M Matsutani

Saitama Medical University, Saitama, Saitama, Japan

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Publications (156)271.44 Total impact

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    ABSTRACT: Object Temozolomide (TMZ) may enhance antitumor immunity in patients with glioblastoma multiforme (GBM). In this paper the authors report on a prospective Phase I/IIa clinical trial of fractionated radiotherapy (FRT) concomitant with TMZ therapy, followed by treatment with autologous formalin-fixed tumor vaccine (AFTV) and TMZ maintenance in patients with newly diagnosed GBM. Methods Twenty-four patients (age 16-75 years, Karnofsky Performance Scale score ≥ 60% before initiation of FRT) with newly diagnosed GBM received a total dose of 60 Gy of FRT with daily concurrent TMZ. After a 4-week interval, the patients received 3 AFTV injections and the first course of TMZ maintenance chemotherapy for 5 days, followed by multiple courses of TMZ for 5 days in each 28-day cycle. Results This treatment regimen was well tolerated by all patients. The percentage of patients with progression-free survival (PFS) ≥ 24 months was 33%. The median PFS, median overall survival (OS), and the actuarial 2- and 3-year survival rates of the 24 patients were 8.2 months, 22.2 months, 47%, and 38%, respectively. The median PFS in patients with a delayed-type hypersensitivity (DTH) response after the third AFTV injection (DTH-2) of 10 mm or larger surpassed the median length of follow-up for progression-free patients (29.5 months), which was significantly greater than the median PFS in patients with a smaller DTH-2 response. Conclusions The treatment regimen was well tolerated and resulted in favorable PFS and OS for newly diagnosed GBM patients. Clinical trial registration no.: UMIN000001426 (UMIN clinical trials registry, Japan).
    Journal of Neurosurgery 07/2014; · 3.15 Impact Factor
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    ABSTRACT: It has long been discussed whether HCG secreting germinomas are more malignant than pure germinomas. The Japanese study group insists of no difference in survival between two kinds of germinomas, whereas the European and American study groups put HCG germinomas into the high risk group. In order to solve the question, we analyzed the treatment results, the titer of a small amount of HCG-β in the cerebrospinal fluid (CSF), and the expression of HCGβ mRNA in germinoma cells.
    Neuro-oncology. 07/2014; 16 Suppl 3:iii27.
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    ABSTRACT: The initial symptoms of pineal region tumors might vary according to histology and era.
    Neuro-oncology. 07/2014; 16 Suppl 3:iii3.
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    ABSTRACT: Carmustine (BCNU) implants (Gliadel(®) Wafer, Eisai Inc., New Jersey, USA) for the treatment of malignant gliomas (MGs) were shown to enhance overall survival in comparison to placebo in controlled clinical trials in the United States and Europe. A prospective, multicenter phase I/II study involving Japanese patients with MGs was performed to evaluate the efficacy, safety, and pharmacokinetics of BCNU implants. The study enrolled 16 patients with newly diagnosed MGs and 8 patients with recurrent MGs. After the insertion of BCNU implants (8 sheets maximum, 61.6 mg BCNU) into the removal cavity, various chemotherapies (including temozolomide) and radiotherapies were applied. After placement, overall and progression-free survival rates and whole blood BCNU levels were evaluated. In patients with newly diagnosed MGs, the overall survival rates at 12 months and 24 months were 100.0% and 68.8%, and the progression-free survival rate at 12 months was 62.5%. In patients with recurrent MGs, the progression-free survival rate at 6 months was 37.5%. There were no grade 4 or higher adverse events noted due to BCNU implants, and grade 3 events were observed in 5 of 24 patients (20.8%). Whole blood BCNU levels reached a peak of 19.4 ng/mL approximately 3 hours after insertion, which was lower than 1/600 of the peak BCNU level recorded after intravenous injections. These levels decreased to less than the detection limit (2.00 ng/mL) after 24 hours. The results of this study involving Japanese patients are comparable to those of previous studies in the United States and Europe.
