Updated on 2023/12/05

写真a

 
HIGA Nayuta
 
Organization
Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area Graduate School of Medical and Dental Sciences Advanced Therapeutics Course Neurology Assistant Professor
Title
Assistant Professor

Degree

  • 博士(医学) ( 2020.3 )

Research Interests

  • 脳腫瘍

  • 脳神経外科

  • グリオーマ

  • ゲノム・エピゲノム解析

Research Areas

  • Life Science / Neurosurgery

Research History

  • Kagoshima University   Assistant Professor

    2021.4

  • Kagoshima University   Hospital

    2019.10

  • Kagoshima University   Medical and Dental Hospital, Medical and Dental Sciences Area Medical and Dental Hospital Clinical Center Emergency Critical Care Center   Assistant Professor

    2019.1 - 2019.9

  • Kagoshima University   Hospital   Assistant Professor

    2019.1 - 2019.9

  • Kagoshima University   Hospital

    2016.2 - 2018.12

Professional Memberships

  • THE JAPAN NEUROSURGICAL SOCIETY

  • 日本分子脳神経外科学会

  • 日本脳腫瘍病理学会

  • 日本脳腫瘍学会

  • 日本神経内視鏡学会

  • 日本小児神経外科学会

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Papers

  • YAMANAKA Sae, TOKIMURA Hiroshi, HIGA Nayuta, IWAMOTO Hirofumi, NISHIMUTA Yosuke, SUEYOSHI Kazunobu, YONEZAWA Hajime, TAJITSU Kenichiro, AKAHANE Toshiaki, TANIMOTO Akihide, HANAYA Ryosuke .  Pilocytic Astrocytoma Presenting with Spontaneous Cerebellar Hemorrhage: A Case Report .  NMC Case Report Journal10 ( 0 ) 303 - 308   2023.12Pilocytic Astrocytoma Presenting with Spontaneous Cerebellar Hemorrhage: A Case Report

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    Language:English   Publisher:The Japan Neurosurgical Society  

    <p>Hemorrhagic pilocytic astrocytomas (PAs) are rare, accounting for 1.1%-8.0% of all PA cases. They are reported to occur more frequently in older populations, with a male predominance. In this study, we report a case of a 14-year-old boy who presented with a headache, vertigo, and diplopia. As per his brain computed tomography scan, a small hematoma was observed in the left inferior cerebellar peduncle. Follow-up magnetic resonance imaging (MRI) revealed repeated minor bleeding from the lesion and mild expansion, with no neurological deficits. Four years later, the patient developed nausea, vomiting, and left abducens palsy. MRI revealed a mulberry-shaped mass surrounded by a hypointense rim, suggesting a cavernous angioma. The lesion was surgically resected via midline occipital craniotomy with the opening of the cerebellomedullary fissure. Histopathological examination of the lesion revealed PA. Next-generation sequencing analyses revealed that PAs harbored mutations in the <i>ARID1A</i>, <i>ATM</i>, and <i>POLE</i> genes but not in the <i>BRAF</i> gene. To the best of our knowledge, there are yet no reported studies on these mutations in PAs to date. Thus, PA should be considered in the differential diagnosis of cerebellar hemorrhage, especially in young adults and children. </p>

    DOI: 10.2176/jns-nmc.2023-0152

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  • Kiyohisa Kamimura, Tsubasa Nakano, Tomohito Hasegawa, Masanori Nakajo, Chihiro Yamada, Yoshiki Kamimura, Kentaro Akune, Fumitaka Ejima, Takuro Ayukawa, Hiroaki Nagano, Koji Takumi, Masatoyo Nakajo, Nayuta Higa, Hajime Yonezawa, Ryosuke Hanaya, Mari Kirishima, Akihide Tanimoto, Takashi Iwanaga, Hiroshi Imai, Thorsten Feiweier, Takashi Yoshiura .  Differentiating primary central nervous system lymphoma from glioblastoma by time-dependent diffusion using oscillating gradient. .  Cancer imaging : the official publication of the International Cancer Imaging Society23 ( 1 ) 114 - 114   2023.11Differentiating primary central nervous system lymphoma from glioblastoma by time-dependent diffusion using oscillating gradient.International journal

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    BACKGROUND: This study aimed to elucidate the impact of effective diffusion time setting on apparent diffusion coefficient (ADC)-based differentiation between primary central nervous system lymphomas (PCNSLs) and glioblastomas (GBMs) and to investigate the usage of time-dependent diffusion magnetic resonance imaging (MRI) parameters. METHODS: A retrospective study was conducted involving 21 patients with PCNSLs and 66 patients with GBMs using diffusion weighted imaging (DWI) sequences with oscillating gradient spin-echo (Δeff = 7.1 ms) and conventional pulsed gradient (Δeff = 44.5 ms). In addition to ADC maps at the two diffusion times (ADC7.1 ms and ADC44.5 ms), we generated maps of the ADC changes (cADC) and the relative ADC changes (rcADC) between the two diffusion times. Regions of interest were placed on enhancing regions and non-enhancing peritumoral regions. The mean and the fifth and 95th percentile values of each parameter were compared between PCNSLs and GBMs. The area under the receiver operating characteristic curve (AUC) values were used to compare the discriminating performances among the indices. RESULTS: In enhancing regions, the mean and fifth and 95th percentile values of ADC44.5 ms and ADC7.1 ms in PCNSLs were significantly lower than those in GBMs (p = 0.02 for 95th percentile of ADC44.5 ms, p = 0.04 for ADC7.1 ms, and p < 0.01 for others). Furthermore, the mean and fifth and 95th percentile values of cADC and rcADC were significantly higher in PCNSLs than in GBMs (each p < 0.01). The AUC of the best-performing index for ADC7.1 ms was significantly lower than that for ADC44.5 ms (p < 0.001). The mean rcADC showed the highest discriminating performance (AUC = 0.920) among all indices. In peritumoral regions, no significant difference in any of the three indices of ADC44.5 ms, ADC7.1 ms, cADC, and rcADC was observed between PCNSLs and GBMs. CONCLUSIONS: Effective diffusion time setting can have a crucial impact on the performance of ADC in differentiating between PCNSLs and GBMs. The time-dependent diffusion MRI parameters may be useful in the differentiation of these lesions.

    DOI: 10.1186/s40644-023-00639-7

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  • Ryutaro Makino, Shingo Fujio, Jun Sugata, Masanori Yonenaga, Tomoko Hanada, Nayuta Higa, Hitoshi Yamahata, Ryosuke Hanaya .  Indocyanine green endoscopic evaluation of pituitary stalk and gland blood flow in craniopharyngiomas. .  Neurosurgical review46 ( 1 ) 312 - 312   2023.11Indocyanine green endoscopic evaluation of pituitary stalk and gland blood flow in craniopharyngiomas.International journal

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    To assess the use of indocyanine green (ICG) fluorescence endoscopy to evaluate pituitary blood flow in craniopharyngioma resection and its possible impact on intraoperative decisions regarding pituitary stalk processing. Patients with craniopharyngiomas who had undergone transsphenoidal surgery since March 2021, when an ICG endoscope was introduced at the Kagoshima University Hospital, were included in the study. When targeted tumor removal was approaching completion, 10 mg of ICG was administered intravenously to evaluate blood flow in the pituitary stalk and gland. ICG signals and endocrinological status before and after surgery were evaluated retrospectively. Pituitary stalk and gland blood flow were evaluated as positive (++), weakly positive (+), and no signal (-).Ten patients with craniopharyngiomas underwent transsphenoidal surgery using an ICG endoscope (mean age 56.6 ± 14.2 years; 40% male). Among the eight patients in whom the pituitary stalk was preserved, pituitary function with positive signal on the stalk was intact in two. Two other patients with weakly positive stalk and positive pituitary gland signals showed intact function or minimal pituitary dysfunction. Four patients had impairments in more than three axes with poor ICG signals in the stalk or pituitary gland. Two patients underwent pituitary amputation because of high tumor invasion and lack of ICG signal in the stalk after tumor removal, resulting in panhypopituitarism. A negative ICG signal in the pituitary stalk is likely to indicate postoperative pituitary function loss. Craniopharyngioma surgery using ICG endoscopy may be useful for predicting endocrine prognosis and improving tumor outcomes.

    DOI: 10.1007/s10143-023-02223-w

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  • Mari Kirishima, Toshiaki Akahane, Tomoko Takajo, Nayuta Higa, Hajime Yonezawa, Hiroyuki Uchida, Kiyohisa Kamimura, Ryosuke Hanaya, Koji Yoshimoto, Michiyo Higashi, Takashi Yoshiura, Akihide Tanimoto .  A case of glioblastoma harboring non-amplified epidermal growth factor receptor variant III: Critical molecular detection using RNA-based panel analysis. .  Pathology, research and practice248   154712 - 154712   2023.7International journal

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    Amplification of the epidermal growth factor receptor gene (EGFR) and its variants are the most commonly detected pathogenic gene alterations in glioblastoma. Herein, we report a case of molecularly defined glioblastoma harboring an EGFR variant III (EGFRvIII) without EGFR amplification. The initial histological diagnosis was isocitrate dehydrogenase (IDH)-wildtype low-grade glioma, due to an absence of anaplasia, necrosis, and microvascular proliferation, and a low Ki-67 labeling index. DNA-based next-generation sequencing (NGS) panel analysis revealed a TERTp promoter mutation but no EGFR mutation or amplification, supporting the diagnosis of "molecular glioblastoma." However, RNA-based NGS panel analysis revealed mRNA expression of EGFRvIII. Therefore, the final integrative diagnosis was glioblastoma with non-amplified EGFRvIII. Our report suggests that non-amplified EGFRvIII might be an early molecular event in glioblastoma tumorigenesis. In addition to the usual DNA-based analysis, RNA-based analysis is required to identify exon-skipping EGFR variants without EGFR amplification.

    DOI: 10.1016/j.prp.2023.154712

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  • Takashi Kawahara, Masamichi Atsuchi, Kazunori Arita, Shingo Fujio, Nayuta Higa, Ryosuke Hanaya .  Paravertebral Cerebrospinal Fluid Exudation in Young Women with Postdural Puncture Headache: A Hypothetical Interpretation based on Anatomical Study on Intervertebral Foramen. .  Asian journal of neurosurgery18 ( 1 ) 117 - 124   2023.3Paravertebral Cerebrospinal Fluid Exudation in Young Women with Postdural Puncture Headache: A Hypothetical Interpretation based on Anatomical Study on Intervertebral Foramen.International journal

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    Background  Postdural puncture headache (PDPH) is defined as a prolonged orthostatic headache secondary to a lumbar puncture. The mechanism underlying this unpleasant complication and the reasons explaining its higher incidence in the young are not well understood. Here, we speculate on the mechanisms underlying PDPH based on spinal magnetic resonance imaging (MRI) in patients with PDPH and an anatomical study on the size of the intervertebral foramen. Methods  Brain and spinal MRI findings were examined in two young women with PDPH. The relationship between age and size of the intervertebral foramen on computed tomography was assessed in 25 female volunteers (22-89 years old) without spinal disease. Results  The causative interventions leading to PDPH were epidural anesthesia for painless delivery in a 28-year-old woman and lumbar puncture for examination of the cerebrospinal fluid (CSF) in a 17-year-old woman. These two patients developed severe orthostatic hypotension following the procedure. Brain MRI showed signs of intracranial hypotension, including subdural effusion, in one patient, but no abnormality in the other. Spinal MRI revealed an anterior shift of the spinal cord at the thoracic level and CSF exudation into the paravertebral space at the lumbar level. Treatment involving an epidural blood patch in one patient and strict bed rest with sufficient hydration in the second led to improvement of symptoms and reduction of paravertebral CSF exudation. The size of the intervertebral foramen at the L2-3 level in the 25 volunteers showed a decrease in an age-dependent manner (Spearman's rho -0.8751, p  < 0.001). Conclusion  We suggest that CSF exudation from the epidural space of the vertebral canal to the paravertebral space through the intervertebral foramen, which is generally larger in the younger population, is the causative mechanism of PDPH.

    DOI: 10.1055/s-0043-1763526

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  • Keisuke Masuda, Nayuta Higa, Hajime Yonezawa, Hiroyuki Uchida, Ryosuke Hanaya .  Difficult differential diagnosis of ectopic germinoma from multiple sclerosis: A case report and literature review. .  International journal of surgery case reports103   107884 - 107884   2023.2International journal

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    INTRODUCTION AND IMPORTANCE: Intracranial germinomas are germ cell tumors that commonly develop in the pineal or neurohypophysis regions. As ectopic germinomas are rarely observed within the cerebrum and are associated with atypical image findings, diagnosis is challenging. CASE PRESENTATION: A 14-year-old boy was admitted to our hospital with complaints of vomiting and headache. Gadolinium-enhanced magnetic resonance imaging revealed ring-enhancing lesions in his left frontal lobe and basal ganglia. Susceptibility-weighted imaging indicated that the subependymal veins passing through the lesion centers were engorged, while electrophoretic analysis of cerebrospinal fluid identified oligoclonal bands (OCBs); both were typical of multiple sclerosis (MS). Tumor biopsy revealed many cells with atypical mitotic figures and nuclear enlargements, suggesting malignant disease. As the tumor rapidly proliferated, we opted for surgical excision of the lesions. Histopathological analyses revealed "two-cell patterns" characteristic of germinoma. Immunohistochemistry was positive for placental alkaline phosphatase and c-KIT. The definitive diagnosis was germinoma. After chemoradiotherapy, the patient was discharged without neurological deficits. CLINICAL DISCUSSION: OCBs and several magnetic resonance imaging features (including open ring enhancement, T2 hypointense rims, mild mass effects, mild perilesional edema, peripheral restriction around the lesion, and vessel-like structures running through the lesion center) are useful diagnostic signs for the radiological discrimination of MS from germinoma. However, owing to these factors, some cases are difficult to diagnose. CONCLUSION: Our case report of an unusual ectopic cerebral germinoma illustrates the difficulty of distinguishing it from MS. Therefore, we recommend proper tissue sampling in such cases, especially in adolescent patients, to make definitive germinoma diagnoses.

