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

Abstract

Application of physical forces, ranging from ultrasound to electric fields, is recommended in various clinical practice guidelines, including those for treating cancers and bone fractures. However, the mechanistic details of such treatments are often inadequately understood, primarily due to the absence of comprehensive study models. In this study, we demonstrate that an alternating magnetic field (AMF) inherently possesses a direct anti‐cancer effect by enhancing oxidative phosphorylation (OXPHOS) and thereby inducing metabolic reprogramming. We observed that the proliferation of human glioblastoma multiforme (GBM) cells (U87 and LN229) was inhibited upon exposure to AMF within a specific narrow frequency range, including around 227 kHz. In contrast, this exposure did not affect normal human astrocytes (NHA). Additionally, in mouse models implanted with human GBM cells in the brain, daily exposure to AMF for 30 min over 21 days significantly suppressed tumor growth and prolonged overall survival. This effect was associated with heightened reactive oxygen species (ROS) production and increased manganese superoxide dismutase (MnSOD) expression. The anti‐cancer efficacy of AMF was diminished by either a mitochondrial complex IV inhibitor or a ROS scavenger. Along with these observations, there was a decrease in the extracellular acidification rate (ECAR) and an increase in the oxygen consumption rate (OCR). This suggests that AMF‐induced metabolic reprogramming occurs in GBM cells but not in normal cells. Our results suggest that AMF exposure may offer a straightforward strategy to inhibit cancer cell growth by leveraging oxidative stress through metabolic reprogramming.

DOI： 10.1111/cas.16243

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

SIGNIFICANCE: The initiation of goal-directed actions is a complex process involving the medial prefrontal cortex and dopaminergic inputs through the mesocortical pathway. However, it is unclear what information the mesocortical pathway conveys and how it impacts action initiation. In this study, we unveiled the indispensable role of mesocortical axon terminals in encoding the execution of movements in self-initiated actions. AIM: To investigate the role of mesocortical axon terminals in encoding the execution of movements in self-initiated actions. APPROACH: We designed a lever-press task in which mice internally determine the timing of the press, receiving a larger reward for longer waiting periods. RESULTS: Our study revealed that self-initiated actions depend on dopaminergic signaling mediated by D2 receptors, whereas sensory-triggered lever-press actions do not involve D2 signaling. Microprism-mediated two-photon calcium imaging further demonstrated ramping activity in mesocortical axon terminals approximately 0.5 s before the self-initiated lever press. Remarkably, the ramping patterns remained consistent whether the mice responded to cues immediately for a smaller reward or held their response for a larger reward. CONCLUSIONS: We conclude that mesocortical dopamine axon terminals encode the timing of self-initiated actions, shedding light on a crucial aspect of the intricate neural mechanisms governing goal-directed behavior.

DOI： 10.1117/1.NPh.11.3.033408

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The increasing prevalence of heated tobacco products (HTPs) has heightened concerns regarding their potential health risks. Previous studies have demonstrated the toxicity of cigarette smoke extract (CSE) from traditional tobacco's mainstream smoke, even after the removal of nicotine and tar. Our study aimed to investigate the cytotoxicity of CSE derived from HTPs and traditional tobacco, with a particular focus on the role of reactive oxygen species (ROS) and intracellular Ca2+. METHODS: A human oral squamous cell carcinoma (OSCC) cell line, HSC-3 was utilized. To prepare CSE, aerosols from HTPs (IQOS) and traditional tobacco products (1R6F reference cigarette) were collected into cell culture media. A cell viability assay, apoptosis assay, western blotting, and Fluo-4 assay were conducted. Changes in ROS levels were measured using electron spin resonance spectroscopy and the high-sensitivity 2',7'-dichlorofluorescein diacetate assay. We performed a knockdown of calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) by shRNA lentivirus in OSCC cells. RESULTS: CSE from both HTPs and traditional tobacco exhibited cytotoxic effects in OSCC cells. Exposure to CSE from both sources led to an increase in intracellular Ca2+ concentration and induced p38 phosphorylation. Additionally, these extracts prompted cell apoptosis and heightened ROS levels. N-acetylcysteine (NAC) mitigated the cytotoxic effects and p38 phosphorylation. Furthermore, the knockdown of CaMKK2 in HSC-3 cells reduced cytotoxicity, ROS production, and p38 phosphorylation in response to CSE. CONCLUSION: Our findings suggest that the CSE from both HTPs and traditional tobacco induce cytotoxicity. This toxicity is mediated by ROS, which are regulated through Ca2+ signaling and CaMKK2 pathways.

DOI： 10.1186/s12576-024-00928-1

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

DOI： 10.1016/j.inat.2024.101974

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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：eLife Sciences Publications, Ltd  

Midbrain dopamine neurons impact neural processing in the prefrontal cortex (PFC) through mesocortical projections. However, the signals conveyed by dopamine projections to the PFC remain unclear, particularly at the single-axon level. Here, we investigated dopaminergic axonal activity in the medial PFC (mPFC) during reward and aversive processing. By optimizing microprism-mediated two-photon calcium imaging of dopamine axon terminals, we found diverse responses in dopamine axons, with some preferring reward and others preferring aversive stimuli, with a strong bias for the latter at the population level. Long-term longitudinal imaging revealed that the preference was maintained in reward- and aversive-preferring axons throughout classical conditioning in which rewarding and aversive stimuli were paired with preceding auditory cues. However, as mice learned to discriminate reward or aversive cues, a cue activity preference gradually developed only in aversive-preferring axons, becoming more selective for aversive processing. We inferred the trial-by-trial cue discrimination based on machine learning using anticipatory licking or facial expressions, and found that successful discrimination was accompanied by sharper selectivity for the aversive cue in aversive-preferring axons. Our findings implicate mesocortical dopamine axon activity in the encoding of aversive processing that is modulated by both classical conditioning across days and trial-by-trial discrimination within a day.

Two-photon calcium imaging revealed that many mesocortical dopamine axons show enhanced selectivity for aversive cue processing during classical conditioning.

DOI： 10.7554/eLife.91136

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Takotsubo cardiomyopathy (TC) is a well-known complication of subarachnoid haemorrhage (SAH), often accompanied by neurogenic myocardial dysfunction. Although TC has been reported to be associated with higher morbidity and mortality among patients with aneurysmal SAH (aSAH), some patients have been reported to recover, the profiles and follow-up outcomes of these survivors remain unclear. MATERIALS AND METHODS: To characterize the profiles of patients with aSAH complicated by TC who experienced favourable outcomes using long-term follow-up data, a consecutive series of patients with aSAH were enrolled and TC diagnosis was based on the revised version of the Mayo Clinic criteria. Clinical outcomes were assessed at 6 months according to modified Rankin Scale scores. RESULTS: Among 165 consecutive patients with aSAH, 15 cases were complicated by TC, corresponding to an occurrence rate of 9.0%. Five patients with aSAH complicated by TC (33.3%) experienced a favourable outcome, and the mean value of systolic blood pressure on arrival was significantly lower than in those who experienced an unfavourable outcome (p = 0.032). CONCLUSION: According to analysis, it is possible cardiac dysfunction with decreased cerebral perfusion pressure and catecholamine toxicity transiently worsens conscious disturbance in aSAH complicated by TC. Therefore, it is important to carefully screen patients with aSAH to identify those complicated by TC, and for close collaboration of the multidisciplinary team to design appropriate treatment strategies.

