研究者詳細 - 村瀬　和幸

論文 - 村瀬　和幸

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Blastic plasmacytoid dendritic cell neoplasm(BPDCN)の2例

執行延明, 西田彩華, 菅野莉英, 藤岡茉生, 大橋隆宏, 堀本浩平, 加藤潤史, 肥田時征, 宇原久, 村瀬和幸, 井山諭, 須釜佑介, 前田和男

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 ) 130 ( 3 ) 418 - 418 2020年03月

Pulmonary metastasectomy is associated with prolonged survival among patients with bone and soft tissue sarcoma

Junya Shimizu, Makoto Emori, Yasutaka Murahashi, Tomoko Sonoda, Taijiro Mishina, Masahiro Miyajima, Atsushi Watanabe, Shintaro Sugita, Kohichi Takada, Kazuyuki Murase, Tadashi Hasegawa, Toshihiko Yamashita

Molecular and Clinical Oncology ( Spandidos Publications ) 2020年02月

DOI

Efficacy of combination therapy with dexmedetomidine for benzodiazepines-induced disinhibition during endoscopic retrograde cholangiopancreatography

Yuki Ikeda, Makoto Yoshida, Kazuma Ishikawa, Tomohiro Kubo, Kazuyuki Murase, Kohichi Takada, Koji Miyanishi, Masayoshi Kobune, Junji Kato

Therapeutic Advances in Gastroenterology ( SAGE Publications ) 13 175628482091182 - 175628482091182 2020年01月

Background: Benzodiazepines (BZDs) and analgesics are widely used for conscious sedation during endoscopic ultrasound (EUS) or endoscopic retrograde cholangiopancreatography (ERCP). However, endoscopic procedures are sometimes discontinued because of BZD-induced disinhibitory reactions such as excessive movement. We evaluated the usefulness of dexmedetomidine (DEX) for BZD-induced disinhibition in ERCP. Methods: Between February 2018 and August 2019, 22 patients who underwent EUS or ERCP were enrolled. All patients showed BZD-induced excessive movement at the first examination (BZD group) and received DEX at the second examination (DEX group). The initial DEX dose was 6 μg/kg/h for a 10-min loading, followed by 0.4 μg/kg/h during the procedure. BZDs and analgesics were administered before scope insertion. An additional sedative was administered to achieve a Ramsay sedation scale (RSS) of 4–5. Sedative effect, procedure completion rate, and changes in circulatory and respiratory dynamics were evaluated. Results: Mean RSS scores were significantly higher ( p < 0.001) in the DEX (5.1 ± 0.5) compared with the BZD (4.0 ± 0.5) group. The movement score ( p < 0.001) and number of additional sedatives required ( p < 0.01) were lower in the DEX group. The procedure completion rate was significantly higher in the DEX (95.5%) compared with the BZD group (63.6%; p < 0.05). Significant differences in the frequency of hypotension ( p = 1.00), bradycardia ( p = 0.22), and respiratory depression ( p = 0.68) were not noted between groups. Conclusions: The addition of DEX to BZD therapy yielded better sedative efficacy, lower excessive movement, a reduction in BZDs used, and a higher procedure complete rate. DEX may be used as an alternative method for BZD-induced inhibition during ERCP.

DOI

Management of Multiple Arteriovenous Malformations of the Small Bowel

Masahiro Hirakawa, Rie Ishizuka, Masanori Sato, Naotaka Hayasaka, Hiroyuki Ohnuma, Kazuyuki Murase, Kohichi Takada, Tatsuya Ito, Takayuki Nobuoka, Koji Miyanishi, Masayoshi Kobune, Ichiro Takemasa, Junji Kato