    DOI: 10.1016/j.ijscr.2023.107884

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  • Kuroki Shinichi, Oyoshi Tatsuki, Higa Nayuta, Sato Masanori, Komasaku Soichiro, Tokimura Hiroshi, Yoshimoto Koji, Hanaya Ryosuke .  A case of progressive hydrocephalus and syringomyelia due to occipital encephalocele: Mechanisms of sibling onset and concomitant hydrocephalus .  Nervous System in Children48 ( 3 ) 290 - 294   2023A case of progressive hydrocephalus and syringomyelia due to occipital encephalocele: Mechanisms of sibling onset and concomitant hydrocephalus

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    <p>Congenital anomalies such as neural tube defects (NTD), microcephaly, Chiari malformation, premature skull fusion, and syringomyelia are associated with 15-20% of occipital encephaloceles. NTDs are thought to develop as a result of environmental or genetic factors, or a combination of the two, and the onset of encephaloceles in siblings is uncommon. We present a case study of occipital encephalocele with hydrocephalus and syringomyelia in a patient with a sibling-onset encephalocele. A newborn girl with an occipital encephalocele is the patient. Her sister was born with an occipital encephalocele as well. Prenatal ultrasound confirmed both frontal bone depression and posterior cervical mass at 27 weeks pregnant. At 32 weeks pregnant, fetal magnetic resonance imaging revealed a posterior cervical encephalocele. The neural tissue had escaped from the cranium. It also revealed the herniation of the hindbrain. Syringomyelia was discovered between the lower cervical cord and the thoraco-lumbar spinal cord junction. At 38 weeks pregnant, the baby was delivered via scheduled cesarean section. A 4 cm diameter mass was discovered in the midline suboccipital to upper cervical vertebrae. She was diagnosed with syringomyelia and an occipital encephalocele. On the first day of her life, the child underwent encephalocele repair surgery. On the ninth day, however, the patient required another repair surgery for a cerebrospinal fluid leak. Following that, the encephalocele vanished and the syringomyelia improved, but the child required a VP shunt for progressive hydrocephalus at 3 months of age. The mechanisms of progressive hydrocephalus in a child with occipital encephalocele will be discussed. Hyperthermia, genetic background, maternal nutritional deficiency, aflatoxin, and other environmental factors are all risk factors for encephalocele. Concerning genetic factors, the incidence of NTDs among siblings is only about 2-5%, and there are still many unknowns in the encephalocele of genetic factors. Hydrocephalus has been reported in 60-90% of patients with occipital encephalocele, with 63% developing hydrocephalus after surgery. The causes of hydrocephalus include stenosis or torsion of the cerebrospinal fluid tract and venous sinus obstruction. After the encephalocele was repaired, subcutaneous fluid retention, which was thought to be CSF leak, was also observed. In this case, we can say that the changes in cerebrospinal fluid circulation and infection caused the hydrocephalus. In contrast to children with an encephalocele that did not have hydrocephalus or brain tissue, the presence of hydrocephalus resulted in a worse prognosis. We will keep a close eye on her future development.</p>

    DOI: 10.34544/jspn.48.3_290

  • Nayuta Higa, Toshiaki Akahane, Seiya Yokoyama, Ryutaro Makino, Hajime Yonezawa, Hiroyuki Uchida, Tomoko Takajo, Mari Kirishima, Taiji Hamada, Naoki Noguchi, Ryosuke Otsuji, Daisuke Kuga, Shohei Nagasaka, Hitoshi Yamahata, Junkoh Yamamoto, Koji Yoshimoto, Akihide Tanimoto, Ryosuke Hanaya .  Favorable prognostic impact of phosphatase and tensin homolog alterations in wild-type isocitrate dehydrogenase and telomerase reverse transcriptase promoter glioblastoma. .  Neuro-oncology advances5 ( 1 ) vdad078   2023International journal

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    BACKGROUND: Telomerase reverse transcriptase promoter (TERTp) mutations are a biological marker of glioblastoma; however, the prognostic significance of TERTp mutational status is controversial. We evaluated this impact by retrospectively analyzing the outcomes of patients with isocitrate dehydrogenase (IDH)- and TERTp-wild-type glioblastomas. METHODS: Using custom next-generation sequencing, we analyzed 208 glioblastoma samples harboring wild-type IDH. RESULTS: TERTp mutations were detected in 143 samples (68.8%). The remaining 65 (31.2%) were TERTp-wild-type. Among the TERTp-wild-type glioblastoma samples, we observed a significant difference in median progression-free survival (18.6 and 11.4 months, respectively) and overall survival (not reached and 15.7 months, respectively) in patients with and without phosphatase and tensin homolog (PTEN) loss and/or mutation. Patients with TERTp-wild-type glioblastomas with PTEN loss and/or mutation were younger and had higher Karnofsky Performance Status scores than those without PTEN loss and/or mutation. We divided the patients with TERTp-wild-type into 3 clusters using unsupervised hierarchical clustering: Good (PTEN and TP53 alterations; lack of CDKN2A/B homozygous deletion and platelet-derived growth factor receptor alpha (PDGFRA) alterations), intermediate (PTEN alterations, CDKN2A/B homozygous deletion, lack of PDGFRA, and TP53 alterations), and poor (PDGFRA and TP53 alterations, CDKN2A/B homozygous deletion, and lack of PTEN alterations) outcomes. Kaplan-Meier survival analysis indicated that these clusters significantly correlated with the overall survival of TERTp-wild-type glioblastoma patients. CONCLUSIONS: Here, we report that PTEN loss and/or mutation is the most useful marker for predicting favorable outcomes in patients with IDH- and TERTp-wild-type glioblastomas. The combination of 4 genes, PTEN, TP53, CDKN2A/B, and PDGFRA, is important for the molecular classification and individual prognosis of patients with IDH- and TERTp-wild-type glioblastomas.

    DOI: 10.1093/noajnl/vdad078

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  • Ryutaro Makino, Nayuta Higa, Toshiaki Akahane, Hajime Yonezawa, Hiroyuki Uchida, Tomoko Takajo, Shingo Fujio, Mari Kirishima, Taiji Hamada, Hitoshi Yamahata, Kiyohisa Kamimura, Takashi Yoshiura, Koji Yoshimoto, Akihide Tanimoto, Ryosuke Hanaya .  Alterations in EGFR and PDGFRA are associated with the localization of contrast-enhancing lesions in glioblastoma. .  Neuro-oncology advances5 ( 1 ) vdad110   2023International journal

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    BACKGROUND: Glioblastoma (GBM) is a malignant brain tumor, with radiological and genetic heterogeneity. We examined the association between radiological characteristics and driver gene alterations. METHODS: We analyzed the driver genes of 124 patients with IDH wild-type GBM with contrast enhancement using magnetic resonance imaging. We used a next-generation sequencing panel to identify mutations in driver genes and matched them with radiological information. Contrast-enhancing lesion localization of GBMs was classified into 4 groups based on their relationship with the subventricular zone (SVZ) and cortex (Ctx). RESULTS: The cohort included 69 men (55.6%) and 55 women (44.4%) with a mean age of 66.4 ± 13.3 years. EGFR and PDGFRA alterations were detected in 28.2% and 22.6% of the patients, respectively. Contrast-enhancing lesion touching both the SVZ and Ctx was excluded because it was difficult to determine whether it originated from the SVZ or Ctx. Contrast-enhancing lesions touching the SVZ but not the Ctx had significantly worse overall survival than non-SVZ lesions (441 days vs. 897 days, P = .002). GBM touching only the Ctx had a better prognosis (901 days vs. 473 days, P < .001) than non-Ctx lesions and was associated with EGFR alteration (39.4% vs. 13.2%, P = .015). Multiple contrast lesions were predominant in PDGFRA alteration and RB1-wild type (P = .036 and P = .031, respectively). CONCLUSIONS: EGFR alteration was associated with cortical lesions. And PDGFRA alteration correlated with multiple lesions. Our results suggest that clarifying the association between driver genes and tumor localization may be useful in clinical practice, including prognosis prediction.

    DOI: 10.1093/noajnl/vdad110

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  • Ryutaro Makino, Shingo Fujio, Tomoko Hanada, Masanori Yonenaga, Shigeru Kawade, Hiroshi Hashiguchi, Yoshihiko Nishio, Nayuta Higa, Kazunori Arita, Koji Yoshimoto, Ryosuke Hanaya .  Delayed postoperative hyponatremia in patients with acromegaly: incidence and predictive factors. .  Pituitary26 ( 1 ) 42 - 50   2022.11International journal

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    PURPOSE: Delayed postoperative hyponatremia (DPH) is a unique complication of transsphenoidal surgery (TSS) in pituitary tumors. Growth hormone (GH) enhances renal sodium reabsorption; however, the association between postoperative GH reduction and DPH in acromegaly is unclear. This study was performed to clarify the incidence of and the predictive factors for DPH in patients with acromegaly who underwent TSS. METHODS: Ninety-four patients with active acromegaly were examined retrospectively. During the postoperative course, patients with serum sodium levels ≤ 134 mEq/L were classified into the DPH group. We compared basic clinical characteristics, tumor characteristics, and preoperative and postoperative examination findings between the DPH and non-DPH groups. RESULTS: DPH occurred in 39 patients (41.5%), and the lowest serum sodium levels were generally observed during postoperative days (PODs) 7-9. They needed a 3-day longer hospital stay than those without DPH. The DPH group had lower preoperative body weight and body mass index. In addition, a transient increase in body weight during PODs 5-7 occurred with a transient decrease in urinary volume in the DPH group. Preoperative and postoperative GH and insulin-like growth factor-1 levels did not differ between the two groups. CONCLUSION: The findings suggested that lower preoperative weight and a postoperative transient gain in body weight are associated with an increased risk of DPH in acromegaly patients undergoing transsphenoidal surgery.

    DOI: 10.1007/s11102-022-01288-y

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  • Mari Kirishima, Toshiaki Akahane, Nayuta Higa, Shinsuke Suzuki, Shinichi Ueno, Hajime Yonezawa, Hiroyuki Uchida, Ryosuke Hanaya, Koji Yoshimoto, Shohei Shimajiri, Ikumi Kitazono, Akihide Tanimoto .  IDH-mutant astrocytoma with an evolutional progression to CDKN2A/B homozygous deletion and NTRK fusion during recurrence: A case report. .  Pathology, research and practice239   154163 - 154163   2022.10International journal

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    We reported a case of molecularly defined isocitrate dehydrogenase (IDH)-mutant astrocytoma that recurred twice with aggressive behavior and increased anaplastic morphology. Primary and recurrent tumors were analyzed using custom-made DNA-based cancer gene and RNA-based fusion panels for next-generation sequencing (NGS). NGS analyses revealed that recurrent astrocytoma, in addition to IDH1 and tumor protein 53 mutations detected in the primary lesion, harbored cyclin-dependent kinase inhibitor (CDKN) 2 A/B homozygous deletion and neurotrophic tropomyosin receptor kinase 2 (NTRK2) fusion genes that consisted of golgin A1- and cyclin-dependent kinase 5 regulatory subunit associated protein 2-NTRK2 fusions. Anaplasia and necrosis were observed in the recurrent tumors, but not in the primary lesion. Therefore, the integrative diagnosis was primary IDH-mutant astrocytoma grade 2 and recurrent IDH-mutant astrocytoma grade 4 with NTRK2 fusions. This is a worthwhile report describing a case of IDH-mutant astrocytoma that showed genomic evolution during tumor recurrence. Our report suggests that NTRK fusion and CDKN2A/B homozygous deletion promote high-grade transformation and indicate an unfavorable prognosis of IDH-mutant astrocytoma.

    DOI: 10.1016/j.prp.2022.154163

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  • HIGA Nayuta, AKAHANE Toshiaki, YOKOYAMA Seiya, YONEZAWA Hajime, UCHIDA Hiroyuki, FUJIO Shingo, KIRISHIMA Mari, TAKIGAWA Kosuke, HATA Nobuhiro, TOH Keita, YAMAMOTO Junkoh, HANAYA Ryosuke, TANIMOTO Akihide, YOSHIMOTO Koji .  Molecular Genetic Profile of 300 Japanese Patients with Diffuse Gliomas Using a Glioma-tailored Gene Panel .  Neurologia medico-chirurgica62 ( 9 ) 391 - 399   2022.9

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:The Japan Neurosurgical Society  

    <p>Rapid technological advances in molecular biology, including next-generation sequencing, have identified key genetic alterations in central nervous system (CNS) tumors. Accordingly, the fifth edition of the World Health Organization (WHO) CNS tumor classification was published in 2021. We analyzed 303 patients with diffuse glioma using an amplicon-based glioma-tailored gene panel for detecting 1p/19q codeletion and driver gene mutations such as <i>IDH1/2</i>, <i>TERTp</i>, <i>EGFR</i>, and <i>CDKN2A/B</i> on a single platform. Within glioblastomas (GBMs), the most commonly mutated genes were <i>TERTp</i>, <i>TP53</i>, <i>PTEN</i>, <i>NF1</i>, and <i>PDGFRA</i>, which was the most frequently mutated tyrosine kinase receptor in GBM, followed by <i>EGFR</i>. The genes that most commonly showed evidence of loss were <i>PTEN</i>, <i>CDKN2A/B</i>, and <i>RB1</i>, whereas the genes that most commonly showed evidence of gain/amplification were <i>EGFR</i>, <i>PDGFRA</i>, and <i>CDK4</i>. In 22 grade III oligodendroglial tumors, 3 (14%) patients had <i>CDKN2A/B</i> homozygous deletion, and 4 (18%) patients had <i>ARID1A</i> mutation. In grade III oligodendroglial tumors, an <i>ARID1A</i> mutation was associated with worse progression-free survival. Reclassification based on the WHO 2021 classification resulted in 62.5% of grade II/III <i>isocitrate dehydrogenase</i> (<i>IDH</i>) -wildtype astrocytomas being classified as <i>IDH</i>-wildtype GBM and 37.5% as not elsewhere classified. In summary, our glioma-tailored gene panel was applicable for molecular diagnosis in the WHO 2021 classification. In addition, we successfully reclassified the 303 diffuse glioma cases based on the WHO 2021 classification and clarified the genetic profile of diffuse gliomas in the Japanese population.</p>

    DOI: 10.2176/jns-nmc.2022-0103

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  • Higa Nayuta, Akahane Toshiaki, Yokoyama Seiya, Yonezawa Hajime, Uchida Hiroyuki, Fujio Shingo, Kirishima Mari, Takigawa Kosuke, Hata Nobuhiro, Toh Keita, Yamamoto Junkoh, Hanaya Ryosuke, Tanimoto Akihide, Yoshimoto Koji .  Molecular Genetic Profile of 300 Japanese Patients with Diffuse Gliomas Using a Glioma-tailored Gene Panel(タイトル和訳中) .  Neurologia medico-chirurgica62 ( 9 ) 391 - 399   2022.9Molecular Genetic Profile of 300 Japanese Patients with Diffuse Gliomas Using a Glioma-tailored Gene Panel(タイトル和訳中)