    Neurologia medico-chirurgica 04/2014; 54(4):290-301. · 0.49 Impact Factor
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    ABSTRACT: Background The initial presentation of central nervous system (CNS) tumors in children frequently mimics other more common and less serious conditions, resulting in diagnostic difficulty and a prolonged time to diagnosis. Yet whether early diagnosis contributes to better life prognosis and functional outcome has not been elucidated. Only a few such reports have originated from Japan, where neuroimaging techniques are the best in the world. We examined the time to diagnosis, the so-called prediagnostic symptomatic interval (PSI), and its impact on prognosis and functional outcome in children with CNS tumors.Methods We reviewed the records of 127 patients aged <15 years with CNS tumors, who were treated at our 2 institutions between November 1993 and October 2011.ResultsThe median age at diagnosis was 7.2 years (range, 3 weeks to 14.9 years). The male-to-female ratio was 63:64. Median PSI was 1.5 months (0 to 36 months). Overall survival and progression free survival did not differ significantly between the groups, regardless of whether the PSI was longer than the median PSI. The PSI was significantly longer in patients with long-lasting clinical signs after the initial treatment than in patients with temporary symptoms only at onset. Both univariate and multivariate analysis showed that high histological grading was statistically correlated with short PSI.ConclusionsA short PSI was significantly associated with high-grade tumors. Earlier diagnosis did not lead to better life prognosis, but possibly to better functional outcome in children with CNS tumors.
    Pediatrics International 04/2014; · 0.88 Impact Factor
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    ABSTRACT: Intracranial germ cell tumors (iGCTs) are the second most common brain tumors among children under 15 in Japan. The pathogenesis of iGCTs is largely unexplored. Although a subset of iGCTs is known to have KIT mutation, its impact on the biology and patients' survival has not been established. In this study, we investigated genes involved in the KIT signaling pathway. 65 iGCTs (30 pure germinomas, 14 teratomas, 18 mixed GCTs, 2 yolk sac tumors, 1 choriocarcinoma) were screened for mutation of KIT, KRAS, NRAS, HRAS, BRAF, PDGFRA, and IDH1 by direct sequencing. KIT expression was examined by immunohistochemistry and quantitative PCR. Chromosomal status was analyzed by array-comparative genomic hybridization (aCGH). Somatic mutations were detected only in KIT and RAS, which were frequently observed in pure germinomas (60.0 %), but rare in non-germinomatous GCTs (NGGCTs) (8.6 %). All KIT/RAS mutations were mutually exclusive. Regardless of the mutation status or mRNA expression, the KIT protein was expressed in all germinomas, while only in 54.3 % of NGGCTs. Amplification of KIT was found in one pure germinoma by aCGH. In pure germinomas, high expression of KIT mRNA was associated with the presence of KIT/RAS alterations and severe chromosomal instability. Our results indicate that alterations of the KIT signaling pathway play an important role in the development of germinomas. Pure germinomas may develop through two distinct pathogeneses: one with KIT/RAS alterations, elevated KIT mRNA expression and severe chromosomal instability, and the other through yet an unidentified mechanism without any of the above abnormalities.
