Details of a Researcher - MURASE Kazuyuki

Papers - MURASE Kazuyuki

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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 2024.03 [International journal]

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 2023.11

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 2023.09 [International journal]

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 2023.06 [International journal]

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 2022.11 [International journal]

DOI PubMed

表在型食道癌ESD後のMM-SM癌における追加化学放射線療法の長期成績

伊藤亮, 大沼啓之, 早坂尚貴, 佐藤昌則, 村瀬和幸, 高田弘一, 福島悠希, 長谷川智一, 土屋高旭, 染谷正則, 宮西浩嗣, 坂田耕一, 加藤淳二

日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 ( 日本消化器病学会-北海道支部 ) 131回・125回 56 - 56 2022.09

食道癌化学放射線療法症例における放射線胃炎のリスク因子の検討

佐藤昌則, 大沼啓之, 早坂尚貴, 伊藤亮, 村瀬和幸, 高田弘一, 福島悠希, 長谷川智一, 土屋高旭, 染谷正則, 宮西浩嗣, 坂田耕一, 加藤淳二

日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 ( 日本消化器病学会-北海道支部 ) 131回・125回 55 - 55 2022.09

食道癌化学放射線療法症例における放射線胃炎のリスク因子の検討

佐藤昌則, 大沼啓之, 早坂尚貴, 伊藤亮, 村瀬和幸, 高田弘一, 福島悠希, 長谷川智一, 土屋高旭, 染谷正則, 宮西浩嗣, 坂田耕一, 加藤淳二

表在型食道癌ESD後のMM-SM癌における追加化学放射線療法の長期成績

伊藤亮, 大沼啓之, 早坂尚貴, 佐藤昌則, 村瀬和幸, 高田弘一, 福島悠希, 長谷川智一, 土屋高旭, 染谷正則, 宮西浩嗣, 坂田耕一, 加藤淳二

Association between Hepatic Oxidative Stress Related Factors and Activation of Wnt/β-Catenin Signaling in NAFLD-Induced Hepatocellular Carcinoma.

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

Cancers 14 ( 9 ) 2022.04 [International journal]

We investigated the association between iron overload, oxidative stress (8-oxo-7,8-dihydroguanine: 8-oxo-dG scores), Wnt/β-catenin pathway activation (expression of glutamine synthetase: GS), and tumor hyperintensity in the Gd-EOB-DTPA-enhanced MRI hepatobiliary phase (relative enhancement ratio: RER). This was a retrospective analysis of 94 hepatocellular carcinoma (HCC) patients who underwent surgical resection. In HBV-, HCV-, and alcohol-associated HCC, serum ferritin levels in the high and low RER groups were equivalent. In contrast, ferritin levels were elevated in the 'high RER' group of patients with nonalcoholic fatty liver disease (NAFLD)-HCC. As predictors of GS positivity, high RER had a sensitivity of 57.2% and a specificity of 100%. High serum ferritin had a sensitivity of 85.7% and a specificity of 85.7%. All cases with serum ferritin ≥275.5 ng/mL and high RER were 8-oxo-dG- and iron staining-positive. Additionally, GS positivity was seen in all cases with "serum ferritin levels above the upper limits or iron staining-positive" and '8-oxo-dG high' cases. Therefore, combining serum ferritin levels with RER may increase the accuracy with which activated Wnt/β-catenin signaling is predicted in NAFLD-HCC. We suggest that 8-oxo-dG accumulates following increased oxidative stress due to hepatic tissue iron deposition; this may activate Wnt/β-catenin signaling and trigger carcinogenesis.

DOI PubMed

A case of acute exacerbation of chronic hepatitis C during the course of adrenal Cushing's syndrome

Takahiro Osuga, Koji Miyanishi, Kota Hamaguchi, Shingo Tanaka, Hiroyuki Ohnuma, Kazuyuki Murase, Kohichi Takada, Junji Kato

Clinical Case Reports ( Wiley ) 10 ( 2 ) 2022.02

DOI

Achievement of a durable response with eribulin for relapsed cardiac metastasis of uterine leiomyosarcoma after surgery: a case report and literature review

Makoto Usami, Kohichi Takada, Hajime Nakamura, Kazuyuki Murase, Yohei Arihara, Naotaka Hayasaka, Tomohiro Kubo, Koji Miyanishi, Junji Kato, Makoto Emori, Shintaro Sugita

Annals of Palliative Medicine ( AME Publishing Company ) 2022.01

DOI

A Case of Unresectable Combined Hepatocellular-Cholangiocarcinoma Successfully Treated with Lenvatinib.

