Lecture: Stem Cells, Cancer, Antineoplastics

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VASUpharm14
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Lecture: Stem Cells, Cancer, Antineoplastics
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2010-09-12 18:58:38
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IBHS: Richard exam 2
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  1. context: cell life
    Proliferation
    • day 1 = 1 cell zygote
    • day 4 = 8 cells morula
    • day 270 (birth) = ~10 trillion cells baby
    • day 5000 = ~75 trillion cells fully grown
    • day 15,000 = ~85 trillion cells older adult
    • NOTE: Starting life with one cell then multiply rapidly
  2. context: cell life
    differentiation
    • day 1 = 1 cell type zygote
    • day 4 = 1 cell type morula
    • day 270 (birth) = ~300 cell types baby
    • day 5000 = ~300 cell types fully grown
    • day 15,000 = ~301 cell types older adult
    • NOTE: someone becoming someone else. extra one can be CANCER
  3. context: cell life (TIME)
    oocytes (eggs)
    lifetime
  4. context: cell life (TIME)
    neurons
    • lifetime? (more connections)
    • You don't make new ones, you make new connections.
    • (more connections)
  5. context: cell life (TIME)
    muscle cells
    • lifetime? (more volume)
    • You don't make new ones, you stretch and bulk.
    • (more volume)
  6. context: cell life (TIME)
    bone cells
    ~25 years
  7. context: cell life (TIME)
    lymphocytes (WBC)
    ~1 year
  8. context: cell life (TIME)
    red blood cells (RBC)
    ~4 months
  9. context: cell life (TIME)
    skin cells
    ~1 month
  10. context: cell life (TIME)
    platelets
    ~10 days
  11. context: cell life (TIME)
    colon cells
    ~3 days
  12. context: cell life (TIME)
    stomach cells
    ~2 days
  13. context: cell life (TIME)
    spermatozoa
    ~2 days
  14. T/F
    cell death is not important to organism life
    False!
  15. context: methods of cell death
    Necrosis or Apoptosis (programmed cell death)?
    homocide
    necrosis
  16. context: methods of cell death
    Necrosis or Apoptosis (programmed cell death)?
    traumatic accident
    necrosis
  17. context: methods of cell death
    Necrosis or Apoptosis (programmed cell death)?
    old age or "seppuku"
    apoptosis
  18. context: methods of cell death
    Necrosis or Apoptosis (programmed cell death)?
    natural or purposeful
    apoptosis
  19. context: why die?
    Necrosis or apoptosis?
    physical/mechanical
    necrosis
  20. context: why die?
    Necrosis or apoptosis?
    lots of chemicals
    necrosis
  21. context: why die?
    Necrosis or apoptosis?
    lots of microbes invade
    necrosis
  22. context: why die?
    Necrosis or apoptosis?
    old age, mutations
    apoptosis
  23. context: why die?
    Necrosis or apoptosis?
    some chemicals
    apoptosis
  24. context: why die?
    Necrosis or apoptosis?
    some microbes invade
    apoptosis
  25. context: how die?
    Necrosis or apoptosis?
    fast death
    necrosis
  26. context: how die?
    Necrosis or apoptosis?
    kill and spill
    necrosis
  27. context: how die?
    Necrosis or apoptosis?
    slow death
    apoptosis
  28. context: how die?
    Necrosis or apoptosis?
    tag and bag
    apoptosis
  29. context: response
    Necrosis or apoptosis?
    inflammation
    necrosis
  30. context: response
    Necrosis or apoptosis?
    minimal
    apoptosis
  31. context: cell death process
    necrosis or apoptosis?
    small blebs form; the structure of the nucleus changes
    necrosis
  32. context: cell death process
    necrosis or apoptosis?
    the blebs fuse and become larger;
    no organelles are located in the blebs
    necrosis
  33. context: cell death process
    necrosis or apoptosis?
    the cell ruptures and releases the cell's contents;
    the organelles are not functional
    necrosis
  34. context: cell death process
    necrosis or apoptosis?
    small blebs form; no nucleus change
    apoptosis
  35. context: cell death process
    necrosis or apoptosis?
    the nucleus begins to break apart, and the DNA breaks into small pieces.
    organelles located in blebs
    apoptosis
  36. context: cell death process
    necrosis or apoptosis?
    the cell breaks into several apoptotic bodies;
    the organelles are still functional.
    • duh!
    • apoptosis (cause it says so lol)
    • remember things are still functional!!
  37. where do new cells come from?
    • STEM CELLS! (booya)
    • with high replication rates too :D
  38. 2 major types of stem cells
    • 1) totipotent (pre-blastocyst stem cells)
    • 2) pluripotent (embryonic --> adult stem cells)
  39. context: stem cells
    totipotent
    • Each cell can develop into ANY cell type.
