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田中 一寛医学部附属病院 脳神経外科講師
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■ 受賞- 2020年11月 第38回日本脳腫瘍病理学会, 優秀ポスター賞(第1位), 第三脳室に発生したEWSR1-CREB1融合遺伝子を有する頭蓋内粘液性間葉系腫瘍の1例
- 2015年10月 神戸大学医学研究科教授会, 平成26年度神戸大学医学部優秀学術論文賞 神戸大学医学研究科教授会, Compensatory glutamine metabolism promotes glioblastoma resistance to mTOR inhibitor treatment.その他の賞
- 2014年09月 Asian Society for Neuro-Oncology (ASNO) and Society for Neuro-Oncology (SNO), Best Abstract Award (ASNO-SNO Travel Award), Glutaminase-mediated metabolic pathway involves glioblastoma resistance to mTOR-targeted therapies国際学会・会議・シンポジウム等の賞
- 2011年04月 The 2011 ASCI/AAP Joint Meeting, Travel Award, EGFRvIII-dependent mTORC2 signaling promotes chemotherapy resistance in glioblastoma through NF-kB国際学会・会議・シンポジウム等の賞
- PURPOSE: Tumor morphology critically influences facial nerve (FN) outcomes following vestibular schwannoma (VS) surgery. This study aimed to develop a nomogram based on preoperative features for preoperative prediction of FN outcomes after VS surgery. METHODS: A retrospective analysis included patients with sporadic VS who underwent surgical resection via the retrosigmoid approach. Tumor size was assessed using the Koos grade, the intrameatal components using the fundal fluid cap (FFC) sign, and the cerebellopontine angle cisternal components using our modified morphological subclassification. Logistic regression analysis was performed to construct a nomogram for predicting immediate postoperative FN function. RESULTS: A total of 265 patients with VS met the inclusion criteria. Of these patients, 62 (23.4%) had poor FN function (House-Brackmann grade ≥ III) immediately after surgery. Univariate logistic regression analysis identified the Koos grade (p = 0.001), FFC sign (p = 0.023), and morphological subtype (p < 0.001) as significant predictors of poor FN function immediately after surgery. In multivariate logistic regression analysis, the FFC sign (OR 2.07, p = 0.042) and morphological subtype (OR 8.21, p < 0.001) remained statistically significant independent predictors of poor FN function. A nomogram constructed based on these indicators demonstrated good discrimination in the training cohort (area under the curve [AUC] 0.80), internal validation cohort (AUC 0.79), and external validation cohort (AUC 0.97). CONCLUSIONS: A simple and reliable nomogram incorporating the Koos grade, FFC sign, and morphological subtype accurately predicts the risk of FN injury during surgery aimed at total resection of VS. This clinically straightforward tool can assist in patient counseling and development of more individualized surgical strategies to improve FN outcomes in patients with VS.2025年03月, Journal of neuro-oncology, 英語, 国際誌研究論文(学術雑誌)
- OBJECTIVE: We investigated whether air in the cisterns or ventricles on postoperative computed tomography (CT) (reflecting the opening of the cerebrospinal fluid spaces during surgery) is a predictor of classical or nodular leptomeningeal disease (LMD) after resection of brain metastases. METHODS: We retrospectively analyzed 73 patients who underwent gross total resection of brain metastases between 2012 and 2020. Patients with air in the cisterns or ventricles on postoperative day 1 CT were categorized into the air-positive group, whereas those without air in the cisterns or ventricles on postoperative day 1 CT were categorized into the air-negative group. The primary outcome was the occurrence of classical or nodular LMD (nLMD), which was assessed using survival analysis. RESULTS: There were 15 (21%) patients in the air-positive group and 58 (79%) in the air-negative group. The air-positive group exhibited significantly more cerebellar and ventricular contact lesions than the air-negative group. The 4-year rate of classical or nLMD was significantly higher in the air-positive group than in the air-negative group (67% vs. 33%, P < 0.001). Multivariate analysis identified air in the cisterns or ventricles on postoperative CT as the only significant predictor of classical or nLMD (P < 0.001). CONCLUSIONS: Postoperative air in the cisterns or ventricles can predict early classical or nodular leptomeningeal disease.2024年11月, World neurosurgery, 英語, 国際誌研究論文(学術雑誌)
- BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) with talaporfin sodium is an intraoperative local therapy administered after the surgical removal of malignant gliomas. However, its clinical efficacy in a large patient population has not been determined. To analyze the clinical outcomes and prognosis in isocitrate dehydrogenase (IDH)-wildtype glioblastoma patients treated with PDT. METHODS: This retrospective study included patients with newly diagnosed IDH-wildtype glioblastoma treated at Kobe University Hospital between January 2013 and December 2022. PDT involves irradiation of the resection cavity with a 664-nm semiconductor laser after an intravenous infusion of talaporfin sodium. The main outcome measures were the recurrence patterns and survival times, which were compared between the PDT and non-PDT groups. Univariate and multivariate analyses were used to determine the prognostic factors. In addition, adverse events and prognostic factors in the PDT group were analyzed. RESULTS: A total of 44 and 56 patients were included in the PDT and non-PDT groups, respectively. The local recurrence rate was significantly lower in the PDT group than in the non-PDT group (51.3% vs 83.9%), whereas the distant recurrence and dissemination rates were significantly higher in the PDT group than in the non-PDT group (48.7% vs 16.1%). Two grade 3 adverse events were observed in the PDT group. The median progression-free survival and overall survival times were significantly longer in the PDT group than in the non-PDT group (progression-free survival: 10.8 vs 9.3 months, respectively, and overall survival: 24.6 vs 17.6 months, respectively). Multivariate analysis of the PDT groups revealed that younger age was an independent prognostic factor. CONCLUSION: PDT with talaporfin sodium provided effective local control with minimal adverse effects. The survival time of the patients treated with PDT was significantly longer than that of the patients who did not receive PDT. Therefore, a randomized controlled clinical trial on PDT is warranted.2024年11月, Neurosurgery, 英語, 国際誌研究論文(学術雑誌)
- PURPOSE: To investigate the relationship between the tumor microenvironment (TME), tumor-related seizures (TRS), and cerebrospinal fluid (CSF) markers that predict preoperative seizures in patients with glioblastoma. METHODS: In total, 47 patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma who underwent preoperative CSF examination, 3-T magnetic resonance spectroscopy (MRS), and neurological surgery between January 2017 and December 2023 were included. We measured the concentrations of soluble CD163 (sCD163), a soluble form of the M2 macrophage marker, in the CSF, the metabolite concentration on MRS, and the number of CD163-positive M2 macrophages in the tumor tissue. Factors associated with preoperative seizures were examined. RESULTS: Twelve patients (25.5%) had preoperative seizures. sCD163 levels in the CSF were positively correlated with the number of CD163-positive M2 macrophages in the tumor tissue, and both were significantly lower in the preoperative seizure group than in the non-preoperative seizure group (p = 0.0124 and p < 0.0001, respectively). MRS indicated that only glutathione (GSH) concentrations were higher in the preoperative seizure group than in the non-preoperative seizure group (2.55 mM and 1.87 mM, respectively; p = 0.0171). CD163-positive M2 macrophages were inversely correlated with GSH levels. sCD163 in the CSF had a high predictive accuracy (sensitivity, 91.7%; specificity, 54.3%; and area under the receiver operator curve, 0.745) for preoperative seizures. CONCLUSIONS: The CSF level of sCD163 is useful for predicting the TME and preoperative seizures in IDH wild-type glioblastoma.2024年10月, Journal of neuro-oncology, 英語, 国際誌研究論文(学術雑誌)
- (一社)日本癌治療学会, 2024年10月, 日本癌治療学会学術集会抄録集, 62回, O88 - 5, 英語播種にて発症した転移性脳腫瘍の特徴
- Pencil-beam presaturation (BeamSAT) magnetic resonance imaging (MRI) produces selective magnetic resonance angiography (MRA) images of specific arteries, including the unilateral internal carotid artery (ICA-selective MRA) or vertebral artery (VA-selective MRA). We evaluate the influence of flow pattern, visualized using BeamSAT MRI, on preoperative cerebral hemodynamic status and postoperative hyperperfusion syndrome (HPS). Patients undergoing carotid artery stenting or carotid endarterectomy were categorized into two groups to evaluate flow pattern. Patients with neither crossflow on BeamSAT MRI nor mismatch in middle cerebral artery (MCA) signal intensity between ICA-selective and conventional MRA were classified into Group I, comprising 29 patients. Group II included all other patients comprising 19 patients, who were suspected of experiencing changes in intracranial flow patterns. Cerebral blood flow and cerebrovascular reactivity (CVR) were assessed using single-photon emission computed tomography, and potential HPS symptoms were retrospectively assessed by chart review. Preoperative ipsilateral CVR was significantly lower in Group II than in Group I (18.0% ± 20.0% vs. 48.3% ± 19.5%; P < 0.0001). Group II showed significantly impaired CVR (odds ratio 17.7, 95% confidence interval 1.82-171; P = 0.013) in multivariate analysis. The partial areas under the curve of the BeamSAT logistic model (0.843) were significantly larger than those of the conventional logistic model (0.626) over the range of high sensitivity (0.6-1) (P = 0.04). The incidence of postoperative HPS symptoms was significantly higher in Group II than in Group I (8/19 vs. 1/29; P = 0.001). BeamSAT MRI may be a valuable and non-invasive tool for assessing cerebral hemodynamics and predicting postoperative HPS.2024年08月, Journal of the neurological sciences, 463, 123114 - 123114, 英語, 国際誌研究論文(学術雑誌)
- 日本脳腫瘍病理学会, 2024年05月, Brain Tumor Pathology, 41(Suppl.) (Suppl.), 092 - 092, 日本語画像と病理2 播種にて発症した転移性脳腫瘍の特徴
- 日本脳腫瘍病理学会, 2024年05月, Brain Tumor Pathology, 41(Suppl.) (Suppl.), 093 - 093, 日本語脳腫瘍の分子診断と治療1 Gliosarcoma with primitive neuronal componentに対するアレイCGH解析
- (株)メディカ出版, 2024年05月, 脳神経外科速報, 34(3) (3), e80 - e87, 日本語マイクロバブルテストが原因検索に有用であった心房中隔欠損症による脳膿瘍の1例
- 日本脳腫瘍病理学会, 2024年05月, Brain Tumor Pathology, 41(Suppl.) (Suppl.), 104 - 104, 日本語悪性リンパ腫の診断・治療の現状と展望 Interleukin 10を元に分類した中枢神経原発悪性リンパ腫の網羅的解析
- 日本脳腫瘍病理学会, 2024年05月, Brain Tumor Pathology, 41(Suppl.) (Suppl.), 104 - 104, 日本語悪性リンパ腫の診断・治療の現状と展望 Interleukin 10を元に分類した中枢神経原発悪性リンパ腫の網羅的解析
- BACKGROUND AND OBJECTIVES: Spinal dural arteriovenous fistulas (SDAVFs) lead to progressive neurological decline with symptoms such as paraparesis, bowel and bladder dysfunction, and sensory disturbances because of impaired spinal cord venous drainage. This study aimed to systematically review the literature on multiple synchronous SDAVFs and present 2 cases from our institution. METHODS: A comprehensive search was performed to identify all published cases of multiple synchronous SDAVFs. Overall, 23 patients with multiple synchronous SDAVFs were identified, including 21 from 19 articles and 2 from this study. The clinical presentation, lesion location, radiographic features, surgical treatment, and outcomes were analyzed in each patient. RESULTS: All patients in this study were male, and the duration from symptom onset to diagnosis in many of these patients was longer than that previously reported. Previous studies suggested that multiple SDAVFs typically occurred within 3 or fewer vertebral levels. However, >50% of the examined patients had remote lesions separated by more than 3 vertebral levels. Patients with remote lesions had a significantly worse outcome (1/7 vs 8/11, 95% CI 0.001-0.998; P = .049). CONCLUSION: Accurately locating fistulas before spinal angiography is critical for managing multiple remote SDAVFs. Considering the possibility of multiple remote SDAVFs, careful interpretation of imaging findings is essential for an accurate diagnosis and appropriate treatment planning.2024年04月, Neurosurgery, 英語, 国際誌研究論文(学術雑誌)
- Abstract Background The EF-14 clinical trial demonstrated the safety and efficacy of tumor-treating fields (TTFields) for newly diagnosed glioblastoma. This study aimed to clarify the current status, safety, and efficacy of TTFields in Japanese patients who meet the EF-14 inclusion criteria. Methods This was a multicenter retrospective cohort study. Background, treatment, and outcome data of patients who satisfied the inclusion criteria of the EF-14 trial were collected from 45 institutions across Japan. The rate, determinants, and current status of TTField use, including its safety and efficacy in terms of progression and survival, were retrospectively investigated. This study was conducted in accordance with the STROBE checklist. Results Among the 607 patients enrolled, 70 were excluded due to progressive disease during radiation and temozolomide therapy, age > 80 years old, and Karnofsky Performance Status score of <70. Among the remaining 537 patients, 210 (39%) underwent TTField treatment. Multivariate analysis revealed younger age and spouse as a caregiver as significant factors for TTField use. The compliance rate of TTField use exceeded 75% in 60% of patients, with a median TTField usage duration of 11 months. Skin disorders requiring medical treatment occurred in 56% of patients. Multivariate Cox proportional hazards analysis in the whole series and propensity score-matched analysis revealed that TTField use was not a prognostic factor for progression-free survival (PFS) or overall survival (OS). Conclusions TTField use did not have a substantial effect on either PFS or OS in Japanese patients with glioblastoma, despite compliance rates comparable to those observed in the EF-14.Oxford University Press (OUP), 2024年01月, Neuro-Oncology Advances, 6(1) (1)研究論文(学術雑誌)
- 日本脳腫瘍病理学会, 2023年05月, Brain Tumor Pathology, 40(Suppl.) (Suppl.), 068 - 068, 日本語脳腫瘍診断におけるliquid biopsyの可能性 グリオーマおよび中枢神経悪性リンパ腫患者の髄液中炎症性マーカーと予後
- OBJECTIVE: Carotid stenosis can lead to both cognitive impairment (CI) and ischemic stroke. Although carotid revascularization surgery, which includes carotid endarterectomy (CEA) and carotid artery stenting (CAS), can prevent future strokes, its effect on cognitive function is controversial. In this study, the authors examined resting-state functional connectivity (FC) in carotid stenosis patients with CI undergoing revascularization surgery, with a particular focus on the default mode network (DMN). METHODS: Twenty-seven patients with carotid stenosis who were scheduled to undergo CEA or CAS between April 2016 and December 2020 were prospectively enrolled. A cognitive assessment, including the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and Japanese version of the Montreal Cognitive Assessment (MoCA), as well as resting-state functional MRI, was performed 1 week preoperatively and 3 months postoperatively. For FC analysis, a seed was placed in the region associated with the DMN. The patients were divided into two groups according to the preoperative MoCA score: a normal cognition (NC) group (MoCA score ≥ 26) and a CI group (MoCA score < 26). The difference in cognitive function and FC between the NC and CI groups was investigated first, and then the change in cognitive function and FC after carotid revascularization was investigated in the CI group. RESULTS: There were 11 and 16 patients in the NC and CI groups, respectively. The FC of the medial prefrontal cortex with the precuneus and that of the left lateral parietal cortex (LLP) with the right cerebellum were significantly lower in the CI group than in the NC group. In the CI group, significant improvements were found in MMSE (25.3 vs 26.8, p = 0.02), FAB (14.4 vs 15.6, p = 0.01), and MoCA scores (20.1 vs 23.9, p = 0.0001) after revascularization surgery. Significantly increased FC of the LLP with the right intracalcarine cortex, right lingual gyrus, and precuneus was observed after carotid revascularization. In addition, there was a significant positive correlation between the increased FC of the LLP with the precuneus and improvement in the MoCA score after carotid revascularization. CONCLUSIONS: These findings suggest that carotid revascularization, including CEA and CAS, might improve cognitive function based on brain FC in the DMN in carotid stenosis patients with CI.2023年03月, Journal of neurosurgery, 1 - 8, 英語, 国際誌研究論文(学術雑誌)
