癌間質のnormalizationによる薬剤送達改善と新規膵癌治療への応用

• 研究課題/領域番号: 25670584
• 研究種目: 挑戦的萌芽研究
• 配分区分: 補助金
• 研究分野: 消化器外科学
• 研究機関: 九州大学
• 研究代表者: 大内田 研宙 九州大学, 先端医療イノベーションセンター, 講師 (20452708)
• 研究分担者: 前山 良 九州大学, 大学病院, 助教研究者 (10611668) ; 森山 大樹 九州大学, 医学研究院, 共同研究員研究者 (70586859)
• 研究期間 (年度): 2013-04-01 – 2014-03-31
• 研究課題ステータス: 完了 (2013年度)
• 配分額: 3,770千円 (直接経費: 2,900千円、間接経費: 870千円); 2013年度: 3,770千円 (直接経費: 2,900千円、間接経費: 870千円)
• キーワード: 膵がん / 膵星細胞 / 細胞外基質 / 膵癌 / 癌間質相互作用 / 癌浸潤

研究概要

本研究では膵癌細胞の膵星細胞による癌間質形成に及ぼす影響とその癌間質のremodelingによるnormalizationの2つに着目しそれらを制御する薬剤を同定し、既存の抗癌剤を併用することで癌間質がもたらす膵癌治療抵抗性を克服し、新たな膵癌治療戦略を開発することを目的とし膵星細胞と膵癌細胞の細胞外基質を通した癌間質相互作用を中心に検討を進めた。その結果、膵星細胞の作りだす細胞外マトリックスは膵癌細胞の遊走や浸潤に影響を与えることが明らかになった。今後この機序を詳細に解析し、関連分子の同定からこの機序をコントロールする手法を明らかにし、in vivoモデルでの薬剤送達効率の検討を進めていく。

