Toshihiro Kumabe

Kitasato University, Edo, Tōkyō, Japan

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Publications (230)551.56 Total impact

  • Human pathology 06/2015; DOI:10.1016/j.humpath.2015.06.008 · 2.81 Impact Factor
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    ABSTRACT: Human chorionic gonadotropin (hCG) production has been utilized as a diagnostic marker for germinoma with syncytiotrophoblastic giant cells (STGC) and choriocarcinoma. Elevated hCG in germinoma is considered to predict less favorable prognosis, and an intensive treatment strategy may accordingly be applied. However, there is some evidence that any germinoma may produce hCG to varying extent. We investigated mRNA expression of the hCG β subunit (hCGβ) using real time quantitative polymerase chain reaction in 94 germ cell tumors (GCTs). Most (93.3 %) GCTs showed higher expression levels compared with that of normal brain tissue (1.09 × 10(0)-1.40 × 10(5) fold). The expression was the highest in GCTs which harbor choriocarcinoma or STGC components. The expression level of hCGβ in germinoma was highly variable (1.09 × 10(0)-5.88 × 10(4) fold) in linear but not bimodal distribution. hCG concentrations in serum and CSF correlated with gene expression, especially when GCTs with single histological component were analyzed separately. The expression was not significantly associated with recurrence in pure germinoma. These results suggest that the serum/CSF hCG levels may need to be interpreted with caution as most GCTs appear to have the capacity of producing hCG irrespective of their histology. The clinical significance of ubiquitous hCG expression in GCTs needs further investigation.
    Journal of Neuro-Oncology 05/2015; 124(1). DOI:10.1007/s11060-015-1809-y · 2.79 Impact Factor
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    ABSTRACT: Background: The aim of this study was to clarify the degree of information provision to children with brain tumors, factors influencing this provision, and the relationship between this provision and psychosocial consequences. Methods: A total of 157 parents completed a questionnaire on the degree of information provision to their children and sociodemographic and medical characteristics. Parents and their children completed subscales of the Pediatric Quality of Life Inventory (PedsQL) Cancer Module. Relevant factors were investigated using ordinal logistic regression analysis and compared with PedsQL scores by degree of information provision with adjustment for age. Results: The majority of children aged 2-4 years received a low level of information only in regard to medical procedure and preparation. The majority of children aged 5-11 years were I. Sato et al. 452 provided information regarding disease symptoms and treatment, but not actual diagnosis. Approximately half of children aged 12-18 years were provided detailed information including their actual diagnosis. Older children generally received more information regarding their disease (odds ratio [OR] = 1.3 per 1 year old, P < 0.001), while children with intellectual disability received less (OR = 0.2, P = 0.006). The provision of information did not worsen scores for Procedural Anxiety , Treatment Anxiety, Worry, or Communication. Conclusions: To our knowledge, this is the first report on the degree of information provision to children with brain tumors. Parents of children with brain tumors in Japan provide information dependent on age and intellectual level. The disclosure of information to children regarding their disease might affect their trust of medical and health care professionals.
    Open Journal of Nursing 04/2015; 5(05):451-464. DOI:10.4236/ojn.2015.55048
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    ABSTRACT: Moyamoya disease more commonly occurs in young people and women, so patients with this disease may experience pregnancy and delivery. Cesarean section (CS) is often chosen as the mode of delivery for these patients in Japan. No appropriate mode of delivery has yet been established for pregnant women with moyamoya disease in terms of stroke prevention. We have used vaginal delivery under epidural analgesia (EA) in such patients unless CS has been indicated for the maternal or fetal reasons. This study retrospectively analyzed our patients with moyamoya disease who gave birth to confirm the safety of vaginal delivery under EA. Twelve consecutive patients diagnosed with moyamoya disease had 14 deliveries at our hospital between September 2004 and January 2013. The incidences of intrapartum stroke were compared between cases of vaginal delivery under EA and CS cases. Ten vaginal deliveries under EA and 4 elective CSs were performed. No intrapartum stroke was observed during either vaginal delivery under EA or CS. Among the patients who underwent vaginal delivery under EA, 1 parturient who experienced 2 deliveries suffered transient ischemic attack during both postpartum periods. All 14 infants were healthy without sequelae. Vaginal delivery under EA is an option for patients with moyamoya disease, provided that close cooperation with neurosurgeons, obstetricians, and anesthesiologists is assured. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 03/2015; 24(5). DOI:10.1016/j.jstrokecerebrovasdis.2014.11.030 · 1.99 Impact Factor
