全身麻酔法における固形癌転移を制御するマイクロRNAへの影響

2010 Fiscal Year Annual Research Report

• Project/Area Number: 21592014
• Research Institution: Kyushu University
• Principal Investigator: 吉武 慎一郎 九州大学, 大学病院, 講師 (80315142)
• Co-Investigator(Kenkyū-buntansha): 石井 秀始 九州大学, 生体防御医学研究所, 学術研究員 (10280736) ; 三森 功士 九州大学, 生体防御医学研究所, 准教授 (50322748)
• Keywords: 全身麻酔薬 / マイクロRNA / 微量癌細胞 / 転移 / マイクロアレイ

Research Abstract

周術期では、手術手技による侵襲の他に、手術に必須である麻酔薬、特に全身麻酔で使用される吸入麻酔薬が直接的に自然免疫、獲得免疫を抑制することが知られている。これまでに、おもに免疫への影響として吸入麻酔薬は静脈麻酔薬に比べ、免疫抑制作用が強いことや(Inada et al. Anesthesia,2004)、オピオイドではモルヒネが、免疫抑制作用が強いことが明らかにされてきた(Franchi et al. Brain Behav Immun.,2007)。
本研究のプライマリ エンドポイントは、免疫不活化状態にある担癌患者において侵襲と発癌、および侵襲と癌進展との関係をマイクロRNAの影響を中心に、明らかにすることにある。現在われわれは免疫担当細胞におけるマイクロRNAの機能に関して詳細な検討を行っている。一連の研究の中で、miR-1XXは細胞免疫に重要な役割を果たすTGFβ経路の重要な構成因子であるSMAD2を抑制することを同定した。細胞にmiR-1XXを強制発現することで、SMAD2抑制によるTGFβ経路の阻害が誘導され、TGFβによるマクロファージの遊走促進やVEGFを介した血管新生、あるいは白血球と血管内皮の接着に関与するICAM-1の発現を変化させる可能性があり、現在研究を進めている。
われわれは大腸癌手術患者の癌部および非癌部、それぞれ300例以上の臨床サンプルを有する。また、Laser microdissectionにて癌細胞を採取しえた症例は108例あり、抽出したgenomic DNAおよびtotal RNAからCGHアレイおよび発現アレイを施行した。このデータからマイクロRNAとその複数の標的候補遺伝子の発現状態を確認し、パスウェイ解析を行うことで、今回着目したマイクロRNAの重要な標的遺伝子の同定、さらには生体内での機能予測が可能になる。手術侵襲・全身麻酔による免疫抑制が、癌進展に関わる機序をマイクロRNAによる制御を中心にさらに探索していきたい。

