Masashi Tamaki

Prognostic significance of Ki-67 labeling indices obtained using MIB-1 monoclonal antibody in patients with supratentorial astrocytomas.

Identification of the prognosis of patients with gliomas is important for selecting and evaluating the effectiveness of treatment. The aim of this study was to evaluate the Ki‐67 labeling index (LI) using the newly generated MIB‐1 monoclonal antibody (MoAb) as a prognostic indicator for patients with astrocytomas.

Immunohistochemical detection of progesterone receptors and the correlation with Ki-67 labeling indices in paraffin-embedded sections of meningiomas

Female sex steroids may play a role in the proliferation of meningiomas. We investigated the progesterone receptor (PgR) immunoreactivities and the Ki-67 labeling indices in the formalin-fixed, paraffin-embedded sections of meningiomas from 39 patients. After autoclave pretreatment of the sections (which were immersed in a citrate buffer), the sections were incubated with the monoclonal antibody for the PgR and the MIB-1 monoclonal antibody for the Ki-67 antigen. In the meningiomas studied, the immunoreactivity for the PgR was moderately to strongly positive in 51%, weakly positive in 21%, and negative in 28%. The nuclear staining for the PgR was clear, and no tumors were positive for the estrogen receptor. The Ki-67 labeling indices of the PgR-positive meningiomas (mean +/- standard deviation, 2.35 +/- 2.12%) were significantly lower than those of the PgR-negative meningiomas (6.53 +/- 4.83%) (P < 0.05). Two meningiomas that had recurred more than once showed high Ki-67 labeling indices and negative immunostaining for the PgR. These findings indicate that the PgR status may be closely related to the growth potentials of the meningiomas. Our results confirm that the immunodetection of the PgR and the Ki-67 antigen on the paraffin sections of meningiomas provides a practical tool for estimating the biological behavior of the meningiomas.

Immunolocalization of matrix metalloproteinases in rabbit carotid arteries after balloon denudation

Abstract Extracellular matrix-degrading enzymes may play a key role in vascular remodeling after arterial wall injury. We investigated the immunolocalization of matrix metalloproteinases (MMPs) in rabbit carotid arteries after balloon denudation. Positive immunostaining for MMP-1, -2, -3, and -9 appeared through the neointima 1 week after balloon denudation. The localization of immunopositive smooth muscle cells (SMCs) for MMP-1, -3, and -9, particularly for MMP-9, was almost similar to that of replicative SMCs and became confined to the luminal surface layer of the neointima at later time periods. However, MMP-2-positive SMCs appeared also in the basal layer of the neointima at 2 weeks, increased at 4 weeks, and then totally occupied the neointima at 6 weeks. The MMP-2-positive SMCs in the basal layer of the neointima at 4 and 6 weeks were negative for proliferation-associated antigens and were surrounded by extracellular matrix proteins. Our results suggest that all MMPs act in coordination to promote replication and migration of SMCs in the earlier phases of neointimal formation and that MMP-2 independently contributes to the later stages by facilitating the migration but not replication of SMCs from the media to the intima.

Cerebellopontine angle pilocytic astrocytoma mimicking acoustic schwannoma.

Abstract We describe a case of pilocytic astrocytoma of the cerebellum mimicking an acoustic schwannoma. The tumour protruded into the porus acusticus and enlarged the internal auditory meatus, which is a quite unusual characteristic of glial tumours.

Marked Growth of a Cerebral Arteriovenous Malformation: Case Report and Review of the Literature

A case demonstrating the marked growth of an angiographically occult arteriovenous malformation is presented. A review of 58 cases in which an increase in the size of an arteriovenous malformation occurred suggested that the patients initial age may have had an important role in such growth and that both the age and the duration of follow-up were related to the extent of growth. Follow-up neuroradiological examinations are thought to be necessary for patients who have had an episode of intracranial hemorrhage of unknown cause during childhood, even if the initial angiograms revealed no vascular lesion.

Localization and effects of hepatocyte growth factor on smooth muscle cells during neointimal formation after balloon denudation

Abstract The migration and proliferation of smooth muscle cells (SMCs) may play a key role in tissue remodeling after arterial wall injury. We investigated the localization and effects of hepatocyte growth factor (HGF) in rabbit carotid arteries after balloon denudation. Immunoreactivity for HGF and the c-Met receptor was clearly observed in neointimal SMCs. The immunoreactivity was not restricted to proliferating cells but was seen even in non-dividing cells in the basal layer of the neointima 4 and 6 weeks after balloon denudation. The distribution of platelet-derived growth factor (PDGF)-positive cells paralleled that of proliferating SMCs. The SMCs in the basal layer of the neointima at 4 and 6 weeks were positive for matrix metalloproteinase (MMP)-2 and membrane type 1-MMP which can activate the proform of MMP-2. HGF significantly stimulated the migration but not proliferation of cultured SMCs. Our results suggest that HGF and PDGF act in coordination to promote the proliferation and migration of SMCs in the earlier phases of neointimal formation and that HGF as well as MMP-2 contribute to the later stages by facilitating the migration but not replication of SMCs.

