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  日本消化器内視鏡学会

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  日本臨床血液学会

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  肝臓

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  日本消化器病学会

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  日本内科学会

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• ライフサイエンス   腫瘍診断、治療学  

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• 札幌医科大学   医学部 腫瘍内科学講座   講師  

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• Notch signaling genes and CD8+ T-cell dynamics: Their contribution to immune-checkpoint inhibitor therapy in oral squamous cell carcinoma: A retrospective study.

  Kazuhiro Ogi, Takahiro Iwamoto, Takashi Sasaya, Koyo Nishiyama, Takaaki Tokura, Takanori Sasaki, Hironari Dehari, Yohei Arihara, Kazuyuki Murase, Masato Saito, Masanori Someya, Kohichi Takada, Akihiro Miyazaki

  Cancer medicine   13 ( 5 ) e6985  2024年03月  [国際誌]

  　概要を見る

  BACKGROUND: Aberrant Notch signaling pathway has been related with the tumorigenesis in head and neck region, involving oral cavity. Here, we report the correlation between mutations in the Notch signaling pathway and CD8+ T-cell infiltration via PD-L1, which lead to enhanced antitumor immunity and may target for immune-checkpoint inhibitors (ICIs) therapy. METHODS: This retrospective study analyzed the results of immunohistochemical staining for PD-L1 and CD8+ T-cell infiltration in 10 patients and whole-exome sequencing (WES) was conducted on five of these patients to identify frequently mutated genes. RESULTS: Four of 10 patients were positive for PD-L1 and CD8+ T. By analyzing WES in three of these four patients, we notably identified the mutations of NOTCH1, FBXW7, and noncoding RNA intronic mutation in NOTCH2NLR in two of these three patients. This study may enable better selection of ICI therapy with CD8+ T-cell infiltration via PD-L1 expression for oral squamous cell carcinoma patients with mutations in Notch signaling pathway.

  DOI PubMed

• Stage IVa進行食道癌におけるDocetaxel/CDGP/5-FU・放射線同時併用療法(DNF-R)の予後解析

  佐藤 昌則, 大沼 啓之, 早坂 尚貴, 濱口 孝太, 村瀬 和幸, 高田 弘一, 宮西 浩嗣, 加藤 淳二, 染谷 正則, 坂田 耕一

  北海道医学雑誌 ( 北海道医学会 )  98 ( 2 ) 139 - 139  2023年11月

• Coefficient of variation of T2-weighted MRI may predict the prognosis of malignant peripheral nerve sheath tumor.

  Makoto Emori, Hiroyuki Tsuchie, Hiroyuki Takashima, Atsushi Teramoto, Yasutaka Murahashi, Yoshinori Imura, Hidetatsu Outani, Sho Nakai, Satoshi Takenaka, Ryosuke Hirota, Naoya Nakahashi, Junya Shimizu, Kazuyuki Murase, Akira Takasawa, Hiroyuki Nagasawa, Shintaro Sugita, Kohichi Takada, Tadashi Hasegawa, Seiji Okada, Naohisa Miyakoshi, Toshihiko Yamashita

  Skeletal radiology    2023年09月  [国際誌]

  　概要を見る

  BACKGROUND: We investigated whether non-enhancement MRI features, including measurement of the heterogeneity of the tumor with MR T2 imaging by calculating coefficient of variation (CV) values, were associated with the prognosis of non-metastatic malignant peripheral nerve sheath tumors (MPNST). METHODS: This retrospective study included 42 patients with MPNST who had undergone surgical resection (mean age, 50 years ± 21; 20 male participants). Non-enhancement MR images were evaluated for signal intensity heterogeneity on T1- and T2-weighted imaging, tumor margin definition on T1- and T2-weighted imaging, peritumoral edema on T2-weight imaging, and CV. We measured the signal intensities of MR T2-weighted images and calculated the corresponding CV values. CV is defined as the ratio of the standard deviation to the mean. The associations between factors and overall survival (OS) were investigated via the Kaplan-Meier method with log-rank tests and the Cox proportional hazards model. RESULTS: The mean CV value of MR T2 images was 0.2299 ± 0.1339 (standard deviation) (range, 0.0381-0.8053). Applying receiver operating characteristics analysis, the optimal cut-off level for CV value was 0.137. This cut-off CV value was used for its stratification into high and low CV values. At multivariate survival analysis, a high CV value (hazard ratio = 3.63; 95% confidence interval = 1.16-16.0; p = 0.047) was identified as an independent predictor of OS. CONCLUSION: The CV value of the signal intensity of heterogenous MPNSTs MR T2-weighted images is an independent predictor of patients' OS.

