研究者業績

大澤 英之

オオザワ ヒデユキ  (Hideyuki Ohzawa)

基本情報

所属
自治医科大学 附属病院腫瘍センター臨床腫瘍部 准教授

J-GLOBAL ID
201901012051989248
researchmap会員ID
B000348091

論文

 154
  • Yuki Kaneko, Hideyuki Ohzawa, Yuki Kimura, Rei Takahashi, Misaki Matsumiya, Kohei Tamura, Yurie Futoh, Hideyo Miyato, Shin Saito, Hironori Yamaguchi, Yoshinori Hosoya, Ryota Watano, Hiroaki Mizukami, Naohiro Sata, Joji Kitayama
    Cancer gene therapy 2024年10月10日  
    This study explores a novel therapeutic approach for peritoneal metastasis (PM) using AAV-mediated delivery of tumor suppressor microRNA-29b (miR-29b) to peritoneal mesothelial cells (PMC). AAV serotypes 2 and DJ demonstrate high transduction efficiency for human and murine PMC, respectively. In vitro analysis indicates that AAV vectors encoding miR-29b precursor successfully elevate miR-29b expression in PMC and their secreted small extracellular vesicle (sEV), thereby inhibiting mesothelial mesenchymal transition and reducing subsequent attachment of tumor cells. A single intraperitoneal (IP) administration of AAV-DJ-miR-29b demonstrates robust and sustained transgene expression, suppressing peritoneal fibrosis and inhibiting the development of PM from gastric and pancreatic cancers. Additionally, AAV-DJ-miR-29b enhances the efficacy of IP chemotherapy using paclitaxel, restraining the growth of established PM. While conventional gene therapy for cancer encounters challenges targeting tumor cells directly but delivering miRNA to the tumor stroma offers a straightforward and efficient means of altering the microenvironment, leading to substantial inhibition of tumor growth. AAV-mediated miR-29b delivery to peritoneum via IP route presents a simple, minimally invasive, and promising therapeutic strategy for refractory PM.
  • Kohei Tamura, Natsuka Kimura, Hideyuki Ohzawa, Hideyo Miyato, Naohiro Sata, Takahiro Koyanagi, Yasushi Saga, Yuji Takei, Hiroyuki Fujiwara, Ryozo Nagai, Joji Kitayama, Kenichi Aizawa
    Cancers 16(16) 2841-2841 2024年8月14日  
    Despite advances in systemic chemotherapy, patients with gastric cancer (GC) and peritoneal metastases (PMs) continue to have poor prognoses. Intraperitoneal (IP) administration of Paclitaxel (PTX) combined with systemic chemotherapy shows promise in treating PMs from GC. However, methods of drug administration need to be optimized to maximize efficacy. In this study, we utilized a mouse model with PMs derived from a human GC cell line, administering PTX either IP or intravenously (IV), and Carboplatin (CBDCA) IV 0, 1, and 4 days after PTX administration. The PMs were resected 30 min later, and concentrations of PTX and CBDCA in resected tumors were measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Results indicated that PTX concentrations were higher with IP administration than with IV administration, with significant differences observed on days 0 and 1. CBDCA concentrations 4 days post-IP PTX administration were higher than with simultaneous IV PTX administration. These findings suggest that IP PTX administration enhances CBDCA concentration in peritoneal tumors. Therefore, sequential IV administration of anti-cancer drugs appears more effective than simultaneous administration with IP PTX, a strategy that may improve prognoses for patients with PMs.
