1. Cancer
  1. Cancer cells undergo uncontrolled growth. Cells not regulated by signals and constraints.
  2. Cancer cells lack differentiation.
    1. Normal cells are specialized.
    2. Cancer cells are not specialized and have an abnormal shape.
    3. Normal cells undergo the cell cycle 20-50x and then die.
    4. Cancer cells are immortal.
    5. Cancer cells will only die if they run out of food, or are killed by their own toxic waste.
  1. Cancer cells have abnormal nuclei.
    1. Enlarged abnormal number of chromosomes.
    2. Mutations, duplications, deletions, gene amplifications, extra copies of genes.
  1. Cancer cells form tumors.
    1. Normal cells anchored to substratum and adhere to neighbors.
    2. Contact neighbor and stop dividing (contact inhibition).
    3. Normal cells form a single layer.
    4. Cancer cells pile on top of each other and grow in layers.
    5. Cancer cells need less epidermal growth factor.
    6. Tumors invade and destroy tissue.
    7. Neoplasia is disorganized.
    8. Anaplasia, a benign tumor is disorganized, encapsulated mass that does not invade adjacent tissue.
  1. Angiogenesis and Metastasis
    1. Angiogenesis is the formation of new blood vessels, nutrients and oxygen to tumor.
    2. Cancer cells release growth factor that causes neighboring blood vessels to branch into cancer tissue.
    3. This is one avenue to explore for cancer treatment.
    4. Cancer in situ is when cancer is in one place, before invasion.
    5. Cancer is a malignant tumor that undergoes metastasis.
    6. Metastasis is when new tumors form in new locations after cancer cells move from one spot.
    7. Cancer cells make their way across the basement membrane into the blood or lymph.
    8. Cancer cells can adhere to basement membranes with receptors and make proteinase enzymes that degrade the membrane and let them invade tissue.
    9. Cancer cells are motile, disorganized internal cytoskeleton, and no intact actin filament bundles.
    10. Prognosis gets worse as cancer progresses to tissue invasion, lymph node involvement.

2. Causes of Cancer

A. Cellular elements

    1. DNA repair enzymes.
    2. Proteins involved in chromatin remodeling.
    3. Telomerase keeps telomeres active.
    4. Proto-oncogenes and tumor suppressor genes.
  1. Carcinogenesis
    1. Initiation- a single cell mutates divides repeatedly.
    2. Promotion- a tumor develops, divides and mutations accumulate.
    3. Progression- one cell undergoes a mutation that gives it an advantage over other cells; finally one cell can invade surrounding tissue.
    4. Can take years, worse in older people.
    5. As you age you have an increasing chance of cancer.
  1. Heredity
    1. Some cancer runs in families.
    2. Breast, lung, colon cancer more likely if first-degree relatives has it.
    3. BRCA1 breast cancer gene.
    4. Retinoblastoma is a dominant gene that causes eye tumors at age 3.
    5. Wilmís tumor is tumor in both kidneys.
  1. Carcinogens
    1. Mutagens increase a chance of a mutation in the DNA.
    1. a. Carcinogen is an environmental gent that leads to cancer.
    2. b. Carcinogens are often mutagenic.
    3. c. Mutagenic carcinogens are organic chemicals, radiation, and viruses.
  1. Organic chemicals are promoters of cancer.
    1. Promoters increase the likelihood of cell division during carcinogenesis.
    2. Estrogen is a promoter in endometrial cancer.
    3. Fat is a promoter for colon cancer and breast cancer.
  1. Cigarette smoke contains organic chemicals that are carcinogenic.
    1. One third of all cancer deaths are attributed to smoking.
    2. Lung cancer is the most common lethal cancer in US.
    3. Smoking is implicated in cancer of the mouth larynx, bladder, kidney, and pancreas.
    4. Smoking and alcohol use increase cancer risk.
    1. Red dye # 2 and saccharin causes cancer at high doses.
    1. Industrial chemicals benzene, carbon tetrachloride, vinyl chloride, and asbestos fibers increase cancer
    2. Pesticides and herbicides contain organic chemicals that cause mutations.
    3. Dioxin, from herbicide agent orange, linked to cancer of lymphoid tissue, muscle tissue, and connective tissue.
    4. In Italy a chemical plant explodes and more cancer was found in that region.
  1. Radiation
    1. Natural radiation and artificial radiation.
    2. UV sunlight and tanning lamps both increase skin cancer rates.
    3. 6 skin cancers occur to every one lung cancer.
    4. Non melanoma skin cancers are curable.
    5. Melanoma skin cancer metastasizes and causes 1-2% of cancer deaths in US.
    6. Radioactive radon gas causes cancer. Found in homes. Equivalent to smoking a pack of cigarettes a day. Smoking and radon is a bad combination and accounts for 2 % of cancer deaths.
    7. Nuclear bombs and power plants increase exposure to radiation and cancer rates.
    8. X-rays produce the most exposure to radiation. Avoid when possible.
  1. Viruses
    1. Hepatitis B virus linked to liver cancer.
    2. a. In China all persons infected with hepatitis B virus, high rate of liver cancer.

