The improvement of drug delivery based on the normalization of cancer stroma and its application for the treatment of pancreatic cancer

• Project/Area Number: 25670584
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: OHUCHIDA Kenoki 九州大学, 先端医療イノベーションセンター, 講師 (20452708)
• Co-Investigator(Kenkyū-buntansha): MAEYAMA Ryo 九州大学, 大学病院, 助教研究者 (10611668) ; MORIYAMA Taiki 九州大学, 医学研究院, 共同研究員研究者 (70586859)
• Project Period (FY): 2013-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: 膵がん / 膵星細胞 / 細胞外基質 / 膵癌 / 癌間質相互作用 / 癌浸潤

Research Abstract

In the present study, we focused on tumor-related stroma and its remodeling and normalization and mainly investigated the mechanism of cancer-stromal interaction between cancer cells and pancreatic stellate cells. Then, we identified the several molecules, which are related with the extracellular matrices derived from pancreatic stellate cells and found that such matrices affect the invasion and migration of pancreatic cancer cells. These data suggest that the remodeling of cancer stroma by normalization based on the novel molecules may lead to the development of new therapy for pancreatic cancer.

Research Products

• [Journal Article] Expression of Glucagon.Like Peptide 1 Receptor and Its Effects on Biological Behavior in Pancreatic Neuroendocrine Tumors (2014)
  • Author(s): 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
  • Journal Title: Pancreas Volume: 43(1) Pages: 1-6
• [Journal Article] Tissue Tablet Method : An Efficient Tissue Banking Procedure Applicable to Both Molecular Analysis and Frozen Tissue Microarray (2014)
  • Author(s): Nobuhiro Torata, Kenoki Ohuchida, Shin Akagawa, Lin Cui, Shingo Kozono, Kazuhiro Mizumoto, Shinichi Aishima, Yoshinao Oda, Masao Tanaka
  • Journal Title: Human Pathology Volume: 45(1) Pages: 143-52
• [Journal Article] 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)
  • Author(s): 大内田研宙、大塚隆生、水元一博、田中雅夫
  • Journal Title: 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 Volume: vol.11 no.1
• [Journal Article] Kindlin-1 expression is involved in migration and invasion in pancreatic cancer (2013)
  • Author(s): Prawej Mahawithitwong, Kenoki Ohuchida, Naoki Ikenaga, Hayato Fujita, Ming Zhao, Shingo Kozono, Koji Shindo, Takao Ohtsuka, Shinichi Aishima, Kazuhiro Mizumoto and Masao Tanaka
  • Journal Title: International Journal of Oncology Volume: 42 Pages: 1360-1366
• [Journal Article] Pancreatic stellate cells in hypoxia enhance pancreatic cancer invasiveness via secretion of connective tissue growth factor (2013)
  • Author(s): Daiki Eguchi , Naoki Ikenaga , Kenoki Ohuchida, Shingo Kozono , Lin Cui, Fujiwara Kenji , Koji Shindo, Takao Ohtsuka, Shunichi Takahata, Kazuhiro Mizumoto and Masao Tanaka
  • Journal Title: Journal of Surgical Research Volume: 181 Pages: 225-33
• [Journal Article] Pirfenidone inhibits desmoplasia of pancreatic cancer by regulating stellate cells (2013)
  • Author(s): Shingo Kozono, Kenoki Ohuchida, Daiki Eguchi, Naoki Ikenaga, Kenji Fujiwara, Ming Zhao, Lin Cui, Koji Shindo, Kazuhiro Mizumoto, and Masao Tanaka
  • Journal Title: Cancer Research Volume: 73 Pages: 2345-56
• [Journal Article] Kindlin-2 expression in peritumoral stroma is associated with poor prognosis in pancreatic ductal adenocarcinoma (2013)
  • Author(s): Prawej Mahawithitwong, Kenoki Ohuchida, Naoki Ikenaga, Hayato Fujita, Ming Zhao, Shingo Kozono, Koji Shindo, Takao Ohtsuka, Shinichi Aishima, Kazuhiro Mizumoto, Masao Tanaka
  • Journal Title: Pancreas Volume: 42 Pages: 663-9
• [Journal Article] Biological evaluation of protein nanocapsules containing doxorubicin (2013)
  • Author(s): Riki Toita, Masaharu Murata, Kana Abe, Sayoko Narahara, Jing Shu Piao, Jeong-Hun Kang, Kenoki Ohuchida, Makoto Hashizume
  • Journal Title: International Journal of Nanomedicine Volume: 8 Pages: 1989-1999
• [Journal Article] Migratory activity of CD105+ pancreatic cancer cells is strongly enhanced by pancreatic stellate cells (2013)
  • Author(s): Kenji Fujiwara, Kenoki Ohuchida, Takao Ohtsuka, Kazuhiro Mizumoto, Koji Shindo, Naoki Ikenaga, Lin Cui, Shunichi Takahata, Shinichi Aishima, and Masao Tanaka
  • Journal Title: Pancreas Volume: 42(8) Pages: 1283-90
• [Journal Article] S100A4 mRNA expression level is a predictor of radiosensitivity of pancreatic cancer cells (2013)
