Induction of Meningioma Stem Signature via Hydrogel Reprogramming and Application of Meningioma Stem Cell Marker CXCR4 to Pathological Diagnosis and Treatment.Yoshitaka Oda; Masumi Tsuda; Lei Wang; Jun Suzuka; Sayaka Yuzawa; Koki Ise; Umma Habiba; Jintao He; Satoshi Tanikawa; Hirokazu Sugino; Zen-Ichi Tanei; Christian Mawrin; Jian Ping Gong; Shinya Tanaka
Biotechnology and bioengineering, 2026年02月27日,
［国際誌］英語, 研究論文（学術雑誌）, Meningiomas account for about 40% of all primary brain tumors. How ever effective treatments for recurrent or inoperable cases remain limited. We previously demonstrated that culturing cancer cells on specific hydrogels efficiently induces cancer stem cells across multiple cancer types, a process we termed hydrogel activated reprogramming (HARP) phenomenon. In this study, we aimed to identify key molecules involved in the induction of meningioma stem cells through hydrogel-based culture. Meningioma cells cultured on hydrogels were analyzed for expression of established stem cell markers and for tumorigenicity. Microarray analysis was performed to identify meningioma stem cell specific markers and to evaluate the application of these marker molecules as a therapeutic targets or as diagnostic tools for pathological grading. Canonical stem cell markers including Nanog, and Oct3/4 were upregulated in culturing meningioma cells on hydrogels. Comprehensive gene expression analysis identified some molecules involved in cancer stem cell activity among which CXCR4 was selected as a potential therapeutic target. Stimulation of CXCR4 with its ligand CXCL12 resulted in increased expression of stem cell markers. In human meningioma pathological specimens and cultured cell lines, there was a correlation between CXCR4 expression levels and NF2 mutations and/or deletions. CXCR4 immunohistochemistry was frequently positive in cases with brain invasion along with brain invasion area. These findings suggest that CXCR4 immunohistochemistry may be useful in suggesting typical CNS WHO grade 1 meningiomas without the need for molecular analysis. We have defined meningioma stem cell signature via HARP phenomenon and identified CXCR4 with biological significance as being diagnostic target. IMPORTANCE OF THE STUDY: In addition to morphological evaluation, immunohistochemistry and genetic alteration increasingly incorporated into the diagnostic criteria for central nervous system (CNS) tumors. From the CNS WHO 5th edition onwards, epigenetic features including DNA methylation profiling, have also been adopted as diagnostic criteria. In this study, we induced epigenetic changes in meningioma cells and successfully promoted cancer stemness highlighting the potential importance of this approach for both meningioma research and meningioma diagnostic development. Furthermore, microarray analysis identified CXCR4 as a molecule consistently upregulated during stem cell induction across all three hydrogel conditions. Subsequent analysis revealed that CXCR4 immunohistochemistry may reflect the distribution of meningioma stem cells, supporting its potential utility as a diagnostic marker. By integrating basic experimental findings with histopathological evaluation of clinical specimens, this report will contribute to the advancement of meningioma research and diagnostic strategies.
Astrocyte-Glioblastoma Stem Cell Interactions via Extracellular Vesicles Contribute to Distinct Vascular Structures.Yusuke Shirai; Masumi Tsuda; Lei Wang; Yoshitaka Oda; Hirokazu Sugizno; Zen-Ichi Tanei; Jian Ping Gong; Shinya Tanaka
Pathology international, 76, 2, e70099, 2026年02月,
［国際誌］英語, 研究論文（学術雑誌）, Glioblastoma (GBM) is a highly malignant astrocytic tumor characterized by marked heterogeneity and therapeutic resistance. Cancer stem-like cells (CSCs) drive recurrence within specialized microenvironments, such as perivascular niches. Glioblastoma stem cells have been considered to interact with surrounding stromal cells, including astrocytes. To investigate these cell communications, we used a co-culture system of glioblastoma KMG4 cells and immortalized human astrocytes (NHA-TS) on hydrogels. Co-culture on hydrogel induced stemness- and epithelial-mesenchymal transition-related genes. Glioblastoma- and astrocyte-derived extracellular vesicles (EVs) were incorporated into reciprocal cells. NHA-TS-derived EVs regulated stemness of KMG4 cells, whereas KMG4-derived EVs increased expression of vascular development-related genes, such as THBS1 and ANGPT1 in astrocytes. Proteomic analysis identified COL1A1 and THBS1 in KMG4 and NHA-TS co-culture EVs. Spatial transcriptomic analysis of human GBM tissue demonstrated THBS1 and COL1A1 expression in perivascular regions. Culturing KMG4 cells on PNaSS gels upregulated pericyte-associated genes such as ACTA2, PDGFRB, HIGD1B. Within the perivascular microenvironment, EV-mediated interactions between glioblastoma cells and astrocytes support the induction of stemness and the differentiation of GBM cells toward a pericyte-like phenotype, promoting perivascular niche formation and microvascular proliferation. The hydrogel-based co-culture model thus provides a simple and effective platform for dissecting tumor-stroma communication in the glioblastoma microenvironment.
Multifocal rosette-forming glioneuronal tumor-like low-grade glioneuronal tumor with dysembryoplastic neuroepithelial tumor features associated with drug-resistant epilepsy: a case report and literature review.Yuuki Ishida; Koki Ise; Kenichi Sato; Taku Asanome; Ryunosuke Yoshihara; Yoko Aburakawa; Masaki Izumi; Yoshitaka Oda; Hirokazu Sugino; Zen-Ichi Tanei; Masumi Tsuda; Shinya Tanaka
Brain tumor pathology, 2026年01月06日,
［国内誌］英語, 研究論文（学術雑誌）, Rosette-forming glioneuronal tumors (RGNTs) are rare, World Health Organization grade 1 tumors that typically arise around the fourth ventricle. However, cerebral hemisphere RGNTs have recently been reported, with some exhibiting clinical features resembling low-grade epilepsy-associated tumor (LEAT). We report a case of multifocal RGNT in a patient with drug-refractory epilepsy. A 14-year-old woman was incidentally found to have multifocal brain tumor involving the left temporal lobe and bilateral thalamus, she developed drug-resistant epilepsy ten years later and underwent surgery. Partial tumor resection and anterior temporal lobectomy were performed. Histopathology revealed a glioneuronal tumor with oligodendroglia-like cells, neurocytic rosette, and perivascular pseudorosette, exhibiting an infiltrative growth pattern extending into the white matter. Genetic analysis revealed Fibroblast Growth Factor Receptor 1 mutation. The methylation profile analysis matched the low-grade glioneuronal tumor class but did not yield to any subclass category. Finally, the tumor was diagnosed as RGNT-like low-grade glioneuronal tumor with dysembryoplastic neuroepithelial tumor (DNT) features. Cases presenting with a LEAT-like clinical course and exhibiting histopathological features of RGNT are often difficult to definitively distinguish from DNT based on histological and genetic findings. Epilepsy-associated RGNT may harbor genetic profiles distinct from those of prototypical RGNTs, highlighting the need for further investigation.
Distinct characteristics of brain metastasis in lung adenocarcinoma: development of high-confidence cell lines.Jintao He; Zen-Ichi Tanei; Dao-Sian Wu; Lei Wang; Yoshitaka Oda; Masumi Tsuda; Shinya Tanaka
Acta neuropathologica communications, 13, 1, 109, 109, 2025年05月21日,
［国際誌］英語, 研究論文（学術雑誌）, Lung cancer is a leading cause of cancer-related deaths worldwide, with brain metastasis occurring in approximately 30-55% of patients, particularly in lung adenocarcinoma. Due to the challenges in obtaining genuine brain metastasis tumor cells, researchers commonly use nude mouse models to establish brain metastasis cell lines, though traditional methods have limitations such as high costs, lengthy timeframes, and the need for specialized imaging equipment. To address these issues, we developed an improved approach by performing low cell number circulating intracranial injections (500-4000 cells) in nude mice, successfully establishing the H1975-BM1, BM2, and BM3 cell lines. Through RNA sequencing and bioinformatics analyses, we identified transcriptomic differences among these cell lines, revealing that H1975-BM1 cells primarily exhibit stem cell function and migration characteristics, while H1975-BM3 cells display enhanced chemotaxis, cell adhesion, and cytokine secretion associated with interactions. Experimental validation, including Transwell assays, CCK8, cell adhesion assays, and subcutaneous tumor implantation in nude mice, further confirmed these findings, with H1975-BM3 forming larger tumors and a more pronounced secretion cystic cavity. In conclusion, our improved methodology successfully established high-confidence brain metastasis lung adenocarcinoma cell lines, elucidating distinct transcriptomic and functional characteristics at different stages of brain metastasis progression.
側脳室に発生した脂肪化細胞を伴う中枢性神経細胞腫の一例
桑原 傑; 小田 義崇; 藤原 雄介; 伊勢 昂生; 王 磊; 種井 善一; 津田 真寿美; 田中 伸哉
Brain Tumor Pathology, 42, Suppl., 128, 128, 日本脳腫瘍病理学会, 2025年05月
英語
Human TIMELESS, a potential circadian clock regulator, plays an essential role in survival and reawakening of metastasis-initiating cells in boneHirokazu Shimizu; Lei Wang; Masumi Tsuda; Reo Maruyama; Yusuke Saito; Kohei Kumegawa; Masato Takahashi; Rie Horii; Hiroaki Suzuki; Kenichi Watanabe; Ryuta Arai; Masaaki Murakami; Norimasa Iwasaki; Shinya Tanaka
Cold Spring Harbor Laboratory, 2025年03月19日
Abstract
Bone metastasis is becoming increasingly common globally. In such cases, cancer cells disseminate from the primary site to bone, subsequently entering a dormant state. Following a certain incubation period, the cells reawaken and grow, forming a metastatic mass. These dormant cells are called metastasis-initiating cells (MICs), but their survival and reawakening are poorly understood. Here, we established anin vivoMIC-reawakening mouse model in bone. Microarray analysis demonstrated enrichment for mitochondrial oxidative phosphorylation (OXPHOS) and fatty acid synthesis in isolated MICs. In addition, transcriptional regulator TIMELESS was identified as an independent poor prognostic factor by using clinical transcriptomic datasets, which was validated by immunostaining on 209 breast cancer cases. TIMELESS-deficient breast, prostate, and bladder cancer cell lines exhibited reduced viability and MIC reawakening in bone. Single-cell analysis on the epigenetic landscape of MICs revealed that motif activities of CLOCK and BMAL1/ARNTL were enhanced in a cluster with increased TIMELESS accessibility scores. As TIMELESS regulates stemness through the OXPHOS metabolic state, an inhibitor targeting the metabolic pathway, MP-A08, was identified to suppress MIC reawakening and growth in bone more efficiently than cisplatin. These results suggest that TIMELESS regulates survival and reawakening in MICs and MP-A08 could contribute to adjuvant therapeutic strategies.
血管周囲ニッシェに潜伏する膠芽腫幹細胞を標的とした治療戦略(Treatment strategy targeting glioblastoma stem cells latent in the perivascular niche)
津田 真寿美; 高村 敦子; 大西 健太; 王 磊; 小田 義崇; 田中 伸哉
日本病理学会会誌, 114, 1, 295, 295, (一社)日本病理学会, 2025年03月
英語
非腫瘍性神経疾患の病理学的解析 北大における病理解剖と神経病理研究(Pathological analysis of non-tumor neurological diseases Autopsy and research of the nervous system at Hokkaido University)
種井 善一; 小田 義崇; 王 磊; 津田 真寿美; 田中 伸哉
日本病理学会会誌, 114, 1, 189, 189, (一社)日本病理学会, 2025年03月
英語
高機能ハイドロゲルを用いた白血病幹細胞の創出(Analysis for of synthelic polymer hydrogel-mediated generation of leuklamia stem cell)
小田 義崇; 澤井 彩織; 齋藤 祐介; 桑原 傑; 王 磊; 種井 善一; 津田 真寿美; 真部 淳; ぐん 剣萍; 田中 伸哉
日本病理学会会誌, 114, 1, 280, 280, (一社)日本病理学会, 2025年03月
英語
AIによる悪性脳腫瘍分類 基盤モデルの転移学習戦略比較(AI-based Brain Tumor Classification: Comparing Transfer Learning Strategies for Foundation Models)
遠田 建; 小田 義崇; 種井 善一; 王 磊; 津田 真寿美; 田中 伸哉
日本病理学会会誌, 114, 1, 281, 281, (一社)日本病理学会, 2025年03月
英語
膠芽腫の単一細胞分子分類と腫瘍関連マクロファージとの局在に関わる空間トランスクリプトーム解析(Spatial transcriptomics of macrophages and single cell molecular classification in glioblastoma)
伊勢 昂生; 種井 善一; 桑原 傑; 遠田 建; 白井 裕介; He Jinto; 小田 義崇; 王 磊; 津田 真寿美; 田中 伸哉
日本病理学会会誌, 114, 1, 294, 294, (一社)日本病理学会, 2025年03月
英語
腫瘍微小環境における膠芽腫幹細胞と星状膠細胞の相互作用の検討(Analysis of interaction between glioblastoma stem cells and astrocytes in tumor microenvironment)
白井 裕介; 津田 真寿美; 王 磊; 小田 義崇; 種井 善一; 田中 伸哉
日本病理学会会誌, 114, 1, 406, 406, (一社)日本病理学会, 2025年03月
英語
低体温症から救命後、急性呼吸窮迫症候群(ARDS)を発症し、死亡した一解剖例
森口 いる麻; 伊勢 昴生; 白神 美織; 中村 海人; 小田 義崇; 種井 善一; 王 磊; 津田 真寿美; 太田 聡; 田中 伸哉
日本病理学会会誌, 114, 1, 451, 451, (一社)日本病理学会, 2025年03月
日本語
高異軽度子宮内膜間質肉腫の1解剖例
小泉 悠; 白井 祐介; 西村 真唯; 小田 義崇; 種井 善一; 王 磊; 津田 真寿美; 和田 真一郎; 太田 聡; 田中 伸哉
日本病理学会会誌, 114, 1, 453, 453, (一社)日本病理学会, 2025年03月
日本語
44歳の脊髄小脳変性症(マシャドジョセフ病)の一解剖例
張 一夫; 伊勢 昴生; 白井 慎一; 小田 義崇; 種井 善一; 王 磊; 津田 真寿美; 田中 伸哉
日本病理学会会誌, 114, 1, 455, 455, (一社)日本病理学会, 2025年03月
日本語
SLC13A5 plays an essential role in the energy shift to oxidative phosphorylation in cisplatin-resistant mesothelioma stem cells.Marie Kato-Shinomiya; Hirokazu Sugino; Lei Wang; Yusuke Saito; Jintao He; Zen-Ichi Tanei; Yoshitaka Oda; Satoshi Tanikawa; Mishie Tanino; Jian Ping Gong; Masumi Tsuda; Shinya Tanaka
Pathology international, 2025年02月06日,
［国際誌］英語, 研究論文（学術雑誌）, Mesothelioma is a highly aggressive tumor affecting an increasing number of patients worldwide. Owing to the poor clinical outcomes associated with current therapies, the development of novel therapies that target cancer stem cells (CSCs) is desirable. Here, we examined the applicability of our previously established hydrogel-based rapid CSC generation method to human mesothelioma cell lines and further analyzed the characteristics of the induced mesothelioma stem cell (MesoSC) -like cells. Human mesothelioma cell lines cultured on hydrogels presented increased expression of pan-stem cell markers and acquired spheroid formation and early tumorigenicity, suggesting that MesoSC-like cells are highly malignant. Microarray analysis demonstrated that the expression of SLC13A5, a citrate transporter involved in TCA cycle, was significantly induced in the resulting MesoSC-like cells. The overexpression of SLC13A5 resulted in a metabolic shift toward oxidative phosphorylation, increased phosphorylation of ERK and YAP, and increased SOX2 expression, leading to increased cisplatin resistance. scRNA-seq database analysis revealed that clinical mesothelioma samples contained a small number of SLC13A5-expressing cells. Our findings suggest that the hydrogel-based CSC generation method is also effective for human mesothelioma cells and that SLC13A5 may contribute to MesoSC survival. The new properties of MesoSCs revealed in this study may provide clues for establishing future treatments.
