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Toshihiko Kubota

Publications and source records attributed to Toshihiko Kubota.

At least 19 recordsLinked to original sources
PubMed2007

Radiological findings for arterial dissection of the anterior cerebral artery.

We treated a patient with anterior cerebral artery (ACA) dissection that caused an ischaemic stroke, and investigated serial changes over time by using three different radiological methods. The conventional angiography findings for ACA dissection corresponded to those of computed tomography (CT) angiography, but not those of magnetic resonance angiography for each phase. We presume that the results were based on the velocity of the blood flow in the pseudolumen of the dissected artery, and we believe that CT angiography is a useful and less invasive diagnostic tool for intracranial arterial dissection.

Adult↗
PubMed2006

Neuronal loss and expression of neurotrophic factors in a model of rat chronic compressive spinal cord injury.

STUDY DESIGN: An experimental animal study about neuronal loss and the expression of neurotrophic factors in the chronic compressive spinal cords. OBJECTIVES: To investigate neuronal loss and the expression of neurotrophic factors in the chronic compressive spinal cords of rats, and to evaluate effects of decompressive procedures for the neuronal loss. SUMMARY OF BACKGROUND DATA: Chronic compression of spinal cords induces the loss of motor neurons in the anterior horn. However, the precise mechanism of this neuronal loss is not still understood completely. Furthermore, it is uncertain whether decompressive procedures prevent this neuronal loss or not. METHODS: A thin expanding polymer sheet was implanted microsurgically underneath T7 laminae of rats. After 6, 9, 12, and 15 weeks, the thoracic spinal cord was harvested and examined histopathologically. The expression of neurotrophic factors, including NGF, BDNF, NT-3, GDNF, CNTF, and VEGF, was analyzed using semiquantitative RT-PCR, enzyme immunoassay, and immunohistochemistry. Decompressive surgery was performed through the removal of T7 laminae and the compression materials 6, 9, and 12 weeks after starting compression. Three weeks later, respectively, the neuronal loss in the anterior horn was estimated. RESULTS: The spinal cords were progressively flattened by the expanding of the implanted polymer sheet, and the number of motor neurons in the anterior horn decreased, especially from 6 to 9 weeks after starting compression. Semiquantitative RT-PCR analysis showed that the expression of NGF and BDNF mRNAs was decreased significantly in the spinal cords of 12-week compression group compared with the 6-week compression group and that NGF mRNA expression was up-regulated significantly in the 6-week compression group relative to the 6-week control group. Any changes of expression of other neurotrophic factors were not significant. Since BDNF, not NGF, has been known to be one of the powerful survival factors for spinal motoneurons, we investigated the levels of BDNF protein in the compressive spinal cords using enzyme immunoassay and immunohistochemistry. We demonstrated the level of BDNF protein in the compressive spinal cords was increased 6 weeks after compression but declined after 12 weeks. The decompressive procedure in the 6 weeks after compression prevented neuronal loss, but the same procedure in the 9 or 12 weeks was ineffective. CONCLUSIONS: From the point of view of neuronal loss, decompressive surgery at an earlier stage, when compensatory mechanisms including the up-regulation of BDNF might be still effective, could provide better therapeutic results against chronic mechanical compressive spinal cord lesions.

Animals↗
PubMed2006

Gene expression profiles of 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU)-resistant C6 rat glioma cells.

Chemotherapy in itself is suspected to cause the development or selection of drug-resistant tumor cells, which have more aggressive phenotypes. The authors investigated the differential changes of gene expression in the 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU)-resistant subline of the C6 rat glioma (C6AR2), which was established from C6 rat glioma cells by exposure to ACNU in vitro. The resistance to ACNU of C6AR2 was confirmed by MTS assay. The increased expression of O6-methylguanine-DNA methyltransferase in C6AR2 cells was shown using RT-PCR. C6AR2 cells displayed a higher proliferative activity relative to C6 cells. Analysis with cDNA array showed that 19 genes were transcriptionally up-regulated and 16 genes down-regulated in C6AR2 cells compared to C6 cells. They belonged to various functional classes of genes beside the drug-resistant system. Among them, the down-regulation of several genes in C6AR2 cells, including c-kit, pleiotrophin, platelet-derived growth factor receptor-alpha, peripheral myelin protein-22 and NG2 chondroitin sulfate proteoglycan, which are expressed originally in developmental glial lineages, were verified using semi-quantitative RT-PCR. In addition, the gene expression of astroglial intermediate filament proteins, including GFAP, vimentin and nestin, were decreased in C6AR2 cells relative to C6 cells in semi-quantitative RT-PCR and immunocytochemistry. These findings may represent an undifferentiated state of ACNU-resistant glioma cells and a more aggressive phenotype in recurrent tumors following chemotherapy.