  • Author(s): Shingo Kozono, Kenoki Ohuchida, Takao Ohtsuka, Lin Cui , Daiki Eguchi , Kenji Fujiwara , Ming Zhao , Kazuhiro Mizumoto, Masao Tanaka
  • Journal Title: Oncology Reports Volume: 30(4) Pages: 1601-8
• [Journal Article] MAL2 expression predicts distant metastasis and short survival in pancreatic cancer (2013)
  • Author(s): 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
  • Journal Title: Surgery Volume: 154(3) Pages: 573-82
• [Journal Article] Fibroblasts expressing podoplanin enhance the tumor progression of invasive ductal carcinoma of pancreas (2013)
  • Author(s): Shindo Koji, Aishima Shinichi, Ohuchida Kenoki, Fujiwara Kenji, Mizumoto Kazuhiro, Tanaka Masao, Oda Yoshinao
  • Journal Title: Molecular Cancer Volume: 12(1) Pages: 168-168
• [Journal Article] 腫瘍内 heterogeneityに着目した膵癌個別化治療の可能性 (2013)
  • Author(s): 大内田研宙大塚隆生水元一博田中雅夫
  • Journal Title: 腫瘍個別化から細胞個別化へ.胆と膵 Volume: Vol.30(2) Pages: 165-9
• [Journal Article] Mass Spectrometry-based Metabolic Profiling of Gemcitabine-sensitive and Gemcitabine-resistant Pancreatic Cancer Cells
  • Author(s): Yoshinori Fujimura, Naoki Ikenaga, Kenoki Ohuchida, Daiki Setoyama, Miho Irie, Daisuke Miura, Hiroyuki Wariishi, Masaharu Murata, Kazuhiro Mizumoto, Makoto Hashizume and Masao Tanaka
  • Journal Title: Pancreas Volume: (in press)
• [Presentation] CD166 Expression Characterized Tumorigenicity, and Invasive and Migratory Activities of Pancreatic Cancer Cell Lines (2013)
  • Author(s): Fujiwara K, Ohuchida K, Akagawa S, Ohtsuka T, Mizumoto K, Tanaka M
  • Organizer: 44th Annual Meeting, Miami
  • Place of Presentation: Ammerican Pancreatic Association
• [Presentation] Expression of Glucagon-like Peptide 1 Recepter and Biological Behavior in Pancreatic Neuroendocrine Tumors (2013)
  • Author(s): Cases A.I., Ohtsuka T, Fujino M, Ideno N, Kzono S, Zhao M, Ikenaga N, Ohuchida K, Oda Y, Mizumoto K, Tanaka M
  • Organizer: 44th Annual Meeting, Miami
  • Place of Presentation: Ammerican Pancreatic Association
• [Presentation] Clinical significance of GNAS mutation for invasive pancreatic carcinoma distinct from/derived from intraductal papillary mucinous neoplasm(IPMN) of the pancreas (2013)
  • Author(s): Ideno N, Ohtsuka T, Tamura K, Aso T, Ohuchida K, Takahata S, Oda Y, Mizumoto K, Tanaka M
  • Organizer: 44th Annual Meeting, Miami
  • Place of Presentation: Ammerican Pancreatic Association
• [Presentation] Salinomycin induced Autophagy and is Related with its Killing Effect for Pancreatic Cells (2013)
  • Author(s): Nakata K, Zhao M, Ohuchida K, Miyasaka Y, Maeyama R, Ohtsuka T, Nagai E, Mizumoto K, Tanaka M
  • Organizer: 44th Annual Meeting, Miami
  • Place of Presentation: Ammerican Pancreatic Association
• [Presentation] 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)
  • Author(s): Tamura K, Ohtsuka T, Ideno N, Aso T, Shindo K, Oda Y, Ohuchida K, Takahata S, Mizumoto K, Tanaka M
  • Organizer: 44th Annual Meeting, Miami, 2013
  • Place of Presentation: Ammerican Pancreatic Association
• [Presentation] Reduced Anterior Gradient 2 Expression is Induced by EMT and Correlated with Poor Outcome in Pancreatic Ductal Adenocarcinoma (2013)
  • Author(s): Mizuuchi Y, Aishima S, Ohuchida K, Shindo S, Mizumoto K, Tanaka M
  • Organizer: 44th Annual Meeting, Miami
  • Place of Presentation: Ammerican Pancreatic Association
• [Presentation] Histon Deacetylase 1 is Responsible for Radioresistance of Pancreatic Cancer cells (2013)
  • Author(s): Tanaka T, Ohuchida K, Mizumoto K, Kozono S, Tanaka M
  • Organizer: 44th Annual Meeting, Miami
  • Place of Presentation: Ammerican Pancreatic Association
• [Presentation] Comparisons of Characteristics of Peritoneal Fibroblasts in Dissemination with those of Mesothelial Cells and Pancreatic Stellate Cells in Pancreatic Cancer (2013)
  • Author(s): Akagawa S, Ohuchida K, Torada N, Eguchi D, Kozono S, Ohtsuka T, Mizumoto K, Tanaka M
  • Organizer: 44th Annual Meeting, Miami
  • Place of Presentation: Ammerican Pancreatic Association
• [Presentation] Clinical Significance of Stromal CD90 and alpha-SMA Expression in Pancreatic Cancer (2013)
  • Author(s): 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
  • Organizer: 44th Annual Meeting, Miami
  • Place of Presentation: Ammerican Pancreatic Association