    3. Human papillomavirus linked to cancer of the cervix.
    4. a. Found in cervical cancers.

    5. Epstein Barr virus linked to Burkittís lymphoma and nasopharyngeal cancer.
    1. In Africa all children have Epstein Barr, high rate of Burkittís lymphoma.
    2. In China nearly all nasopharyngeal cancer specimens have Epstein Barr virus.
    3. Epstein Barr causes mono in the U.S.
    1. Retroviruses cause cancers in animals and humans.
    1. HTLV-1 causes adult T-cell leukemia.
  1. Immunodeficiencies.
    1. Cancer shows up in people who are immune compromised.
    2. AIDS patients get cancer of the blood vessel, Kaposiís sarcoma.
    3. Transplant patients get lymphomas and Kaposiís sarcoma.
    4. You can inherit immunodeficiency and be susceptible to cancers.
    5. Old people have weakened immune system. Active immune system protects from cancer.
  1. Oncogenes and Tumor Suppressors
    1. Activation of oncogenes and inactivation of tumor suppressor genes lead to cancer.
    2. Cell division is controlled by regulatory factors such as growth factors and growth factor receptors.
    3. In muscle and nerve cells the regulatory network is always off.
    4. Skin epidermal cells are controlled in an orderly fashion.
    5. Cancer cell genes can code for mutated proteins in the regulatory network, so that growth is unregulated.
    6. Cell has proto-onocgenes, which mutate to oncogene. An oncogene can make an abnormal protein or abnormally high levels of a normal product.
    7. When a tumor suppressor mutates you get a defective product that canít stop cell division.
    8. Could be a faulty receptor.
    9. Oncogenes
    1. 100 found.
    2. Most frequently involved in human cancer are ras gene families.
    3. One base change converts ras to oncogene.
    4. Ras K is in 25 % of lung cancers, 50 % of colon cancers, and 90 % of pancreatic cancers.
    5. Ras N is leukemiaís, lymphomas.
    6. Ras N and Ras K in thyroid cancers.
    7. Ras in active or inactive, active ras is cell growth.
    8. Ras controlled by GAP.
    9. GAP cause enzyme to inactivate Ras, and no growth.
    10. When growth factor attaches to receptor that phosphorylates GAP, GAP is inactive and RAS is active.
    11. Phosphorylation is the way that signaling proteins are turned on or off. Receptor is a receptor kinase, an enzyme that transfers a phosphate group from an ATP to a protein.
    1. Tumor Suppressors
    1. Prevent uncontrolled growth.
    2. GAP is such a protein. A tumor suppressor gene codes GAP.
    3. Half dozen tumor suppressors found.
    4. Tumor suppressor found from retinoblastoma (RB)
    5. Normal gene mutates; eye tumors develop by age 3.
    6. RB goes wrong in breast, prostate, and bladder cancer.
    7. Small cell lung carcinoma is a loss of RB by chromosome deletion.
    8. Signaling proteins regulate the transcription of genes involved in cell division.
    9. Growth inhibitory factor binds receptor, RB is activated, and RB turns off the expression of a proto-oncogene halting cell division.
    10. P53 is a transcription factor, which turns on genes that are cell cycle inhibitors.
    11. P53 also stimulates apoptosis especially when DNA is very damaged.
    12. Mutated p53 is in many cancers, because damaged cells donít commit suicide.
    13. Bcl-2 can bind and inactivate p53, also found in some cancers.
  1. Treatment, Classification, and Diagnosis
    1. 1/3 people will get cancer in the US and one of 5 will die.
    2. The tissue from which they arise is how cancers are classified.
    1. Carcinomas are cancer of epithelial tissue.
    2. Adenocarcinomas are from glandular epithelial cells. For example: skin, breast, liver, pancreas, intestine, lung, prostate, and thyroid.