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    日本人患者のびまん性神経膠腫にみられる、分子遺伝学的プロファイルについて調査した。著者等の大学で収集した、びまん性神経膠腫患者303例の腫瘍組織試料を用いて、神経膠腫に特化した遺伝子パネルから、分子遺伝学的プロファイルを解析した。その結果、膠芽腫(GBM)患者185例に最も変異が多く認められた遺伝子は、TERTp遺伝子、TP53遺伝子、PTEN遺伝子、NF1遺伝子とPDGFRA遺伝子であった。また、欠失が最も多く認められた遺伝子は、PTEN遺伝子およびCDKN2A/B及びRB1遺伝子で、増加/増幅が最も多く認められた遺伝子は、EGFR遺伝子とPDGFRA遺伝子およびCDK4遺伝子であった。さらに、グレードIII乏突起膠腫22例のうち3例には、CDKN2A/B遺伝子のホモ接合性欠失が、4例にはARID1A遺伝子変異が検出され、ARID1A遺伝子変異が無増悪生存転帰不良と関連することが示唆された。なお、WHO脳腫瘍分類2021により、グレードII/IIIでIDH野生型星状細胞腫の62.5%が、IDH野生型のGBMに再分類された。本報により、神経膠腫に特化した遺伝子パネルが、WHO脳腫瘍分類2021に準じた分子診断に適用可能であることが確認された。

  • 東 拓一郎, 増田 圭亮, 比嘉 那優大, 米澤 大, 内田 裕之, 花谷 亮典 .  神経膠腫におけるてんかん発症に影響する因子 .  てんかん研究40 ( 2 ) 368 - 368   2022.8神経膠腫におけるてんかん発症に影響する因子

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  • Nayuta Higa, Toshiaki Akahane, Seiya Yokoyama, Hajime Yonezawa, Hiroyuki Uchida, Tomoko Takajo, Ryosuke Otsuji, Taiji Hamada, Kei Matsuo, Mari Kirishima, Nobuhiro Hata, Ryosuke Hanaya, Akihide Tanimoto, Koji Yoshimoto .  Prognostic impact of <i>PDGFRA</i> gain/amplification and <i>MGMT</i> promoter methylation status in patients with <i>IDH</i> wild-type glioblastoma .  Neuro-Oncology Advances4 ( 1 ) vdac097   2022.6International journal

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    Abstract

    Background

    Platelet-derived growth factor receptor alpha (PDGFRA) is the second most frequently mutated tyrosine kinase receptor in glioblastoma (GBM). However, the prognostic impact of PDGFRA amplification on GBM patients remains unclear. Herein, we evaluated this impact by retrospectively analyzing outcomes of patients with IDH wild-type GBM.

    Methods

    Using a custom-made oncopanel, we evaluated PDGFRA gain/amplification in 107 GBM samples harboring wild-type IDH, along with MGMT promoter (MGMTp) methylation status.

    Results

    We detected PDGFRA gain/amplification in 31 samples (29.0%). PDGFRA gain/amplification predicted poor prognosis (P = .003). Compared to unamplified PDGFRA, PDGFRA gain/amplification in GBM was associated with higher patient age (P = .031), higher Ki-67 score (P = .019), and lower extent of surgical resection (P = .033). Unmethylated MGMTp also predicted poor prognosis (P = .005). As PDGFRA gain/amplification and unmethylated MGMTp were independent factors for poor prognosis in multivariate analyses, we grouped GBM cases based on PDGFRA and MGMTp status: poor (PDGFRA gain/amplification and unmethylated MGMTp), intermediate (PDGFRA gain/amplification or unmethylated MGMTp), and good (PDGFRA intact and methylated MGMTp) prognosis. The Kaplan-Meier survival analysis indicated that these groups significantly correlated with the OS of GBM patients (P &amp;lt; .001).

    Conclusions

    Here we report that PDGFRA gain/amplification is a predictor of poor prognosis in IDH wild-type GBM. Combining PDGFRA gain/amplification with MGMTp methylation status improves individual prognosis prediction in patients with IDH wild-type GBM.

    DOI: 10.1093/noajnl/vdac097

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    Other Link: https://academic.oup.com/noa/article-pdf/4/1/vdac097/45178840/vdac097.pdf

  • 比嘉 那優大, 吉本 幸司 .  今月の特集2 良性腫瘍の病理と遺伝子異常 良性脳腫瘍の病理と遺伝子異常 .  臨床検査66 ( 6 ) 742 - 746   2022.6

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    <文献概要>Point ●髄膜腫では遺伝子変異と臨床学的特徴との関連を認める.特にTERTプロモーター変異は臨床経過を予測する有用な分子マーカーであることが示唆されている.●髄膜腫では,遺伝子変異以外に,網羅的なメチル化に基づく新たな分類法の有用性も報告されている.●扁平上皮乳頭型頭蓋咽頭腫ではBRAF V600E変異を認め,MAPKシグナル伝達経路を阻害する標的薬の有効性が報告されている.●良性脳腫瘍でも遺伝子変異による新しい腫瘍分類や,遺伝子変異に合わせた標的治療を採用するprecision medicineが発展しつつある.

    DOI: 10.11477/mf.1542203030

    CiNii Books

  • Nayuta Higa, Toshiaki Akahane, Taiji Hamada, Hajime Yonezawa, Hiroyuki Uchida, Ryutaro Makino, Shoji Watanabe, Tomoko Takajo, Seiya Yokoyama, Mari Kirishima, Kei Matsuo, Shingo Fujio, Ryosuke Hanaya, Akihide Tanimoto, Koji Yoshimoto .  Distribution and favorable prognostic implication of genomic EGFR alterations in IDH-wildtype glioblastoma. .  Cancer medicine12 ( 1 ) 49 - 60   2022.6International journal

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    BACKGROUND: We aimed to evaluate the mutation profile, transcriptional variants, and prognostic impact of the epidermal growth factor receptor (EGFR) gene in isocitrate dehydrogenase (IDH)-wildtype glioblastomas (GBMs). METHODS: We sequenced EGFR, evaluated the EGFR splicing profile using a next-generation sequencing oncopanel, and analyzed the outcomes in 138 grade IV IDH-wildtype GBM cases. RESULTS: EGFR mutations were observed in 10% of GBMs. A total of 23.9% of the GBMs showed EGFR amplification. Moreover, 25% of the EGFR mutations occurred in the kinase domain. Notably, EGFR alterations were a predictor of good prognosis (p = 0.035). GBM with EGFR alterations was associated with higher Karnofsky Performance Scale scores (p = 0.014) and lower Ki-67 scores (p = 0.005) than GBM without EGFR alterations. EGFRvIII positivity was detected in 21% of EGFR-amplified GBMs. We identified two other EGFR variants in GBM cases with deletions of exons 6-7 (Δe 6-7) and exons 2-14 (Δe 2-14). In one case, the initial EGFRvIII mutation transformed into an EGFR Δe 2-14 mutation during recurrence. CONCLUSIONS: We found that the EGFR gene profiles of GBM differ among cohorts and that EGFR alterations are good prognostic markers of overall survival in patients with IDH-wildtype GBM. Additionally, we identified rare EGFR variants with longitudinal and temporal transformations of EGFRvIII.

    DOI: 10.1002/cam4.4939

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  • 城之下 唯子, 河村 健太郎, 比嘉 那優大, 衛藤 誠二, 下堂薗 恵 .  症例報告 大脳基底核部ジャーミノーマによる上肢麻痺例への作業療法の経験 .  総合リハビリテーション50 ( 5 ) 503 - 508   2022.5

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    <文献概要>[目的]大脳基底核部のジャーミノーマによる麻痺は,早期診断が難しく腫瘍が画像上消失しても機能回復は困難とされる.今回,複合的な作業療法を継続し上肢機能が良好な結果を呈した症例を報告する.[症例]10歳代後半男性.左上下肢の脱力があり,頭部核磁気共鳴画像法にて右基底核などに病変を認めジャーミノーマと診断された.[経過]化学療法のため3ヵ月間入院した.7ヵ月後,右側脳室前角近傍に再発のため入院し,約6ヵ月間,放射線治療と化学療法を受けた.[作業療法]入院中の各期間,上肢麻痺に対して促通反復療法や課題指向型アプローチ,振動刺激痙縮抑制法,生活環境における麻痺側上肢の動作指導を実施した.[結果]16ヵ月の経過でBox and Block Testは32点から40点へ,簡易上肢機能検査は73点から87点へ変化し,生活動作で実用性が向上した.[結語]大脳基底核部ジャーミノーマは集学的治療により生命予後は良好であり,複合的な作業療法を加えることで麻痺肢の機能向上をめざせる可能性がある.

    DOI: 10.11477/mf.1552202503

    CiNii Books

  • 城之下 唯子, 河村 健太郎, 比嘉 那優大, 衛藤 誠二, 下堂薗 恵 .  大脳基底核部ジャーミノーマによる上肢麻痺例への作業療法の経験 .  総合リハビリテーション50 ( 5 ) 503 - 508   2022.5大脳基底核部ジャーミノーマによる上肢麻痺例への作業療法の経験

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    Language:Japanese   Publisher:(株)医学書院  

    <文献概要>[目的]大脳基底核部のジャーミノーマによる麻痺は,早期診断が難しく腫瘍が画像上消失しても機能回復は困難とされる.今回,複合的な作業療法を継続し上肢機能が良好な結果を呈した症例を報告する.[症例]10歳代後半男性.左上下肢の脱力があり,頭部核磁気共鳴画像法にて右基底核などに病変を認めジャーミノーマと診断された.[経過]化学療法のため3ヵ月間入院した.7ヵ月後,右側脳室前角近傍に再発のため入院し,約6ヵ月間,放射線治療と化学療法を受けた.[作業療法]入院中の各期間,上肢麻痺に対して促通反復療法や課題指向型アプローチ,振動刺激痙縮抑制法,生活環境における麻痺側上肢の動作指導を実施した.[結果]16ヵ月の経過でBox and Block Testは32点から40点へ,簡易上肢機能検査は73点から87点へ変化し,生活動作で実用性が向上した.[結語]大脳基底核部ジャーミノーマは集学的治療により生命予後は良好であり,複合的な作業療法を加えることで麻痺肢の機能向上をめざせる可能性がある.

  • Mari Kirishima, Toshiaki Akahane, Nayuta Higa, Hajime Yonezawa, Hiroyuki Uchida, Ikumi Kitazono, Michiyo Higashi, Koji Yoshimoto, Akihide Tanimoto .  Integrated diagnosis of adult-type glioma according to 2021 World Health Organization classification: Analysis of 184 cases using a custom-made next-generation sequencing panel. .  Pathology international72 ( 3 ) 207 - 210   2022.3International journal

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    DOI: 10.1111/pin.13197

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  • Taiji Hamada, Toshiaki Akahane, Seiya Yokoyama, Nayuta Higa, Mari Kirishima, Kei Matsuo, Michiko Shimokawa, Koji Yoshimoto, Akihide Tanimoto .  An oncogenic splice variant of PDGFRα in adult glioblastoma as a therapeutic target for selective CDK4/6 inhibitors. .  Scientific reports12 ( 1 ) 1275 - 1275   2022.1International journal

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    Understanding human genome alterations is necessary to optimize genome-based cancer therapeutics. However, some newly discovered mutations remain as variants of unknown significance (VUS). Here, the mutation c.1403A > G in exon 10 of the platelet-derived growth factor receptor-alpha (PDGFRA) gene, a VUS found in adult glioblastoma multiforme (GBM), was introduced in human embryonal kidney 293 T (HEK293T) cells using genome editing to investigate its potential oncogenic functions. Genome editing was performed using CRISPR/Cas9; the proliferation, drug sensitivity, and carcinogenic potential of genome-edited cells were investigated. We also investigated the mechanism underlying the observed phenotypes. Three GBM patients carrying the c.1403A > G mutation were studied to validate the in vitro results. The c.1403A > G mutation led to a splice variant (p.K455_N468delinsN) because of the generation of a 3'-acceptor splice site in exon 10. PDGFRA-mutated HEK293T cells exhibited a higher proliferative activity via PDGFRα and the cyclin-dependent kinase (CDK)4/CDK6-cyclin D1 signaling pathway in a ligand-independent manner. They showed higher sensitivity to multi-kinase, receptor tyrosine kinase, and CDK4/CDK6 inhibitors. Of the three GBM patients studied, two harbored the p.K455_N468delinsN splice variant. The splicing mutation c.1403A > G in PDGFRA is oncogenic in nature. Kinase inhibitors targeting PDGFRα and CDK4/CDK6 signaling should be evaluated for treating GBM patients harboring this mutation.

    DOI: 10.1038/s41598-022-05391-9

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  • Masanori Sato, Tatsuki Oyoshi, Hirofumi Iwamoto, Natsuko Tanoue, Soichiro Komasaku, Nayuta Higa, Hiroshi Hosoyama, Hiroshi Tokimura, Satoshi Ibara, Ryosuke Hanaya, Koji Yoshimoto .  The collagen matrix dural substitute graft prevents postoperative cerebrospinal fluid leakage after ventriculoperitoneal shunt surgery in patients aged <1 year. .  Surgical neurology international13   461 - 461   2022International journal

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    Background: Cerebrospinal fluid (CSF) leakage is a common complication of ventriculoperitoneal shunt (VPS) and has the potential to induce shunt infection. Especially in infants and children, these are serious complications. DuraGen is a collagen matrix dural substitute used to reduce the risk of CSF leakage in various neurosurgeries. We report our VPS procedure with DuraGen for preventing postoperative CSF leakage in patients aged <1 year. Methods: We used DuraGen to prevent postoperative CSF leakage in six VPS surgeries. Antibiotic-impregnated shunt catheters and programmable valves with anti-siphon devices were also used in all cases. DuraGen was placed inside and atop the burr hole. All cases had an initial shunt pressure of 5 cmH2O. Fibrin glue was not used. Results: The patients underwent follow-up for a year after VPS surgery. There was no postoperative subcutaneous CSF collection or leakage after all six VPS surgeries. Furthermore, no postoperative shunt infections or DuraGen-induced adverse events were noted. Conclusion: We speculate that DuraGen has a preventive effect on postoperative CSF leakage in VPS cases aged <1 year.