- OBJECTIVE: Adult brainstem gliomas (BSGs) are rare tumors of the CNS that are poorly understood. Upregulation of the oncometabolite 2-hydroxyglutarate (2HG) in the tumor indicates the mutation of isocitrate dehydrogenase (IDH), which can be detected by magnetic resonance spectroscopy (MRS). Although histological examination is required for the definitive diagnosis of BSG, 2HG-optimized MRS (2HG-MRS) may be useful, considering the difficult nature of brainstem lesion biopsy. The aim of this study was to evaluate the utility of 2HG-MRS for diagnosing IDH-mutant adult BSG. METHODS: Patients with a radiographically confirmed brainstem tumor underwent 3T MRS. A single voxel was set in the lesion with reference to the T2 or fluid-attenuated inversion recovery image and analyzed according to the 2HG-tailored MRS protocol (point-resolved spectroscopic sequence; echo time 35 msec). All patients underwent intraoperative navigation-guided or CT-guided stereotactic biopsy for histopathological diagnosis. The status of IDH and H3K27M mutations was confirmed by immunohistochemistry and direct DNA sequencing. In addition, the authors examined the relationship between patients' 2HG concentrations and survival time. RESULTS: Ten patients (7 men, 3 women; median age 33.5 years) underwent 2HG-MRS and biopsy. Four patients had an H3K27M mutation and 4 had an IDH1 mutation (1 R132H canonical IDH mutation, 2 R132S and 1 R132G noncanonical IDH mutations). Two had neither H3K27M nor IDH mutations. The H3K27M and IDH mutations were mutually exclusive. Most tumors were located in the pons. There was no significant radiological difference between mutant H3K27M and IDH on a conventional MRI sequence. A 2HG concentration ≥ 1.8 mM on MRS demonstrated 100% (95% CI 28%-100%) sensitivity and 100% (95% CI 42%-100%) specificity for IDH-mutant BSG (p = 0.0048). The median overall survival was 10 months in IDH-wild-type BSG patients (n = 6) and could not be estimated in IDH-mutant BSG patients (n = 4) due to the small number of deaths (p = 0.008). CONCLUSIONS: 2HG-MRS demonstrated high sensitivity and specificity for the prediction of IDH-mutant BSG. In addition, 2HG-MRS may be useful for predicting the prognosis of adult BSG patients.2023年01月, Journal of neurosurgery, 1 - 8, 英語, 国際誌研究論文(学術雑誌)
- BACKGROUND: Excessive glue injection into the drainage vein in patients with dural arteriovenous fistula (dAVF) can result in venous obstruction. We performed transarterial embolization (TAE) combined with transvenous embolization (TVE) with coils to prevent the glue from migrating into the normal cortical veins. CASE DESCRIPTION: A 57-year-old man was pointed out to have a Borden Type III anterior cranial fossa dAVF during a check-up for putaminal hemorrhage. Because a left frontal normal cortical vein drained into the pathological drainage vein, excessive glue injection into the drainage vein may have caused venous obstruction. We performed TVE with coils at the foot of the draining vein to prevent excessive migration of glue into the drainer, followed by TAE with glue. With this technique, complete obliteration of the shunt without venous ischemia was obtained. CONCLUSION: The combined treatment of TAE and TVE is effective in preventing venous ischemia caused by unintended migration of glue cast into the drainage vein.2023年, Surgical neurology international, 14, 277 - 277, 英語, 国際誌
- Ror1 plays a crucial role in cancer progression by regulating cell proliferation and migration. Ror1 is expressed abundantly in various types of cancer cells and cancer stem-like cells. However, the molecular mechanisms regulating expression of Ror1 in these cells remain largely unknown. Ror1 and its putative ligand Wnt5a are expressed highly in malignant gliomas, especially in glioblastomas, and the extents of Ror1 expression are correlated positively with poorer prognosis in patients with gliomas. We show that Ror1 expression can be upregulated in glioblastoma cells under spheroid culture, but not adherent culture conditions. Notch and hypoxia signaling pathways have been shown to be activated in spheroid-forming glioblastoma stem-like cells (GSCs), and Ror1 expression in glioblastoma cells is indeed suppressed by inhibiting either Notch or hypoxia signaling. Meanwhile, either forced expression of the Notch intracellular domain (NICD) in or hypoxic culture of glioblastoma cells result in enhanced expression of Ror1 in the cells. Consistently, we show that both NICD and hypoxia-inducible factor 1 alpha bind to upstream regions within the Ror1 gene more efficiently in GSCs under spheroid culture conditions. Furthermore, we provide evidence indicating that binding of Wnt5a to Ror1, upregulated by Notch and hypoxia signaling pathways in GSCs, might promote their spheroid-forming ability. Collectively, these findings indicate for the first time that Notch and hypoxia signaling pathways can elicit a Wnt5a-Ror1 axis through transcriptional activation of Ror1 in glioblastoma cells, thereby promoting their stem cell-like property.2022年10月, Cancer science, 英語, 国際誌研究論文(学術雑誌)
- (一社)日本癌学会, 2022年09月, 日本癌学会総会記事, 81回, P - 2118, 英語グリオブラストーマ細胞におけるRor1の発現制御とRor1による幹細胞性維持機構の解析(Molecular mechanism regulating expression of Ror1 in GSCs and the role of Ror1 in maintaining their stemness)
- (一社)日本癌学会, 2022年09月, 日本癌学会総会記事, 81回, P - 2047, 英語グリオーマの悪性化におけるRor2-Nrf2シグナル伝達系の重要な役割(Critical role of Ror2-Nrf2 signaling axis in regulating malignant progression of gliomas)
- BACKGROUND: Symptomatic vasospasm (SVS) is a major cause of morbidity and mortality in aneurysmal subarachnoid hemorrhage (SAH), and serum sodium frequently decreases before SVS. Serum sodium changes might be regulated by sodium metabolism-related hormones. This multi-institutional prospective cohort study therefore investigated the measurement of sodium metabolism-related hormones to elucidate the pathophysiology of serum sodium changes in SAH. METHODS: SAH patients were treated with clipping or coiling from September 2017 to August 2020 at five hospitals. The laboratory data of 133 SAH patients were collected over 14 days and correlations between changes in serum sodium, sodium metabolism-related hormones (plasma adrenocorticotropic hormone (ACTH), serum cortisol, plasma arginine vasopressin (AVP)), and SVS were determined. Serum sodium concentrations were measured every day and serum sodium levels >135 mEq/L were maintained until day 14. RESULTS: Of the 133 patients, 18 developed SVS within 14 days of subarachnoid hemorrhage onset (SVS group) and 115 did not suffer from SVS (non-SVS group). Circulating AVP, ACTH, and cortisol concentrations were significantly higher on day 1 in the SVS group compared with the non-SVS group. Fluctuations in serum sodium in the SVS group were significantly higher than those in the non-SVS group. There were antiparallel fluctuations in serum sodium and potassium from days 2 to 14. CONCLUSIONS: Elevated levels of ACTH/cortisol and AVP on day 1 may be predictive markers for the occurrence of SVS. Multiple logistic regression analysis showed that serum sodium fluctuations were associated with SVS occurrence. Serum sodium fluctuations were associated with stress-related hormonal dynamics. (249 words).2022年09月, Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 103, 131 - 140, 英語, 国際誌研究論文(学術雑誌)
- BACKGROUND AND PURPOSE: ICA-selective MRA using a pencil beam presaturation pulse can accurately visualize anterior communicating artery flow. We evaluated the impact of anterior communicating artery flow on the perioperative hemodynamic status and new ischemic lesions after carotid revascularization. MATERIALS AND METHODS: Eighty-three patients with carotid artery stenosis were included. We assessed anterior communicating artery flow using ICA-selective MRA. The preoperative hemodynamic status was measured using SPECT. We also measured the change in regional cerebral oxygen saturation after temporary ICA occlusion. New ischemic lesions were evaluated by DWI on the day after treatment. RESULTS: Anterior communicating artery flow was detected in 61 patients, but it was not detected in 22 patients. Preoperative cerebrovascular reactivity was significantly higher in patients with (versus without) anterior communicating artery flow with a mean peak systolic velocity of ≥200 cm/s (39.6% [SD, 23.8%] versus 25.2% [SD, 16.4%]; P = .030). The decrease in mean regional cerebral oxygen saturation was significantly greater in patients without (versus with) anterior communicating artery flow (8.5% [SD, 5.6%] versus 3.7% [SD, 3.8%]; P = .002). New ischemic lesions after the procedure were observed in 23 patients. The multivariate logistic regression analysis revealed that anterior communicating artery flow (OR, 0.07; 95% CI, 0.012-0.45; P = .005) was associated with new ischemic lesions. CONCLUSIONS: The absence of anterior communicating artery flow influenced the perioperative hemodynamic status in patients with carotid stenosis and was associated with an increased incidence of new ischemic lesions after carotid revascularization.2022年08月, AJNR. American journal of neuroradiology, 43(8) (8), 1124 - 1130, 英語, 国際誌研究論文(学術雑誌)
- Endoplasmic reticulum (ER) stress is an important process during the progression of atherosclerosis. The aim of this study was to elucidate the association of ER stress and clinical instability of carotid plaque. One hundred ninety-three patients with carotid stenosis undergoing carotid endarterectomies (CEAs) were enrolled. We classified the patients into 3 groups: the asymptomatic, symptomatic, and cTIA (crescendo transient ischemic attack)/SIE (stroke in evolution) groups. Immunohistological staining was performed to assess ER stress and apoptosis. The correlation between ER stress marker expression and clinical instability was analyzed by Tukey-Kramer test and ordinal logistic regression. From the 193 CEAs, 24 asymptomatic plaques and 24 symptomatic plaques were randomly selected, and all 7 plaques in the cTIA/SIE group were selected. Glycophorin A staining demonstrated significant correlation between intraplaque hemorrhage and clinical instability (odds ratio [OR], 1.27; 95%CI, 1.14-1.41). The expression of ER stress markers (glucose-regulated protein 78 [GRP78] and C/EBP homologous protein [CHOP]) exhibited a significant correlation with clinical instability (GRP78: OR, 1.25; 95%CI, 1.14-1.38, CHOP: OR, 1.39; 95%CI, 1.16-1.66). Double-label immunofluorescence demonstrated ER stress markers were detected in CD68-positive cells and smooth muscle actin (SMA)-positive cells. The coexpression of the ER stress markers exhibited a significant correlation with clinical instability (CD68/GRP78: OR, 1.13; 95%CI, 1.05-1.20, CD68/CHOP: OR, 1.092; 95%CI, 1.04-1.14, SMA/CHOP: OR, 1.082; 95%CI, 1.04-1.13). However, the colocalization of CHOP and cleaved caspase-3 (apoptosis marker) did not correlate with clinical instability. These findings indicated that the ER stress pathway may be a potential therapeutic target in the prevention of stroke.2022年06月, Translational stroke research, 13(3) (3), 420 - 431, 英語, 国際誌研究論文(学術雑誌)
- 日本脳腫瘍病理学会, 2022年05月, Brain Tumor Pathology, 39(Suppl.) (Suppl.), 063 - 063, 日本語脳腫瘍のsurrogate marker グリオーマおよび中枢神経悪性リンパ腫患者の髄液中炎症性マーカーの比較検討
- 日本脳腫瘍病理学会, 2022年05月, Brain Tumor Pathology, 39(Suppl.) (Suppl.), 088 - 088, 日本語組織診断に難渋した高齢infratentorial IDH-mutant high-grade astrocytomaの1例
- 日本脳腫瘍病理学会, 2022年05月, Brain Tumor Pathology, 39(Suppl.) (Suppl.), 123 - 123, 日本語頭蓋内に多発病変を認めたRosai-Dorfman病の1例
- 日本脳腫瘍病理学会, 2022年05月, Brain Tumor Pathology, 39(Suppl.) (Suppl.), 063 - 063, 日本語脳腫瘍のsurrogate marker グリオーマおよび中枢神経悪性リンパ腫患者の髄液中炎症性マーカーの比較検討
- 日本脳腫瘍病理学会, 2022年05月, Brain Tumor Pathology, 39(Suppl.) (Suppl.), 088 - 088, 日本語組織診断に難渋した高齢infratentorial IDH-mutant high-grade astrocytomaの1例
- 日本脳腫瘍病理学会, 2022年05月, Brain Tumor Pathology, 39(Suppl.) (Suppl.), 123 - 123, 日本語頭蓋内に多発病変を認めたRosai-Dorfman病の1例
- OBJECTIVE: Epilepsy in glioblastoma patients significantly reduces their quality of life; however, little is known about the association between predicting epilepsy and metabolites in tumors. In this study, we used 3.0-T magnetic resonance imaging and 1H-magnetic resonance spectroscopy (MRS) to quantify metabolite concentrations in patients with varying epilepsy histories. METHODS: Fifty-one patients with glioblastoma underwent pretreatment 3.0-T MRI/1H-MRS scanning. Single-voxel (1.5 cm3) MRS, in an enhanced lesion, was acquired using a double-echo point-resolved spectroscopic sequence with chemical-shift selective water suppression. MRS data were quantified with linear combination model (LC-Model) software. We compared the MRS data between groups with and without epilepsy during the postoperative course (EP). RESULTS: The ratios of glutamate (Glu) and glutamate + glutamine (Glx) to total creatine (Glu/tCr and Glx/tCr) in the tumor were associated with epilepsy history. The receiver operating characteristic curve analysis showed that a Glu/tCr value of 1.81 was 70% sensitive and 90% specific for the prediction of EP (area under curve: 0.82). In the analysis excluding patients with preoperative epilepsy, a Glu/tCr value of 1.81 was 75% sensitive and 88% specific for the prediction (area under curve: 0.87). CONCLUSIONS: Intratumoral metabolite concentrations measured using pretreatment 3.0-T MRI/1H-MRS changed characteristically in the group with EP. Our study suggests that the Glu/tCr ratio in tumors has adequate reliability in predicting EP. Pretreatment MRS is a minimally invasive and simple procedure that can provide useful information on glioblastoma patients.2022年04月, World neurosurgery, 160, e501-e510, 英語, 国際誌研究論文(学術雑誌)
- Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are recommended for high stroke-risk patients with carotid artery stenosis to reduce ischemic events. However, we often face difficulty in determining the best treatment strategy. We aimed to develop an accurate post-CEA/CAS outcome prediction model using machine learning that will serve as a basis for a new decision support tool for patient-specific treatment planning. Retrospectively collected data from 165 consecutive patients with carotid stenosis underwent CEA or CAS and were divided into training and test samples. The following five machine learning algorithms were tuned, and their predictive performance was evaluated by comparison with surgeon predictions: an artificial neural network, logistic regression, support vector machine, random forest, and extreme gradient boosting (XGBoost). Seventeen clinical factors were introduced into the models. Outcome was defined as any ischemic stroke within 30 days after treatment including asymptomatic diffusion-weighted imaging abnormalities. The XGBoost model performed the best in the evaluation; its sensitivity, specificity, positive predictive value, and accuracy were 31.9%, 94.6%, 47.2%, and 86.2%, respectively. These statistical measures were comparable to those of surgeons. Internal carotid artery peak systolic velocity, low-density lipoprotein cholesterol, and procedure (CEA or CAS) were the most contributing factors according to the XGBoost algorithm. We were able to develop a post-procedural outcome prediction model comparable to surgeons in performance. The accurate outcome prediction model will make it possible to make a more appropriate patient-specific selection of CEA or CAS for the treatment of carotid artery stenosis.2022年02月, Neurosurgical review, 45(1) (1), 607 - 616, 英語, 国際誌研究論文(学術雑誌)
