記述言語：英語   掲載種別：研究論文（学術雑誌）  

In the treatment of primary central nervous system lymphoma (PCNSL), intraoperative rapid pathological diagnosis can dramatically change the surgical strategy, and more accurate diagnostic methods are required. In April 2020, we adopted intraoperative rapid immunohistochemistry (IHC) in addition to conventional rapid intraoperative diagnosis based on morphological assessment, mainly for patients with PCNSL. Here, we investigate the usefulness and significance of intraoperative rapid IHC based on our initial experience. We performed intraoperative rapid IHC using antibodies for cluster of differentiation (CD)20, CD3, leukocyte common antigen (LCA) and glial fibrillary acidic protein (GFAP) using enzyme-labeled antibody methods in 25 patients, including PCNSL patients, from April 2020 to July 2022. We examined the utility of this approach in determining treatment strategies for brain tumors. Postoperative final pathological diagnoses from paraffin-embedded sections were as follows: diffuse large B-cell lymphoma, 16 cases; glioblastoma, six cases; pilocytic astrocytoma, one case; adenocarcinoma, one case; and inflammatory disorder, one case. The entire process took 32 min and staining for CD20, CD3, LCA, and GFAP was comparable to that using paraffin-embedded sections. In all cases, the results of intraoperative rapid IHC were consistent with final pathological diagnoses from paraffin-embedded sections. In addition, in two cases, the results of conventional intraoperative rapid pathological diagnosis based on morphological assessments using frozen sections were drastically changed by adding intraoperative rapid IHC. Intraoperative rapid IHC contributes to deciding appropriate treatment strategies and facilitating early initiation of chemotherapy for PCNSL. This may allow new therapeutic strategies not only for PCNSL but also for other brain tumors.

DOI： 10.1111/neup.12864

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: This retrospective analysis of patients treated with endoscopic endonasal transsphenoidal surgery (ETSS) alone or simultaneous combined surgery investigated imaging features suitable for surgical methods and pitfalls in simultaneous combined surgery for giant pituitary adenoma. PATIENTS AND METHODS: Ten patients with giant pituitary adenoma treated by ETSS alone or simultaneous combined endoscopic endonasal and transcranial surgery were enrolled. By analyzing tumor imaging features on magnetic resonance imaging (MRI), operative findings and clinical outcomes, we examined types of imaging features suitable for each surgical method. RESULTS: Four patients received ETSS alone and six patients underwent simultaneous combined endonasal and transcranial surgery. Four patients treated by ETSS alone and three patients treated by combined surgery had high resection rates and good outcomes. The remaining three patients with combined surgery achieved partial resection and visual deterioration in one patient. MRI features suitable for ETSS included an enlarged sella, upward tumor extension, and round surface, whereas those for combined surgery included normal/enlarged sella, anterior and/or unilateral tumor extension, and a multilobulated surface. Tumors extending extensively bilaterally or upward and encasing neurovascular structures could not be effectively resected even under combined surgery. CONCLUSION: Both ETSS alone and simultaneous combined endonasal and transcranial surgery showed good results for giant pituitary adenoma when the surgical methods matched suitable imaging features. Tumors with unilateral or anterior extension and a multilobulated surface were maximally resected without neurological deficit by combined surgery, but tumors showing extensive multi-directional extension and full encasement of neurovascular structures were not effectively resected even with combined surgery.

DOI： 10.1016/j.clineuro.2022.107281

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The incidence of brain metastasis of pancreatic cancer has been reported to be approximately 0.3%. The blood-brain barrier of the central nervous system restricts the transfer of substances, including chemotherapeutic agents, from the bloodstream. It is hypothesized that brain metastasis may occur despite successful chemotherapy for the primary tumor. Herein, we report a case of brain metastases of pancreatic cancer that occurred after chemotherapy and discuss relevant literature. CASE PRESENTATION: A 64-year-old man underwent distal pancreatectomy with D2 lymph node dissection for resectable pancreatic tail cancer. Invasive ductal carcinoma of pancreas, pT3N2M0 pStageIII (TNM Classification of Malignant Tumors, UICC 8th edition) was diagnosed. S-1 adjuvant chemotherapy was initiated. Three months postoperatively, CA19-9 had increased to 619 U/mL. Additionally, contrast-enhanced computed tomography (CT) and fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT revealed local recurrence in the para-aortic lymph nodes. Chemotherapy was revised to a combined regimen of gemcitabine and nab-paclitaxel. After 4 cycles, tumor markers were normalized. After 5 cycles, recurrence could not be identified on contrast-enhanced CT; therefore, the patient was adjudged to be in complete remission. However, after 29 cycles of chemotherapy, the patient had symptoms of raised intracranial pressure. Magnetic resonance imaging showed two metastatic lesions of 20 mm and 32 mm in the left frontal lobe and cerebellum, respectively. Quasi-emergency resection of the metastatic brain tumors was performed. Pathological examination revealed that the resected specimens originated from primary pancreatic cancer. The patient was discharged on postoperative day 12, without any complications. Postoperatively, a total of 53 Gy of local brain radiation therapy was added. On postoperative day 30, blood carcinoembryonic antigen level had decreased to 5.4 ng/dl and all other tumor markers were negative. Additionally, tumor markers of the cerebrospinal fluid were markedly reduced and the cytology was negative for tumor cells. These results suggested complete resection of the metastatic brain tumors. CONCLUSIONS: Aggressive resection and salvage stereotactic radiotherapy for metastatic brain tumors may lead to complete cure and a good long-term prognosis.

DOI： 10.1186/s40792-022-01461-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The effectiveness of carmustine (BCNU) wafers on local recurrence of glioblastoma (GBM) remains contentious. We investigated the accumulating high-dose effects of BCNU released from the wafers on the survival of GBM patients by measuring BCNU concentration in the resection cavity of GBM over time. BCNU wafers (Gliadel®) were implanted with an Ommaya device in 15 patients, including 12 patients with GBM. BCNU concentrations in the tumor resection cavity were measured for 30 days postoperatively. The area under the curve (AUC)all was calculated from BCNU concentration curves, and the relationships between AUCall and survival, tumor phenotypes on MRI, and recurrence patterns were analyzed. The BCNU concentration was maximal 1 h postoperatively, rapidly decreased within 24 h, and remained relatively high for 7 days. GBM patients were classified into two groups: early recurrence (ER) and late or no recurrence (LN), using median progression-free survival as the cut-off. AUCall tended to be lower in the ER group than in the LN group, but the difference was not significant. MRI revealed that all patients in the ER group had highly invasive GBMs, whereas all patients in the LN group had less-invasive GBMs. A total of 9 patients experienced recurrence, with 6 local, 2 diffuse, and 1 disseminated patterns. No differences in AUCall were seen between local and non-local recurrence groups. Total BCNU concentrations did not correlate with tumor progression or survival. However, a high concentration of BCNU may have potential to provide some survival benefit for less-invasive type GBM.

