Faculty Profiles - FUJIWARA Toshiyoshi

Papers - FUJIWARA Toshiyoshi

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食道胃接合部癌に対する治療戦略食道胃接合部癌に対する胸腔鏡腹腔鏡を併用した切除再建術式の有用性

野間和広, 白川靖博, 西脇紀之, 松田達雄, 前田直見, 田辺俊介, 藤原俊義

日本内視鏡外科学会雑誌 23 ( 7 ) SY8 - 2 2018.12

チーム医療における人材育成のためのカダバーサージカルトレーニング

近藤喜太, 前田直見, 黒田新士, 信岡大輔, 白川靖博, 藤原俊義

日本内視鏡外科学会雑誌 23 ( 7 ) OS223 - 1 2018.12

巨大食道裂孔ヘルニアの噴門形成術後に発症した胃噴門部癌に対するRedo surgery

田辺俊介, 白川靖博, 西脇紀之, 松田達雄, 前田直見, 桑田和也, 菊地覚次, 黒田新士, 野間和広, 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 23 ( 7 ) OS148 - 1 2018.12

上腹部開腹歴を有する腹腔鏡下胃切除術における安全性の検討

津村朋子, 黒田新士, 桑田和也, 菊池覚次, 西崎正彦, 香川俊輔, 白川靖博, 藤原俊義

日本内視鏡外科学会雑誌 23 ( 7 ) OS115 - 5 2018.12

陰圧閉鎖療法を極める-NPWTの至適使用法(チーム医療、効果的使用法、使用部位、等)- 消化器外科領域における陰圧閉鎖療法の意義と使用時期に関する検討

近藤喜太, 藤原俊義

日本創傷治癒学会プログラム・抄録集 48回 119 - 119 2018.11

Cancer-Associated Fibroblasts Affect Intratumoral CD8(+) and FoxP3(+) T Cells Via IL6 in the Tumor Microenvironment Reviewed International journal

Kato Takuya, Noma Kazuhiro, Ohara Toshiaki, Kashima Hajime, Katsura Yuki, Sato Hiroaki, Komoto Satoshi, Katsube Ryoichi, Ninomiya Takayuki, Tazawa Hiroshi, Shirakawa Yasuhiro, Fujiwara Toshiyoshi

CLINICAL CANCER RESEARCH 24 ( 19 ) 4820 - 4833 2018.10

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

Purpose: Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) play a central role in tumor progression. We investigated whether CAFs can regulate tumor-infiltrating lymphocytes (TILs) and their role in tumor immunosuppression.Experimental Design: A total of 140 cases of esophageal cancer were analyzed for CAFs and CD8+ or forkhead box protein 3 (FoxP3+) TILs by IHC. We analyzed cytokines using murine or human fibroblasts and cancer cells. Murine-derived fibroblasts and cancer cells were also inoculated into BALB/c or BALB/c-nu/nu mice and the tumors treated with recombinant IL6 or anti-IL6 antibody.Results: CD8+ TILs and CAFs were negatively correlated in intratumoral tissues (P < 0.001), whereas FoxP3+ TILs were positively correlated (P < 0.001) in esophageal cancers. Cocultured Colon26 cancer cells and fibroblasts resulted in accelerated tumor growth in BALB/c mice, along with decreased CD8+ and increased FoxP3+ TILs, compared with cancer cells alone. In vitro, IL6 was highly secreted in both murine and human cancer cell/fibroblast cocultures. IL6 significantly increased Colon26 tumor growth in immune-competent BALB/c (P < 0.001) with fewer CD8+ TILs than untreated tumors (P < 0.001), whereas no difference in BALB/c-nu/nu mice. In contrast, FoxP3+ TILs increased in IL6-treated tumors (P < 0.001). IL6 antibody blockade of tumors cocultured with fibroblasts resulted not only in regression of tumor growth but also in the accumulation of CD8+ TILs in intratumoral tissues.Conclusions: CAFs regulate immunosuppressive TIL populations in the TME via IL6. IL6 blockade, or targeting CAFs, may improve preexisting tumor immunity and enhance the efficacy of conventional immunotherapies. Clin Cancer Res; 24(19); 4820-33. ©2018 AACR.