- PURPOSE: Photodynamic therapy (PDT) subsequent to surgical tumor removal is a novel localized treatment for malignant glioma that provides effective local control. The acute response of malignant glioma to PDT can be detected as linear transient hyperintense signal on diffusion-weighted imaging (DWI) and a decline in apparent diffusion coefficient values without symptoms. However, their long-term clinical significance has not yet been examined. The aim of this study was to clarify the link between hyperintense signal on DWI as an acute response and recurrence after PDT in malignant glioma. METHODS: Thirty patients (16 men; median age, 60.5 years) underwent PDT for malignant glioma at our institution between 2017 and 2020. We analyzed the signal changes on DWI after PDT and the relationship between these findings and the recurrence pattern. RESULTS: All patients showed linear hyperintense signal on DWI at the surface of the resected cavity from day 1 after PDT. These changes disappeared in about 30 days without any neurological deterioration. During a mean post-PDT follow-up of 14.3 months, 19 patients (63%) exhibited recurrence: 10 local, 1 distant, and 8 disseminated. All of the local recurrences arose from areas that did not show hyperintense signal on DWI obtained on day 1 after PDT. CONCLUSIONS: The local recurrence in malignant glioma after PDT occurs in an area without hyperintense signal on DWI as an acute response to PDT. This characteristic finding could aid in the monitoring of local recurrence after PDT.2021年09月, Journal of neuro-oncology, 英語, 国際誌研究論文(学術雑誌)
- Fast-growing tumors satisfy their bioenergetic needs by supplementing glucose with alternative carbon sources. Cancer stem cells are the most versatile and robust cells within malignant tumors. They avoid potentially lethal metabolic and other types of stress through flexible reprogramming of relevant pathways, but it has remained unclear whether alternative carbon sources are important for the maintenance of their tumor-propagating ability. Here we assessed the ability of glycolytic and oxidative murine glioma stem cells (GSCs) to grow in an ultralow glucose medium. Sphere formation assays revealed that exogenous lactate and acetate reversed the growth impairment of oxidative GSCs in such medium. Extracellular flux analysis showed that lactate supported oxygen consumption in these cells, whereas metabolomics analysis revealed that it increased the intracellular levels of tricarboxylic acid cycle intermediates, ATP, and GTP as well as increased adenylate and guanylate charge. Lactate also reversed the depletion of choline apparent in the glucose-deprived cells as well as reprogrammed phospholipid and fatty acid biosynthesis. This metabolic reprogramming was associated with a more aggressive phenotype of intracranial tumors formed by lactate-treated GSCs. Our results thus suggest that lactate is an important alternative energetic and biosynthetic substrate for oxidative GSCs, and that it sustains their growth under conditions of glucose deprivation.2021年05月, Metabolites, 11(5) (5), 英語, 国際誌研究論文(学術雑誌)
- OBJECTIVE: The T2-FLAIR mismatch sign is a useful imaging sign in clinical magnetic resonance imaging studies for detecting isocitrate dehydrogenase (IDH)-mutant 1p/19q non-codeleted astrocytomas. However, the association between the mismatch sign and pathologic findings is poorly understood. Therefore, the aim of this study was to elucidate the relationship of histopathologic and radiologic features with the mismatch sign in IDH-mutant 1p/19q non-codeleted astrocytomas. METHODS: We divided 17 IDH-mutant 1p/19q non-codeleted patients into 2 groups according to mismatch sign presence (WITH, n = 9; WITHOUT, n = 8) and retrospectively analyzed their pathologic findings and apparent diffusion coefficient (ADC) values. We also compared these findings between the tumor Core (central area) and Rim (marginal area). RESULTS: In the pathologic analysis, Core of the WITH group contained numerous microcysts whereas Rim had abundant neuroglial fibrils and cellularity. In contrast, Core of the WITHOUT group had highly concentrated neuroglial fibrils. In ADC analysis, Core of the WITH group had significantly higher ADC values compared with Rim (P < 0.001). However, there was no significant difference between Core and Rim in the WITHOUT group (P = 0.12). The WITH group had a significantly higher Core/Rim ratio of ADC values compared with the WITHOUT group (P < 0.001). CONCLUSIONS: This study provides evidence that a region-dependent microstructural difference could reflect the mismatch sign in IDH-mutant 1p/19q non-codeleted astrocytomas. Core of the mismatch sign characteristically had microcystic changes accompanied by higher ADC values, whereas Rim had abundant neuroglial fibrils and cellularity accompanied by lower ADC values.2021年05月, World neurosurgery, 149, e253-e260, 英語, 国際誌研究論文(学術雑誌)
- 日本脳腫瘍病理学会, 2021年05月, Brain Tumor Pathology, 38(Suppl.) (Suppl.), 060 - 060, 日本語脳腫瘍遺伝子異常の画像診断 MR Spectroscopyを用いた2HG測定による成人脳幹グリオーマの遺伝子診断
- 日本脳腫瘍病理学会, 2021年05月, Brain Tumor Pathology, 38(Suppl.) (Suppl.), 067 - 067, 日本語癌ゲノム医療 神戸大学医学部附属病院におけるがんゲノム医療の現状と課題
- 日本脳腫瘍病理学会, 2021年05月, Brain Tumor Pathology, 38(Suppl.) (Suppl.), 086 - 086, 日本語グリオーマと栄養飢餓環境 グルタミン飢餓におけるセリン合成と一炭素代謝の調整
- Intracranial vessel dissection is a procedural complication associated with endovascular treatment. However, there have been few reports on its potential causes and management during mechanical thrombectomy. In approximately 250 cases of mechanical thrombectomy over the past 5 years at our institution, iatrogenic intracranial dissection occurred in 2 patients (0.8%). In this report, we described these 2 cases that were rescued through emergent stenting. Mechanical thrombectomy, using both a stent retriever and an aspiration catheter, was performed for acute middle cerebral artery M2 occlusion in Patient 1 (a 69-year-old man) and for distal M1 occlusion in Patient 2 (an 83-year-old woman). In both cases, recanalization was achieved with the procedure, but irregular stenosis developed at the initially nonoccluded, but mildly arteriosclerotic, M1, after recanalization. During the thrombectomy procedure, the aspiration catheter sifted up to the arteriosclerotic M1. In both cases, the lesions were considered vessel dissection, due to a shift of the aspiration catheter tip into the arteriosclerotic vessel wall. Repeated percutaneous angiography with antithrombotic therapy failed to improve the lesions and to maintain the antegrade blood flow. Finally, lesions in each patient were successfully rescued through the use of emergent stenting. A drug-eluting stent for coronary use was deployed in Patient 1, and an Enterprise stent was applied in Patient 2. Inadvertent shift of the aspiration catheter into arteriosclerotic vessels can cause a serious intracranial vessel dissection. When performing mechanical thrombectomy, intracranial stents need to be available as rescue treatment devices to manage refractory iatrogenic intracranial vessel dissection.2021年04月, Radiology case reports, 16(4) (4), 835 - 842, 英語, 国際誌
- Springer Science and Business Media LLC, 2021年01月, Acta Neuropathologica Communications, 9(1) (1), 16, 英語, 国際誌
Abstract Cancer cells optimize nutrient utilization to supply energetic and biosynthetic pathways. This metabolic process also includes redox maintenance and epigenetic regulation through nucleic acid and protein methylation, which enhance tumorigenicity and clinical resistance. However, less is known about how cancer cells exhibit metabolic flexibility to sustain cell growth and survival from nutrient starvation. Here, we find that serine and glycine levels were higher in low-nutrient regions of tumors in glioblastoma multiforme (GBM) patients than they were in other regions. Metabolic and functional studies in GBM cells demonstrated that serine availability and one-carbon metabolism support glioma cell survival following glutamine deprivation. Serine synthesis was mediated through autophagy rather than glycolysis. Gene expression analysis identified upregulation of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) to regulate one-carbon metabolism. In clinical samples, MTHFD2 expression was highest in the nutrient-poor areas around “pseudopalisading necrosis.” Genetic suppression of MTHFD2 and autophagy inhibition caused tumor cell death and growth inhibition of glioma cells upon glutamine deprivation. These results highlight a critical role for serine-dependent one-carbon metabolism in surviving glutamine starvation and suggest new therapeutic targets for glioma cells adapting to a low-nutrient microenvironment.[査読有り]研究論文(学術雑誌) - The ketogenic diet (KD) is a high fat and low carbohydrate diet that produces ketone bodies through imitation of starvation. The combination of KD and Bevacizumab (Bev), a VEGF inhibitor, is considered to further reduce the supply of glucose to the tumor. The metabolite changes in U87 glioblastoma mouse models treated with KD and/or Bev were examined using gas chromatography-mass spectrometry. The combination therapy of KD and Bev showed a decrease in the rate of tumor growth and an increase in the survival time of mice, although KD alone did not have survival benefit. In the metabolome analysis, the pattern of changes for most amino acids are similar between tumor and brain tissues, however, some amino acids such as aspartic acid and glutamic acid were different between tumors and brain tissues. The KD enhanced the anti-tumor efficacy of Bev in a glioblastoma intracranial implantation mouse model, based on lowest levels of microvascular density (CD31) and cellular proliferation markers (Ki-67 and CCND1) in KD + Bev tumors compared to the other groups. These results suggested that KD combined with Bev may be a useful treatment strategy for patients with GBM.2021年01月, Scientific reports, 11(1) (1), 79 - 79, 英語, 国際誌研究論文(学術雑誌)
- Japanese Congress of Neurological Surgeons, 2021年, Japanese Journal of Neurosurgery, 30(5) (5), 380 - 390, 日本語研究論文(学術雑誌)
- BACKGROUND: Cerebrospinal fluid (CSF) cytology and spinal MR imaging are routinely performed for staging before treatment of intracranial germinoma. However, the interpretation of the results of CSF cytology poses 2 unresolved clinical questions: (1) Does positive CSF cytology correlate with the presence of spinal lesion before treatment? and (2) Is craniospinal irradiation (CSI) necessary for patients with positive CSF cytology in the absence of spinal lesion? METHODS: Multicenter retrospective analyses were performed based on a questionnaire on clinical features, spinal MR imaging finding, results of CSF cytology, treatments, and outcomes which was sent to 86 neurosurgical and 35 pediatrics departments in Japan. Pretreatment frequencies of spinal lesion on MR imaging were compared between the patients with positive and negative cytology. Progression-free survival (PFS) rates were compared between patients with positive CSF cytology without spinal lesion on MR imaging treated with CSI and with whole brain or whole ventricular irradiation (non-CSI). RESULTS: A total of 92 germinoma patients from 45 institutes were evaluated by both CSF cytology and spinal MR images, but 26 patients were excluded because of tumor markers, the timing of CSF sampling or incomplete estimation of spinal lesion. Of the remaining 66 germinoma patients, spinal lesions were equally identified in patients with negative CSF cytology and positive cytology (4.9% and 8.0%, respectively). Eleven patients treated with non-CSI had excellent PFS comparable to 11 patients treated with CSI. CONCLUSION: CSI is unnecessary for germinoma patients with positive CSF cytology without spinal lesions on MR imaging.2021年, Neuro-oncology advances, 3(1) (1), vdab086, 英語, 国際誌研究論文(学術雑誌)
- TERT promoter mutations are commonly associated with 1p/19q codeletion in IDH-mutated gliomas. However, whether these mutations have an impact on patient survival independent of 1p/19q codeletion is unknown. In this study, we investigated the impact of TERT promoter mutations on survival in IDH-mutated glioma cases. Detailed clinical information and molecular status data were collected for a cohort of 560 adult patients with IDH-mutated gliomas. Among these patients, 279 had both TERT promoter mutation and 1p/19q codeletion, while 30 had either TERT promoter mutation (n = 24) or 1p/19q codeletion (n = 6) alone. A univariable Cox proportional hazard analysis for survival using clinical and genetic factors indicated that a Karnofsky performance status score (KPS) of 90 or 100, WHO grade II or III, TERT promoter mutation, 1p/19q codeletion, radiation therapy, and extent of resection (90-100%) were associated with favorable prognosis (p < 0.05). A multivariable Cox regression model revealed that TERT promoter mutation had a significantly favorable prognostic impact (hazard ratio = 0.421, p = 0.049), while 1p/19q codeletion did not have a significant impact (hazard ratio = 0.648, p = 0.349). Analyses incorporating patient clinical and genetic information were further conducted to identify subgroups showing the favorable prognostic impact of TERT promoter mutation. Among the grade II-III glioma patients with a KPS score of 90 or 100, those with IDH-TERT co-mutation and intact 1p/19q (n = 17) showed significantly longer survival than those with IDH mutation, wild-type TERT, and intact 1p/19q (n = 185) (5-year overall survival, 94% and 77%, respectively; p = 0.032). Our results demonstrate that TERT promoter mutation predicts favorable prognosis independent of 1p/19q codeletion in IDH-mutated gliomas. Combined with its adverse effect on survival among IDH-wild glioma cases, the bivalent prognostic impact of TERT promoter mutation may help further refine the molecular diagnosis and prognostication of diffuse gliomas.2020年11月, Acta neuropathologica communications, 8(1) (1), 201 - 201, 英語, 国際誌研究論文(学術雑誌)
- Elsevier Inc., 2020年10月, Annals of Vascular Surgery, 68, 572 - 572.e14, 英語研究論文(学術雑誌)
- (一社)日本癌治療学会, 2020年10月, 日本癌治療学会学術集会抄録集, 58回, O70 - 6, 英語悪性脳腫瘍に対する光線力学療法の現状と課題
- 日本脳腫瘍病理学会, 2020年08月, Brain Tumor Pathology, 37(Suppl.) (Suppl.), 128 - 128, 日本語第三脳室に発生したEWSR1-CREB1融合遺伝子を有する頭蓋内粘液性間葉系腫瘍の1例
- Elsevier Ltd, 2020年05月, Heliyon, 6(5) (5), 英語研究論文(学術雑誌)
- Tumor biopsy is essential for the definitive diagnosis of central nervous system (CNS) lymphoma. However, the biopsy procedure carries the risk of complications such as bleeding, convulsions, and infection. Cerebrospinal fluid (CSF) β2-microglobulin (β2-MG), soluble IL-2 receptor (sIL-2R), and interleukin-10 (IL-10) are known to be useful diagnostic biomarkers for CNS lymphoma. The C-X-C motif chemokine ligand 13 (CXCL13) was recently reported to be another useful biomarker for CNS lymphoma. The purpose of this study is to establish a diagnostic algorithm that can avoid biopsy by combining these diagnostic biomarkers. In the first, we conducted a case-control study (n = 248) demonstrating that the CSF CXCL13 concentration was significantly increased in CNS lymphoma patients compared with various other brain diseases (AUC = 0.981). We established a multi-marker diagnostic model using CSF CXCL13, IL-10, β2-MG, and sIL-2R from the results of the case-control study and then applied the model to a prospective study (n = 104) to evaluate its utility. The multi-marker diagnostic algorithms had excellent diagnostic performance: the sensitivity, specificity, positive predictive value, and negative predictive value were 97%, 97%, 94%, and 99%, respectively. In addition, CSF CXCL13 was a prognostic biomarker for CNS lymphoma patients. Our study suggests that multi-marker algorithms are important diagnostic tools for patients with CNS lymphoma.2020年04月, Cancer medicine, 英語, 国際誌[査読有り]
- Intracranial myxoid mesenchymal tumors harboring EWSR1 fusions with CREB transcriptional factor gene families were recently described in several case reports and a few case series and this tumor closely resembles the myxoid variant of angiomatoid fibrous histiocytoma. We herein present an intracranial mesenchymal myxoid tumor arising in the third ventricle of a middle-aged woman. The tumor displayed prominent myxoid features consisting of mildly atypical oval to round cells, arranged in reticular and cord-like structures, with starburst-like amianthoid fibers, whereas it lacked pseudoangiomatoid spaces, pseudocapsules and lymphoid cuffing. Immunophenotypically, tumor cells were positive for EMA, desmin, and ALK (focal). EWSR1 and CREB1 rearrangements were identified using FISH assay. The proliferation index was low. It is currently uncertain whether these myxoid tumors represent a variant of angiomatoid fibrous histiocytoma or a novel tumor entity.2020年03月, Brain tumor pathology, 英語, 国内誌[査読有り]