  • Yurie Futoh, Hideyo Miyato, Hironori Yamaguchi, Misaki Matsumiya, Rei Takahashi, Yuki Kaneko, Yuki Kimura, Hideyuki Ohzawa, Naohiro Sata, Joji Kitayama, Yoshinori Hosoya
    Scientific Reports 14(1) 2024年4月3日  
    Abstract The vagus nerve is the only pathway for transmitting parasympathetic signals between the brain and thoracoabdominal organs, thereby exhibiting anti-inflammatory functions through the cholinergic anti-inflammatory pathway. Despite often being resected during lymph node dissection in upper gastrointestinal cancer surgery, the impact of vagotomy on postoperative outcomes in gastric cancer patients remains unclear. Sub-diaphragmatic vagotomy was performed on C57BL/6 mice. Three weeks later, syngeneic murine gastric cancer cell line YTN16P was injected into the peritoneal cavity, and the number of peritoneal metastases (PM) on the mesentery and omentum compared with control mice. The phenotypes of immune cells in peritoneal lavage and omental milky spots one day after tumor inoculation were analyzed using flow cytometry and immunohistochemistry. Intraperitoneal transfer of 3 × 105 YTN16P significantly increased the number of metastatic nodules on the mesentery in the vagotomy group compared to the control group. The omental metastasis grade was also significantly higher in the vagotomy group. Phenotypic analysis of immune cells in peritoneal lavage did not reveal significant differences after vagotomy. However, vagotomized mice exhibited a notable increase in milky spot area, with a higher presence of cytokeratin(+) tumor cells, F4/80(+) macrophages, and CD3(+) T cells. Vagus nerve signaling appears to regulate the immune response dynamics within milky spots against disseminated tumor cells and inhibits the development of PM. Preserving the vagus nerve may offer advantages in advanced gastric cancer surgery to reduce peritoneal recurrence.
  • Yuki Kaneko, Hideyo Miyato, Mineyuki Tojo, Yurie Futoh, Kazuya Takahashi, Yuki Kimura, Akira Saito, Hideyuki Ohzawa, Hironori Yamaguchi, Naohiro Sata, Joji Kitayama, Yoshinori Hosoya
    Scientific Reports 14(1) 2024年2月24日  
    Abstract The spleen is a key source of circulating and tumor-infiltrating immune cells. However, the effect of splenectomy on tumor growth remains unclear. At 3 weeks after splenectomy, we subcutaneously injected LuM1 cells into BALB/c mice and evaluated the growth of primary tumors and lung metastases at 4 weeks after tumor inoculation. In addition, we examined the phenotypes of immune cells in peripheral blood by using flow cytometry and in tumor tissue by using multiplex immunohistochemistry. The growth of primary tumors was reduced in splenectomized mice compared with the sham-operated group. Conversely, splenectomized mice had more lung metastases. Splenectomized mice had fewer CD11b+cells, especially monocytic MDSCs (CD11b+Gr-1neg-lowLy6chigh), and NK cells (CD49b+CD335+). The proportion of NK cells was inversely correlated with the number of lung metastases. In splenectomized mice, the density of CD3+ and granzyme B+ CD8+ T cells was increased, with fewer M2-type macrophages in primary tumors, but NK cells were decreased markedly in lung. Splenectomy concurrently enhances T cell-mediated acquired immunity by reducing the number of monocytic MDSCs and suppresses innate immunity by decreasing the number of NK cells. Splenectomy has opposite effects on primary and metastatic lesions through differential regulation on these two immune systems.
  • Takashi Chinen, Hironori Yamaguchi, Hideyuki Ohzawa, Shiro Matsumoto, Kentaro Kurashina, Shin Saito, Yoshinori Hosoya, Hirofumi Fujii, Joji Kitayama, Naohiro Sata
    Journal of thoracic disease 16(1) 391-400 2024年1月30日  
    BACKGROUND: Adjuvant nivolumab therapy has become the standard therapy for patients with localized advanced esophageal cancer with non-pathological complete response after neoadjuvant chemoradiotherapy followed by curative surgery. However, the necessity of this therapy for patients after neoadjuvant chemotherapy (NAC) with docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen followed by surgery is unclear, and the prognosis of grouping based on the presence or absence of pathological tumor and lymph node findings has not been analyzed. Therefore, our study aimed to address these questions. METHODS: This retrospective cohort study included patients with cT1N1-3M0 and cT2-3N0-3M0 esophageal cancer according to the Japanese Classification of Esophageal Cancer, 11th edition, who received NAC with DCF followed by curative surgery between 2008 and 2020 at Jichi Medical University Hospital. We divided patients with ypT0-3N0-3M0 into four histological groups, namely ypT0N0, ypT+N0, ypT0N+, and ypT+N+, and we evaluated overall survival as the primary outcome and the prognostic relationship of lymph node metastasis as the secondary outcome. RESULTS: A total of 101 patients were included in this study. Kaplan-Meier analysis showed that the curves of the ypT0N0 and ypT+N0 groups were almost identical, while they differed from the other two groups. The hazard ratio of ypN+ was 4.44 (95% confidence interval: 2.03-9.71; P<0.001). CONCLUSIONS: The prognosis of the ypT+N0 group after NAC with DCF followed by surgery was similar to that of pathological complete remission. Grouping patients according to pathological lymph node status is a reasonable predictor of prognosis.
