Faculty Profiles - FUJIWARA Toshiyoshi

Papers - FUJIWARA Toshiyoshi

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Role of Surgery for Pancreatic Ductal Adenocarcinoma in the Era of Multidisciplinary Treatment. Reviewed International journal

Kosei Takagi, Yuzo Umeda, Ryuichi Yoshida, Tomokazu Fuji, Kazuya Yasui, Takahito Yagi, Toshiyoshi Fujiwara

Journal of clinical medicine 12 ( 2 ) 2023.1

Survival Impact of Postoperative Skeletal Muscle Loss in Gastric Cancer Patients Who Underwent Gastrectomy. Reviewed International journal

Kazuya Kuwada, Satoru Kikuchi, Shinji Kuroda, Ryuichi Yoshida, Kosei Takagi, Kazuhiro Noma, Masahiko Nishizaki, Shunsuke Kagawa, Yuzo Umeda, Toshiyoshi Fujiwara

Anticancer research 43 ( 1 ) 223 - 230 2023.1

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND/AIM: It has recently been recognized that preoperative sarcopenia contributes to postoperative complications and overall survival in gastric cancer (GC). However, few studies have investigated the relationship between postoperative skeletal muscle loss (SML) and survival in GC, despite the inevitability of body weight loss after gastrectomy in most GC patients. Herein, we studied the impact of postoperative SML on GC prognosis. PATIENTS AND METHODS: A total of 370 patients with GC who underwent curative gastrectomy were retrospectively evaluated in this study. Postoperative SML was assessed on computed tomography (CT) images taken before surgery and 1 year after surgery. The impact of postoperative SML on survival was evaluated. RESULTS: Postoperative severe SML was significantly associated with presence of comorbidities, higher tumor stage, higher postoperative complication rate and longer hospital stay. Univariate and multivariate analyses of prognostic factors for overall survival revealed that SML was an independent indicator of poor prognosis, along with age, tumor stage, preoperative sarcopenia, and operation time (hazard ratio, 2.65; 95% confidence interval, 1.68-4.20, p<0.0001). There was a strong association of severe postoperative SML with decreased overall survival in patients with preoperative sarcopenia. CONCLUSION: To improve the prognosis of GC patients after surgery, it is important to prevent postoperative SML as well as preoperative sarcopenia. Perioperative multimodal interventions including nutritional counseling, oral nutritional supplements, and exercise are required to prevent SML after gastrectomy.

DOI： 10.21873/anticanres.16153

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Impact of cancer-associated fibroblasts on survival of patients with ampullary carcinoma. Reviewed International journal

Kosei Takagi, Kazuhiro Noma, Yasuo Nagai, Satoru Kikuchi, Yuzo Umeda, Ryuichi Yoshida, Tomokazu Fuji, Kazuya Yasui, Takehiro Tanaka, Hajime Kashima, Takahito Yagi, Toshiyoshi Fujiwara

Frontiers in oncology 13 1072106 - 1072106 2023

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Cancer-associated fibroblasts (CAFs) reportedly enhance the progression of gastrointestinal surgery; however, the role of CAFs in ampullary carcinomas remains poorly examined. This study aimed to investigate the effect of CAFs on the survival of patients with ampullary carcinoma. MATERIALS AND METHODS: A retrospective analysis of 67 patients who underwent pancreatoduodenectomy between January 2000 and December 2021 was performed. CAFs were defined as spindle-shaped cells that expressed α-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP). The impact of CAFs on survival, including recurrence-free (RFS) and disease-specific survival (DSS), as well as prognostic factors associated with survival, was analyzed. RESULTS: The high-α-SMA group had significantly worse 5-year RFS (47.6% vs. 82.2%, p = 0.003) and 5-year DSS (67.5% vs. 93.3%, p = 0.01) than the low-α-SMA group. RFS (p = 0.04) and DSS (p = 0.02) in the high-FAP group were significantly worse than those in the low-FAP group. Multivariable analyses found that high α-SMA expression was an independent predictor of RFS [hazard ratio (HR): 3.68; 95% confidence intervals (CI): 1.21-12.4; p = 0.02] and DSS (HR: 8.54; 95% CI: 1.21-170; p = 0.03). CONCLUSIONS: CAFs, particularly α-SMA, can be useful predictors of survival in patients undergoing radical resection for ampullary carcinomas.