- BACKGROUND: Few studies have examined the usefulness of intraoperative magnetic resonance spectroscopy (iMRS) for identifying abnormal signals at the resection margin during glioma surgery. The aim of this study was to assess the value of iMRS for detecting proliferative remnants of glioma at the resection margin. METHODS: Fifteen patients with newly diagnosed glioma underwent single-voxel 3-T iMRS concurrently with intraoperative magnetic resonance imaging-assisted surgery. Volumes of interest (VOIs) were placed at T2-hyperintense or contrast-enhancing lesions at the resection margin. In addition to technical verification, the correlation between the MIB-1 labeling index (a pathologic feature) and metabolites measured using iMRS (N-acetyl-L-aspartate [NAA], choline [Cho], and Cho/NAA ratio) was analyzed. RESULTS: iMRS was performed for 20 VOIs in 15 patients. Fourteen (70%) of these VOIs were confirmed to be MIB-1-positive. There was a significant positive correlation between the Cho/NAA ratio and MIB-1 index (r = 0.46, P = 0.04). Cho level (P = 0.003) and Cho/NAA ratio (P = 0.002) were significantly higher in VOIs that were MIB-1-positive than in those that were MIB-1-negative. Detection of a Cho level >1.074 mM and a Cho/NAA ratio >0.48 using iMRS resulted in high diagnostic accuracy for MIB-1-positive remnants (Cho level: sensitivity 86%, specificity 100%; Cho/NAA ratio: sensitivity 79%, specificity 100%). CONCLUSIONS: This study provides evidence that 3-T iMRS can detect proliferative remnants of glioma at the resection margin using the Cho level and Cho/NAA ratio, suggesting that intraoperative magnetic resonance imaging-assisted surgery with iMRS would be practicable in glioma.2020年02月, World neurosurgery, 137, 149 - 157, 英語, 国際誌[査読有り]
- BACKGROUND AND PURPOSE: Photodynamic therapy is a novel treatment that provides effective local control, but little is known about photodynamic therapy-induced changes on MR imaging. The aim of this study was to assess the utility of DWI and ADC in monitoring the response of malignant gliomas to photodynamic therapy. MATERIALS AND METHODS: Time-dependent changes in DWI and ADC values after photodynamic therapy were analyzed in a group that received photodynamic therapy in comparison with a group that did not. RESULTS: Twenty-four patients were enrolled (photodynamic therapy, n = 14; non-photodynamic therapy, n = 10). In all patients who received photodynamic therapy, linear high signals on DWI in the irradiated area were detected adjacent to the resection cavity and were 5-7 mm in depth from 1 day posttreatment and disappeared in about 30 days without any neurologic deterioration. The non-photodynamic therapy group did not show this change. The photodynamic therapy group had significantly lower ADC values from 1 day posttreatment (P < .001), which increased steadily and disappeared by 30 days. There was no decline or time-dependent change in ADC values in the non-photodynamic therapy group. CONCLUSIONS: The acute response of malignant gliomas to photodynamic therapy was detected as linear high signals on DWI and as a decrease in ADC values. These findings were asymptomatic and transient. Although the photodynamic therapy-induced acute response on MR imaging disappeared after approximately 30 days, it may be helpful for confirming the photodynamic therapy-irradiated area.American Society of Neuroradiology (ASNR), 2019年11月, American Journal of Neuroradiology, 40(12) (12), 2045 - 2051, 英語, 国際誌研究論文(学術雑誌)
- (NPO)日本脳神経血管内治療学会, 2019年11月, 脳血管内治療, 4(Suppl.) (Suppl.), S212 - S212, 日本語AIの機械学習で頸動脈狭窄症治療後早期の転帰を予測する 実臨床での応用[査読有り]
- (一社)日本癌治療学会, 2019年10月, 日本癌治療学会学術集会抄録集, 57回, P53 - 7, 英語初発中枢神経悪性リンパ腫(PCNSL)に対するR-MPV療法の安全性と有用性について
- 2019年10月, J Clin Neurosci, 68, 281 - 289, 英語[査読有り]研究論文(学術雑誌)
- (一社)日本脳卒中学会, 2019年05月, 脳卒中, 41(3) (3), 177 - 181, 日本語
- 2019年04月, Journal of neuro-oncology, 142(2) (2), 241 - 251[査読有り]
- Japan Stroke Society, 2019年, Japanese Journal of Stroke, 41(3) (3), 177 - 181研究論文(学術雑誌)
- Elsevier BV, 2018年12月, World Neurosurg, 18, 32910 - 32913, 英語[査読有り]研究論文(学術雑誌)
- The 2007 World Health Organization Classification of Tumors of the Central Nervous System (CNS) categorized embryonal tumors of the CNS into three classes: medulloblastoma, CNS primitive neuroectodermal tumor, and atypical teratoid/rhabdoid tumor. Due to the lack of specific histological features, it was sometimes difficult to accurately differentiate CNS embryonal tumors pathologically. Here, we report a case of a young man, who presented with headache. Gadolinium-enhanced magnetic resonance imaging demonstrated massive lesions in the cerebrospinal fluid space, which strongly suggested leptomeningeal dissemination of a brain tumor. The histology showed the tumor comprised densely packed, small cells with scant cytoplasm. Immunoreactivities were positive for synaptophysin and chromogranin A, and negative for glial fibrillary acidic protein, S-100, EMA, and CD20. Because the tumors were located in multiple sites and most of them were within the cerebrospinal fluid space, the primary lesion could not be determined. We diagnosed this case as 'CNS primitive neuroectodermal tumor' by the patient age and predominantly supratentorial distribution of the lesions. After the induction therapy, WHO published its updated classification in 2016. Considering the possibility that the diagnosis is medulloblastoma, we performed additional immunohistochemical analyses, and diagnosed Group 3 medulloblastoma because of the expression of natriuretic peptide receptor 3.2018年08月, Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 54, 125 - 128, 英語, 国際誌[査読有り]
- 近畿脳腫瘍病理検討会, 2018年08月, Neuro-Oncologyの進歩, 25(2) (2), 8 - 18, 日本語グリオーマにおけるマイクロRNAの役割[査読有り]研究論文(学術雑誌)
- Molecular mechanism underlying ischemic stroke remains poorly understood. We previously reported glucose 6-phosphate dehydrogenase (G6PD) activity in pentose phosphate pathway (PPP) is activated via heat shock protein 27 (HSP27) phosphorylation at serine 85 (S85) by ataxia telangiectasia mutated (ATM) kinase during cerebral ischemia. This mechanism seems to be endogenous antioxidative system. To determine whether this system also works during reperfusion, we performed comparative metabolic analysis of reperfusion effect on metabolism in rat cortex using middle cerebral artery occlusion (MCAO). Metabolic profiling using gas-chromatography/mass-spectrometry analysis showed changes in metabolic state that depended on reperfusion time. Enrichment analysis showed PPP was significantly upregulated during ischemia-reperfusion. Significant increases in fructose 6-phosphate and ribulose 5-phosphate after reperfusion also suggested enhancement of PPP. In relation to PPP, ischemia-reperfusion induced an increase of up to 69-fold in HSP27 transcripts after 24-h reperfusion. Immunoblotting showed gradual increase in HSP27 protein and marked increase in HSP27 phosphorylation (S85) that were time-dependent (4.5-fold after 24-h reperfusion). G6PD activity was significantly elevated after 1-h MCAO (20%), reduced after 1-h reperfusion, increased gradually thereafter and significantly elevated after 24-h reperfusion. The NADPH/NAD+ ratio displayed similar increasing pattern. Intracerebroventricular injection of ATM kinase inhibitor (KU-55933) significantly reduced HSP27 phosphorylation and G6PD activity, significantly increased protein carbonyl, and resulted in increase in infarct size (100%) 24-h after reperfusion following 90-min MCAO. Consequently, G6PD activation via HSP27 phosphorylation by ATM kinase may be part of endogenous antioxidant defense neuroprotection mechanism that is activated during ischemia-reperfusion. These findings have important implications for treatment of stroke.2018年05月, Brain research, 1687, 82 - 94, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- 一般社団法人 日本機械学会, 2018年, 年次大会, 2018, K02100, 日本語
- It is sometimes difficult to distinguish gliomas from other tumors on routine imaging. In this study, we assessed whether 3-T magnetic resonance spectroscopy (MRS) with LCModel software might be useful for discriminating glioma from other brain tumors, such as primary central nervous system lymphomas (PCNSLs) and metastatic tumors. A total of 104 cases of brain tumor (66 gliomas, 20 PCNSLs, 6 metastatic tumors, 12 other tumors) were preoperatively investigated with short echo time (35 ms) single-voxel 3-T MRS. LCModel software was used to evaluate differences in the absolute concentrations of choline, N-acetylaspartate, N-acetylaspartylglutamate, glutamate + glutamine, myo-inositol (mIns), and lipid. mIns levels were significantly increased in high-grade glioma (HGG) compared with PCNSL (p < 0.001). In multivariate logistic regression analysis, mIns was the best marker for differentiating HGG from PCNSL (p < 0.0001, odds ratio 1.9927, 95% confidence interval 1.3628-3.2637). Conventional MRS detection of mIns resulted in a high diagnostic accuracy (sensitivity, 64%; specificity, 90%; area under the receiver operator curve, 0.80) for HGG. The expression of inositol 3-phosphate synthase (ISYNA1) was significantly higher in gliomas than in PCNSLs (p < 0.05), suggesting that the increased level of mIns in glioma is due to high expression of ISYNA1, the rate-limiting enzyme in the mIns-producing pathway. In conclusion, noninvasive analysis of mIns using single-voxel MRS may be useful in distinguishing gliomas from other brain tumors, particularly PCNSLs.2018年01月, Journal of neuro-oncology, 136(2) (2), 317 - 326, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- 2017年12月, JOURNAL OF STROKE & CEREBROVASCULAR DISEASES, 26(12) (12), 2793 - 2799, 英語[査読有り]研究論文(学術雑誌)
- 2017年08月, Neuroscience, 357, 414 - 414, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- BACKGROUND: Magnetic resonance spectroscopy (MRS) is a potentially useful modality for evaluating brain metabolites in patients with dural arteriovenous fistula (dAVF). Here we describe a different pattern of MRS-based cerebral metabolism findings in patients with dAVF. CASE DESCRIPTIONS: We performed MRS in 3 patients with transverse sigmoid sinus dAVF associated with cortical venous reflux. In case 1, which was associated with vasogenic edema on T2-weighted magnetic resonance imaging (MRI), decreased preoperative N-acetylaspartate (NAA)/creatine (Cr) and myo-inositol (mIns)/Cr and increased lactate (Lac)/Cr ratios improved after treatment. In case 2, a decreased preoperative NAA/Cr ratio improved after treatment. These 2 patients presented with seizures. In case 3, the patient presented with headache and showed no metabolic changes on preoperative or postoperative MRS. CONCLUSIONS: Our results suggest that patients with dAVF can be classified based on a combination of metabolic and signal changes seen on T2-weighted MRI. MRS may allow significantly expanded evaluation of the metabolic changes associated with dAVF for appropriate classification and management.2017年08月, World neurosurgery, 104, 1050.e7-1050.e11, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- The metabolic pathophysiology underlying ischemic stroke remains poorly understood. To gain insight into these mechanisms, we performed a comparative metabolic and transcriptional analysis of the effects of cerebral ischemia on the metabolism of the cerebral cortex using middle cerebral artery occlusion (MCAO) rat model. Metabolic profiling by gas-chromatography/mass-spectrometry analysis showed clear separation between the ischemia and control group. The decreases of fructose 6-phosphate and ribulose 5-phosphate suggested enhancement of the pentose phosphate pathway (PPP) during cerebral ischemia (120-min MCAO) without reperfusion. Transcriptional profiling by microarray hybridization indicated that the Toll-like receptor and mitogen-activated protein kinase (MAPK) signaling pathways were upregulated during cerebral ischemia without reperfusion. In relation to the PPP, upregulation of heat shock protein 27 (HSP27) was observed in the MAPK signaling pathway and was confirmed through real-time polymerase chain reaction. Immunoblotting showed a slight increase in HSP27 protein expression and a marked increase in HSP27 phosphorylation at serine 85 after 60-min and 120-min MCAO without reperfusion. Corresponding upregulation of glucose 6-phosphate dehydrogenase (G6PD) activity and an increase in the NADPH/NAD+ ratio were also observed after 120-min MCAO. Furthermore, intracerebroventricular injection of ataxia telangiectasia mutated (ATM) kinase inhibitor (KU-55933) significantly reduced HSP27 phosphorylation and G6PD upregulation after MCAO, but that of protein kinase D inhibitor (CID755673) did not affect HSP27 phosphorylation. Consequently, G6PD activation via ischemia-induced HSP27 phosphorylation by ATM kinase may be part of an endogenous antioxidant defense neuroprotection mechanism during the earliest stages of ischemia. These findings have important therapeutic implications for the treatment of stroke.2017年05月, Neuroscience, 349, 1 - 16, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- Urban and Partner, 2017年05月, Neurologia i Neurochirurgia Polska, 51(3) (3), 247 - 251, 英語[査読有り]研究論文(学術雑誌)
- 2017年03月, NEUROLOGIA MEDICO-CHIRURGICA, 57(3) (3), 128 - 135, 英語[査読有り]研究論文(学術雑誌)
- 公立豊岡病院, 2017年03月, 公立豊岡病院紀要, (28) (28), 1 - 5, 日本語ドクターヘリにより広域をカバーする公立豊岡病院における急性期脳梗塞に対する取り組み 血管内治療導入による予後改善効果[査読有り]
- 2017年02月, Eur J Dermatol, 英語Hypothalamic-pituitary germinoma presenting as generalized hypohidrosis[査読有り]研究論文(学術雑誌)
- 2017年02月, Acta neuropathologica, 133(2) (2), 321 - 324, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- Igaku-Shoin Ltd, 2016年12月, Neurological Surgery, 44(12) (12), 1019 - 1023, 日本語Association of deep venous thrombosis with D-dimer values in patients with hemorrhagic stroke研究論文(学術雑誌)
- 2016年12月, Neurological Surgery, 44(12号) (12号), 1019 - 1023, 日本語研究 出血性脳卒中における深部静脈血栓症とDダイマー値の関連性[査読有り]研究論文(学術雑誌)
- 2016年11月, Neuro-oncology, 18(11) (11), 1559 - 1568, 英語[査読有り]
- 2016年09月, JOURNAL OF CLINICAL NEUROSCIENCE, 31, 188 - 192, 英語[査読有り]研究論文(学術雑誌)
- Increased tumor-associated macrophages (TAMs) have been reported to be associated with poor prognosis in various tumors; however, the importance of TAMs in primary central nervous system lymphoma (PCNSL) has not been clarified. In 47 patients with PCNSL who were treated with high-dose methotrexate (MTX) and radiotherapy, the relationships between the infiltration levels of TAMs and the clinicopathological parameters were analyzed. Univariate analysis of the Cox proportional hazards model using continuous scales revealed that increased CD68 positive (+) TAMs was significantly associated with inferior progression-free survival (PFS) (P = 0.04), and trends were observed for the increased CD163(+) TAMs and having shorter PFS (P = 0.05). However, increased TAMs were not associated with overall survival. Because TAMs are known to produce various cytokines, we examined the relationships between cerebrospinal fluid (CSF) cytokines and TAMs. CSF interleukin-6 (IL-6) and soluble IL-2 receptor were not correlated with the infiltration rate of TAMs; however, CSF IL-10 level was correlated with infiltration levels of CD68 and CD163(+) TAMs. We also confirmed the expression of IL-10 in CD68(+) and CD163(+) TAMs by double immunostaining analysis. Our results indicate that a high level of IL-10 in CSF may be positively associated with the infiltration level of TAMs in PCNSLs.2016年07月, Brain pathology (Zurich, Switzerland), 26(4) (4), 479 - 87, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- 2016年05月, Brain Tumor Pathology, 33(Suppl.) (Suppl.), 137, 日本語頭蓋外転移を呈したgliosarcomaの一例[査読有り]研究論文(学術雑誌)