  • Yuki Kimura, Hideyuki Ohzawa, Yuki Kaneko, Hideyo Miyato, Kentaro Kurashina, Shin Saito, Hironori Yamaguchi, Yoshinori Hosoya, Naohiro Sata, Joji Kitayama
    Gan to kagaku ryoho. Cancer & chemotherapy 50(13) 1435-1437 2023年12月  
    Although miR-29b levels in peritoneal exosomes was markedly reduced in patients with peritoneal metastases(PM), their role has not been fully clarified. Bone marrow derived mesenchymal stem cells(BMSC)were transfected with miR-29b- integrating lentivirus and exosomes isolated from culture supernatants using ultracentrifugation. The effects of the exosomes on human peritoneal mesothelial cells(HPMC)were examined in vitro. The in vivo effect of murine BMSC-derived exosomes was examined with a syngeneic PM model. Culture of HPMC with TGF-β1 decreased expression of E-cadherin and calretinin with increased expression of vimentin, totally restored by adding miR-29b-rich exosomes. The exosomes inhibited proliferation and migration of HPMC, and inhibited adhesion of gastric cancer cells to HPMC. Intraperitoneal(IP)transfer of miR- 29b-rich exosomes every 3 days markedly reduced the number of PM of a murine gastric cancer cell, YTN16P, on the mesentery of C57/BL6 mice. IP administration of miR-29b-containing exosome suppresses the development of PM of gastric cancer.
  • 田村 昂平, 松宮 美沙希, 高橋 礼, 金子 勇貴, 風當 ゆりえ, 宮戸 秀世, 大澤 英之, 嵯峨 泰, 竹井 裕二, 藤原 寛行, 北山 丈二
    日本癌治療学会学術集会抄録集 61回 YOA O68-3 2023年10月  
  • 藤沼 香栄, 田口 昌延, 下平 健太郎, 青木 裕一, 目黒 由行, 森嶋 計, 三木 厚, 宮戸 秀世, 大澤 英之, 兼田 裕司, 遠藤 和洋, 小泉 大, 吉田 淳, 笹沼 英紀, 山口 博紀, 佐久間 康成, 北山 丈二, 佐田 尚宏
    膵臓 38(3) A392-A392 2023年7月  
  • 田口 昌延, 笹沼 英紀, 下平 健太郎, 青木 裕一, 目黒 由行, 森嶋 計, 三木 厚, 宮戸 秀世, 大澤 英之, 兼田 裕司, 遠藤 和洋, 小泉 大, 吉田 淳, 山口 博紀, 佐久間 康成, 北山 丈二, 佐田 尚宏
    膵臓 38(3) A405-A405 2023年7月  
  • 田口 昌延, 笹沼 英紀, 下平 健太郎, 森嶋 計, 三木 厚, 宮戸 秀世, 吉田 淳, 大澤 英之, 兼田 裕司, 遠藤 和洋, 小泉 大, 山口 博紀, 佐久間 康成, 北山 丈二, 佐田 尚宏
    日本胆膵病態・生理研究会プログラム・抄録集 40回 24-24 2023年6月  
  • 齋藤 心, 山口 博紀, 金丸 理人, 大澤 英之, 倉科 憲太郎, 宮戸 英世, 細谷 好則, Lefor Alan K., 佐田 尚宏, 北山 丈二
    癌の臨床 67(2) 47-55 2023年5月  
  • 齋藤 心, 山口 博紀, 金丸 理人, 大澤 英之, 倉科 憲太郎, 宮戸 英世, 細谷 好則, Lefor Alan K., 佐田 尚宏, 北山 丈二
    癌の臨床 67(2) 47-55 2023年5月  
  • Yuki Kimura, Hideyuki Ohzawa, Hideyo Miyato, Yuki Kaneko, Takahiro Kuchimaru, Rei Takahashi, Hironori Yamaguchi, Kentaro Kurashina, Shin Saito, Yoshinori Hosoya, Alan Kawarai Lefor, Naohiro Sata, Joji Kitayama
    Cancer Science 2023年4月3日  
  • 藤沼 香栄, 齋藤 心, 山口 博紀, 金丸 理人, 大澤 英之, 倉科 憲太郎, 細谷 好則, 佐野 直樹, 仁木 利郎, Kawarai Lefor Alan, 北山 丈二, 佐田 尚宏
    自治医科大学紀要 45 67-72 2023年3月  
    当院では,2016年1月より腹膜播種陽性胃癌を対象に,パクリタキセル腹腔内投与併用化学療法を導入し,腹膜播種奏功例に対してはConversion Surgeryを行っている。症例は57歳,女性。胃癌術前検査で腹膜播種を疑い,審査腹腔鏡を施行した。播種結節を認めP1,PCI score 15点,腹水細胞診class Vであった。pT4aN1M1(PER)pStage IVと診断し,腹腔ポートを造設,SOX+腹腔内PTX投与を開始した。SOX+IP-PTX 12コース施行後に2nd look審査腹腔鏡を行い,CY0P0であった。R0切除可能と判断し,Conversion Surgeryとして開腹胃全摘術を施行した。本症例は腸回転異常症を伴っていた。胃癌手術で腸回転異常により定型手術が行えず,難渋した報告がある。本症例は腸回転異常を伴う胃癌腹膜播種に腹腔内化学療法が奏功し,Conversion Surgeryを施行しえた初めての報告である。腸回転異常症の術前診断は重要であり,化学療法による腹膜播種奏功例ではConversion Surgeryが予後改善に寄与する可能性がある。(著者抄録)