    DOI: 10.25259/SNI_629_2022

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  • Takashi Kawahara, Masamichi Atsuchi, Kazunori Arita, Shingo Fujio, Nayuta Higa, F M Moinuddin, Koji Yoshimoto, Ryosuke Hanaya .  Dural sac shrinkage signs on spinal magnetic resonance imaging indicate overdrainage after lumboperitoneal shunt for idiopathic normal pressure hydrocephalus. .  Surgical neurology international13   269 - 269   2022International journal

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    Background: We previously found the usefulness of dural sac shrinkage signs (DSSSs), which are the anterior shift of the spinal cord and dura mater behind the cord, detected by magnetic resonance imaging (MRI) at the thoracic level for the diagnosis of spontaneous intracranial hypotension (IH). This is a retrospective survey on the usefulness of DSSSs for the early detection of iatrogenic IH caused by overdrainage through a lumboperitoneal shunt (LPS) for patients with idiopathic normal pressure hydrocephalus (INPH). Methods: Forty-five INPH patients had an LPS using a pressure programmable valve equipped with an anti-siphon device. Results: Nine patients complained of orthostatic headache after the LPS, indicating IH due to overdrainage, which persisted for more than a week in three patients and 2-7days in six patients. The headache was transient/ nonorthostatic in ten patients and absent in 26 patients. The DSSSs and accompanying enlargement of the venous plexus were observed in all three patients with prolonged orthostatic headaches. Only the anterior shift of the dura mater was observed in 1 (4%) among 25 patients who had short-term orthostatic headache, transient/ nonorthostatic headache, or absent headache, and underwent spinal MRI. A patient with prolonged severe orthostatic headache with both DSSSs eventually developed intracranial subdural effusion and underwent tandem valve surgery, which provided a quick improvement of symptoms. The DSSSs on thoracic MRI also disappeared promptly. Conclusion: DSSSs may serve as objective signs for the diagnosis of IH due to overdrainage through an LPS for INPH.

    DOI: 10.25259/SNI_291_2022

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  • Ryutaro Makino, Hitoshi Yamahata, Masanori Yonenaga, Shingo Fujio, Nayuta Higa, Ryosuke Hanaya, Koji Yoshimoto .  Radiological comparison of the midpoint of the nasion-inion line and the external auditory canal for measuring the cranial center of the gravity-sagittal vertical axis .  INTERDISCIPLINARY NEUROSURGERY-ADVANCED TECHNIQUES AND CASE MANAGEMENT26   2021.12

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    Background: Spinal sagittal malalignment affects a patient's quality of life, and the condition has gained increasing importance. The cranial center of the gravity-sagittal vertical axis (CCG-SVA) helps in assessing sagittal alignment. Two major landmarks of the CCG are used for measuring the CCG-SVA: the midpoint of the nasion-inion line (MNI) and the external auditory canal (EAC). However, the correspondence between these two points has not been proved. In this study, we radiologically examined the positional relationship between them.Methods: We obtained lateral skull radiographs from 87 patients aged between 21 and 91 years. We evaluated the following: the vertical distance between the MNI and the upper margin of the EAC (Distance A), the horizontal distance between the plumb line from the MNI and the anterior margin of the EAC (Distance B), and the horizontal distance between the plumb line from the MNI and the center of the EAC (Distance C).Results: The average values of Distances A, B, and C were 19.6 +/- 5.0, 1.65 +/- 5.7, and 5.45 +/- 5.5 mm, respectively, indicating that the plumb lines dropped from the MNI and the EAC did not match exactly. The measured values showed no sex-specific differences (P > 0.05, Mann-Whitney U test).Conclusions: The present study demonstrated that the MNI and EAC locations had minimal horizontal differences. The CCG-SVA should be measured by considering the differences between the MNI and the EAC.

    DOI: 10.1016/j.inat.2021.101299

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  • Shun Onishi, Chihiro Kedoin, Masakazu Murakami, Nayuta Higa, Akihiro Yoshida, Kazutoshi Onitsuka, Takahiro Moriyama, Koji Yoshimoto, Satoshi Ieiri .  Image-guided confirmation of a precision pull-through procedure during laparoscopically assisted anorectoplasty in an open MRI operating theater: first application in an infantile case with anorectal malformation. .  Surgical case reports7 ( 1 ) 211 - 211   2021.9Image-guided confirmation of a precision pull-through procedure during laparoscopically assisted anorectoplasty in an open MRI operating theater: first application in an infantile case with anorectal malformation.International journal

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    BACKGROUND: Image-guided surgery with an open magnetic resonance imaging (MRI) system is applied for brain tumors in the neurosurgery field, but has rarely been reported in pediatric surgery. We report our initial experience of intraoperative confirmation of precision rectal pull-through during laparoscopically assisted anorectoplasty (LAARP) in an open MRI operating theater for pediatric patients with anorectal malformation (ARM). CASE PRESENTATION: A 3.0 kg term male neonate was delivered with anorectal malformation. An invertogram revealed the intermediate type. Transverse colostomy was made on the left upper abdomen. The recto-bulbar urethral fistula (RBUF) was diagnosed by a distal colostogram and voiding cystourethrogram. LAARP was planned at 6 months of age. Because this was the first procedure in which the pediatric abdomen had been scanned in an open MRI operating theater in our institution, we scanned his pelvic floor under sedation 3 weeks before the operation using the open MRI system in our operation room. We performed the operation with 4 trocars. The peritoneal reflection was carefully incised and the rectum was dissected. The RBUF was resected. The center of the muscle complex was detected at the perineal skin with an electrical nerve stimulator, and a 7-mm longitudinal skin incision was made on the perineal lesion for anoplasty. The muscle complex and the pubo-rectal sling were confirmed laparoscopically using a 3.5-mm bipolar forceps connected to the electrical nerve stimulator. Anoplasty was performed between the rectal stump and perineal skin. After anoplasty, the patient was scanned with open MRI under general anesthesia. We attached the quadrature-detection (QD) head coil around the patient's pelvis and inserted him in the gantry. A 0.45-T open MRI clearly revealed that the pulled through rectum was located in the center of the muscle complex on T2-weighted images. The postoperative course was uneventful. Oral intake was started on post-operative day 1. Postoperative dynamic urography showed no complication (e.g., leakage or residual fistula). CONCLUSIONS: We successfully performed LAARP for ARM, with intraoperative confirmation of precision rectal pull-through in an open MRI operating theater. Further cases are required to evaluate the application of open MRI systems in pediatric surgery.

    DOI: 10.1186/s40792-021-01298-1

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  • Takaaki Hiwatari, Hitoshi Yamahata, Masanori Yonenaga, Shingo Fujio, Nayuta Higa, Ryosuke Hanaya, Kazunori Arita, Koji Yoshimoto .  The incidence of depressed skull fractures due to the use of pin-type head frame systems in the adult population: 10-year experience of a single neurosurgical center. .  World neurosurgery155   e395 - e401   2021.8International journal

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    OBJECTIVE: Pin-type head frame systems have become a worldwide standard procedure, but they can cause some complications on rare occasions. This study aimed to examine the incidence and associated risk factors of depressed skull fracture and related intracranial hematoma (DSFH) due to the use of head frames in our institute over the past 10 years. METHODS: This study included 1,749 patients who underwent neurosurgical surgeries using pin-type head frames, including the Mayfield skull clamp (721 cases) and the Sugita head frame (1,028 cases). We retrospectively reviewed hospital records of our institute to identify cases of DSFH, and documented the type of head frame used, as well as patient characteristics. RESULTS: The incidence of DSFH was 0.29% (5/1,749 cases). All 5 cases had an associated epidural hematoma, with a single case having an additional dural laceration (without subdural damage). All perforation sites, located at the parietal bone near the pterion, occurred by the unilateral horizontal screw of the Sugita head frame. None of the patients experienced postoperative neurological decline. CONCLUSIONS: Even in the adult population, the DSFH by the pin-type head frame can occur infrequently. Based on our results, we recommend that the following factors should be considered when the pin-type head frame is used for neurosurgical procedures: the location of pin application, thickness and fragility of the skull, and adequate control of compressive forces exerted by the head frame.

    DOI: 10.1016/j.wneu.2021.08.070

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  • Masahiro Yamamoto, Tomomi Sanomachi, Shuhei Suzuki, Hiroyuki Uchida, Hajime Yonezawa, Nayuta Higa, Tomoko Takajo, Yuki Yamada, Asuka Sugai, Keita Togashi, Shizuka Seino, Masashi Okada, Yukihiko Sonoda, Hirofumi Hirano, Koji Yoshimoto, Chifumi Kitanaka .  Roles for hENT1 and dCK in gemcitabine sensitivity and malignancy of meningioma .  Neuro-Oncology23 ( 6 ) 945 - 954   2021.6International journal

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    <title>Abstract</title>
    <sec>
    <title>Background</title>
    High-grade meningiomas are aggressive tumors with high morbidity and mortality rates that frequently recur even after surgery and adjuvant radiotherapy. However, limited information is currently available on the biology of these tumors, and no alternative adjuvant treatment options exist. Although we previously demonstrated that high-grade meningioma cells were highly sensitive to gemcitabine in vitro and in vivo, the underlying molecular mechanisms remain unknown.


    </sec>
    <sec>
    <title>Methods</title>
    We examined the roles of hENT1 (human equilibrative nucleoside transporter 1) and dCK (deoxycytidine kinase) in the gemcitabine sensitivity and growth of meningioma cells in vitro. Tissue samples from meningiomas (26 WHO grade I and 21 WHO grade II/III meningiomas) were immunohistochemically analyzed for hENT1 and dCK as well as for Ki-67 as a marker of proliferative activity.


    </sec>
    <sec>
    <title>Results</title>
    hENT1 and dCK, which play critical roles in the intracellular transport and activation of gemcitabine, respectively, were responsible for the high gemcitabine sensitivity of high-grade meningioma cells and were strongly expressed in high-grade meningiomas. hENT1 expression was required for the proliferation and survival of high-grade meningioma cells and dCK expression. Furthermore, high hENT1 and dCK expression levels correlated with stronger tumor cell proliferative activity and shorter survival in meningioma patients.


    </sec>
    <sec>
    <title>Conclusions</title>
    The present results suggest that hENT1 is a key molecular factor influencing the growth capacity and gemcitabine sensitivity of meningioma cells and also that hENT1, together with dCK, may be a viable prognostic marker for meningioma patients as well as a predictive marker of their responses to gemcitabine.


    </sec>

    DOI: 10.1093/neuonc/noab015

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  • Masanori Nakajo, Manisha Bohara, Kiyohisa Kamimura, Nayuta Higa, Takashi Yoshiura .  Correlation between amide proton transfer-related signal intensity and diffusion and perfusion magnetic resonance imaging parameters in high-grade glioma .  Scientific Reports11 ( 1 ) 11223   2021.5

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    <title>Abstract</title>Amide proton transfer (APT) imaging is a magnetic resonance (MR) molecular imaging technique that is sensitive to mobile proteins and peptides in living tissue. Studies have shown that APT-related signal intensity (APTSI) parallels with the malignancy grade of gliomas, allowing the preoperative assessment of tumor grades. An increased APTSI in malignant gliomas has been attributed to cytosolic proteins and peptides in proliferating tumor cells; however, the exact underlying mechanism is poorly understood. To get an insight into the mechanism of high APTSI in malignant gliomas, we investigated the correlations between APTSI and several MR imaging parameters including apparent diffusion coefficient (ADC), relative cerebral blood volume and pharmacokinetic parameters obtained in the same regions-of-interest in 22 high-grade gliomas. We found a significant positive correlation between APTSI and ADC (ρ = 0.625 and 0.490 for observers 1 and 2, respectively; p &lt; 0.001 for both), which is known to be inversely correlated with cell density. Multiple regression analysis revealed that ADC was significantly associated with APTSI (p &lt; 0.001 for both observers). Our results suggest possible roles of extracellular proteins and peptides in high APTSI in malignant gliomas.

    DOI: 10.1038/s41598-021-90841-z

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    Other Link: http://www.nature.com/articles/s41598-021-90841-z

  • 内田 裕之, 赤羽 俊章, 比嘉 那優大, 米澤 大, 霧島 茉莉, 谷本 昭英, 吉本 幸司 .  Lower-grade gliomaの遺伝子プロファイル診断と予後についての検討 .  Brain Tumor Pathology38 ( Suppl. ) 077 - 077   2021.5Lower-grade gliomaの遺伝子プロファイル診断と予後についての検討

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  • 米澤 大, 比嘉 那優大, 内田 裕之, 赤羽 俊章, 横山 勢也, 霧島 茉莉, 平木 翼, 谷本 昭英, 吉本 幸司 .  脳腫瘍に特化したがん遺伝子パネル検査の実臨床における有用性 .  Brain Tumor Pathology38 ( Suppl. ) 073 - 073   2021.5脳腫瘍に特化したがん遺伝子パネル検査の実臨床における有用性

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  • 赤羽 俊章, 比嘉 那優大, 霧島 茉莉, 内田 裕之, 米澤 大, 坂本 一平, 野原 祥夫, 吉本 幸司, 谷本 昭英 .  神経膠腫診断用パネル検査で見つかった新規EGFR variantを有する神経膠腫の病理組織学的特徴 .  Brain Tumor Pathology38 ( Suppl. ) 073 - 073   2021.5神経膠腫診断用パネル検査で見つかった新規EGFR variantを有する神経膠腫の病理組織学的特徴

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  • 比嘉 那優大, 赤羽 俊章, 米澤 大, 内田 裕之, 藤尾 信吾, 横山 勢也, 霧島 茉莉, 濱田 大治, 谷本 昭英, 吉本 幸司 .  日本人のhigh grade glioma患者における遺伝子変異の特徴 .  Brain Tumor Pathology38 ( Suppl. ) 074 - 074   2021.5日本人のhigh grade glioma患者における遺伝子変異の特徴

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  • 谷本 昭英, 赤羽 俊章, 比嘉 那優大, 吉本 幸司 .  脳腫瘍の病理 カスタムNGSパネルによる神経膠腫の統合分子病理診断の実践と応用 .  日本病理学会会誌110 ( 1 ) 183 - 183   2021.3脳腫瘍の病理 カスタムNGSパネルによる神経膠腫の統合分子病理診断の実践と応用

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  • Muhammad Kamil, Tatsuki Oyoshi, Soichiro Komasaku, Shinichi Kuroki, Nayuta Higa, Koji Yoshimoto .  Fronto-Orbital Advancement and Posterior Cranial Vault Expansion Using Distraction Osteogenesis in Patients With Multiple Craniosynostosis .  Journal of Craniofacial SurgeryPublish Ahead of Print ( 5 ) 1882 - 1885   2021.1International journal

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Ovid Technologies (Wolters Kluwer Health)  

    ABSTRACT: This study aimed to evaluate the treatment outcomes and the efficiency of techniques of fronto-orbital advancement (FOA) and posterior cranial vault expansion (PCVE) using distraction osteogenesis in patients with multiple craniosynostosis. We assessed the treatment results and outcomes of 8 patients with multiple craniosynostosis at the Kagoshima University Hospital between 2005 and 2019. Each 4 patients underwent FOA and PCVE, respectively, using distraction osteogenesis. The cranial volume and developmental quotient (DQ) were measured at the preoperative period and 1 year after surgery. The mean patient age at surgery was 22 months. The mean preoperative cranial volume was 1027 and 1071 cm3 in the FOA and PCVE groups, respectively. The mean preoperative DQ scores were 74 and 67, respectively. After 1-year of follow-up, the corresponding mean cranial volume became 1108 and 1243 cm3, respectively. The corresponding mean DQ scores also improved to 74 and 81, respectively. The postoperative follow-ups in all cases were uneventful, except for persistent epilepsy in 1 patient. Fronto-orbital advancement and PCVE using distraction osteogenesis might contribute to good outcomes in expanding cranial volume, cosmetic osteogenesis, and infantile development in patients with multiple craniosynostosis. Regarding the cranial volume expansion, especially, PCVE using distraction osteogenesis is more effective than FOA.

