Publications by authors named "Akimoto J"

Our extensive basic research on photodynamic therapy (PDT) application in models of intracranial malignant astrocytoma led to its clinical application for intracranial malignant astrocytoma in Japan. Having considered the safety and effectiveness of this pathology, we initiate a first-in-human clinical study of PDT for spinal cord malignant astrocytoma. This study has an open-label, single-arm design.

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We measured diurnal variations in oxidative stress conditions of cyanobacteria utilizing field observations and laboratory experiments in order to evaluate photoinhibition effects. On clear summer days, transparent bottles filled with surface water were set up at several depths and were collected every three hours together with the measurement of the photosynthetically active radiation (PAR). In the laboratory experiment, two cyanobacterial species were exposed to gradually increasing and then decreasing light intensities.

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This preclinical study was conducted to investigate the efficacy of interstitial PDT (i-PDT) for malignant gliomas arising deep within the brain, which are difficult to remove. C6 glioma cells were implanted into the basal ganglia of rats, and 3 weeks later, the second-generation photosensitizer talaporfin sodium (TPS) was administered intraperitoneally. Ninety minutes after administration, a prototype fine plastic optical fiber was punctured into the tumor tissue, and semiconductor laser light was irradiated into the tumor from a 2-mm cylindrical light-emitting source under various conditions.

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Article Synopsis
  • Intraoperative photodynamic therapy (PDT) using talaporfin sodium is effective for local tumor control in malignant glioma, but its efficacy for cases that cannot be fully resected is unclear.
  • A study involving 18 patients with malignant glioma found some early reduction in residual tumors post-surgery after PDT; however, most patients still experienced recurrence, with distant progression seen in many.
  • The findings suggest that while PDT may slightly improve local tumor control in non-totally resectable malignant gliomas, it does not significantly prevent recurrence or improve overall survival rates.
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To investigate the therapeutic potential of photodynamic therapy (PDT) for malignant gliomas arising in unresectable sites, we investigated the effect of tumor tissue damage by interstitial PDT (i-PDT) using talaporfin sodium (TPS) in a mouse glioma model in which C6 glioma cells were implanted subcutaneously. A kinetic study of TPS demonstrated that a dose of 10 mg/kg and 90 min after administration was appropriate dose and timing for i-PDT. Performing i-PDT using a small-diameter plastic optical fiber demonstrated that an irradiation energy density of 100 J/cm or higher was required to achieve therapeutic effects over the entire tumor tissue.

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Fingolimod is an oral medication for the prevention of multiple sclerosis relapse, and its efficacy has been demonstrated in several clinical trials. Fingolimod has various side effects, such as arrhythmia and hepatic dysfunction. In addition, there have been rare reports of the development of lymphoproliferative disorders in patients undergoing fingolimod therapy, including primary central nervous system lymphoma (PCNSL).

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Article Synopsis
  • A 72-year-old woman with dermatomyositis experienced neurological symptoms, leading to MRI findings of multiple hyperintense brain lesions, initially suspected to be malignant lymphoma, prompting a brain biopsy.
  • Pathological results suggested potential malignant lymphoma, but treatment with high-dose methotrexate resulted in significant reduction of the lesions; however, further tests indicated the presence of the JC virus, confirming a diagnosis of progressive multifocal leukoencephalopathy (PML).
  • The case highlighted the complex immune response in PML, showing varied inflammatory cell types including CD4 and CD8 T cells, with PD-1 and PD-L1 expression, suggesting an interplay between viral infection and immune system reactions.
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Garnet-type Li La Zr O (LLZ) materials are attracting attention as solid electrolytes (SEs) in oxide-based all-solid-state batteries (ASSBs) owing to their high ionic conductivity. Although the electrochemical stability of LLZ against Li metal is demonstrated with possible high energy density, high-temperature sintering above 1000 °C, which is required to achieve high Li-ion conductivity, results in the formation of insulating impurities at the electrode-electrolyte interfaces. Here, nanosized fine-particle samples of Ta-substituted Li La Zr Ta O (LLZT) are successfully prepared at a remarkably low temperature of 400 °C utilizing an amorphous precursor oxide.