  • Kohei Tamura, Hideyo Miyato, Rihito Kanamaru, Ai Sadatomo, Kazuya Takahashi, Hideyuki Ohzawa, Takahiro Koyanagi, Yasushi Saga, Yuji Takei, Hiroyuki Fujiwara, Alan Kawarai Lefor, Naohiro Sata, Joji Kitayama
    Cellular Immunology 384 104663-104663 2023年2月  
  • 金丸 理人, 山口 博紀, 高橋 和也, 金子 勇貴, 加賀谷 丈紘, 高木 徹, 松本 志郎, 倉科 憲太郎, 齋藤 心, 大澤 英之, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本胃癌学会総会記事 95回 273-273 2023年2月  
  • 高橋 和也, 大澤 英之, 金丸 理人, 松本 志郎, 倉科 憲太郎, 齋藤 心, 山口 博紀, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本胃癌学会総会記事 95回 459-459 2023年2月  
  • 齋藤 晶, 大澤 英之, 松宮 美沙希, 高橋 礼, 田村 昂平, 金子 勇貴, 風當 ゆりえ, 高橋 和也, 木村 有希, 宮戸 秀世, 佐田 尚宏, 北山 丈二
    日本成人病(生活習慣病)学会会誌 48 65-65 2023年1月  
  • Atsushi Miki, Yasunaru Sakuma, Hideyuki Ohzawa, Akira Saito, Yoshiyuki Meguro, Jun Watanabe, Kazue Morishima, Kazuhiro Endo, Hideki Sasanuma, Atsushi Shimizu, Alan Kawarai Lefor, Yoshikazu Yasuda, Naohiro Sata
    World Journal of Gastroenterology 28(38) 5614-5625 2022年10月14日  
  • 風當 ゆりえ, 北山 丈二, 金子 勇貴, 高橋 和也, 木村 有希, 熊谷 祐子, 太白 健一, 直井 大志, 佐田友 藍, 大澤 英之, 宮戸 秀世, 鯉沼 広治, 堀江 久永, 山口 博紀, 佐田 尚宏
    日本癌治療学会学術集会抄録集 60回 YOA O15-3 2022年10月  
  • 齋藤 心, 山口 博紀, 金丸 理人, 高橋 和也, 金子 勇貴, 松本 志郎, 加賀谷 丈紘, 風當 ゆりえ, 齋藤 晶, 大澤 英之, 宮戸 秀世, 倉科 憲太郎, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本臨床外科学会雑誌 83(増刊) S87-S87 2022年10月  
  • Mineyuki Tojo, Hisanaga Horie, Koji Koinuma, Hideyo Miyato, Hidenori Tsukui, Yuki Kaneko, Yurie Futoh, Yuki Kimura, Kazuya Takahashi, Akira Saito, Hideyuki Ohzawa, Hironori Yamaguchi, Alan Kawarai Lefor, Naohiro Sata, Joji Kitayama
    Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland 24(10) 1140-1149 2022年10月  
    AIM: The clinical efficacy of chemoradiotherapy (CRT) is largely dependent on host immune status. The aim of this study was to identify possible markers expressed on circulating mononuclear cells to predict tumour response in patients with locally advanced rectal cancer (LARC). METHODS: Peripheral blood samples were obtained from 47 patients diagnosed with LARC before and after CRT. The numbers of lymphocytes and monocyte subsets were analysed using flow cytometry. Based on clinical and pathological findings, patients were classified as high or low responders. RESULTS: Lymphocyte counts were markedly decreased after CRT. Total numbers of lymphocytes (p = 0.030) and CD4(+) T cells (p = 0.041) in post-CRT samples were significantly lower in low responders than in high responders. In contrast, monocyte counts were not reduced and the number of CD14dim (+) CD16(+) nonclassical (patrolling) monocytes were somewhat increased after CRT (p = 0.050). Moreover, the ratios of programmed cell death ligand 1 (PD-L1) (+) cells on patrolling monocytes before and after CRT were significantly higher in low responders than in high responders (p = 0.0046, p = 0.0006). The same trend was observed for classical and intermediate monocytes. The expression of PD-L1 on patrolling monocytes before CRT correlated inversely with the number of T cells and natural killer (NK) cells after CRT. PD-L1(+) ratio in patrolling monocytes was an independent predictor for response to CRT. CONCLUSION: Programmed cell death ligand 1 (PD-L1) expression on patrolling monocytes suppresses cell-mediated immunity in patients receiving CRT which could be related to tumour response, and may be a useful biomarker for decision-making in the management of patients with LARC.
