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PMID: 27626306 Published · ppublish English Journal Article

Assessment of bevacizumab resistance increased by expression of BCAT1 in IDH1 wild-type glioblastoma: application of DSC perfusion MR imaging.

Oncotarget ·Vol. 7 ·No. 43 ·2016-10-25 ·Pages 69606-69615

Cho HR, Hong B, Kim H, Park CK, Park SH, Park S, Choi SH

Abstract

BCAT1 (branched-chain amino acid trasaminase1) expression is necessary for the progression of IDH1 wild-type (WT) glioblastoma multiforme (GBM), which is known to be associated with aggressive tumors. The purpose of our study is to investigate the bevacizumab resistance increased by the expression of BCAT1 in IDH1 WT GBM in a rat model, which was evaluated using DSC perfusion MRI. BCAT1 sh#1 inhibits cell proliferation and limits cell migration potential in vitro. In vivo MRI showed that the increase in both tumor volume and nCBV after bevacizumab treatment in IDH1 WT tumors was significantly higher compared with BCAT1 sh#1tumors. In a histological analysis, more micro-vessel reformation by bevacizumab resistance was observed in IDH1 WT tumors than BCAT1 sh#1 tumors. These findings indicate that BCAT1 expression in IDH1 WT GBM increases resistance to bevacizumab treatment, which could be assessed by DSC perfusion MRI, and that nCBV can be a surrogate imaging biomarker for the prediction of antiangiogenic treatment in GBM.

