Cerebrospinal fluid matrix metalloproteinase-9 increases during treatment of recurrent malignant gliomas

Cerebrospinal Fluid Research
Eric T WongJulian K Wu

Abstract

Matrix metalloproteinases (MMPs) are enzymes that promote tumor invasion and angiogenesis by enzymatically remodeling the extracellular matrix. MMP-2 and MMP-9 are the most abundant forms of MMPs in malignant gliomas, while a 130 kDa MMP is thought to be MMP-9 complexed to other proteinases. This study determined whether doxycycline can block MMP activity in vitro. We also measured MMP-2 and MMP-9 levels in cerebrospinal fluid (CSF) from patients with recurrent malignant gliomas. To determine whether doxycycline can block MMP activity, we measured the extent of doxycyline-mediated MMP-2 and MMP-9 inhibition in vitro using epidermal growth factor receptor (EGFR) transfected U251 glioma cell lines. MMP activity was measured using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) zymography. In addition, patients underwent lumbar puncture for CSF sampling at baseline, after 6 weeks (1 cycle), and after 12 weeks (2 cycles), while being treated with a novel chemotherapy regimen of irinotecan, thalidomide, and doxycycline designed to block growth/proliferation, angiogenesis, and invasion. Irinotecan was given at 125 mg/m2/week for 4 weeks in 6-week cycles, together with continuous doxycycline at 100 mg twice daily ...Continue Reading

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Citations

Aug 27, 2011·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Chia-Hung HsiehRen-Shyan Liu
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Mar 9, 2021·BMJ Neurology Open·Liyen Katrina KanMastura Monif

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Methods Mentioned

BETA
electrophoresis
zymography

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