  DOI PubMed

• Synergistic antitumor effect of histone deacetylase class IIa inhibitor with lenvatinib in hepatocellular carcinoma.

  Ryo Ito, Koji Miyanishi, Tomohiro Kubo, Kota Hamaguchi, Takahiro Osuga, Shingo Tanaka, Hiroyuki Ohnuma, Kazuyuki Murase, Kohichi Takada, Minoru Nagayama, Yasutoshi Kimura, Toru Mizuguchi, Ichiro Takemasa, Junji Kato

  Hepatology international   17 ( 3 ) 735 - 744  2023年06月  [国際誌]

  　概要を見る

  BACKGROUND: Histone deacetylase (HDAC) class I and IIa are highly expressed in hepatocellular carcinoma (HCC) and associated with decreased survival. However, clinically used pan and class I inhibitors have serious adverse events. In this study, we assessed the antitumor effects and tolerability of class IIa HDAC inhibitor (HDACI) with lenvatinib, which is a standard therapy for HCC. METHODS AND RESULT: Combination therapy with class IIa HDACI and lenvatinib exerted synergistic antitumor effect in human HCC cell lines. In mouse models, this therapy showed significant antitumor effects, and few adverse events occurred. In immunoblotting, the expression of fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) was high in cell lines that showed a high antitumor effect. In addition, class IIa HDACI administration decreased the expression of FGFR4. In the small interfering RNA (siRNA) analysis, knockdown of HDAC9, which is an isoform of HDAC class IIa, reduced the expression of FGFR4 and induced apoptosis. Immunohistochemistry of human clinical specimens showed a positivity rate of 32% for FGFR4 and 84% for HDAC9 in HCC, and all FGFR4-positive patients were HDAC9 positive. CONCLUSION: Class IIa HDACI and lenvatinib combination therapy induces apoptosis by downregulating FGFR4 and blocking the FGFR signaling in FGFR4-positive HCC cell lines and has demonstrated synergistic antitumor effects and safety. This combination therapy overcomes the problems of conventional therapies and will be beneficial for FGFR4-positive HCC patients.

  DOI PubMed

• Drastic Multiorgan Dysfunction Due to Severe Leukostasis: A Case Report.

  Akinori Tada, Yasuhiro Kikuchi, Kazuyuki Murase, Kohichi Takada, Akira Takasawa

  Cureus   14 ( 11 ) e31518  2022年11月  [国際誌]

  　概要を見る

  Leukostasis is a life-threatening complication that causes vascular occlusion leading to organ damage in leukemia patients. Organs with impairment due to leukostasis are usually the lungs and kidneys, but other organs may also be damaged. We experienced an autopsy case of severe infarction in multiple organs including the spleen probably due to leukostasis in a patient with acute myeloid leukemia.

  DOI PubMed

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• 低用量IL2はBCL2の発現を誘導することでCD4制御性T細胞のアポトーシスを抑制する(Low-close interleukin-2 induces BCL2 expression and resistance to apoptosis in CD4 regulatory T Cells)