Establishment of a novel method for differentiating into dopaminergic neurons using charged hydrogels.Bin Fan; Satoshi Tanikawa; Lei Wang; Takayuki Nonoyama; Yashitaka Oda; Zen-Ichi Tanei; Jian Ping Gong; Masumi Tsuda; Shinya Tanaka
Biochemical and biophysical research communications, 747, 151280, 151280, 2025年02月02日,
［国際誌］英語, 研究論文（学術雑誌）, Parkinson's disease (PD) is a neurodegenerative disease primarily affecting the central nervous system and impacting both the motor system and non-motor systems. Although administration of L-DOPA is effective, it is not a fundamental treatment and has side effects such as diurnal fluctuation and dyskinesia, highlighting the need for new treatment methods. There is a growing interest in dopaminergic neuron transplantation as a potential treatment. Dopaminergic neurons derived from pluripotent stem (iPS) cells provide a valuable source for transplantation therapies. Developing an efficient method to differentiate iPS cells into dopaminergic cells is essential for cell transplantation therapy. While Cell differentiation is typically controlled by the addition of specific reagents, the physical characteristics of culture substrate, especially in the charge and stiffness, are also crucial factors in regulating differentiation. In this research, we show that two newly developed electrically charged polymeric hydrogels composed of cationic (C) and anionic (A) monomers inratio of 1-9 and 2 to 8 can significantly promote Dopaminergic neuron differentiation. Our findings emphasize the importance of culture substrates in effective dopaminergic cell differentiation.
Analysis of synthetic polymer hydrogel-based generation of leukemia stem cells.Saori Sawai; Yoshitaka Oda; Yusuke Saito; Takeru Kuwabara; Lei Wang; Zen-Ichi Tanei; Shinsuke Hirabayashi; Masumi Tsuda; Jian Ping Gong; Atsushi Manabe; Shinya Tanaka
Biochemical and biophysical research communications, 744, 151149, 151149, 2025年01月,
［国際誌］英語, 研究論文（学術雑誌）, Leukemia stem cells (LSCs), capable of simultaneous self-renewal and differentiation, are resistant to chemotherapy and the cause of relapse in refractory cases of leukemia. As a method to rapidly generate LSCs has not been established, research on LSCs as therapeutic targets has been hampered. Here, we demonstrate that K562 leukemia cells acquired LSC properties with increase in stemness markers such as CD34, Oct3/4, and Nanog and metabolic alterations towards OXPHOS by culturing cells on synthetic polymer hydrogels. In this hydrogel-generated LSCs, single-cell RNA sequencing identified the increase in expression levels of AKR1B1 and TSPYL5, which play an essential role for stemness generation. Decrease in expression of CD34, Oct3/4, and Nanog were observed in K562 cells with knockdown of AKR1B1 and TSPYL5. These results indicate that cell culturing on synthetic polymer hydrogels can be a useful system to generate LSCs and AKR1B1 and TSPYL5 may become therapeutic targets for LSCs.
Molecular and structural insights into SARS-CoV-2 evolution: from BA.2 to XBB subvariantsHisano Yajima; Tomo Nomai; Kaho Okumura; Katsumi Maenaka; Jumpei Ito; Takao Hashiguchi; Kei Sato; Keita Matsuno; Naganori Nao; Hirofumi Sawa; Keita Mizuma; Jingshu Li; Izumi Kida; Yume Mimura; Yuma Ohari; Shinya Tanaka; Masumi Tsuda; Lei Wang; Yoshikata Oda; Zannatul Ferdous; Kenji Shishido; Hiromi Mohri; Miki Iida; Takasuke Fukuhara; Tomokazu Tamura; Rigel Suzuki; Saori Suzuki; Shuhei Tsujino; Hayato Ito; Yu Kaku; Naoko Misawa; Arnon Plianchaisuk; Ziyi Guo; Alfredo A. Hinay; Kaoru Usui; Wilaiporn Saikruang; Spyridon Lytras; Keiya Uriu; Ryo Yoshimura; Shusuke Kawakubo; Luca Nishumura; Yusuke Kosugi; Shigeru Fujita; Jarel Elgin M.Tolentino; Luo Chen; Lin Pan; Wenye Li; Maximilian Stanley Yo; Kio Horinaka; Mai Suganami; Mika Chiba; Kyoko Yasuda; Keiko Iida; Adam Patrick Strange; Naomi Ohsumi; Shiho Tanaka; Eiko Ogawa; Tsuki Fukuda; Rina Osujo; Kazuhisa Yoshimura; Kenji Sadamas; Mami Nagashima; Hiroyuki Asakura; Isao Yoshida; So Nakagawa; Kazuo Takayama; Rina Hashimoto; Sayaka Deguchi; Yukio Watanabe; Yoshitaka Nakata; Hiroki Futatsusako; Ayaka Sakamoto; Naoko Yasuhara; Tateki Suzuki; Kanako Kimura; Jiei Sasaki; Yukari Nakajima; Takashi Irie; Ryoko Kawabata; Kaori Sasaki-Tabata; Terumasa Ikeda; Hesham Nasser; Ryo Shimizu; Mst Monira Begum; Michael Jonathan; Yuka Mugita; Sharee Leong; Otowa Takahashi; Takamasa Ueno; Chihiro Motozono; Mako Toyoda; Akatsuki Saito; Anon Kosaka; Miki Kawano; Natsumi Matsubara; Tomoko Nishiuchi; Jiri Zahradnik; Prokopios Andrikopoulos; Miguel Padilla-Blanco; Aditi Konar
mBio, 15, 10, American Society for Microbiology, 2024年10月16日
研究論文（学術雑誌）, ABSTRACT
Due to the incessant emergence of various SARS-CoV-2 variants with enhanced fitness in the human population, controlling the COVID-19 pandemic has been challenging. Understanding how the virus enhances its fitness during a pandemic could offer valuable insights for more effective control of viral epidemics. In this manuscript, we review the evolution of SARS-CoV-2 from early 2022 to the end of 2023—from Omicron BA.2 to XBB descendants. Focusing on viral evolution during this period, we provide concrete examples that SARS-CoV-2 has increased its fitness by enhancing several functions of the spike (S) protein, including its binding affinity to the ACE2 receptor and its ability to evade humoral immunity. Furthermore, we explore how specific mutations modify these functions of the S protein through structural alterations. This review provides evolutionary, molecular, and structural insights into how SARS-CoV-2 has increased its fitness and repeatedly caused epidemic surges during the pandemic.
Transformed gastric mucosa-associated lymphoid tissue lymphoma originating in the colon and developing metachronously after Helicobacter pylori eradication: A case report.Makoto Saito; Zen-Ichi Tanei; Masumi Tsuda; Toma Suzuki; Emi Yokoyama; Minoru Kanaya; Koh Izumiyama; Akio Mori; Masanobu Morioka; Takeshi Kondo
World journal of gastrointestinal oncology, 16, 10, 4281, 4288, 2024年10月15日,
［国際誌］英語, 研究論文（学術雑誌）, BACKGROUND: Helicobacter pylori (H. pylori) eradication treatment for primary gastric mucosa-associated lymphoid tissue (MALT) lymphoma has already been established. However, t (11;18) (q21;q21)/API2-MALT1 translocation-positive lesions are a type of primary gastric MALT lymphoma in which a response to eradication treatment is difficult to achieve. In addition, trisomy 18 may be associated with diffuse large B-cell lymphoma (DLBCL) transformation of gastric MALT lymphoma. CASE SUMMARY: A 66-year-old man was diagnosed with MALT lymphoma in the ascending colon by colonoscopy and biopsy. Two years later, esophagogastroduodenoscopy revealed chronic atrophic gastritis that was positive for H. pylori, and eradication treatment was administered. Two years and nine months later (at the age of 70), a new ulcerative lesion suggestive of MALT lymphoma appeared in the gastric body, and six months later, a similar lesion was also found in the fundus. One year later (4 years and 3 months after H. pylori eradication), at the age of 72, the lesion in the gastric body had become deeper and had propagated. A biopsy revealed a pathological diagnosis of DLBCL. Both MALT lymphoma lesions in the ascending colon and DLBCL lesions in the stomach were positive for the t (11;18) (q21;q21)/API2-MALT1 translocation, and trisomy 18q21 was also detected. After 6 courses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy, all of the above lesions disappeared [complete remission (CR)], and CR has been maintained for more than 3 years. In addition, both the colonic and gastric lesions were proven to have the same clonality. CONCLUSION: Because the patient had a MALT1 translocation with trisomy 18q21, it was thought that this gastric MALT lymphoma developed independently of H. pylori infection and progressed.
微小血管増生ニッシェに潜在するグリオーマ幹細胞を標的とした治療戦略(Treatment strategy targeting glioma stem cells latent in the microvascular proliferation niche)
津田 真寿美; 王 磊; 小田 義崇; 田中 伸哉; 田中 伸哉
日本癌学会総会記事, 83回, E, 1003, (一社)日本癌学会, 2024年09月
英語
ハイドロゲル上で誘導された膀胱癌幹細胞の特徴と標的治療の探索(Characteristics and targeted therapeutic prospects of bladder cancer stem cells induced on hydrogels)
王 磊; 津田 真寿美; 小田 義崇; 田中 伸哉
日本癌学会総会記事, 83回, P, 1102, (一社)日本癌学会, 2024年09月
英語
Clinical outcome, radiological findings, and genetic features of IDH-mutant brainstem glioma in adults.Sogo Oki; Yukitomo Ishi; Ryosuke Sawaya; Michinari Okamoto; Hiroaki Motegi; Zen-Ichi Tanei; Masumi Tsuda; Takashi Mori; Kentaro Nishioka; Hiromi Kanno-Okada; Hidefumi Aoyama; Shinya Tanaka; Shigeru Yamaguchi; Miki Fujimura
Acta neurochirurgica, 166, 1, 263, 263, 2024年06月12日,
［国際誌］英語, 研究論文（学術雑誌）, BACKGROUND: With the recent advent of genetic testing, IDH-mutant glioma has been found among adult brainstem gliomas. However, the clinical outcome and prognosis of IDH-mutant brainstem gliomas in adults have not been elucidated. This study aimed to investigate the clinical outcome, radiological findings, and genetic features of adult patients with IDH-mutant diffuse brainstem gliomas. METHODS: Data from adult patients with brainstem glioma at Hokkaido University Hospital between 2006 and 2022 were retrospectively analyzed. Patient characteristics, treatment methods, genetic features, and prognosis were evaluated. RESULTS: Of 12 patients with brainstem glioma with proven histopathology, 4 were identified with IDH mutation. All patients underwent local radiotherapy with 54 Gray in 27 fractions combined with chemotherapy with temozolomide. Three patients had IDH1 R132H mutation and one had IDH2 R172G mutation. The median progression-free survival and overall survival were 68.4 months and 85.2 months, respectively, longer than that for IDH-wildtype gliomas (5.6 months and 12.0 months, respectively). At the time of initial onset, contrast-enhanced lesions were observed in two of the four cases in magnetic resonance imaging. CONCLUSION: As some adult brainstem gliomas have IDH mutations, and a clearly different prognosis from those with IDH-wildtype, biopsies are proactively considered to confirm the genotype.
脳腫瘍の分子診断と治療2 バイオマテリアルを用いたグリオーマ幹細胞ニッシェの構築
津田 真寿美; 王 磊; 小田 義崇; 種井 善一; 田中 伸哉
Brain Tumor Pathology, 41, Suppl., 101, 101, 日本脳腫瘍病理学会, 2024年05月
日本語
Virological characteristics of the SARS-CoV-2 Omicron XBB.1.5 variantTamura, Tomokazu; Irie, Takashi; Deguchi, Sayaka; Yajima, Hisano; Tsuda, Masumi; Nasser, Hesham; Mizuma, Keita; Plianchaisuk, Arnon; Suzuki, Saori; Uriu, Keiya; Begum, Mst Monira; Shimizu, Ryo; Jonathan, Michael; Suzuki, Rigel; Kondo, Takashi; Ito, Hayato; Kamiyama, Akifumi; Yoshimatsu, Kumiko; Shofa, Maya; Hashimoto, Rina; Anraku, Yuki; Kimura, Kanako Terakado; Kita, Shunsuke; Sasaki, Jiei; Sasaki-Tabata, Kaori; Maenaka, Katsumi; Nao, Naganori; Wang, Lei; Oda, Yoshitaka; The Genotype to Phenotype Japan (G2P-Japan) Consortium; Ikeda, Terumasa; Saito, Akatsuki; Matsuno, Keita; Ito, Jumpei; Tanaka, Shinya; Sato, Kei; Hashiguchi, Takao; Takayama, Kazuo; Fukuhara, Takasuke
Nature Communications, 15, 2024年02月08日
英語, 研究論文（学術雑誌）, Circulation of SARS-CoV-2 Omicron XBB has resulted in the emergence of XBB.1.5, a new Variant of Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring the S486P spike (S) mutation, subsequent to the acquisition of a nonsense mutation in ORF8. Neutralization assays showed similar abilities of immune escape between XBB.1.5 and XBB.1. We determine the structural basis for the interaction between human ACE2 and the S protein of XBB.1.5, showing similar overall structures between the S proteins of XBB.1 and XBB.1.5. We provide the intrinsic pathogenicity of XBB.1 and XBB.1.5 in hamsters. Importantly, we find that the ORF8 nonsense mutation of XBB.1.5 resulted in impairment of MHC suppression. In vivo experiments using recombinant viruses reveal that the XBB.1.5 mutations are involved with reduced virulence of XBB.1.5. Together, our study identifies the two viral functions defined the difference between XBB.1 and XBB.1.5.
Combining expertise to characterize the SARS-CoV-2 Omicron XBB.1.5 variant. 京都大学プレスリリース. 2024-02-19.
Virological characteristics of the SARS-CoV-2 Omicron XBB.1.5 variant.Tomokazu Tamura; Takashi Irie; Sayaka Deguchi; Hisano Yajima; Masumi Tsuda; Hesham Nasser; Keita Mizuma; Arnon Plianchaisuk; Saori Suzuki; Keiya Uriu; Mst Monira Begum; Ryo Shimizu; Michael Jonathan; Rigel Suzuki; Takashi Kondo; Hayato Ito; Akifumi Kamiyama; Kumiko Yoshimatsu; Maya Shofa; Rina Hashimoto; Yuki Anraku; Kanako Terakado Kimura; Shunsuke Kita; Jiei Sasaki; Kaori Sasaki-Tabata; Katsumi Maenaka; Naganori Nao; Lei Wang; Yoshitaka Oda; Terumasa Ikeda; Akatsuki Saito; Keita Matsuno; Jumpei Ito; Shinya Tanaka; Kei Sato; Takao Hashiguchi; Kazuo Takayama; Takasuke Fukuhara
Nature communications, 15, 1, 1176, 1176, 2024年02月08日,
［国際誌］英語, 研究論文（学術雑誌）, Circulation of SARS-CoV-2 Omicron XBB has resulted in the emergence of XBB.1.5, a new Variant of Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring the S486P spike (S) mutation, subsequent to the acquisition of a nonsense mutation in ORF8. Neutralization assays showed similar abilities of immune escape between XBB.1.5 and XBB.1. We determine the structural basis for the interaction between human ACE2 and the S protein of XBB.1.5, showing similar overall structures between the S proteins of XBB.1 and XBB.1.5. We provide the intrinsic pathogenicity of XBB.1 and XBB.1.5 in hamsters. Importantly, we find that the ORF8 nonsense mutation of XBB.1.5 resulted in impairment of MHC suppression. In vivo experiments using recombinant viruses reveal that the XBB.1.5 mutations are involved with reduced virulence of XBB.1.5. Together, our study identifies the two viral functions defined the difference between XBB.1 and XBB.1.5.
