Functional analysis and therapeutic application of cannabinoid receptor in esophageal carcinoma.

• Project/Area Number: 25460419
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Oita University
• Principal Investigator: Hijiya Naoki 大分大学, 医学部, 助教 (80305036)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: カンナビノイド受容体 / 食道扁平上皮癌 / 転移予測因子 / 予後予測因子 / 細胞増殖 / 食道癌 / 細胞浸潤 / 分子標的治療

Outline of Final Research Achievements

In this study, I found that overexpression of cannabinoid receptor 1 (CB1R) was applicable as a marker for prediction of metastasis in esophageal squamous cell carcinoma (ESCC). CB1R overexpression was detected immunohistochemically in 54 of 88 cases (61.4%). The intensity of CB1R expression was uniform in both intraepithelial and invasive regions in each case, and was significantly correlated with the status of metastasis to lymph nodes and distant organs. Furthermore, multivariate analysis revealed that CB1R overexpression was independently associated with poor prognosis. Biological analysis of CB1R overexpression using ESCC cell lines revealed that CB1R activation appeared to promote cell proliferation. On the basis of these findings, I propose that evaluation of CB1R expression status in biopsy specimens of ESCC using immunohistochemistry might be clinically useful for prediction of metastasis to lymph nodes and distant organs.

Research Products

• [Journal Article] Genomic loss of DUSP4 contributes to the progression of intraepithelial neoplasm of pancreas to invasive carcinoma. (2016)
  • Author(s): Hijiya N, Tsukamoto Y, Nakada C, Tung NL, Kai T, Matsuura K, Shibata K, Inomata M, Uchida T, Tokunaga A, Amada K, Shirao K, Yamada Y, Mori H, Takeuchi I, Seto M, Aoki M, Takekawa M, Moriyama M.
  • Journal Title: Cancer Res. Volume: Epub
  • Peer Reviewed
• [Journal Article] Perirenal lymphatic systems: evaluation using spectral presaturation with inversion recovery T2-weighted MR images with 3D volume isotropic turbo spin-echo acquisition at 3.0-T (2016)
  • Author(s): Matsumoto S, Mori H, Kiyonaga M, Yamada Y, Takaji R, Hijiya N, Moriyama M, Tanoue R, Matsumoto T, Hasebe T
  • Journal Title: Journal of Magnetic Resonance Imaging Volume: 00 Issue: 4 Pages: 00-00
  • DOI: 10.1002/jmri.25244
  • Peer Reviewed / Open Access
• [Journal Article] Kidney-specific knockout of Sav1 in the mouse promotes hyper-proliferation of renal tubular epithelium through suppression of the Hippo pathway. (2016)
  • Author(s): Kai T, Tsukamoto Y, Hijiya N, Tokunaga A, Nakada C, Uchida T, Daa T, Iha H, Takahashi M, Nomura T, Sato F, Mimata H, Ikawa M, Seto M, Matsuura K, Moriyama M.
  • Journal Title: J Pathol. Volume: 印刷中 Issue: 1 Pages: 97-108
  • DOI: 10.1002/path.4706
  • Peer Reviewed / Open Access
• [Journal Article] Downregulation of WDR20 due to loss of 14q is involved in the malignant transformation of clear cell renal cell carcinoma. (2016)
  • Author(s): Takahashi M, Tsukamoto Y, Kai T, Tokunaga A, Nakada C, Hijiya N, Uchida T, Daa T, Nomura T, Sato F, Mimata H, Matsuura K, Moriyama M.
  • Journal Title: Cancer Science Volume: 107(4) Issue: 4 Pages: 417-423
  • DOI: 10.1111/cas.12892
  • Peer Reviewed / Open Access
• [Journal Article] Expression of DDX27 contributes to colony-forming ability of gastric cancer cells and correlates with poor prognosis in gastric cancer. (2015)