DOI： 10.3390/brainsci12050567

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES/HYPOTHESIS: To determine the relationship between signal intensity on gadolinium (Gd)-enhanced magnetic resonance images and growth of vestibular schwannomas (VSs). STUDY DESIGN: Cross-sectional study. METHODS: In this cross-sectional study, we retrospectively reviewed the data of 31 patients with VSs who underwent magnetic resonance imaging (MRI). The mean signal intensities within the regions of interest in the tumor, pons, and temporal muscles were measured on Gd-enhanced T1-weighted MRI. Relative intensity ratios were calculated as follows: T/N pons ratio (T/Np) is the tumor signal intensity/pons signal intensity and T/N muscle ratio (T/Nm) is the tumor signal intensity/temporal muscle signal intensity. Volume measurements were used to assess the tumor size. Growth rate was determined by assessing previous imaging studies. Growing VS was defined as a tumor with a growth rate >100 mm3 /year. RESULTS: The mean (standard deviation) T/Np and T/Nm were 1.47 (0.27) and 1.50 (0.24), respectively, in nongrowing tumors and 1.78 (0.17) and 1.90 (0.12), respectively, in growing tumors. The T/Np and T/Nm differed significantly between the two groups (T/Np, P < .001; T/Nm, P < .001). Receiver operating characteristic curve analysis showed that cutoffs of 1.56 and 1.76 for T/Np (93.33% sensitivity, 75.00% specificity) and T/Nm (100.00% sensitivity, 93.75% specificity), respectively, could be used to diagnose a growth rate of >100 mm3 /year. The area under the curve was 0.85 (95% confidence interval, 0.70-1.00) for T/Np and 0.94 (0.82-1.00) for T/Nm. CONCLUSION: Growing VSs show higher signal intensities on Gd-enhanced MRI. Thus, measuring the signal intensity of VS on Gd-enhanced MRI may aid in predicting VS growth. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:198-203, 2022.

DOI： 10.1002/lary.29834

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: An open-label, non-comparative study assessed the efficacy and safety of nivolumab in Japanese patients with first recurrence glioblastoma. METHODS: Patients with first recurrence of histologically confirmed World Health Organization Grade IV glioma, after treatment with temozolomide and radiotherapy, received nivolumab 3 mg/kg every 2 weeks until confirmed disease progression (Response Assessment in Neuro-Oncology criteria) or toxicity. Primary endpoint was 1-year overall survival rate assessed by Bayesian approach. The prespecified efficacy criterion was that the Bayesian posterior probability threshold for exceeding the 1-year overall survival of bevacizumab (34.5%) from the Japanese phase 2 study (JO22506) would be 93%. RESULTS: Of the 50 enrolled patients, 44 (88.0%) had recurrent malignant glioma (glioblastoma, gliosarcoma), and of these, 26 (59.1%) had at least one measurable lesion at baseline. The Bayesian posterior mean 1-year overall survival (90% Bayesian credible intervals) with nivolumab was 54.4% (42.27-66.21), and the Bayesian posterior probability of exceeding the threshold of the 1-year overall survival rate of bevacizumab (34.5%) was 99.7%. Median (90% confidence interval) overall and progression-free survival was 13.1 (10.4-17.7) and 1.5 (1.4-1.5) months, respectively. One partial response was observed (objective response rate 1/26 evaluable patients [3.8%]). Treatment-related adverse event rates were 14.0% for Grade 3-4 and 2.0% for Grade 5; most adverse events resolved and were manageable. CONCLUSIONS: The 1-year overall survival with nivolumab monotherapy in Japanese patients with glioblastoma met the prespecified efficacy criterion. The safety profile of nivolumab was consistent with that observed in other tumor types. CLINICAL TRIAL REGISTRATION: JapicCTI-152967.

DOI： 10.1007/s10147-021-02028-1

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掲載種別：研究論文（学術雑誌）  

The abilities to invade surrounding tissues and metastasize to distant organs are the most outstanding features that distinguish malignant from benign tumors. However, the mechanisms preventing the invasion and metastasis of benign tumor cells remain unclear. By using our own rat distant metastasis model, gene expression of cells in primary tumors was compared with that in metastasized tumors. Among many distinct gene expressions, we have focused on chloride intracellular channel protein 2 (CLIC2), an ion channel protein of as-yet unknown function, which was predominantly expressed in the primary tumors. We created CLIC2 overexpressing rat glioma cell line and utilized benign human meningioma cells with naturally high CLIC2 expression. CLIC2 was expressed at higher levels in benign human brain tumors than in their malignant counterparts. Moreover, its high expression was associated with prolonged survival in the rat metastasis and brain tumor models as well as with progression-free survival in patients with brain tumors. CLIC2 was also correlated with the decreased blood vessel permeability likely by increased contents of cell adhesion molecules. We found that CLIC2 was secreted extracellularly, and bound to matrix metalloproteinase (MMP) 14. Furthermore, CLIC2 prevented the localization of MMP14 in the plasma membrane, and inhibited its enzymatic activity. Indeed, overexpressing CLIC2 and recombinant CLIC2 protein effectively suppressed malignant cell invasion, whereas CLIC2 knockdown reversed these effects. Thus, CLIC2 suppress invasion and metastasis of benign tumors at least partly by inhibiting MMP14 activity.

