Renal cell carcinoma may adapt to and overcome anti-angiogenic intervention with thalidomide

作者: M.L. Douglas , J.L. Reid , S.I. Hii , J.R. Jonsson , D.L. Nicol

DOI: 10.1046/J.1464-410X.2002.02666.X

关键词: AngiogenesisCancer researchGrowth factorKidneyPathologyThalidomideRenal cell carcinomaFibroblast growth factorMetastasisMedicineVascular endothelial growth factorUrology

摘要: Objective To report on the failure of thalidomide to inhibit tumour growth in an animal model human renal cell carcinoma (RCC). Materials and methods An orthotopic xenograft RCC was used which cells were implanted left kidney male 'severe combined immunodeficient' mice. Thalidomide administered by intraperitoneal injection after 34 days mice killed. The extent compared treated untreated Total RNA extracted from both tumour-affected contralateral kidneys, analysed reverse transcription-polymerase chain reaction for various genes implicated angiogenesis metastasis RCC. Results failed tumours. expression angiogenic genes, e.g. vascular endothelial factor fibroblast type 2 (FGF-2) within normal tissue not reduced thalidomide. Intratumoral transcription Of beta(3)-integrin, a critical component angiogenesis, significantly increased response treatment (P<0.01). There also trend FGF-2 necrosis factor-a thalidomide-treated Conclusions These findings suggest that is capable adapting inhibitory effects current uncertainty surrounding action hi vivo warrants caution about its use humans. Further studies should be carried out models, particularly establish safety effectiveness as part therapeutic strategy.

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