Animals↗
PubMed2006

Mitotic activity of multinucleated giant cells with glial fibrillary acidic protein immunoreactivity in glioblastomas: an immunohistochemical double labeling study.

To investigate the mitotic activity of multinucleated giant cells (MNGCs) with glial fibrillary acidic protein (GFAP) in glioblastomas, double immunohistochemical staining for GFAP and Ki67 was performed in formalin-fixed and paraffin-embedded specimens obtained from 12 primary glioblastomas with MNGCs including three giant cell glioblastomas. The Ki67 labeling index (LI:%) of GFAP+ tumor cells ranged from 0 to 5.6 (2.5+/-1.7, mean+/-standard deviation). The Ki67 LI of GFAP- tumor cells ranged from 18.6 to 35.9 (24.7+/-6.6). The Ki67 LI of GFAP+ cells was significantly lower than that of GFAP- cells (P<0.0001). The number of Ki67+ GFAP- MNGCs ranged from 0 to 23 (8.6+/-8.2). The number of Ki67- GFAP+ MNGCs ranged from 0 to 15 (6.2+/-5.1). There was no significant difference between them (P=0.42). The Ki67 LI of GFAP+ MNGCs was 10.4+/-12.6. The Ki67 LI of GFAP- MNGCs was 45.9+/-29.9. The Ki67 LI of GFAP+ MNGCs was significantly lower than that of GFAP- MNGCs (P<0.01). Our study suggested that MNGCs with mitotic capacity were not dominant and that GFAP+ MNGCs had little mitotic activity in glioblastomas. MNGCs identified in glioblastomas may develop via not only the proliferation of abnormal nuclei in a single tumor cell but also other processes.

Adult↗
PubMed2006

Cervical extradural meningioma with rapidly progressive myelopathy.

A 50-year-old man noticed numbness of both hands. Muscle strength in the upper and lower extremities progressively deteriorated, and he became unable to stand or hold a cup over a five-day period. MRI showed an extradural tumour encasing the anterior, posterior and right lateral aspects of the cervical spinal cord, maximal at C3-4 but extending to C1, and emerging from the right C3-4 intervertebral foramen. At surgery, the tumour was entirely extradural. Histological examination revealed a meningioma. The patient recovered without neurological deficit with no recurrence 3 years after surgery.

Humans↗
PubMed2006

Cell-specific but p53-independent regulation of vascular endothelial growth factor expression by interferons in human glioblastoma cells.

Vascular endothelial growth factor (VEGF) is a key mediator of tumor angiogenesis. Interferons (IFNs) have been widely used in the treatment of malignant or recurrent gliomas with only marginal benefit. The association between IFNs and VEGF expression remains unclear and should be an intensively investigated subject. The present study therefore examined the effects of different types of IFNs on VEGF expression in human T98G, A172 and U251 glioblastoma cells by quantitative RT-PCR and ELISA. Both type I (alpha, beta) and type II (gamma) IFNs upregulated VEGF expression in a cell-specific but p53-independent manner. Actinomycin D experiments demonstrated that IFNs did not alter VEGF mRNA stability. In contrast, induction of VEGF mRNA by IFNs was blocked by the protein synthesis inhibitor cycloheximide. Interestingly, cycloheximide also blocked IFN-induced activation of the p44/p42 mitogen-activated protein kinase, which was partially required for induction of VEGF by IFNs. These findings suggest that VEGF might be an indirect target gene of IFNs, and might provide insights into therapeutic applications of IFNs against angiogenesis-dependent tumors.

Blotting, Western↗
PubMed2006

Acquisition of resistance to antitumor alkylating agent ACNU: a possible target of positron emission tomography monitoring.