DOI： 10.1016/j.neo.2021.06.001

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掲載種別：研究論文（学術雑誌）  

The poor prognosis of glioblastoma multiforme (GBM) is primarily due to highly invasive glioma stem-like cells (GSCs) in tumors. Upon GBM recurrence, GSCs with highly invasive and highly migratory activities must assume a less-motile state and proliferate to regenerate tumor mass. Elucidating the molecular mechanism underlying this transition from a highly invasive phenotype to a less-invasive, proliferative tumor could facilitate the identification of effective molecular targets for treating GBM. Here, we demonstrate that severe hypoxia (1% O2) upregulates CD44 expression via activation of hypoxia-inducible factor (HIF-1α), inducing GSCs to assume a highly invasive tumor. In contrast, moderate hypoxia (5% O2) upregulates osteopontin expression via activation of HIF-2α. The upregulated osteopontin inhibits CD44-promoted GSC migration and invasion and stimulates GSC proliferation, inducing GSCs to assume a less-invasive, highly proliferative tumor. These data indicate that the GSC phenotype is determined by interaction between CD44 and osteopontin. The expression of both CD44 and osteopontin is regulated by differential hypoxia levels. We found that CD44 knockdown significantly inhibited GSC migration and invasion both in vitro and in vivo. Mouse brain tumors generated from CD44-knockdown GSCs exhibited diminished invasiveness, and the mice survived significantly longer than control mice. In contrast, siRNA-mediated silencing of the osteopontin gene decreased GSC proliferation. These results suggest that interaction between CD44 and osteopontin plays a key role in tumor progression in GBM; inhibition of both CD44 and osteopontin may represent an effective therapeutic approach for suppressing tumor progression, thus resulting in a better prognosis for patients with GBM.

DOI： 10.1016/j.tranon.2021.101137

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 61-year-old woman presented with diplopia and headache. The patient had a longstanding history of petrous bone cholesteatoma (PBC) on the left side and had undergone multiple surgeries to address it. Computed tomography (CT) revealed a radiolucent lesion with bony destruction in the left petrous apex. Magnetic resonance imaging of the lesion revealed a hypointense area on T1-weighted images and a hyperintense area on T2-weighted and abnormal diffusion-weighted images. A diagnosis of recurrent petrous apex cholesteatoma was made. The patient was treated by exteriorization using an endoscopic endonasal approach. The patient is in remission and doing well. The ideal treatment of PBC is complete excision, though exteriorization using an endoscopic endonasal approach is considered a second option when excision is not possible.

DOI： 10.5152/iao.2021.9153

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掲載種別：研究論文（学術雑誌）  

Antiangiogenic therapy with bevacizumab (Bev), a monoclonal antibody targeting vascular endothelial growth factor (VEGF), is a common treatment for recurrent glioblastoma (GBM), but its survival benefit is limited. Resistance to Bev is thought to be a major cause of ineffectiveness on Bev therapy. To optimize Bev therapy, identification of a predictive biomarker for responsiveness to Bev is required. Based on our previous study, we focused on the expression and functions of CD44 and VEGF in the Bev therapy. Here, we analyze a relationship between CD44 expression and responsiveness to Bev and elucidate the role of CD44 in anti-VEGF therapy. CD44 and VEGF expression in the tumor core and periphery of 22 GBMs was examined, and the relationship between expression of these molecules and progression-free time on Bev therapy was analyzed. The degree of CD44 expression in the tumor periphery was evaluated by the ratio of the mRNA expression in the tumor periphery to that in the tumor core (P/C ratio). VEGF expression was evaluated by the amount of the mRNA expression in the tumor periphery. To elucidate the roles of CD44 in the Bev therapy, in vitro and in vivo studies were performed using glioma stem-like cells (GSCs) and a GSC-transplanted mouse xenograft model, respectively. GBMs expressing high P/C ratio of CD44 were much more refractory to Bev than those expressing low P/C ratio of CD44, and the survival time of the former was much shorter than that of the latter. In vitro inhibition of VEGF with siRNA or Bev-activated CD44 expression and increased invasion of GSCs. Bev showed no antitumor effects in mice transplanted with CD44-overexpressing GSCs. The P/C ratio of CD44 expression may become a useful biomarker predicting responsiveness to Bev in GBM. CD44 reduces the antitumor effect of Bev, resulting in much more highly invasive tumors.

DOI： 10.1002/cam4.3767

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掲載種別：研究論文（学術雑誌）  

Background: We previously reported that glioma stemlike cells (GSCs) exist in the area of the tumor periphery showing no gadolinium enhancement on magnetic resonance imaging. In the present work, we analyzed glucose metabolism to investigate whether lactate could be predictive of tumor invasiveness and of use in detection of the tumor invasion area in glioblastoma multiforme (GBM). Methods: The expression of lactate dehydrogenase A (LDH-A) and pyruvate dehydrogenase (PDH) was investigated in 20 patients. In GSC lines, LDH-A and PDH expression also was examined in parallel to assessments of mitochondrial respiration. We then investigated the relationship between lactate/creatine ratios in the tumor periphery measured by magnetic resonance spectroscopy, using learning-compression-model algorithms and phenotypes of GBMs. Results: In 20 GBMs, high-invasive GBM expressed LDH-A at significantly higher expression than did low-invasive GBM, whereas low-invasive GBM showed significantly higher expression of PDH than did high-invasive GBM. The highly invasive GSC line showed higher expression of LDH-A and lower expression of PDH compared with low-invasive GSC lines. The highly invasive GSC line also showed the lowest consumption of oxygen and the lowest production of adenosine triphosphate. Lactate levels, as measured by magnetic resonance spectroscopy, showed a significant positive correlation with LDH-A transcript levels, permitting classification of the GBMs into high-invasive and low-invasive phenotypes based on a cutoff value of 0.66 in the lactate/creatine ratio. Conclusions: In the tumor periphery area of the highly invasive GBM, aerobic glycolysis was the predominant pathway for glucose metabolism, resulting in the accumulation of lactate. The level of lactate may facilitate prediction of the tumor-infiltrating area on GBM.