    DOI: 10.1097/scs.0000000000007442

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  • Bureta C. .  Diffuse Large B-Cell Lymphoma of the Central Nervous System Manifesting with Intratumoral Hemorrhage: A Case Report and Literature Review .  World Neurosurgery143   490 - 494   2020.11

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    DOI: 10.1016/j.wneu.2020.07.213

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  • Higa Nayuta, Akahane Toshiaki, Yokoyama Seiya, Yonezawa Hajime, Uchida Hiroyuki, Takajo Tomoko, Kirishima Mari, Hamada Taiji, Matsuo Kei, Fujio Shingo, Hanada Tomoko, Hosoyama Hiroshi, Yonenaga Masanori, Sakamoto Akihisa, Hiraki Tsubasa, Tanimoto Akihide, Yoshimoto Koji .  A tailored next-generation sequencing panel identified distinct subtypes of wildtype IDH and TERT promoter glioblastomas(和訳中) .  Cancer Science111 ( 10 ) 3902 - 3911   2020.10A tailored next-generation sequencing panel identified distinct subtypes of wildtype IDH and TERT promoter glioblastomas(和訳中)

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    今回、神経膠腫の分子病理学的統合診断を目的として、新たに48遺伝子で構成された次世代シークエンサー(NGS)用カスタム遺伝子パネルを構築し、その実行可能性について検討した。なお、本パネルは、1p/2q共欠失とIDH1/2遺伝子、TP53遺伝子、PTEN遺伝子、PDGFRA遺伝子、NF1遺伝子、RB1遺伝子、CDKN2A/B遺伝子およびCDK4遺伝子とTERT遺伝子のプロモーター領域(TERTp)変異を検出するために、神経膠腫診断に特化した遺伝子パネルである。当院で開発した中枢神経系腫瘍組織バンクから、神経膠腫患者106例(グレードII:19例、グレードIII:23例、グレードIV:64例)を選択し、本パネルを用いて解析した結果、乏突起膠腫で1p/19q共欠失が正確に検出され、グレードIV患者64例中56例にはIDH遺伝子が野生型の膠芽腫が同定され、うち33例にTERTp変異が認められた。また、PDGFRA遺伝子の変異と増幅は、TERTp遺伝子が野生型の膠芽腫では43%に、TERTp変異を有する膠芽腫では6%に認められ、分子遺伝情報に基づいた階層分類により、IDH遺伝子が野生型の膠芽腫では、明確に3グループに分類された。さらに、PDGFRA遺伝子変異、CDK4遺伝子およびPFGFRA遺伝子の増幅、CDKN2A/B遺伝子でのホモ接合性欠失やTERTp変異の欠如により特徴付けられた主要なクラスタが、高年齢、Ki-67高スコア、予後不良および脳室周囲腫瘍と有意に関連することが明らかにされた。以上の解析結果から、本パネルにより、PDGFRA遺伝子異常が高頻度に認められ、IDH遺伝子およびTERTp遺伝子変異が野生型を示す膠芽腫患者の各サブタイプが同定された。

  • Nayuta Higa, Toshiaki Akahane, Seiya Yokoyama, Hajime Yonezawa, Hiroyuki Uchida, Tomoko Takajo, Mari Kirishima, Taiji Hamada, Kei Matsuo, Shingo Fujio, Tomoko Hanada, Hiroshi Hosoyama, Masanori Yonenaga, Akihisa Sakamoto, Tsubasa Hiraki, Akihide Tanimoto, Koji Yoshimoto .  A tailored next‐generation sequencing panel identified distinct subtypes of wildtype IDH and TERT promoter glioblastomas .  Cancer Science111 ( 10 ) 3902 - 3911   2020.10International journal

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    Central nervous system tumors are classified based on an integrated diagnosis combining histology and molecular characteristics, including IDH1/2 and H3-K27M mutations, as well as 1p/19q codeletion. Here, we aimed to develop and assess the feasibility of a glioma-tailored 48-gene next-generation sequencing (NGS) panel for integrated glioma diagnosis. We designed a glioma-tailored 48-gene NGS panel for detecting 1p/19q codeletion and mutations in IDH1/2, TP53, PTEN, PDGFRA, NF1, RB1, CDKN2A/B, CDK4, and the TERT promoter (TERTp). We analyzed 106 glioma patients (grade II: 19 cases, grade III: 23 cases, grade IV: 64 cases) using this system. The 1p/19q codeletion was detected precisely in oligodendroglial tumors using our NGS panel. In a cohort of 64 grade Ⅳ gliomas, we identified 56 IDH-wildtype glioblastomas. Within these IDH-wildtype glioblastomas, 33 samples (58.9%) showed a mutation in TERTp. Notably, PDGFRA mutations and their amplification were more commonly seen in TERTp-wildtype glioblastomas (43%) than in TERTp-mutant glioblastomas (6%) (P = .001). Hierarchical molecular classification of IDH-wildtype glioblastomas revealed 3 distinct groups of IDH-wildtype glioblastomas. One major cluster was characterized by mutations in PDGFRA, amplification of CDK4 and PDGFRA, homozygous deletion of CDKN2A/B, and absence of TERTp mutations. This cluster was significantly associated with older age (P = .021), higher Ki-67 score (P = .007), poor prognosis (P = .012), and a periventricular tumor location. We report the development of a glioma-tailored NGS panel for detecting 1p/19q codeletion and driver gene mutations on a single platform. Our panel identified distinct subtypes of IDH- and TERTp-wildtype glioblastomas with frequent PDGFRA alterations.

    DOI: 10.1111/cas.14597

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    Other Link: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cas.14597

  • Higa N. .  A case of developing obstructive hydrocephalus following aqueductal stenosis caused by developmental venous anomalies .  Child's Nervous System36 ( 7 ) 1549 - 1555   2020.7

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    Publisher:Child's Nervous System  

    DOI: 10.1007/s00381-019-04489-2

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  • Kamil M. .  A sellar neuroblastoma showing rapid growth and causing syndrome of inappropriate secretion of antidiuretic hormone: A case report .  Surgical Neurology International11   165   2020.6

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    Publisher:Surgical Neurology International  

    DOI: 10.25259/SNI_97_2020

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  • Manisha Bohara, Masanori Nakajo, Kiyohisa Kamimura, Tomohide Yoneyama, Yoshihiko Fukukura, Yutaro Kiyao, Hajime Yonezawa, Nayuta Higa, Mari Kirishima, Takashi Yoshiura .  Histological Grade of Meningioma: Prediction by Intravoxel Incoherent Motion Histogram Parameters .  Academic Radiology27 ( 3 ) 342 - 353   2020.3International journal

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    RATIONALE AND OBJECTIVES: To evaluate the usefulness of intravoxel incoherent motion (IVIM) histogram analysis for differentiating low-grade meningiomas (LGMs) and high-grade meningiomas (HGMs). MATERIALS AND METHODS: Fifty-nine patients with pathologically confirmed meningiomas (45 LGMs and 14 HGMs) underwent IVIM MR imaging. Maps of IVIM parameters (perfusion fraction, f; true diffusion coefficient, D; and pseudo diffusion coefficient, D*), as well as of the apparent diffusion coefficient (ADC), were generated. Histogram analysis was performed using parametric values from all voxels in regions-of-interest manually drawn to encompass the whole tumor. The histogram results of ADC and IVIM parameters were compared using the Mann-Whitney U test. Area under the receiver operating characteristic curve (AUC) values were generated to evaluate how well each parameter could differentiate LGMs from HGMs. Spearman's rank correlation coefficients were used to evaluate correlations between histogram parameters and Ki-67 expression. RESULTS: Compared to LGM, HGM showed significantly higher standard deviation (SD), variance, and coefficient of variation (CV) of ADC (p< 0.006-0.028; AUC, 0.693-0.748), D (p< 0.004-0.032; AUC, 0.670-0.752), and significantly higher CV of f (p< 0.005-0.024; AUC = 0.737). Means and percentiles of ADC and IVIM parameters did not differ significantly between LGM and HGM. Significant positive correlations were identified between Ki-67 and histogram parameters of ADC (SD, variance, kurtosis, skewness, and CV) and D (SD, variance, kurtosis, and CV), whereas no significant correlation with Ki-67 was shown for mean or percentiles of ADC and IVIM parameters. CONCLUSION: Heterogeneity histogram parameters of ADC, D, and f may be useful for differentiating LGMs from HGMs.

    DOI: 10.1016/j.acra.2019.04.012

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  • Takuro Hirano, Yoshinari Shinsato, Kan Tanabe, Nayuta Higa, Muhammad Kamil, Kohichi Kawahara, Masatatsu Yamamoto, Kentaro Minami, Michiko Shimokawa, Takaaki Arigami, Shigehiro Yanagita, Daisuke Matushita, Yoshikazu Uenosono, Sumiya Ishigami, Yuko Kijima, Kosei Maemura, Ikumi Kitazono, Akihide Tanimoto, Tatsuhiko Furukawa, Shoji Natsugoe .  FARP1 boosts CDC42 activity from integrin αvβ5 signaling and correlates with poor prognosis of advanced gastric cancer .  Oncogenesis9 ( 2 ) 13 - 13   2020.2

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    Publisher:Springer Science and Business Media LLC  

    <title>Abstract</title>Considering the poor prognosis of most advanced cancers, prevention of invasion and metastasis is essential for disease control. Ras homologous (Rho) guanine exchange factors (GEFs) and their signaling cascade could be potential therapeutic targets in advanced cancers. We conducted in silico analyses of The Cancer Genome Atlas expression data to identify candidate Rho-GEF genes showing aberrant expression in advanced gastric cancer and found <italic>FERM, Rho/ArhGEF, and pleckstrin domain protein 1</italic> (<italic>FARP1</italic>) expression is related to poor prognosis. Analyses in 91 clinical advanced gastric cancers of the relationship of prognosis and pathological factors with immunohistochemical expression of FARP1 indicated that high expression of FARP1 is significantly associated with lymphatic invasion, lymph metastasis, and poor prognosis of the patients (<italic>P</italic> = 0.025). In gastric cancer cells, FARP1 knockdown decreased cell motility, whereas FARP1 overexpression promoted cell motility and filopodium formation via CDC42 activation. FARP1 interacted with integrin β5, and a potent integrin αvβ5 inhibitor (SB273005) prevented cell motility in only high FARP1-expressing gastric cancer cells. These results suggest that the integrin αvβ5-FARP1-CDC42 axis plays a crucial role in gastric cancer cell migration and invasion. Thus, regulatory cascade upstream of Rho can be a specific and promising target of advanced cancer treatment.

    DOI: 10.1038/s41389-020-0190-7

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    Other Link: http://www.nature.com/articles/s41389-020-0190-7

  • Bajagain M, Oyoshi T, Hanada T, Higa N, Hiraki T, Kamimura K, Kuroki S, Yoshimoto K .  Histopathological variation in the demyelinating sentinel lesion of primary central nervous system lymphoma. .  Surgical neurology international11   342   2020Histopathological variation in the demyelinating sentinel lesion of primary central nervous system lymphoma.

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  • Bajagain M, Oyoshi T, Hanada T, Higa N, Hiraki T, Kamimura K, Kuroki S, Yoshimoto K .  Histopathological variation in the demyelinating sentinel lesion of primary central nervous system lymphoma. .  Surgical Neurology International11   342 - 342   2020Histopathological variation in the demyelinating sentinel lesion of primary central nervous system lymphoma.

  • Bureta C, Higa N, Makino R, Takajo T, Yonezawa H, Uchida H, Yoshimoto K .  Diffuse large B cell lymphoma of the central nervous system presenting with intratumoral hemorrhage: a case report and literature review .  World Neurosurgery143   490 - 494   2020Diffuse large B cell lymphoma of the central nervous system presenting with intratumoral hemorrhage: a case report and literature review

  • Kamil M, Higa N, Yonezawa H, Fujio S, Sugata J, Takajo T, Hiraki T, Hirato J, Arita K, Yoshimoto K .  A sellar neuroblastoma showing rapid growth and causing syndrome of inappropriate secretion of antidiuretic hormone: A case report .  Surgical Neurology International11   165 - 165   2020A sellar neuroblastoma showing rapid growth and causing syndrome of inappropriate secretion of antidiuretic hormone: A case report

  • Higa N, Dwiutomo R, Oyoshi T, Tanaka S, Bohara M, Yoshimoto K .  A case of developing obstructive hydrocephalus following aqueductal stenosis caused by developmental venous anomalies .  Child’s Nervous System36   1549 - 1555   2020A case of developing obstructive hydrocephalus following aqueductal stenosis caused by developmental venous anomalies

  • Nayuta Higa, Yoshinari Shinsato, Muhammad Kamil, Takuro Hirano, Tomoko Takajo, Michiko Shimokawa, Kentaro Minami, Masatatsu Yamamoto, Kohichi Kawahara, Hajime Yonezawa, Hirofumi Hirano, Tatsuhiko Furukawa, Koji Yoshimoto, Kazunori Arita .  Formin-like 1 (FMNL1) Is Associated with Glioblastoma Multiforme Mesenchymal Subtype and Independently Predicts Poor Prognosis .  International Journal of Molecular Sciences20 ( 24 ) 6355 - 6355   2019.12International journal

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:MDPI AG  

    Glioblastoma multiforme (GBM), the most common primary malignant brain tumor in adults, is characterized by rapid proliferation, aggressive migration, and invasion into normal brain tissue. Formin proteins have been implicated in these processes. However, the role of formin-like 1 (FMNL1) in cancer remains unclear. We studied FMNL1 expression in glioblastoma samples using immunohistochemistry. We sought to analyze the correlation between FMNL1 expression, clinicopathologic variables, and patient survival. Migration and invasion assays were used to verify the effect of FMNL1 on glioblastoma cell lines. Microarray data were downloaded from The Cancer Genome Atlas and analyzed using gene set enrichment analysis (GSEA). FMNL1 was an independent predictor of poor prognosis in a cohort of 217 glioblastoma multiforme cases (p &lt; 0.001). FMNL1 expression was significantly higher in the mesenchymal subtype. FMNL1 upregulation and downregulation were associated with mesenchymal and proneural markers in the GSEA, respectively. These data highlight the important role of FMNL1 in the neural-to-mesenchymal transition. Conversely, FMNL1 downregulation suppressed glioblastoma multiforme cell migration and invasion via DIAPH1 and GOLGA2, respectively. FMNL1 downregulation also suppressed actin fiber assembly, induced morphological changes, and diminished filamentous actin. FMNL1 is a promising therapeutic target and a useful biomarker for GBM progression.