    Acta Neuropathologica 01/2014; · 9.73 Impact Factor
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    ABSTRACT: Intracranial germ cell tumors (GCTs) are rare and heterogeneous with very little is known about their pathogenesis and underlying genetic abnormalities. In order to identify candidate genes and pathways which are involved in the pathogenesis of these tumors, we have profiled 62 intracranial GCTs for DNA copy number alterations (CNAs) and loss of heterozygosity (LOH) by using single nucleotide polymorphism (SNP) array and quantitative real time PCR (qPCR). Initially 27 cases of tumor tissues with matched blood samples were fully analyzed by SNP microarray and qPCR. Statistical analysis using the genomic identification of significant targets in cancer (GISTIC) tool identified 10 regions of significant copy number gain and 11 regions of significant copy number loss. While overall pattern of genomic aberration was similar between germinoma and nongerminomatous germ cell tumors (NGGCTs), a few subtype-specific peak regions were identified. Analysis by SNP array and qPCR was replicated using an independent cohort of 35 cases. Frequent aberrations of CCND2 (12p13) and RB1 (13q14) suggest that Cyclin/CDK-RB-E2F pathway might play a critical role in the pathogenesis of intracranial GCTs. Frequent gain of PRDM14 (8q13) implies that transcriptional regulation of primordial germ cell specification might be an important factor in the development of this tumor. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 11/2013; · 2.35 Impact Factor
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    ABSTRACT: Carmustine (BCNU) implants (Gliadel® Wafer, Eisai Inc., New Jersey, USA) for the treatment of malignant gliomas (MGs) were shown to enhance overall survival in comparison to placebo in controlled clinical trials in the United States and Europe. A prospective, multicenter phase I/II study involving Japanese patients with MGs was performed to evaluate the efficacy, safety, and pharmacokinetics of BCNU implants. The study enrolled 16 patients with newly diagnosed MGs and 8 patients with recurrent MGs. After the insertion of BCNU implants (8 sheets maximum, 61.6 mg BCNU) into the removal cavity, various chemotherapies (including temozolomide) and radiotherapies were applied. After placement, overall and progression-free survival rates and whole blood BCNU levels were evaluated. In patients with newly diagnosed MGs, the overall survival rates at 12 months and 24 months were 100.0% and 68.8%, and the progression-free survival rate at 12 months was 62.5%. In patients with recurrent MGs, the progression-free survival rate at 6 months was 37.5%. There were no grade 4 or higher adverse events noted due to BCNU implants, and grade 3 events were observed in 5 of 24 patients (20.8%). Whole blood BCNU levels reached a peak of 19.4 ng/mL approximately 3 hours after insertion, which was lower than 1/600 of the peak BCNU level recorded after intravenous injections. These levels decreased to less than the detection limit (2.00 ng/mL) after 24 hours. The results of this study involving Japanese patients are comparable to those of previous studies in the United States and Europe.
    Neurologia medico-chirurgica 11/2013; · 0.49 Impact Factor
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    ABSTRACT: Congenital intracranial immature teratomas carry a dismal prognosis, and the usefulness of chemotherapy for these tumors has not been elucidated. The authors report on the successful management of a case of congenital intracranial immature teratoma by using neoadjuvant chemotherapy and surgery after the failure of an initial attempt at resection. The patient was an infant who had begun vomiting frequently at the age of 12 days and had been admitted to a hospital at the age of 18 days with continued vomiting, increased head circumference, and disturbance of consciousness. A CT scan of the brain revealed a large mass in his posterior fossa and hydrocephalus. Surgery was performed on an emergent basis, but only minor tumor resection could be performed due to massive intraoperative hemorrhage. The histopathological diagnosis was immature teratoma. Postoperatively, the infant was in critical condition due to severe postoperative complications, and when he was transferred to the authors' institution 43 days after birth, his respiratory condition was still unstable because of lower cranial nerve palsy. Chemotherapy with carboplatin and etoposide resulted in moderate shrinkage of the tumor. Further chemotherapy led to improvement in the patient's general condition and weight gain, which allowed for a second attempt at resection. During this second surgery, which was performed when the child was 8 months of age, after 8 courses of chemotherapy, the tumor was completely resected with little bleeding. Histological findings from the second operation were consistent with mature teratoma. This case indicates that upfront chemotherapy may be effective for the initial management of such cases. Although the objective response to the treatment was modest, chemotherapy reduced the hemorrhagic nature of the tumor, facilitated improvement of the patient's general condition, and allowed for successful resection.
