Quinacrine synergistically enhances the antivascular and antitumor efficacy of cediranib in intracranial mouse glioma

Merryl R. Lobo, Sarah C. Green, Matthias Schabel, G. Yancey Gillespie, Randall (Randy) Woltjer, Martin Pike

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background. Despite malignant glioma vascularity, anti-angiogenic therapy is largely ineffective.Wehypothesize that efficacy of the antiangiogenic agent cediranib is synergistically enhanced in intracranial glioma via combination with the late-stage autophagy inhibitor quinacrine. Methods. Relative cerebral bloodflowandvolume (rCBF, rCBV), vascular permeability (Ktrans), and tumor volume were assessed in intracranial 4C8 mouse glioma using a dual-bolus perfusionMRI approach. Tumor necrosis and tumor mean vessel density (MVD)were assessed immunohistologically. Autophagic vacuole accumulation and apoptosiswere assessed viaWestern blot in4C8glioma in vitro. Results. Cediranib or quinacrine treatment alone did not alter tumor growth. Survivalwas only marginally improved by cediranib and unchanged by quinacrine. In contrast, combined cediranib/quinacrine reduced tumor growth by >2-fold (P <.05) and increased median survival by >2- fold, compared with untreated controls (P trans compared with untreated controls, while combined cediranib/quinacrine substantially reduced both (P

Original languageEnglish (US)
Pages (from-to)1673-1683
Number of pages11
JournalNeuro-Oncology
Volume15
Issue number12
DOIs
StatePublished - 2013

Fingerprint

Quinacrine
Glioma
Neoplasms
Angiogenesis Inhibitors
Autophagy
Capillary Permeability
Growth
Vacuoles
Tumor Burden
Necrosis
cediranib

Keywords

  • Antiangiogenesis
  • Autophagy
  • Cediranib
  • Glioma
  • MRI

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Clinical Neurology

Cite this

Quinacrine synergistically enhances the antivascular and antitumor efficacy of cediranib in intracranial mouse glioma. / Lobo, Merryl R.; Green, Sarah C.; Schabel, Matthias; Gillespie, G. Yancey; Woltjer, Randall (Randy); Pike, Martin.

In: Neuro-Oncology, Vol. 15, No. 12, 2013, p. 1673-1683.

Research output: Contribution to journalArticle

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T1 - Quinacrine synergistically enhances the antivascular and antitumor efficacy of cediranib in intracranial mouse glioma

AU - Lobo, Merryl R.

AU - Green, Sarah C.

AU - Schabel, Matthias

AU - Gillespie, G. Yancey

AU - Woltjer, Randall (Randy)

AU - Pike, Martin

PY - 2013

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N2 - Background. Despite malignant glioma vascularity, anti-angiogenic therapy is largely ineffective.Wehypothesize that efficacy of the antiangiogenic agent cediranib is synergistically enhanced in intracranial glioma via combination with the late-stage autophagy inhibitor quinacrine. Methods. Relative cerebral bloodflowandvolume (rCBF, rCBV), vascular permeability (Ktrans), and tumor volume were assessed in intracranial 4C8 mouse glioma using a dual-bolus perfusionMRI approach. Tumor necrosis and tumor mean vessel density (MVD)were assessed immunohistologically. Autophagic vacuole accumulation and apoptosiswere assessed viaWestern blot in4C8glioma in vitro. Results. Cediranib or quinacrine treatment alone did not alter tumor growth. Survivalwas only marginally improved by cediranib and unchanged by quinacrine. In contrast, combined cediranib/quinacrine reduced tumor growth by >2-fold (P <.05) and increased median survival by >2- fold, compared with untreated controls (P trans compared with untreated controls, while combined cediranib/quinacrine substantially reduced both (P

AB - Background. Despite malignant glioma vascularity, anti-angiogenic therapy is largely ineffective.Wehypothesize that efficacy of the antiangiogenic agent cediranib is synergistically enhanced in intracranial glioma via combination with the late-stage autophagy inhibitor quinacrine. Methods. Relative cerebral bloodflowandvolume (rCBF, rCBV), vascular permeability (Ktrans), and tumor volume were assessed in intracranial 4C8 mouse glioma using a dual-bolus perfusionMRI approach. Tumor necrosis and tumor mean vessel density (MVD)were assessed immunohistologically. Autophagic vacuole accumulation and apoptosiswere assessed viaWestern blot in4C8glioma in vitro. Results. Cediranib or quinacrine treatment alone did not alter tumor growth. Survivalwas only marginally improved by cediranib and unchanged by quinacrine. In contrast, combined cediranib/quinacrine reduced tumor growth by >2-fold (P <.05) and increased median survival by >2- fold, compared with untreated controls (P trans compared with untreated controls, while combined cediranib/quinacrine substantially reduced both (P

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