Overzicht deel tumoren <ul><li>Hoe ontstaat kanker? </li></ul><ul><ul><li>Proto-oncogenen </li></ul></ul><ul><li>Tumor-sup...
How cancer arises Weinberg, Sci Am 275-3, 1996, 32-40 <ul><li>Proto-oncogenes </li></ul><ul><li>Tumor suppressors </li></u...
Progression to invasive tumor Weinberg, Sci Am 275-3, 1996, 32-40 <ul><li>Sarcoma: tumour of connective tissue </li></ul><...
Signal transduction: on and off Weinberg, Sci Am 275-3, 1996, 32-40 Avoid words such as ‘fires’
Some proto-oncogenes Weinberg, Sci Am 275-3, 1996, 32-40 <ul><li>Receptor </li></ul><ul><ul><li>PDGF: platelet-derived gro...
Some tumor suppressor genes Weinberg, Sci Am 275-3, 1996, 32-40 <ul><li>APC </li></ul><ul><li>NF1 </li></ul><ul><li>Rb </l...
Some tumor suppressor genes Weinberg, Sci Am 275-3, 1996, 32-40 <ul><li>APC </li></ul><ul><li>NF1 </li></ul><ul><li>Rb </l...
The cell cycle Weinberg, Sci Am 275-3, 1996, 32-40
The cell cycle Weinberg, Sci Am 275-3, 1996, 32-40
The cell cycle Weinberg, Sci Am 275-3, 1996, 32-40 <ul><li>Cyclin associates with a cdk </li></ul><ul><ul><li>Cyclin-depen...
The pRb switch Weinberg, Sci Am 275-3, 1996, 32-40 E2F-member
The cell cycle Weinberg, Sci Am 275-3, 1996, 32-40
The pRb switch Weinberg, Sci Am 275-3, 1996, 32-40 E2F-member
Progression to cell division Weinberg, Sci Am 275-3, 1996, 32-40 mdm2 p21 p21 waf : see Vogelstein Proteins involved in DN...
Progression to cell division Weinberg, Sci Am 275-3, 1996, 32-40 mdm2 p21 p21 waf : see Vogelstein Proteins involved in DN...
The Ink4 locus   Kim & Sharpless, 2006, Cell 127, 265-275 <ul><li>ARF: alternative reading frame </li></ul><ul><li>All 3 m...
Effect of activating c-myc (from Alberts et al. 2002)
Effect of activating c-myc (from Alberts et al. 2002)
Aberrant chromosomes: aneuploidy Weinberg, Sci Am 275-3, 1996, 32-40 <ul><li>DNA repair defect </li></ul><ul><li>Normal re...
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GKA deel 1 college 7