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Garnet-type Ta-substituted LiLaZrO materials attract considerable attention as solid electrolytes for use in future oxide-based all-solid-state lithium-ion batteries owing to their superior ionic conductivity and chemical and electrochemical stabilities. However, high-temperature sintering above 1000 °C, which is needed to realize high lithium-ion conductivity, results in the formation of insulating interface impurities at the electrode-electrolyte interface. Herein, the low-temperature sintering of the LiLaZrTaO (LLZT) solid electrolyte at a remarkably low temperature of 400 °C was demonstrated using the submicrometer-sized garnet-type LLZT fine powder sample prepared at 600 °C through a reaction of LiO and LaZrTaO.

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Gliomatosis cerebri (GC) is a unique glial tumor that extensively invades the cerebral white matter and has been recognized as an entity of neuroepithelial tumors since the first edition of the WHO classification of brain tumors in 1979. Thereafter, in the fourth edition of the WHO classification in 2007, it was clearly defined as a specific type of astrocytic tumor. However, in the WHO 2016 classification, which was based on the concept of integrated diagnosis using molecular genetics, GC was deleted as it was considered to be only one growth pattern of diffuse glioma and not a specific pathological entity.

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Article Synopsis
  • Photodiagnosis (PD) and photodynamic therapy (PDT) using talaporfin sodium for treating primary malignant brain tumors is gaining acceptance in Japan, with support from health insurance and therapeutic guidelines.
  • While PD and PDT have been successful for brain tumors, no similar studies exist for malignant spinal cord tumors, leading to poorer clinical outcomes in those cases.
  • This report details the first successful application of PD and PDT on a patient with a metastatic spinal cord tumor, resulting in over 2 years of meaningful survival following treatment.
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Notably, antibiofouling is an important and predominant technique adopted to improve the surfaces of biomaterials. In this study, polyethylene glycol-grafted polyethylene glycols bearing azidophenyl groups were synthesized and immobilized on polystyrene surfaces via photoirradiation. The prepared polymers were found to be highly soluble in water, and photoimmobilization with fluorescent proteins was confirmed based on micropatterning using a photomask.

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Clear cell meningioma is a rare histological variant of meningioma, which often recurs aggressively. This video demonstrates a patient with a petroclival clear cell meningioma, which was resected completely through the anterior transpetrosal approach. The absence of intratumoral spotty signal voids on preoperative susceptibility-weighted imaging (SWI) suggested that the tumor was a meningioma rather than a schwannoma, although typical imaging features of meningioma were not observed.

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A rapid automatic quantitative diagnostic system for multiple SARS-CoV-2 mutant protein-specific antibodies was developed using a microarray with photoreactive polymers. Two types of photoreactive polymers, phenylazide and polyoxyethylene, were prepared. The polymers were coated on a plastic plate.

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In this study, three types of electrospun scaffolds, including furfuryl-gelatin (f-gelatin) alone, f-gelatin with polycaprolactone (PCL) in a 1:1 ratio, and coaxial scaffolds with PCL (core) and f-gelatin (sheath), were developed for tissue engineering applications. Scaffolds were developed through single nozzle electrospinning and coaxial electrospinning, respectively, to serve as scaffolds for cardiac tissue engineering. Uniform fibrous structures were revealed in the scaffolds with significantly varying average fiber diameters of 760 ± 80 nm (f-gelatin), 420 ± 110 nm [f-gelatin and PCL (1:1)], and 810 ± 60 nm (coaxial f-gelatin > PCL) via scanning electron microscopy.

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Single crystals of LiSrLaZrO, having a new crystal structure, were successfully grown in air using the floating zone crystallization method. The obtained crystals were colorless and had a rectangular shape with a maximum dimension of 8(φ) × 50 mm. The elemental composition of the crystal was determined via energy-dispersive X-ray spectroscopy.