DOI： 10.1080/02688697.2024.2334432

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担当区分：責任著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.7759/cureus.52874

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記述言語：英語  

UNLABELLED: Midbrain dopamine neurons impact neural processing in the prefrontal cortex (PFC) through mesocortical projections. However, the signals conveyed by dopamine projections to the PFC remain unclear, particularly at the single-axon level. Here, we investigated dopaminergic axonal activity in the medial PFC (mPFC) during reward and aversive processing. By optimizing microprism-mediated two-photon calcium imaging of dopamine axon terminals, we found diverse responses in dopamine axons, with some preferring reward and others preferring aversive stimuli, with a strong bias for the latter at the population level. Long-term longitudinal imaging revealed that the preference was maintained in reward- and aversive-preferring axons throughout classical conditioning in which rewarding and aversive stimuli were paired with preceding auditory cues. However, as mice learned to discriminate reward or aversive cues, a cue activity preference gradually developed only in aversive-preferring axons, becoming more selective for aversive processing. We inferred the trial-by-trial cue discrimination based on machine learning using anticipatory licking or facial expressions, and found that successful discrimination was accompanied by sharper selectivity for the aversive cue in aversive-preferring axons. Our findings implicate mesocortical dopamine axon activity in the encoding of aversive processing that is modulated by both classical conditioning across days and trial-by-trial discrimination within a day. IMPACT STATEMENT: Two-photon calcium imaging revealed that many mesocortical dopamine axons show enhanced selectivity for aversive cue processing during classical conditioning.

DOI： 10.1101/2023.08.23.554475

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Subarachnoid hemorrhage and thyroid storm are similar in their clinical symptomatology, and diagnosis of these conditions, when they occur simultaneously, is difficult. Here, we report a rare case of concurrent subarachnoid hemorrhage and thyroid storm we encountered at our hospital. CASE PRESENTATION: The patient was a 52-year-old woman. While bathing at home, the patient experienced a sudden disturbance of consciousness and was brought to our hospital. The main physical findings upon admittance were Glasgow Coma Scale score of E1V2M4, elevated blood pressure (208/145 mmHg), and tachycardia with atrial fibrillation (180 bpm) along with body temperature of 36.1 °C. Brain computed tomography revealed subarachnoid hemorrhage associated with a ruptured aneurysm of the posterior communicating artery branching from the left internal carotid artery, and aneurysm clipping was performed. Blood tests upon admission revealed high levels of free T3 and free T4 and low levels of thyroid-stimulating hormone. Upon determining that the patient had hyperthyroidism, thiamazole was administered. However, due to continuous impaired consciousness, fever, and persistence of tachycardia, the patient was diagnosed with thyroid storm. Oral potassium iodide and hydrocortisone were added to the treatment. The treatment was successful as the patient's symptoms improved, and she became lucid. In this case, we believe that in the presence of untreated hyperthyroidism, the onset of subarachnoid hemorrhage induced thyroid storm. Tachycardia of 130 bpm or higher, which is the diagnostic criterion for thyroid storm, rarely occurs with subarachnoid hemorrhage. Therefore, we believe it is an important factor for recognizing the presence of the thyroid storm. In this case, clipping surgery was prioritized which resulted in a favorable outcome. However, it is possible that invasive surgery may have exacerbated thyroid storm, suggesting that treatment should be tailored as per patient's condition. CONCLUSION: If a pulse rate of 130 bpm or higher is observed alongside subarachnoid hemorrhage, we recommend considering the possibility of concomitant thyroid storm and testing for thyroid hormone. If concomitant thyroid storm is present, we believe that a treatment plan tailored to the patient's condition is critical, and early diagnosis will lead to a favorable outcome for the patient.

DOI： 10.1186/s12245-023-00490-4

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: There have been several reports of central nervous system impairments associated with severe coronavirus disease 2019 (COVID-19) infection on head magnetic resonance imaging and angiography (MRI/A). However, head MRI/A is rarely performed in mild cases, and there have been few reports on intracranial changes after COVID-19 infection in these cases. Here, we report a comparative examination of the findings seen in common head MRI/A sequences in mild cases of COVID-19. METHODS: Of the 15,376 patients who underwent head MRI/A examination called "Brain Dock" between June 2020 and June 2021, 746 patients who received a COVID-19 antibody test were evaluated. Positive and negative patients were comparatively examined for head MRI/A findings such as cerebral white matter lesions, ischemic changes, cerebral microbleeds, cerebral aneurysms, arterial stenosis, sinusitis, and other abnormal findings. RESULTS: Overall, 31 (4.2%) patients were COVID-19 positive, and all of them had mild infections not requiring hospitalization. There was no significant difference in patient characteristics and head MRI/A findings between positive and negative patients. All positive patients showed no particular abnormalities in the nasal findings such as olfactory bulb atrophy or thickening of the olfactory mucosa. CONCLUSION: Intracranial lesions in mild patients do not show a clear difference from those in negative patients. This indicates that findings seen in common MRI/A sequences of severe patients are not likely in mild patients, supporting that there is relatively no damage to the central nervous system in mild patients.

DOI： 10.7759/cureus.34229

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担当区分：責任著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：The Japanese Society for Neuroendovascular Therapy  

DOI： 10.5797/jnet.oa.2022-0043

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Observation is the first management option in asymptomatic meningiomas, but when an enlargement or mass effect is observed, surgery is indicated. This study is aimed at exploring risk factors for complications and recurrence after surgery for asymptomatic meningioma. We also examined the impact of preoperative tumor embolization, which is considered controversial. METHODS: We retrospectively reviewed 109 patients with primary asymptomatic meningiomas surgically treated at our institute between April 2007 and March 2021. Patients who only had headaches as a nonspecific complaint were included in the asymptomatic group. Complications, time to recurrence, and Glasgow Outcome Scale (GOS) score were the endpoints of the study. Risk factors for complications and recurrence were explored. Moreover, the effect of the resection on nonspecific headaches was also explored. RESULTS: The permanent postoperative complication rate related to the surgical procedure was 1.8%. Of the total, 107 patients (98.2%) with asymptomatic meningiomas who were surgically treated achieved a GOS score of 5 1 year after the operation. Preoperative headache was present in 31 patients and improved postoperatively in 21 patients. Multivariate analysis using the Cox proportional hazard model showed that preoperative tumor embolization with > 80% resolution of tumor staining (p < 0.001) was negatively related to recurrence, whereas age (p = 0.046) and Simpson grade IV resection (p = 0.041) were positively related to recurrence. CONCLUSION: Although surgery for asymptomatic meningiomas can, in many cases, be safe, it is not free of complications Thus, surgical intervention for asymptomatic meningiomas should be considered cautiously. However, more than half the patients with headaches showed improvement. Simpson grade IV resection cases should be assessed for recurrence, and preoperative tumor embolization might be effective in controlling recurrence.

