Faculty Profiles - FUJIWARA Toshiyoshi

Papers - FUJIWARA Toshiyoshi

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Boosting Replication and Penetration of Oncolytic Adenovirus by Paclitaxel Eradicate Peritoneal Metastasis of Gastric Cancer. International journal

Wataru Ishikawa, Satoru Kikuchi, Toshihiro Ogawa, Motoyasu Tabuchi, Hiroshi Tazawa, Shinji Kuroda, Kazuhiro Noma, Masahiko Nishizaki, Shunsuke Kagawa, Yasuo Urata, Toshiyoshi Fujiwara

Molecular therapy oncolytics 18 262 - 271 2020.9

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

Peritoneal metastasis is the most frequent form of distant metastasis and recurrence in gastric cancer, and the prognosis is extremely poor due to the resistance of systemic chemotherapy. Here, we demonstrate that intraperitoneal (i.p.) administration of a green fluorescence protein (GFP)-expressing attenuated adenovirus with oncolytic potency (OBP-401) synergistically suppressed the peritoneal metastasis of gastric cancer in combination with paclitaxel (PTX). OBP-401 synergistically suppressed the viability of human gastric cancer cells in combination with PTX. PTX enhanced the antitumor effect of OBP-401 due to enhanced viral replication in cancer cells. The combination therapy increased induction of mitotic catastrophe, resulting in accelerated autophagy and apoptosis. Peritoneally disseminated nodules were selectively visualized as GFP-positive spots by i.p. administration of OBP-401 in an orthotopic human gastric cancer peritoneal dissemination model. PTX enhanced the deep penetration of OBP-401 into the disseminated nodules. Moreover, a non-invasive in vivo imaging system demonstrated that the combination therapy of i.p. OBP-401 administration with PTX significantly inhibited growth of peritoneal metastatic tumors and the amount of malignant ascites. i.p. virotherapy with PTX may be a promising treatment strategy for the peritoneal metastasis of gastric cancer.

DOI： 10.1016/j.omto.2020.06.021

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Elimination of MYCN-Amplified Neuroblastoma Cells by Telomerase-Targeted Oncolytic Virus via MYCN Suppression. International journal

Terutaka Tanimoto, Hiroshi Tazawa, Takeshi Ieda, Hiroshi Nouso, Morimichi Tani, Takanori Oyama, Yasuo Urata, Shunsuke Kagawa, Takuo Noda, Toshiyoshi Fujiwara

Molecular therapy oncolytics 18 14 - 23 2020.9

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

Neuroblastoma (NB) is a primary malignant tumor of the peripheral sympathetic nervous system. High-risk NB is characterized by MYCN amplification and human telomerase reverse transcriptase (hTERT) rearrangement, contributing to hTERT activation and a poor outcome. For targeting hTERT-activated tumors, we developed two oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in which the hTERT promoter drives expression of the viral E1 gene for tumor-specific virus replication. In this study, we demonstrate the therapeutic potential of the hTERT-driven oncolytic adenoviruses OBP-301 and OBP-702 using four human MYCN-amplified NB cell lines (IMR-32, CHP-134, NB-1, LA-N-5) exhibiting high hTERT expression. OBP-301 and OBP-702 exhibited a strong antitumor effect in association with autophagy in NB cells. Virus-mediated activation of E2F1 protein suppressed MYCN expression. OBP-301 and OBP-702 significantly suppressed the growth of subcutaneous CHP-134 tumors. Thus, these hTERT-driven oncolytic adenoviruses are promising antitumor agents for eliminating MYCN-amplified NB cells via E2F1-mediated suppression of MYCN protein.