  • 山口 博紀, 金丸 理人, 高橋 和也, 加賀谷 丈紘, 松本 志郎, 倉科 憲太郎, 齋藤 心, 大澤 英之, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本癌治療学会学術集会抄録集 60回 OWS35-7 2022年10月  
  • 高橋 和也, 大澤 英之, 金丸 理人, 松本 志郎, 倉科 憲太郎, 齋藤 心, 山口 博紀, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本癌治療学会学術集会抄録集 60回 O69-3 2022年10月  
  • 田村 昂平, 松宮 美沙希, 高橋 礼, 金子 勇貴, 風當 ゆりえ, 高橋 和也, 木村 有希, 宮戸 秀世, 大澤 英之, 嵯峨 泰, 竹井 裕二, 藤原 寛行, 北山 丈二
    日本癌学会総会記事 81回 P-1156 2022年9月  
  • 金子 勇貴, 宮戸 秀世, 松宮 美沙希, 高橋 礼, 田村 昂平, 風當 ゆりえ, 高橋 和也, 木村 有希, 齋藤 晶, 東條 峰之, 大澤 英之, 佐田 尚宏, 北山 丈二
    日本癌学会総会記事 81回 P-1134 2022年9月  
  • 北山 丈二, 山口 博紀, 大澤 英之, 宮戸 秀世, 木村 有希, 高橋 和也, 金子 勇貴, 風當 ゆりえ, 斎藤 心, 細谷 好則, 佐田 尚宏
    日本癌学会総会記事 81回 SST3-6 2022年9月  
  • 風當 ゆりえ, 北山 丈二, 金子 勇貴, 高橋 和也, 木村 有希, 太田 学, 熊谷 祐子, 太白 健一, 直井 大志, 佐田友 藍, 井上 賢之, 大澤 英之, 宮戸 秀世, 鯉沼 広治, 佐久間 康成, 堀江 久永, 細谷 好則, 佐田 尚宏
    日本大腸肛門病学会雑誌 75(9) A202-A202 2022年9月  
  • Kohei Tamura, Hideyo Miyato, Rihito Kanamaru, Ai Sadatomo, Kazuya Takahashi, Hideyuki Ohzawa, Takahiro Koyanagi, Yasushi Saga, Yuji Takei, Hiroyuki Fujiwara, Alan Kawarai Lefor, Naohiro Sata, Joji Kitayama
    Heliyon 8(6) e09730 2022年6月  
    PURPOSE: Although neutrophil extracellular traps (NETs) are present in various tumors, their roles in tumor biology have not been clarified yet. In this study, we examined how NETs affect the pharmacokinetics and effects of doxorubicin (DOX). METHODS: NETs were generated by neutrophils stimulated with phorbol 12-myristate 13-acetate (PMA) or lipopolysaccharide (LPS). DOX was added to NETs and their distribution was observed under fluorescein microscopy, and the diffusion of DOX through 3 μM pores from lower to upper chambers was evaluated with a fluorescence-based assay. Ovarian cancer cells, KOC-2S and SKOV3, were embedded in collagen gel droplets and cultured in 3D way and their apoptosis was examined with flow cytometry. RESULTS: DOX was mostly co-localized with NETs. The transfer of DOX to upper chambers increased over time, which was significantly decreased by the presence of neutrophils stimulated with PMA or LPS in the lower chamber. DOX outside of the gel increased the rates of annexin V (+) apoptotic cells, which were significantly reduced by the addition of LPS-stimulated neutrophils in media both in KOC-2S and SKOV3. The reduced diffusion and apoptosis were mostly restored by the destruction of the NETs structure with 1000 u/ml DNAse I. CONCLUSION: NETs efficiently trap and inhibit the diffusion of DOX which may attenuate its ability to induce apoptosis of ovarian cancer cells. Degradation of NETs with DNAse I may augment the response of ovarian cancer to DOX.