ハイドロゲルを用いた新規治療耐性細胞株の樹立(Establishment of novel treatment-resistant cell lines using hydrogel)
王 磊; 窪田 武哲; 津田 真寿美; 小田 義崇; 平野 聡; グン 剣萍; 田中 伸哉
日本病理学会会誌, 113, 1, 401, 401, (一社)日本病理学会, 2024年02月
英語
ハムスター肺炎モデルを用いたSARS-CoV-2肺炎の病理組織学的解析(Histopathological analysis of hamster SARS-CoV-2 pneumonia model)
小田 義崇; 津田 真寿美; 王 磊; 種井 善一; 福原 崇介; 佐藤 佳; 田中 伸哉
日本病理学会会誌, 113, 1, 301, 301, (一社)日本病理学会, 2024年02月
英語
神経性食指不振症の病理解剖症例(Autopsy case report of anorexia nervosa)
白井 裕介; 種井 善一; 川内 真; 松居 剛志; 小田 義崇; 津田 真寿美; 篠原 敏也; 太田 聡; 田中 伸哉
日本病理学会会誌, 113, 1, 344, 344, (一社)日本病理学会, 2024年02月
英語
正中弓状靱帯症候群と膵頭部癌により致死的な十二指腸出血を来たした1剖検例(An autopsy case of fatal hemorrhage due to median arch ligament syndrome and pancreatic cancer)
伊勢 昂生; 大塚 拓也; 濱 憲輝; 潟沼 朗生; 小田 義崇; 種井 善一; 津田 真寿美; 太田 聡; 篠原 敏也; 田中 伸哉
日本病理学会会誌, 113, 1, 398, 399, (一社)日本病理学会, 2024年02月
英語
脊髄capillary hemangiomaの病理像(Pathology of the capillary hemangioma of the spinal cord)
種井 善一; 小野 裕介; 小田 義崇; 津田 真寿美; 大竹 安史; 今村 博幸; 小柳 泉; 飛騨 一利; 水上 裕輔; 田中 伸哉
日本病理学会会誌, 113, 1, 436, 436, (一社)日本病理学会, 2024年02月
英語
マントルリンパ腫とびまん性大細胞型B細胞性リンパ腫のdiscordant lymphomaの一解剖例(An autopsy case of discordant lymphoma: mantle cell lymphoma and diffuse large B-cell lymphoma)
岸浪 建; 小田 義崇; 王 磊; 江端 浩; 加藤 万里絵; 種井 善一; 津田 真寿美; 宮城島 拓人; 田中 伸哉
日本病理学会会誌, 113, 1, 453, 453, (一社)日本病理学会, 2024年02月
英語
慢性肺血栓塞栓症の二剖検例
岸本 佳子; 種井 善一; 青木 健志; 棒田 浩基; 小田 義崇; 王 磊; 津田 真寿美; 田中 伸哉
日本病理学会会誌, 113, 1, 468, 468, (一社)日本病理学会, 2024年02月
日本語
14年後に再発したBRAF V600E変異を有するlow-grade gliomaの1例
黒田 花音; 小田 義崇; 岡本 迪成; 村木 岳史; 種井 善一; 王 磊; 津田 真寿美; 高阪 真路; 西原 広史; 田中 伸哉
日本病理学会会誌, 113, 1, 482, 482, (一社)日本病理学会, 2024年02月
日本語
左同名半盲をきたした頭蓋内腫瘍の一例
長野 七海; 種井 善一; 福島 大地; 小田 義崇; 王 磊; 津田 真寿美; 山村 明範; 田中 伸哉
日本病理学会会誌, 113, 1, 482, 482, (一社)日本病理学会, 2024年02月
日本語
BRAF p.V600E変異を有するHigh-grade Gliomaの病理学的研究
京野 里虹; 種井 善一; 伊師 雪友; 小田 義崇; 王 磊; 津田 真寿美; 佐藤 憲市; 寺坂 俊介; 田中 伸哉
日本病理学会会誌, 113, 1, 482, 482, (一社)日本病理学会, 2024年02月
日本語
MELAS様症状とMT-ATP6 m.8639T>C変異を伴う71歳男性の一剖検例
戸田 壮太郎; 小田 義崇; 種井 善一; 王 磊; 大森 優子; 石田 雄介; 津田 真寿美; 松岡 健; 田中 伸哉
日本病理学会会誌, 113, 1, 483, 483, (一社)日本病理学会, 2024年02月
日本語
30代男性のアミロイドアンギオパチーの病理像
馬詰 知佐; 種井 善一; 小田 義崇; 藤井 恭子; 王 磊; 津田 真寿美; 山口 大志; 中村 博彦; 田中 伸哉
日本病理学会会誌, 113, 1, 483, 483, (一社)日本病理学会, 2024年02月
日本語
FFPE検体の質量分析による交感神経節のレビー小体関連分子の探索
宮本 裕也; 種井 善一; 小田 義崇; 王 磊; 津田 真寿美; 田中 伸哉
日本病理学会会誌, 113, 1, 483, 483, (一社)日本病理学会, 2024年02月
日本語
Nerve sheath myxomaのプロテオミクス解析による免疫組織化学マーカー探索
鍵谷 豪太; 種井 善一; 小田 義崇; 王 磊; 津田 真寿美; 飛騨 一利; 田中 伸哉
日本病理学会会誌, 113, 1, 483, 483, (一社)日本病理学会, 2024年02月
日本語
SARS-CoV-2オミクロン株におけるハムスター肺炎モデルの病理組織学的解析
小田 義崇; 津田 真寿美; 王 磊; 種井 善一; 福原 崇介; 佐藤 佳; 田中 伸哉
日本病理学会会誌, 112, 2, 132, 132, (一社)日本病理学会, 2023年10月
日本語
ハイドロゲルPCDMEは、TXNIP上昇を伴うOXPHOS代謝状態の膵臓癌幹細胞を誘導する(Hydrogel PCDME creates pancreatic cancer stem cells in OXPHOS metabolic state with TXNIP elevation)
王 磊; 青木 佑磨; 津田 真寿美; 小田 義崇; 田中 伸哉
日本癌学会総会記事, 82回, 1361, 1361, (一社)日本癌学会, 2023年09月
英語
A Case of Uterine Tumor Resembling Ovarian Sex Cord Tumor With Prominent Myxoid Features.Koki Ise; Zen-Ichi Tanei; Yoshitaka Oda; Satoshi Tanikawa; Hirokazu Sugino; Yusuke Ishida; Masumi Tsuda; Yuko Gotoda; Kunihiko Nishiwaki; Hiroyuki Yanai; Tadashi Hasegawa; Kazuo Nagashima; Shinya Tanaka
International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists, 2023年06月14日,
［国際誌］英語, 研究論文（学術雑誌）, Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare tumor with low malignant potential that commonly occurs in middle age. Although more than 100 cases have been reported to date, myxoid morphology is not well documented. Here, we present a 75-yr-old woman with abnormal vaginal bleeding, with an 8-cm mass in the uterine corpus detected by irregular, high-intensity signaling on T2-weighted imaging. The uterine mass had a glistening mucinous appearance on gross examination. Microscopically, most of the tumor cells were floating in the myxoid stroma. The tumor cells formed clusters or nests with abundant cytoplasm, while some exhibited trabecular or rhabdoid appearances. Immunohistochemically, tumor cells were positive for pancytokeratin (AE1/AE3), α-smooth muscle actin, CD10, progesterone receptor, and some sex cord markers such as calretinin, inhibin, CD56, steroidogenic factor-1. Electron microscopy demonstrated epithelial and sex cord differentiation. This tumor was negative for JAZF1-JJAZ1 fusion gene that is frequently found in low-grade endometrial stromal sarcoma. Fusion genes related to UTROSCT, including NCOA2/3, were not detected by reverse transcription polymerase chain reaction. The present case suggests that UTROSCT should be included in the differential diagnosis of myxoid uterine tumors.
てんかんを発症した72歳女性の右側頭葉内側部病変
種井 善一; 浅野目 卓; 小野 裕介; 小田 義崇; 王 磊; 津田 真寿美; 佐藤 憲市; 水上 裕輔; 田中 伸哉
Brain Tumor Pathology, 40, Suppl., 126, 126, 日本脳腫瘍病理学会, 2023年05月
日本語
脳腫瘍に対する病理研究者としての克服戦略 ハイドロゲルによる髄膜腫幹細胞の探索(Strategies for overcoming the brain tumors presented by pathology researchers Search for meningioma stem cells using hydrogel)
小田 義崇; 津田 真寿美; 湯澤 明夏; 王 磊; 鈴鹿 淳; ハビバ・ウンマ; 種井 善一; モーウリン・クリスチアン; グン 剣萍; 田中 伸哉
日本病理学会会誌, 112, 1, 184, 184, (一社)日本病理学会, 2023年03月
英語
72歳女性のMultinodular and Vacuolating Neuronal Tumor of the cerebrumの1例
寺島 祐樹; 種井 善一; 浅野目 卓; 黒田 花音; 小田 義崇; 谷川 聖; 王 磊; 津田 真寿美; 佐藤 憲市; 田中 伸哉
日本病理学会会誌, 112, 1, 375, 375, (一社)日本病理学会, 2023年03月
日本語
慢性血栓塞栓性肺高血圧症の一剖検例
岸本 佳子; 種井 善一; 青木 健志; 加藤 万里絵; 小田 義崇; 谷川 聖; 津田 真寿美; 田中 伸哉
日本病理学会会誌, 112, 1, 378, 378, (一社)日本病理学会, 2023年03月
日本語
Becker型筋ジストロフィーの兄弟剖検症例の病理組織学的検討
宮本 裕也; 種井 善一; 谷川 聖; 小田 義崇; 津田 真寿美; 加納 崇裕; 横田 卓; 矢部 一郎; 田中 伸哉
日本病理学会会誌, 112, 1, 378, 378, (一社)日本病理学会, 2023年03月
日本語
電子顕微鏡的検討を行ったラブドイド髄膜腫の一症例
戸田 壮太郎; 種井 善一; 京野 里虹; 寺島 祐樹; 谷川 聖; 小田 義崇; 王 磊; 津田 真寿美; 瀬尾 善宣; 田中 伸哉
日本病理学会会誌, 112, 1, 380, 380, (一社)日本病理学会, 2023年03月
日本語
髄膜腫の骨化におけるEpithelial-mesenchymal transitionの関与についての検討
京野 里虹; 種井 善一; 寺島 祐樹; 小田 義崇; 谷川 聖; 王 磊; 津田 真寿美; 田中 伸哉
日本病理学会会誌, 112, 1, 381, 381, (一社)日本病理学会, 2023年03月
日本語
FFPE検体の質量分析による肺小細胞癌の脳転移関連分子の解析
江端 美織; 何 錦涛; 小田 義崇; 谷川 聖; 王 磊; 津田 真寿美; 種井 善一; 田中 伸哉
日本病理学会会誌, 112, 1, 383, 383, (一社)日本病理学会, 2023年03月
日本語
進行性核上性麻痺にTDP43 pathologyを合併した一剖検例
鍵谷 豪太; 種井 善一; 谷川 聖; 小田 義崇; 王 磊; 津田 真寿美; 大槻 美佳; 田中 伸哉
日本病理学会会誌, 112, 1, 379, 379, (一社)日本病理学会, 2023年03月
日本語
拡張型心筋症を発症したEmery-Dreifuss型筋ジストロフィーの一剖検例
佐々木 美羽; 種井 善一; 松島 理明; 石垣 隆弘; 桑原 健; 小田 義嵩; 谷川 聖; 津田 真寿美; 矢部 一郎; 田中 伸哉
日本病理学会会誌, 112, 1, 381, 381, (一社)日本病理学会, 2023年03月
日本語
脳腫瘍に対する病理研究者としての克服戦略 ハイドロゲルによる髄膜腫幹細胞の探索(Strategies for overcoming the brain tumors presented by pathology researchers Search for meningioma stem cells using hydrogel)
小田 義崇; 津田 真寿美; 湯澤 明夏; 王 磊; 鈴鹿 淳; ハビバ・ウンマ; 種井 善一; モーウリン・クリスチアン; グン 剣萍; 田中 伸哉
日本病理学会会誌, 112, 1, 184, 184, (一社)日本病理学会, 2023年03月
英語
TKIs耐性膠芽腫細胞の特性と耐性メカニズムの解析
津田 真寿美; 王 磊; 小田 義崇; 谷川 聖; 種井 善一; 田中 伸哉
日本病理学会会誌, 112, 1, 278, 278, (一社)日本病理学会, 2023年03月
日本語
ハイドロゲルを用いた中皮腫幹細胞の創出および治療標的分子の探索
加藤 万里絵; 杉野 弘和; 津田 真寿美; 王 磊; 種井 善一; 小田 義崇; 谷川 聖; グン 剣萍; 田中 伸哉
日本病理学会会誌, 112, 1, 332, 332, (一社)日本病理学会, 2023年03月
日本語
72歳女性のMultinodular and Vacuolating Neuronal Tumor of the cerebrumの1例
寺島 祐樹; 種井 善一; 浅野目 卓; 黒田 花音; 小田 義崇; 谷川 聖; 王 磊; 津田 真寿美; 佐藤 憲市; 田中 伸哉
日本病理学会会誌, 112, 1, 375, 375, (一社)日本病理学会, 2023年03月
日本語
JCVとCMVの脳幹部重複感染症例におけるウイルスの局在解析
黒田 花音; 種井 善一; 岡崎 ななせ; 工藤 彰彦; 阿部 恵; 寺島 祐樹; 谷川 聖; 津田 真寿美; 矢部 一郎; 田中 伸哉
日本病理学会会誌, 112, 1, 375, 375, (一社)日本病理学会, 2023年03月
日本語
慢性血栓塞栓性肺高血圧症の一剖検例
岸本 佳子; 種井 善一; 青木 健志; 加藤 万里絵; 小田 義崇; 谷川 聖; 津田 真寿美; 田中 伸哉
日本病理学会会誌, 112, 1, 378, 378, (一社)日本病理学会, 2023年03月
日本語
Becker型筋ジストロフィーの兄弟剖検症例の病理組織学的検討
宮本 裕也; 種井 善一; 谷川 聖; 小田 義崇; 津田 真寿美; 加納 崇裕; 横田 卓; 矢部 一郎; 田中 伸哉
日本病理学会会誌, 112, 1, 378, 378, (一社)日本病理学会, 2023年03月
日本語
電子顕微鏡的検討を行ったラブドイド髄膜腫の一症例
戸田 壮太郎; 種井 善一; 京野 里虹; 寺島 祐樹; 谷川 聖; 小田 義崇; 王 磊; 津田 真寿美; 瀬尾 善宣; 田中 伸哉
日本病理学会会誌, 112, 1, 380, 380, (一社)日本病理学会, 2023年03月
日本語
髄膜腫の骨化におけるEpithelial-mesenchymal transitionの関与についての検討
京野 里虹; 種井 善一; 寺島 祐樹; 小田 義崇; 谷川 聖; 王 磊; 津田 真寿美; 田中 伸哉
日本病理学会会誌, 112, 1, 381, 381, (一社)日本病理学会, 2023年03月
日本語
FFPE検体の質量分析による肺小細胞癌の脳転移関連分子の解析
江端 美織; 何 錦涛; 小田 義崇; 谷川 聖; 王 磊; 津田 真寿美; 種井 善一; 田中 伸哉
日本病理学会会誌, 112, 1, 383, 383, (一社)日本病理学会, 2023年03月
日本語
進行性核上性麻痺にTDP43 pathologyを合併した一剖検例
鍵谷 豪太; 種井 善一; 谷川 聖; 小田 義崇; 王 磊; 津田 真寿美; 大槻 美佳; 田中 伸哉
日本病理学会会誌, 112, 1, 379, 379, (一社)日本病理学会, 2023年03月
日本語
拡張型心筋症を発症したEmery-Dreifuss型筋ジストロフィーの一剖検例
佐々木 美羽; 種井 善一; 松島 理明; 石垣 隆弘; 桑原 健; 小田 義嵩; 谷川 聖; 津田 真寿美; 矢部 一郎; 田中 伸哉
日本病理学会会誌, 112, 1, 381, 381, (一社)日本病理学会, 2023年03月
日本語
Geometrical analysis identified morphological features of hydrogel-induced cancer stem cells in synovial sarcoma model cellsZannatul Ferdous; Jean-Emmanuel Clément; Jian Ping Gong; Shinya Tanaka; Tamiki Komatsuzaki; Masumi Tsuda
Biochemical and Biophysical Research Communications, 642, 41, 49, Elsevier BV, 2023年01月,
［査読有り］,
［国際誌］英語, 研究論文（学術雑誌）, Cancer stem cells (CSCs) has been a key target to cure cancer patients completely. Although many CSC markers have been identified, they are frequently cancer type-specific and those expressions are occasionally variable, which becomes an obstacle to elucidate the characteristics of the CSCs. Here we scrutinized the relationship between stemness elevation and geometrical features of single cells. The PAMPS hydrogel was utilized to create the CSCs from mouse myoblast C2C12 and its synovial sarcoma model cells. qRT-PCR analysis confirmed the significant increase in expression levels of Sox2, Nanog, and Oct3/4 on the PAMPS gel, which was higher in the synovial sarcoma model cells. Of note, the morphological heterogeneity was appeared on the PAMPS gel, mainly including flat spreading, elongated spindle, and small round cells, and the Sox2 expression was highest in the small round cells. To examine the role of morphological differences in the elevation of stemness, over 6,400 cells were segmented along with the Sox2 intensity, and 12 geometrical features were extracted at single cell level. A nonlinear mapping of the geometrical features by using uniform manifold approximation and projection (UMAP) clearly revealed the existence of relationship between morphological differences and the stemness elevation, especially for C2C12 and its synovial sarcoma model on the PAMPS gel in which the small round cells possess relatively high Sox2 expression on the PAMPS gel, which supports the strong relationship between morphological changes and the stemness elevation. Taken together, these geometrical features can be useful for morphological profiling of CSCs to classify and distinguish them for understanding of their role in disease progression and drug discovery.