研究成果

• [雑誌論文] Expression of Glucagon.Like Peptide 1 Receptor and Its Effects on Biological Behavior in Pancreatic Neuroendocrine Tumors (2014)
  • 著者名/発表者名: Ana Ines Cases, Takao Ohtsuka, Minoru Fujino, Noboru Ideno, Shingo Kozono, Ming Zhao, Kenoki Ohuchida, Shinichi Aishima, Masatoshi Nomura, Yoshinao Oda, Kazuhiro Mizumoto, Masao Tanaka
  • 雑誌名: Pancreas 巻: 43(1) ページ: 1-6
• [雑誌論文] Tissue Tablet Method : An Efficient Tissue Banking Procedure Applicable to Both Molecular Analysis and Frozen Tissue Microarray (2014)
  • 著者名/発表者名: Nobuhiro Torata, Kenoki Ohuchida, Shin Akagawa, Lin Cui, Shingo Kozono, Kazuhiro Mizumoto, Shinichi Aishima, Yoshinao Oda, Masao Tanaka
  • 雑誌名: Human Pathology 巻: 45(1) ページ: 143-52
• [雑誌論文] 特集タイトル : 臨床検体から導き出す消化器病研究テーマ (2014)
  • 著者名/発表者名: 大内田研宙、大塚隆生、水元一博、田中雅夫
  • 雑誌名: 6)膵液中バイオマーカーで膵疾患の診断、早期発見はできるか分子消化器病 巻: vol.11 no.1
• [雑誌論文] Kindlin-1 expression is involved in migration and invasion in pancreatic cancer (2013)
  • 著者名/発表者名: Prawej Mahawithitwong, Kenoki Ohuchida, Naoki Ikenaga, Hayato Fujita, Ming Zhao, Shingo Kozono, Koji Shindo, Takao Ohtsuka, Shinichi Aishima, Kazuhiro Mizumoto and Masao Tanaka
  • 雑誌名: International Journal of Oncology 巻: 42 ページ: 1360-1366
• [雑誌論文] Pancreatic stellate cells in hypoxia enhance pancreatic cancer invasiveness via secretion of connective tissue growth factor (2013)
  • 著者名/発表者名: Daiki Eguchi , Naoki Ikenaga , Kenoki Ohuchida, Shingo Kozono , Lin Cui, Fujiwara Kenji , Koji Shindo, Takao Ohtsuka, Shunichi Takahata, Kazuhiro Mizumoto and Masao Tanaka
  • 雑誌名: Journal of Surgical Research 巻: 181 ページ: 225-33
• [雑誌論文] Pirfenidone inhibits desmoplasia of pancreatic cancer by regulating stellate cells (2013)
  • 著者名/発表者名: Shingo Kozono, Kenoki Ohuchida, Daiki Eguchi, Naoki Ikenaga, Kenji Fujiwara, Ming Zhao, Lin Cui, Koji Shindo, Kazuhiro Mizumoto, and Masao Tanaka
  • 雑誌名: Cancer Research 巻: 73 ページ: 2345-56
• [雑誌論文] Kindlin-2 expression in peritumoral stroma is associated with poor prognosis in pancreatic ductal adenocarcinoma (2013)
  • 著者名/発表者名: Prawej Mahawithitwong, Kenoki Ohuchida, Naoki Ikenaga, Hayato Fujita, Ming Zhao, Shingo Kozono, Koji Shindo, Takao Ohtsuka, Shinichi Aishima, Kazuhiro Mizumoto, Masao Tanaka
  • 雑誌名: Pancreas 巻: 42 ページ: 663-9
• [雑誌論文] Biological evaluation of protein nanocapsules containing doxorubicin (2013)
  • 著者名/発表者名: Riki Toita, Masaharu Murata, Kana Abe, Sayoko Narahara, Jing Shu Piao, Jeong-Hun Kang, Kenoki Ohuchida, Makoto Hashizume
  • 雑誌名: International Journal of Nanomedicine 巻: 8 ページ: 1989-1999
• [雑誌論文] Migratory activity of CD105+ pancreatic cancer cells is strongly enhanced by pancreatic stellate cells (2013)
  • 著者名/発表者名: Kenji Fujiwara, Kenoki Ohuchida, Takao Ohtsuka, Kazuhiro Mizumoto, Koji Shindo, Naoki Ikenaga, Lin Cui, Shunichi Takahata, Shinichi Aishima, and Masao Tanaka
  • 雑誌名: Pancreas 巻: 42(8) ページ: 1283-90
• [雑誌論文] S100A4 mRNA expression level is a predictor of radiosensitivity of pancreatic cancer cells (2013)
  • 著者名/発表者名: Shingo Kozono, Kenoki Ohuchida, Takao Ohtsuka, Lin Cui , Daiki Eguchi , Kenji Fujiwara , Ming Zhao , Kazuhiro Mizumoto, Masao Tanaka
  • 雑誌名: Oncology Reports 巻: 30(4) ページ: 1601-8
• [雑誌論文] MAL2 expression predicts distant metastasis and short survival in pancreatic cancer (2013)
  • 著者名/発表者名: Daiki Eguchi, Kenoki Ohuchida, Shingo Kozono, Naoki Ikenaga, Koji Shindo, Lin Cui, Kenji Fujiwara, Shin Akagawa, Takao Ohtsuka, Shunichi Takahata, Shoji Tokunaga, Kazuhiro Mizumoto, Masao Tanaka
  • 雑誌名: Surgery 巻: 154(3) ページ: 573-82
• [雑誌論文] Fibroblasts expressing podoplanin enhance the tumor progression of invasive ductal carcinoma of pancreas (2013)
