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Understanding Cancer Developed by: Lewis J. Kleinsmith, Ph.D. Donna Kerrigan, M.S. Jeanne Kelly Brian Hollen A) What is cancer? Cancer is the uncontrolled rapid growth and spread of invasive, abnormal cells. Cell Cycle Normal Cell Growth Normal cell division Cell Suicide or Apoptosis Cell damage— no repair Cancer cell division Damaged cells are programmed to initiate apoptosis. First mutation Second mutation Third Fourth or mutation later mutation Uncontrolled growth Repeated genetic cell mutations may lead to loss of apoptosis ability. Cancer cell division First mutation Second mutation Third Fourth or mutation later mutation Uncontrolled growth B) Characteristics of cancer cells What differences do you observe? Normal Growth: uniform, organized Dead cells shed from outer surface Epidermis Dividing cells in basal layer Cell migration Dermis Tumors (Neoplasms) Underlying tissue Find: • the lung cancer • the normal fibrous tissue For the hotshots , find: • The largest cancer cell (dead), with its nucleus fragmented • a blood vessel Kansas City University of Medicine and Biosciences http://www.bing.com/images/search?q=cancer+cells+vs+normal+cells&view=detail&id=B3EB 6D27D608538D9EE4978F8343588428C479E4&first=60&FORM=IDFRIR Kansas City University of Medicine and Biosciences http://www.bing.com/images/search?q=cancer+cells+vs+normal+cells&view=detail&id=B3EB 6D27D608538D9EE4978F8343588428C479E4&first=60&FORM=IDFRIR Basal cell carcinoma (epidermis) MDBlogger http://www.bing.com/images/search?q=cancer+cells+vs+normal+cells&view=detail&id=E5A26D97E AC8D6530CD998A7993BD7C6F8B29305&first=120&FORM=IDFRIR Basal cell carcinoma MDBlogger http://www.bing.com/images/search?q=cancer+cells+vs+normal+cells&view=detail&id=E5A26D97E AC8D6530CD998A7993BD7C6F8B29305&first=120&FORM=IDFRIR Normal liver Liver cancer C) Malignant vs.Benign Tumors Benign (not cancer) tumor cells only grow locally Time Malignant (cancer) cells invade neighboring tissues, metastasize to different sites D) Metastasis Brain Melanoma cells travel through bloodstream Liver Melanoma (initial tumor) E) Kinds of Cancer common carcinomas: Lung Leukemias: Bloodstream Lymphomas: Lymph nodes Breast (women) Colon Bladder Prostate (men) common sarcomas: Fat Bone Muscle F) Cancer Detection Early Stages of Cancer May NOT Have Any Symptoms! Tumor Stages Five-Year Survival Rates for Patients with Melanoma (by stage) 100% 50% I II III Stage at Time of Initial Diagnosis Biopsy Pathology Proteomic profile Patient’s tissue sample or blood sample Genomic profile F) Causes of Cancer 1. Tobacco Use and Cancer Some Cancer-Causing Chemicals in Tobacco Smoke 20-Year Lag Time Between Smoking and Lung Cancer 4000 Cigarettes Smoked per Person per Year 3000 Cigarette consumption (men) Lung cancer (men) 150 100 2000 50 1000 1900 1920 1940 1960 1980 Year Lung Cancer Deaths (per 100,000 people) 2. Radiation High Dallas Skin Cancer Incidence Pittsburgh Detroit Low Least Most Annual Sunshine (UV radiation) 3. Viruses Virus inserts and changes genes for cell growth Cancer-linked virus Examples of Human Cancer Viruses 4. Cancer Risk and Aging Cancer Risk and Aging 400 Colon 300 Breast Number of Cancer Cases 200 (per 100,000 people) 100 0 20 40 60 80 Age of Person (in years) 5. Heredity and Cancer All Breast Cancer Patients Inherited factors (1 in 20 breast cancer patients) Other factor(s) 6. Environmental carcinogens viruses or bacteria chemicals (carcinogens) Radiation Heredity Diet Hormones G) Cancer: Treatment 1. surgery 2. chemotherapy 3. radiation 4. hormone therapy 5. biologic therapy (antibody) 6. targeted therapy (block blood vessels to tumor) H) Cancer: Prevention cancer Cancer Prevention Carcinogenic chemicals Carcinogenic radiation Cancer viruses or bacteria 1. Avoid Tobacco Lung Cancer Risk Increases with Cigarette Consumption 15x 10x Lung Cancer Risk 5x 0 Non-smoker 15 Cigarettes Smoked per Day 30 2. Protect Yourself From Excessive Sunlight 3. Limit Alcohol and Tobacco Intake Combination of Alcohol and Cigarettes Increases Risk for Cancer of the Esophagus 40x 30x Risk Increase 20x 10x Alcoholic Drinks Consumed per Day AND Packs of Cigarettes Consumed per Day 4a. Limit Fats and Calories Correlation Between Meat Consumption and Colon Cancer Rates in Different Countries 40 Number of Cases (per 100,000 people) 30 20 10 0 80 100 200 300 Grams (per person per day) 4b. Eat Fruits and Vegetables 5. Exercise & maintain healthy body weight 6. Avoid Cancer Viruses High HPV Infection Increases Risk for Cervical Cancer Cervical Cancer Risk Low Noninfected women Women infected with HPV 7. Physical exams & screenings e.g. mammograms, biopsy 8. Reduce exposures to environmental carcinogens What percentage of people survive cancer? * The 5 year survival rate for all cancers diagnosed between 19962002 is 66%, up from 51% in 19751977. * The improvement reflects progress in diagnosing cancers at an earlier stage and improvements in treatment. The remaining are extra slides, not part of the outlined notes How Cancer Starts: Genes & Cancer Viruses Chemicals Radiation Heredity Chromosomes are DNA molecules DNA Mutation DNA CA AG C T A A C T Normal gene CA AG C G A A C T Single base change CA A G G CG C T A A C T Additions C T CA A G A A C T Deletions Cancer Genes: Oncogenes Normal cell Cancer cell Mutated/damaged oncogene Normal genes regulate cell growth Oncogenes accelerate cell growth and division Tumor Suppressor Genes Normal genes prevent cancer Normal cell Remove or inactivate tumor suppressor genes Cancer cell Damage to both genes leads to cancer Mutated/inactivated tumor suppressor genes p53 Tumor Suppressor Protein Triggers Cell Suicide p53 protein Normal cell Excessive DNA damage Cell suicide (Apoptosis) DNA Repair Genes Normal DNA repair T C GA C Base pair mismatch No cancer TC T AC AG C T G TC TAC TCT AC AG C T G Cancer AG TG AG A T G No DNA repair Microscopic Appearance of Cancer Carcinoma in Situ Normal Hyperplasia Mild dysplasia Carcinoma in situ (severe dysplasia) Cancer (invasive) Sources National Cancer Institute (NCI) American Cancer Society (ACS)