Takahiro Osuga, Koji Miyanishi, Ryo Ito, Shingo Tanaka, Kota Hamaguchi, Hiroyuki Ohnuma, Kazuyuki Murase, Kohichi Takada, Minoru Nagayama, Yasutoshi Kimura, Taro Sugawara, Shintaro Sugita, Ichiro Takemasa, Tadashi Hasegawa, Junji Kato

Case reports in oncology 15 ( 1 ) 318 - 325 2022 [International journal]

A 77-year-old man was referred to our hospital because of a hepatic tumor. Blood biochemistry showed elevated serum alfa-fetoprotein, protein induced by vitamin K absence-II, and carbohydrate antigen 19-9 levels. Gd-EOB-DTPA-enhanced magnetic resonance imaging revealed a 95-mm-sized tumor in liver S7. The tumor showed heterogeneous hyperintensity in the arterial phase, slightly washed out from the portal vein phase, and hypointensity in the hepatocellular phase. Post-enlargement segmental resection was performed, and the pathological diagnosis was combined hepatocellular cholangiocarcinoma. Seven months after surgery, multiple liver tumors were found, and biopsy revealed combined hepatocellular-cholangiocarcinoma. Hepatic arterial infusion chemotherapy with cisplatin was initiated. However, the patient developed a pulmonary abscess, which was treated with antibiotics. He then underwent treatment with lenvatinib, 11 months after surgery. At 8 weeks follow-up, a complete response (according to the modified Response Evaluation Criteria in Solid Tumors [RECIST]) and a partial response (RECIST version 1.1) was noted. To the best of our knowledge, thus far, only a single case of lenvatinib treatment of unresectable mixed liver cancer has been reported. In that case, lenvatinib was used as a third-line treatment. The present report is the first to describe lenvatinib as a first-line therapy for unresectable combined hepatocellular-cholangiocarcinoma, which resulted in a meaningful response. This case provides useful insights into the choice of appropriate drug treatment in this disease in the absence of randomized controlled trials of drug treatment.

DOI PubMed

MUTYH is associated with hepatocarcinogenesis in a non-alcoholic steatohepatitis mouse model

Hiroki Sakamoto, Koji Miyanishi, Shingo Tanaka, Ryo Ito, Kota Hamaguchi, Akira Sakurada, Masanori Sato, Tomohiro Kubo, Takahiro Osuga, Kazuyuki Murase, Kohichi Takada, Yusaku Nakabeppu, Masayoshi Kobune, Junji Kato

Scientific Reports ( Springer Science and Business Media LLC ) 11 ( 1 ) 2021.12

AbstractNon-alcoholic steatohepatitis (NASH)-related HCC is associated with oxidative stress. However, the mechanisms underlying the development of NASH-related HCC is unclear. MUTYH is one of the enzymes that is involved in repair of oxidative DNA damage. The aim of this study was to investigate the association between MUTYH and NASH-related hepatocarcinogenesis. MUTYH wild-type (Mutyh^+/+), heterozygous (Mutyh^+/−), and MUTYH-null (Mutyh^−/−) mice were fed a high-fat high-cholesterol (HFHC) diet or HFHC + high iron diet (20 mice per group) for 9 months. Five of 20 Mutyh^−/− mice fed an HFHC + high iron diet developed liver tumors, and they developed more liver tumors than other groups (especially vs. Mutyh^+/+ fed an HFHC diet, P = 0.0168). Immunohistochemical analysis revealed significantly higher accumulation of oxidative stress markers in mice fed an HFHC + high iron diet. The gene expression profiles in the non-tumorous hepatic tissues were compared between wild-type mice that developed no liver tumors and MUTYH-null mice that developed liver tumors. Gene Set Enrichment Analysis identified the involvement of the Wnt/β-catenin signaling pathway and increased expression of c-Myc in MUTYH-null liver. These findings suggest that MUTYH deficiency is associated with hepatocarcinogenesis in patients with NASH with hepatic iron accumulation.