Monitoring fusion kinetics of viral and target cell membranes in living cells using a SARS-CoV-2 spike-protein-mediated membrane fusion assayHesham Nasser; Ryo Shimizu; Jumpei Ito; Akatsuki Saito; Kei Sato; Terumasa Ikeda; Keita Matsuno; Naganori Nao; Hirofumi Sawa; Mai Kishimoto; Shinya Tanaka; Masumi Tsuda; Lei Wang; Yoshikata Oda; Marie Kato; Zannatul Ferdous; Hiromi Mouri; Kenji Shishido; Takasuke Fukuhara; Tomokazu Tamura; Rigel Suzuki; Hayato Ito; Daichi Yamasoba; Izumi Kimura; Naoko Misawa; Keiya Uriu; Yusuke Kosugi; Shigeru Fujita; Mai Suganami; Mika Chiba; Ryo Yoshimura; So Nakagawa; Jiaqi Wu; Akifumi Takaori-Kondo; Kotaro Shirakawa; Kayoko Nagata; Yasuhiro Kazuma; Ryosuke Nomura; Yoshihito Horisawa; Yusuke Tashiro; Yugo Kawai; Takashi Irie; Ryoko Kawabata; MST Monira Begum; Otowa Takahashi; Kimiko Ichihara; Takamasa Ueno; Chihiro Motozono; Mako Toyoda; Yuri L. Tanaka; Erika P. Butlertanaka; Maya Shofa; Kazuo Takayama; Rina Hashimoto; Sayaka Deguchi; Takao Hashiguchi; Tateki Suzuki; Kanako Kimura; Jiei Sasaki; Yukari Nakajima; Kaori Tabata
STAR Protocols, 3, 4, 101773, 101773, Elsevier BV, 2022年12月
研究論文（学術雑誌）
Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 variant.Akatsuki Saito; Tomokazu Tamura; Jiri Zahradnik; Sayaka Deguchi; Koshiro Tabata; Yuki Anraku; Izumi Kimura; Jumpei Ito; Daichi Yamasoba; Hesham Nasser; Mako Toyoda; Kayoko Nagata; Keiya Uriu; Yusuke Kosugi; Shigeru Fujita; Maya Shofa; Mst Monira Begum; Ryo Shimizu; Yoshitaka Oda; Rigel Suzuki; Hayato Ito; Naganori Nao; Lei Wang; Masumi Tsuda; Kumiko Yoshimatsu; Jin Kuramochi; Shunsuke Kita; Kaori Sasaki-Tabata; Hideo Fukuhara; Katsumi Maenaka; Yuki Yamamoto; Tetsuharu Nagamoto; Hiroyuki Asakura; Mami Nagashima; Kenji Sadamasu; Kazuhisa Yoshimura; Takamasa Ueno; Gideon Schreiber; Akifumi Takaori-Kondo; Kotaro Shirakawa; Hirofumi Sawa; Takashi Irie; Takao Hashiguchi; Kazuo Takayama; Keita Matsuno; Shinya Tanaka; Terumasa Ikeda; Takasuke Fukuhara; Kei Sato
Cell host & microbe, 30, 11, 1540, 1555, 2022年11月09日,
［国際誌］英語, 研究論文（学術雑誌）, The SARS-CoV-2 Omicron BA.2.75 variant emerged in May 2022. BA.2.75 is a BA.2 descendant but is phylogenetically distinct from BA.5, the currently predominant BA.2 descendant. Here, we show that BA.2.75 has a greater effective reproduction number and different immunogenicity profile than BA.5. We determined the sensitivity of BA.2.75 to vaccinee and convalescent sera as well as a panel of clinically available antiviral drugs and antibodies. Antiviral drugs largely retained potency, but antibody sensitivity varied depending on several key BA.2.75-specific substitutions. The BA.2.75 spike exhibited a profoundly higher affinity for its human receptor, ACE2. Additionally, the fusogenicity, growth efficiency in human alveolar epithelial cells, and intrinsic pathogenicity in hamsters of BA.2.75 were greater than those of BA.2. Our multilevel investigations suggest that BA.2.75 acquired virological properties independent of BA.5, and the potential risk of BA.2.75 to global health is greater than that of BA.5.
Force-triggered rapid microstructure growth on hydrogel surface for on-demand functionsQifeng Mu; Kunpeng Cui; Zhi Jian Wang; Takahiro Matsuda; Wei Cui; Hinako Kato; Shotaro Namiki; Tomoko Yamazaki; Martin Frauenlob; Takayuki Nonoyama; Masumi Tsuda; Shinya Tanaka; Tasuku Nakajima; Jian Ping Gong
Nature Communications, 13, 1, Springer Science and Business Media LLC, 2022年10月20日
研究論文（学術雑誌）, Abstract
Living organisms share the ability to grow various microstructures on their surface to achieve functions. Here we present a force stamp method to grow microstructures on the surface of hydrogels based on a force-triggered polymerisation mechanism of double-network hydrogels. This method allows fast spatial modulation of the morphology and chemistry of the hydrogel surface within seconds for on-demand functions. We demonstrate the oriented growth of cells and directional transportation of water droplets on the engineered hydrogel surfaces. This force-triggered method to chemically engineer the hydrogel surfaces provides a new tool in addition to the conventional methods using light or heat, and will promote the wide application of hydrogels in various fields.
SARS-CoV-2変異株を用いたハムスター肺炎モデルの病理組織学的解析
小田 義崇; 津田 真寿美; 王 磊; 谷川 聖; 種井 善一; 佐藤 佳; 福原 崇介; 田中 伸哉
日本病理学会会誌, 111, 2, 113, 113, (一社)日本病理学会, 2022年10月
日本語
がんの可塑性・不均一性 バイオマテリアルによるがん幹細胞を誘導する可塑性の制御の解析(Analysis of regulatory mechanism of plasticity towards cancer stemness by hydrogels as biomaterial)
田中 伸哉; 鈴鹿 淳; 小田 義崇; 斎藤 祐介; 王 磊; 津田 真寿美
日本癌学会総会記事, 81回, S6, 3, (一社)日本癌学会, 2022年09月
英語
ハイドロゲルを用いた髄膜腫がん幹細胞マーカーの検索(Identification of novel stemness marker of meningioma by using hydrogel)
小田 義崇; 津田 真寿美; 湯澤 明夏; 王 磊; 谷川 聖; 種井 善一; グン 剣萍; 田中 伸哉
日本癌学会総会記事, 81回, P, 2111, (一社)日本癌学会, 2022年09月
英語
Evaluation of the context of downstream N- and free N-glycomic alterations induced by swainsonine in HepG2 cells.Chie Morikawa; Kanako Sugiura; Keina Kondo; Yurie Yamamoto; Yuma Kojima; Yurika Ozawa; Hiroki Yoshioka; Nobuaki Miura; Jinhua Piao; Kazue Okada; Hisatoshi Hanamatsu; Masumi Tsuda; Shinya Tanaka; Jun-Ichi Furukawa; Yasuro Shinohara
Biochimica et biophysica acta. General subjects, 1866, 9, 130168, 130168, 2022年05月17日,
［国際誌］英語, 研究論文（学術雑誌）, Swainsonine (SWA), a potent inhibitor of class II α-mannosidases, is present in a number of plant species worldwide and causes severe toxicosis in livestock grazing these plants. The mechanisms underlying SWA-induced animal poisoning are not fully understood. In this study, we analyzed the alterations that occur in N- and free N-glycomic upon addition of SWA to HepG2 cells to understand better SWA-induced glycomic alterations. After SWA addition, we observed the appearance of SWA-specific glycomic alterations, such as unique fucosylated hybrid-type and fucosylated M5 (M5F) N-glycans, and a remarkable increase in all classes of Gn1 FNGs. Further analysis of the context of these glycomic alterations showed that (fucosylated) hybrid type N-glycans were not the precursors of these Gn1 FNGs and vice versa. Time course analysis revealed the dynamic nature of glycomic alterations upon exposure of SWA and suggested that accumulation of free N-glycans occurred earlier than that of hybrid-type N-glycans. Hybrid-type N-glycans, of which most were uniquely core fucosylated, tended to increase slowly over time, as was observed for M5F N-glycans. Inhibition of swainsonine-induced unique fucosylation of hybrid N-glycans and M5 by coaddition of 2-fluorofucose caused significant increases in paucimannose- and fucosylated paucimannose-type N-glycans, as well as paucimannose-type free N-glycans. The results not only revealed the gross glycomic alterations in HepG2 cells induced by swainsonine, but also provide information on the global interrelationships between glycomic alterations.
Psammomatous meningioma周囲に脳実質石灰化を認めた一例
岡崎 ななせ; 谷川 聖; 種井 善一; 津田 真寿美; 大澤 崇宏; 松野 吉宏; 田中 伸哉
Brain Tumor Pathology, 39, Suppl., 124, 124, 日本脳腫瘍病理学会, 2022年05月
日本語
Psammomatous meningioma周囲に脳実質石灰化を認めた一例
岡崎 ななせ; 谷川 聖; 種井 善一; 津田 真寿美; 大澤 崇宏; 松野 吉宏; 田中 伸哉
Brain Tumor Pathology, 39, Suppl., 124, 124, 日本脳腫瘍病理学会, 2022年05月
日本語
細胞外基質の電位変化に伴うJCウイルス増殖の制御
谷川 聖; 野々山 貴行; 津田 真寿美; 王 磊; 種井 善一; Gong Jian Ping; 田中 伸哉
日本病理学会会誌, 111, 1, 263, 263, (一社)日本病理学会, 2022年03月
日本語
脊髄capillary hemangiomaの病理像
種井 善一; 津田 真寿美; 小田 義崇; 谷川 聖; 杉野 弘和; 大竹 安史; 今村 博幸; 小柳 泉; 飛騨 一利; 田中 伸哉
日本病理学会会誌, 111, 1, 264, 264, (一社)日本病理学会, 2022年03月
日本語
びまん性大細胞型B細胞性リンパ腫の化学療法中に突然死した1剖検例
加藤 万里絵; 種井 善一; 小島 圭祐; 太田 秀一; ウンマ・ハビバ; 小田 義崇; 谷川 聖; 杉野 弘和; 津田 真寿美; 田中 伸哉
日本病理学会会誌, 111, 1, 308, 308, (一社)日本病理学会, 2022年03月
日本語
内頸動脈瘤術後に急激な意識障害をきたした神経線維腫症1型の一剖検例
京野 里虹; 種井 善一; 岡崎 ななせ; 長内 俊也; 小田 義崇; 谷川 聖; 杉野 弘和; 津田 真寿美; 藤村 幹; 田中 伸哉
日本病理学会会誌, 111, 1, 356, 356, (一社)日本病理学会, 2022年03月
日本語
細胞外基質の電位変化に伴うJCウイルス増殖の制御
谷川 聖; 野々山 貴行; 津田 真寿美; 王 磊; 種井 善一; Gong Jian Ping; 田中 伸哉
日本病理学会会誌, 111, 1, 263, 263, (一社)日本病理学会, 2022年03月
日本語
脊髄capillary hemangiomaの病理像
種井 善一; 津田 真寿美; 小田 義崇; 谷川 聖; 杉野 弘和; 大竹 安史; 今村 博幸; 小柳 泉; 飛騨 一利; 田中 伸哉
日本病理学会会誌, 111, 1, 264, 264, (一社)日本病理学会, 2022年03月
日本語
びまん性大細胞型B細胞性リンパ腫の化学療法中に突然死した1剖検例
加藤 万里絵; 種井 善一; 小島 圭祐; 太田 秀一; ウンマ・ハビバ; 小田 義崇; 谷川 聖; 杉野 弘和; 津田 真寿美; 田中 伸哉
日本病理学会会誌, 111, 1, 308, 308, (一社)日本病理学会, 2022年03月
日本語
内頸動脈瘤術後に急激な意識障害をきたした神経線維腫症1型の一剖検例
京野 里虹; 種井 善一; 岡崎 ななせ; 長内 俊也; 小田 義崇; 谷川 聖; 杉野 弘和; 津田 真寿美; 藤村 幹; 田中 伸哉
日本病理学会会誌, 111, 1, 356, 356, (一社)日本病理学会, 2022年03月
日本語
Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron variant.Rigel Suzuki; Daichi Yamasoba; Izumi Kimura; Lei Wang; Mai Kishimoto; Jumpei Ito; Yuhei Morioka; Naganori Nao; Hesham Nasser; Keiya Uriu; Yusuke Kosugi; Masumi Tsuda; Yasuko Orba; Michihito Sasaki; Ryo Shimizu; Ryoko Kawabata; Kumiko Yoshimatsu; Hiroyuki Asakura; Mami Nagashima; Kenji Sadamasu; Kazuhisa Yoshimura; Hirofumi Sawa; Terumasa Ikeda; Takashi Irie; Keita Matsuno; Shinya Tanaka; Takasuke Fukuhara; Kei Sato
Nature, 603, 7902, 700, 705, 2022年03月,
［査読有り］,
［国際誌］英語, 研究論文（学術雑誌）, The emergence of the Omicron variant of SARS-CoV-2 is an urgent global health concern1. In this study, our statistical modelling suggests that Omicron has spread more rapidly than the Delta variant in several countries including South Africa. Cell culture experiments showed Omicron to be less fusogenic than Delta and than an ancestral strain of SARS-CoV-2. Although the spike (S) protein of Delta is efficiently cleaved into two subunits, which facilitates cell-cell fusion2,3, the Omicron S protein was less efficiently cleaved compared to the S proteins of Delta and ancestral SARS-CoV-2. Furthermore, in a hamster model, Omicron showed decreased lung infectivity and was less pathogenic compared to Delta and ancestral SARS-CoV-2. Our multiscale investigations reveal the virological characteristics of Omicron, including rapid growth in the human population, lower fusogenicity and attenuated pathogenicity.
Engineering of an electrically charged hydrogel implanted into a traumatic brain injury model for stepwise neuronal tissue reconstructionSatoshi Tanikawa; Yuki Ebisu; Tomáš Sedlačík; Shingo Semba; Takayuki Nonoyama; Akira Hirota; Taiga Takahashi; Kazushi Yamaguchi; Masamichi Imajo; Hinako Kato; Takuya Nishimura; Zen-ichi Tanei; Masumi Tsuda; Tomomi Nemoto; Jian Ping Gong; Shinya Tanaka
Cold Spring Harbor Laboratory, 2022年02月19日
Abstract
Neural regeneration is extremely difficult to achieve. In traumatic brain injuries, the loss of brain parenchyma volume hinders neural regeneration. In this study, neuronal tissue engineering was performed by using electrically charged hydrogels composed of cationic and anionic monomers in a 1:1 ratio (C1A1 hydrogel), which served as an effective scaffold for the attachment of neural stem cells (NSCs). In the 3D environment of porous C1A1 hydrogels engineered by the cryogelation technique, NSCs differentiated into neuroglial cells. The C1A1 porous hydrogel was implanted into brain defects in a mouse traumatic damage model. The VEGF-immersed C1A1 porous hydrogel promoted host-derived vascular network formation together with the infiltration of macrophages/microglia and astrocytes into the gel. Furthermore, the stepwise transplantation of GFP-labeled NSCs supported differentiation to glial and neuronal cells. Therefore, this two-step method for neural regeneration may become a new approach for therapeutic brain tissue reconstruction after brain damage in the future.