    Journal of Neurosurgery Pediatrics 10/2013; · 1.63 Impact Factor
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    ABSTRACT: Object Gliomas contain aggressive malignant cancer, and resection rate remains an important factor in treatment. Currently, fluorescence-guided resection using orally administered 5-aminolevulinic acid (5-ALA) has proved to be beneficial in improving the prognosis of patients with gliomas. 5-ALA is metabolized to protoporphyrin IX (PpIX) that accumulates selectively in the tumor and exhibits strong fluorescence upon excitation, but glioma cells do not always respond to 5-ALA, which can result in incomplete or excessive resection. Several possible mechanisms for this phenomenon have been suggested, but they remain poorly understood. To clarify the probable mechanisms underlying the variable induction of fluorescence and to improve fluorescence-guided surgery, the authors searched for key negative regulators of fluorescent signal induced by 5-ALA. Methods A comprehensive gene expression analysis was performed using microarrays in 11 pairs of tumor specimens, fluorescence-positive and fluorescence-negative tumors, and screened genes overexpressed specifically in fluorescence-negative tumors as the possible candidates for key negative regulators of 5-ALA-induced fluorescence. The most possible candidate was selected through annotation analysis in combination with a comparison of expression levels, and the relevance of expression of the selected gene to 5-ALA-induced fluorescence in tumor tissues was confirmed in the quantified expression levels. The biological significance of an identified gene in PpIX accumulation and 5-ALA-induced fluorescence was evaluated by in vitro PpIX fluorescence intensity analysis and in vitro PpIX fluorescence molecular imaging in 4 human glioblastoma cell lines (A1207, NMCG1, U251, and U373). Knockdown analyses using a specific small interfering RNA in U251 cells was also performed to determine the mechanisms of action and genes working as partners in the 5-ALA metabolic pathway. Results The authors chose 251 probes that showed remarkably high expression only in fluorescent-negative tumors (median intensity of expression signal > 1.0), and eventually the cadherin 13 gene (CDH13) was selected as the most possible determinant of 5-ALA-induced fluorescent signal in gliomas. The mean expression level of CDH13 in the fluorescence-negative gliomas was statistically higher than that in positive ones (p = 0.027), and knockdown of CDH13 expression enhanced the fluorescence image and increased the amount of PpIX 13-fold over controls (p < 0.001) in U251 glioma cells treated with 5-ALA. Comprehensive gene expression analysis of the CDH13-knockdown U251 cells demonstrated another two genes possibly involved in the PpIX biosynthesis: ATP-binding cassette transporter (ABCG2) significantly decreased in the CDH13 knockdown, while oligopeptide transporter 1 (PEPT1) increased. Conclusions The cadherin 13 gene might play a role in the PpIX accumulation pathway and act as a negative regulator of 5-ALA-induced fluorescence in glioma cells. Although further studies to clarify the mechanisms of action in the 5-ALA metabolic pathway would be indispensable, the results of this study might lead to a novel fluorescent marker able to overcome the obstacles of existing fluorescence-guided resection and improve the limited resection rate.
    Journal of Neurosurgery 09/2013; · 3.15 Impact Factor
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    ABSTRACT: This single-arm, open-label, Phase II study evaluated the efficacy and safety of single-agent bevacizumab, a monoclonal antibody against vascular endothelial growth factor, in Japanese patients with recurrent malignant glioma. Patients with histologically confirmed, measurable glioblastoma or World Health Organization Grade III glioma, previously treated with temozolomide plus radiotherapy, received 10 mg/kg bevacizumab intravenous infusion every 2 weeks. The primary endpoint was 6-month progression-free survival in the patients with recurrent glioblastoma. Of the 31 patients enrolled, 29 (93.5%) had glioblastoma and 2 (6.5%) had Grade III glioma. Eleven (35.5%) patients were receiving corticosteroids at baseline; 17 (54.8%) and 14 (45.2%) patients had experienced one or two relapses, respectively. The 6-month progression-free survival rate in the 29 patients with recurrent glioblastoma was 33.9% (90% confidence interval, 19.2-48.5) and the median progression-free survival was 3.3 months. The 1-year survival rate was 34.5% with a median overall survival of 10.5 months. There were eight responders (all partial responses) giving an objective response rate of 27.6%. The disease control rate was 79.3%. Eight of the 11 patients taking corticosteroids at baseline reduced their dose or discontinued corticosteroids during the study. Bevacizumab was well-tolerated and Grade ≥3 adverse events of special interest to bevacizumab were as follows: hypertension [3 (9.7%) patients], congestive heart failure [1 (3.2%) patient] and venous thromboembolism [1 (3.2%) patient]. One asymptomatic Grade 1 cerebral hemorrhage was observed, which resolved without treatment. Single-agent bevacizumab provides clinical benefit for Japanese patients with recurrent glioblastoma.