DOI： 10.1016/j.wneu.2021.06.044

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記述言語：英語  

© 2020 Scientific Scholar. All rights reserved. Background: Granular cell tumor (GCT) of the sellar region is a rare tumor of the sellar and suprasellar regions that originate from the neurohypophysis. This tumor is very difficult to differentiate from other pituitary neoplasms, such as pituitary adenoma, pituicytoma, and spindle cell oncocytoma. We report a rare case of GCT arising from the posterior pituitary of the sellar region and suggest a useful indicator for accurate diagnosis and pitfalls for surgical procedures. Case Description: A 42-year-old woman was admitted to our hospital with bitemporal hemianopsia. Neuroimaging showed a large pituitary tumor in the sellar and suprasellar regions with a hypointense part on T2-weighted magnetic resonance imaging, and the enhanced anterior pituitary gland was displaced anteriorly. Laboratory findings showed mild hyperprolactinemia. Subtotal resection of the tumor was achieved using an endoscopic endonasal transsphenoidal approach. Histological findings showed round or polygonal cells with abundant granular eosinophilic cytoplasm staining strongly for thyroid transcription factor 1. The tumor was, therefore, diagnosed as a GCT of the sellar region, belonging to tumors of the posterior pituitary. After surgery, visual impairment and anterior pituitary function were improved. Follow-up neuroimaging after 1 year showed no signs of recurrence. Conclusion: GCT of the sellar region is difficult to diagnose on routine neuroimaging. Therefore, accurate diagnosis requires careful identification of clinical signs, magnetic resonance imaging including hypointensity on T2-weighted imaging, and analysis of combined morphological and immunohistochemical studies.

DOI： 10.25259/SNI_111_2020

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

© 2020 Elsevier B.V. Objectives: Recognizing the anatomical orientation surrounding the sellar floor is crucial in endoscopic endonasal transsphenoidal surgery (ETSS). Zero-echo-time (ZTE) sequences were recently suggested for a new bone identification technique on magnetic resonance imaging (MRI). This study aimed to evaluate the clinical usefulness of three-dimensional (3D)-ZTE-based MRI models in providing anatomical guidance for ETSS. Patients and Methods: ZTE-based MRI and magnetic resonance angiography (MRA) data from 15 consecutive patients with pituitary tumor treated between September 2018 and May 2019 were used to create 3D-MRI models. From these, the architecture surrounding the sellar floor, particularly anatomical relationships between tumors and internal carotid arteries (ICAs), was visualized to preoperatively plan surgical procedures. In addition, 3D-ZTE-based MRI models were compared to actual surgical views during ETSS to evaluate model applicability. Results: These 3D-ZTE-based MRI models clearly demonstrated the morphology of the sellar floor and matched well with intraoperative views, including pituitary tumor, by successively eliminating sphenoidal structures. The models also permitted determination of the maximum marginal line of the opening of the sellar floor by presenting vital structures such as ICAs and tumors. With such 3D-MRI models, the surgeon could access the intracranial area through the sellar floor more safely, and resect the pituitary tumor maximally without complications. Conclusion: Our 3D-MRI models based on ZTE sequences allowed distinct visualization of vital structures and pituitary tumor around the sellar floor. This new method using 3D-ZTE-based MRI models showed low invasiveness for patients and was useful in preoperative planning for ETSS, facilitating maximum tumor resection without complications.

DOI： 10.1016/j.clineuro.2020.105743

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記述言語：英語  

© 2020 Scientific Scholar. All rights reserved. Background: Epithelioid glioblastoma is a rare aggressive variant of glioblastoma multiforme (GBM), which was formally recognized by the World Health Organization classification of the central nervous system in 2016. Clinically, epithelioid GBMs are characterized by aggressive features, such as metastases and cerebrospinal fluid dissemination, and an extremely poor prognosis. A rare case of epithelioid GBM that was discovered as a multicentric glioma with different histopathology is reported. Case Description: A 78-year-old man was admitted to our hospital with mild motor weakness of the right leg. Neuroimaging showed small masses in the left frontal and parietal lobes on magnetic resonance imaging. The abnormal lesion had been increasing rapidly for 3 weeks, and a new lesion appeared in the frontal lobe. 11C-methionine positron emission tomography (PET) showed abnormal uptake corresponding to the lesion. To reach a definitive diagnosis, surgical excision of the right frontal mass lesion was performed. Histological findings showed diffuse astrocytoma. Only radiotherapy was planned, but the left frontal and parietal tumors progressed further within a short period. Therefore, it was thought that these tumors were GBM, and a biopsy of the left parietal tumor was performed. The histological diagnosis was epithelioid GBM. Immunohistochemistry showed that most tumor cells were negatively stained for p53 and isocitrate dehydrogenase 1. BRAF V600E mutations were not identified, but TERT promoter mutations were identified. Immediately after surgery, the patient was given chemotherapy using temozolomide, extended local radiotherapy and then bevacizumab. After 6 months, he showed no signs of recurrence. Conclusion: Epithelioid GBM is one of the rarest morphologic subtypes of GBM and has a strongly infiltrative and aggressive nature. Therefore, careful identification of preoperative imaging studies and detailed evaluation of genetic studies are necessary to select the appropriate treatment for epithelioid GBM.

DOI： 10.25259/SNI_544_2019

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Differentiating tumor from normal pituitary gland is very important for achieving complete resection without complications in endoscopic endonasal transsphenoidal surgery (ETSS) for pituitary adenoma. To facilitate such surgery, we investigated the utility of indocyanine green (ICG) fluorescence endoscopy as a tool in ETSS. Twenty-four patients with pituitary adenoma were enrolled in the study and underwent ETSS using ICG endoscopy. After administering 12.5 mg of ICG twice an operation with an interval > 30 min, times from ICG administration to appearance of fluorescence on vital structures besides the tumor were measured. ICG endoscopy identified vital structures by the phasic appearance of fluorescent signals emitted at specific consecutive elapsed times. Elapsed times for internal carotid arteries did not differ according to tumor size. Conversely, as tumor size increased, elapsed times for normal pituitary gland were prolonged but those for the tumor were reduced. ICG endoscopy revealed a clear boundary between tumors and normal pituitary gland and enabled confirmation of no more tumor. ICG endoscopy could provide a useful tool for differentiating tumor from normal pituitary gland by evaluating elapsed times to fluorescence in each structure. This method enabled identification of the boundary between tumor and normal pituitary gland under conditions of a low-fluorescence background, resulting in complete tumor resection with ETSS. ICG endoscopy will contribute to improve the resection rate while preserving endocrinological functions in ETSS for pituitary adenoma.