One Sentence Summary
Brain tissue reconstruction using charged hydrogel and stepwise NCS injection
Novel rapid immunohistochemistry using an alternating current electric field identifies Rac and Cdc42 activation in human colon cancer FFPE tissues.Masumi Tsuda; Runa Horio; Lei Wang; Tomoko Takenami; Jun Moriya; Jun Suzuka; Hirokazu Sugino; Zenichi Tanei; Mishie Tanino; Shinya Tanaka
Scientific reports, 12, 1, 1733, 1733, 2022年02月02日,
［国際誌］英語, 研究論文（学術雑誌）, It is important to determine the activation status of Rac and Cdc42 in cancer tissues for the prediction of metastasis and patient prognosis. However, it has been impossible to detect their spatial activation on formalin-fixed paraffin embedded (FFPE) surgical specimens thus far. Here, we established a novel detection technique for activated Rac/Cdc42 in human colon cancer FFPE tissues by using a p21-activated kinase (PAK)-Rac binding domain (RBD) detection probe fused with glutathione S-transferase (GST), designated GST-PAK-RBD, and novel rapid-immunohistochemistry (R-IHC) systems using noncontact alterating-current electric field mixing, although there is a technical limitation in that it may not distinguish between Rac members and Cdc42. In 50 cases of colon cancer, various activation patterns of Rac/Cdc42 were observed, which were designated plasma membrane, cytoplasm, mixed pattern, and polarized distribution. The activity was striking in the invasive fronts of tumors and significantly correlated with tumor invasion properties evaluated by TNM classification. Of note, in tissue microarray (TMA) samples, 29 of 33 cases demonstrated higher Rac1/Cdc42 activity in the tumor area than the corresponding normal mucosa. In addition, positive correlations were detected between Rac/Cdc42 activity and clinicopathological factors such as venous and lymphatic vessel invasion. These results suggest that understanding Rac and Cdc42 activations in cancer tissues would be valuable as an option for molecular therapy as personalized medicine.
Aberrant expression of MYD88 via RNA-controlling CNOT4 and EXOSC3 in colonic mucosa impacts generation of colonic cancer.Masumi Tsuda; Misa Noguchi; Tsuyoshi Kurai; Yuji Ichihashi; Koki Ise; Lei Wang; Yusuke Ishida; Mishie Tanino; Satoshi Hirano; Masahiro Asaka; Shinya Tanaka
Cancer science, 112, 12, 5100, 5113, 2021年12月,
［国際誌］英語, 研究論文（学術雑誌）, In 2020, the worldwide incidence and mortality of colorectal cancer (CRC) were third and second, respectively. As the 5-y survival rate is low when CRC is diagnosed at an advanced stage, a reliable method to predict CRC susceptibility is important for preventing the onset and development and improving the prognosis of CRC. Therefore, we focused on the normal colonic mucosa to investigate changes in gene expression that may induce subsequent genetic alterations that induce malignant transformation. Comprehensive gene expression profiling in the normal mucosa adjacent to colon cancer (CC) compared with tissue from non-colon cancer patients was performed. PCR arrays and qRT-PCR revealed that the expression of 5 genes involved in the immune response, including MYD88, was increased in the normal mucosa of CC patients. The expression levels of MYD88 were strikingly increased in precancerous normal mucosa specimens, which harbored no somatic mutations, as shown by immunohistochemistry. Microarray analysis identified 2 novel RNA-controlling molecules, EXOSC3 and CNOT4, that were significantly upregulated in the normal mucosa of CC patients and were clearly visualized in the nuclei. Forced expression of EXOSC3 and CNOT4 in human colonic epithelial cells increased the expression of IFNGR1, MYD88, NFκBIA, and STAT3 and activated ERK1/2 and JNK in 293T cells. Taken together, these results suggested that, in the inflamed mucosa, EXOSC3- and CNOT4-mediated RNA stabilization, including that of MYD88, may trigger the development of cancer and can serve as a potential predictive marker and innovative treatment to control cancer development.
Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation.Akatsuki Saito; Takashi Irie; Rigel Suzuki; Tadashi Maemura; Hesham Nasser; Keiya Uriu; Yusuke Kosugi; Kotaro Shirakawa; Kenji Sadamasu; Izumi Kimura; Jumpei Ito; Jiaqi Wu; Kiyoko Iwatsuki-Horimoto; Mutsumi Ito; Seiya Yamayoshi; Samantha Loeber; Masumi Tsuda; Lei Wang; Seiya Ozono; Erika P Butlertanaka; Yuri L Tanaka; Ryo Shimizu; Kenta Shimizu; Kumiko Yoshimatsu; Ryoko Kawabata; Takemasa Sakaguchi; Kenzo Tokunaga; Isao Yoshida; Hiroyuki Asakura; Mami Nagashima; Yasuhiro Kazuma; Ryosuke Nomura; Yoshihito Horisawa; Kazuhisa Yoshimura; Akifumi Takaori-Kondo; Masaki Imai; Shinya Tanaka; So Nakagawa; Terumasa Ikeda; Takasuke Fukuhara; Yoshihiro Kawaoka; Kei Sato
Nature, 602, 7896, 300, 306, 2021年11月25日,
［査読有り］,
［国際誌］英語, 研究論文（学術雑誌）, During the current SARS-CoV-2 pandemic, a variety of mutations have accumulated in the viral genome, and currently, four variants of concern (VOCs) are considered potentially hazardous to human society1. The recently emerged B.1.617.2/Delta VOC is closely associated with the COVID-19 surge that occurred in India in the spring of 20212. However, its virological properties remain unclear. Here, we show that the B.1.617.2/Delta variant is highly fusogenic and notably more pathogenic than prototypic SARS-CoV-2 in infected hamsters. The P681R mutation in the spike protein, which is highly conserved in this lineage, facilitates spike protein cleavage and enhances viral fusogenicity. Moreover, we demonstrate that the P681R-bearing virus exhibits higher pathogenicity than its parental virus. Our data suggest that the P681R mutation is a hallmark of the virological phenotype of the B.1.617.2/Delta variant and is associated with enhanced pathogenicity.
ハイドロゲルを用いた新規髄膜腫治療標的分子の検討(Analysis of novel therapeutic target for meningioma using hydrogel)
小田 義崇; 津田 真寿美; 湯澤 明夏; 王 磊; Umma Habiba; 杉野 弘和; 種井 善一; グン 剣萍; 田中 伸哉
日本病理学会会誌, 110, 2, 110, 110, (一社)日本病理学会, 2021年10月
英語
ハイドロゲルを用いた新規髄膜腫治療標的分子の検討(Analysis of novel therapeutic target for meningioma using hydrogel)
小田 義崇; 津田 真寿美; 湯澤 明夏; 王 磊; Umma Habiba; 杉野 弘和; 種井 善一; グン 剣萍; 田中 伸哉
日本病理学会会誌, 110, 2, 110, 110, (一社)日本病理学会, 2021年10月
英語
Comprehensive molecular profiling of pulmonary pleomorphic carcinoma.Masaaki Nagano; Shinji Kohsaka; Takuo Hayashi; Toshihide Ueno; Shinya Kojima; Aya Shinozaki-Ushiku; Shigeki Morita; Masumi Tsuda; Shinya Tanaka; Toshiya Shinohara; Yuko Omori; Fumiko Sugaya; Hiroaki Kato; Yoshiaki Narita; Jun Nakajima; Kenji Suzuki; Kazuya Takamochi; Hiroyuki Mano
NPJ precision oncology, 5, 1, 57, 57, 2021年06月22日,
［査読有り］,
［国際誌］英語, 研究論文（学術雑誌）, Information regarding the molecular features of pulmonary pleomorphic carcinoma (PPC) is insufficient. Here, we performed next-generation sequencing to determine the genomic and transcriptomic profiles of PPC. We sequenced the DNAs and RNAs of 78 specimens from 52 patients with PPC. We analyzed 15 PPC cases to identify intratumoral differences in gene alterations, tumor mutation burden (TMB), RNA expression, and PD-L1 expression between epithelial and sarcomatoid components. The genomic alterations of six cases of primary tumors and corresponding metastatic tumors were analyzed. KRAS mutations (27%) were the most common driver mutations, followed by EGFR (8%), and MET (8%) mutations. Epithelial and sarcomatoid components shared activating driver mutations, and there were no significant differences in CD274 expression or TMB between the two components. However, PD-L1 was highly expressed in the sarcomatoid component of several cases compared with the epithelial component. Primary and metastatic tumors shared oncogenic mutations among genes such as KRAS and TP53, and additional alterations including NOTCH4 mutations were specifically identified in the metastatic regions. Our data suggest that therapies targeting activating driver mutations may be effective for patients with PPC and that immune checkpoint inhibitors of PPC may be recommended after careful assessment of PD-L1 expression in each epithelial and sarcomatoid component.
Loss of H3K27 trimethylation is frequent in IDH1-R132H but not in non-canonical IDH1/2 mutated and 1p/19q codeleted oligodendroglioma: a Japanese cohort studyUmma Habiba; Hirokazu Sugino; Roumyana Yordanova; Koki Ise; Zen-ichi Tanei; Yusuke Ishida; Satoshi Tanikawa; Shunsuke Terasaka; Ken-ichi Sato; Yuuta Kamoshima; Masahiko Katoh; Motoo Nagane; Junji Shibahara; Masumi Tsuda; Shinya Tanaka
Acta Neuropathologica Communications, 9, 1, 95, 95, Springer Science and Business Media LLC, 2021年05月21日,
［査読有り］,
［国際誌］英語, 研究論文（学術雑誌）,
AbstractOligodendrogliomas are defined by mutation in isocitrate dehydrogenase (NADP(+)) (
IDH)1/2 genes and chromosome 1p/19q codeletion. World Health Organisation diagnosis endorses testing for 1p/19q codeletion to distinguish IDH mutant (Mut) oligodendrogliomas from astrocytomas because these gliomas require different treatments and they have different outcomes. Several methods have been used to identify 1p/19q status; however, these techniques are not routinely available and require substantial infrastructure investment. Two recent studies reported reduced immunostaining for trimethylation at lysine 27 on histone H3 (H3K27me3) in IDH Mut 1p/19q codeleted oligodendroglioma. However, the specificity of H3K27me3 immunostaining in this setting is controversial. Therefore, we developed an easy-to-implement immunohistochemical surrogate for IDH Mut glioma subclassification and evaluated a validated adult glioma cohort. We screened 145 adult glioma cases, consisting of 45 IDH Mut and 1p/19q codeleted oligodendrogliomas, 30 IDH Mut astrocytomas, 16 IDH wild-type (Wt) astrocytomas, and 54 IDH Wt glioblastomas (GBMs). We compared immunostaining with DNA sequencing and fluorescent in situ hybridization analysis and assessed differences in H3K27me3 staining between oligodendroglial and astrocytic lineages and between IDH1-R132H and non-canonical (non-R132H) IDH1/2 Mut oligodendroglioma. A loss of H3K27me3 was observed in 36/40 (90%) of IDH1-R132H Mut oligodendroglioma. In contrast, loss of H3K27me3 was never seen in IDH1-R132L or IDH2-mutated 1p/19q codeleted oligodendrogliomas. IDH Mut astrocytoma, IDH Wt astrocytoma and GBM showed preserved nuclear staining in 87%, 94%, and 91% of cases, respectively. A high recursive partitioning model predicted probability score (0.9835) indicated that the loss of H3K27me3 is frequent to IDH1-R132H Mut oligodendroglioma. Our results demonstrate H3K27me3 immunohistochemical evaluation to be a cost-effective and reliable method for defining 1p/19q codeletion along with IDH1-R132H and ATRX immunostaining, even in the absence of 1p/19q testing.
脊髄capillary hemangiomaの臨床病理学的特徴
種井 善一; 津田 真寿美; 谷川 聖; 杉野 弘和; 石田 雄介; 大竹 安史; 今村 博幸; 小柳 泉; 飛騨 一利; 田中 伸哉
Brain Tumor Pathology, 38, Suppl., 119, 119, 日本脳腫瘍病理学会, 2021年05月
日本語
Rapid reprogramming of tumour cells into cancer stem cells on double-network hydrogelsJun Suzuka; Masumi Tsuda; Lei Wang; Shinji Kohsaka; Karin Kishida; Shingo Semba; Hirokazu Sugino; Sachiyo Aburatani; Martin Frauenlob; Takayuki Kurokawa; Shinya Kojima; Toshihide Ueno; Yoshihiro Ohmiya; Hiroyuki Mano; Kazunori Yasuda; Jian Ping Gong; Shinya Tanaka
Nature Biomedical Engineering, 5, 8, 914, 925, Springer Science and Business Media LLC, 2021年03月29日,
［査読有り］研究論文（学術雑誌）
ハイドロゲルによる癌幹細胞性の誘導を利用した髄膜腫の新規治療標的分子の検索
小田 義崇; 津田 真寿美; 湯澤 明夏; 王 磊; 杉野 弘和; 鈴鹿 淳; グン 剣萍; 田中 伸哉
日本病理学会会誌, 110, 1, 225, 225, (一社)日本病理学会, 2021年03月
日本語
Involvement of BMP and Wnt Signals Leadingto Epithelial-Mesenchymal Transition in Colon Adenocarcinoma with Heterotopic Ossification.Naho Katono; Masumi Tsuda; Jun Suzuka; Yoshitaka Oda; Lei Wang; Zen-Ichi Tanei; Mishie Tanino; Takanobu Ohata; Eisuke Nagabuchi; Yusuke Ishida; Shunsuke Kimura; Toshihiko Iwanaga; Shinya Tanaka
Annals of clinical and laboratory science, 51, 2, 271, 276, 2021年03月,
［査読有り］,
［国際誌］英語, 研究論文（学術雑誌）, Here we present the case of a 73-year-old male with rectal adenocarcinoma with heterotopic ossification (HO). Cancer-associated HO in the digestive system is rare. Thus, the precise mechanism and clinicopathological significance of HO have not yet been defined. To clarify the molecular mechanisms of HO, we analyzed the expression levels of signaling molecules related to epithelial-mesenchymal transition (EMT) that lead to ossification in the tumor cells discriminating the ossified area (HO-area) and non-ossified area (non-HO area). Expression levels of BMP4 were elevated in both areas, whereas BMP2 was specifically increased in the HO-area by qPCR. EMT-related molecules such as Snail and Slug were especially higher in the HO-area. By immunohistochemistry, the expression of Smad4, nuclear staining of β-catenin, and the phosphorylated form of GSK-3β were detectable in both areas, and GSK-3β was highly phosphorylated in the HO-area. The tumor growth rate was extremely high, with the Ki-67 labeling index at 90%. In the HO-area, osteoblasts with alkaline phosphatase expression were distributed surrounding the tumor cells. This is the first demonstration of the involvement of EMT in HO of colon cancer through BMP/SMAD and WNT/β-catenin signaling pathways, which are especially prominent in the HO-area leading to the osteogenic property.