    Japanese Journal of Clinical Oncology 07/2012; 42(10):887-95. · 1.90 Impact Factor
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    ABSTRACT: Favorable responses to temozolomide chemotherapy have recently been reported in primary central nervous system lymphoma (PCNSL) patients who are refractory to high-dose methotrexate therapy. The gene encoding the DNA repair enzyme O (6)-methylguanine-DNA methyltransferase (MGMT) is transcriptionally silenced by promoter methylation in several human tumors, including gliomas and systemic lymphomas. MGMT promoter methylation is also a prognostic marker in glioblastoma patients treated with temozolomide. To validate temozolomide treatment in PCNSL, we applied methylation-sensitive high resolution melting (MS-HRM) analysis to quantitate MGMT methylation in PCNSL. MGMT promoter methylation was detected in tumors from 23 (51%) of 45 PCNSL patients, 11 of which were considered to have high (more than 70.0%) methylation status. Of the five recurrent PCNSLs treated with temozolomide, four cases responded, with three achieving complete response and one, a partial response. All four responsive PCNSLs had methylated MGMT promoters, whereas the non-responsive recurrent PCNSL did not. Thus, the use of quantitative MS-HRM analysis for the detection of MGMT promoter methylation has been suggested in PCNSL for the first time. The assay allows rapid and high-throughput evaluation of the MGMT methylation status, and seems to be promising in clinical settings. MGMT promoter methylation may become a useful marker for predicting the response of PCNSLs to temozolomide.
    Journal of Neuro-Oncology 03/2012; 107(1):147-53. · 3.12 Impact Factor
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    ABSTRACT: We report a case of pineal parenchymal tumor (PPT) in an 11-year-old girl. Brain magnetic resonance imaging (MRI) revealed a large tumor (48 mm) located in the pineal region with heterogeneous enhancement after gadolinium administration. The patient underwent tumor removal with craniotomy; only partial tumor resection could be performed because of massive intratumoral bleeding. Histopathological examination of the tumor showed lobular proliferation of round cells with moderate atypia. Cellularity varied by area, and focal Homer Wright rosettes were identified. Examination of tumor cells revealed a few mitoses (two mitotic figures per 10 high-powered fields), and immunohistochemical staining revealed positivity for synaptophysin, slight positivity for neurofilament protein (NFP) with antibody clone 2F11, and strong positivity for NFP with clone NF-M+H. The pathological diagnosis was pineal parenchymal tumor of intermediate differentiation grade II according to World Health Organization criteria despite a high (22%) MIB-1 labeling index (LI). The patient had a favorable clinical course after an intensified chemotherapy regimen designed for pineoblastoma and radiotherapy administered to the entire neuraxis, followed by stereotactic radiotherapy. In conclusion, MIB-1 LI could be a useful tool for deciding therapeutic strategies for PPT treatment when there is a discrepancy between clinical findings and pathological grading.
    Brain Tumor Pathology 02/2012; · 1.58 Impact Factor
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    ABSTRACT: To assess outcomes of carbon ion radiotherapy for diffuse astrocytomas in adults. Between October 1994 and February 2002, 14 patients with diffuse astrocytoma, identified as eligible for carbon ion radiotherapy, were enrolled in a phase I/II clinical trial. Carbon ion radiotherapy was administered in 24 fractions over 6 weeks. The normal tissue morbidity was monitored carefully, and the carbon ion dose was escalated from 50.4 Gy equivalent (GyE) to 55.2 GyE. Patients were divided into two groups according to their carbon ion doses: a low-dose group in which 2 patients were irradiated with 46.2 GyE and 7 patients were irradiated with 50.4 GyE, and a high-dose group in which 5 patients were irradiated with 55.2 GyE. Toxicities were within acceptable limits, and none of the patients developed Grade 3 or higher acute or late reactions. The median progression-free survival (PFS) time was 18 months for the low-dose group and 91 months for the high-dose group (p = 0.0030). The median overall survival (OS) time was 28 months for the low-dose group and not reached for the high-dose group (p = 0.0208). High-dose group patients showed significant improvement in PFS and OS rates compared to those in the low-dose group, and both dose groups showed acceptable toxicity.
