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Article ; Online: Current Understanding of Neurofibromatosis Type 1, 2, and Schwannomatosis

Ryota Tamura

International Journal of Molecular Sciences, Vol 22, Iss 5850, p

2021 Volume 5850

Abstract: Neurofibromatosis (NF) is a neurocutaneous syndrome characterized by the development of tumors of the central or peripheral nervous system including the brain, spinal cord, organs, skin, and bones. There are three types of NF: NF1 accounting for 96% of ... ...

Abstract	Neurofibromatosis (NF) is a neurocutaneous syndrome characterized by the development of tumors of the central or peripheral nervous system including the brain, spinal cord, organs, skin, and bones. There are three types of NF: NF1 accounting for 96% of all cases, NF2 in 3%, and schwannomatosis (SWN) in <1%. The NF1 gene is located on chromosome 17q11.2, which encodes for a tumor suppressor protein, neurofibromin, that functions as a negative regulator of Ras/MAPK and PI3K/mTOR signaling pathways. The NF2 gene is identified on chromosome 22q12, which encodes for merlin, a tumor suppressor protein related to ezrin-radixin-moesin that modulates the activity of PI3K/AKT, Raf/MEK/ERK, and mTOR signaling pathways. In contrast, molecular insights on the different forms of SWN remain unclear. Inactivating mutations in the tumor suppressor genes SMARCB1 and LZTR1 are considered responsible for a majority of cases. Recently, treatment strategies to target specific genetic or molecular events involved in their tumorigenesis are developed. This study discusses molecular pathways and related targeted therapies for NF1, NF2, and SWN and reviews recent clinical trials which involve NF patients.
Keywords	neurofibromatosis type 1 ; neurofibromatosis type 2 ; schwannomatosis ; molecular targeted therapy ; clinical trial ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	572
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Critical Overview of Targeted Therapies for Vestibular Schwannoma

Ryota Tamura / Masahiro Toda

International Journal of Molecular Sciences, Vol 23, Iss 5462, p

2022 Volume 5462

Abstract: Vestibular schwannoma (VS) is a benign tumor that originates from Schwann cells in the vestibular component. Surgical treatment for VS has gradually declined over the past few decades, especially for small tumors. Gamma knife radiosurgery has become an ... ...

Abstract	Vestibular schwannoma (VS) is a benign tumor that originates from Schwann cells in the vestibular component. Surgical treatment for VS has gradually declined over the past few decades, especially for small tumors. Gamma knife radiosurgery has become an accepted treatment for VS, with a high rate of tumor control. For neurofibromatosis type 2 (NF2)-associated VS resistant to radiotherapy, vascular endothelial growth factor (VEGF)-A/VEGF receptor (VEGFR)-targeted therapy (e.g., bevacizumab) may become the first-line therapy. Recently, a clinical trial using a VEGFR1/2 peptide vaccine was also conducted in patients with progressive NF2-associated schwannomas, which was the first immunotherapeutic approach for NF2 patients. Targeted therapies for the gene product of SH3PXD2A-HTRA1 fusion may be effective for sporadic VS. Several protein kinase inhibitors could be supportive to prevent tumor progression because merlin inhibits signaling by tyrosine receptor kinases and the activation of downstream pathways, including the Ras/Raf/MEK/ERK and PI3K/Akt/mTORC1 pathways. Tumor-microenvironment-targeted therapy may be supportive for the mainstays of management. The tumor-associated macrophage is the major component of immunosuppressive cells in schwannomas. Here, we present a critical overview of targeted therapies for VS. Multimodal therapy is required to manage patients with refractory VS.
Keywords	schwannoma ; NF2 ; bevacizumab ; VEGF ; SH3PXD2A-HTRA1 fusion ; molecular targeted therapy ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Meningioma Cell Invasion into DuraGen-Derived Dura Mater

Ryota Tamura / Yuki Kuranari / Hideki Orikasa / Makoto Katayama

Medicines, Vol 9, Iss 30, p

A Case Report

2022 Volume 30

Abstract: Background: Dura mater infiltration is the main growth pattern of meningiomas. Local recurrence may occur in any type of meningioma, but it is more likely so in atypical meningiomas. Therefore, a wide resection of tumor cell-invaded dura mater is ... ...