DOI： 10.1007/s10143-020-01382-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Glioblastoma multiforme (GBM) is largely due to glioma stem cells (GSCs) that escape from total resection of gadolinium (Gd)-enhanced tumor on MRI. The aim of this study is to identify the imaging requirements for maximum resection of GBM with infiltrating GSCs. We investigated the relationship of tumor imaging volume between MRI and 11C-methionine (Met)-PET and also the relationship between Met uptake index and tumor activity. In ten patients, tumor-to-contralateral normal brain tissue ratio (TNR) was calculated to evaluate metabolic activity of Met uptake areas which were divided into five subareas by the degrees of TNR. In each GBM, tumor tissue was obtained from subareas showing the positive Met uptake. Immunohistochemistry was performed to examine the tumor proliferative activity and existence of GSCs. In all patients, the volume of Met uptake area at TNR ≦ 1.4 was larger than that of the Gd-enhanced area. The Met uptake area at TNR 1.4 beyond the Gd-enhanced tumor was much wider in high invasiveness–type GBMs than in those of low invasiveness type, and survival was much shorter in the former than the latter types. Immunohistochemistry revealed the existence of GSCs in the area showing Met uptake at TNR 1.4 and no Gd enhancement. Areas at TNR > 1.4 included active tumor cells with relatively high Ki-67 labeling index. In addition, it was demonstrated that GSCs could exist beyond the border of Gd-enhanced tumor. Therefore, to obtain maximum resection of GBMs, including infiltrating GSCs, aggressive surgical excision that includes the Met-positive area at TNR 1.4 should be considered.

DOI： 10.1007/s10143-020-01258-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Intracranial anaplastic hemangiopericytoma (AHPC) is a rare and malignant subset of solitary fibrous tumor/hemangiopericytoma (SFT/HPC) as per the WHO 2016 Classification of Tumors of the Central Nervous System. AHPC portends a poor prognosis and is associated with higher rates of recurrence/metastasis in comparison with SFT/HPC. Accordingly, it is critical to continue to define the clinical course of patients with AHPC and in so doing further refine clinicopathologic/immunohistochemical (IHC) criteria needed for definitive diagnosis. Herein, we describe clinical/histological characteristics of six patients with AHPC. In addition, we reviewed and analyzed the expression of various IHC markers reported within the literature (i.e., a total of 354 intracranial SFT/HPCs and 460 meningiomas). Histologically, tumors from our six patients were characterized by a staghorn-like vascular pattern, mitotic cells, and strong nuclear atypia. Immunohistochemically, all tumors displayed positive nuclear staining for STAT6; other markers, including CD34 and Bcl-2, were expressed only in three patients. Analysis of IHC expression patterns for SFT/HPC and meningioma within the literature revealed that nuclear expression of STAT6 had the highest specificity (100%) for SFT/HPC, followed by ALDH1 (97.2%) and CD34 (93.6%). Of note, SSTR2A (95.2%) and EMA (85%) displayed a high specificity for meningioma. Anaplastic SFT/HPC is a tumor with poor prognosis that is associated with higher rates of recurrence and metastasis in comparison with SFT/HPC. Given that anaplastic SFT/HPC requires more aggressive treatment than meningioma despite of a similar presentation on imaging, it is crucial to be able to distinguish between these tumors.

DOI： 10.1007/s10143-020-01348-6

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記述言語：日本語   出版者・発行元：(一社)日本てんかん学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

© 2018 We report a rare case of pituicytoma occurring in the sellar region resected by endoscopic transsphenoidal surgery (ETSS). We suggest useful indicators for the accurate diagnosis and pitfalls for the surgical procedure. A 38-year-old man was admitted to our hospital with polyuria, erectile dysfunction and bitemporal hemianopsia. Neuroimaging revealed pituitary tumor in the sellar region, and the enhanced anterior pituitary gland was displaced anteriorly. Gross total resection was achieved using ETSS. Histological findings revealed bipolar spindle cells staining strongly for thyroid transcription factor 1 (TTF-1). We diagnosed the tumor as pituicytoma originated from posterior pituitary. Pituicytoma is difficult to diagnose on routine neuroimaging and pathological analysis, so accurate diagnosis requires identification of the forward deviation of anterior pituitary gland and analysis of immunohistochemical studies using TTF-1.

DOI： 10.1016/j.inat.2018.12.013

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Primary central nervous system lymphoma (PCNSL) has been immunohistochemically classified into two subtypes, germinal center (GC) B-cell and non-GC B-cell, but the prognostic impact of these subtypes remains debated. We investigated clinical features and prognostic significance of immunohistochemical subtypes that were identified by expression patterns of three B-cell differentiation markers in PCNSL. We also analyzed a factor related to responsiveness to high-dose methotrexate (HD-MTX) chemotherapy. Tumors from 32 PCNSL patients were immunohistochemically evaluated for expression of cluster of differentiation (CD) 10, B-cell lymphoma-6 (BCL-6), and multiple myeloma oncogene-1 (MUM-1) and classified into subtypes according to the expression patterns of these markers. Clinical features and prognostic outcome of these subtypes were investigated. Twenty-three patients were treated with HD-MTX-based chemotherapy followed by whole-brain radiation therapy (WBRT), and nine were treated with WBRT alone. Three immunohistochemical subtypes were identified, including A-type expressing CD10, BCL-6, and MUM-1 (12 patients), B-type expressing BCL-6 and MUM-1 (12 patients) and C-type expressing MUM-1 only (8 patients). Response rate in the HD-MTX therapy group was 57.1% (4/7) in A-type, 87.5% (7/8) in B-type, and 75% (6/8) in C-type. C-type with the lowest metabolic activity showed significantly longer overall survival than A-type with the higher uptake of methionine (71.6 versus 39.6 months) (P<0.05). Immunohistochemical identification of PCNSL based on the B-cell differentiation stage revealed three types of tumors, showing different metabolic activity and survival time. Refined immunohistochemical classification of PCNSL subtypes may become a useful tool for predicting more accurate prognosis and accessing sensitivity to HD-MTX therapy.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