- 2016年05月, Brain Tumor Pathology, 33(Suppl.) (Suppl.), 112, 日本語中枢神経原発悪性リンパ腫(PCNSL)での腫瘍関連マクロファージ浸潤と臨床学的解析[査読有り]研究論文(学術雑誌)
- AIMS: Primary central nervous system lymphoma (PCNSL) manifest aggressive clinical behaviour and have poor prognosis. Although constitutive activation of the nuclear factor-κB (NF-κB) pathway has been documented, knowledge about the genetic alterations leading to the impairment of the NF-κB pathway in PCNSLs is still limited. This study was aimed to unravel the underlying genetic profiles of PCNSL. METHODS: We conducted the systematic sequencing of 21 genes relevant to the NF-κB signalling network for 71 PCNSLs as well as the pyrosequencing of CD79B and MYD88 mutation hotspots in a further 35 PCNSLs and 46 glioblastomas (GBMs) for validation. RESULTS: The results showed that 68 out of 71 PCNSLs had mutations in the NF-κB gene network, most commonly affecting CD79B (83%), MYD88 (76%), TBL1XR1 (23%), PRDM1 (20%) and CREBBP1 (20%). These mutations, particularly CD79B and MYD88, frequently coincided within each tumour in various combinations, simultaneously affecting diverse pathways within the network. No GBMs had hotspot mutation of CD79B Y196 and MYD88 L265. CONCLUSIONS: The prevalence of CD79B and MYD88 mutations in PCNSLs was considerably higher than reported in systemic diffuse large B-cell lymphomas. This observation could reflect the paucity of antigen stimuli from the immune system in the central nervous system (CNS) and the necessity to substitute them by the constitutive activation of CD79B and MYD88 that would initiate the signalling cascades. These hotspot mutations may serve as a genetic hallmark for PCNSL serving as a genetic marker for diagnose and potential targets for molecular therapy.2016年04月, Neuropathology and applied neurobiology, 42(3) (3), 279 - 90, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- BACKGROUND: Although the usefulness of susceptibility-weighted imaging (SWI) for detecting basal ganglia germinoma has been reported, the technique is not widely used. We recently encountered an unusual case of primary cerebellar germinoma, presenting with progressive ataxia and cranial nerve palsy, characterized by gradually enlarging low-intensity lesions visible with both T2*-weighted imaging (T2*WI), which were the key to the diagnosis. CASE PRESENTATION: A 30-year-old man was referred to our hospital because of slowly progressive dizziness and mild ataxia. Magnetic resonance imaging (MRI) revealed a small, low-intensity spot in the left cerebellar peduncle on the T2*WI and SWI without enhancement. Cerebral angiography revealed no vascular abnormality. The serum α-fetoprotein value was normal. A steroid-pulse was administered as a therapeutic and diagnostic trial, but the symptoms improved little. The patient was discharged from the hospital but soon developed brainstem dysfunction, characterized by dyspnea or hiccups, and he was readmitted. T2*WI imaging revealed expanded and extended spotty lesions in the cerebellum and brainstem, which had not enhanced with contrast agent previously. Targeted stereotactic biopsy of the newly enhanced cerebellar lesion was performed; histopathological examination of the tissue revealed pure germinoma. Serum and cerebral spinal fluid values of beta-human chorionic gonadotropin were not significantly elevated. Chemotherapy with carboplatin and etoposide was initiated. The enhanced lesion disappeared promptly, but the patient continued to require assisted automatic ventilation because of paralysis of respiratory muscles. CONCLUSIONS: We conclude that enlarging low-intensity lesions on T2*WI and SWI may be a reliable clue to the diagnosis of germinomas, irrespective of their location, even without enhancement. Biopsy of the tumor at an early stage is the only way to make the diagnosis conclusively and enable prompt start of treatment.2016年01月, BMC neurology, 16(1) (1), 4 - 4, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- OBJECTIVE: The management of low-grade glioma (LGG) still remains controversial because the effectiveness of early and extensive resection is unclear, and the use of radiation therapy or chemotherapy is not well-defined. In particular, the importance of prognostic factors for survival remains a matter of discussion. The purpose of this study was to validate prognostic factors for survival in patients with LGG. MATERIALS AND METHODS: A consecutive series of 55 patients with WHO grade II LGG treated in our institute between 1983 and 2013 were retrospectively reviewed to determine the prognostic factors for survival. All data were retrospectively analyzed from the aspect of baseline characteristics, pathological findings, genetic change, surgical treatments, adjuvant therapies, and survival time. Cox multivariate analysis was performed to determine the prognostic factors for survival. RESULTS: There were 28 patients with diffuse astrocytoma (DA), 21 patients with oligodendroglioma (OG), and 6 patients with oligoastrocytoma (OA) diagnosed on initial surgery. The median overall survival was 193 months and fifteen patients (27.3%) died. A mutation in isocitrate dehydrogenase-1 (IDH1) was found in 72.9% of LGG, and this mutation was positively correlated with methylation of O6-methylguanine-DNA methyltransferase (MGMT) (p=0.02). A better prognosis was significantly associated with combined IDH1 mutation and MGMT methylation status (both positive vs both negative, HR 0.079 [95% CI 0.008-0.579], p=0.012), as well as histology (OG vs DA and OA, HR 0.158 [95% CI 0.022-0.674], p=0.011) and tumor size (<6 cm vs ≥6 cm, HR 0.120 [95% CI 0.017-0.595], p=0.008). CONCLUSIONS: Tumor histology, size and IDH-mutation status are important predictors for prolonged overall survival in patients with LGG and may provide a reliable tool for standardizing future treatment strategies.2015年11月, Clinical neurology and neurosurgery, 138, 37 - 44, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- 2015年09月, JOURNAL OF NEURO-ONCOLOGY, 124(2) (2), 165 - 174, 英語[査読有り]研究論文(学術雑誌)
- 2015年07月, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 112(30) (30), 9406 - 9411, 英語[査読有り]研究論文(学術雑誌)
- 2015年07月, BRAIN PATHOLOGY, 25(4) (4), 509 - 510, 英語[査読有り]研究論文(学術雑誌)
- 2015年04月, J Clin Invest, 125(4) (4), 1591 - 602, 英語[査読有り]研究論文(学術雑誌)
- 2015年04月, Neurological Surgery, 43(4号) (4号), 344 - 351, 日本語局所放射線治療後に頭蓋内主幹動脈狭窄による脳梗塞を呈した成人神経膠腫の2例[査読有り]研究論文(学術雑誌)
- American Society for Clinical Investigation, 2015年04月, The Journal of clinical investigation, 125(4) (4), 1591 - 1602[査読有り]研究論文(学術雑誌)
- Radiation-induced vasculopathy is a complication of radiation therapy. Most reports regarding post-irradiation ischemic stroke with intracranial tumors are restricted to pediatric cases. Here we report two adult cases of delayed brain infarction due to anterior and middle cerebral artery stenosis or occlusion seemingly caused by focal radiation therapy for malignant glioma. Although radiation-induced ischemic stroke in adults is relatively uncommon, it is possible that the morbidity rate of radiation-induced stroke in malignant glioma patients will increase with prolonged survival due to advances in therapy. Therefore, regular evaluation of intracranial vasculature following radiation therapy is necessary.2015年04月, No shinkei geka. Neurological surgery, 43(4) (4), 344 - 51, 日本語, 国内誌[査読有り]研究論文(学術雑誌)
- 2015年, NEUROLOGIA I NEUROCHIRURGIA POLSKA, 49(6) (6), 446 - 450, 英語[査読有り]研究論文(学術雑誌)
- Here, we describe an extremely rare case of angiosarcoma arising in schwannoma of the cerebellopontine angle and later associating with meningioma in a patient with neurofibromatosis type 2. A 33-year-old disabled Japanese man with right drop foot after surgery for an unspecified tumor demonstrated multiple tumors, suspected to be schwannoma, in the bilateral cerebellopontine angles, the cervical and lumbar spinal cord, and on the right nuchal skin. Also present were several tumors in the medulla and thoracic spinal cord suspected to be ependymoma or astrocytoma. The patient was diagnosed with neurofibromatosis type 2 according to the diagnostic criteria by the U.S. National Institutes of Health. The bilateral tumors in the cerebellopontine angle were resected to reduce symptoms and brain stem compression. Histopathological analysis revealed angiosarcoma arising in schwannoma of the bilateral tumors, and angiosarcoma was proportionally larger in the right tumor than in the left. At age 36, the patient underwent a second resection of the regrown tumor in the left cerebellopontine angle, and histopathology demonstrated mixed angiosarcoma and meningioma. That angiosarcoma arises in schwannoma is a pathogenesis within the realm of conjecture, especially that the phenomenon of mixed meningioma and angiosarcoma has not been reported to date.2014年10月, Brain tumor pathology, 31(4) (4), 293 - 8, 英語, 国内誌[査読有り]研究論文(学術雑誌)
- 2014年05月, Brain Tumor Pathology, 31(Suppl.) (Suppl.), 140, 日本語脱髄疾患を合併するCastleman症候群を呈したChordoid meningiomaの1例研究論文(その他学術会議資料等)
- 2014年05月, Brain Tumor Pathology, 31(Suppl.) (Suppl.), 150, 日本語早期に悪性転化を来したgranular cell astrocytomaの1例[査読有り]研究論文(その他学術会議資料等)
- 2014年05月, Brain Tumor Pathology, 31(Suppl.) (Suppl.), 080, 日本語脊髄播種・転移を起こした膠芽腫のマイクロRNA発現に関する検討[査読有り]研究論文(その他学術会議資料等)
- 2014年05月, Brain Tumor Pathology, 31(Suppl.) (Suppl.), 133, 日本語耳下腺、下顎部に転移を起こしたsecondary glioblastomaの1例研究論文(その他学術会議資料等)
- 2014年05月, NEURO-ONCOLOGY, 16(5) (5), 728 - 734, 英語[査読有り]研究論文(学術雑誌)
- BACKGROUND: We compared the diagnostic yield and morbidity by frame-based computed tomography-guided stereotactic biopsy (CTSTB) with Brown-Roberts-Wells (BRW) unit and by neuronavigation-guided frameless stereotactic biopsy (NSTB) using magnetic resonance imaging (MRI). METHODS: The subjects' age range was 15-83 years. CTSTB with BRW unit was performed for 59 tumors (58 cases, 1988-2007). NSTB was performed for 38 tumors (35 cases, 2007-2013) with the needle sheath attached to the head holder. By NSTB, target locations of sampling points and trajectories were confirmed by using MRI. Diffusion tensor imaging-based fiber tractography was used to achieve safe trajectories. STB by using BRW did not visualize the trajectory virtually; however, the planning images for NSTB were able to show the trajectory virtually before the procedure. RESULTS: Histological diagnoses were established for 93 tumors at the first biopsy. The diagnostic yield was 94.9% by CTSTB and 97.4% by NSTB (P = 0.944). The morbidity rate was 5.1% by CTSTB and 0% by NSTB (P = 0.417). The absolute risk reduction was 23.1% by NSTB when the targets were basal ganglia (putamen, globus pallidus) or thalamus. In the cases of glioma for which the targets were basal ganglia (putamen, globus pallidus) or thalamus, the absolute risk reduction by NSTB was 30%. CONCLUSIONS: There was no significant difference between CTSTB and NSTB concerning the diagnostic yield and morbidity. However, when the target is the basal ganglia (putamen, globus pallidus) or thalamus and glioma is suspected, NSTB by using MRI with virtual trajectory is preferable to CTSTB concerning morbidity.2014年, Surgical neurology international, 5(Suppl 8) (Suppl 8), S421-6 - 6, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- 日本定位・機能神経外科学会事務局, 2013年12月, 機能的脳神経外科, 52, 161 - 165, 日本語バクロフェン髄注療法による治療に難渋した脳性麻痺の1例[査読有り]研究論文(学術雑誌)
- Aerobic glycolysis (the Warburg effect) is a core hallmark of cancer, but the molecular mechanisms underlying it remain unclear. Here, we identify an unexpected central role for mTORC2 in cancer metabolic reprogramming where it controls glycolytic metabolism by ultimately regulating the cellular level of c-Myc. We show that mTORC2 promotes inactivating phosphorylation of class IIa histone deacetylases, which leads to the acetylation of FoxO1 and FoxO3, and this in turn releases c-Myc from a suppressive miR-34c-dependent network. These central features of activated mTORC2 signaling, acetylated FoxO, and c-Myc levels are highly intercorrelated in clinical samples and with shorter survival of GBM patients. These results identify a specific, Akt-independent role for mTORC2 in regulating glycolytic metabolism in cancer.2013年11月, Cell Metab, 18(5) (5), 726 - 39, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- 2013年10月, CLINICAL CANCER RESEARCH, 19(20) (20), 5722 - 5732, 英語[査読有り]研究論文(学術雑誌)
- 2013年06月, NEUROPATHOLOGY, 33(3) (3), 299 - 305, 英語[査読有り]研究論文(学術雑誌)
- 2013年06月, CELL METABOLISM, 17(6) (6), 1000 - 1008, 英語[査読有り]研究論文(学術雑誌)
- 2013年05月, NEURORADIOLOGY, 55(5) (5), 615 - 620, 英語[査読有り]研究論文(学術雑誌)
- 2013年05月, JOURNAL OF NEURO-ONCOLOGY, 113(1) (1), 65 - 74, 英語[査読有り]研究論文(学術雑誌)
- UNLABELLED: Acquired resistance to tyrosine kinase inhibitors (TKI) represents a major challenge for personalized cancer therapy. Multiple genetic mechanisms of acquired TKI resistance have been identified in several types of human cancer. However, the possibility that cancer cells may also evade treatment by co-opting physiologically regulated receptors has not been addressed. Here, we show the first example of this alternate mechanism in brain tumors by showing that EGF receptor (EGFR)-mutant glioblastomas (GBMs) evade EGFR TKIs by transcriptionally de-repressing platelet-derived growth factor receptor β (PDGFRβ). Mechanistic studies show that EGFRvIII signaling actively suppresses PDGFRβ transcription in an mTORC1- and extracellular signal-regulated kinase-dependent manner. Genetic or pharmacologic inhibition of oncogenic EGFR renders GBMs dependent on the consequently de-repressed PDGFRβ signaling for growth and survival. Importantly, combined inhibition of EGFR and PDGFRβ signaling potently suppresses tumor growth in vivo. These data identify a novel, nongenetic TKI resistance mechanism in brain tumors and provide compelling rationale for combination therapy. SIGNIFICANCE: These results provide the fi rst clinical and biologic evidence for receptor tyrosinekinase (RTK) "switching" as a mechanism of resistance to EGFR inhibitors in GBM and provide a molecular explanation of how tumors can become "addicted" to a non amplified, nonmutated, physiologically regulated RTK to evade targeted treatment.2013年05月, Cancer Discov, 3(5) (5), 534 - 47, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- MicroRNAs (miRs) are small, non-coding RNAs that regulate gene expression and contribute to cell proliferation, differentiation and metabolism. Our previous study revealed the extensive modulation of a set of miRs in malignant glioma. In that study, miR microarray analysis demonstrated the upregulation of microRNA-183 (miR-183) in glioblastomas. Therefore, we examined the expression levels of miR-183 in various types of gliomas and the association of miR-183 with isocitrate dehydrogenase 2 (IDH2), which has complementary sequences to miR-183 in its 3'-untranslated region (3'UTR). In present study, we used real-time PCR analysis to demonstrate that miR-183 is upregulated in the majority of high-grade gliomas and glioma cell lines compared with peripheral, non-tumorous brain tissue. The mRNA and protein expression levels of IDH2 are downregulated via the overexpression of miR-183 mimic RNA in glioma cells. Additionally, IDH2 mRNA expression is upregulated in glioma cells expressing anti-miR-183. We verified that miR-183 directly affects IDH2 mRNA levels in glioma cells using luciferase assays. In malignant glioma specimens, the expression levels of IDH2 were lower in tumors than in the peripheral, non-tumorous brain tissues. HIF-1α levels were upregulated in glioma cells following transfection with miR-183 mimic RNA or IDH2 siRNA. Moreover, vascular endothelial growth factor and glucose transporter 1, which are downstream molecules of HIF-1α, were upregulated in cells transfected with miR-183 mimic RNA. These results suggest that miR-183 upregulation in malignant gliomas induces HIF-1α expression by targeting IDH2 and may play a role in glioma biology.2013年02月, J Neurooncol, 111(3) (3), 273 - 83, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- 2012年08月, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 109(35) (35), 14164 - 14169, 英語[査読有り]研究論文(学術雑誌)
