PHRD5015 Lecture 21 - Anatomy and Biology of Tumors

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PHRD5015 Lecture 21 - Anatomy and Biology of Tumors
2013-12-04 05:18:23
Anatomy Biology Tumors

Anatomy and Biology of Tumors
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  1. where carcinomas derive from
    epithelial cells
  2. 2 kinds of epithelial cells that create carcinomas
    • 1) squamous cells (seal cavities/ducts)
    • 2) cells that secrete substances into cavities/ducts
  3. 2 types of carcinomas
    • 1) squamous cell carcinomas
    • 2) adenocarcinomas
  4. where sarcomas derive from
    mesodermal tissues
  5. cells derived from mesoderm (4)
    • 1) fibroblasts
    • 2) adipocytes
    • 3) osteoblasts
    • 4) myocytes
  6. where mesodermal tissue is located
    just underneath the epithelial barrier (separated by basal membrane)
  7. circulating transformed hematopoietic cells that do not clump into tumors
  8. hematopoietic tumors usually found in lymph nodes
  9. tumors derived from tissues of the CNS & PNS
    neuroectodermal tumors
  10. examples of neuroectaldermal tumors (5)
    • 1) gliomas
    • 2) glioblastomas
    • 3) neuroblastomas
    • 4) schwannomas
    • 5) medulloblastomas
  11. example of what transformed epithelial cells within a carcinoma secrete
  12. example of what non-transformed cells in a carcinoma secrete
    IGF-1 (insulin-like growth factor -1)
  13. hallmark structure formed by colon carcinomas
    ductal structures
  14. what cancer cells require in order to be encouraged to grow
    stromal interaction
  15. epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties to become mesenchymal cells
    epithelial-mesenchymal transition (EMT)
  16. after the epithelial sheet is restored, epithelial cells are induced to return to their original phenotype
    mesenchymal-epithelial transition (MET)
  17. cells that play a crucial role in generating signals that induce cancer cells to undergo EMT
  18. 2 major times at which cells become mobile by undergoing EMT
    • 1) embryogenesis
    • 2) wound healing
  19. EMT can be initiated by degrading _____.
    E-cadherin (by MMPs)
  20. protein E-cadherin associates with, that initiates EMT in the nucleus if not bound
  21. carcinoma that has not breached the basement membrane of the tissue
  22. similarities between tumors and wound areas (4)
    • 1) fibrin clumps
    • 2) PDGF secretion
    • 3) matrix remodeling
    • 4) myofibroblast conversion (TGF1)
  23. probability of survival was much greater when patients did not express what types of genes?
    wound-like genes
  24. activation of this transcription factor appears to be essential for EMT 
    (explains how inflammation is associated with cancer and why anti-inflammatory tx's can decrease cancer risk)
  25. 2 cytokines that can induce EMT
    • 1) TGF
    • 2) TNF
  26. secreted by macrophages to contribute to invasiveness
  27. 4 types of cells that promote EMT
    • 1) fibroblasts (FGF)
    • 2) macrophages (EGF)
    • 3) myofibroblasts (TGFb)
    • 4) inflammatory cells (TNFa)
  28. mechanism that prevents epithelial cell transformation
    TGFIIR activates a circuit that helps keep stromal fibroblasts from pushing epithelial cells into a transformed state
  29. _____ co-evolve with their cancer cell partners over many months or years
    stromal cells
  30. type of cell cancer cells attract
  31. tumors have _____ hydrostatic pressure
  32. size of tumor is dependent on activation of this process
  33. why advanced tumors are seldom stopped by VEGF deprivation
    other angiogenic factors can work in place of VEGF (eg: FGF, TGFa)
  34. number of these correlates with malignancy
    capillary number
  35. rate limiting for tumor size
  36. primary tumors liberate these factors from the ECM
  37. major cause of cancer deaths
  38. 6 steps of invasion-metastasis cascade
    • 1) localized invasiveness
    • 2) intravasation
    • 3) transport
    • 4) extravasation
    • 5) formation of micro-metastases
    • 6) colonization
  39. cancer cells use these as shields
  40. average diameter of cancer cells
  41. most inefficient process of metastasis
    colonization (last step)
  42. purpose of uPA to cancer cells
    used to cleave and activate MMPs & TGF
  43. flat, sheet-like structure used in cell motility
  44. long, thing processes extended from lamellipodia
  45. Ras-like protein that controls cytoskeleton reorganization, and binds/hydrolyzes GTP for activation
  46. proteins in focal contacts of lamellipodia
  47. presence of cancer cells in ________ is a measure of the metastatic level of the cancer.
    lymph nodes
  48. prostate cancer preferably metastasizes to...
    bone marrow
  49. pancreatic cancer preferably metastasizes to...
  50. breast cancer preferably metastasizes to...
    bone marrow
  51. colon cancer preferably metastasizes to...
  52. increases likelihood of metastases in a certain region
    chronic inflammatory condition in a particular region
  53. cells that can reseed a tumor when isolated
    cancer stem cells
  54. results of cancer cells remaining quiescent until needed (2)
    • 1) they're not targeted by chemotherapy
    • 2) they repopulate the tumor once the chemo is concluded
  55. requirement of chemotherapy
    target cell must be actively dividing