Milea Timbergen

28 Table 1. (continued) Drug Ref.  Setting Effect PI3K /AKT/ mTOR signalling pathway Tyrosin kinase inhibitor Sorafenib (± Everolimus) 64 Human PCC from DTF ↓ DTF cell proliferation and invasion (sorafenib) ↓ mTOR signalling (↓ phospho-S6K levels (everolimus)) Growth regulatory signalling pathway Cytokines TGF-ß1 65 Human PCC from DTF, fibroma, NF ↔ cell proliferation in DTF, fibroma and NF cell culture ↑ GAG accumulation in extra-cellular matrix ↑ collagen synthesis 66 Human PCC from DTF and NF ↑ active unphosphorylated fraction of ß-catenin Cytokines rhEGF /rhTGF-ɑ 67 Human PCC from DTF Up- and down regulation of genes in response to stimulation with rhEGF /rhTGF-ɑ Cytokines rhEGF/AG1478 /SB431542 68 Human PCC from DTF ↑ DTF cell motility (rhEGF) Oestrogen driven pathway Anti-oestrogen Tamoxifen/ Toremifene 69 Human PCC from DTF ↓ cell growth (tamoxifen ± oestrogen) ↔ cell growth (toremifene ± oestrogen) Anti-oestrogen Toremifene 70 Human PCC from DTF, fibroma and NF ↔ cell proliferation ( 3 H-tymidine incorporation) ↓ GAG (DTF, fibroma and NF cultures) ↓ collagen production ( 3 H-proline incorporation) ↓ TGF-ß1 levels in culture medium ↓ TGF-ß1 mRNA expression levels ↓ TGF-ß1 receptor affinity 71 Human PCC from DTF and NF ↑cell death (DTF and NF culture) ↓ collagen production ( 3 H-proline incorporation) ↓ procollagen α 1 mRNA expression (DTF culture) ↓ type I and III collagen ↑ collagenase activity ↔ MMP-1, ↑ MMP-2, ↓ TIMP-1 72 Human PCC from DTF, Gardner-syndrome related fibroblast and NF ↓ GAG synthesis and secretion ↓ active TGF-ß1, ↔ total (active + latent) TGF-ß1 ↓ number TGF-ß1 receptors (DTF cells) ↓ TNF-α production ↓, decrease; ↑, increase; ↔, no effect; CRC, colorectal cancer; DFMO, Difluoromethylornithine; DFU, selective COX-2 blocker (5,5-dimethyl-3-(3-¯uorophenyl)4-(4-methylsulphonyl)phenyl-2(5H)-furon one); DTF, desmoid-type fibromatosis; FAP, familial adenomatous polyposis; GAG, glycosaminoglycan; PCC, primary cell culture; NF, normal fibroblast; NSAID, Non-steroidal anti-inflammatory drug 2