First Author | Wullschleger S | Year | 2012 |
Journal | Anticancer Res | Volume | 32 |
Issue | 2 | Pages | 415-20 |
PubMed ID | 22287727 | Mgi Jnum | J:299138 |
Mgi Id | MGI:6490043 | Citation | Wullschleger S, et al. (2012) Quantitative MRI establishes the efficacy of PI3K inhibitor (GDC-0941) multi-treatments in PTEN-deficient mice lymphoma. Anticancer Res 32(2):415-20 |
abstractText | 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. |