研究者詳細 - 香川　俊輔

論文 - 香川　俊輔

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腹腔鏡手術は開腹手術と比較して術後の筋肉量減少を予防できる可能性がある

桑田和也, 金谷信彦, 菊地覚次, 黒田新士, 吉田龍一, 西崎正彦, 香川俊輔, 藤原俊義

日本消化器外科学会総会 74回 P46 - 2 2019年7月

Clinical Impact of Sarcopenia on Gastric Cancer. 国際誌

Kazuya Kuwada, Shinji Kuroda, Satoru Kikuchi, Ryuichi Yoshida, Masahiko Nishizaki, Shunsuke Kagawa, Toshiyoshi Fujiwara

Anticancer research 39 ( 5 ) 2241 - 2249 2019年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Sarcopenia is a complex syndrome defined by progressive and generalized loss of skeletal muscle mass and strength. Although sarcopenia is mainly associated with aging, cancer is also one of its causes. Sarcopenia is now drawing attention as a poor prognostic factor in cancer. In patients with gastric cancer associated with eating disorders that often leads to loss of weight and muscle, sarcopenia is particularly important. Its definition and method of assessment, however, vary between studies, thus these need to be standardized. Nevertheless, emerging evidence suggests that sarcopenia contributes independently to postoperative complications and overall survival in gastric cancer. Interventions preventing sarcopenia with targeted nutrition and exercise are currently explored. This review aims to provide an understanding of sarcopenia, emphasizing its importance in the management of gastric cancer.

DOI： 10.21873/anticanres.13340

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テロメラーゼ標的蛍光発現ウイルスを用いた腹腔内腫瘍関連マクロファージの機能解析

桑田和也, 香川俊輔, 菊地覚次, 黒田新士, 吉田龍一, 西崎正彦, 藤原俊義

日本外科学会定期学術集会抄録集 119回 SF - 5 2019年4月

PD-L1 expression combined with microsatellite instability/CD8+ tumor infiltrating lymphocytes as a useful prognostic biomarker in gastric cancer. 査読国際誌

Morihiro T, Kuroda S, Kanaya N, Kakiuchi Y, Kubota T, Aoyama K, Tanaka T, Kikuchi S, Nagasaka T, Nishizaki M, Kagawa S, Tazawa H, Fujiwara T

Scientific reports 9 ( 1 ) 4633 - 4633 2019年3月

Activation of AZIN1 RNA editing is a novel mechanism that promotes invasive potential of cancer-associated fibroblasts in colorectal cancer. 査読国際誌

Takeda S, Shigeyasu K, Okugawa Y, Yoshida K, Mori Y, Yano S, Noma K, Umeda Y, Kondo Y, Kishimoto H, Teraishi F, Nagasaka T, Tazawa H, Kagawa S, Fujiwara T, Goel A

Cancer letters 444 127 - 135 2019年3月

A Novel Combination Cancer Therapy with Iron Chelator Targeting Cancer Stem Cells via Suppressing Stemness. 査読国際誌

Yuki Katsura, Toshiaki Ohara, Kazuhiro Noma, Takayuki Ninomiya, Hajime Kashima, Takuya Kato, Hiroaki Sato, Satoshi Komoto, Toru Narusaka, Yasuko Tomono, Boyi Xing, Yuehua Chen, Hiroshi Tazawa, Shunsuke Kagawa, Yasuhiro Shirakawa, Tomonari Kasai, Masaharu Seno, Akihiro Matsukawa, Toshiyoshi Fujiwara

Cancers 11 ( 2 ) 2019年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Excess iron causes cancer and is thought to be related to carcinogenesis and cancer progression including stemness, but the details remain unclear. Here, we hypothesized that stemness in cancer is related to iron metabolism and that regulating iron metabolism in cancer stem cells (CSCs) may be a novel therapy. In this study, we used murine induced pluripotent stem cells that expressed specific stem cell genes such as Nanog, Oct3/4, Sox2, Klf4, and c-Myc, and two human cancer cell lines with similar stem cell gene expression. Deferasirox, an orally available iron chelator, suppressed expression of stemness markers and spherogenesis of cells with high stemness status in vitro. Combination therapy had a marked antitumor effect compared with deferasirox or cisplatin alone. Iron metabolism appears important for maintenance of stemness in CSCs. An iron chelator combined with chemotherapy may be a novel approach via suppressing stemness for CSC targeted therapy.

DOI： 10.3390/cancers11020177

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Multicenter retrospective study to evaluate the efficacy and safety of the double-flap technique as antireflux esophagogastrostomy after proximal gastrectomy (rD-FLAP Study).