Case Reports in Medicine ( Hindawi Limited ) 2019 1 - 4 2019年12月

A 62-year-old Japanese female was referred to our hospital with gastrointestinal bleeding. Although small-bowel bleeding was suspected, no bleeding source was identified by enhanced computed tomography (CT), video capsule endoscopy (VCE), and double-balloon enteroscopy (DBE). Five years later, the patient had recurrent intermittent bloody stools with a significant decrease in hemoglobin levels. Although no active bleeding was observed on antegrade DBE, we detected a pulsatile submucosal uplift accompanied by a small red patch on the top of the uplift in the jejunum. Arteriovenous malformation (AVM) was suspected as the cause of small-bowel bleeding. Multiple-phase CT showed a number of small vascular ectasias during the arterial phase in the jejunum, and we confirmed the presence of multiple AVMs in the jejunum by selective angiography. To identify the location of the lesions and determine the minimal surgical margins, we performed intraoperative selective angiography with indocyanine green (ICG) injection. This technique allowed us to clearly observe the region and perform segmental small-bowel resection with minimal surgical margin. The patient reported that she has had no gastrointestinal bleeding at the two years follow-up visit.

DOI

BH3 profiling discriminates the anti‑apoptotic status of 5‑fluorouracil‑resistant colon cancer cells.

Kazuma Ishikawa, Yutaka Kawano, Yohei Arihara, Tomohiro Kubo, Kohichi Takada, Kazuyuki Murase, Koji Miyanishi, Masayoshi Kobune, Junji Kato

Oncology reports 42 ( 6 ) 2416 - 2425 2019年12月 [査読有り] [国際誌]

5‑Fluorouracil (5‑FU) is a cytotoxic anticancer drug commonly used for patients with advanced colon cancer. This drug effectively reduces the size of tumors to a certain degree; however, cancer cells can gradually acquire resistance, resulting in disease progression. To identify the mechanism of 5‑FU resistance, we established three 5‑FU‑resistant colon cancer cell lines and analyzed both apoptosis‑related protein expression levels and BH3 profiling. These 5‑FU‑resistant colon cancer cell lines acquired apoptotic resistance to 5‑FU. Although apoptosis‑related protein expression levels were altered in each 5‑FU‑resistant colon cancer cell line variably, BH3 profiling indicated BCLXL dependence in 5‑FU‑resistant HT‑29 cells only. Functional BCLXL inhibition in 5‑FU‑resistant HT‑29 cells not only sensitized the cells to apoptosis but also overcame 5‑FU resistance. The apoptotic BIM protein was preferentially sequestered, thereby resulting in acquired dependence on BCLXL for survival. Additionally, in vivo models showed that BCLXL inhibition controlled tumor progression. These results indicate that BH3 profiling facilitates the identification of the functional role of anti‑apoptotic proteins during drug resistance and has clinical implications for colon cancer in targeting specific proteins such as BCLXL.

DOI PubMed

Exceptionally rapid response to pembrolizumab in a SMARCA4‐deficient thoracic sarcoma overexpressing PD‐L1: A case report

Kohichi Takada, Shintaro Sugita, Kazuyuki Murase, Tomoki Kikuchi, Ginji Oomori, Ryo Ito, Naotaka Hayasaka, Koji Miyanishi, Satoshi Iyama, Hiroshi Ikeda, Masayoshi Kobune, Makoto Emori, Junji Kato, Tadashi Hasegawa

Thoracic Cancer ( Wiley ) 10 ( 12 ) 2312 - 2315 2019年12月

DOI

局所進行食道癌に対するDocetaxel/Nedaplatin/5-FU・放射線同時併用療法(DNF-R)の第II相試験アップデート解析

佐藤昌則, 大沼啓之, 早坂尚貴, 村瀬和幸, 高田弘一, 宮西浩嗣, 加藤淳二, 平川昌宏, 佐川保, 堀正和, 染谷正則, 坂田耕一

北海道医学雑誌 ( 北海道医学会 ) 94 ( 2 ) 121 - 121 2019年11月

Pneumothorax as an Adverse Event in Patients with Lung Metastasis of Soft Tissue Sarcoma under Eribulin Treatment

Kohichi Takada, Kazuyuki Murase, Hajime Nakamura, Naotaka Hayasaka, Yohei Arihara, Satoshi Iyama, Hiroshi Ikeda, Makoto Emori, Shintaro Sugita, Katsuyuki Nakamura, Koji Miyanishi, Masayoshi Kobune, Junji Kato

Internal Medicine ( Japanese Society of Internal Medicine ) 58 ( 20 ) 3009 - 3012 2019年10月