- 2012年06月, SCIENCE TRANSLATIONAL MEDICINE, 4(139) (139), 139ra84, 英語[査読有り]研究論文(学術雑誌)
- 日本脳腫瘍病理学会, 2012年05月, Brain Tumor Pathology, 29(Suppl.) (Suppl.), 184 - 184, 日本語頭蓋内び漫性大細胞性Bリンパ腫における髄液中IL-10値とB細胞分化マーカーとの関連性研究論文(その他学術会議資料等)
- 日本脳腫瘍病理学会, 2012年05月, Brain Tumor Pathology, 29(Suppl.) (Suppl.), 209 - 209, 日本語悪性グリオーマにおけるIDH2およびHIF-1α発現とマイクロRNAによる発現制御研究論文(その他学術会議資料等)
- 日本脳腫瘍病理学会, 2012年05月, Brain Tumor Pathology, 29(Suppl.) (Suppl.), 195 - 195, 日本語Primary leptomeningeal sarcomatosisと考えられた1症例[査読有り]研究論文(その他学術会議資料等)
- 2011年11月, Cancer Discov, 1(6) (6), 524 - 538, 英語[査読有り]研究論文(学術雑誌)
- 2011年10月, CANCER DISCOVERY, 1(5) (5), 442 - 456, 英語[査読有り]研究論文(学術雑誌)
- 2010年04月, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 107(14) (14), 6459 - 6464, 英語[査読有り]研究論文(学術雑誌)
- 2009年, Neurologia Medico-Chirurgica, 49(11) (11), 532 - 535, 英語, 国内誌[査読有り]研究論文(学術雑誌)
- 2008年07月, Journal of neuro-oncology, 88(3) (3), 315-320 - 320[査読有り]研究論文(学術雑誌)
- Trans-4-lodo,4'-boranyl-chalcone induces antitumor activity against malignant glioma cell lines in vitro and in vivo.Chalcones are considered the precursors of flavonoids and have been identified as interesting compounds with antitumor properties. Boronic-chalcone derivatives are more toxic to breast cancer cells compared to normal breast cells. Here, we studied the antitumor activities of trans-4-lodo,4'-boranyl-chalcone (TLBC), which is a boronic-chalcone derivative, in several glioma cell lines. TLBC showed a dose-dependent inhibition with inhibitory concentration 50% value in the muM range (5.5-25.5 microM) in various glioma cell lines. Flow cytometric and western blot assay demonstrated that TLBC induced apoptosis independent of changes to the tumor suppressor p53. This cytotoxic effect was the caspase-dependent manner. Also, TLBC lowered levels of anti-apoptotic Bcl-2 and/or Bcl-X(L) protein in several of the cell lines. To examine the antitumor effect of TLBC in vivo, we used a malignant glioma xenograft model. This result showed that in the mice treated with TLBC at 20 mg/kg, mean tumor volume was reduced by 43.9% (P < 0.01) in comparison with the control group. Immunohistochemical and western blot analysis showed that Bcl-2 protein levels were decreased and Bax protein levels were slightly increased in the tumors injected with 20 mg/kg TLBC compared with the control tumors. Therefore, we conclude that TLBC may be a potential chemotherapeutic agent for human glioma.2007年11月, Journal of neuro-oncology, 85(2) (2), 123 - 32, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- Specific mTOR inhibitor rapamycin enhances cytotoxicity induced by alkylating agent 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) in human U251 malignant glioma cells.Loss of the PTEN tumor suppressor gene and amplification of the epidermal growth factor receptor (EGFR), which is common in malignant gliomas, result in activation of the mammalian target of rapamycin (mTOR). Rapamycin is a highly specific inhibitor of mTOR and induces a cytostatic effect in various glioma cell lines. DNA-damaging agents such as nitrosourea are widely used in malignant glioma treatment; therefore, we investigated the effect of rapamycin on cell growth and death in combination with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU, nimustine hydrochloride) in human glioma cells. In U251 malignant glioma (U251MG) cells, we confirmed that rapamycin enhanced ACNU-induced apoptosis. We found that rapamysin inhibited ACNU-induced p21 induction, and knocking down of p21 protein by siRNA enhanced ACNU-induced apoptosis in U251MG cells. Furthermore, adenovirus-mediated over-expression of p21 protein rescued U251MG cells from apoptosis induced by ACNU and rapamycin. Finally, treatment of intracerebral U251MG xenografts with a combination of rapamycin and ACNU in vivo resulted in statistically prolonged median survival (P<0.05). These results suggest that rapamycin in combination with DNA-damaging agents may be efficacious in the treatment of malignant gliomas.2007年09月, Journal of neuro-oncology, 84(3) (3), 233 - 44, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- Delayed onset massive oedema and deterioration in traumatic brain injury.A 52-year-old man fell from standing and a computed tomography (CT) scan revealed traumatic intracerebral haematoma and subarachnoid haemorrhage in the temporal cortex. He was treated without surgery and discharged. On day 30 after the accident, he had no neurological deficit. On day 37 he complained of headache and urinary incontinence, and on day 39 he was hospitalized due to progressive neurological deterioration (reduced conciousness, dilated pupils, and left hemiplegia). A CT scan revealed a diffuse low-density in the right cerebral hemisphere with marked midline shift. Emergency decompressive craniectomy and right temporal lobectomy were performed. Angiography after surgery revealed moderate vasospasm in the right middle and anterior cerebral arteries. The patient remained severely disabled. Delayed onset neurological deterioration can be caused by brain oedema and vasospasm after traumatic brain injury, despite an intervening period of improvement.2007年02月, Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 14(2) (2), 167 - 70, 英語, 国際誌[査読有り]
- Synthetic Smac peptide enhances the effect of etoposide-induced apoptosis in human glioblastoma cell lines.Smac/DIABLO is a mitochondrial protein released into cytosol during the progression of apoptosis. Smac/DIABLO promotes apoptosis by neutralizing the inhibitory effect of the inhibitor of apoptosis proteins (IAPs) on the processing and activity of the effecter of caspase. Here, we generated synthetic Smac peptide which possesses an IAP-binding domain and Drosophila antennapaedia penetration sequence, and examined whether it enhances the effect of the chemotherapeutic agent etoposide in the human glioblastoma cell line. Cellular uptake of Smac peptide in several glioma cell lines was most prominent at 6-12 h after addition. Caspase activity assay showed that our peptide successfully increased the activity of caspase-3 and caspase-9 in etoposide-induced apoptosis. In addition, Smac peptide increased the amount of cleaved PARP (poly ADP-ribose polymerase), but control peptides did not. Moreover, the addition of z-VAD-fmk, a caspase inhibitor, counterbalanced the effect of Smac peptide. Finally, we demonstrated that Smac peptide could enhance the growth inhibition effect of etoposide compared with control peptides. These results suggest that synthetic Smac peptide may be a new molecular targeting anti-tumor therapy for human glioblastoma.2006年05月, Journal of neuro-oncology, 77(3) (3), 247 - 55, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- Isolated oculomotor nerve paresis in anaplastic astrocytoma with exophytic invasion.A 30-year-old man presented with a supratentorial malignant glioma manifesting as isolated progressive left oculomotor nerve paresis. Computed tomography and magnetic resonance imaging showed an intra-axial tumor in the left temporal lobe, extending to the basal and prepontine cisterns, and compressing the brainstem. The tumor was removed subtotally. The histological diagnosis was anaplastic astrocytoma. Malignant glioma with exophytic growth in the temporal lobe should be considered in the differential diagnosis of isolated oculomotor nerve paresis.2006年04月, Neurologia medico-chirurgica, 46(4) (4), 198 - 201, 英語, 国内誌[査読有り]研究論文(学術雑誌)
- (公財)田附興風会医学研究所北野病院, 2005年12月, 北野病院紀要, 49-50, 48 - 51, 日本語動眼神経麻痺のみを初発症状とした退形成性星細胞腫の一例[査読有り]研究論文(学術雑誌)
- 2005年, Neurosurgery, Vol. 56, No. 2, pp. 214-223, 214 - 223, 英語[査読有り]研究論文(学術雑誌)
- 2004年05月, 脳神経外科ジャーナル, 13巻, 5号, pp. 395-400, 日本語外頸動脈から栄養血管を認めた小脳悪性神経膠腫の1例[査読有り]研究論文(学術雑誌)
- 2004年02月, 脳血管攣縮, 19巻, , pp. 95-99, 日本語塩酸ファスジル動注療法における問題点(第3報)[査読有り]研究論文(学術雑誌)
- 2024年, 日本分子脳神経外科学会プログラム・抄録集, 24thカルベノキソロンの脳虚血再灌流障害に対する保護効果の検証
- 2024年, 日本分子脳神経外科学会プログラム・抄録集, 24th公開データを用いた頚動脈プラークのシングルセルRNA-seq解析
- 2024年, Brain Tumor Pathology. Supplement, 41Gliosarcoma with primitive neuronal componentに対するアレイCGH解析
- 2021年11月, NEURO-ONCOLOGY, 23, 131 - 131, 英語2-HYDROXYGLUTARATE MAGNETIC RESONANCE SPECTROSCOPY IN ADULT BRAINSTEM GLIOMA PATIENTS研究発表ペーパー・要旨(国際会議)
- 2021年11月, NEURO-ONCOLOGY, 23, 202 - 202, 英語GLIOMA CELLS REPROGRAM SERINE-DEPENDENT ONE-CARBON METABOLISM TO SURVIVE GLUTAMINE STARVATION研究発表ペーパー・要旨(国際会議)
- 2021年, 日本分子脳神経外科学会プログラム・抄録集, 21stポリ(ADP-リボース)グリコヒドロラーゼ阻害はNAD+を隔離し,IDH変異腫瘍細胞におけるアルキル化化学療法の代謝致死性を増強する
- 2021年, 日本癌学会学術総会抄録集(Web), 80thPARG阻害はNAD+を隔離し,IDH変異腫瘍細胞におけるアルキル化化学療法の代謝致死性を増強する
- 2021年, 日本癌学会学術総会抄録集(Web), 80th膠芽腫に対するVEGF阻害剤とケトン食療法併用の有用性
- 2021年, 日本癌学会学術総会抄録集(Web), 80thグルタミン飢餓環境にあるグリオーマ細胞のセリン合成と一炭素代謝の調整
- 2021年, 日本脳腫瘍の外科学会プログラム・抄録集, 26th膠芽腫摘出術での脳室開放は播種を促進するか?
- 2019年11月, NEURO-ONCOLOGY, 21, 164 - 164, 英語THE RELATION BETWEEN T2-FLAIR MISMATCH SIGN AND ADC VALUES REFLECTING PATHOLOGICAL MICROSTRUCTURE IN LOWER-GRADE GLIOMAS研究発表ペーパー・要旨(国際会議)
- 2019年11月, NEURO-ONCOLOGY, 21, 153 - 153, 英語MULTIPLE BIOMARKER ALGORITHM BASED ON CXCL13, IL-10, IL-2 RECEPTOR, AND beta 2-MICROGLOBULIN IN CEREBROSPINAL FLUID TO DIAGNOSE CENTRAL NERVOUS SYSTEM LYMPHOMA研究発表ペーパー・要旨(国際会議)
- (NPO)日本脳神経血管内治療学会, 2019年11月, 脳血管内治療, 4(Suppl.) (Suppl.), S212 - S212, 日本語AIの機械学習で頸動脈狭窄症治療後早期の転帰を予測する 実臨床での応用
- 日本脳腫瘍病理学会, 2019年05月, Brain Tumor Pathology, 36(Suppl.) (Suppl.), 075 - 075, 日本語小児松果体部low grade gliomanの1例
- 日本脳腫瘍病理学会, 2019年05月, Brain Tumor Pathology, 36(Suppl.) (Suppl.), 117 - 117, 日本語Gliosarcoma with primitive neuronal componentの1例
- 日本脳腫瘍病理学会, 2019年05月, Brain Tumor Pathology, 36(Suppl.) (Suppl.), 119 - 119, 日本語若年者に発生した鞍上部high-grade small cell gliomaの一例
- 2018年11月, NEURO-ONCOLOGY, 20, 34 - 34, 英語GLUTAMINE DEPRIVATION ALTERS ONE-CARBON METABOLISM TO MAINTAIN GLIOMA CELL SURVIVAL研究発表ペーパー・要旨(国際会議)
- (NPO)日本脳神経血管内治療学会, 2018年11月, 脳血管内治療, 3(Suppl.) (Suppl.), S115 - S115, 日本語AIの機械学習を用いて頸動脈狭窄症の治療後転帰を予測する
- (NPO)日本脳神経血管内治療学会, 2018年11月, 脳血管内治療, 3(Suppl.) (Suppl.), S133 - S133, 日本語動脈硬化性頸部内頸動脈急性閉塞に対する血管内再開通療法
- (NPO)日本脳神経血管内治療学会, 2018年11月, 脳血管内治療, 3(Suppl.) (Suppl.), S142 - S142, 日本語ステント型血栓回収機器の展開時血管撮影所見による再開通および閉塞機序の予測
- (一社)日本癌治療学会, 2018年10月, 日本癌治療学会学術集会抄録集, 56回, O55 - 5, 英語悪性脳腫瘍に対する光線力学療法(PDT)の治療経験 PDTの照射の問題点とコツ
- (NPO)日本レーザー医学会, 2018年09月, 日本レーザー医学会誌, 39(3) (3), 250 - 250, 日本語悪性脳腫瘍に対する光線力学療法(PDT)の治療経験
- 日本脳腫瘍病理学会, 2018年09月, Brain Tumor Pathology, 35(Suppl.) (Suppl.), 139 - 139, 日本語膠芽腫内腫瘍関連マクロファージが膠芽腫細胞に与える影響
- 日本脳腫瘍病理学会, 2018年09月, Brain Tumor Pathology, 35(Suppl.) (Suppl.), 168 - 168, 日本語グリア成分に増殖能亢進と核分裂像増加が見られたRosette-forming glioneuronal tumorの1例
- 日本脳腫瘍病理学会, 2018年09月, Brain Tumor Pathology, 35(Suppl.) (Suppl.), 176 - 176, 日本語頭蓋内lymphomatoid granulomatosisの1例
- 2017年11月, NEURO-ONCOLOGY, 19, 136 - 137, 英語SURVIVAL BENEFIT OF ANTIEPILEPTIC DRUGS IN PATIENTS WITH GLIOBLASTOMA研究発表ペーパー・要旨(国際会議)
- 2017年11月, NEURO-ONCOLOGY, 19, 238 - 238, 英語INTRAOPERATIVE MAGNETIC RESONANCE SPECTROSCOPY (iMRS) FOR GLIOMA SURGERY研究発表ペーパー・要旨(国際会議)
- (NPO)日本脳神経血管内治療学会, 2017年11月, 脳血管内治療, 2(Suppl.) (Suppl.), S127 - S127, 日本語広域医療圏での急性脳主幹動脈閉塞治療におけるドクターヘリの有用性
- (一社)日本癌治療学会, 2017年10月, 日本癌治療学会学術集会抄録集, 55回, O2 - 4, 日本語初発PCNSLに対するリツキシマブ併用大量メトトレキセート療法の有用性について
- John Libbey Eurotext, 2017年05月01日, European Journal of Dermatology, 27(3) (3), 297 - 299, 英語速報,短報,研究ノート等(学術雑誌)
- 日本脳腫瘍病理学会, 2017年05月, Brain Tumor Pathology, 34(Suppl.) (Suppl.), 087 - 087, 日本語左側頭葉に巨大シストを有する膠芽腫の1例
- 日本脳腫瘍病理学会, 2017年05月, Brain Tumor Pathology, 34(Suppl.) (Suppl.), 110 - 110, 日本語長期生存膠芽腫患者の臨床像と病理学的検討
- 日本脳腫瘍病理学会, 2017年05月, Brain Tumor Pathology, 34(Suppl.) (Suppl.), 125 - 125, 日本語Rosette-forming glioneuronal tumor(RGNT)の2症例
- 日本脳腫瘍病理学会, 2017年05月, Brain Tumor Pathology, 34(Suppl.) (Suppl.), 130 - 130, 日本語Glioblastoma with PNET-like componentsの初期病理像を確認できた1例
- 日本脳腫瘍病理学会, 2017年05月, Brain Tumor Pathology, 34(Suppl.) (Suppl.), 139 - 139, 日本語治療なく自然寛解と増悪を認めた中枢神経原発悪性リンパ腫の2例
- (地独)神戸市民病院機構, 2017年03月, 神戸市立病院紀要, (55) (55), 105 - 105, 日本語IDH変異とマイクロRNA異常 IDH変異によるグリオーマ発生メカニズムの解析
- (地独)神戸市民病院機構, 2017年03月, 神戸市立病院紀要, (55) (55), 104 - 104, 日本語メタボローム解析を用いたグリオーマにおける新規バイオマーカーの探索
- (NPO)日本脳神経外科救急学会, 2017年02月, Neurosurgical Emergency, 21(3) (3), 301 - 301, 日本語脳梗塞に対する急性期治療の現状と展望 ドクターヘリにより広大な僻地をカバーする当施設での急性期脳梗塞に対する血管内再開通療法の導入と課題
- 近畿脳腫瘍病理検討会, 2017年02月, Neuro-Oncologyの進歩, 23(3) (3), 9 - 15, 日本語中枢神経原発悪性リンパ腫診断における髄液マーカーの有用性[査読有り]記事・総説・解説・論説等(学術雑誌)
- 2016年11月, NEURO-ONCOLOGY, 18, 111 - 111, 英語CXCL13 AND IL-10 IN CEREBROSPINAL FLUID (CSF) AS AN IMPORTANT BIOMARKER FOR PRIMARY CENTRAL NERVOUS SYSTEM CELL LYMPHOMA (PCNSL)研究発表ペーパー・要旨(国際会議)
- 2016年11月, NEURO-ONCOLOGY, 18, 15 - 15, 英語STANNIOCALCIN-1 EXPRESSION IN GLIOBLASTOMA IS ASSOCIATED WITH LEPTOMENINGEAL DISSEMINATION OR METASTASIS研究発表ペーパー・要旨(国際会議)
- (NPO)日本脳神経血管内治療学会, 2016年11月, 脳血管内治療, 1(Suppl.) (Suppl.), S61 - S61, 日本語80歳以上の高齢者急性主幹動脈閉塞に対する機械的血栓回収術
- (NPO)日本脳神経血管内治療学会, 2016年11月, 脳血管内治療, 1(Suppl.) (Suppl.), S73 - S73, 日本語急性主幹動脈閉塞血管内再開通療法における動脈硬化性病変への対応
- (NPO)日本脳神経血管内治療学会, 2016年11月, 脳血管内治療, 1(Suppl.) (Suppl.), S177 - S177, 日本語ステント型血栓回収機器を第一選択とした前方循環急性主幹動脈閉塞に対する再開通療法 単一施設での連続62例の経験
- 日本脳腫瘍病理学会, 2016年05月, Brain Tumor Pathology, 33(Suppl.) (Suppl.), 112 - 112, 日本語MR Spectroscopyによる原発性中枢神経リンパ腫とグリオーマの鑑別
- 2014年11月, NEURO-ONCOLOGY, 16, 英語研究発表ペーパー・要旨(国際会議)
- (一社)日本頭痛学会, 2014年11月, 日本頭痛学会誌, 41(2) (2), 276 - 276, 日本語脳神経外科診療における疼痛管理を目的としたアセトアミノフェン静注の有用性
- 2014年, INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 34, S125 - S125, 英語Cerebrospinal fluid interleukin-10 is associated with molecular subtype, tumor-associated macrophage infiltration and STAT3 activation in primary central nervous system diffuse large B-cell lymphoma研究発表ペーパー・要旨(国際会議)
- 2014年, INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 34, S73 - S73, 英語Glutaminase-mediated metabolic pathway involves glioblastoma resistance to mTOR-targeted therapies研究発表ペーパー・要旨(国際会議)
- 2013年11月, NEURO-ONCOLOGY, 15, 23 - 24, 英語JAK2-STAT3 ACTIVATION IS ASSOCIATED WITH CEREBROSPINAL FLUID INTERLEUKIN-10 (IL-10) IN PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA研究発表ペーパー・要旨(国際会議)
- 2013年11月, NEURO-ONCOLOGY, 15, 148 - 148, 英語GC/MS-BASED METABOLOMIC ANALYSIS OF CEREBROSPINAL FLUID (CSF) FROM GLIOMA PATIENTS研究発表ペーパー・要旨(国際会議)
- 2013年11月, NEURO-ONCOLOGY, 15, 199 - 199, 英語DIFFERENT SPATIAL DISTRIBUTION BETWEEN GCB AND NON-GCB PCNSL REVEALED BY MR GROUP ANALYSIS OF 100 CASES研究発表ペーパー・要旨(国際会議)
- 1, 2009年, Journal of Clinical Neuroscience, 16(1) (1), 121 - 4, 英語, 国際誌[査読有り]
- 11, 2009年, Neurologia Medico-Chirurgica, 49(11) (11), 546 - 8, 英語, 国内誌[査読有り]
- 日本脳腫瘍病理学会, 2008年05月, Brain Tumor Pathology, 25(Suppl.) (Suppl.), 117 - 117, 日本語多発性放射線誘発性脳腫瘍の1例
- (一社)日本脳神経外科学会, 2007年10月, 日本脳神経外科学会総会CD-ROM抄録集, 66回, 1I - 3, 日本語膠芽腫および退形成星細胞腫におけるOlig2発現量と予後との関係
- (一社)日本脳神経外科学会, 2007年10月, 日本脳神経外科学会総会CD-ROM抄録集, 66回, 2K - 11, 日本語悪性神経膠腫に対するTemozolomideの治療成績と臨床上の問題点
- (一社)日本脳神経外科学会, 2007年10月, 日本脳神経外科学会総会CD-ROM抄録集, 66回, 2H - 1, 日本語頭蓋底脊索腫に対する治療の課題
- 日本脳腫瘍病理学会, 2006年06月, Brain Tumor Pathology, 23(Suppl.) (Suppl.), 134 - 134, 日本語特異な経過をたどり,放射線化学療法後に多核巨細胞が多数出現した小脳anaplastic oligodendrogliomaの1例
- 日本脳腫瘍病理学会, 2006年06月, Brain Tumor Pathology, 23(Suppl.) (Suppl.), 154 - 154, 日本語Stereotactic Radiosurgery後に再増大した聴神経鞘腫におけるVEGF,Flk-1の発現
- 日本脳腫瘍病理学会, 2006年06月, Brain Tumor Pathology, 23(Suppl.) (Suppl.), 167 - 167, 日本語多発性脳転移を認めたfollicular dendritic cell sarcomaと考えられる1例
- 兵庫県外科医会, 2003年07月, 兵庫県全外科医会会誌, 38(4) (4), 44 - 44, 日本語脳血管攣縮に対する塩酸パパベリン動注療法の総括
- (NPO)日本脳神経外科救急学会, 2003年01月, 日本脳神経外科救急学会プログラム・抄録集, 8回, 103 - 103, 日本語診断過程において急性増悪を来たした高血圧性脳内出血の一例
- 第36回日本脳腫瘍学会, 2018年12月, 日本語, 小田原, 国内会議中枢神経悪性リンパ腫の診断バイオマーカーとしてのCXCL13の検討ポスター発表
- 第36回日本脳腫瘍学会, 2018年12月, 日本語, 小田原, 国内会議グルタミン飢餓状態のグリオーマ細胞における一炭素代謝の調整と新規治療標的の探索口頭発表(一般)
- 日本脳神経外科光線力学学会, 2018年11月, 日本語, 東京, 国内会議悪性脳腫瘍に対する光線力学療法 (PDT)の治療経験口頭発表(一般)
- 第34回日本脳神経血管内治療学会総会, 2018年11月, 日本語, 仙台, 国内会議ステント型血栓回収機器の展開時血管撮影所見による再開通および閉塞機序の予測口頭発表(一般)
- 23rd Annual Scientific Meeting and Education Day of the society for Neuro-Oncology (SNO), 2018年11月, 英語, ニューオリンズ, 国際会議Interleukin-6 in Cerebrospinal Fluid as a Prognostic Marker for Glioblastoma Patients口頭発表(一般)
- 23rd Annual Scientific Meeting and Education Day of the society for Neuro-Oncology (SNO), 2018年11月, 英語, New Orleans, 国際会議Glutamine deprivation alters one-carbon metabolism to maintain glioma cell survival口頭発表(一般)