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  • Kamil M. .  High filamin-C expression predicts enhanced invasiveness and poor outcome in glioblastoma multiforme .  British Journal of Cancer120 ( 8 ) 819 - 826   2019.4

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    Publisher:British Journal of Cancer  

    DOI: 10.1038/s41416-019-0413-x

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  • Kamil M, Shinsato Y, Higa N, Hirano T, Idogawa M, Takajo T, Minami K, Shimokawa M, Yamamoto M, Kawahara K, Yonezawa H, Hirano H, Furukawa T, Yoshimoto K, Arita K .  High filamin-C expression predicts enhanced invasiveness and poor outcome in glioblastoma multiforme. .  Br J Cancer120 ( 8 ) 819 - 826   2019High filamin-C expression predicts enhanced invasiveness and poor outcome in glioblastoma multiforme.

  • 山下 麻美, 大吉 達樹, 樫田 祐美, 東 拓一郎, 比嘉 那優大, 田上 なつ子, 細山 浩史, 有田 和徳 .  陥没骨折後に遅発性に発症した頭蓋骨膜洞の1例 .  小児の脳神経43 ( 4 ) 466 - 469   2018.12陥没骨折後に遅発性に発症した頭蓋骨膜洞の1例

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    Publisher:(一社)日本小児神経外科学会  

    頭蓋骨膜洞は頭蓋外静脈と頭蓋内静脈のtranscalvarial emissary veinを介した吻合が、頭皮下腫瘤となった疾患である。多くは先天性だが、我々は外傷後に遅発性に発症した頭蓋骨膜洞を経験したので報告する。症例は2歳女児。頭部外傷にて左前頭部陥没骨折と頭皮下血腫の診断で穿刺排液を施行。受傷2年後も腫瘤は仰臥位で増大、座位で速やかに消退する経過をたどった。画像評価後、止血困難な出血リスクや美容上の観点から摘出術を施行し、術後経過は良好であった。自然経過で改善のない外傷性頭蓋骨膜洞においては周囲骨膜を含めた摘出術が推奨される。(著者抄録)

  • F. M. Moinuddin, Hirofumi Hirano, Yoshinari Shinsato, Nayuta Higa, Kazunori Arita, Tatsuhiko Furukawa .  ATP7B expression in human glioblastoma is related to temozolomide resistance .  ONCOLOGY LETTERS14 ( 6 ) 7777 - 7782   2017.12

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    Publisher:SPANDIDOS PUBL LTD  

    Glioblastoma multiforme (GBM) is one of the most aggressive types of brain malignancy, with resistance to chemotherapy being a primary treatment obstacle. ATPase copper transporting beta (ATP7B) is involved in multidrug resistance; however, its expression in GBM remains to be evaluated. In the present study, GBM specimens from 79 patients who underwent gross total tumor removal followed by concomitant temozolomide (TMZ) chemotherapy and radiotherapy were assessed immunohistochemically. The association between the overall survival times of patients and the expression of ATP7B in neoplastic cells was evaluated. In 12/79 tumors (15.2%) &gt;10% of neoplastic cells were immunohistochemically-positive for ATP7B, and categorized as high-ATP7B GBM. In the remaining 67 tumors (84.8%) the rate of ATP7B-positive cells was &lt;10% and recorded as low-ATP7B GBM. The median overall survival times of patients with high-and low-ATP7B GBM were 14.6, and 24.7 months, respectively. High expression of ATP7B was identified to be associated with shorter overall survival times (hazard ratio, 0.452; 95% confidence interval, 0.206-0.994; P=0.048). Of the 79 patients, 12 underwent a second operation due to recurrence. These tissue samples were also subjected to immunohistochemical study. The ATP7B positivity rate of tumor cells obtained during the second surgery was significantly higher compared with that in the first surgery (9.17 +/- 2.56 vs. 2.75 +/- 0.55%; P=0.008). In addition, two ATP7B-transfected GBM cell lines were identified to be significantly resistant (3.8- and 1.7-fold, respectively) to TMZ compared with the control cell line. The findings of the present study suggest that ATP7B influences GBM resistance to TMZ.

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  • Higa Nayuta, Yokoo Hideaki, Hirano Hirofumi, Yonezawa Hajime, Oyoshi Tatsuki, Goto Yuko, Arita Kazunori .  低悪性度神経膠腫と直接的につながるcalcifying pseudoneoplasm of the neuraxis 1症例報告と文献レビュー(Calcifying pseudoneoplasm of the neuraxis in direct continuity with a low-grade glioma: A case report and review of the literature) .  NEUROPATHOLOGY37 ( 5 ) 446 - 451   2017.10低悪性度神経膠腫と直接的につながるcalcifying pseudoneoplasm of the neuraxis 1症例報告と文献レビュー(Calcifying pseudoneoplasm of the neuraxis in direct continuity with a low-grade glioma: A case report and review of the literature)

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    症例は62歳男性で、慢性頭痛を主訴とし、CTで左帯状回に石灰化腫瘤が認められたが、脳神経学的障害、mass effect、病変周囲の浮腫が認められなかったため保存的管理となった。6年後のCTで、病変周囲の浮腫によるmass effectを伴う石灰化腫瘤が示された。MRIのT1・T2強調画像から局所的浮腫または腫瘍性浸潤が示唆された。病変サイズの著明な増加、病変周囲浮腫の発症、メチオニン摂取量の増加から、腫瘤除去のため部分的開頭術を実施した。腫瘤はクモ膜下に位置していた。腫瘍の亜全摘を行ったが、深部の小さな領域が残存した。術後に頭痛はみられず、新規の神経障害もなかった。ガドリニウム増強MRIで小さな残存病変の増殖が明らかになり、病理学的検査では、石灰化小結節がグリア組織に囲まれ、骨形成を伴った好塩基球性、軟骨粘液基質の小葉を伴った低細胞性線維性血管性組織からなっていた。グリア組織の一部はクモ膜下腔へ隆起し、軟膜動脈および静脈を包含していた。グリア組織はグリア線維酸性蛋白質、S-100蛋白質、ネスチンに陽性であった。石灰化腫瘤に隣接した柵状紡錘細胞、石灰化小結節周囲の組織球およびリンパ球の所見から、低悪性度神経膠腫に生じた石灰化腫瘤はcalcifying pseudoneoplasm of the neuraxisと一致することが示唆された。

  • Nayuta Higa, Hideaki Yokoo, Hirofumi Hirano, Hajime Yonezawa, Tatsuki Oyoshi, Yuko Goto, Kazunori Arita .  Calcifying pseudoneoplasm of the neuraxis in direct continuity with a low-grade glioma: A case report and review of the literature .  NEUROPATHOLOGY37 ( 5 ) 446 - 451   2017.10

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    Calcifying pseudoneoplasms of the neuraxis (CAPNON) are presumed to be a non-neoplastic reactive pathology, based on the frequent finding of granulomatous inflammation. To our knowledge, there are few reports of CAPNON in association with a neoplasm. Here, we report the case of a 62-year-old man presenting with headache, which was caused by CAPNON in the left cingulate gyrus. CT scan revealed a calcified mass exhibiting gradual growth and increasing peritumoral edema. MRI showed an intra-axial hypointense mass on T1- and T2-weighted images. Development of a peri-lesional hyperintense lesion on T2-weighted images suggested local edema or tumoral invasion. Gadolinium-enhanced T1-weighted images revealed mild peripheral enhancement of the calcified nodule. L-methyl-C-11 methionine-positron emission tomography revealed the uptake of tracer in the calcified nodule. The calcified mass and its enveloping brain tissue were removed using a parietal craniotomy. The calcified tissue was surrounded by spindle-shaped cells positive for GFAP and nestin. The MIB-1 labeling index of spindle cells was around 10% (i.e. a hot spot). Fourteen months after surgery, gadolinium-enhanced MRI evidenced growth of a tiny residual lesion. Therefore, this report illustrates a potential case of CAPNON arising from low-grade glial neoplasm.

    DOI: 10.1111/neup.12384

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  • 脳腫瘍診断に特化したOncoPanelの有用性

    比嘉 那優大, 赤羽 俊章, 米澤 大, 坂元 顕久, 内田 裕之, 霧島 茉莉, 平木 翼, 谷本 昭英, 吉本 幸司

    Brain Tumor Pathology   36 ( Suppl. )   104 - 104   2019.5

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  • oligodendrogliomaにおける石灰化は1p/19q-codeletionとよく相関する

    内田 裕之, 比嘉 那優大, 米澤 大, 坂元 顕久, 吉本 幸司

    Brain Tumor Pathology   36 ( Suppl. )   081 - 081   2019.5

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  • 低悪性度腫瘍内にINI1陰性の高悪性度成分を有した頭蓋内下位神経関連腫瘍の一例

    米澤 大, 比嘉 那優大, 霧島 茉莉, 平木 翼, 吉本 幸司, 横尾 英明

    Brain Tumor Pathology   36 ( Suppl. )   126 - 126   2019.5

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  • 脊髄髄膜瘤の手術と長期機能予後 脊髄髄膜瘤の治療と長期機能予後について 自験例を中心に

    大吉 達樹, 比嘉 那優大, 駒柵 宗一郎, 友杉 哲三, 時村 洋, 吉本 幸司

    小児の脳神経   44 ( 2 )   198 - 198   2019.4

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  • 鹿児島大学がんゲノム医療への取り組み 神経膠腫診断用遺伝子パネル検査の開発

    赤羽 俊章, 平木 翼, 比嘉 那優大, 東 美智代, 北薗 育美, 後藤 優子, 霧島 茉莉, 吉本 幸司, 西原 広史, 谷本 昭英

    日本病理学会会誌   108 ( 1 )   312 - 312   2019.4

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  • 鹿児島大学がんゲノム医療への取り組み 神経膠腫用カスタム遺伝子パネルによる脳腫瘍統合診断

    平木 翼, 赤羽 俊章, 比嘉 那優大, 堀之内 道子, 吉本 幸司, 谷本 昭英, 西原 広史

    日本病理学会会誌   108 ( 1 )   414 - 414   2019.4

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  • 非外傷性帽状腱膜下血腫に対して外科的処置を行った一例

    比嘉 那優大, 大吉 達樹, 米永 理法, 佐藤 雅紀, 吉本 幸司

    小児の脳神経   44 ( 2 )   184 - 184   2019.4

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  • 膠芽腫におけるベバシズマブ療法の生存期間延長効果

    米澤大, 比嘉那優大, 内田裕之, 吉本幸司

    日本脳腫瘍学会プログラム・抄録集   37th   2019

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  • 小児中枢神経系腫瘍の臨床学的特徴

    比嘉那優大, 米澤大, 内田裕之, 大吉達樹, 吉本幸司

    日本脳腫瘍学会プログラム・抄録集   37th   2019

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  • グリオーマに特化したオンコパネルによるグリオーマ診断の有用性

    吉本幸司, 比嘉那優太, 赤羽俊章, 米澤大, 内田裕之, 谷本明英

    日本脳腫瘍学会プログラム・抄録集   37th   2019

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  • OncoPanelをもちいたLower grade gliomaの診断分類

    内田裕之, 赤羽俊章, 比嘉那優大, 霧島茉莉, 平木翼, 米澤大, 谷本昭英, 吉本幸司

    日本脳腫瘍学会プログラム・抄録集   37th   2019

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  • Lower grade glioma診断におけるOncoPanelと従来法との比較検討

    内田裕之, 赤羽俊章, 比嘉那優大, 霧島茉莉, 平木翼, 米澤大, 坂元顕久, 谷本昭英, 吉本幸司

    日本分子脳神経外科学会プログラム・抄録集   20th   2019

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  • Glioblastomaにおけるアクチン重合因子であるFormin-like 1(FMNL1)の機能解析

    比嘉那優大, 新里能成, KAMIL Muhammad, 高城朋子, 下川倫子, 南謙太朗, 山本雅達, 河原康一, 米澤大, 内田裕之, 平野宏文, 古川龍彦, 有田和徳, 吉本幸司

    日本分子脳神経外科学会プログラム・抄録集   20th   2019

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  • 80歳以上の超高齢者膠芽腫症例における診療の現状と課題

    米澤大, 比嘉那優大, 花田朋子, 坂元顕久, 内田裕之, 吉本幸司

    日本老年脳神経外科学会プログラム・抄録集   32nd   2019

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  • Late-onset sinus pericranii following depressed skull fracture: a case report

    山下麻美, 大吉達樹, 樫田祐美, 東拓一郎, 比嘉那優大, 田上なつ子, 細山浩史, 有田和徳

    小児の脳神経   43 ( 4 )   466 - 469   2018.12

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  • キアリ2型奇形に合併した重症中枢性無呼吸と嚥下障害の経過を追跡し得た一例

    比嘉 那優大, 大吉 達樹, 佐野 のぞみ, 藤尾 信吾, 有田 和徳

    小児の脳神経   43 ( 2 )   221 - 221   2018.4

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  • 多指症と難治なてんかんを伴った乳児小頭症に対する骨延長術の一例