DOI： 10.1007/s00701-022-05420-6

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担当区分：責任著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.inat.2022.101583

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Meningiomas are often embolized preoperatively to reduce intraoperative blood loss and facilitate tumor resection. However, the procedure is controversial and its effects have not yet been reported. We evaluated preoperative embolization for meningiomas and its effect on postoperative outcome and recurrence. METHODS: We retrospectively reviewed the medical records of 186 patients with WHO grade I meningiomas who underwent surgical treatment at our hospital between January 2010 and December 2020. We used propensity score matching to generate embolization and no-embolization groups (42 patients each) to examine embolization effects. RESULTS: Preoperative embolization was performed in 71 patients (38.2%). In the propensity-matched analysis, the embolization group showed favorable recurrence-free survival (RFS) (mean 49.4 vs 24.1 months; Wilcoxon p=0.049). The embolization group had significantly less intraoperative blood loss (178±203 mL vs 221±165 mL; p=0.009) and shorter operation time (5.6±2.0 hours vs 6.8±2.8 hours; p=0.036). There were no significant differences in Simpson grade IV resection (33.3% vs 28.6%; p=0.637) or overall perioperative complications (21.4% vs 11.9%; p=0.241). Tumor embolization prolonged RFS in a subanalysis of cases who experienced recurrence (n=39) among the overall cases before variable control (mean RFS 33.2 vs 16.0 months; log-rank p=0.003). CONCLUSIONS: After controlling for variables, preoperative embolization for meningioma did not improve the Simpson grade or patient outcomes. However, it might have effects outside of surgical outcomes by prolonging RFS without increasing complications.

DOI： 10.1136/neurintsurg-2022-019080

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記述言語：日本語   出版者・発行元：横浜市立大学医学会  

我々は鉄錯体の一種であるμ-oxo N,N-bis(salicylidene)ethylenediamine iron[以後,Fe(Salen)と呼ぶ]が有機化合物でありながら,抗腫瘍効果を持ち,さらに磁性を持つ(磁石に付き,強磁性の挙動を示す)ことを発見した.無機化合物が磁性を持つことはよく知られるが,有機化合物が常温で磁性を示すという報告は世界で初めてである.また,Fe(Salen)の磁場発生メカニズムの解析のため,結晶構造解析を行ったことで「磁場発生の原因となる化学構造」を同定し,その磁場発生メカニズムを突き止めた.Fe(Salen)は磁性を持つため,主に3つのユニークな特徴を持つ.1)磁力により体外から任意の場所にFe(Salen)を集積させること(ドラッグデリバリー)ができる.2)磁性を持つことでMRIのT2強調画像で低信号を示し,局在や濃度の推定が期待できる.3)磁性体は交流磁場で発熱するという特徴(IHクッキングヒーターと同じ原理)も持つため,温熱療法への応用が期待できる.我々は長年,Fe(Salen)のユニークな特徴を生かすべく,治療法を検討してきた.その後,Fe(Salen)をパクリタキセルと共有結合させ,パクリタキセルの薬効成分の磁性化に成功した.動物実験において磁力で磁性パクリタキセルを局所に集積させ,薬剤濃度を高めることで,治療効果が増強することを確認した.この磁性化技術が確立すれば,様々な市販医薬品を磁性化することが期待でき,薬剤単剤で複数の付加価値を得ることができる.本総説では,我々が10年以上取り組んで来た磁性抗がん剤についての研究内容についてまとめ,今後の展望を試みる.(著者抄録)

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記述言語：日本語   出版者・発行元：横浜市立大学医学会  

我々は鉄錯体の一種であるμ-oxo N,N-bis(salicylidene)ethylenediamine iron[以後,Fe(Salen)と呼ぶ]が有機化合物でありながら,抗腫瘍効果を持ち,さらに磁性を持つ(磁石に付き,強磁性の挙動を示す)ことを発見した.無機化合物が磁性を持つことはよく知られるが,有機化合物が常温で磁性を示すという報告は世界で初めてである.また,Fe(Salen)の磁場発生メカニズムの解析のため,結晶構造解析を行ったことで「磁場発生の原因となる化学構造」を同定し,その磁場発生メカニズムを突き止めた.Fe(Salen)は磁性を持つため,主に3つのユニークな特徴を持つ.1)磁力により体外から任意の場所にFe(Salen)を集積させること(ドラッグデリバリー)ができる.2)磁性を持つことでMRIのT2強調画像で低信号を示し,局在や濃度の推定が期待できる.3)磁性体は交流磁場で発熱するという特徴(IHクッキングヒーターと同じ原理)も持つため,温熱療法への応用が期待できる.我々は長年,Fe(Salen)のユニークな特徴を生かすべく,治療法を検討してきた.その後,Fe(Salen)をパクリタキセルと共有結合させ,パクリタキセルの薬効成分の磁性化に成功した.動物実験において磁力で磁性パクリタキセルを局所に集積させ,薬剤濃度を高めることで,治療効果が増強することを確認した.この磁性化技術が確立すれば,様々な市販医薬品を磁性化することが期待でき,薬剤単剤で複数の付加価値を得ることができる.本総説では,我々が10年以上取り組んで来た磁性抗がん剤についての研究内容についてまとめ,今後の展望を試みる.(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The occipital transtentorial approach (OTA) is a very useful but challenging approach to expose the pineal region because the deep-seated arachnoid membranes usually fold and extend over the great vein of Galen (GVG), leading to dense and poor visibility. In addition, the practical aspects of arachnoid anatomy are not well understood. We aimed to develop a safe surgical procedure for the OTA according to the practical aspects of arachnoid anatomy. METHODS: The procedure is shown through an illustrative video of surgery and cadaver. Five cadavers were analyzed for their arachnoid structures and the surgical procedures via the OTA, in strict compliance with legal and ethical requirements. RESULTS: All cadavers showed a 2-layered arachnoid structure-one belonging to the occipital lobe, and the other to the cerebellum. According to our cadaveric analysis, the arachnoid attachment of the tentorial apex can be peeled bluntly, with an average distance of 10.2 mm. For our clinical presentation, a pineal tumor with hydrocephalus was detected in a 14-year-old boy. While using the OTA and expanding the deep surgical field, we detached the membrane from the tentorial apex and bluntly peeled it to reveal the deep veins. Finally, gross total removal of the tumor was achieved. CONCLUSIONS: A 2-layered arachnoid structure interposes the GVG from above and below the tentorium. The arachnoid membrane below the tentorium can be peeled off bluntly from the GVG to the attachment bundle limited by the penetrating veins. This detachment technique is useful for safe enlargement of the surgical field for the OTA.