Abstract	Background: Dura mater infiltration is the main growth pattern of meningiomas. Local recurrence may occur in any type of meningioma, but it is more likely so in atypical meningiomas. Therefore, a wide resection of tumor cell-invaded dura mater is necessary to avoid recurrence. DuraGen ® (an artificial dural substitute) can be used for dural reconstruction in meningiomas. Here, we report a rare case of a patient with atypical meningioma that invaded into the DuraGen ® -derived mature dura mater. Case presentation: A 66-year-old female showed a three-time recurrence of atypical meningioma. Simpson grade I resection (en bloc tumor with autologous dura mater and DuraGen ® -derived dura mater resection) was achieved at the 3rd recurrence. Collagen fibers running regularly and transversely were observed in the DuraGen ® -derived dura mater resembling the autologous meningeal layer. Meningioma cell invasion, displayed by occasional EMA immunostaining, was observed in the DuraGen ® -derived dura mater. Conclusions: This case indicates that meningioma cells may invade and survive in the DuraGen ®- derived dura mater. Whether or not DuraGen ® is not appropriate as a dural substitute remains unanswered. Further experiences are needed to validate these findings in large sample sizes.
Keywords	meningioma ; invasion ; dura mater ; DuraGen ; artificial ; autologous ; Medicine ; R
Subject code	333
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Stem cell-based therapies for neurological disorders

Ryota Tamura / Masahiro Toda

AIMS Cell and Tissue Engineering, Vol 2, Iss 1, Pp 24-

2018 Volume 46

Abstract: Cell-based therapies have been previously performed using fetal tissues for some central nervous system (CNS) disorders, such as Parkinson’s disease. However, it can be difficult to collect a large number of cells for transplantation. Recent studies ... ...

Abstract	Cell-based therapies have been previously performed using fetal tissues for some central nervous system (CNS) disorders, such as Parkinson’s disease. However, it can be difficult to collect a large number of cells for transplantation. Recent studies revealed that some stem cells can act as potential sources of cell-based therapies for degenerative and damaged areas in the CNS. In addition, stem cells can be used as cellular delivery vehicles for brain tumor because of tumor-tropic migratory capacity. Embryonic stem (ES) cells, mesenchymal stem cells (MSCs), and induced pluripotent stem (iPS) cells are the most attractive stem cells. iPS cells can be efficiently differentiated to neural stem cells and have the possibilities to overcome the ethical issues associated with ES cells. Therefore, cell-based therapies using iPS cells can be developed specifically for neurological disorders. In this article, we review the characteristics of ES cells, MSCs, and iPS cells as cell sources for stem cell-based therapies, and then discuss preclinical data and ongoing clinical trials for the CNS disorders.
Keywords	induced pluripotent stem cell ; embryonic stem cell ; mesenchymal stem cell ; neural stem cell ; neurological disorder ; glioblastoma ; Parkinson’s disease ; Alzheimer’s disease ; Medicine ; R
Subject code	571
Language	English
Publishing date	2018-03-01T00:00:00Z
Publisher	AIMS Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Pilot Study of the Adverse Events Caused by the Combined Use of Bevacizumab and Vascular Endothelial Growth Factor Receptor-Targeted Vaccination for Patients with a Malignant Glioma

Ryota Tamura / Yukina Morimoto / Mizuto Sato / Tetsuro Hikichi / Kazunari Yoshida / Masahiro Toda

Vaccines, Vol 8, Iss 498, p

2020 Volume 498

Abstract: Anti-angiogenic therapy, targeting vascular endothelial growth factor (VEGF)-A/VEGF receptors (VEGFRs), is beneficial for tumor growth prevention in a malignant glioma. A simultaneous blockade using both bevacizumab (Bev), which targets circulating VEGF- ... ...