DOI

Borderline Resectable膵癌に対する治療戦略

吉田真誠, 石川和真, 久保智洋, 伊藤亮, 村瀬和幸, 高田弘一, 宮西浩嗣, 加藤淳二, 本谷雅代, 柾木喜晴, 仲瀬裕志, 木村康利, 永山稔, 今村将史, 竹政伊知朗

日本癌治療学会学術集会抄録集 ( (一社)日本癌治療学会 ) 57回 SY15 - 4 2019年10月

Six-transmembrane epithelial antigen of the prostate 1 protects against increased oxidative stress via a nuclear erythroid 2-related factor pathway in colorectal cancer

Hajime Nakamura, Kohichi Takada, Yohei Arihara, Naotaka Hayasaka, Kazuyuki Murase, Satoshi Iyama, Masayoshi Kobune, Koji Miyanishi, Junji Kato

Cancer Gene Therapy ( Springer Science and Business Media LLC ) 26 ( 9-10 ) 313 - 322 2019年09月

DOI

EPO-R+ myelodysplastic cells with ring sideroblasts produce high erythroferrone levels to reduce hepcidin expression in hepatic cells

Shogo Miura, Masayoshi Kobune, Hiroto Horiguchi, Shohei Kikuchi, Satoshi Iyama, Kazuyuki Murase, Akari Goto, Hiroshi Ikeda, Kohichi Takada, Koji Miyanishi, Junji Kato

Blood Cells, Molecules, and Diseases ( Elsevier BV ) 78 1 - 8 2019年09月

DOI

小型混合型肝癌の1例

大須賀崇裕, 宮西浩嗣, 田中信悟, 中村元, 坂本拡基, 大沼啓之, 村瀬和幸, 高田弘一, 小船雅義, 加藤淳二, 永山稔, 木村康利, 竹政伊知朗, 辻脇光洋, 長谷川匡

肝臓 ( (一社)日本肝臓学会 ) 60 ( 8 ) 294 - 301 2019年08月

症例は56歳男性。B型肝硬変とアルコール性肝障害で当科通院中。2017年7月のEOB-MRIにて肝S4に多血性腫瘍を認められ入院。採血検査では、肝硬変による肝トランスアミナーゼ上昇、血小板減少を認めたが、腫瘍マーカーは陰性であった。EOB-MRIでは、腫瘍は10mm大で早期相で不均一な高信号、肝細胞相で低信号、拡散強調画像で高信号を呈した。肝細胞癌(HCC)Stage1と診断し、腹腔鏡下肝部分切除術を施行した。術後16ヵ月経過し再発は認めていない。病理学的に腫瘍は高分化型HCC、中分化型HCC、HCCと肝内胆管癌の移行部、高-中分化型肝内胆管癌の4領域で構成される混合型肝癌であった。本症例は小型の段階で、HCCの一部が胆管細胞癌へ脱分化又は形質転換した非常に初期の混合型肝癌と考えられた。(著者抄録)

Combination of eribulin plus AKT inhibitor evokes synergistic cytotoxicity in soft tissue sarcoma cells.

Naotaka Hayasaka, Kohichi Takada, Hajime Nakamura, Yohei Arihara, Yutaka Kawano, Takahiro Osuga, Kazuyuki Murase, Shohei Kikuchi, Satoshi Iyama, Makoto Emori, Shintaro Sugita, Tadashi Hasegawa, Akira Takasawa, Koji Miyanishi, Masayoshi Kobune, Junji Kato

Scientific reports 9 ( 1 ) 5759 - 5759 2019年04月 [査読有り] [国際誌]

An activated AKT pathway underlies the pathogenesis of soft tissue sarcoma (STS), with over-expressed phosphorylated AKT (p-AKT) correlating with a poor prognosis in a subset of STS cases. Recently, eribulin, a microtubule dynamics inhibitor, has demonstrated efficacy and is approved in patients with advanced/metastatic liposarcoma and breast cancer. However, mechanisms of eribulin resistance and/or insensitivity remain largely unknown. In this study, we demonstrated that an increased p-AKT level was associated with eribulin resistance in STS cells. We found a combination of eribulin with the AKT inhibitor, MK-2206, synergistically inhibited STS cell growth in vivo as well as in vitro. Mechanistically, eribulin plus MK-2206 induced G1 or G2/M arrest by down-regulating cyclin-dependent kinases, cyclins and cdc2, followed by caspase-dependent apoptosis in STS cells. Our findings demonstrate the significance of p-AKT signaling for eribulin-resistance in STS cells and provide a rationale for the development of an AKT inhibitor in combination with eribulin to treat patients with STS.

