BACKGROUND: Gastrointestinal stromal tumours (GIST) predominantly express activating mutations of the KIT tyrosine kinase receptor and are successfully treated with imatinib mesylate, a KIT inhibitor. As resistance to imatinib causes therapy failure, our aim was to develop an in vivo GIST model to evaluate KIT inhibitors and monitor therapy with small animal positron emission tomography (PET). MATERIALS AND METHODS: The first mouse model of GIST xenografts was successfully established by injecting GIST882 cells subcutaneously into nude mice. RESULTS: Using the small animal PET, FDG up-take in xenografts was significantly decreased after 24 h of treatment with imatinib, which correlated with a response to treatment, e.g., with a decrease in tumour volume, the inhibition of KIT and downstream intermediate phosphorylation and arrest of tumour cell proliferation as evaluated after 7 days of treatment. CONCLUSION: This model is useful to study imatinib resistance and to evaluate novel targeted therapies.
BACKGROUND:Gastrointestinal stromal tumours (GIST) predominantly express activating mutations of the KIT tyrosine kinase receptor and are successfully treated with imatinib mesylate, a KIT inhibitor. As resistance to imatinib causes therapy failure, our aim was to develop an in vivo GIST model to evaluate KIT inhibitors and monitor therapy with small animal positron emission tomography (PET). MATERIALS AND METHODS: The first mouse model of GIST xenografts was successfully established by injecting GIST882 cells subcutaneously into nude mice. RESULTS: Using the small animal PET, FDG up-take in xenografts was significantly decreased after 24 h of treatment with imatinib, which correlated with a response to treatment, e.g., with a decrease in tumour volume, the inhibition of KIT and downstream intermediate phosphorylation and arrest of tumour cell proliferation as evaluated after 7 days of treatment. CONCLUSION: This model is useful to study imatinib resistance and to evaluate novel targeted therapies.
Authors: Giuseppe Floris; Agnieszka Wozniak; Raf Sciot; Haifu Li; Lori Friedman; Thomas Van Looy; Jasmien Wellens; Peter Vermaelen; Christophe M Deroose; Jonathan A Fletcher; Maria Debiec-Rychter; Patrick Schöffski Journal: Clin Cancer Res Date: 2012-12-11 Impact factor: 12.531
Authors: Thomas Mühlenberg; Yixiang Zhang; Andrew J Wagner; Florian Grabellus; James Bradner; Georg Taeger; Hauke Lang; Takahiro Taguchi; Martin Schuler; Jonathan A Fletcher; Sebastian Bauer Journal: Cancer Res Date: 2009-08-25 Impact factor: 12.701
Authors: Ariel Fernández; Angela Sanguino; Zhenghong Peng; Eylem Ozturk; Jianping Chen; Alejandro Crespo; Sarah Wulf; Aleksander Shavrin; Chaoping Qin; Jianpeng Ma; Jonathan Trent; Yvonne Lin; Hee-Dong Han; Lingegowda S Mangala; James A Bankson; Juri Gelovani; Allen Samarel; William Bornmann; Anil K Sood; Gabriel Lopez-Berestein Journal: J Clin Invest Date: 2007-12 Impact factor: 14.808
Authors: M A Pantaleo; L Landuzzi; G Nicoletti; C Nanni; S Boschi; G Piazzi; D Santini; M Di Battista; P Castellucci; F Lodi; S Fanti; P-L Lollini; G Biasco Journal: Clin Exp Med Date: 2009-02-19 Impact factor: 3.984