Keywords
BCAT1 bevacizumab dynamic susceptibility contrast (DSC) glioblastoma
MeSH Terms
Animals Antineoplastic Agents, Immunological/pharmacology,therapeutic use Bevacizumab/pharmacology,therapeutic use Brain Neoplasms/diagnostic imaging,drug therapy,genetics Cell Line, Tumor Cell Movement/drug effects,genetics Cell Proliferation/drug effects,genetics Drug Resistance, Neoplasm/genetics Glioblastoma/diagnostic imaging,drug therapy,genetics Humans Isocitrate Dehydrogenase/genetics,metabolism Magnetic Resonance Imaging/methods Male RNA Interference Rats Transaminases/genetics,metabolism Xenograft Model Antitumor Assays
Chemicals
Antineoplastic Agents, Immunological Bevacizumab Isocitrate Dehydrogenase IDH1 protein, human BCAT1 protein, human Transaminases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Cho Hye Rim
Department of Radiology, Seoul National University Hospital, Seoul, Korea. | Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul, Korea.
Hong Bora
Department of Radiology, Seoul National University Hospital, Seoul, Korea. | Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul, Korea.
Kim Hyeonjin
Department of Radiology, Seoul National University Hospital, Seoul, Korea.
Park Chul-Kee
Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea.
Park Sung-Hye
Department of Pathology, Seoul National University Hospital, Seoul, Korea.
Park Sunghyouk
College of Pharmacy, Natural Product Research Institute, Seoul National University, Seoul, Korea.
Choi Seung Hong
Department of Radiology, Seoul National University Hospital, Seoul, Korea. | Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul, Korea.
References (46)
46 references, click to expand
  1. A randomized trial of bevacizumab for newly diagnosed glioblastoma.
    N Engl J Med. 2014 Feb 20;370(8):699-708 PMID: 24552317
  2. Microenvironmental regulation of tumor progression and metastasis.
    Nat Med. 2013 Nov;19(11):1423-37 PMID: 24202395
  3. Glial tumor grading and outcome prediction using dynamic spin-echo MR susceptibility mapping compared with conventional contrast-enhanced MR: confounding effect of elevated rCBV of oligodendrogliomas [corrected].
    AJNR Am J Neuroradiol. 2004 Feb;25(2):214-21 PMID: 14970020
  4. Handling macromolecule signals in the quantification of the neurochemical profile.
    J Alzheimers Dis. 2012;31 Suppl 3:S101-15 PMID: 22543852
  5. Dynamic contrast-enhanced MRI in clinical trials of antivascular therapies.
    Nat Rev Clin Oncol. 2012 Feb 14;9(3):167-77 PMID: 22330689
  6. Monitoring chemotherapeutic response by hyperpolarized 13C-fumarate MRS and diffusion MRI.
    Cancer Res. 2014 Feb 1;74(3):686-94 PMID: 24285723
  7. Angiogenesis in glioblastoma.
    N Engl J Med. 2013 Oct 17;369(16):1561-3 PMID: 24131182
  8. Low-grade gliomas: do changes in rCBV measurements at longitudinal perfusion-weighted MR imaging predict malignant transformation?
    Radiology. 2008 Apr;247(1):170-8 PMID: 18372467
  9. Metabolism, gliomas, and IDH1.
    N Engl J Med. 2010 Mar 25;362(12 ):1144-5 PMID: 20335593
  10. Correlation of MR imaging-determined cerebral blood volume maps with histologic and angiographic determination of vascularity of gliomas.
    AJR Am J Roentgenol. 1998 Dec;171(6):1479-86 PMID: 9843274
  11. Survival analysis in patients with glioblastoma multiforme: predictive value of choline-to-N-acetylaspartate index, apparent diffusion coefficient, and relative cerebral blood volume.
    J Magn Reson Imaging. 2004 May;19(5):546-54 PMID: 15112303
  12. Relative cerebral blood volume values to differentiate high-grade glioma recurrence from posttreatment radiation effect: direct correlation between image-guided tissue histopathology and localized dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging measurements.
    AJNR Am J Neuroradiol. 2009 Mar;30(3):552-8 PMID: 19056837
  13. Vessel caliber--a potential MRI biomarker of tumour response in clinical trials.
    Nat Rev Clin Oncol. 2014 Oct;11(10):566-84 PMID: 25113840
  14. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis.
    Cancer Cell. 2006 Mar;9(3):157-73 PMID: 16530701
  15. Java-based graphical user interface for the MRUI quantitation package.
    MAGMA. 2001 May;12(2-3):141-52 PMID: 11390270
  16. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas.
    N Engl J Med. 2015 Jun 25;372(26):2481-98 PMID: 26061751
  17. Hyperpolarized [1-13C] glutamate: a metabolic imaging biomarker of IDH1 mutational status in glioma.
    Cancer Res. 2014 Aug 15;74(16):4247-57 PMID: 24876103
  18. Improved perfusion MR imaging assessment of intracerebral tumor blood volume and antiangiogenic therapy efficacy in a rat model with ferumoxytol.
    Radiology. 2011 Dec;261(3):796-804 PMID: 21940504
  19. Advanced magnetic resonance imaging of the physical processes in human glioblastoma.