DOI： 10.1016/j.omto.2020.05.015

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FUCCI Real-Time Cell-Cycle Imaging as a Guide for Designing Improved Cancer Therapy: A Review of Innovative Strategies to Target Quiescent Chemo-Resistant Cancer Cells. International journal

Shuya Yano, Hiroshi Tazawa, Shunsuke Kagawa, Toshiyoshi Fujiwara, Robert M Hoffman

Cancers 12 ( 9 ) 2020.9

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

Progress in chemotherapy of solid cancer has been tragically slow due, in large part, to the chemoresistance of quiescent cancer cells in tumors. The fluorescence ubiquitination cell-cycle indicator (FUCCI) was developed in 2008 by Miyawaki et al., which color-codes the phases of the cell cycle in real-time. FUCCI utilizes genes linked to different color fluorescent reporters that are only expressed in specific phases of the cell cycle and can, thereby, image the phases of the cell cycle in real-time. Intravital real-time FUCCI imaging within tumors has demonstrated that an established tumor comprises a majority of quiescent cancer cells and a minor population of cycling cancer cells located at the tumor surface or in proximity to tumor blood vessels. In contrast to most cycling cancer cells, quiescent cancer cells are resistant to cytotoxic chemotherapy, most of which target cells in S/G2/M phases. The quiescent cancer cells can re-enter the cell cycle after surviving treatment, which suggests the reason why most cytotoxic chemotherapy is often ineffective for solid cancers. Thus, quiescent cancer cells are a major impediment to effective cancer therapy. FUCCI imaging can be used to effectively target quiescent cancer cells within tumors. For example, we review how FUCCI imaging can help to identify cell-cycle-specific therapeutics that comprise decoy of quiescent cancer cells from G1 phase to cycling phases, trapping the cancer cells in S/G2 phase where cancer cells are mostly sensitive to cytotoxic chemotherapy and eradicating the cancer cells with cytotoxic chemotherapy most active against S/G2 phase cells. FUCCI can readily image cell-cycle dynamics at the single cell level in real-time in vitro and in vivo. Therefore, visualizing cell cycle dynamics within tumors with FUCCI can provide a guide for many strategies to improve cell-cycle targeting therapy for solid cancers.

DOI： 10.3390/cancers12092655

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骨肉腫に対するp53誘導性腫瘍融解ウイルスを用いたアブスコパル効果・ワクチン効果の誘導

出宮光二, 田澤大, 近藤宏也, 久禮美穂, 長谷井嬢, 中田英二, 国定俊之, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 94 ( 8 ) S1855 - S1855 2020.9

リアルタイムイメージングによる予後不良間葉型大腸癌の治療抵抗性EMTマーカーの発現の時空間的意義

三村直毅, 矢野修也, 田澤大, 家田偉史, 岡林弘樹, 重安邦俊, 武田正, 吉田一博, 寺石文則, 楳田祐三, 香川俊輔, 藤原俊義

日本分子腫瘍マーカー研究会プログラム・講演抄録 40回 56 - 58 2020.9

がん関連線維芽細胞由来IL-6制御による免疫応答の効率化バイオマーカーとしてのIL-6の可能性

西脇紀之, 野間和広, 大原利章, 河崎健人, 赤井正明, 小林照貴, 加藤卓也, 前田直見, 菊地覚次, 田辺俊介, 田澤大, 白川靖博, 藤原俊義

日本分子腫瘍マーカー研究会プログラム・講演抄録 40回 72 - 73 2020.9

【肝胆膵外科におけるConversion Surgery】大腸癌肝転移に対するConversion Surgery

楳田祐三, 吉田龍一, 杭瀬崇, 吉田一博, 藤原俊義, 八木孝仁

手術 74 ( 10 ) 1427 - 1434 2020.9

High incidence of tracheobronchial diverticulum in esophageal cancer patients: a retrospective survey alerting pitfall during thoracoscopic esophagectomy.

