Dataset Information

Dynamic MR imaging for functional vascularization depends on tissue factor signaling in glioblastoma.

ABSTRACT: Glomeruloid vascular proliferation (GVP) is a diagnostic hallmark and links to aggressive behavior, therapy resistance and poor prognosis in glioblastoma (GBM). It lacks clinical approaches to predict and monitor its formation and dynamic change. Yet the mechanism of GVPs also remains largely unknown. Using an in situ GBM xenograft mouse model, combined clinical MRI images of pre-surgery tumor and pathological investigation, we demonstrated that the inhibition of tissue factor (TF) decreased GVPs in Mouse GBM xenograft model. TF shRNA reduced microvascular area and diameter, other than bevacizumab. TF dominantly functions via PAR2/HB-EGF-dependent activation under hypoxia in endothelial cells (ECs), resulting in a reduction of GVPs and cancer cells invasion. TF expression strongly correlated to GVPs and microvascular area (MVA) in GBM specimens from 56 patients, which could be quantitatively evaluated in an advanced MRI images system in 33 GBM patients. This study presented an approach to assess GVPs that could be served as a MRI imaging biomarker in GBM and uncovered a molecular mechanism of GVPs.

SUBMITTER: Chen X

PROVIDER: S-EPMC5915017 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dynamic MR imaging for functional vascularization depends on tissue factor signaling in glioblastoma.

Chen Xiao X Xie Tian T Fang Jingqin J Xue Wei W Kang Houyi H Tong Haipeng H Guo Yu Y Zhang Bo B Wang Sumei S Yang Yizeng Y Zhang Weiguo W

Cancer biology & therapy 20180206 5

Glomeruloid vascular proliferation (GVP) is a diagnostic hallmark and links to aggressive behavior, therapy resistance and poor prognosis in glioblastoma (GBM). It lacks clinical approaches to predict and monitor its formation and dynamic change. Yet the mechanism of GVPs also remains largely unknown. Using an in situ GBM xenograft mouse model, combined clinical MRI images of pre-surgery tumor and pathological investigation, we demonstrated that the inhibition of tissue factor (TF) decreased GVP ...[more]

PMID: 29333924

Similar Datasets

Project description:Background and purposeA number of parameters derived from dynamic contrast-enhanced MR imaging and separate histologic features have been identified as potential prognosticators in high-grade glioma. This study evaluated the relationships between dynamic contrast-enhanced MRI-derived parameters and histologic features in glioblastoma multiforme.Materials and methodsTwenty-eight patients with newly presenting glioblastoma multiforme underwent preoperative imaging (conventional imaging and T1 dynamic contrast-enhanced MRI). Parametric maps of the initial area under the contrast agent concentration curve, contrast transfer coefficient, estimate of volume of the extravascular extracellular space, and estimate of blood plasma volume were generated, and the enhancing fraction was calculated. Surgical specimens were used to assess subtype and were graded (World Health Organization classification system) and were assessed for necrosis, cell density, cellular atypia, mitotic activity, and overall vascularity scores. Quantitative assessment of endothelial surface area, vascular surface area, and a vascular profile count were made by using CD34 immunostaining. The relationships between MR imaging parameters and histopathologic features were examined.ResultsHigh values of contrast transfer coefficient were associated with the presence of frank necrosis (P = .005). High values of the estimate of volume of the extravascular extracellular space were associated with a fibrillary histologic pattern (P < .01) and with increased mitotic activity (P < .05). No relationship was found between mitotic activity and histologic pattern, suggesting that the correlation between the estimate of volume of the extravascular extracellular space and mitotic activity was independent of the histologic pattern.ConclusionsA correlation between the estimate of volume of the extravascular extracellular space and mitotic activity is reported. Further work is warranted to establish how dynamic contrast-enhanced MRI parameters relate to more quantitative histologic measurements, including markers of proliferation and measures of vascular endothelial growth factor expression.

Project description:Background and purposeAlthough resection of a tumor by trans-sphenoidal surgery is considered the criterion standard for successful surgical treatment of functional pituitary microadenoma, MR imaging occasionally fails to visualize and identify the tumor and supplementary imaging modalities are necessary. We tested the possibility of dynamic contrast-enhanced multisection CT of the pituitary gland accompanying image reconstruction of contrast agent dynamics to identify the localizations of microadenomas and compared the diagnostic performance with conventional pituitary-targeted MR imaging.Materials and methodsTwenty-eight patients with surgically confirmed functional pituitary microadenomas (including growth hormone-, adrenocorticotropic hormone-, and prolactin-secreting adenomas) who underwent pituitary-targeted dynamic contrast-enhanced multisection CT were retrospectively investigated. We undertook image reconstruction of the dynamics of the contrast agent around the pituitary gland in a voxelwise manner, visualizing any abnormality and enabling qualification of contrast dynamics within the tumor.ResultsFifteen cases were correctly diagnosed by MR imaging, while dynamic contrast-enhanced multisection CT correctly diagnosed 26 cases. The accuracy of localization was markedly better for adrenocorticotropic hormone-secreting microadenomas, increasing from 32% on MR imaging to 85% by dynamic contrast-enhanced multisection CT. Compared with the normal pituitary gland, adrenocorticotropic hormone-secreting adenoma showed the least difference in contrast enhancement of the different functional microadenomas. Images acquired at 45-60 seconds after contrast agent injection showed the largest difference in contrast enhancement between an adenoma and the normal pituitary gland.ConclusionsDynamic contrast-enhanced multisection CT combined with image reconstruction of the contrast-enhanced dynamics holds promise in detecting MR imaging-occult pituitary microadenomas.

Dataset Information

Dynamic MR imaging for functional vascularization depends on tissue factor signaling in glioblastoma.

Publications

Dynamic MR imaging for functional vascularization depends on tissue factor signaling in glioblastoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets