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Tomography
Volume 5
Issue 1
10.18383/j.tom.2018.00031
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Article

Assessing Treatment Response of Glioblastoma to an HDAC Inhibitor Using Whole-Brain Spectroscopic MRI

by
Saumya S. Gurbani
1,2,
Younghyoun Yoon
1,
Brent D. Weinberg
3,
Eric Salgado
1,
Robert H. Press
1,
J. Scott Cordova
1,
Karthik K. Ramesh
1,2,
Zhongxing Liang
1,
Jose Velazquez Vega
4,
Alfredo Voloschin
5,
Jeffrey J. Olson
6,
Eduard Schreibmann
1,
Hyunsuk Shim
1,2,3,* and
Hui-Kuo G. Shu
1,*
1
Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA
2
Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA 30332, USA
3
Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA
4
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
5
Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA
6
Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA 30322, USA
*
Authors to whom correspondence should be addressed.
Tomography 2019, 5(1), 53-60; https://doi.org/10.18383/j.tom.2018.00031
Submission received: 6 December 2018 / Revised: 4 January 2019 / Accepted: 8 February 2019 / Published: 1 March 2019
Versions Notes

Abstract

Histone deacetylases regulate a wide variety of cellular functions and have been implicated in redifferentiation of various tumors. Histone deacetylase inhibitors (HDACi) are potential pharmacologic agents to improve outcomes for patients with gliomas. We assessed the therapeutic efficacy of belinostat (PXD-101), an HDACi with blood–brain barrier permeability. Belinostat was first tested in an orthotopic rat glioma model to assess in vivo tumoricidal effect. Our results showed that belinostat was effective in reducing tumor volume in the orthotopic rat glioma model in a dose-dependent manner. We also tested the antidepression activity of belinostat in 2 animal models of depression and found it to be effective. Furthermore, we confirmed that myo-inositol levels improved by belinostat treatment in vitro. In a human pilot study, it was observed that belinostat in combination with chemoradiation may delay initial recurrence of disease. Excitingly, belinostat significantly improved depressive symptoms in patients with glioblastoma compared with control subjects. Finally, spectroscopic magnetic resonance imaging of 2 patient cases from this pilot study are presented to indicate how spectroscopic magnetic resonance imaging can be used to monitor metabolite response and assess treatment effect on whole brain. This study highlights the potential of belinostat to be a synergistic therapeutic agent in the treatment of gliomas.
Keywords: glioblastoma; spectroscopic MRI; histone deacetylase inhibitor; belinostat; orthotopic rat glioma model glioblastoma; spectroscopic MRI; histone deacetylase inhibitor; belinostat; orthotopic rat glioma model

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MDPI and ACS Style

Gurbani, S.S.; Yoon, Y.; Weinberg, B.D.; Salgado, E.; Press, R.H.; Cordova, J.S.; Ramesh, K.K.; Liang, Z.; Vega, J.V.; Voloschin, A.; et al. Assessing Treatment Response of Glioblastoma to an HDAC Inhibitor Using Whole-Brain Spectroscopic MRI. Tomography 2019, 5, 53-60. https://doi.org/10.18383/j.tom.2018.00031

AMA Style

Gurbani SS, Yoon Y, Weinberg BD, Salgado E, Press RH, Cordova JS, Ramesh KK, Liang Z, Vega JV, Voloschin A, et al. Assessing Treatment Response of Glioblastoma to an HDAC Inhibitor Using Whole-Brain Spectroscopic MRI. Tomography. 2019; 5(1):53-60. https://doi.org/10.18383/j.tom.2018.00031

Chicago/Turabian Style

Gurbani, Saumya S., Younghyoun Yoon, Brent D. Weinberg, Eric Salgado, Robert H. Press, J. Scott Cordova, Karthik K. Ramesh, Zhongxing Liang, Jose Velazquez Vega, Alfredo Voloschin, and et al. 2019. "Assessing Treatment Response of Glioblastoma to an HDAC Inhibitor Using Whole-Brain Spectroscopic MRI" Tomography 5, no. 1: 53-60. https://doi.org/10.18383/j.tom.2018.00031

APA Style

Gurbani, S. S., Yoon, Y., Weinberg, B. D., Salgado, E., Press, R. H., Cordova, J. S., Ramesh, K. K., Liang, Z., Vega, J. V., Voloschin, A., Olson, J. J., Schreibmann, E., Shim, H., & Shu, H. -K. G. (2019). Assessing Treatment Response of Glioblastoma to an HDAC Inhibitor Using Whole-Brain Spectroscopic MRI. Tomography, 5(1), 53-60. https://doi.org/10.18383/j.tom.2018.00031

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