DOI： 10.1016/j.wneu.2021.04.041

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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) is an isolated type of lymphoma of the central nervous system and has a dismal prognosis despite intensive chemotherapy. Recent genomic analyses have identified highly recurrent mutations of MYD88 and CD79B in immunocompetent PCNSL, whereas LMP1 activation is commonly observed in Epstein-Barr virus (EBV)-positive PCNSL. However, a lack of clinically representative preclinical models has hampered our understanding of the pathogenic mechanisms by which genetic aberrations drive PCNSL disease phenotypes. Here, we establish a panel of 12 orthotopic, patient-derived xenograft (PDX) models from both immunocompetent and EBV-positive PCNSL and secondary CNSL biopsy specimens. PDXs faithfully retained their phenotypic, metabolic, and genetic features, with 100% concordance of MYD88 and CD79B mutations present in PCNSL in immunocompetent patients. These models revealed a convergent functional dependency upon a deregulated RelA/p65-hexokinase 2 signaling axis, codriven by either mutated MYD88/CD79B or LMP1 with Pin1 overactivation in immunocompetent PCNSL and EBV-positive PCNSL, respectively. Notably, distinct molecular alterations used by immunocompetent and EBV-positive PCNSL converged to deregulate RelA/p65 expression and to drive glycolysis, which is critical for intracerebral tumor progression and FDG-PET imaging characteristics. Genetic and pharmacologic inhibition of this key signaling axis potently suppressed PCNSL growth in vitro and in vivo. These patient-derived models offer a platform for predicting clinical chemotherapeutics efficacy and provide critical insights into PCNSL pathogenic mechanisms, accelerating therapeutic discovery for this aggressive disease. SIGNIFICANCE: A set of clinically relevant CNSL xenografts identifies a hyperactive RelA/p65-hexokinase 2 signaling axis as a driver of progression and potential therapeutic target for treatment and provides a foundational preclinical platform. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/23/5330/F1.large.jpg.

DOI： 10.1158/0008-5472.CAN-20-2425

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Thiel's embalming method provides natural coloration, flexibility, and tissue plasticity, and is used widely to prepare specimens for cadaver surgical training. However, this method causes brain softening, thereby restricting the cadaver surgical training of intra-cranial procedures. In this study, three cadavers were embalmed using formalin fixation, Thiel's embalming method, and Thiel's embalming method with additional intra-cerebral ventricular formalin injection, respectively. We also established rat models of the three embalming methods to develop and determine the best method for retaining adequate brain elasticity. The intra-ventricular formalin injection in the cadaver was performed through the Kocher's point, as in the classical external ventricular drain procedure. Both, the cadaver brains and rat models yielded consistent shear wave measurements and brain surface stiffness data. Notably, the Thiel's embalming method with additional intra-cerebral ventricular formalin injection yielded suitable elasticity for brain cadaver surgical training in terms of brain mobilization and surgical field deployment, and also discharged formaldehyde in undetectable quantities. To our knowledge, this is the first report in which a fixed quality, namely, brain elasticity for the performance of head and brain cadaver surgical training, has been evaluated in a cadaver subjected to the Thiel's embalming method with immersion fixation in the cerebrospinal fluid space. We conclude that the Thiel's embalming method with additional intra-cerebral ventricular formalin injection can maintain the brain elasticity, and may therefore improve the quality of head and brain cadaver surgical training safely and easily.

DOI： 10.1007/s12565-020-00545-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: This study aimed to clarify the relationship between tumor redox reaction evaluated by Cu-diacetyl-bis (N4-methylthiosemicarbazone) (Cu-ATSM) PET/computed tomography (CT) and disease-free survival (DFS) in patients with primary diffuse large B-cell lymphoma of the central nervous system (DLBCL-CNS). METHODS: Fifteen consecutive patients with histologically confirmed DLBCL-CNS underwent preoperative Cu-ATSM PET/CT and F-fluorodeoxyglucose (FDG) PET/CT. Statistical features of seven first-order parameters, including the standardized uptake value (SUV); 12 second-order parameters, including gray-level co-occurrence matrices and gray-level zone size matrices; and 5 high-order parameters, including neighborhood gray-tone difference matrices, were calculated from the volume of interest. We compared DFS with parameters, including SUVmax and tumor-to-background (T/B) ratio of FDG, and SUVmax, T/B ratio, and other textural features of Cu-ATSM. RESULTS: The mean follow-up duration after PET/CT was 458 (range, 41-1071) days. The SUVmax of FDG was significantly higher than that of Cu-ATSM (P = 0.001), but the T/B ratio was not significantly different between the scans (3.49 ± 2.29 vs 2.48 ± 1.18; P = 0.244). A Mantel-Cox log-rank test revealed no significant association between SUVmax of FDG and DFS (P = 0.641). A high SUVmax of Cu-ATSM had a tendency of shorter DFS (P = 0.055). Total lesion reduction, reductive tumor volume, and T/B ratio of Cu-ATSM were significantly correlated with poor DFS by univariate analysis (P = 0.049, 0.031, and 0.007, respectively). Neighborhood gray-level co-occurrence matrix dissimilarity was significantly correlated with poor DFS (P = 0.015). CONCLUSIONS: Metabolic and textural features derived from pretreatment Cu-ATSM PET/CT could be used for predicting DFS and establishing a novel treatment strategy in DLBCL-CNS patients.

DOI： 10.1097/MNM.0000000000001197

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cortical plasticity is fundamental to motor recovery following cortical perturbation. However, it is still unclear how this plasticity is induced at a functional circuit level. Here, we investigated motor recovery and underlying neural plasticity upon optogenetic suppression of a cortical area for eye movement. Using a visually-guided eye movement task in mice, we suppressed a portion of the secondary motor cortex (MOs) that encodes contraversive eye movement. Optogenetic unilateral suppression severely impaired contraversive movement on the first day. However, on subsequent days the suppression became inefficient and capability for the movement was restored. Longitudinal two-photon calcium imaging revealed that the regained capability was accompanied by an increased number of neurons encoding for ipsiversive movement in the unsuppressed contralateral MOs. Additional suppression of the contralateral MOs impaired the recovered movement again, indicating a compensatory mechanism. Our findings demonstrate that repeated optogenetic suppression leads to functional recovery mediated by the contralateral hemisphere.

