Causes of Cancer

1. Causes of Cancer • Defective cellular growth • Stem cells • Generation time • Contact Inhibitor • Defective cellular differentiation • Exposure to carcinogens • Moves to less mature form • Leads to invasion and metastasis

2. Characteristics of Normal Cells • Limited Cell Division • Specific Morphology • Small Nuclear-Cytoplasmic Ratio • Perform Specific Differentiated Functions • Adhere tightly together… • Are nonmigratory • Grow in an orderly and well differentiated manner • Are contact inhibited

3. Characteristics of Early Embryonic Cells • Demonstrate rapid and continuous cell division • Show anaplastic morphology • Have a large nuclear-cytoplasmic ratio • Perform no differentiated functions • Adhere loosely together • Are able to migrate • Are not contact inhibited.

4. Characteristics of Benign Cells • Demonstrate continuous or inappropriate cell growth. • Show specific morphology • Have a smallnuclear-cytoplasmic ratio • Perform differentiated functions • Adhere tightly together • Are nonmigratory • Grow in an orderly and well regulated fashion.

5. Characteristics of Malignant Cells • Demonstrate rapid or continuous cellular division. • Show anaplastic morphology • Have alargenuclear-cytoplasmic ratio • Lose some or all differentiated functions • Adhere loosely together • Are able to migrate • Grow by invasion • Are not contact-inhibited

6. Definitions • Anaplasia • Anaplastic • Carcinogen • Carcinoma

7. Hyperplasia • Hypertrophy • Metastasis • Neoplasia • Neoplasm

8. Stages of Carcinogenesis(Oncogenesis) • Initiation • Promotion • Progression • Metastasis

9. Common Steps in Metastasis • Extension into Surrounding Tissues • Penetration into Blood Vessels • Release of Tumor Cells • Invasion of Tissue at the Site of Arrest

10. Immune Response • Attempts to destroy abnormal cells • Surface Antigens • Used as tracers to indicate success of treatment • CEA (carcinoembrionic antigen) - GI tract • AFP (alphafetoprotein) - liver • CA 125 - ovarian • PSA – prostate

11. Cancer Grade and Stage • Grading; Classifies cellular aspects of a cancer. • Staging; Classifies clinical aspects of the cancer.

12. Histologic Class • I - Well differentiated • II - Moderate differentiation • III - Poor differentiation • IV - Immature & Undifferentiated

13. Clinical Staging • O - Ca in situ • I (A) - Localized growth • II (B) - Limited local growth • III (C) - Extensive local and regional growth • IV (D) - Metastasis

14. TNM Classification • T - Primary tumor • N - Regional lymph nodes • M - Distant metastasis • Tis No Mo • T4N3M1

15. Goal • Education and early detection • C • A • U • T • I • O • N

16. Surgical Interventions • Biopsy • Cure • Control - Debulking • Palliative • Staging • Reconstructive • Prophylaxis

17. Radiation • Destroys cells, causes inflammatory response • Side Effects • Goals: • Cure • Control • Palliative • Radiation Recall • External • Implants • Isotopes

18. Chemotherapy • Cell Cycle Non-specific • Alkylating –Cytoxan, Leukeran, N.Mustard • Antitumor antibiotics - Adriamycin • Nitrosoureas –Carmustine, Hydrourea • Corticosteroids –Prednisone, Decadron • Hormones –Estrogen, Provera, Androgen • Cell Cycle Specific • Antimetabolities –Methotrexate, 5-FU • Plant Alkaloids (Miotic Inhibitors) –Vinblastine, Vincristine • Cisplatin • Tamoxifen

19. Synergistic Effect • The total is greater than the individual parts • Each agent has: • action against cancer • different site of action • different organ toxicity or time of toxicity

20. Complete response Agent Action Toxicity 20% Mustargen DNA Marrow – 10 days  10% Oncovin Mitosis Neurotoxic  10% Procarbazine RNA Synthesis Marrow – 21 days  5% Prednisone Cell membrane Immune suppression 80% Synergistic Effect MOPP Protocol

21. Side Effects Cluster the common ones: bone marrow suppression alopecia nausea and vomiting Adriamycin - Cardiac Cisplatin – Renal

22. Complications • Pain Control • Bone Marrow Suppression • Infection - Neutropenia • Hemorrhage • Anemia • Infarction • Superior Vena Cava Syndrome • Spinal Cord Compression • Tumor Lysis Syndrome

23. Common Problems/Complications Associated With Cancer • Tumor Lysis Syndrome (TLS); Destruction of cells (lysis) Release of Purine and Potassium (K+) into Bloodstream Purines converted to uric acid (in liver) K+ into Bloodstream Hyperuricemia Hyperkalemia Obstruction of Kidney Tubules ARF

24. Paraneoplastic Syndromes • Secretion of Insulin • Secretion of ACTH • Hypercalcemia • SIADH

25. SIADH - Syndrome of Inappropriate ADH • ADH release • Water Reabsorption into circulation -Renal Tubules • Extravascular Fluid • Plasma Osmolality • Glomerular Filtration Rate • Serum Sodium Levels CEREBRAL EDEMA

26. Leukemia • AML - Acute Myelogenous • Age of Onset (15-39 yrs), usually affects adults • Prognosis is generally poor, best with bone marrow transplant • Most common type of leukemia • Equal incidence in males and females • ALL - Acute Lymphocytic • Age of Onset (<15 yrs), usually affects children, accounts for approx 10% of adult leukemia's • Prognosis is poorer for adults than for children • Fever & Bleeding • Increased incidence in males

27. Leukemia • CML - Chronic Myelogenous • Age of Onset (>50 yrs) • Involves liver & spleen • Blastic Crisis • CLL - Chronic Lymphocytic • Older patients – over 50 • Lymph node involvement

28. Lymphoma • Lymph system • Lymphocytes & histiocytes (macrophages) • Hodgkins • 15-35 and over 50 yrs. • Non-Hodgkins • Outside of lymph nodes • Wide spread before Dx • Multiple Myeloma • Infiltrates marrow • destroys bone

29. Breast • Early detection - Education • Treatment options • Mastectomy care • Referrals

30. Gynecological • Cervical • Endometrial • Ovarian

31. Genetics and Cancer • BRCA