MCB-2 Block 1 Gems-4 – Flashcards
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| Stimulation of angiogenesis |
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| Hypoxia -> HIF(TF) -> VEGF and bFGF VEGF binds to VEGFR(RTK) Causes endothelial cells to proliferate New vessels stabilized by pericytes |
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| MMMPs |
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| MMPs(collagenases) are released to degrade ECM TIMP(proteinase inhibitor) inhibits MMPs |
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| Regulation of HIF-1 |
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| Under normoxia Proline hydroxylase adds OH to HIF-1 -> HIF-OH pVHL binds HIF-1-OH. ubiquinates Hypoxia. pVHL does not bind and inhibit HIF |
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| von Hippel-Linadau(VHL) syndrome |
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| AD. Multiple hemangioblastomas of retina VHL normally (inhibits)ubquinates HIF-1 HIF-1 dimerizes and induces VEGF regardless of O2 availibilty. |
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| Haemangioma |
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| 3x more common in females Increase in VEGF, bfGF. Decrease in inhibitors Strawberry skin* |
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| Drug Targetting of angiogenic GF and GFRs |
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| VEGF: bevacizumab(Avastin) inhibits Thrombospondin: angeiogenesis inhibitor Thrombospondin secretes FasL FasL - FasR = apoptosis(extrinsic) Will only kill new blood vessels Endostatin: Stabilizes new BVwall Inhibits new vessel sprouting |
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| Venous leg ulcers |
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| increase in angiostatin and endostatin |
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| Cellular Invasion part 1 |
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| Loss of E-cadherin(cell-cell) Attachment to ECM: Increase in CD 44 hyaluronon binding protein(Binds mmp) |
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| Cellular Invasion part 2 |
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| Degradation of ECM: Serine proteases(uPA, tPA) Plasminogen-> plasmin -> MMps Digests ECM and clots MMPs: TIMP unbalanced at invading edge MMPs degradation of ECM reveals cryptic sites(laminin -> chemotactic factor) |
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| Tumor Cell Migration |
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| Tumor Motiliy factors: AMF, HGF< EGF Signal via Rho GTPases; Rho,Rac, Cdc42. Changes in cytoskeleton -> movement Intravasation: VEGF -> endocytosis of VE-cadherin. Increase in vascular permeability. Increased entry of tumor cells |
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| Chemokine regulation of breast cancer |
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| CXCR4 binds CXCL12 CCR7 binds CCL21 |
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| Summary of changes during metastatis (migration) Increase / Decrease of what? |
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| Increase: VEGF, bfGF, PDGF, EGF, HGF Integrins proteases(MMPs) Decrease: Cell-Cell adhesion's(cadherins) ECM proteins Protease inhibitors(TIMPs) |