DOI： 10.1158/1078-0432.CCR-18-0205

Web of Science

PubMed

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Cancer-associated fibroblasts (CAFs) promote the lymph node metastasis of esophageal squamous cell carcinoma. Reviewed International journal

Kashima H, Noma K, Ohara T, Kato T, Katsura Y, Komoto S, Sato H, Katsube R, Ninomiya T, Tazawa H, Shirakawa Y, Fujiwara T

International journal of cancer 144 ( 4 ) 828 - 840 2018.10

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

Lymph node metastasis is a pathognomonic feature of spreading tumors, and overcoming metastasis is a challenge in attaining more favorable clinical outcomes. Esophageal cancer is an aggressive tumor for which lymph node metastasis is a strong poor prognostic factor, and the tumor microenvironment (TME), and cancer-associated fibroblasts (CAFs) in particular, has been implicated in esophageal cancer progression. CAFs play a central role in the TME and have been reported to provide suitable conditions for the progression of esophageal cancer, similar to their role in other malignancies. However, little is known concerning the relevance of CAFs to the lymph node metastasis of esophageal cancer. Here, we used clinical samples of esophageal cancer to reveal that CAFs promote lymph node metastasis and subsequently verified the intercellular relationships in vitro and in vivo using an orthotopic metastatic mouse model. In the analysis of clinical samples, FAP+ CAFs were strongly associated with lymph node metastasis rather than with other prognostic factors. Furthermore, CAFs affected the ability of esophageal cancer cells to acquire metastatic phenotypes in vitro; this finding was confirmed by data from an in vivo orthotopic metastatic mouse model showing that the number of lymph node metastases increased upon injection of cocultured cancer cells and CAFs. In summary, we verified in vitro and in vivo that the accumulation of CAFs enhances the lymph node metastasis of ESCC. Our data suggest that CAF targeted therapy can reduce lymph node metastasis and improve the prognosis of patients with esophageal cancer in the future.

DOI： 10.1002/ijc.31953

PubMed

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Integrated fluorescent cytology with nano-biologics in peritoneally disseminated gastric cancer. Reviewed

Watanabe M, Kagawa S, Kuwada K, Hashimoto Y, Shigeyasu K, Ishida M, Sakamoto S, Ito A, Kikuchi S, Kuroda S, Kishimoto H, Tomida S, Yoshida R, Tazawa H, Urata Y, Fujiwara T

