In vivo modulation of angiogenic gene expression by acyclic nucleoside phosphonates PMEDAP and PMEG.
Acyclic nucleoside phosphonates PMEDAP and PMEG modulate expression of selected proangiogenic genes in SD-lymphoma bearing rats. Antiangiogenic efficacy of PMEDAP is relatively weak and is manifested mainly by down-regulation of vascular endothelial growth factor (VEGF) and its receptor VEGFR detectable 24 hours after treatment. Compound PMEG (an active metabolite of the prodrug GS-9219) down-regulates selected proangiogenic genes EGF, FGF, PDGF, VEGF, EGFR, FGFR, PDGFR and VEGFR much more efficiently. Its antiangiogenic potency persists and is more intensive 48 hours after treatment. Findings show that in vivo antitumour efficacy of both antimitotic acyclic nucleoside phosphonates PMEDAP and PMEG consequently affect the angiogenesis in T-cell lymphoma.
Institute of Biology and Medical Genetics, Charles University, Prague, Czech Republic. boto@lf1.cuni.cz
Berta
B
Otová
Jirí
J
Hrdy
Ivan
I
Votruba
Antonín
A
Holy
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D016220:Fibroblast Growth Factor 1 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism
D009943:Organophosphorus Compounds; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C075278:platelet-derived growth factor A; C467498:vascular endothelial growth factor A, rat; D016220:Fibroblast Growth Factor 1; C063380:9-((2-phosphonylmethoxy)ethyl)guanine; C059499:9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine; D006147:Guanine; D004815:Epidermal Growth Factor; C483803:Egfr protein, rat; D066246:ErbB Receptors; C496350:Fgfr1 protein, rat; D051496:Receptor, Fibroblast Growth Factor, Type 1; D020797:Receptor, Platelet-Derived Growth Factor beta; D040281:Vascular Endothelial Growth Factor Receptor-1; D000225:Adenine