  • Mineyuki Tojo, Hideyo Miyato, Koji Koinuma, Hisanaga Horie, Hidenori Tsukui, Yuki Kimura, Yuki Kaneko, Hideyuki Ohzawa, Hironori Yamaguchi, Kotaro Yoshimura, Alan Kawarai Lefor, Naohiro Sata, Joji Kitayama
    Scientific Reports 12(1) 2022年5月4日  
    Abstract Although preoperative chemoradiation therapy can down-stage locally advanced rectal cancer (LARC), it has little effect on distant metastases. Metformin exerts an anti-cancer effect partly through the activation of host immunity. LuM1, a highly lung metastatic subclone of colon 26, was injected subcutaneously (sc) in BALB/c mice and treated with metformin and/or local radiation (RT). Lung metastases and the primary tumors were evaluated and the phenotypes of immune cells in the spleen and lung metastases were examined with flow cytometry and immunohistochemistry. Local RT, but not metformin, partially delayed the growth of sc tumor which was augmented with metformin. Lung metastases were unchanged in metformin or RT alone, but significantly reduced in the combined therapy. The ratios of splenic T cells tended to be low in the RT group, which were increased by the addition of metformin. IFN-γ production of the splenic CD4(+) and CD8(+) T cells was enhanced and CD49b (+) CD335(+) activated NK cells was increased after combined treatment group. Density of NK cells infiltrating in lung metastases was increased after combination treatment. Metformin effectively enhances local and abscopal effects of RT though the activation of cell-mediated immunity and might be clinically useful for LARC.
  • 高橋 和也, 大澤 英之, 金丸 理人, 倉科 憲太郎, 齋藤 心, 山口 博紀, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本胃癌学会総会記事 94回 255-255 2022年3月  
  • Yuki Kimura, Hideyuki Ohzawa, Hideyo Miyato, Yuki Kaneko, Akira Saito, Kazuya Takahashi, Mineyuki Tojo, Hironori Yamaguchi, Kentaro Kurashina, Shin Saito, Yoshinori Hosoya, Alan Kawarai Lefor, Naohiro Sata, Joji Kitayama
    Scientific reports 12(1) 205-205 2022年1月7日  
    Peritoneal dissemination is a major metastatic pathway for gastrointestinal and ovarian malignancies. The miR-29b family is downregulated in peritoneal fluids in patients with peritoneal metastases (PM). We examined the effect of miR-29b on mesothelial cells (MC) which play critical a role in the development of PM through mesothelial-mesenchymal transition (MMT). Human peritoneal mesothelial cells (HPMCs) were isolated from surgically resected omental tissue and MMT induced by stimulation with 10 ng/ml TGF-β1. MiR-29b mimics and negative control miR were transfected by lipofection using RNAiMAX and the effects on the MMT evaluated in vitro. HPMC produced substantial amounts of miR-29b which was markedly inhibited by TGF-β1. TGF-β1 stimulation of HPMC induced morphological changes with decreased expression of E-cadherin and calretinin, and increased expression of vimentin and fibronectin. TGF-β1 also enhanced proliferation and migration of HPMC as well as adhesion of tumor cells in a fibronectin dependent manner. However, all events were strongly abrogated by simultaneous transfection of miR-29b. MiR-29b inhibits TGF-β1 induced MMT and replacement of miR-29b in the peritoneal cavity might be effective to prevent development of PM partly through the effects on MC.