Shinji Kuroda, Yasuhiro Choda, Shinya Otsuka, Satoshi Ueyama, Norimitsu Tanaka, Atsushi Muraoka, Shinji Hato, Toshikazu Kimura, Kohji Tanakaya, Satoru Kikuchi, Shunsuke Tanabe, Kazuhiro Noma, Masahiko Nishizaki, Shunsuke Kagawa, Yasuhiro Shirakawa, Yasuaki Kamikawa, Toshiyoshi Fujiwara

Annals of gastroenterological surgery 3 ( 1 ) 96 - 103 2019年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Aim: As a result of the difficulty in effective prevention of gastroesophageal reflux, no standard reconstruction procedure after proximal gastrectomy (PG) has yet been established. The double-flap technique (DFT), or Kamikawa procedure, is an antireflux reconstruction procedure in esophagogastrostomy. The efficacy of DFT has recently been reported in several studies. However, these were all single-center studies with a limited number of cases. Methods: We conducted a multicenter retrospective study in which patients who underwent DFT, irrespective of disease type and reconstruction approach, at each participating institution between 1996 and 2015 were registered. Primary endpoint was incidence of reflux esophagitis at 1-year after surgery, and secondary endpoint was incidence of anastomosis-related complications. Results: Of 546 patients who were eligible for this study, 464 patients who had endoscopic examination at 1-year follow up were evaluated for reflux esophagitis. Incidence of reflux esophagitis of all grades was 10.6% and that of grade B or higher was 6.0%. Male gender and anastomosis located in the mediastinum/intra-thorax were independent risk factors for grade B or higher reflux esophagitis (odds ratio [OR]: 4.21, 95% confidence interval [CI]: 1.44-10.9, P = 0.0109). Total incidence of anastomosis-related complications was 7.2%, including leakage in 1.5%, strictures in 5.5% and bleeding in 0.6% of cases. Laparoscopic reconstruction was the only independent risk factor for anastomosis-related complications (OR: 3.93, 95% CI: 1.93-7.80, P = 0.0003). Conclusion: Double-flap technique might be a feasible option after PG for effective prevention of reflux, although anastomotic stricture is a complication that must be well-prepared for.

DOI： 10.1002/ags3.12216

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Photoimmunotherapy for cancer-associated fibroblasts targeting fibroblast activation protein in human esophageal squamous cell carcinoma. 査読国際誌

Watanabe S, Noma K, Ohara T, Kashima H, Sato H, Kato T, Urano S, Katsube R, Hashimoto Y, Tazawa H, Kagawa S, Shirakawa Y, Kobayashi H, Fujiwara T

Cancer biology & therapy 20 ( 9 ) 1234 - 1248 2019年

Intraperitoneal cancer-immune microenvironment promotes peritoneal dissemination of gastric cancer. 査読国際誌

Sakamoto S, Kagawa S, Kuwada K, Ito A, Kajioka H, Kakiuchi Y, Watanabe M, Kagawa T, Yoshida R, Kikuchi S, Kuroda S, Tazawa H, Fujiwara T

Oncoimmunology 8 ( 12 ) e1671760 - e1671760 2019年

多発小腸GISTに対し手術を施行した神経線維腫症1型の1例

母里淑子, 藤原俊義, 重安邦俊, 吉岡貴裕, 永坂岳司, 原賀順子, 香川俊輔, 寺石文則, 豊岡伸一, 平沢晃

家族性腫瘍 19 ( 2 ) 77 - 82 2019年

記述言語：日本語出版者・発行元：日本家族性腫瘍学会

症例は54歳男性．大量出血を伴う小腸多発GIST（Gastrointestinal stromal tumor）を認めて緊急入院となった．姉が神経線維腫症1型（neurofibromatosis type 1:NF1）と診断されており，患者にもおよそ20個の神経線維腫を疑う腫瘤とcafé au lait斑を6個以上認めたためNF1と診断した．出血コントロール目的に開腹手術を行ったが，GISTはおよそ20個多発しており，大量小腸切除を避けるために10mm以上の腫瘍のみ外科的切除を行い，多発微小腫瘍は経過観察とした不完全切除を選択した．切除標本の病理検査では紡錘形核と好酸性胞体を有する紡錘形細胞が密に錯綜する腫瘍を認め，免疫染色でKIT陽性．核分裂数は5以下/50HPFsであり低悪性度GISTと診断した．NF1に伴うGISTは比較的予後が良いとの報告もあるが，このような多発微小病変については明らかな治療指針がない．今後さらなる症例の集積と検討を要する．

DOI： 10.18976/jsft.19.2_77

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The epithelial-to-mesenchymal transition induced by tumor-associated macrophages confers chemoresistance in peritoneally disseminated pancreatic cancer 査読国際誌

