Comparison of multiple parameters obtained on 3T pulsed arterial spin-labeling, diffusion tensor imaging, and MRS and the Ki-67 labeling index in evaluating glioma grading.

BACKGROUND AND PURPOSE: Pulsed arterial spin-labeling, DTI, and MR spectroscopy provide useful data for tumor evaluation. We evaluated multiple parameters by using these pulse sequences and the Ki-67 labeling index in newly diagnosed supratentorial gliomas. MATERIALS AND METHODS: All 32 patients, with grade II (3 each of diffuse astrocytoma, oligodendroglioma, and oligoastrocytoma), grade III (3 anaplastic astrocytomas, 4 anaplastic oligodendrogliomas, and 1 anaplastic oligoastrocytoma), and grade IV (14 glioblastomas and 1 glioblastoma with an oligodendroglioma component) cases underwent pulsed arterial spin-labeling, DTI, and MR spectroscopy studies by using 3T MR imaging. The following variables were used to compare the tumors: relative cerebral blood flow, fractional anisotropy; ADC tumor/normal ratios; and the Cho/Cr, NAA/Cho, NAA/Cr, and lactate/Cr ratios. A logistic regression and receiver operating characteristic analysis were used to assess parameters with a high sensitivity and specificity to identify the threshold values for separate grading. We compared the Ki-67 index with various MR imaging parameters in tumor specimens. RESULTS: Significant correlations were observed between the Ki-67 index and the mean, maximum, and minimum ADC, Cho/Cr, and lactate/Cr ratios. The receiver operating characteristic analysis showed that the combination of the minimum ADC and Cho/Cr ratios could differentiate low-grade and high-grade gliomas, with a sensitivity and specificity of 87.0% and 88.9%, respectively. The mean and maximum relative cerebral blood flow ratios were used to classify glioblastomas from other-grade astrocytomas, with a sensitivity and specificity of 92.9% and 83.3%, respectively. CONCLUSIONS: Our findings indicate that pulsed arterial spin-labeling, DTI, and MR spectroscopy are useful for predicting glioma grade. Additionally, the parameters obtained on DTI and MR spectroscopy closely correlated with the proliferative potential of gliomas.

Up-regulation of urokinase-type plasminogen activator and its receptor correlates with enhanced invasion activity of human glioma cells mediated by transforming growth factor-alpha or basic fibroblast growth factor.

Glioblastoma multiforme is a highly malignant tumor that is extremely refractory to therapy. One reason is its highly invasive nature into brain tissue. Metalloproteinases and their inhibitors, plasminogen activators (PA) and their inhibitors and cathepsins are thought to be involved in invasion by tumor cells. In this study, we determined if the urokinase-type plasminogen activator (uPA) and/or the urokinase-type plasminogen activator receptor (uPAR) were responsible for the invasion activity of a human glioma cell line. We determined the invasion activity of a human glioma U251 cell line using an in vitro invasion assay system. A 2.4- to 5.8-fold increase in invasion activity was observed in the presence of basic fibroblast growth factor (bFGF) or transforming growth factor (TGF)-alpha. Northern blot analysis showed that bFCF and TGF-alpha treatment was associated with increases in cellular mRNA levels of uPA and uPAR. Zymographic activity correlated to mRNA levels of uPA and uPAR. Addition of an anti-uPAR monoclonal antibody significantly inhibited the invasion activity induced by bFGF- and TGF-alpha. Irsogladine, an inhibitor of uPA synthesis, also blocked the invasion activity. These observations suggest that uPA and its receptor have a role in the invasion process of human gliomas.

The ability in adhesion and invasion of drug-resistant human glioma cells.

Drug-resistance is critical in treating malignant tumors, and a variety of treatments are given to control it. Little study has been done, however, on biological changes in tumor cell activity in the course of acquiring drug-resistance. We used a glioma cell line to study changes in cell adhesion and invasion on acquiring drug-resistance. Human glioma culture cell line IN157 was used to establish the cell lines resistant to etoposide (VP-16), vincristine sulfate (VCR), and doxorubicin hydrochloride (DOX). Expressions of integrin alpha2, alpha3, alpha5, and beta1, neuronal cell adhesion molecule (NCAM), and matrix metalloproteinases (MMPs) were examined by flow cytometry. In drug-resistant cells, integrin expression was enhanced and NCAM expression was reduced. Adhesions to the extracellar matrix (ECM) proteins (laminin, fibronectin or type IV collagen) were studied. The adhesive ability of all cell lines increased in a concentration-dependent manner. Adhesion of drug-resistant cells was significantly stronger than that of IN157. The cell invasion of drug-resistant cell lines to the basal membrane was significantly lower than that of IN157. The cell invasion of IN157 was significantly suppressed by adding anti-NCAM antibody. In the case of IN157 with the acquisition of drug-resistance, an increase in the expression of integrins may have enhanced the adhesion to ECM proteins. This finding may be concerned with the decreased activity of drug-resistant cell lines in invading the basement membrane. NCAM expression in drug-resistant cell lines was reduced and anti-NCAM antibody abated invasion of IN157, suggesting that NCAM is involved in IN157 invasion.