Noriyuki Nishiwaki, Kazuhiro Noma, Naoaki Maeda, Shunsuke Tanabe, Kazufumi Sakurama, Yasuhiro Shirakawa, Toshiyoshi Fujiwara

General thoracic and cardiovascular surgery 68 ( 9 ) 1018 - 1023 2020.9

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

OBJECTIVES: Although tracheobronchial diverticulum (DV) rarely cause problems, attention should be paid during esophagectomy, which requires careful dissection around the trachea and bronchi. Here, we retrospectively review cases of tracheobronchial DVs among esophageal cancer patients and report two cases of bronchial DV injury during thoracoscopic esophagectomy that were successfully repaired. METHODS: The thin-section CT images of esophageal cancer patients who underwent thoracoscopic esophagectomy from January 2013 to December 2015 were retrospectively reviewed. The localization, number, and size (largest axial diameter) of all detected DVs were recorded. RESULTS: A total of 180 patients were enrolled in this study. The incidence of tracheal DV was 5.0%, and that of bronchial DV was 40.0%. The median diameter of the tracheal diverticula was 2.45 [interquartile range (IQR) 2.00-8.17] mm and that of the bronchial diverticula was 1.90 (IQR 1.51-2.46) mm. All tracheal diverticula presented at the right tracheal wall 4.5-6.0 cm below the vocal cords; bronchial diverticula presented at the subcarinal lesions. We experienced two cases with bronchial diverticulum injuries during thoracoscopic esophagectomy, which were repaired by primary closure and confirmed that there was no air leak. No postoperative complications associated with bronchial injury occurred in either patient. CONCLUSION: Since tracheobronchial DVs are not as rare as previously thought, careful evaluation of thin-slice CT scans is necessary before thoracoscopic esophagectomy. If a tracheobronchial DV is injured during surgery, it is important to carefully repair it and confirm that there is no air leak to avoid complications.

DOI： 10.1007/s11748-020-01421-3

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Fibroblast activation protein-α(FAP)を標的とした癌関連線維芽細胞(CAFs)に対する光免疫療法 Sunrise of targeting tumor microenvironment therapy

小林照貴, 野間和広, 赤井正明, 西脇紀之, 鳴坂徹, 河本慧, 前田直見, 大原利章, 田辺俊介, 田澤大, 白川靖博, 藤原俊義

日本外科学会定期学術集会抄録集 120回 SF - 8 2020.8

発生学・拡大視局所微細解剖に基づく最新の手術手技【Video】進行横行結腸癌に対する複雑な幅広いD3郭清手技を結腸の成り立ちから理解することにより単純化し定型手術として言語化する

矢野修也, 近藤喜太, 寺石文則, 黒田新士, 重安邦俊, 母里淑子, 菊池覚次, 藤本卓也, 岸本浩行, 香川俊輔, 白川靖博, 藤原俊義

日本外科学会定期学術集会抄録集 120回 WS - 5 2020.8

噴門側胃切除術後再建法-食道残胃吻合 vs 食道空腸吻合-【食道残胃】噴門側胃切除術後標準再建法としての観音開き法再建の可能性

黒田新士, 西崎正彦, 丁田泰宏, 石田道拡, 村岡篤, 田中則光, 羽藤慎二, 菊地覚次, 高田暢夫, 庄司良平, 重安邦俊, 矢野修也, 近藤喜太, 田辺俊介, 野間和広, 寺石文則, 香川俊輔, 白川靖博, 上川康明, 藤原俊義

日本外科学会定期学術集会抄録集 120回 DB - 2 2020.8

局所進行直腸癌に対する術前治療における放射線治療の意義放射線療法を併用しない術前化学療法との治療成績の比較

寺石文則, 藤本卓也, 重安邦俊, 矢野修也, 近藤喜太, 香川俊輔, 藤原俊義

日本外科学会定期学術集会抄録集 120回 SF - 7 2020.8

肝内胆管癌における免疫微小環境と治療予後の関連性

小西大輔, 吉田一博, 楳田祐三, 重安邦俊, 矢野修也, 武田正, 吉田龍一, 杭瀬崇, 藤智和, 安井和也, 松田達雄, 田澤大, 白川靖博, 八木孝仁, 藤原俊義