DOI： 10.7554/eLife.50855

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記述言語：日本語   出版者・発行元：(一社)日本臨床神経生理学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We previously identified a novel nanomagnetic particle, N,N'-bis(salicylidene)ethylenediamine iron [Fe(Salen)]. Fe(Salen) not only shows antitumor effects but also magnetic properties. We found that Fe(Salen) can be used for magnet-guided drug delivery and visualization of accumulated drug by magnetic resonance imaging (MRI) because of its magnetism. In addition, Fe(Salen) can generate heat by itself when exposed to an alternating current magnetic field (AMF), resulting in a hyperthermia effect. Herein, we partly elucidated the antitumor mechanism of Fe(Salen) and carried out an i.v. repeated dose toxicity study to decide the therapeutic amount. Furthermore, we evaluated the antitumor effect of selective intra-arterial injection or i.v. injection of Fe(Salen) by catheter and the hyperthermia effect of Fe(Salen) when exposed to AMF in vivo. We used a rabbit model grafted with VX2 cells (rabbit squamous cell carcinoma) on the right leg. Intra-arterial injection of Fe(Salen) showed a greater antitumor effect than did i.v. injection. The combination of Fe(Salen) intra-arterial injection and AMF exposure showed a greater antitumor effect than did either Fe(Salen) or methotrexate (MTX) without AMF exposure, suggesting that AMF exposure greatly enhanced the antitumor effect of Fe(Salen) by arterial injection by catheter. This is the first report that the effectiveness of Fe(Salen) was evaluated in the point of administration route; that is, selective intra-arterial injection by catheter. Taken together, these results indicate a new administration route; that is, selective arterial injection of Fe(Salen) by catheter, and the development of a new strategy of simultaneous hyperthermia-chemotherapy in the future.

DOI： 10.1111/cas.13851

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Erythropoietin (EPO) is a clinically available hematopoietic cytokine. EPO has shown beneficial effects in the context of spinal cord injury and other neurological conditions. The aim of this study was to evaluate the effect of EPO on a rat model of spinal cord compression-induced cervical myelopathy and to explore the possibility of its use as a pharmacological treatment. METHODS: To develop the compression-induced cervical myelopathy model, an expandable polymer was implanted under the C5-C6 laminae of rats. EPO administration was started 8 weeks after implantation of a polymer. Motor function of rotarod performance and grip strength was measured after surgery, and motor neurons were evaluated with H-E, NeuN and choline acetyltransferase staining. Apoptotic cell death was assessed with TUNEL and Caspase-3 staining. The 5HT, GAP-43 and synaptophysin were evaluated to investigate the protection and plasticity of axons. Amyloid beta precursor protein (APP) was assessed to evaluate axonal injury. To assess transfer of EPO into spinal cord tissue, the EPO levels in spinal cord tissue were measured with an ELISA for each group after subcutaneous injection of EPO. RESULTS: High-dose EPO maintained motor function in the compression groups. EPO significantly prevented the loss of motor neurons and significantly decreased neuronal apoptotic cells. Expression of 5HT and synaptophysin was significantly preserved in the EPO group. APP expression was partly reduced in the EPO group. The EPO levels in spinal cord tissue were significantly higher in the high-dose EPO group than other groups. CONCLUSION: EPO improved motor function in rats with compression-induced cervical myelopathy. EPO suppressed neuronal cell apoptosis, protected motor neurons, and induced axonal protection and plasticity. The neuroprotective effects were produced following transfer of EPO into the spinal cord tissue. These findings suggest that EPO has high potential as a treatment for degenerative cervical myelopathy.

DOI： 10.1371/journal.pone.0214351

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We previously reported the efficacy of anti-cancer therapy with hyperthermia using an alternating magnetic field (AMF) and a magnetic compound. In the course of the study, unexpectedly, we found that an AMF enhances the cytotoxicity of Compound C, an activated protein kinase (AMPK) inhibitor, although this compound is not magnetic. Therefore, we examined the cellular mechanism of AMF-induced cytotoxicity of Compound C in cultured human glioblastoma (GB) cells. An AMF (280 kHz, 250 Arms) for 30 minutes significantly enhanced the cytotoxicity of Compound C and promoted apoptosis towards several human GB cell lines in vitro. The AMF also increased Compound C-induced cell-cycle arrest of GB cells at the G2 phase and, thus, inhibited cell proliferation. The AMF increased Compound C-induced reactive oxygen species production. Furthermore, the AMF decreased ERK phosphorylation in the presence of Compound C and suppressed the protective autophagy induced by this compound. The application of an AMF in cancer chemotherapy may be a simple and promising method, which might reduce the doses of drugs used in future cancer treatment and, therefore, the associated side effects.

DOI： 10.1111/cas.13781

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Paragangliomas are generally benign, slow-growing tumors. However, approximately 10%-20% are malignant, characterized by distant metastasis. Recently, a germ line mutation in succinate dehydrogenase B subunit (SDHB) has been shown to be associated with malignant behavior in paraganglioma. Here we present a case of SDHB-negative malignant paraganglioma of the jugular foramen with a pseudohypoxic microenvironment and unique imaging features on [18F]-fluoro-2-deoxy-d-glucose positron emission tomography ([18F]-FDG PET), and discuss the significance of SDHB immunohistochemistry and the potential of [18F]-FDG PET for clinical management. CASE DESCRIPTION: A 55-year-old woman was diagnosed with jugular foramen paraganglioma. Initial surgical resection was performed; however, follow-up [18F]-FDG PET indicated multiple uptake regions throughout the body. Biopsies for multiple recurrent lesions revealed consistent pathological features, suggesting distant metastasis. Immunohistochemical analysis revealed a lack of SDHB immunostaining in all specimens. Pseudohypoxic markers, including hypoxia-inducible factor-1α and downstream glycolysis enzymes, were strongly expressed. [18F]-FDG PET demonstrated increased uptake in the lesions, and the patient died 3 years after initial metastasis. CONCLUSION: In patients with head and neck paraganglioma without SDHB expression, close follow-up should be considered because of the risk for metastasis. In such cases, [18F]-FDG PET might be useful for detecting metastasis due to atypical accumulation from pseudohypoxia-induced glycolysis.

DOI： 10.1016/j.wneu.2018.02.147

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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 Tokyo  

OBJECTIVE: The potential of positron emission tomography/computed tomography using 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) (62Cu-ATSM PET/CT), which was originally developed as a hypoxic tracer, to predict therapeutic resistance and prognosis has been reported in various cancers. Our purpose was to investigate prognostic value of 62Cu-ATSM PET/CT in patients with glioma, compared to PET/CT using 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG). METHOD: 56 patients with glioma of World Health Organization grade 2-4 were enrolled. All participants had undergone both 62Cu-ATSM PET/CT and 18F-FDG PET/CT within mean 33.5 days prior to treatment. Maximum standardized uptake value and tumor/background ratio were calculated within areas of increased radiotracer uptake. The prognostic significance for progression-free survival and overall survival were assessed by log-rank test and Cox's proportional hazards model. RESULTS: Disease progression and death were confirmed in 37 and 27 patients in follow-up periods, respectively. In univariate analysis, there was significant difference of both progression-free survival and overall survival in age, tumor grade, history of chemoradiotherapy, maximum standardized uptake value and tumor/background ratio calculated using 62Cu-ATSM PET/CT. Multivariate analysis revealed that maximum standardized uptake value calculated using 62Cu-ATSM PET/CT was an independent predictor of both progression-free survival and overall survival (p < 0.05). In a subgroup analysis including patients of grade 4 glioma, only the maximum standardized uptake values calculated using 62Cu-ATSM PET/CT showed significant difference of progression-free survival (p < 0.05). CONCLUSIONS: 62Cu-ATSM PET/CT is a more promising imaging method to predict prognosis of patients with glioma compared to 18F-FDG PET/CT.