Abstract	Anti-angiogenic therapy, targeting vascular endothelial growth factor (VEGF)-A/VEGF receptors (VEGFRs), is beneficial for tumor growth prevention in a malignant glioma. A simultaneous blockade using both bevacizumab (Bev), which targets circulating VEGF-A, and a multi-kinase inhibitor on VEGFRs was more effective for advanced solid cancers, including melanoma and renal cell carcinoma. However, previous clinical trials demonstrated a high adverse event rate. Additionally, no studies previously assessed treatment efficacy and safety using both VEGF-A and VEGFR-targeted agents for malignant gliomas. We had conducted clinical trials investigating VEGFRs peptide vaccination in patients with malignant gliomas, in which the treatment exhibited safety and yielded therapeutic effects in some patients. The combined use of Bev and VEGFRs vaccination may enhance the anti-tumor effect in malignant gliomas. In this pilot study, the adverse event profile in patients treated with Bev after the vaccination was investigated to establish this treatment strategy, in comparison to those treated with Bev collected from the published data or treated with the vaccination alone. In our previous clinical studies on patients with malignant gliomas, Bev was administered to 13 patients after VEGFRs vaccinations. One patient had a Grade 4 pulmonary embolism. Two patients had Grade 2 cerebral infarctions. There were no significant differences in the adverse event rates among patients treated with Bev, with the vaccination, or with Bev after the vaccination. Although careful observation is imperative for patients after this combination treatment strategy, VEGFRs-targeted vaccination may coexist with Bev for malignant gliomas.
Keywords	bevacizumab ; VEGF-A ; VEGFR ; peptide vaccine ; adverse event ; malignant glioma ; Medicine ; R
Subject code	616 ; 610
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Bilaterally Asymmetric Helical Myofibrils in Ascidian Tadpole Larvae

Koichi Matsuo / Ryota Tamura / Kohji Hotta / Mayu Okada / Akihisa Takeuchi / Yanlin Wu / Koh Hashimoto / Hidekazu Takano / Atsushi Momose / Atsuo Nishino

Frontiers in Cell and Developmental Biology, Vol

2021 Volume 9

Abstract: The locomotor system is highly bilateral at the macroscopic level. Homochirality of biological molecules is fully compatible with the bilateral body. However, whether and how single-handed cells contribute to the bilateral locomotor system is obscure. ... ...

Abstract	The locomotor system is highly bilateral at the macroscopic level. Homochirality of biological molecules is fully compatible with the bilateral body. However, whether and how single-handed cells contribute to the bilateral locomotor system is obscure. Here, exploiting the small number of cells in the swimming tadpole larva of the ascidian Ciona, we analyzed morphology of the tail at cellular and subcellular scales. Quantitative phase-contrast X-ray tomographic microscopy revealed a high-density midline structure ventral to the notochord in the tail. Muscle cell nuclei on each side of the notochord were roughly bilaterally aligned. However, fluorescence microscopy detected left-right asymmetry of myofibril inclination relative to the longitudinal axis of the tail. Zernike phase-contrast X-ray tomographic microscopy revealed the presence of left-handed helices of myofibrils in muscle cells on both sides. Therefore, the locomotor system of ascidian larvae harbors symmetry-breaking left-handed helical cells, while maintaining bilaterally symmetrical cell alignment. These results suggest that bilateral animals can override cellular homochirality to generate the bilateral locomotor systems at the supracellular scale.
Keywords	bilateral symmetry ; left-right asymmetry ; Ciona robusta ; muscle cell ; myofibrils ; synchrotron radiation ; Biology (General) ; QH301-705.5
Subject code	612
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Improvement of long-term blindness caused by compression from inner-third sphenoid wing meningioma after optic canal decompression

Ryota Tamura / Satoshi Takahashi / Tomo Horikoshi / Kazunari Yoshida

Surgical Neurology International, Vol 7, Iss 1, Pp 67-

An extremely rare case report

2016 Volume 67

Abstract: Background: There has been no previous case report of a patient whose visual acuity improved after long-term blindness caused by tumor invasion into the optic canal. Case Description: A 65-year-old Asian woman presented with a 6-month history of ... ...

Abstract	Background: There has been no previous case report of a patient whose visual acuity improved after long-term blindness caused by tumor invasion into the optic canal. Case Description: A 65-year-old Asian woman presented with a 6-month history of blindness caused by a meningioma located on the inner third of the sphenoid ridge. An operation was performed to prevent further tumor invasion into the cavernous sinus and contralateral optic nerve. During surgery, optic canal decompression was performed using an epidural approach. Subtotal removal of the tumor was achieved. Two days after the surgery, her left visual acuity recovered from blindness. Conclusion: Normally, long-term blindness caused by optic nerve compression by a brain tumor is regarded as irreversible, and even a surgical excision of the optic nerve is performed in some cases. However, because we experienced a case in which the patient recovered from long-term blindness after optic canal decompression, we believe that this surgical procedure should definitely be considered as an option.
Keywords	Blindness ; inner-third sphenoid wing meningioma ; optic canal decompression ; Medicine ; R ; Surgery ; RD1-811 ; Internal medicine ; RC31-1245 ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571 ; Neurology. Diseases of the nervous system ; RC346-429
Subject code	616
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Medknow Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Long-Term Clinical Outcome of First Recurrence Skull Base Meningiomas

Yuki Kuranari / Ryota Tamura / Noboru Tsuda / Kenzo Kosugi / Yukina Morimoto / Kazunari Yoshida / Masahiro Toda

Journal of Clinical Medicine, Vol 9, Iss 1, p

2019 Volume 106

Abstract: Skull base meningiomas (SBMs) are considered to be less aggressive and have a slower growth rate than non-SBMs. However, SBMs often develop local recurrences after surgical resection. Gross total removal is difficult because SBMs are deep-seated tumors ... ...