Early detection of tumor response to chemotherapy is of great importance for appropriate treatment of tumors. In this study, characteristics of two positron emission tomography (PET) tracers, [(18)F]2-fluoro-2-deoxy-D-glucose (FDG) and[(18)F]3'-fluoro-3'-deoxy-thymidine (FLT), in the early detection of tumor cell response as well as tolerance development to chemotherapy was compared using rat C6 glioma cells and 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosoureahydrochloride (ACNU). ACNU is an alkylating agent known to induce drug resistance through expression of O(6)-methylguanine-deoxyribonucleic acid methyl transferase (O(6)-MGMT). We established an ACNU-resistant C6 glioma cell line (C6/ACNU) and investigated the effect of ACNU on the uptake of FLT and FDG. In C6 cells, DNA synthesis presented as [(3)H]thymidine ([(3)H]Thd) incorporation into DNA was quickly suppressed by ACNU. In C6/ACNU cells, the suppression was recovered promptly, indicating that DNA alkylation occurs initially but highly expressed O(6)-MGMT repairs DNA, leading to the recovery of DNA synthesis. The patterns of FLT uptake in C6 and C6/ACNU were difficult to distinguish in the very early stage of the treatment, though it was reported that FLT uptake well correlated with proliferation in certain conditions. FDG uptake showed different patterns between the resistant and control cells, with significantly decreased uptake in C6 cells and unchanged uptake in C6/ACNU cells at 18-24 h after the treatment. Though difficult to be directly translated into clinical situation, the present study will provide a base to develop an appropriate protocol to assess tumor response to treatment by PET and to design effective treatment plans.

Animals↗
PubMed2006

Astroblastoma: immunohistochemical and ultrastructural study of distinctive epithelial and probable tanycytic differentiation.

We report the clinicopathological findings of astroblastoma found in an 8-year-old girl who was subsequently treated for 11 years. The primary superficially circumscribed tumor was located in the frontoparietal lobe, while the recurrent and the second recurrent tumor were restricted to the same region 11 years later. The tumors obtained on these three occasions showed fundamentally the same histological, immunohistochemical and fine structural features. They exhibited astrocytic as well as ependymal tanycytic features with apparent epithelial cell lineage. The tumor cells showed typical features of astroblastoma comprising prominent perivascular pseudorosettes with remarkable vascular sclerosis. The immunohistochemical study revealed intensive positivity of GFAP, vimentin, epithelial membrane antigen (EMA), cytokeratin, connexin 26 and 32, desmocollin 1 and neuronal cadherin. The fine structure revealed divergent types of junctional complexes, some of which were connected with tonofilament bundles. Numerous microvilli protruded and basal lamina abutted on the tumor cell surface. We report these unique histological features, and stress that astroblastoma should be categorized as a specific type of neuroepithelial tumor.

Biomarkers, Tumor↗
PubMed2006

Atlas hypoplasia associated with non-traumatic retro-odontoid mass.

A 38-year-old man presented with progressive cervical myelopathy due to atlas hypoplasia associated with non-traumatic retro-odontoid mass. The neuroimaging findings suggested hypertrophy of the transverse ligament of the atlas. No histological confirmation of the retro-odontoid mass was obtained. Clinical manifestations improved after posterior decompression. Decompressive laminectomy of the atlas with or without fusion can achieve a good outcome in such cases.

Adult↗
PubMed2006

Meningeal plasma cell granuloma with relapsing polychondritis. Case report.

Relapsing polychondritis (RP) is a rare systemic disease characterized by recurrent inflammation of the cartilaginous structures and connective tissue. Central nervous system lesions in association with RP have occasionally been reported, but intracranial mass lesions have not been described. The authors report the first such case, in which a 51-year-old man presented with parasagittal meningeal plasma cell granuloma with RP. The mass was subtotally resected and adjuvant radiotherapy was administered. The patient did not experience any recurrence of the lesion during an 8-year follow-up period. In this case, the exact diagnosis of RP was made based on symptoms of respiratory tract chondritis, which was successfully treated by the placement of tracheobronchial stents.

Granuloma, Plasma Cell↗
PubMed2005

Glioma cells under hypoxic conditions block the brain microvascular endothelial cell death induced by serum starvation.