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Article Synopsis
  • Intracranial epidermoid cysts are rare and usually benign but can undergo malignant transformation, although this is uncommon.
  • The case presented involves a 59-year-old woman whose benign cyst in the cerebellopontine angle transformed malignantly after 6 years, as indicated by changes in MRI findings and histopathological features.
  • The study emphasizes the need for careful monitoring of benign epidermoid cysts, especially when signs of squamous metaplasia or p53 mutations are present, to catch any potential malignant changes early.
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  • The study highlights the difficulty of fully removing malignant glioma cells during surgery, emphasizing the importance of minimizing remaining tumor cells for better outcomes.
  • Researchers developed an intraoperative rapid fluorescence cytology system to detect infiltrating tumor cells in the brain-tumor interface, using a photosensitizer and semiconductor laser for imaging.
  • Results showed a correlation between tumor fluorescence intensity and cell density, suggesting that real-time fluorescence detection can help guide more complete surgical resection of malignant gliomas.
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Isocitrate dehydrogenase-mutant low-grade gliomas (IDHmut-LGG) grow slowly but frequently undergo malignant transformation, which eventually leads to premature death. Chemotherapy and radiotherapy treatments prolong survival, but can also induce genetic (or epigenetic) alterations involved in transformation. Here, we developed a mathematical model of tumor progression based on serial tumor volume data and treatment history of 276 IDHmut-LGGs classified by chromosome 1p/19q codeletion (IDH/1p19q and IDH/1p19q) and performed genome-wide mutational analyses, including targeted sequencing and longitudinal whole-exome sequencing data.

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Oxide-type all-solid-state lithium-ion batteries have attracted great attention as a candidate for a next-generation battery with high safety performance. However, batteries based on oxide systems exhibit much lower energy densities and rate performances than liquid-type lithium-ion batteries, owing to the difficulty in preparing the ion- and electron-transfer path between particles. In this study, LiSO-LiCO-LiX (X = Cl, Br, and I) glass systems are investigated as highly deformable and high-ionic-conductive oxide electrolytes.

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Background: We previously reported that the absolute value of O-methylguanine-DNA methyltransferase (MGMT) messenger RNA (mRNA) obtained using real-time reverse transcription polymerase chain reaction (RT-PCR) might be useful for predicting both the prognosis and the results of therapy for glioblastoma (GB) treated by temozolomide (TMZ).

Methods: MGMT mRNA was measured in 55 newly diagnosed cases of GB less than 75 and had a Karnofsky performance status (KPS) of at least 60 by real-time reverse transcription polymerase chain reaction (RT-PCR) using the TaqMan probe. A receiver operating characteristic analysis was performed to determine the cutoff points for progression free survival (PFS) and overall survival (OS).

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Monoclonal antibodies have been developed as anticancer agents to block immune checkpoint pathways associated with programmed cell death 1 (PD-1) and its ligand PD-L1. However, the high cost of antibodies has encouraged researchers to develop other inhibitor types. Here, biphenyl compounds were conjugated with poly(ethylene glycol) (PEG) to enhance the activity of small molecular inhibitors.

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A photosensitizer is a molecular drug for photodynamic diagnosis and photodynamic therapy (PDT) against cancer. Many studies have developed photosensitizers, but improvements in their cost, efficacy, and side effects are needed for better PDT of patients. In the present study, we developed a novel photosensitizer β-mannose-conjugated chlorin e6 (β-M-Ce6) and investigated its PDT effects in human glioblastoma U251 cells.

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Control of the cross-linking reaction is imperative when developing a sophisticated forming hydrogel in the body. In this study, a heteroarmed thermoresponsive (TR) nanoparticle was designed to investigate the mechanism of controlling reactivity of the functional groups introduced into the nanoparticles. The coupling reaction was suppressed/proceeded by utilizing temperature-induced morphological changes of the TR polymer.

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Photoreactive polymers that generate active species upon irradiation with light are very useful for modifying the surfaces of substrates. However, water solubility decreases as the number of photoreactive functional groups on the polymer increases because most photoreactive functional groups are hydrophobic. In order to improve the hydrophilicity of the photoreactive polymer, we synthesized polyethylene glycol-based photoreactive polymers bearing hydrophobic azidophenyl groups on their side chains.

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