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CHAPTER 11- ONCOLOGY.txt

  1. Cancer is what # cause of death in the united states?
    #2
  2. What is the most common cancer in women?
    breast Ca
  3. What is the most common cause of cancer related death in women?
    lung cancer
  4. Most common cause of cancer in men?
    prostate cancer
  5. most common cause of cancer related death in men?
    lung cancer
  6. What scan can be used to identify metastases?
    PET (positron emission tomography) scan- used to identify metastases--> detects fluorodeoxyglucose molecules
  7. What do T cells need in order to attack tumor?
    T cells need MHC complex to attack tumor
  8. What do natural killer cells need in order to kill tumor cells?
    Natural killer cells can independently attack tumor cells
  9. Tumor antigens:
    tumor antigens are random unless viral induced tumor
  10. Hyperplasia:
    increased number of cells
  11. Metaplasia:
    replacement of one tissue with another (GERD squamous epithelium in esophagus changed to columnar gastric tissue)
  12. Dysplasia:
    altered size, shape, and organization (Barrett's esophagus)
  13. Tumor markers (to follow):
  14. Colon cancer:
    CEA
  15. Liver cancer:
    AFP
  16. Pancreatic cancer:
    CA 19-9
  17. Ovarian cancer:
    CA 125
  18. Testicular cancer/choriocarcinoma:
    Beta-HCG
  19. Prostate Cancer:
    PSA (thought to be the tumor marker with the highest sensitivity).
  20. Small cell lung cancer, neuroblastoma
    NSE
  21. Breast Ca:
    BRCA I and II
  22. What are the half lives of some of these markers?
    • CEA: 18 days
    • PSA: 18 days
    • AFP: 5 days
  23. Oncogenesis:
    • Cancer Transformation:
    • 1) heritable alteration in genome
    • 2) loss of growth regulation

    • Latency period- time between exposure and formation of clinially detectable tumor
    • Initiation- carcinogen acts with DNA
    • Promotion of cancer cells
    • Progression of cancer cells to clinically detectable tumor
  24. Neoplasms can arise from:
    • 1) carcinogens (i.e. smoking)
    • 2) viruses (i.e. EBV)
    • 3) immunodeficiency (i.e. HIV)
  25. Retroviruses contain oncogenes:
    Epstein-Barr virus- associated with Burkitt's lymphoma (8:14 translocation) and nasopharyngeal Ca (c-myc)
  26. Malignancies Associated with Infectious Agents:
    Cervical Ca:
    Gastric Ca:
    Hepatocellular Ca:
    Kaposi's sarcoma:
    Primary effusion lymphoma:
    Splenic lymphoma:
    Nasopharyngeal Ca:
    Burkitt's lymphoma:
    Adult T-cell leukemia/lymphoma:
    Various lymphomas:
    • Cervical Ca: human papillomavirus
    • Gastric Ca: Helicobacter pylori
    • Hepatocellular Ca: hepatitis B and hepatitis C
    • Kaposi's sarcoma: HHV-8
    • Primary effusion lymphoma: HHV-8
    • Splenic lymphoma: Hepatitis C
    • Nasopharyngeal Ca: EBV
    • Burkitt's lymphoma: EBV
    • Adult T-cell leukemia/lymphoma: Human T-cell leukemia virus-1
    • Various lymphomas: HIV
  27. What are proto-oncogenes?
    proto-oncogenes are human genes with malignant potential
  28. Radiation therapy (XRT)- slides to follow
  29. What stage of the cell cycle is most vulnerable to XRT
    M phase- most vulnerable stage of cell cycle for XRT
  30. How is the damage done in XRT?
    most damage done by formation of oxygen radicals--> maximal effect with high oxygen levels
  31. what is the main cellular target of XRT?
    Main target is DNA- oxygen radicals cause damage of DNA and other molecules