    大吉 達樹, 花田 朋子, 永野 祐志, 比嘉 那優大, 細山 浩史, 米澤 大, 有田 和徳

    小児の脳神経   43 ( 2 )   268 - 268   2018.4

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  • GlioblastomaにおけるFormin-like 1(FMNL1)の機能について

    比嘉那優大, 新里能成, モハマド カミール, 高城朋子, 下川倫子, 南謙太朗, 山本雅達, 河原康一, 米澤大, 平野宏文, 古川龍彦, 有田和徳, 吉本幸司

    日本脳腫瘍学会プログラム・抄録集   36th   2018

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  • Formin-like 1(FMNL1)はGlioblastomaの独立した予後不良因子であり,浸潤・遊走能を促進させる

    比嘉那優大, 新里能成, KAMIL Muhammad, 高城朋子, 下川倫子, 南謙太朗, 山本雅達, 河原康一, 米澤大, 平野宏文, 古川龍彦, 有田和徳, 吉本幸司

    日本分子脳神経外科学会プログラム・抄録集   19th   2018

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  • diffuse glioma診断におけるFISH法による1p/19q共欠失解析のpitfall

    内田裕之, 比嘉那優大, 米澤大, 吉本幸司, 平野宏文

    日本脳腫瘍学会プログラム・抄録集   36th   2018

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  • 脳梁関連悪性神経膠腫における治療戦略-後方視的検討-

    米澤大, 平野宏文, 内田裕之, 比嘉那優大, 吉本幸司

    日本脳腫瘍の外科学会プログラム・抄録集   23rd   2018

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  • 脳腫瘍症例におけるベバシズマブ療法中に発生した脳心血管イベントについての検討

    米澤大, 内田裕之, 比嘉那優大, 花田朋子, 吉本幸司

    日本脳腫瘍学会プログラム・抄録集   36th   2018

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  • The Efficacy of Electromagnetic Neuronavigation System Using CT and MRI Fusion Images in Transsphenoidal Surgery

    藤尾信吾, 米澤大, 大吉達樹, 比嘉那優大, 羽生未佳, 平野宏文, 時村洋, 有田和徳

    CI研究   39 ( 2 )   87 - 91   2017.11

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  • Microcystic meningiomaの細胞内環境と酸化ストレス

    平野 宏文, 内田 裕之, 米澤 大, 比嘉 那優大, 義岡 孝子, 羽生 未佳, 藤尾 信吾, 花田 朋子, 大吉 達樹, 有田 和徳

    Brain Tumor Pathology   34 ( Suppl. )   108 - 108   2017.5

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  • Ping pong型骨折後に遅発性に発症した頭蓋骨膜洞の一例

    大吉 達樹, 樫田 祐美, 東 拓一郎, 比嘉 那優大, 細山 浩史, 時村 洋, 有田 和徳

    小児の脳神経   42 ( 2 )   147 - 147   2017.4

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  • 術前診断に難渋した脊髄圧迫症状にて発症した神経芽腫の1例

    比嘉 那優大, 大吉 達樹, 山畑 仁志, 児玉 祐一, 時村 洋, 河野 嘉文, 有田 和徳

    小児の脳神経   42 ( 2 )   215 - 215   2017.4

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  • 術中MRI使用経験と術中MRIの意義

    平野宏文, 内田裕之, 米澤大, 羽生未佳, 比嘉那優大, 花田朋子, 細山浩史, 大吉達樹, 花谷亮典, 有田和徳

    日本脳腫瘍の外科学会プログラム・抄録集   22nd   2017

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  • 脳室内腫瘍性病変に対する神経内視鏡手術

    平野宏文, 大吉達樹, 米澤大, 羽生未佳, 花田朋子, 内田裕之, 藤尾信吾, 比嘉那優大, 細山浩史, 有田和徳

    日本神経内視鏡学会プログラム・抄録集   24th   2017

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  • ベバシズマブ適応拡大後の多形膠芽腫の生存期間

    平野宏文, 米澤大, 内田裕之, 比嘉那優大, 羽生未佳, 花田朋子, 細山浩史, 大吉達樹, 花谷亮典, 有田和徳

    日本脳腫瘍学会プログラム・抄録集   35th   2017

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  • エベロリムスにて加療された原発巣不明の脳内神経内分泌癌の一例

    米澤大, 平野宏文, 内田裕之, 羽生未佳, 花田朋子, 比嘉那優大, 花谷亮典, 有田和徳

    日本脳腫瘍学会プログラム・抄録集   35th   2017

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  • 脳梁関連悪性神経膠腫例における予後規定因子についての検討

    米澤大, 平野宏文, 内田裕之, 羽生未佳, 花田朋子, 比嘉那優大, 大吉達樹, 花谷亮典, 有田和徳

    日本脳腫瘍の外科学会プログラム・抄録集   22nd   2017

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Presentations

  • 赤羽 俊章, 平木 翼, 比嘉 那優大, 東 美智代, 北薗 育美, 後藤 優子, 霧島 茉莉, 吉本 幸司, 西原 広史, 谷本 昭英   鹿児島大学がんゲノム医療への取り組み 神経膠腫診断用遺伝子パネル検査の開発  

    日本病理学会会誌  2019.4  (一社)日本病理学会

  • 平木 翼, 赤羽 俊章, 比嘉 那優大, 堀之内 道子, 吉本 幸司, 谷本 昭英, 西原 広史   鹿児島大学がんゲノム医療への取り組み 神経膠腫用カスタム遺伝子パネルによる脳腫瘍統合診断  

    日本病理学会会誌  2019.4  (一社)日本病理学会

  • 比嘉 那優大, 大吉 達樹, 米永 理法, 佐藤 雅紀, 吉本 幸司   非外傷性帽状腱膜下血腫に対して外科的処置を行った一例  

    小児の脳神経  2019.4  (一社)日本小児神経外科学会

  • 比嘉 那優大, 大吉 達樹, 山畑 仁志, 児玉 祐一, 時村 洋, 河野 嘉文, 有田 和徳   術前診断に難渋した脊髄圧迫症状にて発症した神経芽腫の1例  

    小児の脳神経  2017.4  (一社)日本小児神経外科学会

  • 比嘉 那優大, 赤羽 俊章, 米澤 大, 坂元 顕久, 内田 裕之, 霧島 茉莉, 平木 翼, 谷本 昭英, 吉本 幸司   脳腫瘍診断に特化したOncoPanelの有用性  

    Brain Tumor Pathology  2019.5  日本脳腫瘍病理学会

  • 赤羽 俊章, 比嘉 那優大, 霧島 茉莉, 平木 翼, 北薗 育美, 内田 裕之, 米澤 大, 吉本 幸司, 谷本 昭英   脳腫瘍の遺伝子診断とゲノム医療1 神経膠腫診断用パネルKBT-48で認めたEGFR mutation gliomaの病理組織学的所見  

    Brain Tumor Pathology  2020.8  日本脳腫瘍病理学会

  • 大吉 達樹, 比嘉 那優大, 駒柵 宗一郎, 友杉 哲三, 時村 洋, 吉本 幸司   脊髄髄膜瘤の手術と長期機能予後 脊髄髄膜瘤の治療と長期機能予後について 自験例を中心に  

    小児の脳神経  2019.4  (一社)日本小児神経外科学会

  • 佐野 のぞみ, 今塩屋 聡伸, 松永 愛香, 水流 尚志, 松藤 まゆみ, 細山 浩史, 藤尾 慎吾, 比嘉 那優大, 吉本 幸司, 黒野 祐一   突然の嚥下障害を呈した舌咽・迷走神経麻痺の1例  

    脳と発達  2020.8  (一社)日本小児神経学会

  • 比嘉 那優大, 赤羽 俊章, 横山 勢也, 米澤 大, 内田 裕之, 霧島 茉莉, 平木 翼, 谷本 昭英, 吉本 幸司   神経膠腫診断に特化した遺伝子パネルによるGlioblastoma、IDH-wildの解析結果  

    Brain Tumor Pathology  2020.8  日本脳腫瘍病理学会

  • 川出 茂, 有村 洋, 足達 沙織, 松崎 かおり, 児島 奈弥, 長友 理笑, 比嘉 那優大, 有村 愛子, 藤尾 信吾, 内田 裕之, 橋口 裕, 有田 和徳, 吉本 幸司, 西尾 善彦   破壊性甲状腺炎によりTRH負荷試験低反応を認めた先端巨大症の1例  

    日本内分泌学会雑誌  2019.10  (一社)日本内分泌学会

  • 霧島 茉莉, 赤羽 俊章, 平木 翼, 比嘉 那優大, 吉本 幸司, 谷本 昭英   次世代シークエンサー解析で統合診断を行ったDiffuse Midline Glioma,H3 K27M-mutantの4症例  

    日本病理学会会誌  2020.3  (一社)日本病理学会

  • 大吉 達樹, 花田 朋子, 永野 祐志, 比嘉 那優大, 細山 浩史, 米澤 大, 有田 和徳   多指症と難治なてんかんを伴った乳児小頭症に対する骨延長術の一例  

    小児の脳神経  2018.4  (一社)日本小児神経外科学会

  • 米澤 大, 比嘉 那優大, 霧島 茉莉, 平木 翼, 吉本 幸司, 横尾 英明   低悪性度腫瘍内にINI1陰性の高悪性度成分を有した頭蓋内下位神経関連腫瘍の一例  

    Brain Tumor Pathology  2019.5  日本脳腫瘍病理学会

  • 比嘉 那優大, 大吉 達樹, 駒柵 宗一郎, 黒木 伸一, 時村 洋, 吉本 幸司   乳幼児でのBactisealシャントカテーテルの使用経験  

    小児の脳神経  2020.10  (一社)日本小児神経外科学会

  • 比嘉 那優大, 大吉 達樹, 佐野 のぞみ, 藤尾 信吾, 有田 和徳   キアリ2型奇形に合併した重症中枢性無呼吸と嚥下障害の経過を追跡し得た一例  

    小児の脳神経  2018.4  (一社)日本小児神経外科学会

  • 大吉 達樹, 樫田 祐美, 東 拓一郎, 比嘉 那優大, 細山 浩史, 時村 洋, 有田 和徳   Ping pong型骨折後に遅発性に発症した頭蓋骨膜洞の一例  

    小児の脳神経  2017.4  (一社)日本小児神経外科学会

  • 内田 裕之, 比嘉 那優大, 米澤 大, 坂元 顕久, 吉本 幸司   oligodendrogliomaにおける石灰化は1p/19q-codeletionとよく相関する  

    Brain Tumor Pathology  2019.5  日本脳腫瘍病理学会

  • 平野 宏文, 内田 裕之, 米澤 大, 比嘉 那優大, 義岡 孝子, 羽生 未佳, 藤尾 信吾, 花田 朋子, 大吉 達樹, 有田 和徳   Microcystic meningiomaの細胞内環境と酸化ストレス  

    Brain Tumor Pathology  2017.5  日本脳腫瘍病理学会

  • 大吉 達樹, 佐藤 雅紀, 比嘉 那優大, 駒柵 宗一郎, 黒木 伸一, 時村 洋, 吉本 幸司   Chiari malformation type 3とSyringomyeliaを伴ったLarge occipital meningo-encephaloceleの一例  

    小児の脳神経  2020.10  (一社)日本小児神経外科学会

  • 赤羽 俊章, 平木 翼, 比嘉 那優大, 東 美智代, 北薗 育美, 後藤 優子, 霧島 茉莉, 吉本 幸司, 西原 広史, 谷本 昭英   鹿児島大学がんゲノム医療への取り組み 神経膠腫診断用遺伝子パネル検査の開発  

    日本病理学会会誌  2019.4  (一社)日本病理学会

  • 平木 翼, 赤羽 俊章, 比嘉 那優大, 堀之内 道子, 吉本 幸司, 谷本 昭英, 西原 広史   鹿児島大学がんゲノム医療への取り組み 神経膠腫用カスタム遺伝子パネルによる脳腫瘍統合診断  

    日本病理学会会誌  2019.4  (一社)日本病理学会

  • 比嘉 那優大, 大吉 達樹, 米永 理法, 佐藤 雅紀, 吉本 幸司   非外傷性帽状腱膜下血腫に対して外科的処置を行った一例  

    小児の脳神経  2019.4  (一社)日本小児神経外科学会

  • 比嘉 那優大, 大吉 達樹, 山畑 仁志, 児玉 祐一, 時村 洋, 河野 嘉文, 有田 和徳   術前診断に難渋した脊髄圧迫症状にて発症した神経芽腫の1例  

    小児の脳神経  2017.4  (一社)日本小児神経外科学会

  • 比嘉 那優大, 赤羽 俊章, 米澤 大, 坂元 顕久, 内田 裕之, 霧島 茉莉, 平木 翼, 谷本 昭英, 吉本 幸司   脳腫瘍診断に特化したOncoPanelの有用性  

    Brain Tumor Pathology  2019.5  日本脳腫瘍病理学会

  • 赤羽 俊章, 比嘉 那優大, 霧島 茉莉, 平木 翼, 北薗 育美, 内田 裕之, 米澤 大, 吉本 幸司, 谷本 昭英   脳腫瘍の遺伝子診断とゲノム医療1 神経膠腫診断用パネルKBT-48で認めたEGFR mutation gliomaの病理組織学的所見  

    Brain Tumor Pathology  2020.8  日本脳腫瘍病理学会

  • 大吉 達樹, 比嘉 那優大, 駒柵 宗一郎, 友杉 哲三, 時村 洋, 吉本 幸司   脊髄髄膜瘤の手術と長期機能予後 脊髄髄膜瘤の治療と長期機能予後について 自験例を中心に  

    小児の脳神経  2019.4  (一社)日本小児神経外科学会

  • 佐野 のぞみ, 今塩屋 聡伸, 松永 愛香, 水流 尚志, 松藤 まゆみ, 細山 浩史, 藤尾 慎吾, 比嘉 那優大, 吉本 幸司, 黒野 祐一   突然の嚥下障害を呈した舌咽・迷走神経麻痺の1例  

    脳と発達  2020.8  (一社)日本小児神経学会

  • 比嘉 那優大, 赤羽 俊章, 横山 勢也, 米澤 大, 内田 裕之, 霧島 茉莉, 平木 翼, 谷本 昭英, 吉本 幸司   神経膠腫診断に特化した遺伝子パネルによるGlioblastoma、IDH-wildの解析結果  