- 23rd Annual Scientific Meeting and Education Day of the society for Neuro-Oncology (SNO), 2018年11月, 英語, New Orleans, 国際会議Anti-tumor effect of VEGF inhibitor plus ketogenic diet therapy for glioblastomaポスター発表
- 日本脳神経外科学会第77回学術総会, 2018年10月, 日本語, 仙台, 国内会議膠芽腫における髄腔内播種の予測因子と予防手段口頭発表(一般)
- 日本脳神経外科学会第77回学術総会, 2018年10月, 日本語, 仙台, 国内会議膠芽腫におけるVEGF阻害剤、ケトン食による代謝リモデリング、抗腫瘍効果の基礎的検討ポスター発表
- 日本放射線腫瘍学会第31回学術大会, 2018年10月, 日本語, 日本放射線腫瘍学会, 京都, 国内会議当院における悪性脳神経膠腫に対するIMRTの治療成績口頭発表(一般)
- 第56回日本癌治療学会, 2018年10月, 日本語, 横浜, 国内会議悪性脳腫瘍に対する光線力学療法 (PDT)の治療経験-PDTの照射のコツと問題点について-口頭発表(一般)
- 第77回日本脳神経外科学会総会, 2018年10月, 日本語, 仙台, 国内会議ステント型血栓回収機器を用いた血栓回収術におけるステント展開時の血管撮影所見による再開通および閉塞機序の予測口頭発表(一般)
- 日本脳神経外科学会第77回学術総会, 2018年10月, 日本語, 仙台, 国内会議カルムスチン脳内留置用剤(ギリアデル)の治療効果と問題点口頭発表(一般)
- 15th Meeting of the Asian Society for Neuro-Oncology (ASNO), 2018年10月, 英語, Beijing, 国際会議The experience of Photodynamic therapy (PDT) for malignant brain tumors口頭発表(一般)
- 15th Meeting of the Asian Society for Neuro-Oncology (ASNO), 2018年10月, 英語, Beijing, 国際会議Safety and benefit of carmustine wafers implantation in patients with glioblastoma口頭発表(一般)
- 日本脳神経外科学会第77回学術総会, 2018年10月, 日本語, 仙台, 国内会議H3K27M mutationおよび解剖学的局在によるmidline gliomaの予後予測口頭発表(一般)
- 15th Meeting of the Asian Society for Neuro-Oncology (ASNO), 2018年10月, 英語, Beijing, 国際会議Embryonal brain tumor with unknown primary lesion and massive cerebrospinal fluid disseminationポスター発表
- 第36回日本脳腫瘍病理学会, 2018年09月, 日本語, 東京, 国内会議膠芽腫内腫瘍関連マクロファージが膠芽腫細胞に与える影響口頭発表(一般)
- 第36回日本脳腫瘍病理学会学術集会, 2018年09月, 日本語, 日本脳腫瘍病理学会, 東京都, 国内会議膠芽腫内腫瘍関連マクロファージが膠芽腫細胞に与える影響口頭発表(一般)
- 日本機械学会, 2018年09月, 日本語, 大阪, 国内会議脳腫瘍の診断技術,発生因子の解析と治療応用[招待有り]口頭発表(招待・特別)
- 第36回日本脳腫瘍病理学会, 2018年09月, 日本語, 東京, 国内会議頭蓋内lymphomatoid granulomatosisの1例ポスター発表
- 日本脳腫瘍の外科学会, 2018年09月, 日本語, 和歌山, 国内会議悪性脳腫瘍に対する光線力学療法 (PDT)の治療経験口頭発表(一般)
- 第36回日本脳腫瘍病理学会, 2018年09月, 日本語, 東京, 国内会議グリア成分に増殖能亢進と核分裂像増加が見られたRosette-forming glioneuronal tumorの1例ポスター発表
- 日本分子脳神経外科学会, 2018年08月, 日本語, 大坂, 国内会議膠芽腫における播種および予後因子 stanniocalcin-1(STC1)の解析口頭発表(一般)
- 日本分子脳神経外科学会, 2018年08月, 日本語, 大坂, 国内会議膠芽腫におけるVEGF阻害剤、ケトン食による代謝リモデリング、抗腫瘍効果の基礎的検討口頭発表(一般)
- 22nd International Conference on Brain Tumor Research and Therapy (ICBTRT), 2018年06月, 英語, Bergen, 国際会議Magnetic resonance spectroscopy of glutamate and 2-hydroxyglutarate in patients with the IDH1 mutant glioma: A prospective validation study口頭発表(一般)
- 第47回日本神経放射線学会, 2018年02月, 日本語, 日本神経放射線学会, 茨城, 国内会議術前MR SpectroscopyによるグリオーマIDH1遺伝子変異予測の検討[招待有り]シンポジウム・ワークショップパネル(指名)
- 第35回日本脳腫瘍学会, 2017年11月, 日本語, 日本脳腫瘍学会, 香川, 国内会議脳幹グリオーマに対するMR Spectroscopyを用いたIDH遺伝子変異診断の有用性ポスター発表
- 第35回日本脳腫瘍学会, 2017年11月, 日本語, 日本脳腫瘍学会, 香川, 国内会議悪性グリオーマに対するベバシズマブ治療後の画像変化口頭発表(一般)
- 日本脳神経外科学会第76回学術総会, 2017年10月, 日本語, 日本脳神経外科学会, 愛知, 国内会議当院における悪性グリオーマに対するベバシズマブ治療の現状と課題口頭発表(一般)
- 日本脳神経外科学会第76回学術総会, 2017年10月, 日本語, 日本脳神経外科学会, 愛知, 国内会議MR Spectroscopyを用いた2HG測定によるIDH遺伝子変異陽性脳幹グリオーマ診断の有用性ポスター発表
- 第4回心血管脳卒中学会, 2017年06月, 日本語, 心血管脳卒中学会, 福岡, 国内会議急性脳主幹動脈閉塞治療における血管内再開通療法の導入効果口頭発表(一般)
- 第20回日本臨床救急医学会総会・学術集会, 2017年05月, 日本語, 日本臨床救急医学会, 東京, 国内会議脳卒中から日本を救え! ~救急システムの活用と 連携強化の重要性~ 救急システムの活用事例と患者予後[招待有り]口頭発表(招待・特別)
- 第35回日本脳腫瘍病理学会, 2017年05月, 日本語, 日本脳腫瘍病理学会, 宇都宮市, 国内会議長期生存膠芽腫患者の臨床像と病理学的検討口頭発表(一般)
- 第35回日本脳腫瘍病理学会, 2017年05月, 日本語, 日本脳腫瘍病理学会, 宇都宮市, 国内会議治療なく自然寛解と増悪を認めた中枢神経原発悪性リンパ腫の2例ポスター発表
- 第35回日本脳腫瘍病理学会, 2017年05月, 日本語, 日本脳腫瘍病理学会, 宇都宮市, 国内会議左側頭葉に巨大シストを有する膠芽腫の1例公開講演,セミナー,チュートリアル,講習,講義等
- 第35回日本脳腫瘍病理学会, 2017年05月, 日本語, 日本脳腫瘍病理学会, 宇都宮市, 国内会議Rosette-forming glioneuronal tumor (RGNT)の2症例ポスター発表
- 第35回日本脳腫瘍病理学会, 2017年05月, 日本語, 日本脳腫瘍病理学会, 宇都宮市, 国内会議Glioblastoma with PNET-like componentsの初期病理像を確認できた1例ポスター発表
- 第35回脳腫瘍病理学会, 2017年05月, 日本語, 脳腫瘍病理学会, 栃木, 国内会議glioblastoma with PNET-like componentsの初期病理像を確認できた1例ポスター発表
- 第73回日本脳神経外科学会近畿支部学術集会, 2017年04月, 日本語, 日本脳神経外科学会近畿支部, 大阪, 国内会議脳梗塞とくも膜下出血を同時に呈した可逆性脳血管攣縮症候群の1例口頭発表(一般)
- 第30回老年脳神経外科学会, 2017年04月, 日本語, 老年脳神経外科学会, 東京, 国内会議高齢者の急性脳主幹動脈閉塞に対する機械的血栓回収術の予後規定因子の検討口頭発表(一般)
- 第21回日本脳神経外科救急学会, 2016年01月, 日本語, 日本脳神経外科救急学会, 東京, 国内会議ドクターヘリと連携した 急性期脳梗塞血管内治療口頭発表(一般)
- 第33回日本脳腫瘍学会学術集会, 2015年12月, 日本語, 日本脳腫瘍学会, 京都, 国内会議術前MR SpectroscopyによるグリオーマIDH1変異の予測可能性口頭発表(一般)
- 第33回日本脳腫瘍学会学術集会, 2015年12月, 日本語, 日本脳腫瘍学会, 京都, 国内会議悪性グリオーマのmTORシグナル阻害薬に対する代償的グルタミン代謝機構口頭発表(一般)
- 20th Annual Society for Neuro-OncologyAnnual Scientific Meeting and Education Day, 2015年11月, 英語, Society for Neuro-Oncology, Texas, USA, 国際会議Preoperative prediction of IDH1 mutation in glioma tissue by MR Spectroscopy口頭発表(一般)
- 20th Annual Society for Neuro-OncologyAnnual Scientific Meeting and Education Day, 2015年11月, 英語, Society for Neuro-Oncology, Texas, USA, 国際会議Increasing expression of glutaminase C (GAC) mRNA in malignant gliomasポスター発表
- 第74回日本脳神経外科学会学術総会, 2015年10月, 日本語, 日本脳神経外科学会, 札幌, 国内会議悪性グリオーマのmTORシグナル阻害薬に対する代償的グルタミン代謝機構口頭発表(一般)
- 第13回日本Awake surgery学会, 2015年09月, 日本語, 日本Awake surgery学会, 名古屋, 国内会議初発・再発時に覚醒下手術を2度行った優位半球言語野近傍グリオーマの1例口頭発表(一般)
- 第20回日本脳腫瘍の外科学会, 2015年09月, 日本語, 日本脳腫瘍の外科学会, 名古屋, 国内会議再発膠芽腫に対する再摘出術の有効性および問題点シンポジウム・ワークショップパネル(公募)
- 第70回日本脳神経外科近畿支部学術集会, 2015年09月, 日本語, 日本脳神経外科学会, 大阪, 国内会議硬膜浸潤および頭蓋外転移を来したgliosarcomaの1例口頭発表(基調)
- 第16回日本分子脳神経外科学会, 2015年08月, 日本語, 日本分子脳神経外科学会, 静岡, 国内会議中枢神経原発悪性リンパ腫での腫瘍関連マクロファージ浸潤と髄液サイトカインとの関連性ポスター発表
- 第18回日本臨床脳神経外科学会, 2015年07月, 日本語, 日本臨床脳神経外科協会, 兵庫, 国内会議術中3Tesla MRIシステムの導入と初期使用経験口頭発表(一般)
- 第3回がんと代謝研究会, 2015年07月, 日本語, がんと代謝研究会, 金沢, 国内会議悪性グリオーマのグルタミン代謝による代償的mTOR阻害薬耐性機構ポスター発表
- 第3回がんと代謝研究会, 2015年07月, 日本語, がんと代謝研究会, 金沢, 国内会議グリオーマでのmiR-183によるIDH2発現調節と代謝との関連ポスター発表
- 第18回日本臨床脳神経外科学会, 2015年07月, 日本語, 日本臨床脳神経外科学会, 神戸, 国内会議MR SpectroscopyによるグリオーマIDH1変異の予測可能性口頭発表(一般)
- 第3回がんと代謝研究会, 2015年07月, 日本語, がんと代謝研究会, 金沢, 国内会議IDH1変異グリオーマとグルタミン代謝ポスター発表
- 第15回日本術中画像情報学会, 2015年06月, 日本語, 日本術中画像情報学会, 東京, 国内会議術中3Tesla MRIシステムの導入と初期運用経験口頭発表(一般)
- 第69回日本脳神経外科近畿支部学術集会, 2015年04月, 日本語, 日本脳神経外科学会, 大阪, 国内会議T2*およびSWIで低信号を呈した小脳原発胚細胞腫の一例口頭発表(一般)
- The 4th International CNS Germ Cell Tumor Symposium, 2015年04月, 英語, Department of Neuro-Oncology/NeurosurgerySaitama International Medical CenterSaitama Medical University, 東京, 国際会議A rapidly expanding immature teratoma originating from a neurohypophyseal germinomaポスター発表
- 第27回臨床MR脳機能研究会, 2015年03月, 日本語, 臨床MR脳機能研究会, 徳島, 国内会議術前MR SpectroscopyによるグリオーマIDH1変異の予測可能性口頭発表(一般)
- 第32回日本脳腫瘍学会, 2014年12月, 日本語, 日本脳腫瘍学会, 千葉, 悪性髄膜腫は良性髄膜腫と比較すると圧倒的に頻度が少なく、臨床データも多くはない。しかしながら臨床的には諸治療に抵抗性で何度も再発し、対応に苦慮することが多い。また、初回手術時の病理学的な悪性度と臨床的悪性度が必ずしも一致しない症例も少なからず存在する。そこで、病理所見に関わらず臨床的に悪性と判断した再発性髄膜腫の自験例をまとめ、問題点を考察することとした。【対象と方法】当該施設において1986年以降2010年までの初回手術後に3回以上再発を繰り返し、その都度何らかの追加治療を要した症例を「臨床的悪性髄膜腫」と定義して集計したところ、28例が該当し、これらを対象として後方視的に検討を行った。【結果】性別は男性11例女性17例、発症時平均年齢は57.3歳であった。初回手術時の病理診断はGrade Iが16例、IIが7例、IIIが5例であった。追加手術を行, 国内会議再発(難治)性髄膜腫における初回手術時病理gradeの意義についてポスター発表
- 第32回日本脳腫瘍学会学術集会, 2014年11月, 日本語, 日本脳腫瘍学会, 千葉, 【序言】滑膜肉腫は10-40歳に発生し、四肢の関節近傍、特に膝関節周辺に好発する悪性軟部腫瘍である。約30%に転移を認めるが、大半が肺への転移であり頭蓋内転移の報告は極めて稀である。今回我々は、脳内出血を来たした滑膜肉腫の脳転移の症例を経験したので、症例の詳細に文献的考察を加えて報告する。脳内出血を来たした滑膜肉腫の脳転移の1例
【症例】39歳男性。2年前に右大腿部の増大する腫瘤を主訴に、当院整形外科へ紹介となった。生検の結果、滑膜肉腫と診断され広範囲切除術後に化学療法が行われたが、肺転移病巣が増大し外科的切除を検討する予定であった。3日前に左上肢の痙攣発作が出現し、頭部CTで右前頭葉に直径4cm大の腫瘍性病変を認めたため当科へ紹介となった。MRI等の術前精査を予定していたが、初診より2日後に意識障害(JCS II-10)と左完全片麻痺が出現し救急搬送となった。頭部CT・MRIで腫瘍, 国内会議ポスター発表 - 第32回日本脳腫瘍学会学術集会, 2014年11月, 日本語, 日本脳腫瘍学会, 千葉, 国内会議初発PCNSLに対するリツキシマブ併用大量メトトレキセート療法の有用性についてポスター発表
- 第32回日本脳腫瘍学会学術集会, 2014年11月, 日本語, 日本脳腫瘍学会, 千葉, 国内会議術前MR SpectroscopyによるグリオーマIDH1変異の予測可能性ポスター発表
- 第32回日本脳腫瘍学会学術集会, 2014年11月, 日本語, 日本脳腫瘍学会, 千葉, 国内会議ギリアデル留置後の脳浮腫および腫瘍摘出腔拡大と病理学的変化ポスター発表
- 19th Annual Scientific Meeting and Education Day of the society for Neuro-Oncology, 2014年11月, 英語, Society for Neuro-Oncology, Miami, Florida, USA, 国際会議Glutaminase-mediated metabolic pathway involves glioblastoma resistance to mTOR-targeted therapies口頭発表(一般)
- 日本脳神経外科学会第73回学術総会, 2014年10月, 日本語, 日本脳神経外科学会, 東京, 国内会議当院における悪性神経膠腫再発例に対するアバスチン(Bevacizumab)療法ポスター発表
- 19th World Congress on Advances in Oncology & 17th International Symposium on Molecular Medicine, 2014年10月, 英語, Spandidos publication, Athens, Greece, 国際会議Glutaminase-mediated metabolic pathway involves glioblastoma resistance to mTOR-targeted therapies口頭発表(一般)
- 20th World Congress on Advances in Oncology, 2014年10月, 英語, Spandidos, Athens, Greece, 国際会議Cerebrospinal fluid interleukin-10 is associated with molecular subtype, tumor-associated macrophage infiltration and STAT3 activation in primary central nervous system diffuse large B-cell lymphoma.口頭発表(一般)
- 第68回日本脳神経外科学会近畿支部学術集会, 2014年09月, 日本語, 日本脳神経外科学会, 大阪, 国内会議カルムスチン脳内留置用剤留置後急性に摘出腔拡大および脳浮腫を来した一例口頭発表(一般)
- 2nd International Congress on Minimally Invasive Technique in Neurosurgery, 2014年09月, 英語, Asian Society for Neuro-Oncology, Istanbul, Turkey, 国際会議Glutaminase-mediated metabolic pathway involves glioblastoma resistance to mTOR-targeted therapies口頭発表(一般)
- 11th Meeting of the Asian Society for Neuro-Oncology, 2014年09月, 英語, the Asian Society for Neuro-Oncology, Istanbul, Turkey, INTRODUCTUION: Glioblastomas (GBMs) occasionally metastasize or disseminateto distant lesions from the primary tumor. The incidence of metastasized or disseminated GBMs ranges from 8% to 27%. Several biomarkers have been proposed as useful parameters to specify the prognosis or to delineate newtherapeutic strategies for such patients. MicroRNAs (miRs) are small, noncoding RNAs,, 国際会議Characteristics of microRNA expressions in glioblastoma with metastases to the medulla oblongata or spinal cord.口頭発表(一般)
- 11th Meeting of the Asian Society for Neuro-Oncology, 2014年09月, 英語, the Asian Society for Neuro-Oncology, Istanbul, Turkey, 国際会議Cerebrospinal fluid interleukin-10 is associated with STAT3 activation、molecular subtype and M2 macrophage infiltration in primary central nervous system diffuse large B-cell lymphomaポスター発表
- 第44回兵庫県脳神経外科医懇話会, 2014年07月, 日本語, 兵庫県脳神経外科医懇話会, 神戸, 国内会議放射線治療誘発性と考えられる脳梗塞を起こした3例口頭発表(一般)
- 第2回がんと代謝研究会, 2014年07月, 日本語, がんと代謝研究会, 東京, 国内会議グリオーマにおける脳脊髄液を用いたメタボローム解析口頭発表(一般)
- 第2回がんと代謝研究会, 2014年07月, 日本語, がんと代謝研究会, 東京, 国内会議mTORシグナル阻害による悪性グリオーマ細胞内グルタミン代謝機構の変化ポスター発表
- 第2回癌と代謝学会, 2014年07月, 日本語, がんと代謝研究会, 東京, 国内会議MR SpectroscopyによるIDH1変異の予測ポスター発表
- 第32回日本脳腫瘍病理学会, 2014年05月, 日本語, 日本脳腫瘍病理学会, 徳島, 国内会議特異な経過をたどった 原発不明の転移性脳腫瘍の1例口頭発表(一般)
- 第32回日本脳腫瘍病理学会, 2014年05月, 日本語, 日本脳腫瘍病理学会, 徳島, 国内会議脱髄疾患を合併するCastleman症候群を呈したChordoid meningiomaの1例ポスター発表
- 第32回日本脳腫瘍病理学会, 2014年05月, 日本語, 日本脳腫瘍病理学会, 徳島, 国内会議早期に悪性転化を来したgranular cell astrocytoma の1例ポスター発表
- 第32回日本脳腫瘍病理学会, 2014年05月, 日本語, 日本脳腫瘍病理学会, 徳島, 国内会議脊髄播種・転移を起こした膠芽腫のマイクロRNA発現に関する検討口頭発表(一般)
- 第67回日本脳神経外科学会近畿支部学術集会/第69回近畿脊髄外科研究会, 2014年04月, 日本語, 日本脳神経外科学会, 大阪, 国内会議偶然発見された副咽頭間隙へ伸展を示した三叉神経鞘腫の1例口頭発表(一般)
- 第31回日本脳腫瘍学会学術集会, 2013年12月, 日本語, 日本脳腫瘍学会, 宮崎, 【症例】24歳女性。記銘力障害を主訴に精査の結果、鞍上部腫瘍を指摘された。視力、視野異常、眼球運動障害、下垂体機能異常は認めず、軽度の記銘力障害を認めた。頭部CTでは石灰化を伴う最大径22mmの円形の鞍上部腫瘍であり、一見頭蓋咽頭腫を疑う所見であった。頭部MRIでは、視交叉後方で鞍上部から第3脳室に至る腫瘍で、内部不均一であり、T2WIでは腫瘍周囲に低信号帯を認めた。脳室拡大は認めなかった。頭蓋咽頭腫を第1に疑い、両側前頭開頭によるbasal inter hemispheric trans laminaterminalis approachによる腫瘍摘出術を行った。【手術所見】組織内には拡張した血管が多数存在し、時期の異なる血腫や周囲にグリオーシスを伴っており、海綿状血管腫が疑われた。肉眼的に全摘出を行った。内視鏡を挿入したが第3脳室天井の脈絡叢な, 国内会議第3脳室底に発生した海綿状血管腫の1例ポスター発表
- 第31回日本脳腫瘍学会学術集会, 2013年12月, 日本語, 日本脳腫瘍学会, 宮崎, 頭蓋内GBMで脊髄・脳幹転移の頻度は約10%であった。初回手術から転移までの期間は平均約9か月であり、転移から死亡までの期間は平均3か月と非常に短かった。脳室や脳槽の開放が無い症例でも転移を認めた。頭蓋内に造影病変を認めない症例が3例認められた。MGMTのメチレーションとの関連性は無く、p53の発現が高い症例が多い傾向を認めた。, 国内会議脊髄播種・転移を起こした膠芽腫の臨床的・組織学的検討ポスター発表
- 第31回日本脳腫瘍学会学術集会, 2013年12月, 日本語, 日本脳腫瘍学会, 宮崎, 【目的】悪性グリオーマを含む多くのがん細胞のエネルギー代謝がグルコースに依存していることはWarburg効果として明らかである。PI3K/mTORシグナルがグルコース代謝に強く関与していることは既に報告されているが、他の代謝リモデリングに及ぼす影響については未だ不明である。今回、mTORシグナル抑制が細胞内代謝に及ぼす影響をグルタミン代謝に着目して解析した。【方法】ヒト悪性グリオーマ細胞株や初期継代培養細胞に対して、mTORシグナルを抑制し、ガスクロマトグラフィー/質量分析計(GC/MS)によるメタボローム解析を行い、細胞内代謝産物の変化についてグルタミン代謝関連物質を中心に解析した。次に、細胞内のグルコースおよびグルタミン代謝がどのように変化するかを特定の代謝関連遺伝子に着目してreal-time PCRなどで解析を行った。【結果】ラパマイシンまた, 国内会議mTORシグナルによる悪性グリオーマ細胞内グルタミン代謝機構の制御ポスター発表
- 4th Quadrennial Meeting of the Woeld Federation of Neuro-Oncology, 2013年11月, 英語, Quadrennial Meeting of the Woeld Federation of Neuro-Oncology, San Francisco, USA, Objective: The diagnosis of primary central nervous system lymphoma (PCNSL) is often difficult. The objective of this work is to evaluate the diagnostic value of interleukin-10 (IL-10), IL-6, soluble IL-2 receptor (sIL-2R), and ?2-microglobulin (?2-M) levels in the cerebrospinal fluid (CSF). Methods: (1) Case-control study: the CSF levels of IL-10, IL-6, sIL-2R, and ?2-M in 66, 国際会議The combination of interleukin-10 and bate2-microglobulin in cerebrospinal fluid is a useful biomarker in immunocompetent primary central nervous system lymphoma(PCNSL)口頭発表(一般)
- 4th Quadrennial Meeting of the Woeld Federation of Neuro-Oncology, 2013年11月, 英語, Quadrennial Meeting of the Woeld Federation of Neuro-Oncology, San Francisco, USA, Objective: The management of low-grade gliomas (LGGs) still remains controversial, although some physicians advocate early and extensive surgery or early radiation therapy. In particular, prognostic factors for survival should help the strategy of treatment for patients with LGG, but the importance of them remains a matter of discussion. The purpose of this study was to validat, 国際会議Prognostic factors for survival in patients with cerebral low-grade glioma口頭発表(一般)
- 4th Quadrennial Meeting of the Woeld Federation of Neuro-Oncology, 2013年11月, 英語, Quadrennial Meeting of the Woeld Federation of Neuro-Oncology, San Francisco, USA, ObjectThe Janus kinase 2(JAK2)-signal transducers and activators of transcription 3(STAT3) signaling pathway is constitutively activated in various cancers. In the present study, we examined JAK2-STAT3 activation in primary central nervous system lymphoma (PCNSL) and analyzed a relationship between the activation of the JAK2-STAT3 pathway and the CSF levels of IL-10 and IL-6. M, 国際会議JAK2-STAT3 activation is associated with cerebrospinal fluid interleukin-10(IL-10) in primary central nervous system lymphoma口頭発表(一般)
- 日本脳神経外科学会第72回学術総会, 2013年10月, 日本語, 日本脳神経外科学会, 横浜, 【目的】low-grade glioma (LGG) 患者に対する治療方針には未だ統一した見解がない。今回、当科におけるLGG患者の予後規定因子について報告する。【方法】神戸大学附属病院にて1983年から2012年に治療されたLGG患者112人のうち、天幕上WHO grade II astrocytoma (DA) 40例、oligodendroglioma (OG) 14例、oligodendroastrocytoma (OA) 4例を対象とした。患者背景や治療方法、組織学的診断、遺伝子解析(MGMT, IDH1, p53)などから全生存期間について後向き解析を行った。Cox多変量解析にて予後規定因子を同定した。【結果】天幕上LGG患者58人すべての生存期間中央値は166か月(95% CI, 49.14-282.86)であった。DAおよびOG患者の, 国内会議天幕上low-grade glioma患者の予後規定因子についてポスター発表
- 日本脳神経外科学会第72回学術総会, 2013年10月, 日本語, 日本脳神経外科学会, 横浜, 中枢神経悪性リンパ腫の再発に対する確立した治療法はなく、予後も極めて不良である。我々は、再発中枢神経悪性リンパ腫の予後および予後因子について解析した。【対象】2003年1月から2012年12月までに当院で治療を施行された中枢神経悪性リンパ腫54例のうち、中枢神経での再発を認め、積極的加療が施行された18例を対象とした。年齢、再発までの期間、再発時治療法、リンパ腫サブタイプなどと再発時治療効果、再発後生存期間との関連について検討した。 【結果】 患者18例の平均年齢は60歳(45~77歳)。初期治療は1例を除き、大量メトトレキセート療法+放射線療法が施行され、1例は放射線量療法のみ施行。18例全体の全生存期間(OS)中央値は31か月(7~106か月)、無増悪生存期間(PFS)中央値は15か月(4~88か月)であった。再発時治療は個々の病状や全身状態など, 国内会議再発中枢神経悪性リンパ腫治療後の予後に関する検討ポスター発表
- 日本脳神経外科学会第72回学術総会, 2013年10月, 日本語, 日本脳神経外科学会, 横浜, 【緒語】放射線治療の合併症として放射線誘発性血管障害があるが、悪性脳腫瘍では問題とされることが少ない。当施設で2000年から2012年の期間に放射線治療を行った神経膠腫と悪性リンパ腫のうち4例で、放射線治療に起因すると考えられる脳梗塞を認めた。症例の詳細に若干の文献的考察を加えて報告する。【対象】2000年1月から2012年12月の期間に治療を行った神経膠腫と悪性リンパ腫を対象とした。神経膠腫197例中175例と悪性リンパ腫63例中43例に対して、定位放射線治療単独以外の放射線治療が行われた。【結果】発症時の平均年齢は54.2歳。全218例のうち4例(1.8%)が観察期間中に脳梗塞を発症した。初回放射線治療より24ヶ月以上の生存期間が得られた群では3.3%(90例中3例)であった。原疾患は膠芽腫3例と悪性リンパ腫1例であり、膠芽腫3例に対しては60G, 国内会議悪性脳腫瘍放射線治療後の脳梗塞ポスター発表
- 第66回日本脳神経外科学会近畿支部学術集会、第14回近畿脳神経血管内治療学会, 2013年09月, 日本語, 日本脳神経外科学会近畿支部、近畿脳神経血管内治療学会, 大阪, epidermoid cystはCT上、くも膜嚢胞との鑑別が困難であることが多く、MRIのDWIで高信号を呈することが診断に有用である。しかしDWIでは病変を解剖学的に正確に把握することは困難である。我々はMRI balanced Fast-Field Echo(bFFE)法を用いて術前の治療戦略および術後評価に有用であった症例を経験したので報告する。症例は41歳女性。左三叉神経痛の精査にて左小脳橋角部腫瘍を指摘され当院紹介となった。左三叉神経第2、3枝領域に疼痛、左軽度感音性難聴を認めた。頭部CTでは中脳左外側から左延髄外側にかけて髄液と等信号の病変を認め、MRIではT1低信号、T2高信号、DWIにて著明な高信号を示した。術前診断はepidermoid cystを第一に考えた。bFFE法では解剖学的な病変の広がりを把握することが可能で、腫瘍内や周囲, 国内会議MRI balanced Fast-Field Echo法による評価が有用であったepidermoid cystの一例口頭発表(一般)
- ニューロ・オンコロジィの会, 2013年07月, 日本語, ニューロ・オンコロジィの会, 東京, 頭蓋内GBMで脊髄・脳幹転移の頻度は約10%であった。初回手術から転移までの期間は平均約9か月であり、転移から死亡までの期間は平均3か月と非常に短かった。脳室や脳槽の開放が無い症例でも転移を認めた。頭蓋内に造影病変を認めない症例が3例認められた。MGMTのメチレーションとの関連性は無く、p53の発現が高い症例が多い傾向を認めた。, 国内会議脊髄播種・転移を起こした膠芽腫の臨床学的・組織学的検討口頭発表(一般)
- 第28回日本脳神経外科国際学会フォーラム,第27回日本脳神経外科同時通訳夏季研修会, 2013年07月, 英語, 日本脳神経外科国際学会, 横浜, Objective: The management of low-grade gliomas (LGGs) still remains controversial, although some physicians advocate early and extensive surgery or early radiation therapy. In particular, prognostic factors for survival should help the strategy of treatment for patients with LGG, but the importance of them remains a matter of discussion. The purpose of this study was to validat, 国際会議Prognostic factors for survival in patients with cerebral low-grade glioma口頭発表(一般)