  • 著者名/発表者名: Shindo Koji, Aishima Shinichi, Ohuchida Kenoki, Fujiwara Kenji, Mizumoto Kazuhiro, Tanaka Masao, Oda Yoshinao
  • 雑誌名: Molecular Cancer 巻: 12(1) ページ: 168-168
• [雑誌論文] 腫瘍内 heterogeneityに着目した膵癌個別化治療の可能性 (2013)
  • 著者名/発表者名: 大内田研宙大塚隆生水元一博田中雅夫
  • 雑誌名: 腫瘍個別化から細胞個別化へ.胆と膵 巻: Vol.30(2) ページ: 165-9
• [雑誌論文] Mass Spectrometry-based Metabolic Profiling of Gemcitabine-sensitive and Gemcitabine-resistant Pancreatic Cancer Cells
  • 著者名/発表者名: Yoshinori Fujimura, Naoki Ikenaga, Kenoki Ohuchida, Daiki Setoyama, Miho Irie, Daisuke Miura, Hiroyuki Wariishi, Masaharu Murata, Kazuhiro Mizumoto, Makoto Hashizume and Masao Tanaka
  • 雑誌名: Pancreas 巻: (in press)
• [学会発表] CD166 Expression Characterized Tumorigenicity, and Invasive and Migratory Activities of Pancreatic Cancer Cell Lines (2013)
  • 著者名/発表者名: Fujiwara K, Ohuchida K, Akagawa S, Ohtsuka T, Mizumoto K, Tanaka M
  • 学会等名: 44th Annual Meeting, Miami
  • 発表場所: Ammerican Pancreatic Association
• [学会発表] Expression of Glucagon-like Peptide 1 Recepter and Biological Behavior in Pancreatic Neuroendocrine Tumors (2013)
  • 著者名/発表者名: Cases A.I., Ohtsuka T, Fujino M, Ideno N, Kzono S, Zhao M, Ikenaga N, Ohuchida K, Oda Y, Mizumoto K, Tanaka M
  • 学会等名: 44th Annual Meeting, Miami
  • 発表場所: Ammerican Pancreatic Association
• [学会発表] Clinical significance of GNAS mutation for invasive pancreatic carcinoma distinct from/derived from intraductal papillary mucinous neoplasm(IPMN) of the pancreas (2013)
  • 著者名/発表者名: Ideno N, Ohtsuka T, Tamura K, Aso T, Ohuchida K, Takahata S, Oda Y, Mizumoto K, Tanaka M
  • 学会等名: 44th Annual Meeting, Miami
  • 発表場所: Ammerican Pancreatic Association
• [学会発表] Salinomycin induced Autophagy and is Related with its Killing Effect for Pancreatic Cells (2013)
  • 著者名/発表者名: Nakata K, Zhao M, Ohuchida K, Miyasaka Y, Maeyama R, Ohtsuka T, Nagai E, Mizumoto K, Tanaka M
  • 学会等名: 44th Annual Meeting, Miami
  • 発表場所: Ammerican Pancreatic Association
• [学会発表] Treatment Strategy for Main Duct Intraductal Papillary Mucinous Neoplasms of the Pancreatic Based on the Assessment of Recurrence in the Remnant Pancreas after Resection : A Retrospective Review (2013)
  • 著者名/発表者名: Tamura K, Ohtsuka T, Ideno N, Aso T, Shindo K, Oda Y, Ohuchida K, Takahata S, Mizumoto K, Tanaka M
  • 学会等名: 44th Annual Meeting, Miami, 2013
  • 発表場所: Ammerican Pancreatic Association
• [学会発表] Reduced Anterior Gradient 2 Expression is Induced by EMT and Correlated with Poor Outcome in Pancreatic Ductal Adenocarcinoma (2013)
  • 著者名/発表者名: Mizuuchi Y, Aishima S, Ohuchida K, Shindo S, Mizumoto K, Tanaka M
  • 学会等名: 44th Annual Meeting, Miami
  • 発表場所: Ammerican Pancreatic Association
• [学会発表] Histon Deacetylase 1 is Responsible for Radioresistance of Pancreatic Cancer cells (2013)
  • 著者名/発表者名: Tanaka T, Ohuchida K, Mizumoto K, Kozono S, Tanaka M
  • 学会等名: 44th Annual Meeting, Miami
  • 発表場所: Ammerican Pancreatic Association
• [学会発表] Comparisons of Characteristics of Peritoneal Fibroblasts in Dissemination with those of Mesothelial Cells and Pancreatic Stellate Cells in Pancreatic Cancer (2013)
  • 著者名/発表者名: Akagawa S, Ohuchida K, Torada N, Eguchi D, Kozono S, Ohtsuka T, Mizumoto K, Tanaka M
  • 学会等名: 44th Annual Meeting, Miami
  • 発表場所: Ammerican Pancreatic Association
• [学会発表] Clinical Significance of Stromal CD90 and alpha-SMA Expression in Pancreatic Cancer (2013)
  • 著者名/発表者名: Sada M, Ohuchida K, Fujiwara K, Horioka K, Tanaka T, Zheng B, Cases A.I., Akagawa S, Shindo K, Ohtsuka T, Takahata S, Oda Y, Mizumoto K, Tanaka M
  • 学会等名: 44th Annual Meeting, Miami
  • 発表場所: Ammerican Pancreatic Association