    Cancer Res. 2014 Sep 1;74(17 ):4622-37 PMID: 25183787
  20. Clinical relevance of diffusion and perfusion magnetic resonance imaging in assessing intra-axial brain tumors.
    Neuroradiology. 2006 Mar;48(3):150-9 PMID: 16470375
  21. BCAT1 defines gliomas by IDH status.
    Nat Med. 2013 Jul;19(7):816-7 PMID: 23836221
  22. Dynamic magnetic resonance imaging assessment of vascular targeting agent effects in rat intracerebral tumor models.
    Neuro Oncol. 2011 Jan;13(1):51-60 PMID: 21123368
  23. In vivo chemical exchange saturation transfer imaging allows early detection of a therapeutic response in glioblastoma.
    Proc Natl Acad Sci U S A. 2014 Mar 25;111(12 ):4542-7 PMID: 24616497
  24. Glioblastoma resistance to anti-VEGF therapy is associated with myeloid cell infiltration, stem cell accumulation, and a mesenchymal phenotype.
    Neuro Oncol. 2012 Nov;14 (11):1379-92 PMID: 22965162
  25. Increased survival of glioblastoma patients who respond to antiangiogenic therapy with elevated blood perfusion.
    Cancer Res. 2012 Jan 15;72(2):402-7 PMID: 22127927
  26. IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas.
    Clin Cancer Res. 2009 Oct 1;15(19):6002-7 PMID: 19755387
  27. Gliomas: predicting time to progression or survival with cerebral blood volume measurements at dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging.
    Radiology. 2008 May;247(2):490-8 PMID: 18349315
  28. Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors.
    N Engl J Med. 2015 Jun 25;372(26):2499-508 PMID: 26061753
  29. Mechanism for enhanced 5-aminolevulinic acid fluorescence in isocitrate dehydrogenase 1 mutant malignant gliomas.
    Oncotarget. 2015 Aug 21;6(24):20266-77 PMID: 26008980
  30. IDH1 and IDH2 mutations in gliomas.
    N Engl J Med. 2009 Feb 19;360(8):765-73 PMID: 19228619
  31. Cerebral blood volume maps of gliomas: comparison with tumor grade and histologic findings.
    Radiology. 1994 Apr;191(1):41-51 PMID: 8134596
  32. Over-expression of BCAT1, a c-Myc target gene, induces cell proliferation, migration and invasion in nasopharyngeal carcinoma.
    Mol Cancer. 2013 Jun 08;12:53 PMID: 23758864
  33. Mechanisms of angiogenesis in gliomas.
    J Neurooncol. 2006 Jul;78(3):281-93 PMID: 16554966
  34. Bevacizumab has differential and dose-dependent effects on glioma blood vessels and tumor cells.
    Clin Cancer Res. 2011 Oct 1;17(19):6192-205 PMID: 21788357
  35. Time-domain quantitation of 1H short echo-time signals: background accommodation.
    MAGMA. 2004 May;16(6):284-96 PMID: 15168136
  36. Genomic mapping and survival prediction in glioblastoma: molecular subclassification strengthened by hemodynamic imaging biomarkers.
    Radiology. 2013 Apr;267(1):212-20 PMID: 23238158
  37. Gene expression profiling reveals molecularly and clinically distinct subtypes of glioblastoma multiforme.
    Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5814-9 PMID: 15827123
  38. Differentiation of recurrent glioblastoma multiforme from radiation necrosis after external beam radiation therapy with dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging.
    Radiology. 2009 Nov;253(2):486-96 PMID: 19789240
  39. Structural determinants for branched-chain aminotransferase isozyme-specific inhibition by the anticonvulsant drug gabapentin.
    J Biol Chem. 2005 Nov 4;280(44):37246-56 PMID: 16141215
  40. Localized short-echo-time proton MR spectroscopy with full signal-intensity acquisition.
    Magn Reson Med. 2006 Nov;56(5):965-70 PMID: 16991116
  41. Radiological progression of cerebral metastases after radiosurgery: assessment of perfusion MRI for differentiating between necrosis and recurrence.
    J Neurol. 2009 Jun;256(6):878-87 PMID: 19274425
  42. BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1.
    Nat Med. 2013 Jul;19(7):901-8 PMID: 23793099
  43. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1.
    Cancer Cell. 2010 Jan 19;17(1):98-110 PMID: 20129251
  44. Proton NMR chemical shifts and coupling constants for brain metabolites.
    NMR Biomed. 2000 May;13(3):129-53 PMID: 10861994
  45. Non-invasive imaging of glioma vessel size and densities in correlation with tumour cell proliferation by small animal PET and MRI.
    Eur J Nucl Med Mol Imaging. 2013 Oct;40(10 ):1595-606 PMID: 23754761
  46. Angiogenesis as a therapeutic target.
    Nature. 2005 Dec 15;438(7070):967-74 PMID: 16355214
Article Info
Journal
Oncotarget
Abbr.
Oncotarget
ISSN
1949-2553
DOI
10.18632/oncotarget.11901
Published
2016-10-25
Pages
69606-69615
Language
English
Region
United States
NLM ID
101532965
PMCID
PMC5342501
Subset
IM
External Links
PubMed source DOI: 10.18632/oncotarget.11901 PMC Full Text View journal details
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