DOI： 10.3389/fonc.2023.1072106

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p53-armed oncolytic adenovirus induces autophagy and apoptosis in KRAS and BRAF-mutant colorectal cancer cells. Reviewed International journal

Shuta Tamura, Hiroshi Tazawa, Naoto Hori, Yuncheng Li, Motohiko Yamada, Satoru Kikuchi, Shinji Kuroda, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara

PloS one 18 ( 11 ) e0294491 2023

Language：English Publishing type：Research paper (scientific journal)

Colorectal cancer (CRC) cells harboring KRAS or BRAF mutations show a more-malignant phenotype than cells with wild-type KRAS and BRAF. KRAS/BRAF-wild-type CRCs are sensitive to epidermal growth factor receptor (EGFR)-targeting agents, whereas KRAS/BRAF-mutant CRCs are resistant due to constitutive activation of the EGFR-downstream KRAS/BRAF signaling pathway. Novel therapeutic strategies to treat KRAS/BRAF mutant CRC cells are thus needed. We recently demonstrated that the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 exhibit therapeutic potential against KRAS-mutant human pancreatic cancer cells. In this study, we evaluated the therapeutic potential of OBP-301 and OBP-702 against human CRC cells with differing KRAS/BRAF status. Human CRC cells with wild-type KRAS/BRAF (SW48, Colo320DM, CACO-2), mutant KRAS (DLD-1, SW620, HCT116), and mutant BRAF (RKO, HT29, COLO205) were used in this study. The antitumor effect of OBP-301 and OBP-702 against CRC cells was analyzed using the XTT assay. Virus-mediated modulation of apoptosis, autophagy, and the EGFR-MEK-ERK and AKT-mTOR signaling pathways was analyzed by Western blotting. Wild-type and KRAS-mutant CRC cells were sensitive to OBP-301 and OBP-702, whereas BRAF-mutant CRC cells were sensitive to OBP-702 but resistant to OBP-301. Western blot analysis demonstrated that OBP-301 induced autophagy and that OBP-702 induced autophagy and apoptosis in human CRC cells. In BRAF-mutant CRC cells, OBP-301 and OBP-702 suppressed the expression of EGFR, MEK, ERK, and AKT proteins, whereas mTOR expression was suppressed only by OBP-702. Our results suggest that p53-armed oncolytic virotherapy is a viable therapeutic option for treating KRAS/BRAF-mutant CRC cells via induction of autophagy and apoptosis.

DOI： 10.1371/journal.pone.0294491

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チームでベッドサイドに寄り添う周術期栄養管理食道癌外科治療予後向上のための院内横断的周術期管理術前から術後までサポート

野間和広, 河崎健人, 國友知義, 橋本将志, 加藤卓也, 前田直見, 菊地覚次, 藤原俊義

外科と代謝・栄養 57 ( 3 ) 89 - 89 2023

RNA editing is a valuable biomarker for predicting carcinogenesis in ulcerative colitis. International journal

Kazutaka Takahashi, Kunitoshi Shigeyasu, Yoshitaka Kondo, Kazuyoshi Gotoh, Shuya Yano, Yuzo Umeda, Toshihiro Inokuchi, Caiming Xu, Kazuhiro Yoshida, Hibiki Umeda, Toshiaki Takahashi, Sho Takeda, Ryuichi Yoshida, Fuminori Teraishi, Hiroyuki Kishimoto, Yoshiko Mori, Kazuhiro Noma, Yoshinaga Okugawa, Sakiko Hiraoka, Hiroyuki Michiue, Hiroshi Tazawa, Osamu Matsushita, Ajay Goel, Toshiyoshi Fujiwara

Journal of Crohn's & colitis 17 ( 5 ) 754 - 766 2022.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND AND AIMS: Ulcerative colitis (UC) can develop colitis-associated colorectal neoplasm (CAN). Adenine-to-inosine RNA editing, which is regulated by adenosine deaminase acting on RNA (ADAR), induces the posttranscriptional modification of critical oncogenes, including antizyme inhibitor 1 (AZIN1), leading to colorectal carcinogenesis. Therefore, we hypothesized that ADAR1 might be involved in the development of CAN in UC. METHODS: We systematically analyzed a cohort of 139 UC cases (40 acute phase, 73 remission phase, 26 CAN). The degree of inflammation was evaluated using the Mayo endoscopic score (MES). RESULTS: The type 1 IFN-related inflammation pathway was upregulated in the rectum of active UC, rectum of UC-CAN, and tumor site of UC-CAN patients. ADAR1 expression was upregulated in the entire colon of CAN cases, while it was down-regulated in non-CAN MES0 cases. ADAR1 expression in the rectum predicted the development of CAN better than p53 or β-catenin, with an area under the curve of 0.93. The high expression of ADAR1 and high AZIN1 RNA editing in UC was triggered by type 1 IFN stimulation from UC-specific microbiomes, such as Fusobacterium in vitro analyses. The induction of AZIN1 RNA editing by ADAR1, whose expression is promoted by Fusobacterium, may induce carcinogenesis in UC. CONCLUSIONS: The risk of CAN can be evaluated by assessing ADAR1 expression in the rectum of MES0 UC patients, freeing UC patients from unnecessary colonoscopy and reducing their physical burden. RNA editing may be involved in UC carcinogenesis, and may be used to facilitate the prevention and treatment of CAN in UC.

