Tomokazu Goya

Glioma cell extracellular matrix metalloproteinase inducer (EMMPRIN) (CD147) stimulates production of membrane-type matrix metalloproteinases and activated gelatinase A in co-cultures with brain-derived fibroblasts

Extracellular matrix metalloproteinase inducer (EMMPRIN) also called CD147, basigin or M6 in the human is a member of the immunoglobulin superfamily that is enriched on the surface of tumor cells and stimulates adjacent stromal cells to produce several matrix metalloproteinases (MMPs). In this study, we have demonstrated that coculturing of EMMPRIN-expressing human glioblastoma multiforme cells (U251) with brain-derived human fibroblasts not only stimulates production, but also activation of pro-gelatinase A (proMMP-2), an enzyme that is enriched in malignant gliomas and most likely crucial to tumor progression. Production of membrane types 1 and 2-MMPs (MT1-MMP and MT2-MMP), which are activators of proMMP-2, was also stimulated in these cocultures. Stimulation of MMP-2, MT1-MMP and MT2-MMP production was inhibited by anti-EMMPRIN monoclonal antibody in a dose-dependent manner. Thus, we have shown, for the first time, that EMMPRIN causes increased expression of MT1-MMP and MT2-MMP, as well as increased production and activation of MMP-2.

Expression of emmprin (CD147), a cell surface inducer of matrix metalloproteinases, in normal human brain and gliomas

EMMPRIN (extracellular matrix metalloproteinase inducer), also called CD147, basigin or M6 in the human, is a member of the immunoglobulin superfamily that is present on the surface of tumor cells and stimulates adjacent fibroblasts to produce matrix metalloproteinases (MMPs). In our study, we investigated expression of EMMPRIN in human normal brain and gliomas, since mouse basigin and chicken HT7, the species homologues of human EMMPRIN, are associated with neuronal interactions and normal blood‐brain barrier function, respectively. EMMPRIN expression was detected in all samples of non‐neoplastic brain and glioma tissues examined. However, expression levels of EMMPRIN mRNA and protein were significantly higher in gliomas than in non‐neoplastic brain. Moreover, levels of mRNA expression and immunohistochemical staining correlated with tumor progression in gliomas: They were highest in the most malignant form of glioma, glioblastoma multiforme, followed by anaplastic astrocytoma and then low‐grade astrocytoma. Also, immunolocalization revealed quite different distributions in non‐neoplastic brain and glioma: EMMPRIN was demonstrated only in vascular endothelium in non‐neoplastic regions of the brain, whereas it was present in tumor cells but not in proliferating blood vessels in malignant gliomas. These data indicate that an MMP inducer molecule EMMPRIN is differently expressed in human normal brain and gliomas and could be associated with astrocytoma progression. Possible mechanisms whereby glioma cell EMMPRIN could influence tumor progression will be discussed. Int. J. Cancer 88:21–27, 2000.

Prediction of hemorrhagic complications after thrombolytic therapy for middle cerebral artery occlusion: value of pre- and post-therapeutic computed tomographic findings and angiographic occlusive site.