    XRT itself can also cause some damage by causing small breaks in DNA
  32. What type of radiation has skin-preserving effect?
    High-energy radiation has skin-preserving effect (maximal ionizing potential not reached until deeper structures)
  33. Fractionate doses:
    • 1) allows repair of normal cells
    • 2) allows reoxygenation of tumor
    • 3) allows redistribution of tumor cells in cell cycle
  34. Very radiosensitive tumors:
    • 1) seminomas
    • 2) lymphomas
  35. Very radioresistant tumors
    • 1) epithelial
    • 2) sarcoma
  36. What structures have increased sensitivity to XRT?
    • 1) kidneys
    • 2) lungs
    • 3) liver
    • 4) lymphocytes
  37. Large tumors and XRT:
    Large tumors- less responsive to XRT due to lack of oxygen in the tumor
  38. Brachytherapy
    source of radiation in or next to tumor (Au-198. I-128); delivers high, concentrated doses of radiation
  39. Chemotherapy agents (following slides)
  40. Cell cycle-specific agents:
    • 1) i.e. 5-FU, methotrexate
    • 2) exhibit plateau in cell-killing ability
  41. Cell cycle-nonspecific agents
    linear response to cell killing
  42. Tamoxifen
    • 1) blocks estrogen receptor
    • 2) decreases short-term (5 year) risk of breast Ca 45%
    • 3) 1% risk of blood clots
    • 4) 0.1% risk of endometrial cancer
  43. Taxol
    1) promotes microtubule formation and stabilization that cannot be broken down; cells are ruptured
  44. Which two chemotherapy agents cause pulmonary fibrosis?
    • 1) bleomycin
    • 2) busulfan
  45. Cisplatin
    • 1) platinum alkylating agent
    • 2) Side effects:
    • 1- nephrotoxic
    • 2- neurotoxic
    • 3- ototoxic
  46. Carboplatin
    • 1) platinum alkylating agent
    • 2) bone (myelo) suppression
  47. Vincristine
    • 1) microtubule inhibitor
    • 2) peripheral neuropathy
    • 3) neurotoxic
  48. Vinblastin
    • 1) microtubule inhibitor
    • 2) bone (myelo) suppression
  49. Alkylating agents
    1) transfer alkyl groups; form covalent bonds

    • Cyclophosphamide
    • 1- acrolein is the active metabolite
    • 2) Side effects:
    • 1- gonadal dysfunction
    • 2- hemorrhagic cystitis
    • 3- SIADH

    3)- Mesna can help with hemorrhagic cystitis

    Isofosfamide
  50. Levamisole
    antihelminthic drug thought to stimulate immune system against cancer
  51. Methotrexate
    • 1) inhibits dihydrofolate reductase (DHFR), which inhibits purine and DNA synthesis
    • 2) Side effects: 1) renal toxicity 2) radiation recall
    • 3) Leucovorin rescue- decrease folate (tetrahydrofolic acid); reverses effects of methotrexate
  52. 5-Fluorouracil (5FU)
    • 1) inhibits thymidylate synthesis, which inhibits purine and DNA synthesis
    • 2) Leucovorin- increases toxicity of 5FU
  53. Doxorubicin:
    • 1) DNA intercalator
    • 2) O2 radical formation
    • 3) heart toxicity secondary to O2 radicals at >500mg/m2
  54. Etoposide (VP-16)
    inhibits topoisomerase (which normally unwinds DNA)
  55. Which chemotherapy agents have least myelosuppression:
    • 1) bleomycin
    • 2) busulfan
    • 3) vincristine
    • 4) cisplatin
  56. GCSF (granulocyte colony-stimulating factor):
    • 1) used for neutrophil recovery after chemo
    • 2) Side effects: Sweet's syndrome (acute febrile neutropenic dermatitis)
  57. In which conditions would you resect a normal organ to prevent cancer?
    Colon- FAP

    Breast- BRCA I or II with strong family history

    Thyroid- RET proto-oncogene or MENIN gene with family history of MEN or thyroid cancer
  58. Tumor suppressor genes (on slides to follow):
  59. Retinoblastoma:
    • Retinoblastoma (Rb1)-
    • 1- chromosome 13
    • 2- involved in cell cycle
  60. p53:
    • 1) chromosome 17
    • 2) involved in cell cycle (normal gene induces cell cycle arrest and apoptosis; abnormal gene allows unrestrained cell growth.
  61. APC:
    • 1) chromosome 5
    • 2) involved with cell adhesion and cytoskeleton function
  62. DCC:
    • 1) chromosome 18
    • 2) involved in cell adhesion
  63. bcl
    involved in apoptosis (programmed cell death)