DOI： 10.1093/ecco-jcc/jjac186

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An oncolytic virus as a promising candidate for the treatment of radioresistant oral squamous cell carcinoma. International journal

Shunsuke Gohara, Kosuke Shinohara, Ryoji Yoshida, Ryusho Kariya, Hiroshi Tazawa, Masashi Hashimoto, Junki Inoue, Ryuta Kubo, Hikaru Nakashima, Hidetaka Arita, Sho Kawaguchi, Keisuke Yamana, Yuka Nagao, Asuka Iwamoto, Junki Sakata, Yuichiro Matsuoka, Hisashi Takeshita, Masatoshi Hirayama, Kenta Kawahara, Masashi Nagata, Akiyuki Hirosue, Yoshikazu Kuwahara, Manabu Fukumoto, Seiji Okada, Yasuo Urata, Toshiyoshi Fujiwara, Hideki Nakayama

Molecular therapy oncolytics 27 141 - 156 2022.12

Language：English Publishing type：Research paper (scientific journal)

We evaluated the usefulness of an oncolytic virus (Suratadenoturev; OBP-301) against radioresistant oral squamous cell carcinoma. We confirmed the expression of human telomerase reverse transcriptase and the coxsackievirus and adenovirus receptor in cell lines. Also, we examined the potential presence in a patient who has received existing therapy that is amenable to treatment with OBP-301. We evaluated: (1) the antitumor effects of OBP-301 alone and in combination with radiotherapy on radioresistant cell lines, (2) the molecular mechanism underlying the radiosensitizing effect and cell death increased by the combination therapy, and (3) the antitumor effect of the combination therapy in vivo using xenograft models (a radioresistant cell line-derived xenograft in mouse and a patient-derived xenograft). Human telomerase reverse transcriptase and the coxsackievirus and adenovirus receptor were expressed in all cell lines. OBP-301 decreased the proliferative activity of these cell lines in a concentration-dependent manner, and significantly enhanced the antitumor effect of irradiation. Phosphorylated STAT3 and its downstream molecules, which correlated with apoptosis and autophagy, showed significant changes in expression after treatment with OBP-301. The combination therapy exerted a significant antitumor effect versus radiotherapy alone in both xenograft models. Combination of OBP-301 with radiotherapy exerts a synergistic effect and may represent a promising treatment for radioresistant oral squamous cell carcinoma.

DOI： 10.1016/j.omto.2022.10.001

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Oncolytic virus-mediated p53 overexpression promotes immunogenic cell death and efficacy of PD-1 blockade in pancreatic cancer. International journal

Hiroyuki Araki, Hiroshi Tazawa, Nobuhiko Kanaya, Yoshinori Kajiwara, Motohiko Yamada, Masashi Hashimoto, Satoru Kikuchi, Shinji Kuroda, Ryuichi Yoshida, Yuzo Umeda, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara

Molecular therapy oncolytics 27 3 - 13 2022.12

Language：English Publishing type：Research paper (scientific journal)

Immune checkpoint inhibitors, including anti-programmed cell death 1 (PD-1) antibody, provide improved clinical outcome in certain cancers. However, pancreatic ductal adenocarcinoma (PDAC) is refractory to PD-1 blockade therapy due to poor immune response. Oncolytic virotherapy is a novel approach for inducing immunogenic cell death (ICD). We demonstrated the therapeutic potential of p53-expressing telomerase-specific oncolytic adenovirus OBP-702 to induce ICD and anti-tumor immune responses in human PDAC cells with different p53 status (Capan-2, PK-59, PK-45H, Capan-1, MIA PaCa-2, BxPC-3) and murine PDAC cells (PAN02). OBP-702 significantly enhanced ICD with secretion of extracellular adenosine triphosphate and high-mobility group box protein B1 by inducing p53-mediated apoptosis and autophagy. OBP-702 significantly promoted the tumor infiltration of CD8+ T cells and the anti-tumor efficacy of PD-1 blockade in a subcutaneous PAN02 syngeneic tumor model. Our results suggest that oncolytic adenovirus-mediated p53 overexpression augments ICD and the efficacy of PD-1 blockade therapy against cold PDAC tumors. Further in vivo experiments would be warranted to evaluate the survival benefit of tumor-bearing mice in combination therapy with OBP-702 and PD-1 blockade.