    International journal of radiation oncology, biology, physics 11/2011; 83(1):100-6. · 4.59 Impact Factor
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    ABSTRACT: The objective of the present study was analysis of results of the prospective clinical trial directed toward the evaluation of therapeutic efficacy of the administration of autologous formalin-fixed tumor vaccine (AFTV) concomitant with fractionated radiotherapy in cases of newly diagnosed glioblastoma multiforme. Twenty-four patients were enrolled into the clinical trial, while 2 cases were excluded from the final analysis of results. The treatment protocol included aggressive tumor resection, fractionated radiotherapy up to a total dose of 60 Gy, and 3 concomitant courses of AFTV administered with an interval of one week at the late stage of irradiation. Two delayed-type hypersensitivity (DTH) tests were done--one 48 hours before the initial course of vaccination (DTH-1) and one 2 weeks after the third (DTH-2). All but one of the patients received salvage therapy at the time of tumor progression. The defined primary end point was overall survival; secondary end points were progression-free survival and safety of concomitant treatment. The median duration of overall survival was 21.4 months (95% CI 13.8-31.3 months). The actuarial 2-year survival rate was 40%. The median duration of progression-free survival was 7.6 months (95% CI 4.3-13.6 months). Overall survival showed a statistically significant association with recursive partitioning analysis class (p < 0.05); progression-free survival showed a statistically significant association with p53 staining index (p < 0.05) and size of DTH-2 response (p < 0.001). AFTV injection concomitant with fractionated radiotherapy was well tolerated by all patients and in no case did treatment-related adverse effects exceed Grade 1 toxicity; adverse effects were limited to local erythema, induration, and swelling at the site of injection. The results of this study demonstrate that AFTV treatment concomitant with fractionated radiotherapy may be effective in patients with newly diagnosed glioblastoma. Further clinical testing is warranted.
    Journal of Neurosurgery 05/2011; 115(2):248-55. · 3.15 Impact Factor
  • European Journal of Cancer - EUR J CANCER. 01/2011; 47.
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    ABSTRACT: The prognosis of recurrent glioblastoma multiforme (GBM) remains unsatisfactory. The authors conducted a Phase II study of ifosfamide, carboplatin, and etoposide (ICE) for a first recurrence of GBM to determine whether it prolonged a patient's good-quality life. This trial was an open-label, single-center Phase II study. Forty-two patients with a first GBM relapse after surgery followed by standard radiotherapy (60 Gy) and first-line temozolomide- or nimustine-based chemotherapy were eligible to participate. The primary end point was progression-free survival at 6 months after the ICE treatment (PFS-6), and secondary end points were response rate, toxicity, and overall survival. Chemotherapy consisted of ifosfamide (1000 mg/m(2) on Days 1, 2, and 3), carboplatin (110 mg/m(2) on Day 1), etoposide (100 mg/m(2) on Days 1, 2, and 3), every 6 weeks. Progression-free survival at 6 months after ICE treatment was 35% (95% CI 22-50%). The median duration of PFS was 17 weeks (95% CI 10-24 weeks). The response rate was 25% (95% CI 9-34%). Adverse events were generally mild and consisted mainly of alopecia. This regimen was well tolerated and has some activity and could be one of the options for patients with recurrent GBM.
    Journal of Neurosurgery 07/2009; 112(1):50-6. · 3.15 Impact Factor
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    ABSTRACT: Retrospective data analysis. To clarify the clinical features and surgical management of spinal cord hemangioblastomas in patients with von Hippel-Lindau disease (VHL). Clinical VHL Research Group in Japan, Japan. Forty-eight out of 66 patients with associated spinal cord hemangioblastoma among 142 VHL patients were retrospectively examined with respect to clinical features, accompanying lesions and outcome of surgical treatment. Among these 48 patients, 46 of them (95.8%) also had a central nervous system (CNS) hemangioblastoma at another site: 42 (87.5%) with cerebellar hemangioblastoma and 11 (22.9%) with brain stem hemangioblastoma. Twenty-three patients (47.9%) had more than one spinal cord hemangioblastoma. The 48 patients with spinal cord hemangioblastomas collectively had a total of 74 tumors. The tumor was accompanied with a syrinx in 64 and without it in 10 patients. Forty of the 48 patients underwent surgical treatment for their spinal cord hemangioblastomas, and 7 of these 40 underwent surgical treatment twice. When functional changes in the patients after these 47 operations were examined by postoperative evaluation by McCormick's classification, 39 of these operations (83.0%) resulted in improvement/no change and 8 (17.0%) in aggravation of symptoms. Von Hippel-Lindau disease patients bearing spinal cord hemangioblastomas mostly had a CNS hemangioblastoma at another site. These tumors can be removed in the majority of VHL patients without aggravation. In these patients, when the timing of treatment for spinal cord hemangioblastoma is determined, the probability of occurrence and treatment of other lesions should be considered.