Angiogenesis is one of essential components for the growth of neoplasms, including malignant gliomas. However, tumor vascularization is often poorly organized and marginally functional due to tumor structural abnormalities, inducing regional or temporal hypoxic conditions and nutritional shortages in tumor tissues. We investigated how during angiogenesis migrating endothelial cells survive in these hypoxic and reduced nutritional conditions. Human brain microvascular endothelial cells (HBMECs) underwent apoptosis and necrosis after serum withdrawal. This endothelial cell death was blocked by recombinant VEGF protein or the culture medium of U251 glioma cells exposed to hypoxia (H-CM). Hypoxic treatment increased vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha (TNF-alpha) expression in U251 glioma cells. H-CM activated nuclear factor-kappaB (NFkappaB) protein and increased the gene expression of antiapoptotic factors including Bcl-2, Bcl-X(L), survivin and X-chromosome-linked inhibitor of apoptosis protein (XIAP) in endothelial cells. The survival activity of H-CM for endothelial cells was abolished by two kinds of VEGF inhibitors {Cyclopeptidic VEGF inhibitor and a VEGF receptor tyrosine kinase inhibitor (4-[(4'-chloro-2'-fluoro) phenylamino]-6, 7-dimethoxyquinazoline)} or NFkappaB inhibitors (ALLN and BAY 11-7082). These VEGF inhibitors did not block the activation of NFkappaB induced by H-CM in endothelial cells. On the contrary, TNF-alpha antagonist WP9QY enhanced the survival activity of H-CM for endothelial cells and blocked NFkappaB activation induced by H-CM under serum-starved conditions. Taken together, our data suggest that both the secretion of VEGF from glioma cells and activation of NFkappaB in endothelial cells induced by TNF-alpha are necessary for endothelial cell survival as they increase the expression of antiapoptotic genes in endothelial cells under conditions of serum starvation. These pathways may be one of the mechanisms by which angiogenesis is maintained in glioma tissues.

Apoptosis↗
PubMed2005

Clival chordoma manifesting as nasal bleeding. A case report.

Chordoma is a rare cartilaginous tumor, for which bleeding presentation is unusual. We report a case of rare hemorrhaged clival chordoma, which was diagnosed correctly by magnetic resonance imaging. A 32-year-old man presented with nasal bleeding. The tumor was totally removed via a trans-sphenoidal approach, from which the surgical specimen confirmed chordoma. Epistaxis seemed to be caused by the spreading of the intratumoral hemorrhage into the sphenoid sinus. This case demonstrates the importance of an exact differential diagnostic evaluation, including chordoma, by use of modern imaging techniques for nasal bleeding.

Adult↗
PubMed2005

Interferons upregulate thymidine phosphorylase expression via JAK-STAT-dependent transcriptional activation and mRNA stabilization in human glioblastoma cells.

Overexpression of the angiogenic enzyme thymidine phosphorylase (TP) in tumor cells and/or infiltrating macrophages correlates with increased microvessel density and poor prognosis in various tumor types including glioma. The present study examined how the TP gene expression is regulated by different types of interferons (IFNs) in human T98G and A172 glioblastoma cells. Both type I (alpha, beta) and type II (gamma) IFNs upregulated TP mRNA and protein expression while inhibiting cell proliferation. IFN-induced TP mRNA accumulation was not inhibited by the protein synthesis inhibitor cycloheximide, but was strongly blocked by the transcription inhibitor actinomycin D, as well as by transcription factor decoy oligodeoxynucleotides containing the putative IFN response element or the gamma-activated sequence in the TP promoter. The Janus kinase (JAK) inhibitor AG-490 blocked both IFN-induced STAT1 (signal transducers and activators of transcription 1) phosphorylation and TP expression. All IFNs increased the stability of TP mRNA as well. In addition, IFN-evoked TP enzyme activity enhanced the cytotoxicity of 5-fluorouracil (5-FU). These findings indicate that TP expression may be upregulated by IFNs via the JAK-STAT signaling pathway and both transcriptional and posttranscriptional mechanisms. Combined treatment with IFN and 5-fluorouracil may be a useful therapeutic strategy for malignant gliomas.

Antimetabolites, Antineoplastic↗
PubMed2005

Prognostic significance of microvessel density determined by an anti-CD105/endoglin monoclonal antibody in astrocytic tumors: comparison with an anti-CD31 monoclonal antibody.