CMKLR1は肝癌幹細胞標的治療のための候補分子である
谷 道夫; 津田 真寿美; 鈴鹿 淳; 王 磊; 武冨 紹信; 田中 伸哉
日本癌学会総会記事, 79回, PJ14, 1, (一社)日本癌学会, 2020年10月
英語
CMKLR1は肝癌幹細胞標的治療のための候補分子である
谷 道夫; 津田 真寿美; 鈴鹿 淳; 王 磊; 武冨 紹信; 田中 伸哉
日本癌学会総会記事, 79回, PJ14, 1, (一社)日本癌学会, 2020年10月
英語
バイオマテリアルによる肝癌幹細胞の新規誘導法の開発とその解析
谷 道夫; 津田 真寿美; 鈴鹿 淳; 王 磊; 杉野 弘和; 谷川 聖; 石田 雄介; グン 剣萍; 田中 伸哉; 武冨 紹信
日本外科学会定期学術集会抄録集, 120回, DP, 6, (一社)日本外科学会, 2020年08月
日本語
バイオマテリアルによる肝癌幹細胞の新規誘導法の開発とその解析
谷 道夫; 津田 真寿美; 鈴鹿 淳; 王 磊; 杉野 弘和; 谷川 聖; 石田 雄介; グン 剣萍; 田中 伸哉; 武冨 紹信
日本外科学会定期学術集会抄録集, 120回, DP, 6, (一社)日本外科学会, 2020年08月
日本語
Integrin α4 Mediates ATDC5 Cell Adhesion to Negatively Charged Synthetic Polymer Hydrogel Leading to Chondrogenic DifferentiatioDaiki Hashimoto; Shingo Semba; Masumi Tsuda; Takayuki Kurokawa; Nobuto Kitamura; Kazunori Yasuda; Jian Ping Gong; Shinya Tanaka
Biochemical and Biophysical Research Communications, 528, 1, 120, 126, 2020年05月,
［査読有り］,
［国際誌］英語, 研究論文（学術雑誌）, Negatively charged synthetic hydrogels have been known to facilitate various cellular responses including cell adhesion, proliferation, and differentiation; however, the molecular mechanism of hydrogel-dependent control of cell behavior remains unclear. Recently, we reported that negatively charged poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) gel induces chondrogenic differentiation of ATDC5 cells via novel protein reservoir function. In this study, we identified the cell adhesion molecules binding to PAMPS gels that act as mechanoreceptors. First, we performed a pull-down assay by particle gels using cell membrane proteins of ATDC5, and found that multiple membrane proteins bound to the PAMPS gel, whereas the uncharged poly(N,N'-dimethylacrylamide) gel as control did not bind to any membrane proteins. Western blot analysis indicated differential binding of integrin (ITG) isoforms to the PAMPS gel, in which the α4 isoform, but not α5 and αv, efficiently bound to the PAMPS gel. ITG α4 knockdown decreased cell spreading of ATDC5 on PAMPS gels, whereas the enhanced expression increased the behavior. Furthermore, ITG α4 depletion suppressed PAMPS gel-induced expression of bone morphogenic protein (BMP) 4 contributing to chondrogenic differentiation, in concordance with the reduction of ERK activation. These results demonstrated that membrane protein binding to PAMPS gels occurred in a charge-dependent manner, and that ITG α4 plays a crucial role in cell spreading on PAMPS gels and acts as a mechanoreceptor triggering cellular signaling leads to chondrogenic differentiation.
Signaling adaptor protein Crk is involved in malignant feature of pancreatic cancer associated with phosphorylation of c-Met.Satoko Uemura; Lei Wang; Masumi Tsuda; Jun Suzuka; Satoshi Tanikawa; Hirokazu Sugino; Toru Nakamura; Tomoko Mitsuhashi; Satoshi Hirano; Shinya Tanaka
Biochemical and biophysical research communications, 524, 2, 378, 384, 2020年04月02日,
［査読有り］,
［国際誌］英語, 研究論文（学術雑誌）, Signaling adaptor protein Crk has been shown to play an important role in various human cancers. Crk links tyrosine kinases and guanine nucleotide exchange factors (GEFs) such as C3G and Dock180 to activate small G-proteins Rap and Rac, respectively. In pancreatic cancer, various molecular targeted therapies have provided no significant therapeutic benefit for the patients so far due to constitutive activation of KRAS by frequent KRAS mutation. Therefore, the establishment of novel molecular targeted therapy in KRAS-independent manner is required. Here, we investigated a potential of Crk as a therapeutic target in pancreatic cancer. Immunohistochemistry on human pancreatic cancer specimens revealed that the patients with high expression of Crk had a worse prognosis than those with low expression. We established Crk-knockdown pancreatic cancer cells by siRNA using PANC-1, AsPC-1, and MIA PaCa-2 cells, which showed decreased cell proliferation, invasion, and adhesion. In Crk-knockdown pancreatic cancer cells, the decrease of c-Met phosphorylation was observed. In the orthotopic xenograft model, Crk depletion prolonged survival of mice significantly. Thus, signaling adaptor protein Crk is involved in malignant potential of pancreatic cancer associated with decrease of c-Met phosphorylation, and Crk can be considered to be a potential therapeutic molecular target.
ハイドロゲルを用いた髄膜腫治療標的分子の検索
小田 義崇; 津田 真寿美; 湯澤 明夏; 王 磊; 杉野 弘和; 鈴鹿 淳; 廣田 聡; 今城 正道; グン 剣萍; 田中 伸哉
日本病理学会会誌, 109, 1, 319, 319, (一社)日本病理学会, 2020年03月
日本語
Emery-Dreifuss型筋ジストロフィーに伴う心不全の1剖検例
五味川 龍; 石田 雄介; 桑原 健; 石垣 隆弘; 谷川 聖; 小田 義崇; 王 磊; 杉野 弘和; 津田 真寿美; 田中 伸哉
日本病理学会会誌, 109, 1, 492, 492, (一社)日本病理学会, 2020年03月
日本語
前立腺癌のGleason pattern評価のためのSemantic segmentationモデル及びRaspberry Pi端末を用いた応用
遠田 建; 伊勢 昂生; 石田 雄介; 桑原 健; 谷川 聖; 小田 義崇; 王 磊; 杉野 弘和; 津田 真寿美; 田中 伸哉
日本病理学会会誌, 109, 1, 496, 496, (一社)日本病理学会, 2020年03月
日本語
新規変異BRAFV601K変異を認める良性脳腫瘍(毛様体性星細胞腫)の一例
榎枝 未紗; 小田 義崇; 津田 真寿美; 飛弾 一利; 杉野 弘和; 谷川 聖; 鈴鹿 淳; 王 磊; 石田 雄介; 田中 伸哉
日本病理学会会誌, 109, 1, 497, 497, (一社)日本病理学会, 2020年03月
日本語
Emery-Dreifuss型筋ジストロフィーに伴う心不全の1剖検例
五味川 龍; 石田 雄介; 桑原 健; 石垣 隆弘; 谷川 聖; 小田 義崇; 王 磊; 杉野 弘和; 津田 真寿美; 田中 伸哉
日本病理学会会誌, 109, 1, 492, 492, (一社)日本病理学会, 2020年03月
日本語
前立腺癌のGleason pattern評価のためのSemantic segmentationモデル及びRaspberry Pi端末を用いた応用
遠田 建; 伊勢 昂生; 石田 雄介; 桑原 健; 谷川 聖; 小田 義崇; 王 磊; 杉野 弘和; 津田 真寿美; 田中 伸哉
日本病理学会会誌, 109, 1, 496, 496, (一社)日本病理学会, 2020年03月
日本語
新規変異BRAFV601K変異を認める良性脳腫瘍(毛様体性星細胞腫)の一例
榎枝 未紗; 小田 義崇; 津田 真寿美; 飛弾 一利; 杉野 弘和; 谷川 聖; 鈴鹿 淳; 王 磊; 石田 雄介; 田中 伸哉
日本病理学会会誌, 109, 1, 497, 497, (一社)日本病理学会, 2020年03月
日本語
Role of Dimerized C16orf74 in Aggressive Pancreatic Cancer: A Novel Therapeutic Target.Toshihiro Kushibiki; Toru Nakamura; Masumi Tsuda; Takahiro Tsuchikawa; Koji Hontani; Kazuho Inoko; Mizuna Takahashi; Toshimichi Asano; Keisuke Okamura; Soichi Murakami; Yo Kurashima; Yuma Ebihara; Takehiro Noji; Yoshitsugu Nakanishi; Kimitaka Tanaka; Nako Maishi; Katsunori Sasaki; Woong-Ryeon Park; Toshiaki Shichinohe; Kyoko Hida; Shinya Tanaka; Satoshi Hirano
Molecular cancer therapeutics, 19, 1, 187, 198, 2020年01月,
［査読有り］,
［国際誌］英語, 研究論文（学術雑誌）, Over the past 30 years, the therapeutic outcome for pancreatic ductal adenocarcinoma (PDAC) has remained stagnant due to the lack of effective treatments. We performed a genome-wide analysis to identify novel therapeutic targets for PDAC. Our analysis showed that Homo sapiens chromosome 16 open reading frame 74 (C16orf74) was upregulated in most patients with PDAC and associated with poor prognosis. Previously, we demonstrated that C16orf74 interacts with the catalytic subunit alpha of protein phosphatase 3 and plays an important role in PDAC invasion. However, the pathophysiologic function of C16orf74 is still unclear. In this study, through the analysis of C16orf74 interaction, we demonstrate a new strategy to inhibit the growth and invasion of PDAC. C16orf74 exists in the homodimer form under the cell membrane and binds integrin αVβ3 and is also involved in invasion by activating Rho family (Rac1) and MMP2. Considering that this dimeric form was found to be involved in the function of C16orf74, we designed an 11R-DB (dimer block) cell-permeable dominant-negative peptide that inhibits the dimer form of C16orf74. 11R-DB suppressed invasion and proliferation of PDAC cell lines by inhibiting phosphorylation of Akt and mTOR and also by inactivation of MMP2. 11R-DB also showed antitumor effects in an orthotopic xenograft model and peritoneal metastasis model. Thus, this study demonstrates that dimerized C16orf74, present in the cell membrane, is involved in pancreatic cancer invasion and proliferation. In addition, the C16orf74 dimer block cell-permeable peptide (11R-DB) has a potent therapeutic effect on PDAC in vitro and in vivo.
Exosomes containing ErbB2/CRK induce vascular growth in premetastatic niches and promote metastasis of bladder cancer.Yoshida K; Tsuda M; Matsumoto R; Semba S; Wang L; Sugino H; Tanino M; Kondo T; Tanabe K; Tanaka S
Cancer science, 110, 7, 2119, 2132, 2019年07月,
［査読有り］,
［責任著者］,
［国際誌］英語, Locally advanced and metastatic invasive bladder cancer (BC) has a poor prognosis, and no advanced therapies beyond cisplatin-based combination chemotherapy have been developed. Therefore, it is an urgent issue to elucidate the underlying mechanisms of tumor progression and metastasis of invasive BC for the development of new therapeutic strategies. Here, we clarified a novel role of exosomes containing ErbB2 and CRK in a formation of premetastatic niches and subsequent metastases. CRK adaptors were overexpressed in invasive UM-UC-3 BC cells. In an orthotopic xenograft model, metastases to lung, liver, and bone of UM-UC-3 cells were completely abolished by CRK elimination. Mass spectrometry analysis identified that ErbB2 was contained in UM-UC-3-derived exosomes in a CRK-dependent manner; the exosomes significantly increased proliferation and invasion properties of low-grade 5637 BC cells and HUVECs through FAK and PI3K/AKT signaling pathways. In athymic mice educated with UM-UC-3-derived exosomes, i.v. implanted UM-UC-3 cells were trapped with surrounding PKH67-labeled exosomes in lung and led to development of lung metastasis with disordered vascular proliferation. In contrast, exosomes derived from CRK-depleted BC cells failed to induce these malignant features. Taken together, we showed that CRK adaptors elevated the expression of ErbB2/3 in BC cells, and these tyrosine kinase/adaptor units were transferred from host BC cells to metastatic recipient cells by exosomes, leading to vascular leakiness and proliferation and contributing to the formation of distant metastasis. Thus, CRK intervention with ErbB2/3 blockade might be a potent therapeutic strategy for patients with ErbB2 overexpressing advanced and metastatic BC.
miR-23a-HOXD10経路はglial-mesenchymal transitionを介して膠芽腫浸潤能を亢進する
津田 真寿美; 谷地 一博; 高阪 真路; 王 磊; 小田 義崇; 谷川 聖; 大場 雄介; 田中 伸哉
日本病理学会会誌, 108, 1, 311, 312, (一社)日本病理学会, 2019年04月
日本語
バイオマテリアルによる肝癌幹細胞の新規誘導法
谷 道夫; 津田 真寿美; 鈴鹿 淳; 王 磊; 杉野 弘和; 谷川 聖; 石田 雄介; グン 剣萍; 田中 伸哉; 武冨 紹信
日本外科学会定期学術集会抄録集, 119回, PS, 6, (一社)日本外科学会, 2019年04月
日本語
病理IT化、情報化とAI研究 病理診断と人工知能 スタートアップから脳腫瘍への応用まで
石田 雄介; 桑原 健; 小田 義崇; 谷川 聖; 杉野 弘和; 津田 真寿美; 田中 伸哉
日本病理学会会誌, 108, 1, 192, 192, (一社)日本病理学会, 2019年04月
日本語
解剖で偶然見つかった無症候性胸髄内神経鞘腫の一例
有田 梨乃; 谷川 聖; 津田 真寿美; 石田 雄介; 杉野 弘和; 田中 伸哉
日本病理学会会誌, 108, 1, 459, 459, (一社)日本病理学会, 2019年04月
日本語
髄膜腫におけるTERTプロモーター遺伝子変異の検討
久世 瑞穂; 小田 義崇; 津田 真寿美; 湯澤 明夏; 谷川 聖; 杉野 弘和; 石田 雄介; 田中 伸哉
日本病理学会会誌, 108, 1, 463, 463, (一社)日本病理学会, 2019年04月
日本語
次世代シーケンサーを用いた肺原発多形癌の遺伝子変異解析
長野 匡晃; 高阪 真路; 牛久 綾; 林 大久生; 田中 伸哉; 津田 真寿美; 篠原 敏也; 大森 優子; 菅谷 文子; 加藤 弘明; 成田 吉明; 高持 一矢; 鈴木 健司; 中島 淳; 間野 博行
日本呼吸器外科学会雑誌, 33, 3, RO1, 3, (NPO)日本呼吸器外科学会, 2019年04月, ［査読有り］
日本語
"Integrated diagnosis" of pilocytic astrocytoma: Molecular diagnostic procedure for an unusual case.Ishida Y; Tsuda M; Sawamura Y; Fujii K; Murai H; Horiuchi N; Orba Y; Sawa H; Hall WW; Nagashima K; Tanaka S
Pathology international, 68, 12, 694, 699, 2018年12月,
［査読有り］,
［国際誌］英語, 研究論文（学術雑誌）, A 24 year-old female presented with a mass lesion in the right temporal lobe. This case was difficult to diagnose using histological and immunological methods and therefore molecular analyses were applied to provide a definitive diagnosis. The tumor was well-demarcated, partially cystic, and irregularly-enhanced on gadolinium-enhanced T1-weighted magnetic resonance images. Pathologically, a large part of the tumor consisted of cells with fine cytoplasmic processes on a myxoid and mucinous background. Cells formed a microcystic structure around the mucinous tissue. Numerous eosinophilic granular bodies, but not Rosenthal fibers, were present. The solid and compact regions of the tumor were composed of fasciculation of dense fibrous glial tissues and occasional multinucleated giant cells. Tumor cells and their fragmented cytoplasmic processes were positively stained with GFAP, while eosinophilic granular bodies were both positive and negative. Xanthomatous changes were not detected and the reticulin fibers were restricted to vascular tissues. The MIB1 index was scored as approximately 10%. In molecular analyses of BRAF, the KIAA1549-BRAF (K16-B9) fusion gene was detected in all tumor regions, whereas BRAF V600E mutation was not detected by either conventional Sanger sequencing or the Eprobe-PCR method. Based on the results of the molecular analyses, this case was diagnosed as pilocytic astrocytoma.
