Synergistic antivascular and antitumor efficacy with combined cediranib and SC6889 in intracranial mouse glioma

Merryl R. Lobo, Ayaka Kukino, Huong Tran, Matthias Schabel, Charles Jr Springer, G. Yancey Gillespie, Marjorie Grafe, Randall (Randy) Woltjer, Martin Pike

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Prognosis remains extremely poor for malignant glioma. Targeted therapeutic approaches, including single agent anti-Angiogenic and proteasome inhibition strategies, have not resulted in sustained anti-glioma clinical efficacy.We tested the anti-glioma efficacy of the anti-Angiogenic receptor tyrosine kinase inhibitor cediranib and the novel proteasome inhibitor SC68896, in combination and as single agents. To assess anti-Angiogenic effects and evaluate efficacy we employed 4C8 intracranial mouse glioma and a dual-bolus perfusion MRI approach to measure Ktrans, relative cerebral blood flow and volume (rCBF, rCBV), and relative mean transit time (rMTT) in combination with anatomical MRI measurements of tumor growth.While single agent cediranib or SC68896 treatment did not alter tumor growth or survival, combined cediranib/SC68896 significantly delayed tumor growth and increased median survival by 2-fold, compared to untreated. This was accompanied by substantially increased tumor necrosis in the cediranib/SC68896 group (p

Original languageEnglish (US)
Article number0144488
JournalPLoS One
Volume10
Issue number12
DOIs
StatePublished - Dec 1 2015

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Glioma
Tumors
neoplasms
mice
proteasome endopeptidase complex
Magnetic resonance imaging
Neoplasms
Cerebrovascular Circulation
Growth
Proteasome Inhibitors
blood volume
Receptor Protein-Tyrosine Kinases
Proteasome Endopeptidase Complex
blood flow
prognosis
tyrosine
necrosis
phosphotransferases (kinases)
Blood
Necrosis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Synergistic antivascular and antitumor efficacy with combined cediranib and SC6889 in intracranial mouse glioma. / Lobo, Merryl R.; Kukino, Ayaka; Tran, Huong; Schabel, Matthias; Springer, Charles Jr; Gillespie, G. Yancey; Grafe, Marjorie; Woltjer, Randall (Randy); Pike, Martin.

In: PLoS One, Vol. 10, No. 12, 0144488, 01.12.2015.

Research output: Contribution to journalArticle

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AU - Springer, Charles Jr

AU - Gillespie, G. Yancey

AU - Grafe, Marjorie

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