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GKA deel 1 college 7

  1. 2. Overzicht deel tumoren <ul><li>Hoe ontstaat kanker? </li></ul><ul><ul><li>Proto-oncogenen </li></ul></ul><ul><li>Tumor-suppressors </li></ul><ul><ul><li>Plus DNA repair </li></ul></ul><ul><ul><li>p53 </li></ul></ul><ul><li>Immunotherapie </li></ul><ul><li>Apoptose </li></ul><ul><li>Metastasering </li></ul><ul><ul><li>Uitzaaiing </li></ul></ul><ul><li>Angiogenese </li></ul><ul><ul><li>Nieuwe bloedvaten </li></ul></ul><ul><li>De zeven processen </li></ul><ul><ul><li>Overzicht en afsluiting </li></ul></ul>Nature 442, 2006, 140
  2. 3. How cancer arises Weinberg, Sci Am 275-3, 1996, 32-40 <ul><li>Proto-oncogenes </li></ul><ul><li>Tumor suppressors </li></ul><ul><li>DNA repair </li></ul><ul><li>Apoptosis </li></ul><ul><li>Telomeres </li></ul><ul><li>Angiogenese </li></ul><ul><li>Metastasis </li></ul>
  3. 4. Progression to invasive tumor Weinberg, Sci Am 275-3, 1996, 32-40 <ul><li>Sarcoma: tumour of connective tissue </li></ul><ul><li>Glioma: tumour of non-neuronal brain cells </li></ul><ul><li>Carcinoma: tumor of epithelial cells </li></ul>
  4. 5. Signal transduction: on and off Weinberg, Sci Am 275-3, 1996, 32-40 Avoid words such as ‘fires’
  5. 6. Some proto-oncogenes Weinberg, Sci Am 275-3, 1996, 32-40 <ul><li>Receptor </li></ul><ul><ul><li>PDGF: platelet-derived growth factor </li></ul></ul><ul><ul><ul><li>glioma, a brain cancer </li></ul></ul></ul><ul><ul><li>erbB: EGF receptor </li></ul></ul><ul><ul><ul><li>glioblastoma, borstkanker </li></ul></ul></ul><ul><ul><li>erbB2/HER-2/neu: EGF-R; </li></ul></ul><ul><ul><ul><li>borstkanker, speekselklier, ovariumkanker </li></ul></ul></ul><ul><ul><li>RET </li></ul></ul><ul><ul><ul><li>schildklierkanker </li></ul></ul></ul><ul><li>Cytoplasmic, stimulatory </li></ul><ul><ul><li>Ki-Ras </li></ul></ul><ul><ul><ul><li>long-, ovarium-, pancreaskanker </li></ul></ul></ul><ul><li>Transcriptiefactoren </li></ul><ul><ul><li>C-myc </li></ul></ul><ul><ul><ul><li>leukemie, long-, borst-, maagkanker </li></ul></ul></ul><ul><li>Andere (apoptose!) Niet echt proto-oncogenen genoemd! </li></ul><ul><ul><li>Bcl2; B - c ell l eukemia; blokkeert apoptose </li></ul></ul><ul><ul><li>Mdm2; m ouse d ouble m inute; sarcoma; p53 antagonist </li></ul></ul>======================================================
  6. 7. Some tumor suppressor genes Weinberg, Sci Am 275-3, 1996, 32-40 <ul><li>APC </li></ul><ul><li>NF1 </li></ul><ul><li>Rb </li></ul><ul><li>p53 </li></ul><ul><li>WT1 </li></ul><ul><li>BRCA1 </li></ul><ul><li>BRCA2 </li></ul><ul><li>VHL </li></ul><ul><li>Betrokken bij darm en maag kanker </li></ul><ul><li>Remt Ras; neurofibroma, leukemie </li></ul><ul><li>Retinoblastoma, oog-, blaas-, borstkanker </li></ul><ul><li>Stopt celdeling, stimuleert apoptose </li></ul><ul><li>Wilms tumor (nier) </li></ul><ul><li>Br east ca ncer: Borst en ovariumkanker </li></ul><ul><li>Als BRCA1; cytokinese? </li></ul><ul><li>Von Hippel Lindau: nierkanker </li></ul>
  7. 8. Some tumor suppressor genes Weinberg, Sci Am 275-3, 1996, 32-40 <ul><li>APC </li></ul><ul><li>NF1 </li></ul><ul><li>Rb </li></ul><ul><li>p53 </li></ul><ul><li>WT1 </li></ul><ul><li>BRCA1 </li></ul><ul><li>BRCA2 </li></ul><ul><li>VHL </li></ul><ul><li>Betrokken bij darm en maag kanker </li></ul><ul><li>Remt Ras; neurofibroma, leukemie </li></ul><ul><li>Retinoblastoma, oog-, blaas-, borstkanker </li></ul><ul><li>Stopt celdeling, stimuleert apoptose </li></ul><ul><li>Wilms tumor (nier) </li></ul><ul><li>Br east ca ncer: Borst en ovariumkanker </li></ul><ul><li>Als BRCA1; cytokinese? </li></ul><ul><li>Von Hippel Lindau: nierkanker </li></ul>DNA repair genen geen tumor suppressors noemen!
  8. 9. The cell cycle Weinberg, Sci Am 275-3, 1996, 32-40
  9. 10. The cell cycle Weinberg, Sci Am 275-3, 1996, 32-40
  10. 11. The cell cycle Weinberg, Sci Am 275-3, 1996, 32-40 <ul><li>Cyclin associates with a cdk </li></ul><ul><ul><li>Cyclin-dependent kinase </li></ul></ul><ul><li>Cdk only active in complex with a cyclin </li></ul>Most cells are not cycling but in G 0 -stage
  11. 12. The pRb switch Weinberg, Sci Am 275-3, 1996, 32-40 E2F-member
  12. 13. The cell cycle Weinberg, Sci Am 275-3, 1996, 32-40
  13. 14. The pRb switch Weinberg, Sci Am 275-3, 1996, 32-40 E2F-member
  14. 15. Progression to cell division Weinberg, Sci Am 275-3, 1996, 32-40 mdm2 p21 p21 waf : see Vogelstein Proteins involved in DNA synthesis Liberated Transcription factors Active pRb protein complexed with inactive transcription factors (master brake) Transforming growth factor ß (an inhibitor) Cell division DNA synthesis Growth promoting signals issued vy neighboring cells
  15. 16. Progression to cell division Weinberg, Sci Am 275-3, 1996, 32-40 mdm2 p21 p21 waf : see Vogelstein Proteins involved in DNA synthesis Liberated Transcription factors Active pRb protein complexed with inactive transcription factors (master brake) Transforming growth factor ß (an inhibitor) Cell division DNA synthesis Growth promoting signals issued vy neighboring cells
  16. 17. The Ink4 locus Kim & Sharpless, 2006, Cell 127, 265-275 <ul><li>ARF: alternative reading frame </li></ul><ul><li>All 3 members inhibit progression of the cell cycle </li></ul><ul><li>Tumor suppressors </li></ul><ul><li>Ink4 is an E2F target gene </li></ul><ul><ul><li>Feedback mechanism </li></ul></ul>Inserted 4-12-07 http://www.mtmlabs.com/cda/science_technology/ p16supink4a/sup/content-121885.html
  17. 18. Effect of activating c-myc (from Alberts et al. 2002)
  18. 19. Effect of activating c-myc (from Alberts et al. 2002)
  19. 20. Aberrant chromosomes: aneuploidy Weinberg, Sci Am 275-3, 1996, 32-40 <ul><li>DNA repair defect </li></ul><ul><li>Normal reaction: </li></ul><ul><ul><li>Apoptosis </li></ul></ul><ul><ul><li>Senescence </li></ul></ul><ul><ul><ul><li>Telomeres </li></ul></ul></ul>Karyotype ============

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