DOI PubMed

リツキシマブが原因と考えられたTEN型薬疹の1例

松井馨之, 澄川靖之, 箕輪智幸, 熊谷綾子, 神谷崇文, 宇原久, 村瀬和幸

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 ) 129 ( 1 ) 45 - 45 2019年01月

miR-7977 inhibits the Hippo-YAP signaling pathway in bone marrow mesenchymal stromal cells.

Masahiro Yoshida, Hiroto Horiguchi, Shohei Kikuchi, Satoshi Iyama, Hiroshi Ikeda, Akari Goto, Yutaka Kawano, Kazuyuki Murase, Kohichi Takada, Koji Miyanishi, Junji Kato, Masayoshi Kobune

PloS one 14 ( 3 ) e0213220 2019年 [査読有り] [国際誌]

We and others have demonstrated that various abnormalities of the bone marrow (BM) mesenchymal stromal cells (MSCs) such as aberrant cytokine expression, abnormal hedgehog signaling, and impaired miRNA biogenesis are observed in patients with acute myeloid leukemia (AML). However, underlying mechanisms to induce the dysfunction of BM MSCs have not yet been clarified. We previously showed that AML cells release abundant exosomal miR-7977, which, in turn, enters BM mesenchymal stromal cells (MSCs). However, the precise function of miR-7977 is not known. In this study, we performed transduction of a miR-7977 mimic into MSCs, compared transcriptomes between control-transduced (n = 3) and miR-7977-transduced MSCs (n = 3), and conducted pathway analysis. The array data revealed that the expression of 0.05% of genes was reduced 2-fold and the expression of 0.01% of genes was increased 2-fold. Interestingly, approximately half of these genes possessed a miR-7977 target site, while the other genes did not, suggesting that miR-7977 regulates the gene expression level directly and indirectly. Gene set enrichment analysis showed that the gene sets of Yes-associated protein 1 (YAP1) _up were significantly enriched (p<0.001, q<0.25), suggesting that miR-7977 modulates the Hippo-YAP signaling pathway. Visualization of pathway and network showed that miR-7977 significantly reduced the expression of Hippo core kinase, STK4. miR-7977 inactivated the Hippo-YAP signaling pathway as proven by GFP-tagged YAP nuclear trans localization and TEAD reporter assay. The miR-7977-transduced MSC cell line, HTS-5, showed elevated saturation density and enhanced entry into the cell cycle. These results suggest that miR-7977 is a critical factor that regulates the Hippo-YAP signaling pathway in BM-MSCs and may be involved in the upregulation of leukemia-supporting stroma growth.

DOI PubMed

Early Lymph Node Metastasis May Predict Poor Prognosis in Soft Tissue Sarcoma.

Makoto Emori, Hiroyuki Tsuchie, Hiroyuki Nagasawa, Tomoko Sonoda, Arihiko Tsukamoto, Junya Shimizu, Yasutaka Murahashi, Emi Mizushima, Kohichi Takada, Kazuyuki Murase, Kotoe Iesato, Keita Igarashi, Tsukasa Hori, Masaki Yamamoto, Shintaro Sugita, Naohisa Miyakoshi, Tadashi Hasegawa, Yoichi Shimada, Toshihiko Yamashita

International journal of surgical oncology 2019 6708474 - 6708474 2019年 [国際誌]

