HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Quantitative MRI establishes the efficacy of PI3K inhibitor (GDC-0941) multi-treatments in PTEN-deficient mice lymphoma.

AbstractAIM:
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.
AuthorsStephan Wullschleger, Juan M García-Martínez, Suzanne L Duce
JournalAnticancer research (Anticancer Res) Vol. 32 Issue 2 Pg. 415-20 (Feb 2012) ISSN: 1791-7530 [Electronic] Greece
PMID22287727 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine
  • Enzyme Inhibitors
  • Indazoles
  • Phosphoinositide-3 Kinase Inhibitors
  • Sulfonamides
  • PTEN Phosphohydrolase
  • Pten protein, mouse
Topics
  • Animals
  • Cell Line, Tumor
  • Disease Models, Animal
  • Enzyme Inhibitors (pharmacology)
  • Female
  • Head and Neck Neoplasms (drug therapy, enzymology, pathology)
  • Indazoles (pharmacology)
  • Longitudinal Studies
  • Lymphoma, B-Cell (drug therapy, enzymology, pathology)
  • Lymphoma, Follicular (drug therapy, enzymology, pathology)
  • Magnetic Resonance Imaging (methods)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • PTEN Phosphohydrolase (deficiency)
  • Phosphoinositide-3 Kinase Inhibitors
  • Sulfonamides (pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: