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Abstract Recent studies have shown that D-allose, a rare sugar, elicits antitumor effects on different types of solid cancers, such as hepatocellular carcinoma, non-small-cell lung cancer, and squamous cell carcinoma of the head and neck. In this study, we examined the effects of D-allose on the proliferation of human glioblastoma (GBM) cell lines (i.e., U251MG and U87MG) in vitro and in vivo and the underlying mechanisms. D-allose treatment inhibited the proliferation of U251MG and U87MG cells in a dose-dependent manner (3–50 mM). However, D-allose treatment did not affect cell cycles or apoptosis in these cells but significantly decreased the cell division frequency in both GBM cell lines. In a subcutaneous U87MG cell xenograft model, intraperitoneal injection of D-allose (100 mg/kg/day) significantly reduced the tumor volume in 28 days. These data indicate that D-allose-induced reduction in cell proliferation is associated with a subsequent decrease in the number of cell divisions, independent of cell-cycle arrest and apoptosis. Thus, D-allose could be an attractive additive to therapeutic strategies for GBM.

Abstract Glioblastoma is characterized by a strong self-renewal potential and poor differentiated state. We have reported previously that the (pro)renin receptor [(P)RR] is a potential target for glioma therapy by silencing the (P)RR gene. Here, we have examined the effects of a monoclonal antibody against (P)RR on gliomagenesis. Human glioma cell lines (U251MG and U87MG) and a glioma stem cell line (MGG23) were used for the in vitro study. The expressions of the Wnt/β-catenin signaling pathway (Wnt signaling pathway) components and stemness markers were measured by Western blotting. The effects of the (P)RR antibody on cell proliferation, sphere formation, apoptosis and migration were also examined. Subcutaneous xenografts were also examined in nude mice. Treatment with the (P)RR antibody reduced expression of Wnt signaling pathway components and stemness markers. Furthermore, the (P)RR antibody reduced cell proliferation and decreased sphere formation significantly. The treatment also suppressed migration and induced apoptosis. In a subcutaneous xenograft model, systemic administration of the (P)RR antibody reduced tumor volume significantly. These data show that treatment with the (P)RR antibody is a potential therapeutic strategy for treating glioblastoma.

Abstract Background Tumor hypoxia and glycolysis have been recognized as determinant factors characterizing tumor aggressiveness in malignant gliomas. To clarify in vivo hypoxia and glucose metabolism in relation to isocitrate dehydrogenase (IDH) mutation and chromosome 1p and 19q (1p/19q) codeletion status, we retrospectively analyzed hypoxia as assessed by positron emission tomography (PET) with [18F]-fluoromisonidazole (FMISO) and glucose metabolism as assessed by PET with [18F]-fluoro-2-deoxy-d-glucose (FDG) in newly diagnosed malignant gliomas. Methods In total, 87 patients with newly diagnosed supratentorial malignant (WHO grade III and IV) gliomas were enrolled in this study. They underwent PET studies with FMISO and FDG before surgery. The molecular features and histopathological diagnoses based on the 2016 WHO classification were determined using surgical specimens. Maximal tumor-to-normal ratio (TNR) was calculated for FDG PET, and maximal tumor-to-blood SUV ratio (TBR) was calculated for FMISO PET. The PET uptake values in relation to IDH mutation and 1p/19q codeletion status were statistically analyzed. Results In all tumors and malignant astrocytomas, the median FMISO TBR in IDH-wildtype tumors was significantly higher than that in IDH-mutant tumors (P

Neurofibromatosis type 2 (NF2) causes bilateral vestibular schwannomas (VSs), leading to deafness. VS is treated by surgery or radiation, but neither treatments prevent hearing loss. Bevacizumab was found to be effective in suppressing the tumor’s growth and may help to improve hearing. We are conducting a randomized, double-blind, multicenter clinical trial to verify the efficacy and safety of bevacizumab in NF2-related VS. The primary objective is to evaluate the efficacy of bevacizumab in improving hearing in the affected ear. One of the secondary objectives is to evaluate bevacizumab’s efficacy in rechallenge treatment in relapsed cases. Sixty patients will randomly receive either bevacizumab or a placebo and will be clinically observed for 48 weeks in the initial intervention phase. In the first half (24 weeks), they will receive either 5 mg/kg of bevacizumab or a placebo drug. In the second half, all patients will receive 5 mg/kg of bevacizumab. If hearing function deteriorated in a patient who had shown improvement during the first phase, a rechallenge dose with bevacizumab would be offered.

Abstract Background The molecular features of isocitrate dehydrogenase (IDH) mutation and chromosome 1p and 19q (1p/19q) codeletion status have pivotal role for differentiating gliomas and have been integrated in the World Health Organization (WHO) classification in 2016. Positron emission tomography (PET) with 3′-deoxy-3′-[18F]fluorothymidine (FLT) has been used to evaluate tumour grade and proliferative activity and compared with l-[methyl-11C]-methionine (MET) in glioma patients. Herein, we evaluated tracer uptakes of MET-PET/CT and FLT-PET/CT for differentiating glioma based on the 2016 WHO classification especially in relation to IDH1 mutation status. Methods In total, 81 patients with newly diagnosed supratentorial glioma were enrolled in this study. They underwent PET/CT studies with MET and FLT before surgery. The molecular features and histopathological diagnosis based on the 2016 WHO classification were determined using surgical specimens. The ratios of the maximum standardized uptake value (SUV) of the tumours to the mean SUV of the contralateral cortex (T/N ratios) were calculated on MET-PET/CT and FLT-PET/CT images. Results The mean T/N ratios of MET-PET/CT and FLT-PET/CT in IDH1-wildtype tumours were significantly higher than those in IDH1-mutant tumours (P < 0.001 and P < 0.001, respectively). Receiver operating characteristic analysis for differentiating IDH1 mutation status showed that the area under the curve of the FLT T/N ratio was significantly larger than that of the MET T/N ratio (P < 0.01). The mean T/N ratio of FLT-PET/CT in IDH1-wildtype tumours was significantly higher than that in IDH1-mutant tumours among grade II and III gliomas (P = 0.005), but this was not the case for MET-PET/CT. Both MET-PET/CT and FLT-PET/CT were able to distinguish between grade II and III gliomas in IDH1-mutant tumours (P = 0.002 and P < 0.001, respectively), but only FLT-PET/CT was able to distinguish between grade III and IV gliomas in IDH1-wildtype tumours (P = 0.029). Conclusion This study showed that FLT-PET/CT can be used to determine the IDH1 mutation status and evaluate glioma grade more accurately than MET-PET/CT. FLT-PET/CT can improve glioma differentiation based on the 2016 WHO classification, but caution must be paid for tumours without contrast enhancement and further studies should be conducted with more cases.

Purpose: The aim of this study was to compare the failure rates of insertion of a 10/12-Fr ureteral access sheath (UAS) during retrograde intrarenal surgery (RIRS) in cases with and without stones and to analyze the risk factors for UAS insertion failure. Materials and Methods: A total of 640 RIRS cases (538 with and 102 without stones) were evaluated. The primary outcome of interest was the failure rate of insertion of a 10/12-Fr UAS. Associated risk factors were assessed using univariate and multivariate logistic regression analyses. Propensity score (PS) matching and inverse probability of treatment weighting (IPTW) were used to ensure the robustness of the results. Results: The overall failure rate of 10/12-Fr UAS insertion in the cases without stones was significantly higher than that in the cases with stones (39.2% vs. 7.2%; p

Abstract Background In patients with aneurysmal subarachnoid hemorrhage (SAH), an association between hypocapnia and poor clinical outcomes has been reported. However, the optimal arterial carbon dioxide tension (PaCO2) remains unknown. The present retrospective study aimed to examine the association of abnormal PaCO2 levels with neurological outcomes and investigate the optimal target PaCO2 level in patients with SAH. Methods We retrospectively selected consecutive adult patients hospitalized in the intensive care unit (ICU) for SAH between January 2009 and April 2017. Univariate and multivariate analyses were performed to identify the independent predictors of unfavorable neurological outcomes (i.e., modified Rankin scale score of 3–6 on hospital discharge). Results Among 158 patients with SAH, 73 had unfavorable neurological outcomes. During the first 2 weeks in the ICU, the median number of PaCO2 measurements per patient was 43. The factors significantly associated with unfavorable neurological outcomes were age, Hunt and Kosnik grade, maximum lactate levels during the first 24 h, and maximum (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.03–1.21; p

The purpose of this research was to investigate the usefulness of three-dimensional print models (3D models) in endoscopic endonasal transsphenoidal surgery (EeTSS) for pituitary adenoma. Eleven patients underwent EeTSS for pituitary adenoma using 3D models. We manufactured a 3D virtual surgical planning image using the patient's Digital Imaging and Communication in Medicine dataset. Based on the image, a life-size model was created by a 3D printer using multi-material acrylic-based resin. Our results suggest that such 3D models could be useful in EeTSS for pituitary adenoma. Keywords: Multi material acrylic-based resin 3D–model, Endoscopic endonasal transsphenoidal surgery (EeTSS), Pituitary adenoma

A teleoperated robotic catheter operating system is a solution to avoid occupational hazards caused by repeated exposure radiation of the surgeon to X-ray during the endovascular procedures. However, inadequate force feedback and collision detection while teleoperating surgical tools elevate the risk of endovascular procedures. Moreover, surgeons cannot control the force of the catheter/guidewire within a proper range, and thus the risk of blood vessel damage will increase. In this paper, a magnetorheological fluid (MR)-based robot-assisted catheter/guidewire surgery system has been developed, which uses the surgeon’s natural manipulation skills acquired through experience and uses haptic cues to generate collision detection to ensure surgical safety. We present tests for the performance evaluation regarding the teleoperation, the force measurement, and the collision detection with haptic cues. Results show that the system can track the desired position of the surgical tool and detect the relevant force event at the catheter. In addition, this method can more readily enable surgeons to distinguish whether the proximal force exceeds or meets the safety threshold of blood vessels.

This data article contains supporting information regarding the research article entitled “Traumatic brain injury accelerates amyloid-β deposition and impairs spatial learning in the triple-transgenic mouse model of Alzheimer׳s disease” (H. Shishido, Y. Kishimoto, N. Kawai, Y. Toyota, M. Ueno, T. Kubota, Y. Kirino, T. Tamiya, 2016) [1]. Triple-transgenic (3×Tg)-Alzheimer׳s disease (AD) model mice exhibited significantly poorer spatial learning than sham-treated 3×Tg-AD mice 28 days after traumatic brain injury (TBI). Correspondingly, amyloid-β (Aβ) deposition within the hippocampus was significantly greater in 3×Tg-AD mice 28 days after TBI. However, data regarding the short-term and long-term influences of TBI on amyloid precursor protein (APP) accumulation in AD model mice remain limited. Furthermore, there is little data showing whether physical activity and motor learning are affected by TBI in AD model mice. Here, we provide immunocytochemistry data confirming that TBI induces significant increases in APP accumulation in 3×Tg-AD mice at both 7 days and 28 days after TBI. Furthermore, 3×Tg-AD model mice exhibit a reduced ability to acquire conditioned responses (CRs) during delay eyeblink conditioning compared to sham-treated 3×Tg-AD model mice 28 days after TBI. However, physical activity and motor performance are not significantly changed in TBI-treated 3×Tg-AD model mice.

Background/Aims: The nucleolar 58-kDa microspherule protein (MSP58) has important transcriptional regulation functions and plays a crucial role in the tumorigenesis and progression of cancers. 3'-deoxy-3'-[18F]fluorothymidine (FLT) has emerged as a promising positron emission tomography (PET) tracer for evaluating tumor malignancy and cell proliferation. Methods: In the present study, the expression of MSP58 was evaluated by immunohistochemistry and the corresponding PET image was examined using FLT-PET in 55 patients with various grades of gliomas. Results: The immunoreactivity score (IRS) of MSP58 increased with tumor grade with grade IV gliomas exhibiting the highest expression and showed a highly significant positive correlation with the Ki-67 index (r = 0.65, P r = 0.61, P r = 0.59, P Conclusion: These results indicate that MSP58 plays an important role in cell proliferation and will be one of the potential candidates of molecular therapy targeting proliferation. FLT-PET might be used as an early measure of treatment response in the proliferation-targeted therapy.

There has been growing awareness of the correlation between an episode of traumatic brain injury (TBI) and the development of Alzheimer’s disease (AD) later in life. It has been reported that TBI accelerated amyloid-β (Aβ) pathology and cognitive decline in the several lines of AD model mice. However, the short-term and long-term effects of TBI by the weight-drop method on amyloid-β pathology and cognitive performance are unclear in wild-type (WT) mice. Hence, we examined AD-related histopathological changes and cognitive impairment after TBI in wild-type C57BL6J mice. Five- to seven-month-old WT mice were subjected to either TBI by the weight-drop method or a sham treatment. Seven days after TBI, the WT mice exhibited significantly lower spatial learning than the sham-treated WT mice. However, 28 days after TBI, the cognitive impairment in the TBI-treated WT mice recovered. Correspondingly, while significant amyloid-β (Aβ) plaques and amyloid precursor protein (APP) accumulation were observed in the TBI-treated mouse hippocampus 7 days after TBI, the Aβ deposition was no longer apparent 28 days after TBI. Thus, TBI induced transient amyloid-β deposition and acute cognitive impairments in the WT mice. The present study suggests that the TBI could be a risk factor for acute cognitive impairment even when genetic and hereditary predispositions are not involved. The system might be useful for evaluating and developing a pharmacological treatment for the acute cognitive deficits.

Background: Pain is regarded as one of the most common nonmotor symptoms in Parkinson's disease (PD). In particular, musculoskeletal pain has been reported as the most common type of PD-associated pain. Crowned dens syndrome (CDS), related to microcrystalline deposition in the periodontoid process, is the main cause of acute or chronic cervical pain. Case Presentation: This report describes the case of an 87-year-old woman who had severe bradykinesia, muscle rigidity, gait disturbance and neck pain. Laboratory examination revealed marked elevations of white blood cells (10,100/µl) and C-reactive protein (CRP; 8.63 mg/dl). She was primarily diagnosed with severe and untreated PD, corresponding to Hoehn and Yahr scale score IV, with musculoskeletal pain and urinary tract infection. The patient was treated with antiparkinsonism drugs, antibiotic agents and nonsteroidal anti-inflammatory drugs, but they had only limited effects. Cervical plain computed tomography (CT) scanning detected remarkable crown-like calcification surrounding the odontoid process. Based on CT findings, the patient was diagnosed as having CDS with PD, and was immediately treated with corticosteroid. The severe neck rigidity with pain and the serum CRP level (0.83 mg/dl) of the patient were drastically improved within a week by the additional corticosteroid therapy. Conclusion: Severe neck rigidity and bradykinesia in this patient might have strengthened the chondrocalcinosis around the odontoid process. Cervical plain CT scan is necessary and useful for the definitive diagnosis of CDS. CDS should be considered as a differential diagnosis of a possible etiology for musculoskeletal pain related to rigidity and bradykinesia in PD.

Background: Myelitis is one of the rarest neurological complications of the varicella zoster virus (VZV) infection. Focal muscle weakness with or without sensory disturbance occurs in approximately 5% of the cases after acute VZV infection, with complete recovery in 50-70%. Case Presentation: This report describes two rare cases of elderly patients with VZV myelitis secondary to dermatomal zoster rash. Patient 1 was a 79-year-old woman who developed paraplegia, numbness and decreased sensation in the left arm and below thoracic (Th)-10 after sacral zoster. Spinal cord MRI showed a high-signal-intensity lesion at the cervical spinal nerve 2 on a T2-weighted image. Patient 2 was a 73-year-old man who developed right flaccid leg weakness and urinary retention after right dorsal Th 5-8 zoster. Spinal cord MRI showed a high-signal-intensity lesion at Th 3-4 on a T2-weighted image. In both cases, although the conventional single polymerase chain reaction (PCR) assays all showed negative results, the original nested PCR assay detected VZV DNA in the cerebrospinal fluid (CSF) specimen collected on admission. In addition, the anti-VZV IgG antibody by enzyme immunoassay and antibody index were elevated in the CSF specimens during the clinical courses of both patients. On the basis of these findings, both patients were diagnosed with VZV myelitis and were treated with high-dose acyclovir and corticosteroid. This combined treatment was appropriate and effective for the improvement of their functional outcomes. Conclusion: The detection of VZV DNA in CSF by nested PCR assay and the evaluation of the antibody index to VZV had significant diagnostic value.

Intravascular large B-cell lymphoma (IVL) is a rare type of extranodal lymphoma with an aggressive clinical course characterized by the proliferation of lymphoma cells within the lumen of small vessels. Diagnosis is often difficult because of marked variability in clinical presentation and nonspecific laboratory and radiological findings, especially when central nervous system (CNS) symptoms are the only manifestation. Modern metabolic imaging techniques such as positron emission tomography (PET) and 1H-magnetic resonance spectroscopy (MRS) have been reported to be useful in the diagnosis of conventional primary CNS lymphoma. We report the case of a 69-year-old man who presented with a progressive leukoencephalopathic syndrome. The patient was examined by 18F-fluorodeoxyglucose and 11C-methionine PET and MRS, but none of these examinations were able to show the presence of a tumor in the lesions or to clarify the tumor characteristics. Brain biopsy was the only way to obtain a definite diagnosis of IVL. The patient was treated intensively with standard immunochemotherapy but died 6 months after the diagnosis. Here, we discuss the insufficiency of modern metabolic imaging techniques, including PET and MRS, and recommend a rapid decision of brain biopsy in the diagnosis of IVL only involving the CNS.