Assessment of bevacizumab resistance increased by expression of BCAT1 in IDH1 wild-type glioblastoma: application of DSC perfusion MR imaging.
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.
Department of Radiology, Seoul National University Hospital, Seoul, Korea.|Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul, Korea.
Hye Rim
HR
Cho
Department of Radiology, Seoul National University Hospital, Seoul, Korea.|Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul, Korea.
Bora
B
Hong
Department of Radiology, Seoul National University Hospital, Seoul, Korea.
Hyeonjin
H
Kim
Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea.
Chul-Kee
CK
Park
Department of Pathology, Seoul National University Hospital, Seoul, Korea.
Sung-Hye
SH
Park
College of Pharmacy, Natural Product Research Institute, Seoul National University, Seoul, Korea.
Sunghyouk
S
Park
Department of Radiology, Seoul National University Hospital, Seoul, Korea.|Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul, Korea.
Seung Hong
SH
Choi
D000818:Animals; D000074322:Antineoplastic Agents, Immunological / Q000494:pharmacology / Q000627:therapeutic use; D000068258:Bevacizumab / Q000494:pharmacology / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D034622:RNA Interference; D051381:Rats; D000637:Transaminases / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000074322:Antineoplastic Agents, Immunological; D000068258:Bevacizumab; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; C490590:BCAT1 protein, human; D000637:Transaminases
BCAT1; bevacizumab; dynamic susceptibility contrast (DSC); glioblastoma