    3. Sarcomas are from muscles, connective tissue, and bone.
    4. Leukemia is cancer of blood.
    5. Lymphomas are tumors of lymphoid tissue
    1. Treatment
    1. Size of tumor and degree of metastasis is important when deciding how to treat.
    2. Condition of primary tumor.
    3. Extent of lymph node involvement.
    4. Extent of distant metastasis.
    1. Diagnosis
    1. It is hard to diagnose cancer before metastasis.
    2. Treatment is more effective before metastasis.
    3. Look for CAUTION
    4. Change in bowel or bladder habits.
    5. A sore that does not heal.
    6. Unusual bleeding or discharge.
    7. Thickening or lump in breast or elsewhere.
    8. Indigestion or difficulty in swallowing.
    9. Obvious change in wart or mole.
    10. Nagging cough or hoarseness.
    1. Routine Screening
    1. Pap-smears are credited with preventing 90 % of deaths from cervical cancer.
    2. Monthly breast exam, yearly physical and mammography screen for breast cancer.
    3. Digital rectal exam, stool blood test, colonoscopy, X-ray and barium enemas can check for colon cancer.
    4. Blood test for leukemia.
    5. Urinalysis for bladder cancer.
    6. Tumor marker tests for oncogenes.
    7. Tumors release antigens, which can be detected with antibodies.
    8. Colon cancer (CEA), Prostate cancer (PSA), Ovarian cancer (CA 125), and liver tumors (AFP).
    9. Test for RAS in stool samples in colon cancer or BRCA 1 gene for breast cancer.
    1. Confirming Diagnosis
    1. Needle biopsies remove a few cells.
    2. Laparoscopy to view body parts
    3. CAT scan, uses computer analysis of Xray image to make cross sectional pictures of tumor size and location.
    4. MRI useful with bone encased tissue.
    5. Administer radioactive isotope and scan to check abnormal accumulation due to tumor.
    6. Ultrasound can show size, shape and location of tumor.
    1. Treatment
    1. Surgery, radiation and chemotherapy.
    2. Surgery works for cancer in situ. Follow up with radiation therapy that affects dividing cancer cells more than normal cells. Can use proton beams that are aimed at tumor like a rifle.
    3. Chemotherapy uses chemicals that damage DNA or stop DNA synthesis.
    4. 75 % of kids with leukemia are cured. ĺ of Hodgkinís patients live using 4 drugs.
    5. Chemotherapy after surgery in colon and breast cancer prevents reoccurrence.
    6. Taxol (bark of pacific yew tree) interferes with microtubule assembly. Effective in ovarian, breast, head and neck cancer.
    7. Cancer cells become resistant to chemotherapeutic drugs. They can mutate to produce pumps that remove drug.
    8. Bone marrow transplant
    9. 1. Remove bone marrow; treat to remove cancerous cells, returned after chemotherapy.

    10. Anti-hormone therapy
    11. 1. Use tamoxifen to block receptors for estrogen or testosterone which promote cancer.

    12. Immunotherapy
    1. Levamisole stimulates immune system.
    2. Interferon and lymphokine help in hairy cell leukemia
    1. Monoclonal antibodies
    2. 1. Zero in on cancer cell receptors and carry radiation or chemodrug.

    3. Anti-metastatic Drugs.

1. Prevent metastasis

    1. Prevention
    1. Survival rate is 53-38 %.
    2. Donít smoke
    3. Donít sunbathe
    4. Donít drink
    5. Avoid radiation.
    6. Get tested for cancer.
    7. Be aware of occupational hazards.
    8. Follow dietary guidelines and avoid obesity, lower fat intake, eat high fiber foods, increase foods with vitamins A and C.
    9. Cut down on salt cured, smoked or nitrite cured food.
    10. Include vegetables of the cabbage family in diet.