日本外科学会定期学術集会抄録集 120回 SF - 3 2020.8

直腸癌に対するtaTMEの意義-あり vs なし-【なし】解剖学的知識と内視鏡技術に卓越しなければtaTMEの意義はない

近藤喜太, 重安邦俊, 矢野修也, 寺石文則, 藤原俊義

日本外科学会定期学術集会抄録集 120回 DB - 3 2020.8

腹腔内アプローチ困難と予想される症例に対する、taTMEの役割と安全性

藤本卓也, 近藤喜太, 矢野修也, 重安邦俊, 母里淑子, 寺石文則, 藤原俊義

日本外科学会定期学術集会抄録集 120回 DP - 2 2020.8

病的肥満症に対する腹腔鏡下スリーブ状胃切除術導入と初期10例の治療成績

香川俊輔, 黒田新士, 菊地覚次, 高田暢夫, 庄司良平, 西崎正彦, 寺石文則, 近藤喜太, 矢野修也, 重安邦俊, 野間和広, 田辺俊介, 白川靖博, 藤原俊義

日本外科学会定期学術集会抄録集 120回 DP - 5 2020.8

癌微小環境が引き起こす腫瘍免疫抑制の解明 "Drug repositioning"による免疫応答賦活化の可能性

西脇紀之, 野間和広, 赤井正明, 小林照貴, 鳴坂徹, 河本慧, 加藤卓也, 前田直見, 田辺俊介, 大原利章, 田澤大, 白川靖博, 藤原俊義

日本外科学会定期学術集会抄録集 120回 SF - 4 2020.8

Systematic review on immunonutrition in partial pancreatoduodenectomy. International journal

Kosei Takagi, Yuzo Umeda, Ryuichi Yoshida, Takahito Yagi, Toshiyoshi Fujiwara

Langenbeck's archives of surgery 405 ( 5 ) 585 - 593 2020.8

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

BACKGROUND: The effect of immunonutrition (IM) on postoperative outcomes has been investigated in gastrointestinal cancer surgery; however, strong evidence regarding IM in partial pancreatoduodenectomy (PD) is lacking. This study evaluated the effect of IM on short-term outcomes in patients undergoing PD. METHODS: A systematic literature review of randomized controlled trials was conducted to identify the studies investigating the IM effect on outcomes in PD. Random-effects meta-analyses were conducted to calculate the pooled risk ratio (RR). Studies were evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Five studies were included in the meta-analysis. IM was associated with a lower incidence of overall complications (RR 0.74; 95% confidence interval (CI) 0.58, 0.94; P = 0.01; I2 = 0%) and infectious complications (RR 0.60; 95% CI 0.42, 0.84; P = 0.003; I2 = 0%). However, no significant association was noted in the incidence of major complications (RR 0.68; 95% CI 0.41, 1.12; P = 0.13), mortality (RR 0.79; 95% CI 0.16, 3.99; P = 0.78), postoperative pancreatic fistula (RR 0.92, 95% CI 0.59, 1.46; P = 0.74), and delayed gastric emptying (RR 1.09; 95% CI 0.55, 2.15; P = 0.81). CONCLUSIONS: IM administration in PD can prevent the incidence of overall and infectious complications postoperatively (GRADE recommendation: moderate). However, IM has no impact on major complications, mortality, and PD-specific complications (GRADE recommendation: low).

DOI： 10.1007/s00423-020-01916-w

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食道胃接合部癌の手術-アプローチ法・郭清範囲・再建術式のdecision making- Siewert I型およびII型食道胃接合部癌の縦隔リンパ節転移に関するリスク因子(Risk factor for mediastinal lymph node metastasis of siewert type I and II esophagogastric junction tumors)

野間和広, 白川靖博, 赤井正明, 西江尚貴, 前田直見, 田辺俊介, 櫻間教文, 藤原俊義

日本外科学会定期学術集会抄録集 120回 PD - 2 2020.8

胃粘膜下腫瘍に対するClosed-LECSの成績と早期胃癌、十二指腸病変への応用

菊地覚次, 西崎正彦, 黒田新士, 高田暢夫, 庄司良平, 香川俊輔, 白川靖博, 藤原俊義

日本外科学会定期学術集会抄録集 120回 SF - 7 2020.8

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Papers - FUJIWARA Toshiyoshi