Recurrence in meningeal hemangiopericytomas

BACKGROUND Meningeal hemangiopericytomas are more aggressive than typical meningiomas, with a high rate of recurrence and distant metastases. The question of whether a correlation exists between prognosis and histologic features remains controversial. CASE DESCRIPTION We report two cases of recurrent meningeal hemangiopericytomas. Although local growth control of the tumor was obtained by tumor removal and irradiation in a 38-year-old male patient (Case 1) with a recurrent tentorial tumor, the tumor disseminated and metastasized extracranially within a short period after treatment, leading to rapid deterioration. Another 38-year-old female patient (Case 2) with a recurrent orbital tumor had a favorable outcome after tumor removal. The Ki-67 proliferative index using the MIB-1 monoclonal antibody increased as the tumor recurred in Case 1 (2.5%, 7.9%, and 15.7%), but did not change between primary and recurrent tumors of Case 2 (4.2%, 3.1%). Immunostaining for p53 protein in Case 1 was negative at the first resection, and became positive at the second and third resections, whereas in Case 2, it was negative in both the primary and recurrent tumors. CONCLUSIONS Our results suggest that p53 protein accumulation with a high proliferative potential is a useful marker to estimate malignant progression in meningeal hemangiopericytomas.

Peritumoral cerebral edema in meningiomas: the role of the tumor-brain interface

We investigated the role of the tumor-brain interface in the production of peritumoral cerebral edema in meningiomas by analysing the size, shape, histological type and location of the tumor, and radiological and operative findings. Our results suggest that changes of the boundary zone between the tumor and the brain such as the disappearance of the subarachnoid space, cortical thinning or loss, and possibly partial loss of the arachnoid membrane are the most important factors in edema production, and that multiple other factors determine the morphological changes which occur at the tumor-brain interface.

Impairment of Both Apoptotic and Cytoprotective Signalings in Glioma Cells Resistant to the Combined Use of Cisplatin and Tumor Necrosis Factor α

Purpose: Tumor necrosis factor (TNF)-α elicits two opposing effects, the induction of apoptosis and the transcription of antiapoptotic genes. We have recently shown that cisplatin sensitizes glioma cells to TNF-induced apoptosis, but only in some cell lines. To understand the mechanism involved in the different susceptibilities, we examined both the activation of caspases and cytoprotective signaling by TNF-α. Experimental Design: Caspase activation was examined by estimating the cleavage of substrate peptides and by immunoblot to identify the cleavage of procaspases. Peptide inhibitors of caspases were used to reverse the cytotoxicity. The binding of TNF-α to the receptor was analyzed by flow cytometry. Nuclear factor (NF)-κB activation was assayed by the binding of NF-κB to oligonucleotides containing the consensus binding site. Interleukin (IL)-1β, IL-6, IL-8, and manganous superoxide dismutase (MnSOD) were measured by enzyme-linked immunoassays. Results: T98G and U87MG underwent apoptosis on treatment with cisplatin and TNF-α, but U373MG and A172 were resistant. Caspases 2, 3, and 6–10, but not caspases 1, 4, and 5, were activated in sensitive cells, and none were activated in resistant cells. The binding of TNF-α to the receptor was the same in all four of the cell lines. In the sensitive cells, NF-κB activation and the production of IL-1β, IL-6, IL-8, and MnSOD were significantly elevated by TNF-α. However, in the resistant cells, the production of IL-1β and IL-6 were specifically impaired in response to TNF-α. Conclusions: Our results indicate that both apoptotic and cytoprotective pathways are impaired in glioma cells that are resistant to treatment with cisplatin and TNF-α.

Sensitization of human malignant glioma cell lines to tumor necrosis factor-induced apoptosis by cisplatin

Most tumors, including gliomas, are resistant to tumor necrosis factor (TNF) cytotoxicity unless protein or RNA synthesis is inhibited. We investigated the effects of the combined use of TNF-α and cisplatin (CDDP) on cultured malignant glioma cells, T98G, U373MG, A172, and U87MG. All glioma cell lines were sensitive to treatment with CDDP but resistant to TNF-α during 24 h-incubation. The combined use of CDDP and TNF-α had synergistic effects on T98G and U87MG but not on U373MG and A172 cells. Sequential treatments showed that only pretreatment with CDDP for 2 h followed by TNF-α for 22 h was synergistic on cell cytotoxicity. Annexin V-flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling assay showed that TNF-α can induce apoptosis in cells treated with CDDP. Although only sensitive cell lines express transcripts for p75 TNF receptor 2, changes in TNF receptors were not found to contribute to the susceptibility to TNF-α. The production of interleukin-6, a representative cytoprotective cytokine, from glioma cells stimulated by TNF-α was suppressed by the combined use of actinomycin D, but not CDDP. Our results indicate that CDDP can sensitize glioma cells to TNF-α-induced apoptosis by a mechanism other than blocking the cytoprotective protein production.