© AANS 2018, except where prohibited by US copyright law OBJECTIVE High invasiveness of malignant gliomas frequently causes early local recurrence of the tumor, resulting in extremely poor outcome. To control such recurrence, novel therapies targeted toward infiltrating glioma cells around the tumor border are required. Here, the authors investigated the antitumor activity of sonodynamic therapy (SDT) combined with a sonosensitizer, 5-aminolevulinic acid (5-ALA), on malignant gliomas to explore the possibility for clinical use of 5-ALA-mediated SDT (5-ALA-SDT). METHODS In vitro cytotoxicity of 5-ALA-SDT was evaluated in U87 and U251 glioma cells and in U251Oct-3/4 glioma stemlike cells. Treatment-related apoptosis was analyzed using flow cytometry and TUNEL staining. Intracellular reactive oxygen species (ROS) were measured and the role of ROS in treatment-related cytotoxicity was examined by analysis of the effect of pretreatment with the radical scavenger edaravone. Effects of 5-ALA-SDT with high-intensity focused ultrasound (HIFU) on tumor growth, survival of glioma-transplanted mice, and histological features of the mouse brains were investigated. RESULTS The 5-ALA-SDT inhibited cell growth and changed cell morphology, inducing cell shrinkage, vacuolization, and swelling. Flow cytometric analysis and TUNEL staining indicated that 5-ALA-SDT induced apoptotic cell death in all gliomas. The 5-ALA-SDT generated significantly higher ROS than in the control group, and inhibition of ROS generation by edaravone completely eliminated the cytotoxic effects of 5-ALA-SDT. In the in vivo study, 5-ALA-SDT with HIFU greatly prolonged survival of the tumor-bearing mice compared with that of the control group (p < 0.05). Histologically, 5-ALA-SDT produced mainly necrosis of the tumor tissue in the focus area and induced apoptosis of the tumor cells in the perifocus area around the target of the HIFU-irradiated field. The proliferative activity of the entire tumor was markedly decreased. Normal brain tissues around the ultrasonic irradiation field of HIFU remained intact. CONCLUSIONS The 5-ALA-SDT was cytotoxic toward malignant gliomas. Generation of ROS by the SDT was thought to promote apoptosis of glioma cells. The 5-ALA-SDT with HIFU induced tumor necrosis in the focus area and apoptosis in the perifocus area of the HIFU-irradiated field, whereas the surrounding brain tissue remained normal, resulting in longer survival of the HIFU-treated mice compared with that of untreated mice. These results suggest that 5-ALA-SDT with HIFU may present a less invasive and tumor-specific therapy, not only for a tumor mass but also for infiltrating tumor cells in malignant gliomas.

DOI： 10.3171/2017.6.JNS162398

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor and a subpopulation of glioma stem-like cells (GSCs) is likely responsible for the invariable recurrence following maximum resection and chemoradiotherapy. As most GSCs that are located in the perivascular and perinecrotic niches should be removed during tumor resection, it is very important to know where surviving GSCs are localized. Here, we investigated the existence and functions of GSCs in the tumor periphery, which is considered to constitute the invasion niche for GSCs in GBM, by analyzing expression of stem cell markers and stem cell-related molecules and measuring particular activities of cultured GSCs. In addition, the relationship between GSCs expressing particular stem cell markers and pathological features on MRI and prognosis in GBM patients was analyzed. We showed that GSCs that express high levels of CD44 are present in the tumor periphery. We also found that vascular endothelial growth factor (VEGF) is characteristically expressed at a high level in the tumor periphery. Cultured GSCs obtained from the tumor periphery were highly invasive and have enhanced migration phenotype, both of which were markedly inhibited by CD44 knockdown. Higher expression of CD44 in the tumor periphery than in the core was correlated with a highly invasive feature on MRI and was associated with early tumor progression and worse survival, whereas lower expression of CD44 in the tumor periphery corresponded to low invasion and was associated with longer survival. The low invasion type on MRI tended to show high levels of VEGF expression in the tumor periphery, thus presenting the tumor with high proliferative activity. These results imply the significance of GSCs with high levels of CD44 expression in the tumor periphery compared to the core, not only in tumor invasion but also rapid tumor progression and short survival in patients with GBM.

DOI： 10.1155/2018/5387041

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記述言語：英語  

Background: Chordoid glioma of the third ventricle is a rare neuroepithelial tumor characterized by a unique histomorphology within the third ventricular region, but with radiological and histopathological features mimicking benign lesions such as meningioma. We report a case of chordoid glioma of the third ventricle and suggest a useful indicator for accurate diagnosis. Case Description: A previously healthy 46-year-old woman was admitted to our hospital with mild headache. Neuroimaging revealed a large tumor measuring approximately 18 mm in the suprasellar region, and perifocal edema in the optic tract and internal capsule on magnetic resonance imaging. Laboratory findings revealed no pituitary dysfunction including diabetes insipidus. Gross total resection of the tumor was performed by the interhemispheric translamina terminalis approach. Histological findings revealed nests of regular epithelioid cells with large nuclei and abundant eosinophilic cytoplasm within myxoid stroma. Immunohistochemical studies demonstrated diffuse cytoplasmic expression of glial fibrillary acidic protein (GFAP) and CD34, and strong nuclear staining for thyroid transcription factor 1 (TTF-1). We, therefore, histologically classified the tumor as chordoid glioma of the third ventricle. Headache improved immediately postoperatively, and follow-up neuroimaging after 12 months showed no signs of recurrence. Conclusions: Chordoid glioma of the third ventricle is a very rare tumor that is difficult to diagnose on routine neuroimaging. Accurate diagnosis requires detailed analysis of neuroimaging and immunohistochemical studies using CD34 and TTF-1 staining.

DOI： 10.4103/sni.sni_306_18

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER HEIDELBERG  

© 2016, Springer-Verlag Berlin Heidelberg. Purpose: Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is also used to manage seizures in glioblastoma patients. HDAC inhibitors can protect normal cells and tissues from the deleterious effects of radiotherapy, and VPA is reported to improve the survival of glioblastoma patients receiving chemoradiation therapy. VPA also promotes hair growth, and thus has the potential to reduce the radiotherapy side effect of hair loss while improving the survival of patients with glioblastoma. The purpose of this study was to determine whether VPA use during radiotherapy for high-grade glioma is associated with decreased side effects of radiotherapy and an improvement in overall survival (OS) and progression-free survival (PFS). Methods: Medical records of 112 patients with high-grade glioma were retrospectively reviewed. We grouped patients by VPA use or non-use during radiotherapy, and evaluated hair loss, OS, and PFS. Results: The radiation dose and fractionation at the onset of hair loss were 4 Gy and two fractions higher, respectively, in the VPA group compared with the VPA non-use group (P < 0.01). Median OS was 42.2 and 20.3 months in the VPA use and non-use groups, respectively (P < 0.01; hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.18–0.74). Median PFS was 22.7 and 11.0 months in the VPA use and non-use groups, respectively (P = 0.099; HR, 0.62; 95% CI, 0.36–1.09). Conclusions: VPA use during radiotherapy for glioma is associated with delayed hair loss and improvement in survival. Hair loss prevention benefits patients suffering from the deleterious effects of radiation.