Research Products

• [Journal Article] Clinical Significance of Circulating Tumor Cells, Including Cancer Stem-Like Cells, in Peripheral Blood for Recurrence and Prognosis in Patients With Dukes' Stage B and C Colorectal Cancer (2011)
  • Author(s): Iinuma, H., Watanabe, T., Mimori, K., et al.
  • Journal Title: J Clin Oncol Volume: (CD-R)
  • Peer Reviewed
• [Journal Article] Identification of HLA-A*0201/-A*2402-restricted CTL epitope-peptides derived from a novel cancer/testis antigen, MCAK, and induction of a specific antitumor immune response (2011)
  • Author(s): Kawamoto, M., Tanaka, F., Mimori, K., et al.
  • Journal Title: Oncol Rep Volume: 25 Pages: 469-76
  • Peer Reviewed
• [Journal Article] STC2 : a predictive marker for lymph node metastasis in esophageal squamous-cell carcinoma (2011)
  • Author(s): Kita, Y., Mimori, K., et al.
  • Journal Title: Ann Surg Oncol Volume: 18 Pages: 261-72
  • Peer Reviewed
• [Journal Article] The correlation between clinical laboratory data and telomeric status of male patients with metabolic disorders and no clinical history of vascular events (2011)
  • Author(s): Maeda, T., Oyama, J., Higuchi, Y., Koyanagi, M., Sasaki, M., Arima, T., Mimori, K., et al.
  • Journal Title: Aging Male Volume: 14 Pages: 21-6
  • Peer Reviewed
• [Journal Article] The physical ability of Japanese female elderly with cerebrovascular disease correlates with the telomere length and subtelomeric methylation status in their peripheral blood leukocytes (2011)
  • Author(s): Maeda, T., Oyama, J., Higuchi, Y., Nishiyama, Y., Kudo, Y., Yamori, T., Nakazono, T., Arima, T., Mimori, K., et al.
  • Journal Title: Gerontology Volume: 57 Pages: 137-43
  • Peer Reviewed
• [Journal Article] Kinesin 18A expression clinical relevance to colorectal cancer progression (2011)
  • Author(s): Nagahara, M., Nishida, N., Iwatsuki, M., Ishimaru, S., Mimori, K., et al.
  • Journal Title: Int J Cancer Volume: (CD-R)
  • Peer Reviewed
• [Journal Article] MicroRNA-125a-5p is an independent prognostic factor in gastric cancer, and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab (2011)
  • Author(s): Nishida, N., Mimori, K., et al.
  • Journal Title: Clin Cancer Res Volume: (CD-R)
  • Peer Reviewed
• [Journal Article] FOXC2 is a Novel Prognostic Factor in Human Esophageal Squamous Cell Carcinoma (2011)
  • Author(s): Nishida, N., Mimori, K., et al.
  • Journal Title: Ann Surg Oncol Volume: 18 Pages: 535-42
  • Peer Reviewed
• [Journal Article] Identification of recurrence-related microRNAs in the bone marrow of breast cancer patients (2011)
  • Author(s): Nishida, N., Mimori, K., et al.
  • Journal Title: Int J Oncol Volume: 38 Pages: 955-62
  • Peer Reviewed
• [Journal Article] Significance of Lgr5(+ve) Cancer Stem Cells in the Colon and Rectum (2011)
  • Author(s): Takahashi, H., Ishii, H., Nishida, N., Takemasa, I., Mizushima, T., Ikeda, M., Yokobori, T., Mimori, K., et al.
  • Journal Title: Ann Surg Oncol Volume: 18 Pages: 1166-74
  • Peer Reviewed
• [Journal Article] Hypoxia-inducible Adrenomedullin in Colorectal Cancer (2011)
  • Author(s): Uemura, M., Yamamoto, H., Takemasa, I., Mimori, K., et al.
  • Journal Title: Anticancer Res Volume: 31 Pages: 507-14
  • Peer Reviewed
• [Journal Article] CD13 is a therapeutic target in human liver cancer stem cells. (2010)
  • Author(s): Haraguchi, N., Ishii, H., Mimori, K., et al.
  • Journal Title: J Clin Invest Volume: (CD-R)
  • Peer Reviewed
• [Journal Article] Notch pathway as candidate therapeutic target in Her2/Neu/ErbB2 receptor-negative breast tumors (2010)
  • Author(s): Hirose, H., Ishii, H., Mimor, K., et al.
  • Journal Title: Oncol Rep Volume: 23 Pages: 35-43
  • Peer Reviewed
• [Journal Article] Clinical Significance of Human Kallikrein7 Gene Expression in Colorectal Cancer. (2010)
  • Author(s): Inoue, Y., Yokobori, T., Yokoe, T., Toiyama, Y., Miki, C., Mimori, K., et al.
  • Journal Title: Ann Surg Oncol Volume: (CD-R)
  • Peer Reviewed
• [Journal Article] The Clinical Significance of Vimentin-Expressing Gastric Cancer Cells in Bone Marrow (2010)
  • Author(s): Iwatsuki, M., Mimori, K., et al.
  • Journal Title: Ann Surg Oncol Volume: (CD-R)
  • Peer Reviewed
• [Journal Article] Overexpression of SUGT1 in human colorectal cancer and its clinicopathological significance (2010)
  • Author(s): Iwatsuki, M., Mimori, K., et al.
  • Journal Title: Int J Oncol Volume: 36 Pages: 569-75
  • Peer Reviewed
• [Journal Article] Epithelial-mesenchymal transition in cancer development and its clinical significance (2010)
  • Author(s): Iwatsuki, M., Mimori, K., et al.
  • Journal Title: Cancer Sci Volume: 101 Pages: 293-9
  • Peer Reviewed
• [Journal Article] STC2 : A Predictive Marker for Lymph Node Metastasis in Esophageal Squamous-Cell Carcinoma (2010)
  • Author(s): Kita, Y., Mimori, K., et al.
  • Journal Title: Ann Surg Oncol Pages: 4