  • Author(s): Tsukamoto Y, Fumoto S, Noguchi T, Yanagihara K, Hirashita Y, Nakada C, Hijiya N, Uchida T, Matsuura K, Hamanaka R, Murakami K, Seto M, Inomata M, Moriyama M.
  • Journal Title: Am J Cancer Res. Volume: 15 Pages: 2998-3014
  • Peer Reviewed
• [Journal Article] Downregulation of NDUFB6 due to 9p24.1-p13.3 loss is implicated in metastatic clear cell renal cell carcinoma. (2015)
  • Author(s): Narimatsu T, *Matsuura K, Nakada C, Tsukamoto Y, Hijiya N, Kai T, Inoue T, Uchida T, Nomura T, Sato F, Seto M, Takeuchi I, Mimata H, Moriyama M
  • Journal Title: Cancer Medicine Volume: 4(1) Issue: 1 Pages: 112-124
  • DOI: 10.1002/cam4.351
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pancreatic neuroendocrine tumor with extensive intraductal invasion of the main pancreatic duct: a case report. (2014)
  • Author(s): Kiyonaga M, Matsumoto S, Mori H, Yamada Y, Takaji R, Hijiya N, Yoshizumi F, Aramaki M.
  • Journal Title: JOP Volume: 15 Pages: 497-500
  • DOI: 10.6092/1590-8577/2741
  • Peer Reviewed
• [Journal Article] CCAAT/enhancer-binding protein  is epigenetically silenced by histone deacetylation in endometriosis and promotes the pathogenesis of endometriosis. (2013)
  • Author(s): Kawano Y, Nasu K, Hijiya N, Tsukamoto Y, Amada K, Abe W, Kai K, Moriyama M, Narahara H
  • Journal Title: J Clin Endocrinol Metab Volume: 98 Issue: 9 Pages: E1474-E1482
  • DOI: 10.1210/jc.2013-1608
  • Peer Reviewed
• [Journal Article] Death receptor 6 is epigenetically silenced by histone deacetylation in endometriosis and promotes the pathogenesis of endometriosis. (2013)
  • Author(s): Kai K, Nasu K, Kawano Y, Aoyagi Y, Tsukamoto Y, Hijiya N, Abe W, Okamoto M, Moriyama M, Narahara H.
  • Journal Title: Am J Reprod Immunol Volume: 70 Issue: 6 Pages: 485-496
  • DOI: 10.1111/aji.12155
  • Peer Reviewed
• [Journal Article] 【膵炎・膵腫瘍の画像診断-稀な疾患との鑑別も含めて-】 膵管癌 (2013)
  • Author(s): 松本 俊郎, 森 宣, 山田 康成, 泥谷 直樹
  • Journal Title: 画像診断 Volume: 33 Pages: 869-878
• [Journal Article] 画像診断とIVRのための腹部血管解剖 肝・胆・膵・脾 胆嚢・膵臓・脾臓(その2) 膵胆道周囲のリンパ網・神経叢解剖 画像診断医の立場から (2013)
  • Author(s): 才 道昭, 山田 康成, 松本 俊郎, 森 宣, 泥谷 直樹
  • Journal Title: 日独医報 Volume: 58 Pages: 125-130
• [Presentation] 膵上皮内癌が浸潤性膵癌へ形質転換するメカニズムの解明 (2016)
  • Author(s): 泥谷直樹
  • Organizer: 第53回日本臨床分子医学会学術集会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
  • Year and Date: 2016-04-15
  • Invited
• [Presentation] 脾静脈に穿通し門脈系に粘液栓を形成した膵体部IPMCの1例 (2015)
  • Author(s): 清永 麻紀, 森 宣, 松本 俊郎, 山田 康成, 高司 亮, 矢田 一宏, 太田 正之, 泥谷 直樹, 守山 正胤
  • Organizer: 第 51回日本医学放射線学会秋季臨床大会
  • Place of Presentation: アイーナ(いわて県民情報交流センター)（岩手県盛岡市）
  • Year and Date: 2015-10-02
• [Presentation] 腎細胞癌移植モデルにおいてSAV1はTGF-β pathwayを抑制することで腫瘍増生を阻害する (2015)
  • Author(s): 甲斐 友喜, 松浦 恵子, 泥谷 直樹, 佐藤 文憲, 小林 隆志, 守山 正胤, 三股 浩光
  • Organizer: 第103回日本泌尿器科学会総会
  • Place of Presentation: 石川県立音楽堂（石川県金沢市）
  • Year and Date: 2015-04-18
• [Presentation] 腎細胞癌移植モデルにおいてSAV1遺伝子は腫瘍増殖を抑制する (2014)
  • Author(s): 甲斐 友喜, 松浦 恵子, 泥谷 直樹, 佐藤 文憲, 守山 正胤, 三股 浩光
  • Organizer: 日本泌尿器科学会総会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2014-04-24 – 2014-04-27
• [Presentation] 転移性肝癌に随伴するMDCT上のperiportal low attenuation 病理所見との対比 (2013)
  • Author(s): 高司 亮, 松本 俊郎, 清永 麻紀, 山田 康成, 森 宣, 太田 正之, 北野 正剛, 泥谷 直樹, 守山 正胤, 中山 朋子, 高木 一, 福澤 謙吾, 米増 博俊
  • Organizer: 第49回日本医学放射線学会秋季臨床大会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）