馬尾原発の髄外性形質細胞腫の1例
小田 義崇; 杉野 弘和; 小柳 泉; 谷川 聖; 石田 雄介; 津田 真寿美; 田中 伸哉
Brain Tumor Pathology, 35, Suppl., 177, 177, 日本脳腫瘍病理学会, 2018年09月
日本語
新規技術を用いた新しい研究アプローチ 高分子ハイドロゲルによる癌幹細胞へのリプログラミング誘導技術
津田 真寿美; 鈴鹿 淳; 王 磊; 仙葉 慎吾; 油谷 幸代; 黒川 孝幸; 近江谷 克裕; 安田 和則; グン 剣萍; 田中 伸哉
日本病理学会会誌, 107, 1, 217, 217, (一社)日本病理学会, 2018年04月
日本語
神経再生工学における両電荷を有するハイドロゲルの開発
谷川 聖; 仙葉 慎吾; 津田 真寿美; 王 磊; 谷野 美智枝; 石田 雄介; 杉野 弘和; 鈴鹿 淳; 田中 伸哉
日本病理学会会誌, 107, 1, 329, 329, (一社)日本病理学会, 2018年04月
日本語
悪性神経膠腫におけるIDH1遺伝子変異による放射線照射後変化の解析(Analysis of the effect of IDH1 mutation on the radiosensitivity in malignant glioma)
北崎 アリサ; 谷野 美智枝; 九笹 めい; 杉野 弘和; 王 磊; 石田 雄介; 津田 真寿美; 五十嵐 香織; 曽我 朋義; 田中 伸哉
日本病理学会会誌, 107, 1, 379, 379, (一社)日本病理学会, 2018年04月
英語
脳腫瘍組織像の画像解析と遺伝子プロファイルに対応したDeep-Learning法の応用
石田 雄介; 杉野 弘和; 谷野 美智枝; 津田 真寿美; 田中 伸哉
日本病理学会会誌, 107, 1, 380, 380, (一社)日本病理学会, 2018年04月
日本語
悪性中皮腫におけるOTUB1の役割
九笹 めい; 谷野 美智枝; 北崎 アリサ; 杉野 弘和; 石田 雄介; 王 磊; 津田 真寿美; 高澤 啓; 平野 博嗣; 田中 伸哉
日本病理学会会誌, 107, 1, 406, 406, (一社)日本病理学会, 2018年04月
日本語
中枢神経系に生じたメトトレキサート関連リンパ増殖性疾患の一例
杉野 弘和; 佐藤 憲市; 笠井 康弘; 孫 慧; 石田 雄介; 谷野 美智枝; 津田 真寿美; 松野 吉宏; 田中 伸哉
日本病理学会会誌, 107, 1, 449, 449, (一社)日本病理学会, 2018年04月
日本語
脳死肝移植後に感染源不明の敗血症を繰り返し死亡した一例の死後画像および病理解剖所見
伊勢 昂生; 山下 たんぽぽ; 石田 雄介; 桑原 健; 川村 典生; 菊池 穏香; 杉野 弘和; 谷野 美智枝; 津田 真寿美; 田中 伸哉
日本病理学会会誌, 107, 1, 530, 530, (一社)日本病理学会, 2018年04月
日本語
Tough and Self‐Recoverable Thin Hydrogel Membranes for Biological Applications
Ye YN; Frauenlob M; Wang L; Tsuda M; Sun TL; Cui K; Takahashi R; Ahang HJ; Nakajima T; Nonoyama T; Kurokawa T; Tanaka S; Gong JP
Advanced Functional Materials, 29, 1801489, 1, 11, 2018年03月, ［査読有り］
Chorionic Gonadotropin-β Modulates Epithelial-Mesenchymal Transition in Colorectal Carcinoma Metastasis.Kawamata F; Nishihara H; Homma S; Kato Y; Tsuda M; Konishi Y; Wang L; Kohsaka S; Liu C; Yoshida T; Tanino M; Tanaka S; Kawamura H; Kamiyama T; Taketomi A
The American journal of pathology, 188, 1, 204, 215, 2018年01月,
［査読有り］,
［国際誌］英語, 研究論文（学術雑誌）, Ectopic production of free β human chorionic gonadotropin (hCGβ) has been associated with aggressive behavior in non-trophoblastic tumors. hCGβ shares common evolutionary sequences with transforming growth factor-β (TGF-β), which represents a major driving force of epithelial-to-mesenchymal transition (EMT). In this study, we examined the biological roles of hCGβ during EMT and its clinical significance in colorectal cancer (CRC) progression. Eighty CRC specimens and 54 preoperative serum samples were analyzed. hCGβ-overexpressing human CRC cell lines were examined for invasiveness and tumorigenicity, and the expression of EMT-associated genes was investigated. In human CRC, histologic hCGβ positivity [13/80 (16.3%)] was lower than serologic hCGβ positivity [13/54 (24.1%)]. However, it was significantly correlated with several clinicopathological features and unfavorable outcome (P < 0.05). hCGβ-overexpressing cell lines had increased invasiveness, migratory ability, and metastatic potential in mice (P < 0.01). Western blot, PCR, and microarray analyses showed hCGβ altered expression of EMT-related genes, including E-cadherin, phosphorylated SMAD2, SNAIL, and TWIST. hCGβ-induced SNAIL and TWIST overexpression levels were reversible by type I and type II TGF-β receptor inhibitors (P < 0.05). hCGβ thus induces EMT via the TGF-β signaling pathway, and it may represent a molecular target in CRC treatment.
ハイドロゲルを用いた癌幹細胞新規誘導法の開発
鈴鹿 淳; 津田 真寿美; 王 磊; 仙葉 愼吾; 油谷 幸代; 黒川 孝幸; 近江谷 克裕; 安田 和則; きょう 剣萍; 田中 伸哉
生命科学系学会合同年次大会, 2017年度, [1P, 0964], 生命科学系学会合同年次大会運営事務局, 2017年12月
日本語
悪性中皮腫におけるOTUB1の発現
九笹 めい; 谷野 美智枝; 北崎 アリサ; 杉野 弘和; 石田 雄介; 王 磊; 津田 真寿美; 高澤 啓; 平野 博嗣; 田中 伸哉
日本癌学会総会記事, 76回, P, 3277, 日本癌学会, 2017年09月
英語
多形黄色星細胞腫におけるBRAF遺伝子変異(BRAF V600E)とp16の発現の検討
谷野 美智枝; 南條 博; 津田 真寿美; 杉野 弘和; 王 磊; 石田 雄介; 田中 伸哉
日本癌学会総会記事, 76回, P, 3317, 日本癌学会, 2017年09月
英語
悪性神経膠腫においてIDH1遺伝子変異は放射線照射後のアポトーシスを亢進する
北崎 アリサ; 谷野 美智枝; 九笹 めい; 杉野 弘和; 王 磊; 石田 雄介; 仙葉 慎吾; 津田 真寿美; 五十嵐 香織; 曽我 朋義; 田中 伸哉
日本癌学会総会記事, 76回, P, 3323, 日本癌学会, 2017年09月
英語
皮膚悪性黒色腫に対するオプジーボ投与後に出現し免疫染色にてS-100陰性を呈した転移性脳腫瘍の1例
石田 雄介; 高橋 達郎; 佐藤 行真; 池田 正起; 守田 玲菜; 武井 英博; 木村 太一; 津田 真寿美; 谷野 美智枝; 田中 伸哉
日本病理学会会誌, 106, 1, 477, 477, (一社)日本病理学会, 2017年03月
日本語
Aldo-keto reductase 1C1 induced by interleukin-1β mediates the invasive potential and drug resistance of metastatic bladder cancer cells.Matsumoto R; Tsuda M; Yoshida K; Tanino M; Kimura T; Nishihara H; Abe T; Shinohara N; Nonomura K; Tanaka S
Scientific reports, 6, 34625, 34625, 2016年10月04日,
［査読有り］,
［国際誌］英語, 研究論文（学術雑誌）, In treating bladder cancer, determining the molecular mechanisms of tumor invasion, metastasis, and drug resistance are urgent to improving long-term patient survival. One of the metabolic enzymes, aldo-keto reductase 1C1 (AKR1C1), plays an essential role in cancer invasion/metastasis and chemoresistance. In orthotopic xenograft models of a human bladder cancer cell line, UM-UC-3, metastatic sublines were established from tumors in the liver, lung, and bone. These cells possessed elevated levels of EMT-associated markers, such as Snail, Slug, or CD44, and exhibited enhanced invasion. By microarray analysis, AKR1C1 was found to be up-regulated in metastatic lesions, which was verified in metastatic human bladder cancer specimens. Decreased invasion caused by AKR1C1 knockdown suggests a novel role of AKR1C1 in cancer invasion, which is probably due to the regulation of Rac1, Src, or Akt. An inflammatory cytokine, interleukin-1β, was found to increase AKR1C1 in bladder cancer cell lines. One particular non-steroidal anti-inflammatory drug, flufenamic acid, antagonized AKR1C1 and decreased the cisplatin-resistance and invasion potential of metastatic sublines. These data uncover the crucial role of AKR1C1 in regulating both metastasis and drug resistance; as a result, AKR1C1 should be a potent molecular target in invasive bladder cancer treatment.
合成PAMPSゲルはタンパク質レザバーとして機能し、軟骨細胞ATDC5細胞に軟骨形成分化を誘導する(Synthetic PAMPS gel functions as protein reservoir, which induces a chondrogenic differentiation of chondrocytic ATDC5 cells)
仙葉 愼吾; 後藤 佳子; 北村 信人; 黒野 定; 近江谷 克裕; 津田 真寿美; 黒川 孝幸; グン・チェンピン; 田中 伸哉; 安田 和則
日本生化学会大会プログラム・講演要旨集, 89回, [1T18, 405)], (公社)日本生化学会, 2016年09月
英語
BRAF V600E変異検索およびKIAA1549-BRAF融合遺伝子検索により診断に至った若年成人発症毛様細胞性星細胞腫
石田 雄介; 津田 真寿美; 澤村 豊; 村井 宏; 堀内 成好; 長嶋 和郎; 田中 伸哉
日本病理学会会誌, 105, 2, 75, 75, (一社)日本病理学会, 2016年09月
日本語
Identification and analysis of CXCR4-positive synovial sarcoma-initiating cellsKimura T; Wang L; Tabu K; Tsuda M; Tanino M; Maekawa A; Nishihara H; Hiraga H; Taga T; Oda Y; Tanaka S
Oncogene, 35, 30, 3932, 3943, Oncogene, 2016年07月28日
Synovial sarcoma accounts for almost 10% of all soft tissue sarcomas, and its prognosis is poor with 5-year survival rates at 36%. Thus, new treatments and therapeutic targets for synovial sarcoma are required. Tumor-initiating cells have been defined by the ability for self-renewal and multipotent differentiation, and they exhibit higher tumorigenic capacity, chemoresistance and radiation resistance, expecting to be a new therapeutic target. In synovial sarcoma, the presence of such stemness remains largely unclear; thus, we analyzed whether synovial sarcoma possessed tumor-initiating cells and explored specific markers, and we discovered that synovial sarcoma cell lines possessed heterogeneity by way of containing a sphere-forming subpopulation highly expressing NANOG, OCT4 and SOX2. By expression microarray analysis, CXCR4 was identified to be highly expressed in the sphere subpopulation and correlated with stem-cell-Associated markers. Inhibition of CXCR4 suppressed the cell proliferation of synovial sarcoma cell lines in vitro. The tumor-initiating ability of CXCR4-positive cells was demonstrated by xenograft propagation assay. CXCR4-positive cells showed higher tumorigenicity
Adaptor protein CRK induces epithelial-mesenchymal transition and metastasis of bladder cancer cells through HGF/c-Met feedback loop.Ryuji Matsumoto; Masumi Tsuda; Lei Wang; Nako Maishi; Takashige Abe; Taichi Kimura; Mishie Tanino; Hiroshi Nishihara; Kyoko Hida; Yusuke Ohba; Nobuo Shinohara; Katsuya Nonomura; Shinya Tanaka
Cancer science, 106, 6, 709, 17, 2015年06月,
［査読有り］,
［国際誌］英語, 研究論文（学術雑誌）, We have previously reported that an adaptor protein CRK, including CRK-I and CRK-II, plays essential roles in the malignant potential of various aggressive human cancers, suggesting the validity of targeting CRK in molecular targeted therapy of a wide range of cancers. Nevertheless, the role of CRK in human bladder cancer with marked invasion, characterized by distant metastasis and poor prognosis, remains obscure. In the present study, immunohistochemistry indicated a striking enhancement of CRK-I/-II, but not CRK-like, in human bladder cancer tissues compared to normal urothelium. We established CRK-knockdown bladder cancer cells using 5637 and UM-UC-3, which showed a significant decline in cell migration, invasion, and proliferation. It is noteworthy that an elimination of CRK conferred suppressed phosphorylation of c-Met and the downstream scaffold protein Gab1 in a hepatocyte growth factor-dependent and -independent manner. In epithelial-mesenchymal transition-related molecules, E-cadherin was upregulated by CRK elimination, whereas N-cadherin, vimentin, and Zeb1 were downregulated. A similar effect was observed following treatment with c-Met inhibitor SU11274. Depletion of CRK significantly decreased cell proliferation of 5637 and UM-UC-3, consistent with reduced activity of ERK. An orthotopic xenograft model with bioluminescent imaging revealed that CRK knockdown significantly attenuated not only tumor volume but also the number of circulating tumor cells, resulted in a complete abrogation of metastasis. Taken together, this evidence uncovered essential roles of CRK in invasive bladder cancer through the hepatocyte growth factor/c-Met/CRK feedback loop for epithelial-mesenchymal transition induction. Thus, CRK might be a potent molecular target in bladder cancer, particularly for preventing metastasis, leading to the resolution of clinically longstanding critical issues.