Background: Lymph node metastasis (LNM) is a relatively rare event in soft tissue sarcoma. An association between the timing of LNM detection and patient prognosis is presently unknown. Patients and Methods: We retrospectively analyzed the clinicopathological features of 33 patients with LNM between 2001 and 2015. Analysis of the timing of LNM diagnosis was grouped according to patients presenting LNM in either <8 months (the median time from primary tumor diagnosis to LNM) or ≥8 months after primary tumor diagnosis. Results: A relationship between the primary tumor size and the timing of the LNM was not significantly found (Rs = 0.0088, p=0.96). Sixteen patients had an LNM detection duration of <8 months, and 17 patients had a duration of ≥8 months. The 5-year survival for patients with an LNM detection duration of <8 months and ≥8 months was 19% and 71%, respectively (p=0.0016). There were 19 patients with pulmonary metastases. Among them, there were 13 patients with a duration of primary tumor diagnosis to LNM of <8 months and 6 with a duration of ≥8 months (p=0.01). Conclusion: Early LNM (<8 months) may predict poor prognosis in soft tissue sarcoma.

DOI PubMed

A case of small combined hepatocellular-cholangiocellular carcinoma

Takahiro Osuga, Koji Miyanishi, Shingo Tanaka, Hajime Nakamura, Hiroki Sakamoto, Hiroyuki Onuma, Kazuyuki Murase, Koichi Takada, Masayoshi Kobune, Junji Kato, Minoru Nagayama, Yasutoshi Kimura, Ichiro Takemasa, Mitsuhiro Tsujiwaki, Tadashi Hasegawa

Acta Hepatologica Japonica ( Japan Society of Hepatology ) 60 ( 8 ) 294 - 301 2019年

DOI

Trastuzumab-Based Combination Chemotherapy in Patients with Human Epidermal Growth Factor Receptor-2-Positive Metastatic Carcinoma ex Pleomorphic Adenoma

Yohei Arihara, Kazuyuki Murase, Kohichi Takada, Naotaka Hayasaka, Shogo Miura, Koji Miyanishi, Masayoshi Kobune, Makoto Kurose, Yukinori Akiyama, Shintaro Sugita, Junji Kato

Case Reports in Oncology ( S. Karger AG ) 11 ( 3 ) 835 - 841 2018年12月

Background: Carcinoma ex pleomorphic adenoma (CXPA) is a rare histologic subtype of lacrimal gland and submandibular gland cancer. Currently, there is no standard treatment for metastatic CXPA, although some case reports have explored the role of targeted agents in chemotherapy. A few histopathologic analyses have shown that some of these tumors overexpress human epidermal growth factor receptor-2 (HER2), suggesting a potential role for HER2-based therapy. We report here two cases of metastatic CXPA that were treated with trastuzumab-based chemotherapy (IRB approved) with rapid and significant responses. Case Report 1: A 66-year-old male was diagnosed as HER2-positive CXPA of the right lacrimal gland with multiple bone and lymph node metastases. Combination chemotherapy with trastuzumab (Tmab) and nanoparticle albumin-bound paclitaxel (nabPTX) was initiated. A rapid response was confirmed, and after seven cycles of treatment, CR(complete response) was achieved. Case Report 2: A 67-year-old female was diagnosed with HER2 positive CXPA of the right submandibular gland. Multiple pulmonary metastatic lesions were detected after surgery, and combination chemotherapy with Tmab and nab-PTX was initiated. A rapid partial response (PR) was confirmed, and she eventually became disease-free. Conclusion: In the absence of definitive clinical trials, which are unlikely to be performed due to the rarity of HER2-positive CXPA, therapeutic information must be obtained from case reports. Some reports, such as this one, have suggested a potential utility of trastuzumab-based chemotherapy.

DOI

Denosumab prevents bone loss in newly diagnosed malignant lymphoma patients undergoing corticosteroid-containing chemotherapy: A prospective, non-randomized study

Ayumi Tatekoshi, Tsutomu Sato, Satoshi Iyama, Kohichi Takada, Kazuyuki Murase, Masahiro Yoshida, Soushi Ibata, Akari Hashimoto, Yusuke Kamihara, Hiroto Horiguchi, Koji Miyanishi, Masayoshi Kobune, Junji Kato

Sapporo Medical journal ( Sapporo Medical University ) 87 ( 1-6 ) 35 - 47 2018年12月

DOI

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 [査読有り]

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)

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