DOI： 10.1007/s12149-018-1241-4

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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：ELSEVIER SCIENCE INC  

BACKGROUND: Intracranial mycotic aneurysm (IMA) is a rare neurovascular disease and a well-known complication after infective endocarditis. IMAs potentially carry a high mortality risk resulting from intracranial hemorrhage. Therefore, initial treatment is crucial for IMA patients, but an optimal treatment strategy remains unknown. Herein, we report 1 cases of IMA patients treated with the current usual modalities, and we provide a comprehensive literature review to propose an optimal initial treatment strategy for IMAs. CASE DESCRIPTIONS: Case 1: An 80-year-old man received a diagnosis of ruptured IMA. He immediately underwent trapping surgery and was discharged without neurologic deficit. Case 2: A 36-year-old man with previous aortic root replacement received a diagnosis of ruptured IMA. His general condition was considered too unstable to allow him to undergo direct surgery, and the angiographic access route was limited because of the previous aortic replacement surgery. Therefore, we selected conservative therapy; however, the patient subsequently died after complications from a huge intracerebral hemorrhage during medical treatment. CONCLUSIONS: On the basis of 129 IMA cases across 54 reports published from 2006 to 2016, we propose initial surgical intervention as an optimal treatment for patients with ruptured, and even unruptured, IMAs. Regarding surgical intervention, there was no significant difference in postoperative modified Rankin scale scores between direct surgery and endovascular treatment. By contrast, because antibiotic treatment significantly decreased IMA size in unruptured IMAs, antibiotic treatment might be a reasonable alternative for patients with unruptured IMAs, depending on the patient's situation.

DOI： 10.1016/j.wneu.2017.07.016

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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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：JAPANESE PHARMACOLOGICAL SOC  

Iron-salen, i.e., μ-oxo-N,N'-bis(salicylidene)ethylenediamine iron (Fe(Salen)) was a recently identified as a new anti-cancer compound with intrinsic magnetic properties. Chelation therapy has been widely used in management of metallic poisoning, because an administration of agents that bind metals can prevent potential lethal effects of particular metal. In this study, we confirmed the therapeutic effect of deferoxamine mesylate (DFO) chelation against Fe(Salen) as part of the chelator antidote efficacy. DFO administration resulted in reduced cytotoxicity and ROS generation by Fe(Salen) in cancer cells. DFO (25 mg/kg) reduced the onset of Fe(Salen) (25 mg/kg)-induced acute liver and renal dysfunction. DFO (300 mg/kg) improves survival rate after systematic injection of a fatal dose of Fe(Salen) (200 mg/kg) in mice. DFO enables the use of higher Fe(Salen) doses to treat progressive states of cancer, and it also appears to decrease the acute side effects of Fe(Salen). This makes DFO a potential antidote candidate for Fe(Salen)-based cancer treatments, and this novel strategy could be widely used in minimally-invasive clinical settings.

DOI： 10.1016/j.jphs.2017.07.002

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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 JAPAN KK  

Melanoma has an extremely poor prognosis due to its rapidly progressive and highly metastatic nature. Several therapeutic drugs have recently become available, but are effective only against melanoma with specific BRAF gene mutation. Thus, there is a need to identify other target molecules. We show here that Transient receptor potential, canonical 3 (TRPC3) is widely expressed in human melanoma. We found that pharmacological inhibition of TRPC3 with a pyrazole compound, Pyr3, decreased melanoma cell proliferation and migration. Similar inhibition was observed when the TRPC3 gene was silenced with short-hairpin RNA (shRNA). Pyr3 induced dephosphorylation of signal transducer and activator of transcription (STAT) 5 and Akt. Administration of Pyr3 (0.05 mg/kg) to mice implanted with human melanoma cells (C8161) significantly inhibited tumor growth. Our findings indicate that TRPC3 plays an important role in melanoma growth, and may be a novel target for treating melanoma in patients.

DOI： 10.1007/s12576-016-0480-1

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

OBJECTIVE: Microvascular decompression(MVD)surgery has been established as a standard treatment for hemifacial spasm. However, because decompression surgery results in unfavorable outcomes in some cases, a more critical monitoring strategy is required. To improve surgical outcome for hemifacial spasms, abnormal muscle response(AMR)has been proposed as a tool for intraoperative electrophysiological monitoring during MVD surgery. Here, we report a single case of surgical MVD monitoring using artery wall stimulating electromyography(AWS-EMG). AWS-EMG was developed as a new monitoring method in addition to AMR. CASE DESCRIPTION: A 60-year-old woman was diagnosed with hemifacial spasm using magnetic resonance imaging and magnetic resonance angiography fusion imaging. We performed MVD surgery using AWS-EMG and AMR. We successfully identified AWS-EMG before decompression and confirmed immediate AWS-EMG loss after decompression. This behavior was consistent with AMR. After surgery, the patient showed no further symptoms of hemifacial spasm. CONCLUSIONS: In addition to AMR, AWS-EMG might be a promising candidate for intraoperative monitoring for patients with hemifacial spasm.

DOI： 10.11477/mf.1436203487

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記述言語：日本語   出版者・発行元：(株)医学書院  

60歳女性。左顔面痙攣を主訴とした。頭部単純MRI/MRAにて左後下小脳動脈(左PICA)による左顔面神経の圧迫所見を認めたため、治療目的に入院となった。左顔面痙攣に対し、異常筋反応モニタリング(AMR)併用下に動脈刺激筋反応モニタリング(AWS-EMG)を行い、術中に異常波形を確認し、微小血管減圧術を施行した。術後AMR、AWS-EMGの異常波形は消失し、顔面痙攣も改善が得られた。

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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：NATURE PUBLISHING GROUP  

We previously reported that μ-oxo N,N'-bis(salicylidene)ethylenediamine iron [Fe(Salen)], a magnetic organic compound, has direct anti-tumor activity, and generates heat in an alternating magnetic field (AMF). We showed that Fe(Salen) nanoparticles are useful for combined hyperthermia-chemotherapy of tongue cancer. Here, we have examined the effect of Fe(Salen) on human glioblastoma (GB). Fe(Salen) showed in vitro anti-tumor activity towards several human GB cell lines. It inhibited cell proliferation, and its apoptosis-inducing activity was greater than that of clinically used drugs. Fe(Salen) also showed in vivo anti-tumor activity in the mouse brain. We evaluated the drug distribution and systemic side effects of intracerebrally injected Fe(Salen) nanoparticles in rats. Further, to examine whether hyperthermia, which was induced by exposing Fe(Salen) nanoparticles to AMF, enhanced the intrinsic anti-tumor effect of Fe(Salen), we used a mouse model grafted with U251 cells on the left leg. Fe(Salen), BCNU, or normal saline was injected into the tumor in the presence or absence of AMF exposure. The combination of Fe(Salen) injection and AMF exposure showed a greater anti-tumor effect than did either Fe(Salen) or BCNU alone. Our results indicate that hyperthermia and chemotherapy with single-drug nanoparticles could be done for GB treatment.

