Pancreato-biliary cancer microenvironment formation is based on the regulation of clock genes.

• Project/Area Number: 15H06007
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Human pathology
• Research Institution: Hirosaki University
• Principal Investigator: Yoshizawa Tadashi 弘前大学, 医学研究科, 客員研究員 (70761071)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 癌 / 胆道 / 癌微小環境 / 時計遺伝子 / 上皮間葉転換 / 胆管癌 / 癌関連線維芽細胞 / 膵癌

Outline of Final Research Achievements

Pancreato-biliary cancer is one of the most aggressive malignancies in humans. Its aggressive phenotypes are thought to be associated with invasive tumour growth via epithelial mesenchymal transition. We clarified that in a co-culture model of cholangiocarcinoma and human mesenchymal stem cell lines, carcinoma cells indicate mesenchymal transition by morphological changes and immunohistochemical staining. In addition, using RT-PCR, it was clarified
that the expression of DEC1 is elevated in a co-cultured model, and it was suggested that the cancer microenvironment is formed under the control of the clock gene. Furthermore, we could obtain an image of cancer cells infiltrating the lymph vessel in a cancer microenvironment model (three-dimensional culture model including the lymphatic vessel tissue).

Research Products

• [Journal Article] Prognostic Impact of CD163+ Macrophages in Tumor Stroma and CD8+ T-Cells in Cancer Cell Nests in Invasive Extrahepatic Bile Duct Cancer. (2017)
  • Author(s): Miura T, Yoshizawa T, Hirai H, Seino H, Morohashi S, Wu Y, Wakiya T, Kimura N, Kudo D, Ishido K, Toyoki Y, Kijima H, Hakamada K.
  • Journal Title: Anticancer Res Volume: 37 Issue: 1 Pages: 183-190
  • DOI: 10.21873/anticanres.11304
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 幽門前庭部に発症した胃リンパ球浸潤癌の1例 (2017)
  • Author(s): 境 雄大, 吉澤 忠司, 岩渕 圭, 八木橋 信夫, 鬼島 宏
  • Journal Title: 外科 Volume: 79 Pages: 81-84
  • Peer Reviewed
• [Journal Article] Basic helix-loop-helix transcription factor DEC2 functions as an anti-apoptotic factor during paclitaxel-induced apoptosis in human prostate cancer cells. (2016)
  • Author(s): Liu Q, Wu Y, Yoshizawa T, Yan X, Morohashi S, Seino H, Kato Y, Kijima H.
  • Journal Title: Int J Mol Med Volume: 38 Issue: 6 Pages: 1727-1733
  • DOI: 10.3892/ijmm.2016.2798
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Myofibroblast distribution is associated with invasive growth types of colorectal cancer. (2016)
  • Author(s): Takatsuna M, Morohashi S, Yoshizawa T, Hirai H, Haga T, Ota R, Saito K, Wu Y, Seino H, Aoyagi Y, Terai S, Kijima H.
  • Journal Title: Oncol Rep Volume: 36 Issue: 6 Pages: 3154-3160
  • DOI: 10.3892/or.2016.5202
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Myofibroblasts of the muscle layer stimulate the malignant potential of colorectal cancer. (2016)
  • Author(s): Takatsuna M, Morohashi S, Yoshizawa T, Hirai H, Haga T, Ota R, Wu Y, Morohashi H, Hakamada K, Terai S, Kijima H.
  • Journal Title: Oncol Rep Volume: 36 Issue: 3 Pages: 1251-1257
  • DOI: 10.3892/or.2016.4932
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] <b>Clinicopathological significance of gastric poorly differentiated medullary car</b><b>cinoma </b> (2016)
  • Author(s): Hirai H, Yoshizawa T, Morohashi S, Haga T, Wu Y, Ota R, Takatsuna M, Akasaka H, Hakamada K, Kijima H.
  • Journal Title: Biomedical Research Volume: 37 Issue: 2 Pages: 77-84
  • DOI: 10.2220/biomedres.37.77
  • NAID: 130005147429
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Podoplanin-mediated TGF-β-induced epithelial-mesenchymal transition and its correlation with bHLH transcription factor DEC in TE-11 cells. (2016)