    BRCA is also a tumor suppressor gene
  64. Proto-oncogenes (on following slides):
  65. ras proto-oncogene
    G-protein defect
  66. src proto-oncogene
    tyrosine kinase defect
  67. sis proto-oncogene
    platelet-derived growth factor (PDGF) receptor defect
  68. erb B proto-oncogene
    epidermal growth factor receptor defect
  69. myc (c-myc, n-myc, l-myc) proto-oncogenes-
    transcription factors
  70. Li-Fraumeni Syndrome:
    • 1) defect in p53 gene
    • 2) Patients get:
    • 1- childhood sarcomas
    • 2- brain tumors
    • 3- leukemia
    • 4- adrenal cancer
  71. Medullary Ca of the thyroid:
    • 1) associated with Ret proto-oncogene (chromosome 10)
    • 2) patients with Ret gene defect plus family history--> 90% get medullary Ca of thyroid; need prophylactic thyroidectomy
  72. Genes involved in development of Colon Ca:
    Comment on metastatic trend of Colon Ca.
    • 1) Genes involved in development include:
    • 1-APC
    • 2- p53
    • 3- DCC
    • 4- K-ras

    APC involved in cell adhesion and cytoskeleton function- thought to be the initial mutation in the development of colon Ca

    Colon Ca usually does not go to bone
  73. Carcinogens:
    • Coal tar:
    • 1) skin
    • 2) larynx
    • 3) bronchial Ca

    • Beta-Naphthylamine:
    • 1) urinary tract Ca/bladder Ca

    • Benzene:
    • leukemia

    • Asbestos:
    • methothelioma
  74. Cancer spread (following cards):
  75. Suspicious supraclavicular nodes:
    • 1) neck
    • 2) breast
    • 3) lung
    • 4) stomach (virchow's node)
    • 5) pancreas
  76. Suspicious axillary node:
    • 1) lymphoma (#1)
    • 2) breast
    • 3) melanoma
  77. Suspicious periumbilical node-
    pancreas (Sister Mary Joseph's node)
  78. Ovarian metastases
    • 1) stomach (Krukenberg tumor)
    • 2) colon
  79. Bone mets:
    • 1) breast (#1)
    • 2) prostate
  80. skin mets:
    • 1) breast
    • 2) melanoma
  81. small bowel metastases
    melanoma (#1)
  82. Clinical trials:
    • Phase I- is it safe and at what dose?
    • Phase II- is it effective?
    • Phase III- is it better than existing therapy?
    • Phave IV- implementation and marketing
  83. Types of therapy (cards to follow):
  84. Induction:
    • 1) sole treatment
    • 2) often used for advanced disease or when no other treatment exists
  85. Primary (neoadjuvant)
    • 1) chemotherapy given 1st
    • 2) followed by another (secondary) therapy
  86. Adjuvant:
    • 1) combined with another modality
    • 2) given after other therapy is used
  87. Salvage:
    for tumors that fail to respond to initial chemotherapy
  88. What is the barrier function of lymph nodes?
    Lymph nodes have poor barrier function--> better to view them as signs of probable metastasis
  89. En bloc multiorgan resection:
    • 1) can be attempted for some tumors (colon into uterus, adrenal into liver, gastric into diaphram)
    • 2) aggressive local invasiveness is different from metastatic disease
  90. Palliative surgery:
    • 1) tumors of hollow viscus causing obstruction or bleeding (colon Ca)
    • 2) pancreatic Ca with biliary obstruction
    • 3) breast Ca with skin or chest wall involvement
  91. Sentinel lymph node biopsy:
    no role in patients with clinically palpable nodes; you need to go after and sample these nodes
  92. Colon metastases to the liver:
    25% 5 year survival rate if successfully resected
  93. Most successfully cured metastases with surgery:
    • 1) colon Ca in liver
    • 2) sarcoma to the lung
    • but survival still low overall for these
  94. See charts on pg.53:
    1) Predictors of Mortality and Survival Following Resection of Hepatic Colorectal Metastases
    2)Survival Based on # of factors
  95. Ovarian cancer and surgical debulking:
    Ovarian Ca- one of the few tumors for which surgical debulking improves chemotherapy (not seen in other tumors)
  96. Curable solid tumors with chemotherapy only
    • 1) hodgkin's disease
    • 2) non-hodgkin's lymphoma
    • 3) most lymphomas are B-cell
  97. T-cell lymphomas
    • 1) HTLV-1 (skin lesions)
    • 2) mycosis fungoides (sezary cells)
  98. HIV-related malignancies
    • 1) kaposi's sarcoma
    • 2) non-hodgkins lymphoma
Author
scottmreis
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Card Set
CHAPTER 11- ONCOLOGY.txt
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