample Question: • A client receives a report from a biopsy with results TO, NO and MO. This indicates: • A. no evidence of a primary tumor, lymph node involvement and metastasis. • B. no primary tumor, but evidence of a degree of distant metastasis. • C. a primary tumor and regional nodes involvement. • D. carcinoma in situ.

50. Answer to previous question is: A