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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 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 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. Characteristics of Benign Cells Demonstrate continuous or inappropriate cell growth. Show specific morphology Have a small nuclear-cytoplasmic ratio Perform differentiated functions Adhere tightly together Are nonmigratory Grow in an orderly and well regulated fashion. Characteristics of Malignant Cells Demonstrate rapid or continuous cellular division. Show anaplastic morphology Have a large nuclear-cytoplasmic ratio Lose some or all differentiated functions Adhere loosely together Are able to migrate Grow by invasion Are not contact-inhibited Definitions Anaplasia Anaplastic Carcinogen Carcinoma Hyperplasia Hypertrophy Metastasis Neoplasia Neoplasm Stages of Carcinogenesis (Oncogenesis) Initiation Promotion Progression Metastasis Common Steps in Metastasis Extension into Surrounding Tissues Penetration into Blood Vessels Release of Tumor Cells Invasion of Tissue at the Site of Arrest 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 Cancer Grade and Stage Grading; Classifies cellular aspects of a cancer. Staging; Classifies clinical aspects of the cancer. Histologic Class I - Well differentiated II - Moderate differentiation III - Poor differentiation IV - Immature & Undifferentiated 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 TNM Classification T - Primary tumor N - Regional lymph nodes M - Distant metastasis –Tis No Mo –T4 N3 M1 Goal Education and early detection C A U T I O N Surgical Interventions Biopsy Cure Control - Debulking Palliative Staging Reconstructive Prophylaxis Radiation Destroys cells, causes inflammatory response Side Effects Goals: – Cure – Control – Palliative Radiation Recall External Implants Isotopes 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 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 MOPP Protocol Complete response Agent Action Toxicity Mustargen DNA Marrow – 10 days 10% Oncovin Mitosis Neurotoxic 10% Procarbazine Marrow – 21 days 5% Prednisone RNA Synthesis Cell membrane 20% 80% Synergistic Effect Immune suppression Side Effects Cluster the common ones: bone marrow suppression alopecia nausea and vomiting Adriamycin - Cardiac Cisplatin – Renal Complications Pain Control Bone Marrow Suppression – Infection - Neutropenia – Hemorrhage – Anemia Infarction Superior Vena Cava Syndrome Spinal Cord Compression Tumor Lysis Syndrome 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) Hyperuricemia Obstruction of Kidney Tubules ARF K+ into Bloodstream Hyperkalemia Paraneoplastic Syndromes Secretion of Insulin Secretion of ACTH Hypercalcemia SIADH 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 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 Leukemia CML - Chronic Myelogenous – Age of Onset (>50 yrs) – Involves liver & spleen – Blastic Crisis CLL - Chronic Lymphocytic – Older patients – over 50 – Lymph node involvement 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 Breast Early detection - Education Treatment options Mastectomy care Referrals Gynecological Cervical Endometrial Ovarian Genetics and Cancer BRCA