  • 山口 博紀, 大澤 英之, 知念 崇, 金丸 理人, 倉科 憲太郎, 斎藤 心, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本成人病(生活習慣病)学会会誌 47 38-38 2022年1月  
  • 齋藤 晶, 大澤 英之, 田村 昂平, 金子 勇貴, 風當 ゆりえ, 高橋 和也, 木村 有希, 東條 峰之, 宮戸 秀世, 佐田 尚宏, 北山 丈二
    日本成人病(生活習慣病)学会会誌 47 75-75 2022年1月  
  • Kazuya Takahashi, Kentaro Kurashina, Hironori Yamaguchi, Rihito Kanamaru, Hideyuki Ohzawa, Hideyo Miyato, Shin Saito, Yoshinori Hosoya, Alan Kawarai Lefor, Naohiro Sata, Joji Kitayama
    Frontiers in immunology 13 969468-969468 2022年  
    Background: The peritoneal cavity contains many site-specific immune cells which constitute a unique immune microenvironment. However, it is unclear how the local immune signature is altered in patients with peritoneal metastases (PM). Methods: Peritoneal lavage fluid or ascites were obtained from 122 patients with various stages of gastric cancer (GC). Cells recovered from peritoneal fluids were immunostained with mAbs for lymphocyte-, macrophage- and tumor cell-specific antigens and the frequencies of leukocyte subsets and antigen expression levels were evaluated with multi-color flowcytometry. Results: The proportions of CD8(+) T cells, CD3(+)CD56(+) NKT-like cells, and CD3(-)CD56(+) NK cells to CD45(+) leukocytes were significantly reduced in patients with PM compared to those without PM. In patients with PM, the rates of CD8 (+) T cells and NKT-like cells correlated inversely with the tumor leukocyte ratio (TLR), the relative frequency of CD326(+) tumor cells to CD45(+) leukocytes. In contrast, the proportion of CD19(+) B cells was significantly increased in patients with PM, and their proportion correlated positively with the TLR and peritoneal carcinomatosis index (PCI) score. In patients with PM, CD14(+) macrophages tended to be increased with enhanced expression of CD14, CD16 and a M2-macrophage marker, CD163. In particular, macrophages in patients with high TLR contained many granules with high side scatter and CD14 expression in their flow profile compared to those without PM. Conclusion: PM are accompanied by a drastic change in phenotypes of lymphocyte and macrophage in the peritoneal cavity, which might be involved in the development and progression of intraperitoneal tumor growth.
  • YUKO KUMAGAI, YURIE FUTOH, HIDEYO MIYATO, HIDEYUKI OHZAWA, HIRONORI YAMAGUCHI, SHIN SAITO, KENTARO KURASHINA, YOSHINORI HOSOYA, ALAN KAWARAI LEFOR, NAOHIRO SATA, JOJI KITAYAMA
    In Vivo 36(3) 1126-1135 2022年  
  • 齋藤 晶, 大澤 英之, 田村 昂平, 金子 勇貴, 風當 ゆりえ, 高橋 和也, 木村 有希, 東條 峰之, 宮戸 秀世, 北山 丈二
    日本癌治療学会学術集会抄録集 59回 O26-6 2021年10月  
  • 東條 峰之, 津久井 秀則, 金子 勇貴, 風當 ゆりえ, 木村 有希, 高橋 和也, 齋藤 晶, 大澤 英之, 宮戸 秀世, 鯉沼 広治, 堀江 久永, 佐田 尚宏, 北山 丈二
    日本癌治療学会学術集会抄録集 59回 O57-4 2021年10月  
  • 金子 勇貴, 大澤 英之, 高橋 和也, 金丸 理人, 倉科 憲太郎, 宮戸 秀世, 齋藤 心, 山口 博紀, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本癌治療学会学術集会抄録集 59回 O31-5 2021年10月  
  • 高橋 和也, 大澤 英之, 金丸 理人, 倉科 憲太郎, 齋藤 心, 山口 博紀, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本癌治療学会学術集会抄録集 59回 O46-3 2021年10月  
  • 齋藤 晶, 大澤 英之, 金子 勇貴, 田村 昂平, 風當 ゆりえ, 高橋 和也, 木村 有希, 東條 峰之, 宮戸 秀世, 北山 丈二
    日本癌学会総会記事 80回 [E12-2] 2021年9月  