  • Author(s): Wu Y, Liu Q, Yan X, Kato Y, Tanaka M, Inokuchi S, Yoshizawa T, Morohashi S, Kijima H.
  • Journal Title: Int J Oncol. Volume: 48 Issue: 6 Pages: 2310-2320
  • DOI: 10.3892/ijo.2016.3445
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A new histological therapeutic classification system to predict eradicated and residual lymph nodes in breast cancer after neoadjuvant chemotherapy. (2016)
  • Author(s): Morohashi S, Yoshizawa T, Seino H, Hirai H, Haga T, Ota R, Wu Y, Yoshida E, Hakamada K, Kijima H.
  • Journal Title: Oncol Rep. Volume: 35 Issue: 5 Pages: 3592-3598
  • DOI: 10.3892/or.2016.4635
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Imaging hamster model of bile duct cancer in vivo using fluorescent L-glucose derivatives. (2016)
  • Author(s): Yokoyama H, Sasaki A, Yoshizawa T, Kijima H, Hakamada K, Yamada K.
  • Journal Title: Hum Cell. Volume: 29 Issue: 3 Pages: 111-121
  • DOI: 10.1007/s13577-015-0131-5
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Clinicopathological significance of vascular endothelial growth factor, thymidine phosphorylase and microvessel density in colorectal cancer. (2016)
  • Author(s): 5.Kimura Y, Morohashi S, Yoshizawa T, Suzuki T, Morohashi H, Sakamoto Y, Koyama M, Murata A, Kijima H, Hakamada K.
  • Journal Title: Mol Med Rep. Volume: 13 Issue: 2 Pages: 1551-1557
  • DOI: 10.3892/mmr.2015.4687
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 上行結腸癌に対する外科的治療後に偶然に発見された低異型度虫垂粘液性腫瘍の1例 (2016)
  • Author(s): 境 雄大, 吉澤 忠司, 鬼島 宏, 岩渕 圭, 八木橋 信夫
  • Journal Title: 外科 Volume: 78 Pages: 1535-1539
  • Peer Reviewed
• [Journal Article] 子宮癌放射線治療後に発症したS状結腸癌の1例 (2016)
  • Author(s): 境 雄大, 諸橋 聡子, 吉澤 忠司, 岩渕 圭, 八木橋 信夫, 鬼島 宏
  • Journal Title: 外科 Volume: 78 Pages: 1003-1006
  • Peer Reviewed
• [Journal Article] Involvement of c-Myc in the proliferation of MCF-7 human breast cancer cells induced by bHLH transcription factor DEC2. (2015)
  • Author(s): Wu Y
  • Journal Title: Int J Mol Med. Volume: 35 Issue: 3 Pages: 815-20
  • DOI: 10.3892/ijmm.2014.2042
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Invasive micropapillary carcinoma of the biliary tract (2015)
  • Author(s): Kijima H, Yoshizawa T, Hirai H, Morohashi S, Hakamada K.
  • Journal Title: Nihon Rinsho Volume: 73 Pages: 3774-8
  • Peer Reviewed
• [Journal Article] リンパ節転移を伴った十二指腸原発gangliocytic paragangliomaの1例 (2015)
  • Author(s): 木村 俊郎, 豊木 嘉一, 石戸 圭之輔, 工藤 大輔, 木村 憲央, 櫻庭 伸悟, 鍵谷 卓司, 吉澤 忠司, 鬼島 宏, 袴田 健一
  • Journal Title: 日本消化器外科学会雑誌 Volume: 48 Pages: 984-992
  • NAID: 130005116859
  • Peer Reviewed
• [Journal Article] 診断に苦慮した乳輪部に発生した巨大尖圭コンジローマの1例 (2015)
  • Author(s): 諸橋 聡子, 吉澤 忠司, 平井 秀明, 羽賀 敏博, 清野 浩子, 呉 雲燕, 泉 美貴, 鬼島 宏
  • Journal Title: 診断病理 Volume: 32 Pages: 159-163
  • Peer Reviewed
• [Journal Article] 【進展度に応じた胆嚢癌の治療戦略】 進行度から見た胆嚢癌の病理学的特徴 (2015)
  • Author(s): 鬼島 宏, 吉澤 忠司, 羽賀 敏博, 平井 秀明, 桜庭 伸吾, 岡野 健介, 高綱 将史, 清野 浩子, 呉 雲燕, 諸橋 聡子
  • Journal Title: 胆と膵 Volume: 36 Pages: 19-23
  • Peer Reviewed
• [Presentation] Dedifferentiated liposarcoma of the pancreas: A case report (2017)
  • Author(s): 吉澤 忠司, 諸橋 聡子, 羽賀 敏博, 清野 浩子, 呉 雲燕, 鬼島 宏
  • Organizer: 第106回日本病理学会総会
  • Place of Presentation: 京王プラザホテル (東京)
  • Year and Date: 2017-04-27
• [Presentation] 羊水塞栓症の一剖検例 (2016)
  • Author(s): 吉澤 忠司, 諸橋 聡子, 清野 浩子, 呉 雲燕, 田中 幹二, 田中 正則, 鬼島 宏
  • Organizer: 第62回日本病理学会秋季特別総会
  • Place of Presentation: 金沢市文化ホール(石川県・金沢市)
  • Year and Date: 2016-11-10
• [Presentation] Two cases of synchronous intraductal papillary-mucinous carcinoma and bile duct carcinoma (2016)
  • Author(s): 吉澤 忠司, 諸橋 聡子, 平井 秀明, 羽賀 敏博, 呉 雲燕, 鬼島 宏
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台国際センター(宮城県・仙台市)
  • Year and Date: 2016-05-13