Cancer science 109 ( 10 ) 3263 - 3271 2018.10

食道癌鏡視下手術における拡大視野での新しい外科解剖胸腔鏡下食道癌手術における高精細画像がもたらす微細解剖

白川靖博, 橋本将志, 西脇紀之, 松田達雄, 前田直見, 田辺俊介, 野間和広, 楳田祐三, 菊地覚次, 黒田新士, 西崎正彦, 香川俊輔, 藤原俊義

日本臨床外科学会雑誌 79 ( 増刊 ) 409 - 409 2018.10

胃癌・低侵襲手術-ロボット手術と鏡視下手術- ロボット支援下幽門側胃切除術の導入と噴門側胃切除術・胃全摘術への応用

西崎正彦, 黒田新士, 菊地覚次, 桑田和也, 津村朋子, 香川俊輔, 白川靖博, 藤原俊義

日本臨床外科学会雑誌 79 ( 増刊 ) 394 - 394 2018.10

【消化器外科ロボット支援手術の実際】ロボット支援腹腔鏡下噴門側胃切除術

西崎正彦, 黒田新士, 菊地覚次, 野間和広, 白川靖博, 藤原俊義

手術 72 ( 11 ) 1589 - 1594 2018.10

高齢者に対する食道裂孔ヘルニア手術によるQOL改善への貢献

田辺俊介, 白川靖博, 前田直見, 二宮卓之, 野間和広, 藤原俊義

日本老年医学会雑誌 55 ( 4 ) 719 - 719 2018.10

重複癌の治療戦略〜食道癌〜食道癌手術症例の同時性異時性重複癌の検討

田辺俊介, 白川靖博, 西脇紀之, 松田達雄, 前田直見, 野間和広, 楳田祐三, 藤原俊義

日本臨床外科学会雑誌 79 ( 増刊 ) 335 - 335 2018.10

食道癌の鏡視下手術のトラブルシューティング腹臥位鏡視下食道癌手術のヒヤリハットとトラブルシューティング

野間和広, 白川靖博, 西脇紀之, 松田達雄, 前田直見, 田辺俊介, 櫻間教文, 藤原俊義

日本臨床外科学会雑誌 79 ( 増刊 ) 308 - 308 2018.10

【食道癌(第2版)-基礎・臨床研究の進歩-】食道癌の治療外科治療食道胃接合部癌に対する手術経裂孔的食道切除術腹腔鏡手術

白川靖博, 前田直見, 田辺俊介, 野間和広, 藤原俊義

日本臨床 76 ( 増刊8 食道癌 ) 305 - 310 2018.10

膵鈎部癌に対する上腸間膜動脈周囲郭清の郭清手技腫瘍進展に基づいたleft-lateral approach

吉田一博, 楳田祐三, 吉田龍一, 信岡大輔, 杭瀬崇, 安井和也, 田渕幹康, 西山岳芳, 白川靖博, 八木孝仁, 藤原俊義

日本臨床外科学会雑誌 79 ( 増刊 ) 448 - 448 2018.10

遠隔転移を有する膵神経内分泌腫瘍の治療戦略膵神経内分泌腫瘍(panNEN)における、肝転移症例の検討と外科的治療戦略

田渕幹康, 杭瀬崇, 西山岳芳, 安井和也, 吉田一博, 信岡大輔, 吉田龍一, 楳田祐三, 八木孝仁, 藤原俊義

日本臨床外科学会雑誌 79 ( 増刊 ) 332 - 332 2018.10

消化管がん治療の新展開食道癌におけるがん細胞及びがん関連線維芽細胞に対するDual-targeting Photoimmunotherapy(Developments in gastrointestinal cancer treatments Dual-targeting Photoimmunotherapy for esophageal cancer and cancer-associated fibroblasts in tumor microenvironment) Reviewed

佐藤浩明, 野間和広, 鳴坂徹, 河本慧, 大原利章, 田澤大, 藤原俊義

日本癌学会総会記事 77回 96 - 96 2018.9

[The Elucidation of Tumor Immunosuppression Affected by Cancer-Associated Fibroblasts]. Reviewed

Takuya Kato, Kazuhiro Noma, Yuki Katsura, Hiroaki Sato, Satoshi Kohmoto, Takayuki Ninomiya, Toshiaki Ohara, Hiroshi Tazawa, Shunsuke Kagawa, Yasuhiro Shirakawa, Toshiyoshi Fujiwara

Gan to kagaku ryoho. Cancer & chemotherapy 45 ( 9 ) 1279 - 1281 2018.9

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

Development of immunotherapy, especially checkpoint inhibitors, dramatically improved the prognosis of some malignancies. However, problems on the occurrence of severe adverse effects and limited responses to these checkpoint inhibitors remain. Recently, tumor infiltrating lymphocytes(TILs)are the predictive markers of immunotherapies based on clinical evidence. The proportion of cytotoxic T cells in the tumor has been reported to affect the antitumor effect. TILs in the tumor are thought to be controlled by the interaction between cancer and tumor microenvironment. As a cause of tumor immunosuppression, cancer-associated fibroblasts(CAFs)play the main role in the tumor microenvironment. We considered the strong involvement of tumor microenvironment, particularly the role of CAFs, and reported the interaction between CAFs and proliferation, invasion, angiogenesis, and resistance in the conventional therapy. The correlation between CAFs and tumor immunity and the immunosuppression promoted by CAFs were also evaluated. Their effects will be reported in our future studies.

PubMed

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炎症性微小環境-大腸がんクロストークにおけるEMTイメージング(Visualization of epithelial-mesenchymal transition in inflammatory microenvironment-colorectal cancer crosstalk) Reviewed

田澤大, 家田偉史, 矢野修也, 重安邦俊, 黒田新士, 大原利章, 野間和広, 岸本浩行, 西崎正彦, 香川俊輔, 斎藤卓, 今村健志, 藤原俊義

日本癌学会総会記事 77回 1204 - 1204 2018.9

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Papers - FUJIWARA Toshiyoshi