    • "Totally powerful"
  40. context: stem cells
    pluripotent
    Each cell can develop into a LIMITED selection of cell types
  41. what type of stem cell inside bone marrow?
    what cell type does it make?
    hemopoietic stem cells; blood cells
  42. context: contemporary stem cell therapies
    problems
    • damage stem cells.
    • Disease or chemotherapy can kill off hematopoietic stem cells in bone marrow
  43. context: SOLUTIONS in contemporary stem cell therapies
    bone marrow
    • good: Concentrated source of hematopoietic stem cells
    • bad: Needs to be close genetic match AND Painful
  44. context: SOLUTIONS in contemporary stem cell therapies
    blood transplant
    • good: less painful
    • bad: Needs to be close genetic match AND dilute source
  45. context: SOLUTIONS in contemporary stem cell therapies
    cord blood
    • good: Concentrated source of hematopoietic stem cells
    • bad: Does not need to be close genetic match
  46. context: POTENTIAL stem cell therapy sources
    Embryonic stem cells
    • pros: controversy of sources. (in vitro fertilization extra blastocysts. aborted/miscarried fetuses/embryos)
    • cons: easy to isolate, easy to coax to another cell type
  47. context: POTENTIAL stem cell therapy sources
    adult stem cells
    • pros: less controversy about sources (found in most tissues)
    • cons: hard to isolate, less easy to coax to another cell type
  48. context: stem cell updates
    Year?
    isolated adult stem cells from liposuctioned fat
    2001
  49. context: stem cell updates
    Year?
    isolate single stem cell from embryo without harming it
    2006 (Nature)
  50. context: stem cell updates
    Year?
    isolate embryonic stem cells from human amniotic fluid
    2007 (Nature Biotech.)
  51. context: stem cell updates
    Year?
    isolated stem cell from newborn foreskin cells (ouch)
    2007 (Science)
  52. context: stem cell updates
    Year?
    isolated adult stem cell from menstruated endometrium
    2007 (J of Translat. Med.)
  53. context: stem cell updates
    Year?
    coaxed adult cheek cell into 200 cell types
    2007 (Cell)
  54. Good news about Stem Cells
    • useful for therapies
    • potential: Human neuronal cells for: Parkinsons, Spinal Cord injury, Alzheimers
    • achieved: Success in mice for: Parkinson’s, Diabetes Mellitus
    • Success in humans for: Incontinence (bladder problems), Multiple Sclerosis
  55. Bad news about Stem Cells
    • cancer causing (lose regulation)
    • Stem cells discovered as source for several cancers: Leukemia (WBCs), breast, brain, prostate, ovarian, colon, pancreatic
  56. context: stem cells vs tumor cells
    3 similarities
    • 1) high rate of proliferation
    • 2) may remain quiescent for a long time (only replicate when triggered)
    • 3) resistent to apoptosis = immortal = increased longevity (enhanced telomerase activity, DNA repair activities,
    • Membrane bound transporters that exclude foreign agents
    • Good: keep your wanted stem cells
    • Bad: difficult to kill unwanted cancer cells resistant to chemotherapeutic agents
  57. context: tumor cells
    tumor
    • aka neoplasm
    • “A mass or swelling produced by abnormal cell growth and division”
  58. context: tumor cells
    benign
    • "good" compared to malignant
    • 1) remains within connective tissue area
    • 2) Less threatening, remove via surgery
    • 3)Technically not “Cancer”
  59. context: tumor cells
    malignant
    • "bad"
    • 1) spread to other tissues
    • 2) More threatening, difficult to remove
    • 3) Technically called “Cancer”
  60. How many tumor types?
    • 300 = 300 cell types in body
    • THIS. IS. SPARTA!!!!!
  61. context: tumor types
    Epithelial tissue (skin, orifices, G.I. tract)
    • carcinoma
    • adenocarcinoma - glandular epithelia
  62. context: tumor types
    connective tissue
    • 1. Leukemia- WBCs and precursors
    • 2. Osteoma- bone
    • 3. Chondroma - cartilage
    • Remember: LOC ... as in Pop it and LOC it. (sadly this is how lame I can get)
  63. context: tumor types
    muscle tissue
    • myoma
    • leiomyoma - smooth muscle
  64. context: tumor types
    neural tissue
    • glioma - neuroglia
    • neuroma- neurons
  65. context: tumor types
    Suffix?
    Benign
    • -OMA
    • ex: lipoma = benign tumor of fat cells
  66. context: tumor types
    Suffix?