  • Peer Reviewed
• [Journal Article] Expression of C4.4A at the invasive front is a novel prognostic marker for disease recurrence of colorectal cancer (2010)
  • Author(s): Konishi, K., Yamamoto, H., Mimori, K., et al.
  • Journal Title: Cancer Sci Volume: 101 Pages: 2269-77
  • Peer Reviewed
• [Journal Article] FHIT Suppresses Inflammatory Carcinogenic Activity by Inducing Apoptosis in Esophageal Epithelial Cells (2010)
  • Author(s): Mimori, K., et al.
  • Journal Title: J Nucleic Acid Invest Volume: 101 Pages: 2269-77
  • Peer Reviewed
• [Journal Article] Identification of Recurrence-Related microRNAs in the Bone Marrow of Breast Cancer Patients. (2010)
  • Author(s): Mimori, K., et al.
  • Journal Title: Int J Oncol Volume: (CD-R)
  • DOI: 10.3892/ijo.2011.926
  • Peer Reviewed
• [Journal Article] Serum Matrix-Metalloproteinase-1 is a Bona Fide Prognostic Marker for Colorectal Cancer (2010)
  • Author(s): Mimori, K., et al.
  • Journal Title: Ann Surg Oncol Volume: (CD-R)
  • Peer Reviewed
• [Journal Article] Abnormal Expression of PFDN4 in Colorectal Cancer : A Novel Marker for Prognosis (2010)
  • Author(s): Miyoshi, N., Ishii, H., Mimori, K., et al.
  • Journal Title: Ann Surg Oncol Volume: (CD-R)
  • Peer Reviewed
• [Journal Article] TDGF1 is a novel predictive marker for metachronous metastasis of colorectal cancer (2010)
  • Author(s): Mimori, K., et al.
  • Journal Title: Int J Oncol Volume: 36 Pages: 563-8
  • Peer Reviewed
• [Journal Article] SCRN1 is a novel marker for prognosis in colorectal cancer (2010)
  • Author(s): Miyoshi, N., Ishii, H., Mimori, K., et al.
  • Journal Title: J Surg Oncol Volume: 101 Pages: 156-9
  • Peer Reviewed
• [Journal Article] TGM2 is a novel marker for prognosis and therapeutic target in colorectal cancer (2010)
  • Author(s): Miyoshi, N., Ishiii, H., Mimori, K., et al.
  • Journal Title: Ann Surg Oncol Volume: 17 Pages: 967-72
  • Peer Reviewed
• [Journal Article] ATP11A is a novel predictive marker for metachronous metastasis of colorctal cancer (2010)
  • Author(s): Miyoshi, N., Ishii, H., Mimori, K., et al.
  • Journal Title: Oncol Rep Volume: 23 Pages: 505-10
  • Peer Reviewed
• [Journal Article] Defined factors induce reprogramming of gastrointestinal cancer cells (2010)
  • Author(s): Miyoshi, N., Ishii, H., Mimori, K., et al.
  • Journal Title: Proc Natl Acad Sci U S A Volume: 107 Pages: 40-5
  • Peer Reviewed
• [Journal Article] Clinicopathological and prognostic significance of PDCD4 and microRNA-21 in human gastric cancer (2010)
  • Author(s): Miyoshi, N., Ishii, H., Mimori, K., et al.
  • Journal Title: Int J Oncol Volume: 36 Pages: 1089-95
  • Peer Reviewed
• [Journal Article] Correlated expression of CD47 and SIRPA in bone marrow and in peripheral blood predicts recurrence in breast cancer patients (2010)
  • Author(s): Nagahara, M., Mimori, K., et al.
  • Journal Title: Clin Cancer Res Volume: 16 Pages: 4625-35
  • Peer Reviewed
• [Journal Article] FOXC2 is a Novel Prognostic Factor in Human Esophageal Squamous Cell Carcinoma (2010)
  • Author(s): Nishida, N., Mimori, K., et al.
  • Journal Title: Ann Surg Oncol Volume: (CD-R)
  • Peer Reviewed
• [Journal Article] FANCD2 mRNA overexpression is a bona fide indicator of lymph node metastasis in human colorectal cancer (2010)
  • Author(s): Ozawa, H., Iwatsuki, M., Mimori, K., et al.
  • Journal Title: Ann Surg Oncol Volume: 17 Pages: 2341-8
  • Peer Reviewed
• [Journal Article] Strong interaction between the effects of alcohol consumption and smoking on oesophageal squamous cell carcinoma among individuals with ADH1B and/or ALDH2 risk alleles (2010)
  • Author(s): Tanaka, F., Yamamoto, K., Suzuki, S., Inoue, H., Tsurumaru, M., Kajiyama, Y., Kato, H., Igaki, H., Furuta, K., Fujita, H., Tanaka, T., Tanaka, Y., Kawashima, Y., Natsugoe, S., Setoyama, T., Tokudome, S., Mimori, K., et al.
  • Journal Title: Gut Volume: (CD-R)
  • Peer Reviewed
• [Journal Article] Clinical significance of ASB9 in human colorectal cancer (2010)
  • Author(s): Tokuoka, M., Miyoshi, N, Hitora, T., Mimori, K., et al.
  • Journal Title: Int J Oncol Volume: 37 Pages: 1105-11
  • Peer Reviewed
• [Journal Article] Jumonji domain containing 1A is a novel prognostic marker for colorectal cancer : in vivo identification from hypoxic tumor cells (2010)
  • Author(s): Uemura, M., Yamamoto, H., Takemasa, I., Mimori, K., et al.
  • Journal Title: Clin Cancer Res Volume: 16 Pages: 4636-46
  • Peer Reviewed
• [Journal Article] Clinical Significance of Stanniocalcin 2 as a Prognostic Marker in Gastric Cancer (2010)
  • Author(s): Yokobori, T., Mimori, K., et al.
  • Journal Title: Ann Surg Oncol Volume: (CD-R)
  • Peer Reviewed
• [Presentation] 大腸癌細胞のゲノムCGHクラスター解析および発現アレイpathway解析による5-FU適応症例の決定 (2010)
  • Author(s): 三森功士, 他8名
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-04-09