OBJECTIVE To evaluate the usefulness of pre- and post-therapeutic computed tomographic (CT) findings in predicting hemorrhagic complications, we retrospectively examined 35 patients treated with intra-arterial thrombolytic therapy for middle cerebral artery (MCA) occlusion. METHODS The presence or absence of early CT findings (loss of the insular ribbon, obscuration of the lentiform nucleus, and cortical effacement) and the presence and location of extravasation of contrast medium were evaluated on pre- and post-therapeutic CT scans, respectively. According to the angiographic occlusive site, the patients were classified into the following three groups: Group 1 (n = 13), MCA trunk occlusion involved lenticulostriate arteries; Group 2 (n = 11), occlusion of the MCA trunk without involvement of the lenticulostriate arteries; Group 3 (n = 11), occlusion of a branch of the MCA. Hemorrhagic complications (hemorrhagic transformation and/or massive brain swelling) were evaluated by reviewing CT scans obtained 3 to 14 days after thrombolytic therapy. RESULTS No patient without extravasation (n = 17) showed hemorrhagic complications, and extravasation is the most useful finding in predicting hemorrhagic complications. There was significant correlation between extravasation and hemorrhagic complications (P < 0.01). In Groups 1 and 2, there was also significant correlation between early CT findings and hemorrhagic complications (P < 0.01), indicating that early CT findings are also useful in predicting hemorrhagic complications. In Group 1, 10 of 13 (76.9%) patients had both early CT findings and extravasation, and 6 of these 10 patients had hemorrhagic complications with clinical deterioration, suggesting the difficulty of thrombolytic therapy in this group. On the contrary, in Group 2, 8 of 11 (72.7%) patients had neither early CT findings nor extravasation and none of these 8 patients had hemorrhagic complications. In Group 3, however, early CT findings and extravasation had no correlation. Because the affected area was small in this group, it was difficult to evaluate cortical effacement. Although negative early CT findings did not always mean absence of extravasation and hemorrhagic complications in this group, the patients with hemorrhagic complications did not clinically deteriorate because of the small affected area. CONCLUSION Hemorrhagic complications could be predicted by evaluation of angiographic occlusive site and pre- and post-therapeutic CT findings.

Comparative analysis of expression of hepatocyte growth factor and its receptor, c-met, in gliomas, meningiomas and schwannomas in humans

Expression of hepatocyte growth factor (HGF) and c-met, a proto-oncogene that encodes a receptor for HGF, was examined in 45 cases of human primary intracranial tumors by means of RT-PCR. In gliomas, HGF and c-met mRNAs were preferentially expressed in high-grade tumors. Co-expression of both genes was observed in glioblastomas (6/15) and in one anaplastic astrocytoma (1/5) but not in low-grade astrocytomas (0/3). By contrast, the c-met gene was consistently expressed in meningiomas (12/14) and schwannomas (8/8). The presence of c-Met protein was confirmed in the tumor cells of glioblastoma, meningioma and schwannoma by immunohistochemical staining. Moreover, all of the schwannoma cases co-expressed the HGF gene. These observations suggest that HGF/c-met expression is somehow related to the disease progression in gliomas, whereas c-Met protein might have an important fundamental biological role in meningioma and schwannoma. Moreover, since all of the schwannoma cases concomitantly expressed the ligand (HGF) and the receptor (c-met) genes, HGF may act in an autocrine fashion in schwannoma.

A rosette-forming glioneuronal tumor of the spinal cord: the first case of a rosette-forming glioneuronal tumor originating from the spinal cord.

Rosette-forming glioneuronal tumors of the fourth ventricle are rare brain tumors, and only 19 such lesions have been previously reported. This report presents the first case of a rosette-forming glioneuronal tumors arising from the spinal cord. A 44-year-old woman presented with a 15-year history of dissociated sensory disturbance of the lower extremities that gradually spread through her upper extremities. She also experienced continuing motor disturbance. Magnetic resonance imaging demonstrated a mass in the cervicothoracic spinal cord that suggested an intramedullary spinal tumor. A total gross resection of the tumor was performed. As is typical of rosette-forming glioneuronal tumors of the fourth ventricle, this spinal cord example manifested neurocytic and astrocytic components. Neurocytic rosettes were detected in the neurocytic component, and the center of rosettes showed positive immunostaining for synaptophysin. The astrocytic component showed characteristic features of a pilocytic astrocytoma, as is often the case in the fourth ventricle examples.

A combination of wrapping and clipping using a collagen-impregnated dacron fabric (Hemashield)

BACKGROUND We describe techniques combining wrapping and clipping using a collagen-impregnated Dacron knitted fabric (Hemashield) for accidental arterial perforations and broad-based aneurysms. The results of these techniques in seven patients are presented. METHODS Clip-reinforced wrapping was performed to obtain hemostasis in two patients with arterial perforations and in a patient with a ruptured broad-based aneurysm in the internal carotid artery. Clipping of the broad neck of the aneurysm and wrapping with Hemashield (wrap-clipping) was performed in four patients with unruptured aneurysms (one internal carotid artery, two middle cerebral artery, one basilar artery). RESULTS In the three patients treated with clip-reinforced wrapping, complete hemostasis was obtained just after clip application. In the patient with a ruptured broad-based aneurysm, postoperative angiography demonstrated that the dome of the aneurysm was well compressed. In the four patients treated with wrap-clipping, postoperative angiography revealed successful clipping of the broad neck of the aneurysm. CONCLUSION In this early experience, there were no problems in the use of Hemashield for clip-reinforced wrapping or wrap-clipping.