DOI

Combination of psoas muscle mass index and neutrophil/lymphocyte ratio as a prognostic predictor for patients undergoing nonsurgical hepatocellular carcinoma therapy

Yusuke Sugama, Koji Miyanishi, Takahiro Osuga, Shingo Tanaka, Kota Hamaguchi, Ryo Ito, Hiroki Sakamoto, Tomohiro Kubo, Hiroyuki Ohnuma, Kazuyuki Murase, Kohich Takada, Masayoshi Kobune, Junji Kato

JGH Open ( Wiley ) 5 ( 12 ) 1335 - 1343 2021.12

DOI

Complete Response Induced by Concurrent Chemoradiotherapy in a Patient with NUT Carcinoma: A Case Report.

Joji Muramatsu, Kohichi Takada, Shintaro Sugita, Takaaki Tsuchiya, Keisuke Yamamoto, Masaru Takagi, Kazuyuki Murase, Saki Ameda, Yohei Arihara, Koji Miyanishi, Koh-Ichi Sakata, Junji Kato

Internal medicine (Tokyo, Japan) 2021.10 [Domestic journal]

An 18-year-old man presented with sudden vision loss in his left eye. Magnetic resonance imaging revealed a tumor that had invaded the left optic nerve, originating from the left posterior ethmoid sinus. Immunohistochemical analyses identified positive staining for NUT protein in the nuclei of tumor cells. We diagnosed locally advanced NUT carcinoma (NC) and initiated concurrent chemoradiotherapy (CCRT), consisting of chemotherapy with vincristine, doxorubicin, and cyclophosphamide, alternating with ifosphamide and etoposide, plus radiation therapy. The patient achieved a complete response. CCRT can be a useful treatment option for adolescent and young-adult patients with locally advanced unresectable NC.

DOI PubMed

進行食道癌に対するdocetaxel、nedaplatin、5-fluorouracil、放射線併用療法(DNF-R)による根治的化学放射線療法の第I/II相試験-アップデート解析

佐藤昌則, 大沼啓之, 早坂尚貴, 濱口孝太, 村瀬和幸, 高田弘一, 福島悠希, 長谷川智一, 土屋高旭, 染谷正則, 宮西浩嗣, 坂田耕一, 加藤淳二

日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 ( 日本消化器病学会-北海道支部 ) 129回・123回 26 - 26 2021.09

血液疾患患者におけるCOVID-19感染症4例の報告(Four cases of COVID-19 patients with hematological malignancy)

小野賢人, 堀口拓人, 下山紗央莉, 藤田千紗, 後藤亜香利, 池田博, 井山諭, 村瀬和幸, 高田弘一, 藤谷好弘, 高橋聡, 黒沼幸治, 小船雅義

日本血液学会学術集会 ( (一社)日本血液学会 ) 83回 OS3 - 4 2021.09

Programmed cell death ligand 1 expression in a case of poorly differentiated lymphocyte‐rich hepatocellular carcinoma

Ginji Omori, Takahiro Osuga, Koji Miyanishi, Kota Hamaguchi, Shingo Tanaka, Hiroyuki Ohnuma, Kazuyuki Murase, Kohichi Takada, Minoru Nagayama, Yasutoshi Kimura, Ichiro Takemasa, Yasuhiro Kikuchi, Toshihiko Torigoe, Junji Kato

Clinical Case Reports ( Wiley ) 9 ( 9 ) 2021.09

DOI

Survival benefit of conversion surgery after intensive chemotherapy for unresectable metastatic gastric cancer: a propensity score-matching analysis

Hiroyuki Ohnuma, Yasushi Sato, Naoki Onoyama, Kota Hamaguchi, Naotaka Hayasaka, Masanori Sato, Kazuyuki Murase, Kohichi Takada, Koji Miyanishi, Takeshi Murakami, Tatsuya Ito, Takayuki Nobuoka, Ichiro Takemasa, Junji Kato

Journal of Cancer Research and Clinical Oncology ( Springer Science and Business Media LLC ) 147 ( 8 ) 2385 - 2396 2021.08

DOI

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Papers - MURASE Kazuyuki