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    ABSTRACT: This retrospective study was aimed to compare the perioperative complications for internal carotid artery stenosis (ICS) in a Japanese single institute between the use of carotid artery stenting (CAS) alone or the use of an appropriate individualized treatment method allowing either carotid endarterectomy (CEA) or CAS based on patient risk factors. Based on the policy at our hospital, only CAS was performed on patients (n = 33) between January 2005 and November 2009. From December 2009 to December 2012, either CEA or CAS (tailored treatment) was selected for patients (n = 61) based on individual patient risk factors. CEA was considered the first-line treatment in all cases. In high-risk CEA cases, CAS was performed instead (n = 11), whereas in low-risk CEA cases, CEA was performed (n = 19). Further, in moderate-risk CEA cases based on own criteria, CAS was considered first, whereas for high-risk CAS cases, CEA was performed (n = 17). For low-risk CAS cases, CAS was performed (n = 9). Perioperative clinical complications (any stroke, myocardial infarction, or death within 30 days) were compared between both periods. Significantly reduced perioperative complications were observed during the tailored period (4/61 sites, 6.6%) as compared with the CAS period (8/33 sites, 24.2%) [Fisher's exact test p = 0.022; odds ratio, 4.56 (CAS/tailored); 95% confidence interval, 1.26-16.5]. Selecting an appropriate individualized treatment method according to patient risk factors, as opposed to adhering to a single treatment approach such as CAS, may contribute to improved overall outcomes in patients with ICS.
    Neurologia medico-chirurgica 02/2015; 55(2). DOI:10.2176/nmc.oa.2014-0049 · 0.65 Impact Factor
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    ABSTRACT: Glioblastoma is the most malignant human brain tumor and has a dismal prognosis; however, some patients show long-term survival. The interaction between the costimulatory molecule OX40 and its ligand OX40L generates key signals for T-cell activation. The augmentation of this interaction enhances antitumor immunity. In this present study, we explored whether OX40 signaling is responsible for antitumor adaptive immunity against glioblastoma and also established therapeutic antiglioma vaccination therapy. Tumor specimens were obtained from patients with primary glioblastoma (n = 110) and grade III glioma (n = 34). Quantitative polymerase chain reaction (PCR), flow cytometry, and immunohistochemistry were used to analyze OX40L expression in human glioblastoma specimens. Functional consequences of OX40 signaling were studied using glioblastoma cell lines, mouse models of glioma, and T cells isolated from human subjects and mice. Cytokine production assay with mouse regulatory T cells was conducted under hypoxic conditions (1.5% O2). OX40L mRNA was expressed in glioblastoma specimens and higher levels were associated with prolonged progression-free survival of patients with glioblastoma, who had undergone gross total resection. In this regard, OX40L protein was expressed in A172 human glioblastoma cells and its expression was induced under hypoxia, which mimics the microenvironment of glioblastoma. Notably, human CD4 T cells were activated when cocultured in anti-CD3-coated plates with A172 cells expressing OX40L, as judged by the increased production of interferon-γ. To confirm the survival advantage of OX40L expression, we then used mouse glioma models. Mice bearing glioma cells forced to express OX40L did not die during the observed period after intracranial transplantation, whereas all mice bearing glioma cells lacking OX40L died. Such a survival benefit of OX40L was not detected in nude mice with an impaired immune system. Moreover, compared with systemic intraperitoneal injection, the subcutaneous injection of the OX40 agonist antibody together with glioma cell lysates elicited stronger antitumor immunity and prolonged the survival of mice bearing glioma or glioma-initiating cell-like cells. Finally, OX40 triggering activated regulatory T cells cultured under hypoxia led to the induction of the immunosuppressive cytokine IL10. Glioblastoma directs immunostimulation or immunosuppression through OX40 signaling, depending on its microenvironment.