    Brain Tumor Pathology  2020.8  日本脳腫瘍病理学会

  • 川出 茂, 有村 洋, 足達 沙織, 松崎 かおり, 児島 奈弥, 長友 理笑, 比嘉 那優大, 有村 愛子, 藤尾 信吾, 内田 裕之, 橋口 裕, 有田 和徳, 吉本 幸司, 西尾 善彦   破壊性甲状腺炎によりTRH負荷試験低反応を認めた先端巨大症の1例  

    日本内分泌学会雑誌  2019.10  (一社)日本内分泌学会

  • 霧島 茉莉, 赤羽 俊章, 平木 翼, 比嘉 那優大, 吉本 幸司, 谷本 昭英   次世代シークエンサー解析で統合診断を行ったDiffuse Midline Glioma,H3 K27M-mutantの4症例  

    日本病理学会会誌  2020.3  (一社)日本病理学会

  • 大吉 達樹, 花田 朋子, 永野 祐志, 比嘉 那優大, 細山 浩史, 米澤 大, 有田 和徳   多指症と難治なてんかんを伴った乳児小頭症に対する骨延長術の一例  

    小児の脳神経  2018.4  (一社)日本小児神経外科学会

  • 米澤 大, 比嘉 那優大, 霧島 茉莉, 平木 翼, 吉本 幸司, 横尾 英明   低悪性度腫瘍内にINI1陰性の高悪性度成分を有した頭蓋内下位神経関連腫瘍の一例  

    Brain Tumor Pathology  2019.5  日本脳腫瘍病理学会

  • 比嘉 那優大, 大吉 達樹, 駒柵 宗一郎, 黒木 伸一, 時村 洋, 吉本 幸司   乳幼児でのBactisealシャントカテーテルの使用経験  

    小児の脳神経  2020.10  (一社)日本小児神経外科学会

  • 比嘉 那優大, 大吉 達樹, 佐野 のぞみ, 藤尾 信吾, 有田 和徳   キアリ2型奇形に合併した重症中枢性無呼吸と嚥下障害の経過を追跡し得た一例  

    小児の脳神経  2018.4  (一社)日本小児神経外科学会

  • 大吉 達樹, 樫田 祐美, 東 拓一郎, 比嘉 那優大, 細山 浩史, 時村 洋, 有田 和徳   Ping pong型骨折後に遅発性に発症した頭蓋骨膜洞の一例  

    小児の脳神経  2017.4  (一社)日本小児神経外科学会

  • 内田 裕之, 比嘉 那優大, 米澤 大, 坂元 顕久, 吉本 幸司   oligodendrogliomaにおける石灰化は1p/19q-codeletionとよく相関する  

    Brain Tumor Pathology  2019.5  日本脳腫瘍病理学会

  • 平野 宏文, 内田 裕之, 米澤 大, 比嘉 那優大, 義岡 孝子, 羽生 未佳, 藤尾 信吾, 花田 朋子, 大吉 達樹, 有田 和徳   Microcystic meningiomaの細胞内環境と酸化ストレス  

    Brain Tumor Pathology  2017.5  日本脳腫瘍病理学会

  • 大吉 達樹, 佐藤 雅紀, 比嘉 那優大, 駒柵 宗一郎, 黒木 伸一, 時村 洋, 吉本 幸司   Chiari malformation type 3とSyringomyeliaを伴ったLarge occipital meningo-encephaloceleの一例  

    小児の脳神経  2020.10  (一社)日本小児神経外科学会

  • 米澤 大, 比嘉 那優大, 内田 裕之, 赤羽 俊章, 横山 勢也, 霧島 茉莉, 平木 翼, 谷本 昭英, 吉本 幸司   脳腫瘍に特化したがん遺伝子パネル検査の実臨床における有用性  

    Brain Tumor Pathology  2021.5  日本脳腫瘍病理学会

  • 赤羽 俊章, 比嘉 那優大, 霧島 茉莉, 内田 裕之, 米澤 大, 坂本 一平, 野原 祥夫, 吉本 幸司, 谷本 昭英   神経膠腫診断用パネル検査で見つかった新規EGFR variantを有する神経膠腫の病理組織学的特徴  

    Brain Tumor Pathology  2021.5  日本脳腫瘍病理学会

  • 比嘉 那優大, 赤羽 俊章, 米澤 大, 内田 裕之, 藤尾 信吾, 横山 勢也, 霧島 茉莉, 濱田 大治, 谷本 昭英, 吉本 幸司   日本人のhigh grade glioma患者における遺伝子変異の特徴  

    Brain Tumor Pathology  2021.5  日本脳腫瘍病理学会

  • 内田 裕之, 赤羽 俊章, 比嘉 那優大, 米澤 大, 霧島 茉莉, 谷本 昭英, 吉本 幸司   Lower-grade gliomaの遺伝子プロファイル診断と予後についての検討  

    Brain Tumor Pathology  2021.5  日本脳腫瘍病理学会

  • 谷本 昭英, 赤羽 俊章, 比嘉 那優大, 吉本 幸司   脳腫瘍の病理 カスタムNGSパネルによる神経膠腫の統合分子病理診断の実践と応用  

    日本病理学会会誌  2021.3  (一社)日本病理学会

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  • 名取 香奈子, 周 尓東, 北惠 郁緒里, 上田 裕子, 長谷 拓明, 神宮司 健太郎, 古川 龍彦, 比嘉 那優大, 吉本 幸司, 辻川 和丈   膠芽腫の悪性化プログラムにおけるエピトランスクリプトミクス制御  

    日本薬学会年会要旨集  2021.3  (公社)日本薬学会

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  • 赤羽 俊章, 比嘉 那優大, 霧島 茉莉, 内田 裕之, 米澤 大, 吉本 幸司, 谷本 昭英   頭頸部・脳腫瘍用カスタム融合遺伝子パネルで認められた、IDH1変異陽性神経膠腫のNTRK融合遺伝子  

    Brain Tumor Pathology  2022.5  日本脳腫瘍病理学会

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  • 東 拓一郎, 増田 圭亮, 比嘉 那優大, 米澤 大, 内田 裕之, 花谷 亮典   神経膠腫におけるてんかん発症に影響する因子  

    てんかん研究  2022.8  (一社)日本てんかん学会

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  • 黒木 伸一, 佐藤 雅紀, 比嘉 那優大, 駒柵 宗一郎, 大吉 達樹, 時村 洋, 吉本 幸司   同胞間で発症し、水頭症と脊髄空洞症を合併したキアリ3型を伴う巨大後頭部脳瘤の1例 同胞間発症と水頭症併発のメカニズムについて  

    小児の脳神経  2022.4  (一社)日本小児神経外科学会

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  • 比嘉 那優大, 原田 敦子, 久徳 茂雄, 浅香 明紀, 和田 雄樹, 大吉 達樹, 森川 将行, 花田 朋子, 花谷 亮典, 吉本 幸司   乳児期に段階的手術を行ったPfeiffer症候群の1例  

    小児の脳神経  2022.4  (一社)日本小児神経外科学会

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  • 比嘉 那優大, 赤羽 俊章, 横山 勢也, 米澤 大, 内田 裕之, 浜田 大治, 霧島 茉莉, 谷本 昭英, 花谷 亮典, 吉本 幸司   IDH wild-type GBMにおけるPDGFRA amplificationおよびMGMTpの予後への影響  

    Brain Tumor Pathology  2022.5  日本脳腫瘍病理学会

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  • 堀口 達史, 田井村 依里, 山崎 雄一, 関 祐子, 比嘉 那優大, 福重 寿郎   Basedow病、若年性特発性関節炎の治療中に小脳梗塞を合併したDown症候群の15歳女子  

    日本小児科学会雑誌  2022.7  (公社)日本小児科学会

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  • 米澤 大, 比嘉 那優大, 増田 圭亮, 内田 裕之, 花谷 亮典   AYA世代の脳腫瘍病理 思春期・若年成人astrocytic tumorの臨床像と遺伝子学的特徴  

    Brain Tumor Pathology  2022.5  日本脳腫瘍病理学会

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  • 渋谷 望美, 比嘉 那優大, 大吉 達樹, 花谷 亮典   乳児期早期に縫合切除術とヘルメット治療を行ったApert症候群の1例  

    小児の脳神経  2023.4  (一社)日本小児神経外科学会

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  • 赤羽 俊章, 坂本 一平, 比嘉 那優大, 霧島 茉莉, 牧野 隆太郎, 米澤 大, 内田 裕之, 吉本 幸司, 花谷 亮典, 谷本 昭英   がんゲノム診断とバイオインフォマティクス 神経膠腫の統合分子病理診断のための自動レポーティングシステムの構築とバイオインフォマティクスの重要性  

    Brain Tumor Pathology  2023.5  日本脳腫瘍病理学会

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  • 牧野 隆太郎, 比嘉 那優大, 赤羽 俊章, 米澤 大, 内田 裕之, 霧島 茉莉, 山本 淳考, 吉本 幸司, 谷本 昭英, 花谷 亮典   がんゲノム診断 日本人膠芽腫患者におけるチロシンキナーゼ受容体変異と臨床像  

    Brain Tumor Pathology  2023.5  日本脳腫瘍病理学会

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  • 比嘉 那優大, 赤羽 俊章, 横山 勢也, 米澤 大, 内田 裕之, 霧島 茉莉, 山本 淳考, 吉本 幸司, 谷本 昭英, 花谷 亮典   IDH wildtype-TERTp wildtype glioblastomaにおけるPTENの予後への影響  

    Brain Tumor Pathology  2023.5  日本脳腫瘍病理学会

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Awards

  • 公益財団法人新日本先進医療研究財団 令和4年度(第8回)研究助成金

    2022.12   公益財団法人 新日本先進医療研究財団   機械学習を用いたゲノム・エピゲノム解析に基づくグリオーマの診断・予後バイオマーカーの創出と個別化医療への基盤構築

    比嘉 那優大

  • 鹿児島県医師会医学研究助成

    2022.6   鹿児島県医師会   悪性神経膠腫のゲノム・エピゲノム解析:Precision Medicineを目指して

    比嘉 那優大

Research Projects

  • 膠芽腫におけるドライバー遺伝子変異の空間的プロテオミクスへの基盤構築

    Grant number:23K08546  2023.4 - 2026.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    比嘉 那優大, 花谷 亮典, 谷本 昭英, 米澤 大, 横山 勢也, 濱田 大治, 赤羽 俊章

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    Grant amount:\4810000 ( Direct Cost: \3700000 、 Indirect Cost:\1110000 )

  • 膠芽腫におけるEGFR意義不明変異の機能解析

    Grant number:23K08526  2023.4 - 2026.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    霧島 茉莉, 谷本 昭英, 横山 勢也, 濱田 大治, 赤羽 俊章, 比嘉 那優大

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    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

  • 機械学習によるグリオーマの診断・予後バイオマーカーの創出と個別化医療への基盤構築

    Grant number:23K08525  2023.4 - 2026.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    花谷 亮典, 比嘉 那優大, 米澤 大, 藤尾 信吾, 高城 朋子

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    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

  • 先進的マルチパラメトリックMRIに基づく新分類に即した神経膠腫の診断と予後予測法の開発

    Grant number:23K07113  2023.4 - 2026.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    上村 清央, 吉浦 敬, 米澤 大, 中野 翼, 中條 正典, 長谷川 知仁, 比嘉 那優大

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    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

  • HDAC7とNNTの相互作用が膠芽腫悪性化に及ぼす影響の解明ー細胞レベルで探るー

    Grant number:23K08524  2023.4 - 2026.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    高城 朋子, 花谷 亮典, 比嘉 那優大

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    Grant amount:\3380000 ( Direct Cost: \2600000 、 Indirect Cost:\780000 )

  • 膠芽腫におけるLPPを中心とした新規浸潤・遊走機構の解明

    Grant number:22K09238  2022.4 - 2025.3

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    増田 圭亮, 比嘉 那優大, 米澤 大, 内田 裕之, 花谷 亮典

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    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

  • 悪性神経膠腫におけるテモゾロミド耐性獲得においてオートファジーが果たす役割の解明

    Grant number:22K09290  2022.4 - 2025.3

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    米澤 大, 比嘉 那優大, 内田 裕之, 吉本 幸司

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    Grant amount:\3120000 ( Direct Cost: \2400000 、 Indirect Cost:\720000 )

  • PDGFRA遺伝子変異の抗がん剤感受性マップの作製

    Grant number:22K07305  2022.4 - 2025.3

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    濱田 大治, 谷本 昭英, 横山 勢也, 比嘉 那優大

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    Grant amount:\4030000 ( Direct Cost: \3100000 、 Indirect Cost:\930000 )

  • グリオーマ遺伝子パネルによる日本人グリオーマ患者での網羅的ゲノム・エピゲノム 解析

    2021.4 - 2023.3

    文科省  科学研究費助成事業 

    比嘉那優大

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\4550000 ( Direct Cost: \3500000 、 Indirect Cost:\1050000 )

  • グリオーマ遺伝子パネルによる日本人グリオーマ患者での網羅的ゲノム・エピゲノム解析

    Grant number:21K16636  2021.4 - 2023.3

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    比嘉 那優大

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    Grant amount:\4550000 ( Direct Cost: \3500000 、 Indirect Cost:\1050000 )

  • ミトコンドリア機能に着目した膠芽腫におけるHDAC7の機能解析

    Grant number:20K09395  2020.4 - 2023.3

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    吉本 幸司, 比嘉 那優大

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    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

  • glioblastomaにおけるFMNL1を中心とした新規浸潤・遊走機構の解明

    2018.4 - 2020.3

    文科省  科学研究費助成事業 

    比嘉那優大

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    Authorship:Principal investigator 

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

  • New invasion and migration mechanisms associated with FMNL1 in glioblastoma

    Grant number:18K16590  2018.4 - 2020.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists  Grant-in-Aid for Early-Career Scientists

    HIGA Nayuta

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    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    This study was conducted to elucidate the FMNL1 function in the acquisition of malignant features of GBM. Our study showed FMNL1 was an independent predictor of poor prognosis in a cohort of 217 glioblastoma multiforme cases (P < 0.001). Furthermore, FMNL1 expression was significantly higher in the mesenchymal subtype. FMNL1 upregulation and downregulation were associated with mesenchymal and proneural markers in the GSEA, respectively. These data highlight the important role of FMNL1 in neural-to-mesenchymal transition. Contrarily, FMNL1 downregulation suppressed glioblastoma multiforme cell migration and invasion via DIAPH1 and GOLGA2, respectively. FMNL1 downregulation also suppressed actin fibers assembly, induced morphological changes, and diminished filamentous actin. FMNL1 is a promising therapeutic target and a useful biomarker for GBM progression.

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