AIM: To assess the efficacy of multiple treatment of phosphatidylinositol-3-kinase (PI3K) inhibitor on autochthonous tumours in phosphatase and tensin homologue (Pten)-deficient genetically engineered mouse cancer models using a longitudinal magnetic resonance imaging (MRI) protocol. MATERIALS AND METHODS: Using 3D MRI, B-cell follicular lymphoma growth was quantified in a Pten(+/-)Lkb1(+/hypo) mouse line, before, during and after repeated treatments with a PI3K inhibitor GDC-0941 (75 mg/kg). RESULTS: Mean pre-treatment linear tumour growth rate was 16.5±12.8 mm(3)/week. Repeated 28-day GDC-0941 administration, with 21 days 'off-treatment', induced average tumour regression of 41±7%. Upon cessation of the second treatment (which was not permanently cytocidal), tumours re-grew with an average linear growth rate of 40.1±15.5 mm(3)/week. There was no evidence of chemoresistance. CONCLUSION: This protocol can accommodate complex dosing schedules, as well as combine different cancer therapies. It reduces biological variability problems and resulted in a 10-fold reduction in mouse numbers compared with terminal assessment methods. It is ideal for preclinical efficacy studies and for phenotyping molecularly characterized mouse models when investigating gene function.
AIM: To assess the efficacy of multiple treatment of phosphatidylinositol-3-kinase (PI3K) inhibitor on autochthonous tumours in phosphatase and tensin homologue (Pten)-deficient genetically engineered mousecancer models using a longitudinal magnetic resonance imaging (MRI) protocol. MATERIALS AND METHODS: Using 3D MRI, B-cell follicular lymphoma growth was quantified in a Pten(+/-)Lkb1(+/hypo) mouse line, before, during and after repeated treatments with a PI3K inhibitor GDC-0941 (75 mg/kg). RESULTS: Mean pre-treatment linear tumour growth rate was 16.5±12.8 mm(3)/week. Repeated 28-day GDC-0941 administration, with 21 days 'off-treatment', induced average tumour regression of 41±7%. Upon cessation of the second treatment (which was not permanently cytocidal), tumours re-grew with an average linear growth rate of 40.1±15.5 mm(3)/week. There was no evidence of chemoresistance. CONCLUSION: This protocol can accommodate complex dosing schedules, as well as combine different cancer therapies. It reduces biological variability problems and resulted in a 10-fold reduction in mouse numbers compared with terminal assessment methods. It is ideal for preclinical efficacy studies and for phenotyping molecularly characterized mouse models when investigating gene function.
Authors: Xu Huang; Stephan Wullschleger; Natalia Shpiro; Victoria A McGuire; Kei Sakamoto; Yvonne L Woods; Wendy McBurnie; Stewart Fleming; Dario R Alessi Journal: Biochem J Date: 2008-06-01 Impact factor: 3.857
Authors: P Workman; E O Aboagye; F Balkwill; A Balmain; G Bruder; D J Chaplin; J A Double; J Everitt; D A H Farningham; M J Glennie; L R Kelland; V Robinson; I J Stratford; G M Tozer; S Watson; S R Wedge; S A Eccles Journal: Br J Cancer Date: 2010-05-25 Impact factor: 7.640
Authors: Adrian J Folkes; Khatereh Ahmadi; Wendy K Alderton; Sonia Alix; Stewart J Baker; Gary Box; Irina S Chuckowree; Paul A Clarke; Paul Depledge; Suzanne A Eccles; Lori S Friedman; Angela Hayes; Timothy C Hancox; Arumugam Kugendradas; Letitia Lensun; Pauline Moore; Alan G Olivero; Jodie Pang; Sonal Patel; Giles H Pergl-Wilson; Florence I Raynaud; Anthony Robson; Nahid Saghir; Laurent Salphati; Sukhjit Sohal; Mark H Ultsch; Melanie Valenti; Heidi J A Wallweber; Nan Chi Wan; Christian Wiesmann; Paul Workman; Alexander Zhyvoloup; Marketa J Zvelebil; Stephen J Shuttleworth Journal: J Med Chem Date: 2008-09-25 Impact factor: 7.446