C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinomaFutoshi Kawamata; Shigenori Homma; Hirofumi Kamachi; Takahiro Einama; Yasutaka Kato; Masumi Tsuda; Shinya Tanaka; Masahiro Maeda; Kazunori Kajino; Okio Hino; Norihiko Takahashi; Toshiya Kamiyama; Hiroshi Nishihara; Akinobu Taketomi; Satoru Todo
JOURNAL OF GASTROENTEROLOGY, 49, 1, 81, 92, 2014年01月,
［査読有り］英語, 研究論文（学術雑誌）
脳腫瘍の現代病理学 BRAF異常とグリオーマ
田中 伸哉; 谷野 美智枝; 津田 真寿美; 石田 雄介; 木村 太一; 西原 広史; 長嶋 和郎
日本病理学会会誌, 102, 1, 203, 203, (一社)日本病理学会, 2013年04月
日本語
Biosensors for BCR-ABL activity and their application to cancer
Yusuke Ohba; Stephanie Darmanin; Tatsuaki Mizutani; Masumi Tsuda; Takeshi Kondo
Biosensors and Cancer, 268, 283, CRC Press, 2012年01月01日
英語, 論文集(書籍)内論文
[Visualization of cellular signaling by fluorescent proteins].Ohba Y; Tsuda M
Nihon yakurigaku zasshi. Folia pharmacologica Japonica, 138, 1, 13, 17, 1, 2011年07月,
［査読有り］日本語, 下村脩博士によって，<I>Aequorea victoria</I> の発光器官から緑色蛍光タンパク質GFP（green fluorescent protein）が発見され，1992年にそのcDNAが単離されて以来，生細胞イメージングは生物学研究の必須ツールになっている．GFPはcDNAの細胞導入のみで，生理的環境下での目的タンパク質の局在や局在変化を可視化し，種々のカラーバリアントが入手可能な現在では複数のタンパク質の挙動の同時観察も可能である．また，フェルスター共鳴エネルギー移動（FRET: Förster resonance energy transfer）や蛍光タンパク質再構成法（BiFC: bimolecular fluorescence complementation）等の技術を用いることで，個々のタンパク質の局在や動態のみならずタンパク質の質的変化，つまりタンパク質間相互作用・構造変化等の時間的・空間的な変化の解析も可能である．これらの手法は細胞内シグナル伝達のダイナミクスを解析するために，最も適したツールと言っても過言ではない．本稿では，蛍光イメージングの基礎や応用例の紹介と各実験系が持つ得失を比較し，それぞれの実験系が何を可視化するのに適しているかを議論したい．
Elmo1 inhibits ubiquitylation of Dock180Y Makino; M Tsuda; S Ichihara; T Watanabe; M Sakai; H Sawa; K Nagashima; S Hatakeyama; S Tanaka
JOURNAL OF CELL SCIENCE, 119, 5, 923, 932, 2006年03月,
［査読有り］英語, 研究論文（学術雑誌）
Analysis of transforming activity of human synovial sarcoma-associated chimeric protein SYT-SSX1 bound to chromatin remodeling factor hBRM/hSNF2Nagai, M; Tanaka, S; Tsuda, M; Endo, S; Kato, H; Sonobe, H; Minami , A; Hiraga, H; Yamawaki, S; Nishihara, H; Sawa, H; Nagashima, K
Proc.Natl.Acad.Sci.USA, 98, 7, 3843, 3848, 2001年
脳腫瘍の細胞像と病理像種井善一; 小田義崇; 王磊; 王磊; 津田真寿美; 津田真寿美; 田中伸哉; 田中伸哉, 日本臨床細胞学会雑誌(Web), 63, 2024年
「首下がり」症候群を伴う筋萎縮性側索硬化症の初期段階における剖検所見Tanikawa Satoshi; Tanino Mishie; Wang Lei; Ishikawa Marin; Miyazaki Masaya; Tsuda Masumi; Tsuda Masumi; Tsuda Masumi; Orba Yasuko; Sawa Hirofumi; Matoba Kotarou; Nakamura Nishio; Nagashima Kazuo; Hall William W.; Tanaka Shinya; Tanaka Shinya; Tanaka Shinya, Neuropathology (Web), 39, 5, 2019年
低分化胃癌におけるSox10発現の臨床病理学的検討
石川 麻倫; 西原 広史; 林 秀幸; 木村 太一; 石田 雄介; 王 磊; 津田 真寿美; 谷野 美智枝; 坂本 直哉; 田中 伸哉, 日本消化器病学会雑誌, 115, 臨増総会, A375, A375, 2018年03月
(一財)日本消化器病学会, 日本語
Expression of OTUB1 in human malignant mesotheliomaMei Kuzasa; Mishie Tanino; Arisa Kitazaki; Hirokazu Sugino; Yusuke Ishida; Lei Wang; Masumi Tsuda; Akira Takasawa; Hiroshi Hirano; Shinya Tanaka, CANCER SCIENCE, 109, 1109, 1109, 2018年01月
英語, 研究発表ペーパー・要旨（国際会議）
骨形成に再利用される合成HAp系インプラントの同位体顕微鏡観察野々山貴行; 鈴木裕貴; 木山竜二; WANG Lei; 津田真寿美; 安田和則; 田中伸哉; 永田康祐; 藤田龍介; 坂本直哉; 圦本尚義; GONG Jian Ping, 日本セラミックス協会秋季シンポジウム講演予稿集(CD-ROM), 31st, 2018年
アダプター分子CRKはエクソソームのErbB2を制御し、膀胱癌の増殖・転移を亢進する
津田 真寿美; 吉田 一彦; 松本 隆児; 近藤 恒徳; 篠原 信雄; 田中 伸哉, 日本癌学会総会記事, 76回, E, 1059, 2017年09月
日本癌学会, 英語
miR-23aによる膠芽腫の浸潤能亢進分子メカニズムの解明
津田 真寿美; 谷地 一博; 高阪 真路; 三浪 友輔; 王 磊; 木村 太一; 谷野 美智枝; 西原 広史; 田中 伸哉, Brain Tumor Pathology, 34, Suppl., 093, 093, 2017年05月
日本脳腫瘍病理学会, 日本語
グリオーマの日常診断におけるintegrated diagnosisの現状
谷野 美智枝; 谷川 聖; 石田 雄介; 木村 太一; 岡田 佳奈子; 佐藤 真実; 津田 真寿美; 西原 広史; 長嶋 和郎; 田中 伸哉, Brain Tumor Pathology, 34, Suppl., 102, 102, 2017年05月
日本脳腫瘍病理学会, 日本語
髄膜腫におけるPOLR2A遺伝子変異の検討
鈴木 佑季; 津田 真寿美; 湯澤 明夏; 木村 太一; 石田 雄介; 谷野 美智枝; 西原 広史; 田中 伸哉, 日本病理学会会誌, 106, 1, 508, 508, 2017年03月
(一社)日本病理学会, 日本語
髄膜発生孤在性線維性腫瘍/血管周皮腫(SFT/HPC)におけるNAB2-STAT6融合遺伝子の解析
四宮 万里絵; 津田 真寿美; 湯澤 明夏; 木村 太一; 石田 雄介; 谷野 美智枝; 西原 広史; 田中 伸哉, 日本病理学会会誌, 106, 1, 508, 509, 2017年03月
(一社)日本病理学会, 日本語
浸潤性膀胱癌の転移および薬剤耐性獲得におけるAKR1C1の役割
津田 真寿美; 松本 隆児; 吉田 一彦; 谷野 美智枝; 木村 太一; 西原 広史; 阿部 崇重; 篠原 信雄; 野々村 克也; 田中 伸哉, 日本病理学会会誌, 106, 1, 340, 340, 2017年03月
(一社)日本病理学会, 日本語
合成ハイドロゲルが誘導する軟骨分化促進機序の解明仙葉愼吾; 後藤佳子; 北村信人; 北村信人; 黒野定; 近江谷克裕; 津田真寿美; 津田真寿美; 黒川孝幸; 黒川孝幸; 田中伸哉; 田中伸哉; GONG Jian Ping; GONG Jian Ping; 安田和則, 再生医療, 16, 267, 2017年02月01日
日本語
チロシンキナーゼ阻害剤耐性膠芽腫細胞における腫瘍幹細胞性獲得とSFRP1の関連性
鈴鹿 淳; 津田 真寿美; 王 磊; 谷野 美智枝; 木村 太一; 西原 広史; 田中 伸哉, 日本癌学会総会記事, 75回, J, 2036, 2016年10月
日本癌学会, 英語
肺癌においてアダプター蛋白CrkはTGF-βシグナルと協調してEMTを誘導する
谷野 美智枝; Elimansuri Aiman; Mahabir Roshan; 王 磊; 木村 太一; 西原 広史; 津田 真寿美; 田中 伸哉, 日本癌学会総会記事, 75回, P, 1092, 2016年10月
日本癌学会, 英語
AKR1C1は膀胱癌の浸潤・転移と薬剤耐性を制御する
津田 真寿美; 松本 隆児; 吉田 一彦; 谷野 美智枝; 木村 太一; 西原 広史; 阿部 崇重; 篠原 信雄; 野々村 克也; 田中 伸哉, 日本癌学会総会記事, 75回, E, 1057, 2016年10月
日本癌学会, 英語
多形黄色星細胞腫におけるBRAFV600Eの遺伝子変異とリン酸化ERK及びp16の発現の検討
谷野 美智枝; 津田 真寿美; 石田 雄介; 木村 太一; 西原 広史; 長嶋 和郎; 田中 伸哉, 日本病理学会会誌, 105, 2, 75, 75, 2016年09月
(一社)日本病理学会, 日本語
脳腫瘍術中迅速病理診断における迅速免疫染色装置(ラピート)の使用経験
森谷 純; 谷野 美智枝; 木村 太一; 石田 雄介; 津田 真寿美; 西原 広史; 田中 伸哉, 日本病理学会会誌, 105, 2, 76, 76, 2016年09月
(一社)日本病理学会, 日本語
Synthetic PAMPS gel functions as protein reservoir, which induces a chondrogenic differentiation of chondrocytic ATDC5 cells(和訳中)
仙葉 愼吾; 後藤 佳子; 北村 信人; 黒野 定; 近江谷 克裕; 津田 真寿美; 黒川 孝幸; グン・チェンピン; 田中 伸哉; 安田 和則, 日本生化学会大会プログラム・講演要旨集, 89回, [1T18, 05(1P, 2016年09月
(公社)日本生化学会, 英語
髄膜発生SFT/HPCのNAB2-STAT6融合遺伝子パターンと臨床病理学的検討
湯澤 明夏; 西原 広史; 王 磊; 津田 真寿美; 木村 太一; 谷野 美智枝; 田中 伸哉, Brain Tumor Pathology, 33, Suppl., 102, 102, 2016年05月
日本脳腫瘍病理学会, 日本語
臨床的シークエンス分析による髄膜腫の予後的影響(Prognostic impact for meningioma by clinical sequence system)
湯澤 明夏; 西原 広史; 山口 秀; 毛利 普美; 王 磊; 木村 太一; 津田 真寿美; 谷野 美智枝; 佐藤 典宏; 田中 伸哉, 日本病理学会会誌, 105, 1, 356, 356, 2016年04月
(一社)日本病理学会, 英語
CRKアダプター蛋白質はHGF/c-Metフィードバックループを介して膀胱癌のEMTと転移を誘導する
王 磊; 松本 隆児; 津田 真寿美; 間石 奈湖; 安部 崇重; 木村 太一; 谷野 美智枝; 西原 広史; 樋田 京子; 大場 雄介; 篠原 信雄; 田中 伸哉, 日本癌学会総会記事, 74回, J, 1142, 2015年10月
日本癌学会, 英語
膀胱癌転移巣におけるAldo-keto reductase(AKR)1C1の発現亢進は浸潤能と抗癌剤耐性能を反映する
松本 隆児; 津田 真寿美; 安部 崇重; 篠原 信雄; 田中 伸哉; 野々村 克也, 日本泌尿器科学会総会, 103回, 471, 471, 2015年04月
(一社)日本泌尿器科学会総会事務局, 日本語
迅速免疫組織化学染色を用いた膠腫におけるIDH1染色の術中応用
廣嶋 優子; 南條 博; 前田 大地; 後藤 明輝; 笹嶋 寿郎; 清水 宏明; 南谷 佳弘; 津田 真寿美; 田中 伸哉, 日本病理学会会誌, 104, 1, 296, 296, 2015年03月
(一社)日本病理学会, 日本語
インフルエンザウイルスのCa2+シグナルを介した宿主細胞侵入機構
藤岡 容一朗; 津田 真寿美; 南保 明日香; 服部 ともえ; 佐々木 純子; 佐々木 雄彦; 宮崎 忠昭; 大場 雄介, 日本細胞生物学会大会講演要旨集, 66回, 103, 103, 2014年05月
(一社)日本細胞生物学会, 日本語
インフルエンザウイルスのCa2+シグナルを介した宿主細胞侵入機構
藤岡 容一朗; 津田 真寿美; 南保 明日香; 服部 ともえ; 佐々木 純子; 佐々木 雄彦; 宮崎 忠昭; 大場 雄介, 日本細胞生物学会大会講演要旨集, 66回, 146, 146, 2014年05月
(一社)日本細胞生物学会, 日本語
大腸癌浸潤・転移におけるchorionic gonadotropin-βの機能解析とその臨床応用
川俣 太; 本間 重紀; 西原 広史; 長津 明久; 旭 よう; 蒲池 浩文; 高橋 典彦; 津田 真寿美; 田中 伸哉; 神山 俊哉; 武冨 紹信, 日本大腸肛門病学会雑誌, 67, 3, 240, 240, 2014年03月
(一社)日本大腸肛門病学会, 日本語
Ras-PI3Kシグナルが制御する外来因子取込み機構の解析
藤岡 容一朗; 津田 真寿美; 服部 ともえ; 佐々木 純子; 佐々木 雄彦; 宮崎 忠昭; 大場 雄介, 日本生理学雑誌, 76, 2, 81, 81, 2014年03月
(一社)日本生理学会, 日本語
消化器癌におけるERC/Mesothelinの分子病理学的検討(Molecular and clinicopathological analysis for ERC/Mesothelin in digestive cancers)
西原 広史; 川俣 太; 永生 高広; 津田 真寿美; 王 磊; 樋野 興夫; 武冨 紹信; 田中 伸哉, 日本癌学会総会記事, 72回, 308, 308, 2013年10月
日本癌学会, 英語
Ras-PI3Kシグナルが制御する外来因子取込み機構の解析
藤岡 容一朗; 津田 真寿美; 服部 ともえ; 佐々木 純子; 佐々木 雄彦; 大場 雄介, 日本細胞生物学会大会講演要旨集, 65回, 153, 153, 2013年05月
(一社)日本細胞生物学会, 日本語
SrcおよびAuroraキナーゼ2重阻害による滑膜肉腫の相乗的in vivo抗腫瘍効果(Dual inhibition of Src and Aurora kinases abrogates tumor growth, invasion, and angiogenesis of synovial sarcoma in vivo)
津田 真寿美; 新井 隆太; 渡部 琢哉; 尾瀬 農之; 小布施 力史; 前仲 勝実; 三浪 明男; 大場 雄介, 日本癌学会総会記事, 70回, 274, 274, 2011年09月
日本癌学会, 英語
慢性骨髄白血病に対する分子標的治療薬の反応性・抵抗性判定試験(Seeing response and resistance to BCR-ABL inhibition in chronic myeloid leukemia)
大場 雄介; 金安 顕子; 水谷 龍明; ダルマニン・ステファニー; 近藤 健; 津田 真寿美, 日本癌学会総会記事, 70回, 242, 242, 2011年09月
日本癌学会, 英語
RANKLは口腔癌細胞のインテグリンα2の発現と細胞接着を亢進する(RANKL upregulates integrin α2 expression and cell adhesion in oral cancer cells)
大場 雄介; 山田 珠希; 藤岡 容一朗; 甲斐原 拓真; 戸塚 泰則; 進藤 正信; 津田 真寿美, 日本細胞生物学会大会講演要旨集, 63回, 156, 156, 2011年05月
(一社)日本細胞生物学会, 英語
染色体・核・遺伝子発現・シグナル伝達 インフルエンザウイルスは、カルシウムシグナル伝達によって、Ras-PI3K-仲介エンドサイトーシスを活性化する(Signal transduction/Chromosome/Cell nucleus/Gene expression Influenza viruses activate Ras-PI3K-mediated endocytosis via calcium signaling)
藤岡 容一朗; 津田 真寿美; 服部 ともえ; 佐々木 純子; 佐々木 雄彦; 宮崎 忠昭; 大場 雄介, 日本細胞生物学会大会講演要旨集, 63回, 112, 112, 2011年05月
(一社)日本細胞生物学会, 英語
RANKL発現は腫瘍形成とEMTを亢進する(RANKL expression promotes tumorigenesis and epithelial mesenchymal transition)
山田 珠希; 津田 真寿美; 戸塚 靖則; 進藤 正信; 大場 雄介, 日本癌学会総会記事, 69回, 494, 494, 2010年08月
日本癌学会, 英語
RANKLは微小環境特異的に発現し細胞接着・EMT・腫瘍形成を促進する生体内特異的機能マーカーである(RANKJL expression specifically observed in vivo promotes cell adhesion, epithelial mesenchymal transition, and tumor progression)
山田 珠希; 津田 真寿美; 進藤 正信; 戸塚 泰則; 大場 雄介, 日本細胞生物学会大会講演要旨集, 62回, 196, 196, 2010年05月
(一社)日本細胞生物学会, 英語
メンブレントラフィック Ras-PI3Kシグナル経路がエンドサイトーシスとインフルエンザ感染を調節する(Membrane traffic The Ras-PI3K signaling pathway mediates endocytosis and the incorporation of influenza viruses)
藤岡 容一朗; 津田 真寿美; 服部 ともえ; 佐々木 純子; 佐々木 雄彦; 宮崎 忠昭; 大場 雄介, 日本細胞生物学会大会講演要旨集, 62回, 117, 117, 2010年05月
(一社)日本細胞生物学会, 英語
生体内腫瘍形成における腫瘍微小環境誘発性のRANKL発現の必要性(Requirement for tumor microenvironment-induced RANKL expression in the tumorigenesis in vivo)
山田 珠希; 津田 真寿美; 戸塚 靖則; 進藤 正信; 大場 雄介, 日本癌学会総会記事, 68回, 47, 47, 2009年08月
日本癌学会, 英語
FRETバイオセンサーを用いたCML分子標的薬剤の薬効評価系の構築(A FRET-based biosensor for the evaluation of the efficacy of molecular targeted drugs for chronic myeloid leukemia)
水谷 龍明; 近藤 健; ダルマニン・ステファニー; 津田 真寿美; 田中 伸哉; 浅香 正博; 大場 雄介, 日本癌学会総会記事, 68回, 457, 457, 2009年08月
日本癌学会, 英語
EGFシグナル伝達はPTHrPの発現を誘導し、口腔癌細胞の悪性化に関与する(EGF signaling regulates PTHrP expression and malignancies in oral cancer cells)
山田 珠希; 津田 真寿美; 大場 雄介; 戸塚 靖則; 進藤 正信, 日本癌学会総会記事, 66回, 501, 501, 2007年08月
日本癌学会, 英語