    Molecular Cancer 02/2015; 14(1):41. DOI:10.1186/s12943-015-0307-3 · 5.40 Impact Factor
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    ABSTRACT: This report presents rosette-forming glioneuronal tumor (RGNT) of the tectum in a 24-year-old woman in whom spontaneous disappearance of contrast enhancement (CE) on magnetic resonance (MR) imaging was observed during 9-year follow-up period before therapeutic intervention. MR imaging obtained 9 years ago when she first visited local hospital with headaches showed a mass of the brain stem with CE. Follow-up MR imaging showed disappearance of CE without tumor growth. Nine years later, she was admitted to our hospital with headache and nausea, due to obstructive hydrocephalus. She underwent endoscopic third ventriculostomy (ETV) and tumor biopsy. Histological study revealed RGNT. To our knowledge, this is the first report presenting that the RGNT may show spontaneous disappearance of CE without tumor growth. It is unclear what this phenomenon means, however, knowledge of this phenomenon may be helpful for correct diagnosis and for follow up of RGNT.
    01/2015; 2(2):65-67. DOI:10.2176/
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    ABSTRACT: TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%¿±¿8.7%, respectively (p¿<¿0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%¿±¿2% vs. 57.4%¿±¿1.8% (p¿<¿0.01)). In contrast, ß-catenin mutation sensitized TP53 mutant cells to radiation (p¿<¿0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%¿±¿1.5% in lithium treated cells vs. 56.6¿±¿3% (p¿<¿0.01)) accompanied by increased number of ¿H2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%¿±¿8% for lithium treated cells vs. 27%¿±¿3% for untreated controls (p¿=¿0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.
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    ABSTRACT: The aim of this study was to determine if molecular alterations are associated with tumor location and radiological characteristics in anaplastic gliomas. We performed a retrospective analysis of 122 anaplastic gliomas for molecular alterations (IDH1/2 mutations, TP53 mutations, and 1p19q co-deletion) to compare MRI features (location and image characteristics). We observed that IDH mutation is strongly associated with frontal location (P = 0.001). However, 13 tumors not located in the cerebral cortex were IDH intact tumors (P < 0.0001). While IDH mutation and TP53 mutation are significantly associated with AA (p < 0.0001), IDH mutation and 1p19q co-deletion were significantly associated with AO/AOA (p < 0.0001). No tumors with IDH mutation and 1p19q co-deletion infiltrated the temporal lobe (P = 0.003). The tumors with 1p19q co-deletion and histologically diagnosed as AO/AOA were associated with contrast enhancement on MR images (p = 0.007, p = 0.002, respectively) and those with TP53 mutation had a weak association with sharp tumor borders (p = 0.043). MRI features might be useful to predict molecular profiles in anaplastic gliomas.
    Brain Tumor Pathology 12/2014; DOI:10.1007/s10014-014-0211-3 · 2.28 Impact Factor
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    ABSTRACT: We describe differentiation of a spinal intramedullary lipoma from an intramedullary hematoma on magnetic resonance images(MRI)with fast spin-echo(FSE)sequences. A 60-year-old man with dysesthesia in the legs and gait disturbance, was suspected of having myelopathy at a middle thoracic lesion. MRI with FSE sequences revealed an intramedullary lesion at T7 to T8. On the basis of hyperintensity on both T1-and T2-weighted images and a perilesional hypointense rim on T2-weighted images we made a diagnosis of subacute hematoma and planned observation. However, computed tomography for associated vertebral degeneration revealed a hypodense area(-97 Hounsfield units)in the region corresponding to the lesion depicted by MRI. We revised our diagnosis to an intramedullary lipoma and debulked the lesion. The lipoma was surrounded by a thick whitish capsule. Histopathologically, the capsule contained mature fat tissue and abundant collagen. The initial diagnosis was mainly attributable to specific FSE characteristics, i. e., the depiction of fat tissue as hyperintense on both T1-and T2-weighted images. Conventional spin-echo MRI depicts fat tissue as hyperintense on T1-and as hypointense on T2-weighted images. Other factors contributing to our initial diagnosis were MRI findings suggestive of an intramedullary hematoma, i. e., the intrinsic location of the lesion and the perilesional hypointense rim on T2-weighted images ascribable to collagen present in the capsule. The accurate diagnosis of an intramedullary lipoma on FSE requires correct interpretation of the signal, which is different from the signal on conventional spin-echo MRI.
    No shinkei geka. Neurological surgery 11/2014; 42(11):1045-50. DOI:10.11477/mf.1436200031 · 0.13 Impact Factor
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    ABSTRACT: Nuclear factor erythroid 2-related factor 2 (NRF2) plays pivotal roles in cytoprotection. We aimed at clarifying the contribution of the NRF2 pathway to malignant glioma pathology.