DOI： 10.1038/srep42783

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中の外科学会  

DOI： 10.2335/scs.44.81

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その他リンク： https://search.jamas.or.jp/link/ui/2016193880

記述言語：日本語   出版者・発行元：一般社団法人 日本脳卒中の外科学会  

The basic procedure of carotid endarterectomy (CEA) has been almost established. However, beginners sometimes have difficulty dissecting the plaque at the same plane and treating the distal end of the plaque, even in typical cases. A simple, safe, and standardized procedure is important for beginners. We use the internal shunt in all cases to secure adequate blood flow and take advantage of the shunt tube as the tool for plaque dissection at the distal end.<br>We introduce our surgical technique and review our procedure from a beginner's point of view. We tack up the skin, muscle, and carotid sheath by using sutures to make wide and shallow operative fields without retractors. We insert the internal shunt tube after arteriotomy. Beginners need to rehearse the tube insertion before the procedure. At the proximal side of the plaque, we connect both sides of the dissection plane across the shunt to secure the same plane.<br>The distal end of the intima of the internal carotid artery (ICA) is fastened by using a shunt tube and tourniquet. The plaque can be easily cut off at the position of the tourniquet. If the plaque remains, we can peel off the plaque remnant like peeling onion skin. A shunt tube is used as the template of the ICA lumen in the distal end.<br>Beginners can easily master these procedures, which can be performed safely without distress, even in high-positioned stenosis. These procedures enable the beginners to accomplish CEA securely.

DOI： 10.2335/scs.44.352

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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  

OBJECTIVES: The aim of this study was to clarify the relationship between tumor hypoxia and microscopic diffusion capacity in primary brain tumors using (62)Cu-Diacetyl-Bis (N4-Methylthiosemicarbazone) ((62)Cu-ATSM) PET/CT and diffusion-weighted MR imaging (DWI). METHODS: This study was approved by the institutional human research committee and was HIPAA compliant, and informed consent was obtained from all patients. (62)Cu-ATSM PET/CT and DWI were performed in a total of 40 primary brain tumors of 34 patients with low grade glioma (LGG, n = 13), glioblastoma (GBM, n = 20), and primary central nervous system lymphoma (PCNSL, n = 7). (62)Cu-ATSM PET/CT parameters and apparent diffusion coefficient (ADC) obtained by DWI were compared. RESULTS: High intensity signals by (62)Cu-ATSM PET/CT and DWI in patients with GBM and PCNSL, and low intensity signals in LGG patients were observed. An inverse correlation was found between maximum SUV (SUVmax) and minimum ADC (ADCmin) (r = -0.583, p < 0.0001), and between tumor/brain ratio (T/Bratio) and ADCmin for all tumors (r = -0.532, p < 0.0001). Both SUVmax and T/Bratio in GBM were higher than LGG (p < 0.0001 and p < 0.0001), and those in PCNSL were also higher than GBM (p = 0.033 and p = 0.044). The ADCmin was lower in GBM (p = 0.011) and PCNSL (p = 0.01) than in LGG, while no significant difference was found between GBM and PCNSL (p = 0.90). CONCLUSION: Tumor hypoxia assessed by (62)Cu-ATSM PET/CT correlated with microscopic diffusion capacity obtained by DWI in brain tumors. Both (62)Cu-ATSM PET/CT and DWI were considered feasible imaging methods for grading glioma. However, (62)Cu-ATSM PET/CT provided additional diagnostic information to differentiate between GBM and PCNSL.

DOI： 10.1007/s00259-014-2714-x

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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 SOC NEURORADIOLOGY  

BACKGROUND AND PURPOSE: Cu-62-diacetyl-bis(N-4-methylthiosemicarbazone) was developed as a hypoxic radiotracer in PET. We compared imaging features among MR imaging and Cu-62-diacetyl-bis(N-4-methylthiosemicarbazone)-PET, FDG-PET, and L-methyl-[C-11]methionine)-PET in gliomas.
MATERIALS AND METHODS: We enrolled 23 patients who underwent Cu-62-diacetyl-bis(N-4-methylthiosemicarbazone)-PET and FDG-PET and 19 (82.6%) who underwent L-methyl-[C-11]methionine)-PET, with all 23 patients undergoing surgery and their diagnosis being then confirmed by histologic examination as a glioma. Semiquantitative and volumetric analysis were used for the comparison.
RESULTS: There were 10 newly diagnosed glioblastoma multiforme and 13 nonglioblastoma multiforme (grades II and III), including 4 recurrences without any adjuvant treatment. The maximum standardized uptake value and tumor/background ratios of Cu-62-diacetyl-bis(N-4-methylthiosemicarbazone), as well as L-methyl-[C-11]methionine, were significantly higher in glioblastoma multiforme than in nonglioblastoma multiforme (P = .03 and P = .03, respectively); no significant differences were observed on FDG. At a tumor/background ratio cutoff threshold of 1.9, Cu-62-diacetyl-bis(N-4-methylthiosemicarbazone) was most predictive of glioblastoma multiforme, with 90.0% sensitivity and 76.9% specificity. The positive and negative predictive values, respectively, for glioblastoma multiforme were 75.0% and 85.7% on Cu-62-diacetyl-bis(N-4-methylthiosemicarbazone), 83.3% and 60.0% on L-methyl-[C-11]methionine, and 72.7% and 75.0% on MR imaging. In glioblastoma multiforme, volumetric analysis demonstrated that Cu-62-diacetyl-bis(N-4-methylthiosemicarbazone) uptake had significant correlations with FDG (r = 0.68, P = .03) and L-methyl-[C-11]methionine (r = 0.87, P = .03). However, the Cu-62-diacetyl-bis(N-4-methylthiosemicarbazone)-active region was heterogeneously distributed in 50.0% (5/10) of FDG-active and 0% (0/6) of L-methyl-[C-11]methionine)-active regions.
CONCLUSIONS: Cu-62-diacetyl-bis(N-4-methylthiosemicarbazone) may be a practical radiotracer in the prediction of glioblastoma multiforme. In addition to FDG-PET, L-methyl-[C-11]methionine)-PET, and MR imaging, Cu-62-diacetyl-bis(N-4-methylthiosemicarbazone)-PET may provide intratumoral hypoxic information useful in establishing targeted therapeutic strategies for patients with glioblastoma multiforme.

