CancerCell CycleMitosisPDGF ReceptorsCancer CellsCancer DrugsSlide 7Cell TransformationCancerCell Cycle•G0 is resting phase•Platelets are necessary for blood clotting•Platelets also release growth factors to start cell growth at the sides of the wound•One of the most important factor is Platelet derived growth factor PDGF•PDGF is an important growth factor for fibroblasts (cells that make connective tissue)•Once cells pass restriction point, they will go all the way around the growth cycle until they look for growth factor againMitosis•Restriction point at the end of G1G1G1G0G0Growth InhibitorsMMIn the absence of growth factorsSSIn the presence of growth factorsG2G2Restriction PointPDGF ReceptorsPDB 1h9o>1H9O:B|PDBID|CHAIN|SEQUENCEYVPML>1H9O:A|PDBID|CHAIN|SEQUENCEGSPIPHHDEKTWNVGSSNRNKAENLLRGKRDGTFLVRESSKQGCYACSVVVDGEVKHCVINKTATGYGFAEPYNLYSSLKELVLHYQHTSLVQHNDSLNVTLAYPVYAQQRRCancer Cells•Deregulated growth•Release Growth Factors for their own Growth factor receptors•Larger number of growth factor receptors–Overexpressed normal 500, in carcinomas 100,000•Truncated receptors –Fire constitutively (not regulated)Cancer Drugs•Iressa - only 10% responded (those who had mutation that caused structural alterations)•Iressa® was reported to be effective in 24 or 29 patients with EGFR mutations compared to 2 of 21 patients without these mutations.•Those who did respond had truncated external receptorsCancer•Human cells 3*1013•Tumor cells 109–All cells in tumor mass descend from one mutated cell–They form populations from genetic material of a single ancestor •Normal Cells have contact inhibition–The signal growth stoppage when receptors detect another cell in contact•Cancerous cells do not have planar growthCell Transformation•Random Mutations•Mutagens – Smoking, xrays, drugs increase mutation probability•When a mutation hits in one of these sites, you can get uncontrolled
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