    Neuro-Oncology 10/2014; 17(4). DOI:10.1093/neuonc/nou282 · 5.29 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):4264-4264. DOI:10.1158/1538-7445.AM2014-4264 · 9.28 Impact Factor
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    ABSTRACT: Object Maximum resection of gliomas with minimum surgical complications usually leads to optimum outcomes for patients. Radical resection of insulo-opercular gliomas is still challenging, and selection of ideal patients can reduce risk and obtain better outcomes. Methods This retrospective study included 83 consecutively treated patients with newly diagnosed gliomas located at the insulo-opercular region and extending to the sylvian fissure around the primary motor and somatosensory cortices. The authors selected 4 characteristics as surgical indicators: clear tumor boundaries, negative enhancement, intact lenticulostriate arteries, and intact superior extremity of the central insular sulcus. Results Univariate analysis showed that tumors with clear boundaries were associated with higher rates of gross-total resection than were tumors with ambiguous boundaries (75.7% vs 19.6%). Tumors with negative enhancement compared with enhanced tumors were associated with lower frequency of tumor progression (32.0% vs 81.8%, respectively) and lower rates of surgical complications (14.0% vs 45.5%, respectively). Tumors with intact lenticulostriate arteries were associated with higher rates of gross-total resection than were tumors with involved lenticulostriate arteries (67.3% vs 11.8%, respectively). Tumors with intact superior extremity of the central insular sulcus were associated with higher rates of gross-total resection (57.4% vs 20.7%, respectively) and lower rates of surgical complications (18.5% vs 41.4%, respectively) than were tumors with involved anatomical structures. Multivariate analysis showed that clear tumor boundaries were independently associated with gross-total resection (p < 0.001). Negative enhancement was found to be independently associated with surgical complications (p = 0.005), overall survival times (p < 0.001), and progression-free survival times (p = 0.004). Independent associations were also found between intact lenticulostriate arteries and gross-total resection (p < 0.001), between intact lenticulostriate arteries and progression-free survival times (p = 0.026), and between intact superior extremity of the central insular sulcus and gross-total resection (p = 0.043). Among patients in whom all 4 indicators were present, prognosis was good (5-year survival rate 93.3%), resection rate was maximal (gross-total resection 100%), and surgical complication rate was minimal (6.7%). Also among these patients, overall rates of survival (p = 0.003) and progression-free survival (p = 0.005) were significantly higher than among patients in whom fewer indicators were present. Conclusions The authors propose 4 simple indicators that can be used to identify ideal candidates for radical resection of insulo-opercular gliomas, improve the outcomes, and promote maximum resection without introducing neurological complications. The indicators are clear tumor boundaries, negative enhancement, intact lenticulostriate arteries, and intact superior extremity of the central insular sulcus.
    Journal of Neurosurgery 08/2014; 121(5):1-9. DOI:10.3171/2014.7.JNS13899 · 3.23 Impact Factor
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    ABSTRACT: Optic pathway cavernous malformations (CMs) are extremely rare, accounting for less than 1 % of all intracranial CMs. We report a case of optic pathway CM mimicking optic glioma because the initial magnetic resonance (MR) images did not disclose hemorrhagic findings such as popcorn-like lesion or hemosiderin ring.
    Child s Nervous System 07/2014; DOI:10.1007/s00381-014-2465-9 · 1.16 Impact Factor
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    ABSTRACT: Intracranial germ cell tumors (iGCTs) are rare in the Western countries, however they are the second most common brain tumors in patients under 14 in Japan. Unlike other common pediatric brain tumors, the biology of iGCTs is largely unknown.
    Neuro-Oncology 07/2014; 16 Suppl 3:iii23. DOI:10.1093/neuonc/nou208.2 · 5.29 Impact Factor
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    ABSTRACT: Glioblastoma carries a poor prognosis primarily because of its high rate of recurrence. Similarly, anaplastic gliomas without IDH mutation present poor prognosis similar to glioblastoma. The ability to predict the recurrence pattern and timing would be highly useful for determining effective treatment strategies. We here examined high grade glioma to determine their recurrence pattern and the expression of CD133, a cell surface marker of glioma stem cells.
