Peptid antagonists for the therapy of renal cell carcinoma

Conclusion: Peptide antagonist are able to interfere the growth factor initiated cell response cascade by downregulation of growth factor receptor expression or by the impairment of the expression of growth factors themselves in human kidney carcinoma. Introduction: Peptide antagonist are known to interfere growth and proliferation in several tumors like lung, pancreas, prostate and digestive tract carcinoma by autocrinal or paracrinal pathways. The aim of this study was to show the efficancy of peptide antagonists on renal cell carcinoma cell lines xenographted in athymic male nude mice. Material and methods: in vitro experiments: RCC-cell lines CaKi-2, and A-498 were treated with certain concentrations of petid antagonist and agonist (see below) for 72 hours; Dose dependent growth curves were established using photometric assays. In vivo experiments: For each experiment 9 to 15 animals were used for verum group and placebo group respectively. The RCC cell lines were inocculated subcutaneously and daily treated with suitable concentrations of antagonists according to their individual application protocol. The progression of tumor growth was measured twice a week. After 28 days the tumors were excised and used for further histological, immunocytochemical and biochemical examinations. RCC-cell lines: CaKi-2, A-498; antagonists: Cetrorelix (GnRH-antagonist), JV-1-36 (GHRH-antagonist), and RC 3940-II (Bombesin-antagonist). Quantitative assays for: VEGF, VEGF-R, bFGF, EGF-R Results: In all experiments the antagonists used caused a significantly reduced tumor growth, a downregulation of tumor cell progression and a regression in tumor vascularisation. These data were confirmed by quantitative estimation of EGF-R, VEGF, VEGF-R and bFGF. The results were presented at the AUA Meeting 2000 as a poster presentation, at the seminar and workshop in New Orleans (Prof. Schally) 2001, and at the Congress of the "Bavarian and Austrian Society of Urology, Graz, 2001, and are going now to be prepared for two publications in the journal "Cancer Research". Due to comments of internal reviewers, two additional in vitro and in vivo experiments were requested for statistical confirmation, and are still ongoing. They will be finished in December this year. The the final addition of the papers will be submitted to the journal in February 2002.