Kazuya Kuwada, Shunsuke Kagawa, Ryuichi Yoshida, Shuichi Sakamoto, Atene Ito, Megumi Watanabe, Takeshi Ieda, Shinji Kuroda, Satoru Kikuchi, Hiroshi Tazawa, Toshiyoshi Fujiwara

Journal of experimental & clinical cancer research 37 ( 1 ) 307 - 307 2018年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: The peritoneum is one of the most frequent metastatic sites in pancreatic cancer patients, and peritoneal dissemination makes this disease refractory due to aggressive progression and chemoresistance. Although the role of the tumor microenvironment in cancer development is recognized, the correlation between the peritoneal environment and refractoriness of peritoneal dissemination remains unclear. The intraperitoneal tumor-microenvironment and its potential role in the progression of peritoneal dissemination and chemo-refractoriness, focusing especially on macrophages, were investigated.
Materials and methods: Peritoneal washes were obtained from pancreatic cancer patients, and cellular components were subjected to immunofluorescence assays. The effects of macrophages induced from monocytic THP-1 cells on pancreatic cancer cells were examined in co-culture conditions. The in vivo effects of macrophages on tumor growth and chemo-sensitivity were investigated by subcutaneously or intraperitoneally co-injecting cancer cells with macrophages into mice.
Results: CD204-positive macrophages were present along with cancer cells in the peritoneal washes. In in vitro co-culture, tumor-associated macrophages affected pancreatic cancer cells, induced the epithelial-to-mesenchymal transition (EMT), and made them more resistant to chemotherapeutic agents. M2 macrophages promoted growth of both subcutaneous tumors and peritoneal dissemination in mice. Furthermore, co-inoculation of M2 macrophages conferred chemoresistance in the peritoneal dissemination mouse model, which significantly shortened their survival.
Conclusion: Intraperitoneal tumor-associated macrophages potentially play an important role in promotion of peritoneal dissemination and chemoresistance of pancreatic cancer via EMT induction.

DOI： 10.1186/s13046-018-0981-2

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taTMEを安全に導入、普及させるためのcadaver surgical trainingの役割

戸嶋俊明, 近藤喜太, 信岡大輔, 黒田新士, 前田直見, 寺石文則, 白川靖博, 香川俊輔, 藤原俊義

日本内視鏡外科学会雑誌 23 ( 7 ) OS78 - 7 2018年12月

Integrated fluorescent cytology with nano-biologics in peritoneally disseminated gastric cancer. 査読国際誌

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年10月

The elucidation of tumor immunosuppression affected by cancer-associated fibroblasts

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

Japanese Journal of Cancer and Chemotherapy 45 ( 9 ) 1279 - 1281 2018年9月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Japanese Journal of Cancer and Chemotherapy Publishers Inc.

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.

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癌関連線維芽細胞が及ぼす腫瘍免疫逃避の解明査読

加藤卓也, 野間和広, 桂佑貴, 佐藤浩明, 河本慧, 二宮卓之, 大原利章, 田澤大, 香川俊輔, 白川靖博, 藤原俊義

癌と化学療法 45 ( 9 ) 1279 - 1281 2018年9月

記述言語：日本語出版者・発行元：(株)癌と化学療法社

近年、免疫チェックポイント阻害薬をはじめがん免疫療法の発展により、飛躍的に予後の改善を認める癌腫が散見される。しかしながら、致命的な有害事象の発生や効果の得られる症例が限定的であることなど、克服すべき問題点も指摘されている。免疫チェックポイント阻害薬の治療効果予測因子として腫瘍浸潤リンパ球が注目されており、特に細胞傷害性T細胞の腫瘍内浸潤の程度が抗腫瘍効果に影響を与えていると報告されている。リンパ球の腫瘍浸潤においては、癌とがん微小環境の相互作用によって制御している可能性が指摘されている。そのなかで中心的な役割を担っている癌関連線維芽細胞(cancer-associated fibroblasts:CAFs)が注目されている。以前よりわれわれは、がん微小環境の強い関与を推測し、特にCAFsの作用に注目して癌の増殖・浸潤・血管新生・治療抵抗性について報告してきた。この度CAFsと腫瘍免疫に着目し、CAFsが寄与する腫瘍免疫抑制について検討している。今後、検討結果を随時報告する予定である。(著者抄録)

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HER2-targeted gold nanoparticles potentially overcome resistance to trastuzumab in gastric cancer 査読国際誌

Kubota Tetsushi, Kuroda Shinji, Kanaya Nobuhiko, Morihiro Toshiaki, Aoyama Katsuyuki, Kakiuchi Yoshihiko, Kikuchi Satoru, Nishizaki Masahiko, Kagawa Shunsuke, Tazawa Hiroshi, Fujiwara Toshiyoshi

NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 14 ( 6 ) 1919 - 1929 2018年8月