Direct percutaneous transluminal angioplasty for acute embolic middle cerebral artery occlusion: Report of two cases

Two patients with cardioembolic middle cerebral artery (MCA) trunk occlusion were treated by direct percutaneous transluminal angioplasty (PTA).

Intraoperative squash and touch cytology of chondroid chordoma of the skull base. Report of a case with immunocytochemical and immunohistochemical studies.

BACKGROUND Chondroid chordoma is a rare variant of chordoma and is usually located in the sphenooccipital region. This tumor shows clinical and histologic features common to both conventional chordoma and low grade chondrosarcoma and has a better prognosis than either of those lesions. To our knowledge, there has been no English language report describing its cytologic features. CASE The cytologic features of skull base chondroid chordoma observed in intraoperative crush and touch preparations from a 33-year-old female are reported. Touch cytology revealed round or stellate cells distributed in a mucoid background without a typical epithelial cordlike arrangement. The cells had variably vacuolated cytoplasm and round or oval nuclei and showed slight cellular pleomorphism. May-Giemsa staining was superior to Papanicolaou staining in demonstrating the mucoid matrix and vacuolated cytoplasm of the tumor cells. Additionally, crush preparations were effective in demonstrating well-differentiated chondroid elements. Immunocytochemistry with positivity for S-100 protein and cytokeratins was an essential adjunct in the cytologic diagnosis of chordoma and helped in distinguishing it from other chondrogenic tumors. CONCLUSION It is possible and advantageous to diagnose chondroid chordoma with a combination of cytologic and immunocytochemical studies of intraoperative crush and touch preparations in conjunction with clinical and radiographic information.

MRA as a primary screening technique for intra- and extracranial arterial occlusive diseases

We designed a protocol of 3-dimensional phase contrast (3D-PC-) magnetic resonance angiography (MRA), which was performed in the axial plane to assess the circle of Willis and in the coronal plane to assess the arteries of the head and neck, for screening of the intra- and extracranial arterial occlusive diseases. We evaluated the accuracy of 3D-PC-MRA comparing it with intraarterial angiography. In 52 consecutive patients presenting with clinical suspicion of a stroke, common carotid bifurcation (CCB), petrous segment of internal carotid artery (C5 segment), carotid siphon, middle cerebral artery (MCA), posterior cerebral artery (PCA), vertebral artery (VA), and basilar artery (BA) were evaluated. Both examinations were blindly graded as normal, mild (0–29% stenosis), moderate (30–69% stenosis), severe (70–99% stenosis), or occluded. In the two readers experienced and inexperienced in MR interpretation, Spearman rank correlations between the two techniques were 0.917/0.866 (CCB), 0.803/0.758 (C5 segment), 0.837/0.702 (carotid siphon), 0.841/0.787 (MCA), 0.899/0.886 (PCA), 0.935/0.889 (VA), and 0.932/0.900 (BA), respectively (p<0.0001). 3D-PC-MRA and intraarterial angiography had a good overall agreement, suggesting its use as a primary screening technique for intra- and extracranial arterial occlusive diseases, although the diagnostic accuracy of MRA was relatively poor in the C5 segment, carotid siphon, and MCA presumably due to phase dispersion.

Magnetic resonance imaging of a malignant transformation of an intracranial cellular blue nevus. A case report

As a follow-up to a case previously reported, a rare case of malignant transformation of cellular blue nevus (CBN) in the central nervous system preoperatively diagnosed by magnetic resonance imaging (MRI) is reported. On MRI, the malignant portion of the nevus was slightly hyperintense on both T1- and T2-weighted images. In contrast, the benign portion with a great deal of melanin was hyperintense on T1-weighted image and hypointense on T2-weighted image. MRI was useful and indispensable for detecting the malignant transformation of CBN.