DOI： 10.1007/s00228-016-2167-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

© 2015, Springer Science+Business Media New York. Carmustine wafers are approved for localized treatment of malignant glioma. In this study, overall changes in computed tomography (CT) and magnetic resonance (MR) images of malignant glioma patients treated with carmustine wafer implantation were evaluated. The subjects were 25 patients undergoing craniotomy for malignant glioma resection and carmustine wafer implantation. Changes in the appearance of wafers, the resection cavity, and the adjacent parenchyma on CT and MR imaging were evaluated retrospectively. On CT, the wafers changed from an initially high-dense to an iso-dense appearance. All MR studies showed a low-intense wafer within 2 days. The wafers changed to a high- or iso-intense appearance on fluid attenuated inversion recovery and T1-weighted imaging, whereas they changed to an iso- to low-intense appearance on T2-weighted imaging. Gas in the cavity increased gradually after surgery, achieved a peak at 1 week postoperatively, and then disappeared in 1–3 months. Increased volume of the resection cavity was observed in 48 % of patients. Regarding changes in the adjacent parenchyma, obvious contrast enhancement at the wall of the resection cavity was seen in 91 % of cases at 1 month, but this disappeared gradually. Edema around the resection cavity was increased in 7 patients (28 %), of whom only two experienced symptoms due to edema. We conclude that these radiological changes after carmustine wafer implantation should be carefully followed up, because these changes can easily be mistaken for infectious disease or recurrent tumors.

DOI： 10.1007/s11060-015-1941-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

©2015 AACR. Glioma-initiating cells (GIC) have stem-like cell properties thought to be sufficient for recurrence, progression, and drug resistance in glioblastomas. In the present study, we defined miRNA (miR)-340 as a differentially expressed miRNA in human GICs that inhibit GIC-mediated tumorigenesis. Furthermore, we defined tissue plasminogen activator (PLAT) as a critical direct target of miR340 for inhibition. Among miRNAs screened, we found that miR340 expression was decreased in all human GICs and in human glioblastoma tissues, compared with human neural stem cells and normal brain tissues. miR340 overexpression in GICs suppressed their proliferative, invasive, and migratory properties in vitro, triggering cell senescence in vitro and inhibiting GIC-induced tumorigenesis in mouse brains. shRNA-mediated silencing of PLAT in GICs phenocopied the effects of miR340 overexpression in vitro and in vivo, suggesting a potential role for tissue factor in stem-like cell function. Taken together, our results identified miR340 as a tumor suppressor that functions in GIC to enforce PLAT blockade and ablate their stem-like functions.

DOI： 10.1158/0008-5472.CAN-14-0938

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

© 2014, Springer-Verlag Berlin Heidelberg. The current optimal surgery for glioblastomas (GBMs) near the pyramidal tract (PT) is to remove as much tumor as possible and to preserve motor function. The purpose of this study is to investigate the usefulness of tractography-integrated navigation-guided fence-post catheter techniques and motor-evoked potentials (MEPs) for preserving postoperative motor function after GBM surgery. We retrospectively examined 49 patients who underwent resection for GBM near the PT. Diffusion tensor (DT) imaging-based tractography of the PT was performed preoperatively and integrated into the navigation system. When possible, silicon catheters were used as “fence-posts” and were inserted along the tumor boundaries, avoiding the PT, before tumor removal using the navigation system (fence-post catheter techniques). Cortical and subcortical MEPs were also monitored during resection of the tumor. Fence-post catheter techniques using a tractography-integrated navigation system were used in 45 of 49 patients. This technique enabled placement of the catheters, avoided the motor pathways, and allowed easier resection of the tumors. Tumors near the PT were resected using subcortical and cortical MEPs. The amplitudes of cortical MEPs after tumor removal were maintained at over 33 % of those obtained before resection. Thirty-six patients showed obvious responses of subcortical MEPs at ≤20 mA. The degree of resection was gross total in 21 patients, subtotal in 21, and partial in seven. One month after surgery, only one patient showed worsened motor function. Therefore, fence-post catheter techniques using a tractography-integrated navigation system and MEPs may contribute to preserving motor function after surgery for GBMs that are near the PT.

DOI： 10.1007/s10143-014-0593-z

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Relapsing polychondritis (RP) is a rare, generalized autoimmune disorder that is characterized by recurrent inflammation of various cartilaginous structures. Involvement of the central nervous system is rarely observed in RP. Here we report a case of encephalitis associated with RP. A 60-year-old man presented with headache and bilateral ear swelling. Three weeks later, he came to our hospital because of the acute onset of a speech impediment. A non-contrast computed tomography scan of the head showed slight high-density areas in his left frontal lobe, but he refused to be admitted and went home. On the next day, he developed acalculia, agraphia, right-left disorientation, and mild right hemiparesis. Brain MRI revealed hyperintensity areas in the left frontal sulcus on fluid-attenuated inversion recovery (FLAIR) images, and these hyperintensity areas were enhanced by gadolinium. Therefore, the patient's symptoms were diagnosed as focal epilepsy caused by meningoencephalitis. Other examinations, including laboratory blood tests, cerebrospinal fluid tests, and a cerebral angiography, were all negative. Therefore, a brain biopsy of the left frontal cortex was performed 5 days after the patient's admission. Pathological findings revealed chronic inflammation of the meninges, so prednisone was administered. After receiving oral prednisone, the patient's bilateral ear swelling dramatically improved and the lesions apparent on cranial MRI gradually subsided. The patient was diagnosed with RP by a neurologist after discharge from the hospital. In this study, early diagnosis and steroid treatment is recommended for patients with neurological complications due to RP.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN NEUROSURGICAL SOC  