There are conflicting reports as to whether the degree of angiogenesis as measured by microvessel density (MVD) has a prognostic value in astrocytic tumors. This may be due to the use of different antibodies against endothelial cells to highlight microvessels. It has been reported that unlike pan-endothelial antibodies, such as CD31, anti-CD105 antibodies preferentially react with endothelial cells in angiogenic tissues. To clarify the validity of anti-CD105 antibody in the evaluation of angiogenesis, we assessed MVD using an anti-CD105 monoclonal antibody (mAb) (CD105-MVD) and an anti-CD31 mAb (CD31-MVD) in a series of 50 astrocytic tumors, and correlated MVD with expression of the key angiogenic factor vascular endothelial growth factor (VEGF) and prognosis. The mean CD31-MVD and CD105-MVD was 36.7 and 24.8 for low-grade astrocytoma (LGA), 48.0 and 42.7 for anaplastic astrocytoma, 55.3 and 51.9 for glioblastoma multiforme (GBM), respectively. CD105-MVD was more closely correlated with VEGF expression than CD31-MVD. Patients with LGA and GBM showing higher CD105-MVD had a significantly shorter mean survival time (MST) than those with lower CD105-MVD tumors (P = 0.0381 and 0.0131, respectively). Whereas the MST of patients with higher CD31-MVD tumors seemed to be shorter than that of lower CD31-MVD patients within each tumor grade, the differences were not statistically significant. These findings suggest that anti-CD105 mAb may be a better marker than anti-CD31 mAb in evaluation of angiogenesis and prediction of prognosis in astrocytic tumors.

Adolescent↗
PubMed2005

Spinal tanycytic ependymoma with hematomyelia--case report--.

A 58-year-old man presented with an extremely rare case of "pure type" spinal tanycytic ependymoma associated with hematomyelia manifesting as sensory disturbance of the bilateral hands and weakness of the right arm. Magnetic resonance imaging demonstrated a tumor in the spinal cord from C-2 to C-4 levels. The soft gelatinous tumor was subtotally resected and the adjacent chronic liquid hematoma was aspirated. The immunohistochemical and ultrastructural findings indicated a diagnosis of tanycytic ependymoma.

Arm↗
PubMed2004

Ultrastructure of capillary endothelium in pilocytic astrocytomas.

The aim of this study was to assess the capillary ultrastructure of pilocytic astrocytomas with gadolinium contrast enhancement on magnetic resonance imaging (MRI). Cysts were identified in all cases with pilocytic astrocytoma. Histological investigation focusing on the vascular structure was performed by light microscopy and electron microscopy in four pilocytic astrocytomas. In the pilocytic astrocytomas, light microscopic examination demonstrated vascular abnormalities (fibrosis, hyalinization, and vascular proliferation), and electron microscopic examination revealed fenestration and vesicles in the capillary endothelium. Fenestration of the vessels and vascular abnormalities with degeneration are suggested to develop both contrast enhancement on neuroimaging and cystic formation in pilocytic astrocytomas.

Adolescent↗
PubMed2004

Successful removal after radiotherapy and vascular embolization in a huge tentorial epithelioid hemangioendothelioma: a case report.

Intracranial epithelioid hemangioendothelioma (E-HE) is an extremely rare, vasoformative tumor with variable biological behavior. A huge E-HE confined to the upper side of the tentorium has not been documented previously. Recognizing E-HE as a specific vascular tumor is important, and complete tumor removal guarantees long-term survival. Here, we report an intracranial E-HE of a 24-year-old woman with the initial symptoms of progressive headache over several years. Magnetic resonance imaging revealed a huge tumor attached to the upper side of the right tentorium, with tentorial and tonsillar herniation, and secondary syringomyelia in the upper cervical spinal cord. The initial surgical attempt to remove the lesion was abandoned due to profuse bleeding from the tumor. One year after irradiation and 5 days after vascular embolization, the tumor could be removed totally. The final definitive diagnosis as E-HE was made by special immunohistochemical and electron microscopic study. The patient is free from the tumor 9 years after the second operation. Thus, E-HE is a highly vascular-rich tumor to excise, and we stress need for preoperative embolization and/or irradiation to remove huge tumor completely.

Adult↗