DOI： 10.3174/ajnr.A3679

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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：ELSEVIER SCIENCE INC  

PURPOSE: Semiquantitative analysis of thallium-201 chloride single photon emission computed tomography (201Tl SPECT) was evaluated for the discrimination between recurrent brain tumor and delayed radiation necrosis after gamma knife surgery (GKS) for metastatic brain tumors and high-grade gliomas. METHODS AND MATERIALS: The medical records were reviewed of 75 patients, including 48 patients with metastatic brain tumor and 27 patients with high-grade glioma who underwent GKS in our institution, and had suspected tumor recurrence or radiation necrosis on follow-up neuroimaging and deteriorating clinical status after GKS. Analysis of 201Tl SPECT data used the early ratio (ER) and the delayed ratio (DR) calculated as tumor/normal average counts on the early and delayed images, and the retention index (RI) as the ratio of DR to ER. RESULTS: A total of 107 tumors were analyzed with 201Tl SPECT. Nineteen lesions were removed surgically and histological diagnoses established, and the other lesions were evaluated with follow-up clinical and neuroimaging examinations after GKS. The final diagnosis was considered to be recurrent tumor in 65 lesions and radiation necrosis in 42 lesions. Semiquantitative analysis demonstrated significant differences in DR (P=.002) and RI (P<.0001), but not in ER (P=.372), between the tumor recurrence and radiation necrosis groups, and no significant differences between metastatic brain tumors and high-grade gliomas in all indices (P=.926 for ER, P=.263 for DR, and P=.826 for RI). Receiver operating characteristics analysis indicated that RI was the most informative index with the optimum threshold of 0.775, which provided 82.8% sensitivity, 83.7% specificity, and 82.8% accuracy. CONCLUSIONS: Semiquantitative analysis of 201Tl SPECT provides useful information for the differentiation between tumor recurrence and radiation necrosis in metastatic brain tumors and high-grade gliomas after GKS, and the RI may be the most valuable index for this purpose.

DOI： 10.1016/j.ijrobp.2012.03.008

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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 NEUROLOGICAL SURGEONS  

OBJECT: The authors retrospectively studied the mechanism of cyst formation and enlargement after Gamma Knife surgery (GKS) for arteriovenous malformations (AVMs). METHODS: Eighteen patients in whom cyst formation developed following GKS for AVM were retrospectively identified among 775 patients who underwent GKS for AVM at Yokohama Rosai Hospital. The study group was composed of 12 male and 6 female patients ranging in age from 17 to 47 years. RESULTS: Chronic encapsulated expanding hematoma was associated with the cyst in 5 patients. The AVM nidus volume at the time of GKS ranged from 1.9 to 36 cm(3), and the prescription radiation dose was 18-25 Gy. Complete obliteration of the AVM nidus was obtained in 13 patients and partial obliteration in 5 patients. Cyst formation was detected between 2.6 and 15 years after GKS. Craniotomy was performed in 10 patients, including 2 patients in whom the incompletely obliterated nidus was removed at the same time, and an Ommaya reservoir was placed in 2 patients. Spontaneous regression of the cyst was observed in 1 patient. Serial MR imaging was performed in the other patients because the size of the cyst was stable or the lesion was asymptomatic. Histological examination of the cyst wall revealed linear hemosiderin deposits with gliosis. The nodular lesion, which was enhanced on MR images, contained granulation tissue with chronic hemorrhage from newly developed capillary vessels. CONCLUSIONS: Cysts developing after GKS for AVM enlarge mainly due to repeated minor hemorrhages from a reddish nodular angiomatous lesion that develops within an adjacent brain area. Thus, the optimal treatment is wide opening of the cyst with removal of the associated angiomatous lesion by craniotomy.

DOI： 10.3171/2012.6.GKS12318

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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：ELSEVIER SCI LTD  

Germinoma mainly occurs in the pituitary stalk, pineal region, and basal ganglia. Sex predominance of the tumor in males in the pineal region and basal ganglia is well known. Primary germinoma of the medulla oblongata is rare, with only eight reports, mostly in females. We report the second male patient with primary medulla oblongata germinoma, without chromosomal abnormality, who was successfully treated with surgery, chemotherapy, and radiotherapy.

DOI： 10.1016/j.jocn.2011.06.036

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記述言語：日本語   出版者・発行元：(一社)日本臨床神経生理学会  

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記述言語：日本語   出版者・発行元：一般社団法人 日本脳卒中の外科学会  

We report herein five cases of symptomatic brainstem cavernous malformations (CM). Specific surgical approaches were designed to directly access each lesion. Neuronavigation and intraoperative monitoring were used. Four lesions underwent gross total resection, and one was subtotally partially removed. None of the patients developed new neurological deficits and all cases showed an improvement based on the modified Rankin Scale and the Karnofsky Performance Status. Although brainstem CM have a relatively high rate of re-bleeding, thus adversely affecting the neurological status of the patient, recent reports have demonstrated favorable outcomes after their resection. Hence, surgical removal can be recommended for cases of symptomatic brainstem CM, particularly those with re-bleeding. An optimal surgical approach, providing direct access to the lesion, is critical for successfully resecting brainstem CM.

DOI： 10.2335/scs.46.58

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中の外科学会  

手術を施行した脳幹海綿状血管腫5例(男性2例、女性3例、32〜67歳)を対象とした。部位は、中脳1例、中脳-橋1例、橋2例、橋-延髄1例で、腹側病変2例、背側病変3例であった。全例出血発症で、発症から手術までの期間は2〜156ヵ月、再出血回数は1〜5回、最終出血から手術までの期間は6〜60週であった。手術時の最大径は19〜43mmであった。手術アプローチは原則として脳幹表面から病変までの距離が最短となるものを選択した。全摘出4例、部分摘出1例であった。腹側病変に対してはtemporopolar approach、anterior transpetrosal approach、背側病変に対しては、trans 4th ventricle approach、infratentorial supracerebellar approachで摘出した。術後入院期間は平均36.2日で、4例が自宅退院した。mRSは手術により4.0±0.70から2.0±0.78と改善傾向がみられ、全例において術後の新たな神経学的後遺症は生じなかった。

DOI： 10.2335/scs.46.58

J-GLOBAL

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：JAPANESE PHARMACOLOGICAL SOC  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：JAPANESE PHARMACOLOGICAL SOC  

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J-GLOBAL

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J-GLOBAL

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2015-4371

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2015-4398

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2015-4548

Web of Science

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J-GLOBAL

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2014-5399

Web of Science

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J-GLOBAL

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J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(株)メディカ出版  

穿頭血腫ドレナージ術を施行した109例のうち再発した11例(男8例、女3例、年齢51〜91歳)を対象に、再発に影響を及ぼす因子について多変量解析を用いて検討した。11例中6例に先行する頭部打撲があり、抗血栓・凝固薬使用では抗凝固薬1例、高血圧あり2例、糖尿病あり2例であった。その結果、「手術翌日の残存空気が1/4(25%)以上」と「1週間後の脳の膨張率が悪い」のみが有意な因子であった。年齢、性別、先行する頭部打撲、抗血栓・凝固療法の有無、高血圧・糖尿病の既往については再発因子としては有意ではなかった。また、手術翌日に残存空気が25%以上ある群は、残存空気が少ない群と比較して優位に1週間後の脳の膨張率が悪い結果となった。

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記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

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