DOI： 10.1016/j.omto.2022.09.003

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膵癌に対する低侵襲手術のエビデンス膵体尾部癌に対するSupracolic Anterior SMAアプローチを用いたロボット支援下RAMPSの定型化と短期成績

吉田龍一, 高木弘誠, 楳田祐三, 藤智和, 安井和也, 木村次郎, 畑七々子, 藤原俊義

日本内視鏡外科学会雑誌 27 ( 7 ) 1282 - 1282 2022.12

小網アプローチによるロボット支援下脾温存膵体尾部切除

高木弘誠, 楳田祐三, 吉田龍一, 藤智和, 安井和也, 木村次郎, 畑七々子, 藤原俊義

日本内視鏡外科学会雑誌 27 ( 7 ) 1708 - 1708 2022.12

症例数の限られた地方病院での安全かつ有効な新規代謝改善手術導入の課題

賀島肇, 菊地覚次, 香川俊輔, 黒田新士, 半澤俊哉, 庄司良平, 垣内慶彦, 松三雄騎, 野間和広, 楳田祐三, 寺石文則, 藤原俊義

日本内視鏡外科学会雑誌 27 ( 7 ) 298 - 298 2022.12

縦隔郭清を伴う食道胃接合部癌に対する岡山大学病院での取り組み

橋本将志, 野間和広, 前田直見, 菊地覚次, 重安邦俊, 近藤喜太, 田辺俊介, 黒田新士, 吉田龍一, 寺石文則, 楳田祐三, 白川靖博, 藤原俊義

日本内視鏡外科学会雑誌 27 ( 7 ) 789 - 789 2022.12

術後再発困難症例に対する前方臓器温存のための集学的治療を併用したTaAPRの有用性

庄司良平, 近藤喜太, 垣内慶彦, 賀島肇, 松三雄騎, 寺石文則, 菊地覚次, 黒田新士, 田辺俊介, 野間和広, 吉田龍一, 楳田祐三, 香川俊輔, 藤原俊義

日本内視鏡外科学会雑誌 27 ( 7 ) 775 - 775 2022.12

神経モニタリングを用いたより低侵襲なロボット支援下食道手術

野間和広, 橋本将志, 前田直見, 菊地覚次, 田辺俊介, 近藤喜太, 黒田新士, 吉田龍一, 寺石文則, 楳田祐三, 白川靖博, 藤原俊義

日本内視鏡外科学会雑誌 27 ( 7 ) 1150 - 1150 2022.12

術前治療後の腹腔鏡下直腸癌手術の治療成績

寺石文則, 庄司良平, 賀島肇, 垣内慶彦, 松三雄騎, 重安邦俊, 近藤喜太, 黒田新士, 香川俊輔, 藤原俊義

日本内視鏡外科学会雑誌 27 ( 7 ) 1138 - 1138 2022.12

胸腔鏡下食道癌手術のコンセプトと成績、教育方法

前田直見, 野間和広, 橋本将志, 菊地覚次, 黒田新士, 近藤喜太, 田辺俊介, 吉田龍一, 寺石文則, 楳田祐三, 白川靖博, 藤原俊義

日本内視鏡外科学会雑誌 27 ( 7 ) 1722 - 1722 2022.12

内視鏡外科手術における遠隔医療の現状と課題内視鏡外科手術におけるカダバーサージカルトレーニング遠隔手術指導シミュレーションの実際

近藤喜太, 庄司良平, 垣内慶彦, 前田直見, 菊地覚次, 重安邦俊, 黒田新士, 田辺俊介, 野間和広, 吉田龍一, 寺石文則, 楳田祐三, 西崎正彦, 香川俊輔, 藤原俊義

日本内視鏡外科学会雑誌 27 ( 7 ) 1268 - 1268 2022.12

胃癌に対する噴門側胃切除:手技の工夫と成績観音開き法(上川法)再建における吻合部狭窄ゼロを目指した手技の改変

黒田新士, 菊地覚次, 垣内慶彦, 野間和広, 楳田祐三, 寺石文則, 香川俊輔, 藤原俊義

日本内視鏡外科学会雑誌 27 ( 7 ) 1848 - 1848 2022.12

食道良性疾患に対する胸腔鏡・腹腔鏡手術:手技の工夫と成績食道裂孔ヘルニアの腹腔鏡下根治手術における手技の工夫とQOL改善への貢献

田辺俊介, 野間和広, 橋本将志, 前田直見, 菊地覚次, 重安邦俊, 黒田新士, 近藤喜太, 吉田龍一, 寺石文則, 楳田祐三, 白川靖博, 藤原俊義

日本内視鏡外科学会雑誌 27 ( 7 ) 86 - 86 2022.12

低侵襲食道癌手術における専門医制度:食道外科専門医vs技術認定医食道外科医における技術認定制度、認定医とは?技術認定合格に必須なコンセプト

野間和広, 橋本将志, 前田直見, 菊地覚次, 田辺俊介, 近藤喜太, 黒田新士, 吉田龍一, 寺石文則, 楳田祐三, 白川靖博, 藤原俊義

日本内視鏡外科学会雑誌 27 ( 7 ) 428 - 428 2022.12

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Papers - FUJIWARA Toshiyoshi