Abstract	Skull base meningiomas (SBMs) are considered to be less aggressive and have a slower growth rate than non-SBMs. However, SBMs often develop local recurrences after surgical resection. Gross total removal is difficult because SBMs are deep-seated tumors and involve critical neurovascular structures. The treatment strategy for recurrent SBMs remains controversial. The present study aimed to evaluate the long-term clinical course and prognostic factors associated with shorter progression-free survival (PFS) of recurrent SBMs. This retrospective study included 85 recurrent SBMs from 65 patients who underwent surgery from January 2005 to September 2018. Overall survival (OS) and PFS were evaluated, and the associations among shorter PFS and age, sex, tumor size, lesions, World Health Organization (WHO) grading, removal rate, and time since prior surgery were analyzed. The median follow-up period for PFS was 68 months. The 2-, 5-, and 10-year PFS rates were 68.0%, 52.8%, and 22.7%, respectively. WHO grade II or III, multiple lesions, and tumor size were significantly associated with shorter PFS ( p < 0.0001, p = 0.030, and p = 0.173, respectively). Although, radiotherapy did not improve PFS and OS for overall patients, PFS of the patients with subtotal and partial removal for WHO grade II SBMs was significantly improved by the radiotherapy. Multivariate analysis identified WHO grade II or III and multiple lesions as independent prognostic factors for shorter PFS ( p < 0.0001 and p = 0.040, respectively). It is essential to estimate the risks associated with shorter PFS for patients with recurrent SBMs to aid in the development of appropriate postoperative strategies.
Keywords	skull base meningioma ; recurrence ; atypical ; anaplastic ; adjuvant radiotherapy ; Medicine ; R
Subject code	610
Language	English
Publishing date	2019-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Analyzing Brain Functions by Subject Classification of Functional Near-Infrared Spectroscopy Data Using Convolutional Neural Networks Analysis

Satoru Hiwa / Kenya Hanawa / Ryota Tamura / Keisuke Hachisuka / Tomoyuki Hiroyasu

Computational Intelligence and Neuroscience, Vol

2016 Volume 2016

Abstract: Functional near-infrared spectroscopy (fNIRS) is suitable for noninvasive mapping of relative changes in regional cortical activity but is limited for quantitative comparisons among cortical sites, subjects, and populations. We have developed a ... ...

Abstract	Functional near-infrared spectroscopy (fNIRS) is suitable for noninvasive mapping of relative changes in regional cortical activity but is limited for quantitative comparisons among cortical sites, subjects, and populations. We have developed a convolutional neural network (CNN) analysis method that learns feature vectors for accurate identification of group differences in fNIRS responses. In this study, subject gender was classified using CNN analysis of fNIRS data. fNIRS data were acquired from male and female subjects during a visual number memory task performed in a white noise environment because previous studies had revealed that the pattern of cortical blood flow during the task differed between males and females. A learned classifier accurately distinguished males from females based on distinct fNIRS signals from regions of interest (ROI) including the inferior frontal gyrus and premotor areas that were identified by the learning algorithm. These cortical regions are associated with memory storage, attention, and task motor response. The accuracy of the classifier suggests stable gender-based differences in cerebral blood flow during this task. The proposed CNN analysis method can objectively identify ROIs using fNIRS time series data for machine learning to distinguish features between groups.
Keywords	Computer applications to medicine. Medical informatics ; R858-859.7 ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571
Subject code	150
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Primary Neuroendocrine Tumor in Brain

Ryota Tamura / Yoshiaki Kuroshima / Yoshiki Nakamura

Case Reports in Neurological Medicine, Vol

2014 Volume 2014

Keywords	Neurology. Diseases of the nervous system ; RC346-429 ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571 ; Internal medicine ; RC31-1245 ; Medicine ; R
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Hindawi Publishing Corporation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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