A 25-year-old man presented with an intraorbital encephalocele manifesting as progressive left pulsatile exophthalmos. He had a history of frontal lobe contusion from a motorbike accident 10 years before the onset of the symptom. Computed tomography and magnetic resonance imaging revealed an oval-shaped defect in the left orbital roof with an underlying intracranial cystic lesion, herniated into the orbit. Intraoperative findings included disruption of the dura mater around the bony defect. The loculated arachnoid membrane and protruding brain tissue were excised with primary dural closure and reconstructive cranioplasty with a titanium mesh. The postoperative course was uneventful, and the pulsatile proptosis disappeared immediately after the procedure. Intracranial cyst may be important in the development of progressive pulsatile exophthalmos and intraorbital encephalocele.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Dexmedetomidine is a central α2 adrenoceptor agonist recently shown to be a safe and acceptable sedative agent for patients requiring sedation after brain surgery. We report two patients successfully treated by carotid endarterectomy (CEA) with postoperative management under dexmedetomidine anesthesia for transient ischemic attack (TIA) resulting from severe stenosis of the internal carotid artery (ICA). Case 1: A 75-year-old man was admitted to our hospital with aphasia and weakness of the right side of his body. Although no evidence of acute cerebral infarction was obtained on magnetic resonance imaging (MRI)/diffusion-weighted image (DWI), MR angiography (MRA) revealed severe stenosis of the left cervical ICA. 123I-IMP-single photon emission tomography (SPECT) and transcranial Doppler (TCD) revealed marked reduction of cerebral blood flow in the left cerebral hemisphere. Although CEA induced hyperperfusion, aggressive control of blood pressure under dexmedetomidine anesthesia enabled effective management of the resulting hyperperfusion syndrome. The patient was discharged without neurological deficits. Case 2: A 68-year-old man was admitted to our hospital with amaurosis fugax and numbness of the right side of his body. Although no evidence of acute cerebral infarction was obtained on MRI/DWI, MRA disclosed severe stenosis of the left cervical ICA. 123I-IMP-SPECT revealed extremely low perfusion and disturbance of vascular reactivity in the territory of the left ICA. Although conservative therapy was performed, crescendo TIA was noted. Revascularization using CEA was therefore performed. After surgery, hyperperfusion was observed in the same fashion as in case 1, and again aggressive control of blood pressure under dexmedetomidine anesthesia enabled effective management of the resulting hyperperfusion syndrome. The patient was discharged 1 month postoperatively without neurological deficits. Dexmedetomidine is a safe and acceptable sedative drugs preventing hyperperfusion syndrome after CEA.

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記述言語：日本語   出版者・発行元：(株)医学書院  

症例1:75歳男。失語と右半身脱力を主訴とした。症例2:68歳男。右半身痺れと左眼前暗黒感を主訴とした。2例とも10年以上の高血圧が存在し、頸部内頸動脈の高度狭窄に伴う脳血流低下(健側比10%以上)と血管反応性低下を認め、特に症例2では頻回に脳虚血症状を認めた。2例に対し頸動脈内膜剥離術を施行し、術後は厳格な血圧管理を優先し、術当日は覚醒を行わず、プロポフォールを用いた鎮静と血圧管理を行った。しかし、transcranial DopplerおよびPAO-SPECT所見より術後過灌流が疑われ、更なる鎮静が必要と考え、デクスメデトミジンによる鎮静と血圧管理を追加した。その結果、重篤な合併症を起こすことなく、過灌流が落ち着いた安全な時点で完全覚醒を行うことが出来た。いずれも術後29日に独歩退院した。

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：日本語   出版者・発行元：産業開発機構映像情報メディカル編集部  

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記述言語：英語   出版者・発行元：日本癌学会  

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担当区分：筆頭著者   記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：日本語   出版者・発行元：愛媛医学会  

悪性神経膠腫、中でも最も悪性度の高い膠芽腫は、外科的切除・放射線照射・化学療法を組み合わせた最良の集学的治療を行っても、生存期間中央値は約14ヵ月と極めて予後不良の悪性脳腫瘍である。近年、microRNA(miRNA)の発現異常が腫瘍形成や増殖・浸潤における種々の遺伝子の発現制御を介して、癌幹細胞の特性に深く関与していることが明らかとなり、その細胞外運搬を担うエクソソームが新たなバイオマーカーの情報源として注目されている。そこで、私達は腫瘍再発に深く関わっていると考えられているグリオーマ幹細胞に注目し、腫瘍形成および悪性化に関わるグリオーマ幹細胞に特異的な新規miRNAの探索を行った。まず、ヒトグリオーマ幹細胞を用いて網羅的なマイクロアレイ解析を行い、新規miRNAとしてmiR-340を同定した。miR-340の発現が正常神経幹細胞および正常脳組織と比較してグリオーマ幹細胞および悪性神経膠腫組織で有意に抑制されていること、miR-340の強制発現によりグリオーマ幹細胞の増殖能・浸潤能・遊走能・腫瘍形成能が抑制され、細胞老化やapoptosisが誘導されることを明らかにした。次に、miR-340の標的遺伝子としてtissue plasminogen activator(PLAT)を同定し、PLATのノックダウンにより、増殖能・浸潤能・遊走能がmiR-340強制発現時と同様に有意に抑制されることも証明した。さらに、グリオーマ幹細胞および神経膠腫患者血清由来のエクソソーム内miRNAの発現プロファイリングを行い、患者血清と共通してグリオーマ幹細胞で特異的な発現を示す11種類のmiRNAを同定した。これらは全て正常対照に比べ、発現が低下しており、この中にmiR-340も含まれていた。以上の結果より、miR-340は、悪性神経膠腫において腫瘍形成および悪性化に関わる重要な遺伝子の発現を制御しているtumor suppressorであり、腫瘍幹細胞を標的とした新たな核酸医薬としての臨床応用が示唆された。一方、現段階では、エクソソーム中のmiRNAで、診断のバイオマーカーとなり得る特異的なものは同定することができなかった。(著者抄録)

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記述言語：日本語  

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担当区分：筆頭著者   記述言語：日本語  

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記述言語：日本語  

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担当区分：筆頭著者   記述言語：日本語   出版者・発行元：(一社)日本脳神経超音波学会  

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：愛媛医学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

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記述言語：日本語  

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担当区分：筆頭著者   記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語   出版者・発行元：愛媛医学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：愛媛医学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経外科救急学会  

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