- The 6th Annual World Cancer Congress 2013, 2013年05月, 英語, BITeomics, Xi'an, China, The diagnosis of primary central nervous system lymphoma (PCNSL) by radiographical examination is often difficult because of its similarity to other brain tumors. To test whether interleukin-10 (IL-10) and IL-6 can be used to distinguish PCNSL from other brain tumors that are radiographically similar, cerebrospinal fluid (CSF) levels of IL-10 and IL-6 were measured in 66 patien, 国際会議Cerebrospinal fluid interleukin-10 is a potentially useful biomarker in immunocompetent primary centralnervous system lymphoma (PCNSL)口頭発表(一般)
- 第65回日本脳神経外科学会近畿支部学術集会、第67回近畿脊髄外科研究会, 2013年04月, 日本語, 日本脳神経外科学会近畿支部、近畿脊髄外科研究会, 大阪, 【症例】35歳男性 【主訴】頭痛、嘔吐 【現病歴】数ヶ月前から頭痛および嘔吐があり、近医にて後頭蓋窩腫瘍を指摘され精査加療目的で紹介となった。 【現症】意識清明、うっ血乳頭 【神経放射線学的所見】頭部単純CTにて左小脳に長径約4cmの高吸収、低吸収の混在する腫瘍を認め、脳室拡大を認めた。MRIでは内部にflow voidを認め均一に増強される腫瘤で、周囲小脳と脳幹に著明な浮腫を伴っていた。また硬膜に付着部を有すると思われた。血管撮影では著明な腫瘍濃染像を認め、栄養血管は主に中硬膜動脈、上行咽頭動脈、後頭動脈、上小脳動脈であった。左S状静脈洞は概ね閉塞していた。術前診断としてhemangiopericytomaを考え左S状静脈洞を含めて全摘出を行うこととした。 【入院経過】外側後頭下開頭に後方経錐体到達法を併用し開頭腫瘍摘出術を行った。術中所見では腫瘍, 国内会議診断に苦慮した後頭蓋窩hemangioblastomaの一例口頭発表(一般)
- 10th Meeting of Asian Society for Neuro-Oncology, 2013年03月, 英語, Asian Society of Neuro-Oncology, India, Surgical management of cerebral low-grade gliomasKazuhiro Tanaka, Takashi Sasayama, Katsu Mizukawa, and Eiji Kohmura Department of Neurosurgery, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanObjective: The management of low-grade gliomas (LGGs) still remains controversial, although several prognostic factors were well established with recent ongoing translati, 国際会議Surgical management of cerebral low-grade gliomas口頭発表(一般)
- 10th Meeting of Asian Society for Neuro-Oncology, 2013年03月, 英語, Asian Society of Neuro-Oncology, India, ObjectThe Janus kinase 2(JAK2)-signal transducers and activators of transcription 3(STAT3) signaling pathway is constitutively activated in various cancers. In the present study, we examined JAK2-STAT3 activation in primary central nervous system lymphoma (PCNSL) and analyzed a relationship between the activation of the JAK2-STAT3 pathway and the CSF levels of IL-10 and IL-6. M, 国際会議JAK2-STAT3 activation is associated with cerebrospinal fluid interleukin-10(IL-10) in primary central nervous system lymphoma口頭発表(一般)
- 10th Meeting of Asian Society for Neuro-Oncology, 2013年03月, 英語, Asian Society of Neuro-Oncology, India, Metabolomics has recently undergone rapid development, however, metabolomic analysis in cerebrospinal fluid (CSF) has not become a common practice. We analyzed the metabolite profiles of preoperative CSF samples from 32 patients with histologically confirmed glioma using gas chromatography/mass spectrometry (GC/MS). We assessed how alterations in the metabolite levels were rela, 国際会議GC/MS-based metabolomic analysis of cerebrospinal fluid (CSF) from glioma patients口頭発表(一般)
- 10th Meeting of Asian Society for Neuro-Oncology, 2013年03月, 英語, Asian Society of Neuro-Oncology, India, (Background) Postoperative standard therapy for glioblastoma(GBM) is concomitant radiotherapy(RT) and temozolomide (TMZ). However, interferon- (IFN-) has been used for the treatment of GBM for about thirty years in Japan. The aim of this study is to evaluate the effectiveness of concomitant RT, TMZ, and IFN- combination therapy in newly diagnosed GBM. (Methods) This study r, 国際会議Concomitant radiotherapy,temozolomide and interferon-beta combination therapy for newly diagnosed glioblastoma口頭発表(一般)
- 第30回日本脳腫瘍学会学術集会, 2012年11月, 日本語, 日本脳腫瘍学会, 広島, 悪性リンパ腫細胞から IL-10が分泌され、IL-10によりJAK1、JAK2、STAT3のリン酸化が誘導された。髄液IL-10が高値群の悪性リンパ腫は、低値群に比べて、有意にJAK2, STAT3のリン酸化が多く認められ、JAK2-STAT3経路が活性化されていると考えられる。JAK2 inhibitorは、JAK-STAT経路が亢進している頭蓋内悪性リンパ腫に対する治療ターゲットとなる可能性がある。, 国内会議頭蓋内原発悪性リンパ腫におけるJAK-STAT経路の活発化口頭発表(一般)
- 第30回日本脳腫瘍学会学術集会, 2012年11月, 日本語, 日本脳腫瘍学会, 広島, 【緒言】Castleman病は腫脹したリンパ節から放出されるIL-6により、血清グロブリン高値、CRP上昇、貧血、発熱、体重減少などの症状を呈する稀な疾患であり、リンパ節病変を伴わないCastleman症候群の存在も報告されている。今回我々は、Chordoid meningiomaが原因で生じ、脱髄疾患も合併したCastleman症候群の1例を経験したので報告する。, 国内会議脱髄疾患を合併するCastleman症候群を呈したChordoid meningiomaの1例口頭発表(一般)
- 第30回日本脳腫瘍学会学術集会, 2012年11月, 日本語, 日本脳腫瘍学会, 広島, 【緒言】中枢神経系原発リンパ腫が他臓器に転移することは、極めて稀とされている。今回我々は、開頭生検術で中枢神経系原発リンパ腫と診断され、術後に放射線化学療法を行い、診断から約2年後に左口蓋扁桃に転移した1例を経験した。症例の詳細に文献的考察を加えて報告する。【症例】61歳、女性。運動性失語で発症し、頭蓋内に腫瘍性病変を認めたため、当院へ紹介となった。頭部MRIでは左前頭葉に広範な脳浮腫を伴い、均一に造影効果を受ける脳実質内病変を認めた。開頭生検術を行ったところ、Diffuse large B-cell lymphomaと診断された。MTX療法を1クールを行ったところで病変の増大を認めたため、放射線治療(64.8Gy)を行った。その後、脳梁膨大部と右小脳半球、左後頭葉に再発病変を認め、何れもガンマナイフ治療を行い消失した。診断から約2年後に左口蓋扁桃の, 国内会議左口蓋扁桃に転移を認めた中枢神経系原発リンパ腫の1例:症例報告口頭発表(一般)
- 第30回日本脳腫瘍学会学術集会, 2012年11月, 日本語, 日本脳腫瘍学会, 広島, EGFレセプターの恒常的活性化によるmTORC2-NF-B経路の制御Oncogenic EGFR signaling activates an mTORC2-NF-B pathway.田中一寛1、Paul S. Mischel2-4, 甲村英二11神戸大学大学院医学系研究科 脳神経外科2Department of Pathology and Laboratory Medicine, 3Henry Singleton Brain Tumor Program, 4Jonsson Comprehensive Cancer Center, David Geffen UCLA School of Medicine【目的】上皮成長因子受容体(EGFR)-PI3Kシグナルの下流にあるmTORタンパク質複合体はRaptorと結合するmTORC1とRictorと結, 国内会議EGFレセプターの恒常的活性化によるmTORC2-NFkB経路の抑制口頭発表(一般)
- 第71回日本脳神経外科学会学術総会, 2012年10月, 日本語, 日本脳神経外科学会, 大阪, 目的:小脳橋角部腫瘍において、術前に顔面神経の走行や腫瘍との位置関係を把握できれば、 術操作上有用となる。我々は前回の発表で、balanced fast-field echo(bFFE)を用いた術前予 測では、大型の腫瘍において神経描出が困難であることを報告した。今回、大型腫瘍に対して diffusion tensor imaging(DTI)を併用し、検討を行った。方法:2011年5月~2012年5月に手 術を行ったMax CPA 25mm以上の聴神経鞘腫14例、小脳橋角部髄膜腫4例を対象とした。3T- MRI(Philips Achieva)を用い、Gd-bFFE(voxel size: 0.29×0.29×0.7 mm)およびDTI(15 sensing directions, voxel size:2.0×2.0 mm, sli, 国内会議大型小脳橋角部腫瘍症例における顔面神経の走行予測についてbalanced fast field echo(bFFE)およびdiffusion tensor imaging(DTI)を用いた術前予後と手術所見との比較検討ポスター発表
- 第71回日本脳神経外科学会学術総会, 2012年10月, 日本語, 日本脳神経外科学会, 大阪, 【はじめに】Glioblastomaは放射線療法+テモゾロミド療法が標準治療である。しかし、様々 な事情により標準治療が施行出来ない症例も少なからず存在する。我々は、当院で実際に施行 された個々の治療方法を調べ、治療成績を比較し、今後の対応を検討した。【対象】2007年1月から2012年4月までに、当院で治療を受けた連続glioblastoma患者85例(脳 幹悪性グリオーマ6例を含む)を対象とし、実際に施行された治療、標準治療不能の割合、原 因などについて検討した。また、標準治療施行の有無をふくめ、生存期間に影響を与える因子 を総合的に解析した。【結果】放射線治療が施行できなかった症例は5例(6%)で、高齢あるいはperformance status (PS)が不良な症例であった。放射線治療が施行された80例の, 国内会議Glioblastoma標準治療の課題口頭発表(一般)
- 第71回日本脳神経外科学会学術総会, 2012年10月, 日本語, 日本脳神経外科学会, 大阪, 【目的】上皮成長因子受容体(EGFR)-PI3Kシグナルの下流にあるmTORタンパク質複合体は Raptorと結合するmTORC1とRictorと結合するmTORC2の2種類が存在する。Rictorは glioblastomaで高発現している報告もあるが、mTORC2の機能は十分に解明されていない。今 回、EGFRの恒常的活性化がmTORC2に及ぼす影響をNFkBに着目して解析した。【方法】ヒト悪性グリオーマ細胞株U87に変異型EGFR(EGFRvIII)および野生型EGFRを安定発 現させた細胞を用いて、mTORC2およびその下流のAkt等の関連蛋白のリン酸化状態をWestern blotting法で解析した。mTORC2とNFkBとの関連性を検討するため、Rictorのノックダウンある いは細胞内強制発現を行い、NFkBの, 国内会議EGFレセプターの恒常的活性化によるmTORC2-NFkB経路の抑制シンポジウム・ワークショップパネル(公募)
- 第13回日本分子脳神経外科学会, 2012年09月, 日本語, 日本分子脳神経外科学会, 熊本, 悪性リンパ腫細胞から IL-10が分泌され、IL-10によりJAK1、JAK2、STAT3のリン酸化が誘導された。髄液IL-10が高値群の悪性リンパ腫は、低値群に比べて、有意にJAK2, STAT3のリン酸化が多く認められ、JAK2-STAT3経路が活性化されていると考えられる。JAK2 inhibitorは、JAK-STAT経路が亢進している頭蓋内悪性リンパ腫に対する治療ターゲットとなる可能性がある。, 国内会議頭蓋内悪性リンパ腫患者における髄液中IL-10,IL-6とJAL-STAT経路の活性化口頭発表(一般)
- 第17回日本脳腫瘍の外科学会, 2012年09月, 日本語, 日本脳腫瘍の外科学会, 横浜, 目的:小脳橋角部腫瘍において、術前に顔面神経の走行や腫瘍との位置関係を把握できれば、術操作上有用となる。我々は前回の発表で、balanced fast-field echo(bFFE)を用いた術前予測では、大型の腫瘍において神経描出が困難であることを報告した。今回、大型腫瘍に対してdiffusion tensor imaging(DTI)を併用し、検討を行った。方法:2011年4月〜2012年4月に手術を行ったMax CPA 25mm以上の聴神経鞘腫14例、小脳橋角部髄膜腫4例を対象とした。3T-MRI(Philips Achieve)を用い、Gb-bFFG(voxel size :0.29×0.63×0.63mm)およびDTI(15 sensing directions,voxel size:2.0×2.0)にて術前撮影を行い、脳槽部での顔面神経の, 国内会議小脳橋角部大型腫瘍における顔面神経走行の術前予測とその検証シンポジウム・ワークショップパネル(公募)
- 第64回日本脳神経外科学会近畿支部学術集会, 2012年09月, 日本語, 日本脳神経外科学会近畿支部, 大阪, 【緒言】Castleman病は腫脹したリンパ節から放出されるIL-6により、血清グロブリン高値、CRP上昇、貧血、発熱、体重減少などの症状を呈する稀な疾患であり、リンパ節病変を伴わないCastleman症候群の存在も報告されている。今回我々は、Chordoid meningiomaが原因で生じたと考えられるCastleman症候群の1例を経験したので報告する。【症例】39歳、女性。半年前から不明熱が続き、血液検査で貧血とCRP、IgGの著明な上昇を認めていた。頭痛と眩暈の精査のため施行した頭部MRIで異常を指摘され、当院へ紹介となった。神経学的には、左眼の急激な視力低下と左不全片麻痺、左半身の温痛覚障害の出現を認めた。頭部MRIで左小脳半球に広範な浮腫を伴う腫瘍性病変を認めたが、視神経に明らかな異常は認めなかった。また、頚髄MRIで右側索に脱髄疾患を, 国内会議Castleman症候群を呈したChordoid meningiomaの1例口頭発表(一般)
- 第27回日本脳神経外科国際学会フォーラム, 2012年07月, 英語, 日本脳神経外科学会, 石川, Oncogenic EGFR signaling activates an mTORC2-NF-B pathway that promotes chemotherapy resistanceKazuhiro Tanaka1, Paul S. Mischel2-4, Eiji Kohmura11Department of Neurosurgery, Kobe University Graduate Scholl of Medicine, Kobe, JAPAN; 2Department of Pathology and Laboratory Medicine, 3Henry Singleton Brain Tumor Program, 4Jonsson Comprehensive Cancer Center, David Geffen UCLA Sc, 国際会議Oncogenic EGFR signaling activates an mTORC2-NF-B pathway that promotes chemotherapy resistance口頭発表(一般)
- 第30回日本脳腫瘍病理学会、第4回国際脳腫瘍病理シンポジウム, 2012年05月, 日本語, 日本脳腫瘍病理学会, 名古屋, IL-10はリンパ腫の発生、維持に関与している可能性が報告されている。そこで我々は、髄液中IL-10値とB細胞分化マーカーとの関連性について検討した。(対象および方法)治療前の髄液採取が施行され、組織診断された頭蓋内び慢性大細胞性B細胞リンパ腫29例(4例は全身性悪性リンパ腫の頭蓋内進展)を対象とした。リンパ腫の分化マーカーとしてCD10, Bcl-6, MUM1を用い、腫瘍組織に対して免疫染色を行い、陰性、弱陽性、陽性と発現量を評価した。また、腫瘍細胞でのIL-10の発現も免疫染色で検討した。髄液中IL-10値を高値群と低値群とに分け、2群間でIL-10、分化マーカーの発現量に差が無いかを統計学的に検討した。(結果)男性21例、女性8例、平均年齢65歳(36~83歳)。治療前の髄液中IL-10中央値は42 pg/ml(<2~1280p, 国内会議頭蓋内び慢性大細胞性Bリンパ腫における髄液中IL-10値とB細胞分化マーカーとの関連性口頭発表(一般)
- 第30回日本脳腫瘍病理学会、第4回国際脳腫瘍病理シンポジウム, 2012年05月, 日本語, 日本脳腫瘍病理学会, 名古屋, 近年、代謝酵素であるイソクエン酸脱水素酵素(IDH)の異常と腫瘍形成との関連が報告されている。今回我々はグリオーマで発現が亢進しているmicroRNA-183 (miR-183)とIDH2との関連を検討し、さらにHIF-1αへの影響について検討したので報告する。(対象および方法)6症例の同一患者でそれぞれの膠芽腫組織および腫瘍周囲脳組織を採取して、腫瘍におけるIDH2, HIF-1αのmRNAおよびmiR-183の相対的発現量をリアルタイムPCRを用いて比較検討した。また、悪性グリオーマ48例および腫瘍周囲脳組織5例を用いて、腫瘍におけるIDH2, HIF-1αのmRNAおよびmiR-183の相対的発現量をリアルタイムPCRを用いて比較検討した。グリオーマ細胞株(A172, U87MG, T98G, U251)に対して、miR-183 mimicを細, 国内会議悪性グリオーマにおけるIDH2およびHIF-1α発現とマイクロRNAによる発現抑制口頭発表(一般)
- 第30回日本脳腫瘍病理学会、第4回国際脳腫瘍病理シンポジウム, 2012年05月, 日本語, 日本脳腫瘍病理学会, 名古屋, Primary leptomeningeal sarcomatosisは髄膜に原発し、硬膜病変を主にび慢性に広がる肉腫で、発生頻度は極めて少ない。我々はPrimary leptomeningeal sarcomatosisと考えられた症例を経験したので報告する。(症例)40歳、女性。2010年10月より頭痛、嘔吐出現。頭部MRIで頚髄の腫脹と延髄腹側、脳底槽、側頭葉、脊髄などの硬膜、軟膜の造影所見が認められた。血液検査などでは異常を認めず、髄液検査では蛋白上昇、糖低下を認める以外異常所見は認めず、腫瘍マーカー、細胞診、培養検査もすべて陰性であった。胸腹部CTも異常所見無く、炎症性疾患を考えステロイドパルス治療を施行。一時症状の軽減は認められたが、MRI所見に変化を認めず、2011年3月に側頭部硬膜の造影部位の生検術が施行された。H.E.染色では、紡錘, 国内会議Primary leptomeningeal sarcomatiosisと考えられた1症例口頭発表(一般)
- 9th Meeting of Asian Society for Neuro-Oncorogy, 2012年04月, 英語, Meeting of Asian Society for Neuro-Oncorogy, Taipei, Objective;MicroRNAs (miRNAs) are small, non-coding RNAs, which regulate gene expression and contribute to cell proliferation, differentiation and metabolism. Our previous study demonstrated the up-regulation of microRNA-183 (miR-183) in malignant glioma by miRNA microarray analysis. miR-183 has complementary sequences in the 3'-untranslated region (3'UTR) of isocitrat, 国際会議Regulation of IDH2 and HIF-lalpha by microRNA in malignant glioma口頭発表(一般)
- 9th Meeting of Asian Society for Neuro-Oncorogy, 2012年04月, 英語, Meeting of Asian Society for Neuro-Oncorogy, Taipei, Title; Oncogenic EGFR signaling activates an mTORC2-NF-B pathway that promotes chemotherapy resistanceAuthors: Kazuhiro Tanaka1, Paul S. Mischel2-4, Eiji Kohmura1Affiliations: 1Department of Neurosurgery, Kobe University Graduate Scholl of Medicine, Kobe 650-0017, Japan; 2Department of Pathology and Laboratory Medicine, 3Henry Singleton Brain Tumor Program, 4Jonsson Comprehens, 国際会議Oncogenic EGFR signaling activates an mTORC2-NF-B pathway that promotes chemotherapy resistance口頭発表(一般)
- 9th Meeting of Asian Society for Neuro-Oncorogy, 2012年04月, 英語, Meeting of Asian Society for Neuro-Oncorogy, Taipei, Objective;The diagnosis of primary central nervous system lymphoma (PCNSL) by radiographical examination is often difficult because of its similarity to other brain tumors. Because early diagnosis and treatment of PCNSL attenuates disease progression and neurologic deterioration, useful biomarkers are required.Study Design;To test whether interleukin-10 (IL-10) can be a useful, 国際会議Cerebrospinal fluid interleukin-10(IL-10) is a potentially useful biomarker in immunocompetent primary central nervous system lymphoma(PCNSL)口頭発表(一般)
- 第24回日本脳神経外科国際フォーラム(JNEF), 2009年09月, 英語, 岐阜, 国際会議Cavernous malformations with and without venous malformatios:Pitfalls of MR images.口頭発表(一般)
- 第26回日本脳腫瘍病理学会, 2008年05月, 日本語, 日本脳腫瘍病理学会, 東京, 国内会議多発性放射線誘発性脳腫瘍の1例口頭発表(一般)
- 第11回日本脳腫瘍の外科学会, 2007年11月, 日本語, 日本脳腫瘍の外科学会, 神戸, 国内会議頭蓋内病変に対する定位的生検術の問題点の検討口頭発表(一般)
- 第66回社団法人日本脳神経外科学会総会, 2007年10月, 日本語, 社団法人日本脳神経外科学会, 東京, 国内会議膠芽腫および退形成星細胞腫におけるOlig2発現量と予後との関係口頭発表(一般)
- 第66回社団法人日本脳神経外科学会総会, 2007年10月, 日本語, 社団法人日本脳神経外科学会, 東京, 国内会議頭蓋底脊索腫に対する治療の課題口頭発表(一般)
- 第66回社団法人日本脳神経外科学会総会, 2007年10月, 日本語, 社団法人日本脳神経外科学会, 東京, 国内会議悪性神経膠腫に対するTemozolomideの治療成績と臨床上の問題点ポスター発表
- 第54回日本脳神経外科学会近畿支部学術集会・第66回近畿脳腫瘍研究会, 2007年09月, 日本語, 日本脳神経外科学会近畿支部学術集会・近畿脳腫瘍研究会, 大阪, 国内会議グリオーマにおけるマイクロRNAの発現について口頭発表(一般)
- 第19回日本頭蓋底外科学会, 2007年07月, 日本語, 日本頭蓋底外科学会, 東京, 国内会議大孔部腫瘍摘出手術における声帯筋電図付気管内チューブの有用性口頭発表(一般)
- 第19回日本頭蓋底外科学会, 2007年07月, 日本語, 日本頭蓋底外科学会, 東京, 国内会議右中頭蓋窩から側頭下窩へ進展した斜台原発巨大脊索腫に対する1手術例口頭発表(一般)
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 2024年04月01日 - 2027年03月31日膠芽腫患者のケトン食療法による腸内細菌叢の変化とシンバイオティクスによる増強効果
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 2023年04月01日 - 2026年03月31日低酸素環境下にあるグリオーマ細胞の膜脂質代謝リモデリングと分子機構の解析悪性グリオーマでは網羅的DNA解析の発達によって多くの遺伝子異常や癌シグナル経路が 明らかとなってきたが、細胞内代謝に関する分子生物学的メカニズムは不明な点が多い。特に、腫瘍微小環境における酸素・栄養状態はグリオーマ細胞の悪性化や治療抵抗性の獲得に繋がると考えられる。本研究では低酸素環境下のグリオーマ細胞の膜脂質代謝変化(リモデリング)を明らかにすべく、リピドーム解析や分子生物学的解析で、細胞膜を構成するリン脂質やコレステロール、脂肪酸の組成変化および機能解析を行うことである。また、悪性グリオーマに対する標準的治療薬であるテモゾロミド(アルキル化剤)はDNA損傷によりアポトーシスを誘導するが、低酸素環境下においてグリオーマ細胞が治療抵抗性を獲得する機序について、膜脂質代謝の変化に着目して細胞膜の機能を解明する。 グリオーマ培養細胞(U87およびT98グリオーマ細胞)を用いたリピドーム定量分析法では、低酸素状態においてコレステロールやホスファチジルセリン(PS)やホスファチジルエタノールアミン(PE)の含有率が増加していた。また、ホスファチジルコリン(PC)の含有率は変化しないが、リン脂質の疎水性尾部を形成する2本の脂肪酸について不飽和脂肪酸より飽和脂肪酸の割合が増加していた。また、膜脂質代謝に関与する遺伝子発現解析をリアルタイムPCR法やWestern blot法で行い、低酸素によって飽和脂肪酸を含むホスファチジルコリン(PC)の生合成に強く関与するリゾリン脂質アシル転移酵素LPCAT1の発現が増加していることを確認した。
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 2022年04月01日 - 2025年03月31日マクロファージ機能を標的とした髄芽腫の新規治療法の開発
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 2020年04月01日 - 2023年03月31日悪性グリオーマのグルタミン飢餓状態による一炭素代謝経路の調整と新規治療標的の探索悪性グリオーマの腫瘍内環境は一様でなく、特に中心部は低酸素・低栄養状態に曝されており、グリオーマ細胞の増殖停止や細胞死の原因になるが、一部の細胞は代謝的順応・適応に成功し、その変化は更なる悪性化プロセスの転機になると考えられる。本研究は悪性グリオーマの腫瘍内代謝環境が不均一であることに着目し、腫瘍細胞が栄養飢餓状態(グルタミン飢餓状態)に適合していくメカニズムを明らかにすることである。 グリオーマ患者の術前MRスペクトロスコピー検査のLC-modelによるデータ解析やグリオーマ手術検体(組織)およびグリオーマ培養細胞を用いたガスクロマトグラフィー/質量分析計によるメタボローム解析によって、グルタミン飢餓状態を代償するグリオーマの細胞内代謝機構が働いていると想定された。 特にセリン合成や一炭素代謝に注目して、その関連する代謝遺伝子の発現解析をリアルタイムPCR法で行い、セリン合成に関する代謝関連遺伝子Phosphoserine aminotransferase 1 (PSAT1)、葉酸・一炭素代謝関連遺伝子Serine hydroxymethyl transferase 2 (SHMT12), Methylenetetrahydrofolate dehydrogenase 1L/2 (MTHFD1L/2)の発現上昇を確認した。グリオーマ腫瘍検体でもWestern blotによる蛋白発現を解析し、腫瘍では正常脳組織よりSHMT2やMTHFD2の発現が高いことを確認した。特にMTHFD2遺伝子に注目し、siRNAによるMTHFD2遺伝子発現抑制によってグルタミン飢餓状態にあるグリオーマ細胞に効果的な細胞死を誘導すること、それにはreactive oxygen species (ROS)が関与することを同定した。これらの結果から、グルタミン飢餓状態にあるグリオーマ細胞の生存に一炭素代謝に関与するMTHFD2遺伝子が重要な役割を担っていることが示唆された。 さらにセリン合成の機序については、代謝Flux解析によってグルタミン飢餓によるオートファジーが強く影響することを見出して解析を進めている。
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 2020年04月01日 - 2023年03月31日膠芽腫に対するアミノ酸代謝阻害併用ケトン食療法の基礎的研究87、SVGp12グリオーマ細胞をを10cm dishで培養し、グルタミナーゼ阻害剤(GLSi)を10μM投与したものと、していないもので48時間後、96時間後の細胞増殖抑制効果を検討した結果、2つの細胞で増殖が抑制され、生存細胞割合が低下していた。また、グルタミナーゼ阻害剤に化学療法薬であるテモゾロミドを投与して併用効果を検討した結果、併用群の方は細胞生存割合が低下していた。特にT98細胞とU87Viii細胞で効果が著明であった。また、グリオーマ細胞にグルタミナーゼ阻害剤と血管新生阻害剤を投与して生存割合を検討した結果、併用しなかったものと比べて有意な差は認めなかった。以上より、グルタミナーゼ阻害剤は、抗がん剤のテモゾロミドとの併用でより効果があることが分かった。 次に、U87膠芽腫細胞をヌードマウスの脳内に移植し、ケトン食を摂取させると、通常の食事に比べて有意では無かったが、生存期間が延長した。ケトン食を投与したマウスの腫瘍内代謝物をGC/MSを用いてメタボローム解析を行うと、グルタミン酸、アスパラギン酸、セリン、スレオニン、メチオニン、バリン等のアミノ酸が著明に上昇していた。これは、グルコースを低下させているのでアミノ酸の取り込みが亢進し、アミノ酸代謝が亢進していることが示唆された。腫瘍組織を採取して細胞分裂の指標であるKi-67indexを調べると、ケトン食と通常食では有意な差を認めなかった。脳腫瘍移植マウスにケトン食に加えグルタミナーゼ阻害剤のGLSiを腹腔内投与するとマウスの生存期間は有意では無かったが、コントロールに比較して若干生存期間の延長を認めた。 今後、マウスの数を増やして検討する。
- 学術研究助成基金助成金/基盤研究(C), 2018年04月 - 2021年03月競争的資金
- 学術研究助成基金助成金/基盤研究(C), 2018年04月 - 2021年03月競争的資金
- 学術研究助成基金助成金/基盤研究(C), 2017年04月 - 2020年03月競争的資金
- 学術研究助成基金助成金/基盤研究(C), 2017年04月 - 2020年03月競争的資金
- 学術研究助成基金助成金/基盤研究(C), 2017年04月 - 2020年03月, 研究代表者競争的資金
- 学術研究助成基金助成金/基盤研究(C), 2015年04月 - 2018年03月競争的資金
- 学術研究助成基金助成金/基盤研究(C), 2014年04月 - 2017年03月競争的資金
- 学術研究助成基金助成金/基盤研究(C), 2014年04月 - 2017年03月, 研究代表者競争的資金
- 科学研究費一部基金/基盤研究(B)特設, 2013年04月 - 2016年03月競争的資金
- 学術研究助成基金助成金/基盤研究(C), 2013年04月 - 2016年03月競争的資金
- 科学研究費補助金/若手研究(B), 2012年04月 - 2014年03月, 研究代表者競争的資金
- 日本学術振興会, 科学研究費助成事業, 若手研究(B), 神戸大学, 2009年 - 2009年Oligー1,Oligー2遺伝子導入による悪性グリオーマ治療の試み