  • 木村 有希, 大澤 英之, 金子 勇貴, 風當 ゆりえ, 田村 昂平, 高橋 和也, 齋藤 晶, 東條 峰之, 宮戸 秀世, 佐田 尚宏, 北山 丈二
    日本癌学会総会記事 80回 [J10-5] 2021年9月  
  • 風當 ゆりえ, 北山 丈二, 田村 昂平, 金子 勇貴, 高橋 和也, 木村 有希, 齋藤 晶, 東條 峰之, 大澤 英之, 宮戸 秀世, 山口 博紀, 佐田 尚宏
    日本癌学会総会記事 80回 [P12-5] 2021年9月  
  • 金子 勇貴, 大澤 英之, 木村 有希, 田村 昂平, 風當 ゆりえ, 高橋 和也, 齋藤 晶, 東條 峰之, 宮戸 秀世, 佐田 尚宏, 北山 丈二
    日本癌学会総会記事 80回 [P21-3] 2021年9月  
  • 田村 昂平, 金子 勇貴, 風當 ゆりえ, 高橋 和也, 木村 有希, 齋藤 晶, 東條 峰之, 金丸 理人, 佐田友 藍, 宮戸 秀世, 大澤 英之, 嵯峨 泰, 竹井 裕二, 藤原 寛行, 北山 丈二
    日本癌学会総会記事 80回 [E12-2] 2021年9月  
  • Yuji Kaneda, Yuki Kimura, Akira Saito, Hideyuki Ohzawa, Ryusuke Ae, Hiroshi Kawahira, Alan K Lefor, Naohiro Sata
    Cureus 13(9) e18238 2021年9月  
    Introduction Although new techniques and devices have been introduced, the incidence of postoperative pancreatic fistula (POPF) after distal pancreatectomy remains high. To reduce the risk of POPF, we developed an innovative ligation band and conducted this pilot study to assess the possibility of reducing the incidence of POPF and pancreatic necrosis after distal pancreatectomy. Methods Distal pancreatectomy was performed in three pigs. In two animals, ligation of the pancreas was performed while maintaining arterial blood flow to the stump, and in one animal, the arterial blood flow was occluded. After ligation, the pancreas was sharply divided. Animals were sacrificed seven days later, and the remnant pancreas was assessed histologically. POPF was defined as amylase in ascites > 3x the preoperative serum amylase level. The following equation was used to quantify the extent of necrotic tissue: necrotic tissue residual rate = necrotic tissue area/ cross-sectional area. Results All animals survived, and no POPF developed. For two animals in which arterial blood flow to the stump was maintained, necrotic tissue residual rates at the ligation line were 24% and 31%. At the pancreatic stump, necrotic tissue residual rates were 37% and 50%. In the animal in which arterial blood flow to the stump was occluded, the necrotic tissue residual rate at the ligation line was 83% and that at the pancreatic stump was 78%, both higher than that in animals in which arterial blood flow was maintained. In all animals, there was no injury to pancreatic tissue at the ligation line. Conclusion The pancreas ligation band can potentially prevent POPF after distal pancreatectomy by atraumatic ligation, and the band ligates the pancreatic stump while maintaining arterial blood flow and limiting pancreatic necrosis.
  • 風當 ゆりえ, 宮戸 英世, 金子 勇貴, 高橋 和也, 木村 有希, 齋藤 晶, 東條 峰之, 大澤 英之, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 76回 P212-5 2021年7月  
  • Saito Shin, Yamaguchi Hironori, Kanamaru Rihito, Ohzawa Hideyuki, Kurashina Kentaro, Takahashi Kazuya, Kaneko Yuki, Hosoya Yoshinori, Sata Naohiro, Kitayama Joji
    日本消化器外科学会総会 76回 SY5-1 2021年7月  
  • 高橋 和也, 大澤 英之, 金丸 理人, 倉科 憲太郎, 齋藤 心, 山口 博紀, 細谷 好則, 北山 丈二, 佐田 尚宏
    日本消化器外科学会総会 76回 P022-4 2021年7月  
  • 金丸 理人, 山口 博紀, 齋藤 心, 倉科 憲太郎, 大澤 英之, 高橋 和也, 金子 勇貴, 細谷 好則, 佐田 尚宏, 北山 丈二
    日本消化器外科学会総会 76回 PD3-3 2021年7月  

MISC

 30

講演・口頭発表等

 98

共同研究・競争的資金等の研究課題

 8