    Spinal Cord 12/2008; 47(6):447-52. · 1.90 Impact Factor
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    ABSTRACT: Podocalyxin is an anti-adhesive mucin-like transmembrane sialoglycoprotein that has been implicated in the development of aggressive forms of cancer. Podocalyxin is also known as keratan sulfate (KS) proteoglycan. Recently, we revealed that highly sulfated KS or another mucin-like transmembrane sialoglycoprotein podoplanin/aggrus is upregulated in malignant astrocytic tumors. The aim of this study is to examine the relationship between podocalyxin expression and malignant progression of astrocytic tumors. In this study, 51 astrocytic tumors were investigated for podocalyxin expression using immunohistochemistry, Western blot analysis, and quantitative real-time PCR. Immunohistochemistry detected podocalyxin on the surface of tumor cells in six of 14 anaplastic astrocytomas (42.9%) and in 17 of 31 glioblastomas (54.8%), especially around proliferating endothelial cells. In diffuse astrocytoma, podocalyxin expression was observed only in vascular endothelial cells. Podocalyxin might be associated with the malignant progression of astrocytic tumors, and be a useful prognostic marker for astrocytic tumors.
    Biochemical and Biophysical Research Communications 09/2008; 374(2):394-8. · 2.41 Impact Factor
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    ABSTRACT: Keratan sulfate (KS) proteoglycans are expressed on a subpopulation of microglia in normal adult brain. We previously showed the up-regulated expression of KS in one of glioblastoma cell lines using anti-KS antibody (5D4). However, it has not been clarified whether KS is expressed in brain tumors and is involved in their malignancy. In this study, 54 astrocytic tumors were investigated about KS-expression using Western-blot with 5D4. In six of 14 anaplastic astrocytomas (43%) and 23 of 34 glioblastomas (68%), KS was detected by 5D4. KS was hardly detected by 5D4 in diffuse astrocytoma, suggesting that KS-expression is significantly expressed in malignant astrocytic tumors. In immunohistochemistry, KS is highly expressed in cell surface of malignant astrocytic tumors. Taken together, KS might be associated with the malignancy of astrocytic tumors, and be useful for a prognostic factor of astrocytic tumors.
    Biochemical and Biophysical Research Communications 06/2008; 369(4):1041-6. · 2.41 Impact Factor

Publication Stats

2k Citations
271.44 Total Impact Points

Institutions

  • 1997–2014
    • Saitama Medical University
      • • Department of Neurosurgery
      • • Department of Pathology
      Saitama, Saitama, Japan
  • 2012
    • Kyorin University
      • Department of Neurosurgery
      Edo, Tōkyō, Japan
  • 2007–2009
    • Tazuke Kofukai Medical Research Institute, Kitano Hospital
      Ōsaka, Ōsaka, Japan
  • 1979–2006
    • The University of Tokyo
      • • Faculty & Graduate School of Medicine
      • • Department of Neuroscience
      Tokyo, Tokyo-to, Japan
  • 1979–1996
    • Tokyo Metropolitan Komagome Hospital
      Edo, Tōkyō, Japan
  • 1991–1994
    • Tokyo Medical University
      • Department of Neurosurgery
      Tokyo, Tokyo-to, Japan
    • University of Toronto
      • Division of Neurosurgery
      Toronto, Ontario, Canada
  • 1988
    • Teikyo University Hospital
      Edo, Tōkyō, Japan
    • Japan Red Cross Fukuoka Hospital
      Hukuoka, Fukuoka, Japan
  • 1983
    • Teikyo University
      • Department of Neurosurgery
      Edo, Tōkyō, Japan