  松野 鉄平, 村瀬 和幸, 高田 弘一, 河野 豊, 平川 昌宏, 宮西 浩嗣, 小船 雅義, 加藤 淳二

  札幌医学雑誌 ( 札幌医科大学 )  87 ( 1-6 ) 49 - 61  2018年12月

  　概要を見る

  制御性T細胞(Treg)は自己免疫寛容や恒常性の維持に重要な役割を果たしている。インターロイキン2(IL-2)はTregの増加、活動、生存に非常に重要である。既報では低用量IL-2はTregの増加に選択的に作用し、自己免疫疾患の臨床症状を改善させると報告されている。IL-2がTregの内因性アポトーシスにどのように作用するのかを調べるために、我々はBH3プロファイリングを用い、ミトコンドリアのアポトーシスプライミングを定量的に測定した。BH3ペプチドパターンではTregのプライミングがTconより多く、それがBCL2に依存していることを示した。実際に、TregではTconよりもBCL2の発現が低かった。IL-2の作用を調べるために、TregとTconに分け、異なった用量のIL-2で培養した。Tregでは低用量のIL-2(10 IU/ml)でプライミングは低下しBCL2発現は増加したが、Tconではプライミングの低下とBCL2発現の増加には高用量のIL-2(>100 IU/ml)が必要であった。また、低用量IL-2はTregにおいてのみアポトーシスへの感受性を減らすことがアポトーシスアッセイによって判明した。ABT-199というBCL2選択的阻害剤はTregとTcon両者のプライミングとアポトーシスを増加させる。IL2はTregにおいてのみこのABT-199の効果を打ち消した。このことからTregにおけるIL2による内因性アポトーシスの阻害がBCL2に依存していることが判明した。(著者抄録)

• 消化器癌におけるVEGF阻害剤関連血栓症に対する直接経口抗凝固薬(DOAC)の有用性

  平川昌宏, 早坂尚貴, 佐藤昌則, 松野鉄平, 三浦省吾, 藤田千紗, 大沼啓之, 村瀬和幸, 高田弘一, 宮西浩嗣, 加藤淳二

  日本消化器病学会雑誌(Web)   115  2018年

  J-GLOBAL

• P53-RESTORING SMALL MOLECULE CP-31398 INDUCES APOPTOSIS VIA INDUCTION OF REACTIVE OXIDATIVE SPECIES IN HUMAN MULTIPLE MYELOMA

  Y. Arihara, K. Takada, Y. Kawano, N. Hayasaka, H. Nakamura, S. Kikuchi, Y. Kamihara, K. Murase, H. Ikeda, S. Iyama, T. Sato, K. Miyanishi, M. Kobune, J. Kato

  HAEMATOLOGICA ( FERRATA STORTI FOUNDATION )  102   498 - 498  2017年06月

  研究発表ペーパー・要旨（国際会議）  

• CD34/EPO-R Double Positive MDS Cells Produce Erythroferrone in Response to Erythropoietin

  Shogo Miura, Masayoshi Kobune, Soushi Ibata, Masahiro Yoshida, Satoshi Iyama, Tsutomu Sato, Kazuyuki Murase, Kohichi Takada, Kaoru Ono, Akari Hashimoto, Ayumi Tatekoshi, Yusuke Kamihara, Yusuke Sugama, Wataru Jomen, Shohei Kikuchi, Hiroshi Ikeda, Hiroto Horiguchi, Yutaka Kawano, Koji Miyanishi, Hiroyuki Kuroda, Masahiro Maeda, Junji Kato

  BLOOD ( AMER SOC HEMATOLOGY )  128 ( 22 )  2016年12月

  研究発表ペーパー・要旨（国際会議）  

• Extracellular Vesicle microRNAs from Acute Myeloid Leukemia Are Involved in the Regulation of Adherence Junction in Bone Marrow Microenvironment.

  Masahiro Yoshida, Masayoshi Kobune, Shogo Miura, Soushi Ibata, Satoshi Iyama, Tsutomu Sato, Kazuyuki Murase, Kohichi Takada, Kaoru Ono, Akari Hashimoto, Ayumi Tatekoshi, Yusuke Kamihara, Yusuke Sugama, Shohei Kikuchi, Hiroshi Ikeda, Hiroto Horiguchi, Yutaka Kawano, Koji Miyanishi, Hiroyuki Kuroda, Masahiro Maeda, Junji Kato

  BLOOD ( AMER SOC HEMATOLOGY )  128 ( 22 )  2016年12月

  研究発表ペーパー・要旨（国際会議）  

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• 線維化治療