Clinical characteristics and management of gastric tube cancer after esophagectomy 査読

Yasuhiro Shirakawa, Kazuhiro Noma, Naoaki Maeda, Takayuki Ninomiya, Shunsuke Tanabe, Satoru Kikuchi, Shinji Kuroda, Masahiko Nishizaki, Shunsuke Kagawa, Yoshiro Kawahara, Hiroyuki Okada, Toshiyoshi Fujiwara

Esophagus 15 ( 3 ) 180 - 189 2018年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Tokyo

Background: Gastric cancer is the second most common malignancy, overlapping with thoracic esophageal cancer (TEC). Among them, metachronous gastric tube cancers after TEC surgery have been increasing. The aims of this study were to examine the clinicopathological factors and treatment outcomes of gastric tube cancer (GTC) after TEC surgery. Methods: Thirty-three GTCs in 30 cases after TEC treated between 1997 and 2016 were investigated retrospectively. Results: Most cases were males. The median interval from TEC surgery to GTC occurrence was 57 (6.5–107.5) months. Almost 2/3 lesions occurred in the lower third of the gastric tube (21/33)
29 lesions (in 26 cases) were superficial cancers, and 4 lesions were advanced cancers. Twenty-two lesions of superficial cancer were differentiated type, and the remaining seven lesions were undifferentiated type. Treatment for superficial cancer had previously been performed with partial gastric tube resection (10 lesions), and the number of cases undergoing endoscopic submucosal dissection (ESD) had increased recently (19 lesions). Most cases with superficial cancer survived without relapse. Four lesions of advanced cancer were found after a relatively long interval following TEC surgery. Most lesions of advanced cancer were scirrhous, undifferentiated type, and they died due to GTC. Conclusion: GTCs may occur late in the postoperative course following TEC surgery. If they are discovered at an early stage, these lesions can be cured with ESD. Long-term periodic endoscopic examinations after TEC surgery are important.

DOI： 10.1007/s10388-018-0611-2

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Sarcopenia and Comorbidity in Gastric Cancer Surgery as a Useful Combined Factor to Predict Eventual Death from Other Causes 査読国際誌

Kazuya Kuwada, Shinji Kuroda, Satoru Kikuchi, Ryuichi Yoshida, Masahiko Nishizaki, Shunsuke Kagawa, Toshiyoshi Fujiwara

Annals of Surgical Oncology 25 ( 5 ) 1160 - 1166 2018年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer New York LLC

Background: Sarcopenia is recognized as an important prognostic factor in various types of cancer, including gastric cancer. While long-term survival analyses typically focus on overall and disease-specific survival, death from other causes has received far less attention. Methods: We reviewed medical records of 491 gastric cancer patients who underwent gastrectomy from January 2005 to March 2014 and whose preoperative computed tomography (CT) images were available for evaluation of sarcopenia. Sarcopenia was defined as the SMA/BSA index (skeletal muscle area divided by body surface area) below the sex-specific lowest quartile. Results: Sarcopenia was significantly associated with age, high body mass index (BMI), presence of comorbidity, high American Society of Anesthesiologists physical status (ASA-PS), high T score, advanced stage, large blood loss, and long hospital stay, but was not significantly associated with postoperative complications. Univariate and multivariate analyses of prognostic factors for overall survival revealed that sarcopenia is an independent predictor of poor prognosis [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.01–2.09, p = 0.0454]. Our analysis of death due to other causes found that non-gastric cancer-related deaths were more frequent among sarcopenia patients with comorbidities than in the rest of our study population (p = 0.0001), while univariate and multivariate analyses revealed that sarcopenia with comorbidity was an independent risk factor for non-gastric cancer-related death (HR 1.84, 95% CI 1.31–3.61, p = 0.0308), as was age. Conclusion: For gastric cancer patients, sarcopenia increases the risk of death from other causes following surgery, which reveals the importance of developing treatment strategies based not only on cancer status but also on other clinical factors, including sarcopenia and comorbidity.

DOI： 10.1245/s10434-018-6354-4

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大腸癌多発肝転移に対する肝切除多回肝切除と化学療法を見据えたParenchymal sparing & skeletonized hepatectomy

楳田祐三, 八木孝仁, 永坂岳司, 吉田龍一, 信岡大輔, 杭瀬崇, 伏見卓郎, 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 118回 1085 - 1085 2018年4月

サルコペニアは胃癌術後の予後に関連する(Sarcopenia is associated with prognosis in gastric cancer patients undergoing gastrectomy)

桑田和也, 香川俊輔, 菊地覚次, 黒田新士, 吉田龍一, 西崎正彦, 藤原俊義

日本胃癌学会総会記事 90回 268 - 268 2018年3月

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