    Neuro-Oncology 07/2014; 16 Suppl 3(suppl 3):iii46. DOI:10.1093/neuonc/nou209.18 · 5.29 Impact Factor
  • Neuro-Oncology 2014; 16(Suppl 1): i99-i104. 16th International Symposium on Pediatric Neuro-Oncology., Singapore; 06/2014
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    ABSTRACT: Diagnosis of WHO grade III anaplastic gliomas does not always correspond to its clinical outcome because of the isocitrate dehydrogenase (IDH) gene status. Anaplastic gliomas without IDH mutation result in a poor prognosis, similar to grade IV glioblastomas. However, the malignant features of anaplastic gliomas without IDH mutation are not well understood. The aim of this study was to examine anaplastic gliomas, in particular those without IDH mutation, with regard to their malignant features, recurrence patterns, and association with glioma stem cells.
    Neuro-Oncology 06/2014; 17(1). DOI:10.1093/neuonc/nou112 · 5.29 Impact Factor
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    ABSTRACT: Abstract In cases of malignant brain tumors, infiltrating tumor cells that exist at the tumor-surrounding brain tissue always escape from cytoreductive surgery and, protected by blood-brain barrier (BBB), survive the adjuvant chemoradiotherapy, eventually leading to tumor recurrence. Local interstitial delivery of chemotherapeutic agents is a promising strategy to target these cells. During our effort to develop effective drug delivery methods by intra-tumoral infusion of chemotherapeutic agents, we found consistent pattern of leakage from the tumor. Here we describe our findings and propose promising strategy to cover the brain tissue surrounding the tumor with therapeutic agents by means of convection-enhanced delivery. First, the intracranial tumor isograft model was used to define patterns of leakage from tumor mass after intra-tumoral infusion of the chemotherapeutic agents. Liposomal doxorubicin, although first distributed inside the tumor, distributed diffusely into the surrounding normal brain once the leakage happen. Trypan blue dye was used to evaluate the distribution pattern of peri-tumoral infusions. When infused intra- or peri-tumorally, infusates distributed robustly into the tumor border. Subsequently, volume of distributions with different infusion scheduling; including intra-tumoral infusion, peri-tumoral infusion after tumor resection, peri-tumoral infusion without tumor removal with or without systemic infusion of steroids, were compared with Evans-blue dye. Peri-tumoral infusion without tumor removal resulted in maximum volume of distribution. Prior use of steroids further increased the volume of distribution. Local interstitial drug delivery targeting tumor surrounding brain tissue before tumor removal should be more effective when targeting the invading cells.
    Drug Delivery 05/2014; DOI:10.3109/10717544.2014.914987 · 2.20 Impact Factor
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    ABSTRACT: Although distraction osteogenesis has been widely accepted to treat craniosynostosis, it occasionally results in wound complications. Positing that they are attributable to the tense pericranium under the scalp, we developed a simple technique to relax the pericranial flap. In 12- to 15-month-old infants (mean 13 months), we placed a coronal skin incision and dissected the scalp at the subgaleal layer. Then, we peeled the intact pericranium away from the skull along the planned osteotomy to obtain flaps with pedicles on the caudal part. After osteotomy and setting of the distraction device, the pericranial flaps freed from the scalp flap were repositioned to fit the osteotomy line, dura, and distraction device. The galea and skin were approximated layer by layer. The shape of the skull was successfully corrected, and the bone defect created by expansion was filled by osteogenesis in all patients. During a mean follow-up period of 42.2 months, we encountered no wound complications. The replaced relaxed pericranium closely adhered to the osteotomy, and the distraction device facilitated vascular growth and bone restoration. Bone resorption was prevented and skin expansion promoted. In patients with iatrogenic dural injury, the pericranium over the injured dura serves as a barrier to prevent cerebrospinal fluid leakage.
    Child s Nervous System 05/2014; 30(7). DOI:10.1007/s00381-014-2406-7 · 1.16 Impact Factor

Publication Stats

3k Citations
551.56 Total Impact Points


  • 2013–2015
    • Kitasato University
      Edo, Tōkyō, Japan
    • University of Toronto
      Toronto, Ontario, Canada
  • 2014
    • National Cancer Center, Japan
      Edo, Tōkyō, Japan
  • 1994–2014
    • Tohoku University
      • Department of Neurosurgery
      Sendai-shi, Miyagi, Japan
  • 2005–2013
    • Sendai City Hospital
      Sendai, Kagoshima, Japan
  • 2007
    • Rinku General Medical Center
      Ōsaka, Ōsaka, Japan
  • 1999–2005
    • Kohnan Hospital
      Sendai, Kagoshima, Japan