    Malignant
    • -SARCOMA
    • ex: liposarcoma = malignant tumor (cancer) of fat cells
  67. context: malignancy
    primary site/primary tumor
    origin of tumor
  68. context: malignancy
    spreads to other sites
    Into circulation --> another tissue
  69. context: malignancy
    Metastasis (verb)
    action of leaving site
  70. context: malignancy
    Malignant (adjective)
    some cells have left primary site
  71. context: malignancy
    Cancerous (adjective)
    some cells have left primary site
  72. context: malignancy
    Secondary sites/Secondary tumors
    • Metastasis (noun): secondary site/tumor
    • Malignancy (noun): secondary site/tumor
    • Cancer (noun) = tumor cells at primary AND secondary sites
  73. context: cancer identification
    Oncology
    detection, identification, and treatment of cancers
  74. context: cancer identification
    Biopsy
    • identification
    • 1) examine primary or secondary tissue site
    • 2) examine routes between tissues. (ex: lymph node biopsy = common route for cancer cells to spread)
  75. needs to appear big in x-ray to detect!
  76. 2 causes of cancer and percentages
    • 1) 25% -inherited (genetic) - bad gene
    • 2) 75% - environment: a) radiation (UV, X-ray), b) carcinogens (smoking, asbestos), c) viruses (Human papilloma, hepatitis B - insert viral DNA)
  77. context: causes of cancer
    cells affected by environmental factors
    • 1) interaction - UV = skin cancer, Smoking = lung cancer
    • 2) sensitivity - replicating cells are more sensitive
  78. Oncogenes
    • A normal cell is converted to a cancer cell via one of the following:
    • A mutated gene (via mutagen or carcinogen)
    • An inserted gene (via virus)
  79. How many Oncogenes are there?
    50 different human genes have potential to mutate to oncogenes
  80. context: oncogenes
    mutations that turn ON proteins
    • Stimulating cell replication
    • ex: RAS gene/protein (mutated ON in 25-30% of all cancers)
    • kinase normally stimulates growth/ cell replication
  81. context: oncogenes
    mutations that turn OFF proteins
    • Inhibiting cell replication, metabolizing toxins, repairing DNA damage
    • Identification or destruction of abnormal cells
    • ex: P16 gene/protein: (mutated OFF in 50% of all cancers) = normally inhibits cell cycle
    • ex: p53 gene/protein: (mutated OFF in 50% of all cancers) = normally inhibits cell cycle, monitors damage to DNA, stimulates apoptosis
  82. T/F
    Cancer is just marked by proliferation
    • FALSE
    • Cancer is not just about “proliferation”
  83. context: cancer pathophysiology
    6 pathophysiologies that WILL happen
    • 1) loss of contact inhibition - Density inhibition usually via Cadherins
    • 2) unregulated proliferation - Abnormal replication
    • 3) evasive - Escape detection by Natural Killer Cells (WBCs)
    • 4) invasive - Have capacity to invade other tissues
    • 5) angiogenesis- Tumors stimulate blood vessels to grow toward them. Need lots of nutrients
    • 6) loss of apoptotic termination - Normal cells have programmed self-termination
  84. context: cancer pathophysiology
    3 pathophysiologies that MAY happen
    • 1) May interfere at primary and secondary sites - Organ disabled
    • 2) May interfere with nearby structures - Pressure on nerves, blood vessels, organs
    • 3) May alter control and coordination - Endocrine tissue tumors release excess hormones
  85. ? % will develop cancer
    25%
  86. ?% will die from cancer
    13%
  87. context: cancer treatment
    remission
    cessation or decrease of size of tumor(s)
  88. context: cancer treatment
    2 ways to obtain remission
    • 1) Targeted removal or destruction - with: Surgery, radiation, heat, freezing, immunotherapy
    • 2) Non-targeted destruction - with: Systemic chemotherapy (cytotoxic chemicals)
    • --Most work by inhibiting cell replication
    • --hair loss and vomiting (Epithelial cells largely effected)
  89. context: anti-cancer drugs
    General goal
    inhibit cell replication (directly or indirectly)
  90. context: anti-cancer drugs
    General tactics
    Pro-hormone
    inhibit replication by adding hormones
  91. context: anti-cancer drugs
    General tactics
    anti-hormone
    inhibit replication by inhibiting hormones
  92. context: anti-cancer drugs
    General tactics
    anti-tumor cell surface
    target specific surface proteins
  93. context: anti-cancer drugs
    General tactics
    anti-tumor cell signaling
    inhibit specific signaling proteins
  94. context: anti-cancer drugs
    General tactics
    anti-mitosis
    Inhibit mitotic-specific activity (eg tubulin)
  95. context: anti-cancer drugs
    General tactics
    anti-metabolites
    • Alter precursors/enzymes needed for
    • a) DNA replication
    • b) DNA transcription
    • c) RNA translation to protein.
  96. context: anti-cancer drugs
    General tactics
    anti-DNA
    Inhibit DNA from replicating /transcribing

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