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A higher immune system model by combination of several types of artificial tissues (connective tissue, carcinoma tissue, and lymphoid tissue)

Research Project

Project/Area Number 13470240
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionKyushu University

Principal Investigator

KATANO Mitsuo  Kyushu University, Graduate School of Medical Sciences, Prof., 大学院・医学研究院, 教授 (10145203)

Co-Investigator(Kenkyū-buntansha) UCHIYAMA Akihiko  Kyushu University, Faculty of Medicine University Hospital, Ass., 医学部附属病院, 助手 (20294936)
MORISAKI Takashi  Kyushu University, Graduate School of Medical Sciences, Ass., 大学院・医学研究院, 助手 (90291517)
SUEISHI Katsuo  Kyushu University, Graduate School of Medical Sciences, Prof., 大学院・医学研究院, 教授 (70108710)
MATSUDA Takehisa  Kyushu University, Graduate School of Medical Sciences, Prof., 大学院・医学研究院, 教授 (60142189)
TANAKA Masao  Kyushu University, Graduate School of Medical Sciences, Prof., 大学院・医学研究院, 教授 (30163570)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥16,100,000 (Direct Cost: ¥16,100,000)
Fiscal Year 2002: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 2001: ¥10,600,000 (Direct Cost: ¥10,600,000)
Keywordsartificial connective tissue / artificial carcinoma tissue / artificial lymphoid tissue / higher immune system / immunotherapy / tumor immunity / 人工結合織 / 人工血管 / 人工リンパ節 / 高次免疫組織
Research Abstract

This study was focused on the construction of "a higher in vitro immune system model" by combining several types of artificial tissues, including connective tissues, carcinoma tissues, lymphoid tissues, and blood vessel. To perform the research plan, a new research area "tumor technology" was organized by collaboration of "Division of tumor immunology" and "Division of medical technology".
Data obtained for duration of this study are as follows:
(1) Development of artificial connective tissue: we reconstituted an in vitro connective tissue model which is made up of human fifroblasts and human umbrical vein-derived endothelial cells (HUVEC) in a type-I collagen gel. In this model, HUVEC migrate and form nets of fine blood vessels without addition of any special growth factors.
(2) Development of artificial carcinoma tissue: we reconstituted two types of artificial carcinoma tissue. One is a soft tissue type in which we are able to observe microscopically the growth of the two cell types (c … More arcinoma cells and fibroblasts) in real time for more than 30 days. Another is a hard tissue type which is prepared for immunohistochemical analysis. In this model, we can control the growth pattern of carcinoma cells, i.e., expansive or invasive growth, by combination of cytokines used.
(3) Development of artificial lymphoid tissue: artificial lymphoid tissue is organized in a type I collagen net supplemented with OKT-3 and fibrinogen, human fibroblasts, lymphocytes, and IL-2. In this model, lymphocytes well proliferate and secrete several types of cytokines such as IFN-g for more than 10 days.
(4) Development of preliminary immune system model: we reconstituted a preliminary higher immune system model which is organized in three layers, i.e., dendritic cell layer (lower), carcinoma tissue layer (middle), and lymphoid tissue layer (upper). In this model, we are able to observe microscopically migration of dendritic cells into carcinoma tissue and capture of necrotic carcinoma cells by migrating dendritic cells in real time. We also estimate simply and quickly immunological quality of dendritic cells by measuring IL-12 concentration secreted by dendritic cells.
We succeed in developing several types of artificial tissues using various types of cells obtained from surgically resected specimens. However, we did not succeed in connecting these artificial tissues with artificial blood vessel within this research period. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (56 results)

All Other

All Publications (56 results)

  • [Publications] Zhang H: "PSK-mediated NF-kB inhibition augments docetaxel-induced apoptosis in human pancreatic cancer cells NOR-P1"Oncogene. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Onishi H: "A large quantity of CD3-/CD19-/CD16-lymphocytes in malignant pleural effusion from a patient with recurrent cholangio cell carcinoma"Immunological Inveastigations. 31. 121-135 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura K: "Simulated microgravity culture system for a 3-D carcinoma tissue model"Bio Techniques. 33. 1068-1076 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hashizume K: "Candidate host marker for peritoneal dissemination"Anticancer Research. 22. 1781-1786 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saimura M: "Tumor suppression through angiogenesis inhibition by SUIT-2 pancreatic cancer cells genetically engineered to secrete NK4"Clinical Cancer Research. 8. 3243-3249 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saimura M: "Intraperitoneal injection of adenovirus-mediated NK4 gene suppresses peritoneal dissemination of pancreatic cancer cell line AsPC-1 in nude mice"Cancer Gene Therapy. 9. 799-806 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sasazuki T: "Identification of a novel transcriptional activator, BSAC, by a functional cloning to inhibit tumor necrosis factor-induced cell death"The Journal of Biological Chemistry. 32. 28853-28860 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Onishi H: "Dysfunctional and short-lived subsets in monocyte-derived dendritic cells from patients with advanced cancer"Clinical Immunology. 105. 286-295 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kojima M: "Association of enhanced cyclooxygenase-2 expression with possible local immunosuppression in human colorectal carcinomas"Annals of Surgical Oncology. 8. 458-465 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sasaki N: "Nuclear factor kappa B/p65(RelA) is constitutive activation in human gastric carcinoma"Clinical Cancer Research. 7. 4136-4142 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sato N: "Telomerase activity of cultured human pancreatic carcinoma cell lines correlates with their potential for migration and invasion"Cancer. 91. 496-504 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masaki I: "Recombinant Sendai virus-mediated gene transfer to vasculature : a new class of efficient gene transfer vector to the vascular system"The FASEB Journal. 15. 1294-1296 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sonoda H: "Small-diameter compliant arterial graft prothesis : Design concept of coaxial double tubular graft and its fabrication"Journal of Biomedical Material Research. 55. 266-276 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohya S: "Thermoresponsive artificial extracellular matrix for tissue engineering hyaluronic acid bioconjugated with poly (N-isopropylacrylamide) grafts"Biomacromolecules. 2. 856-863 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Gohda M: "Terminally alkylated heparin. 2. Potent antiproliferative agent for vascular smooth muscle cells"Biomacromolecules. 2. 1178-1183 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zhang H.: "PSK-mediated NF-kB inhibition augments docetaxel-induced apoptosis in human pancreatic cancer cells NOR-P1"Oncogene. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Onishi H.: "A large quantity of CD3-/CD19-/CD16- lymphocytes in malignant pleural effusion from a patient with recurrent cholangio cell carcinoma"Immunological Inveastigations. 31. 121-135 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura K.: "Simulated microgravity culture system for a 3-D carcinoma tissue model"Bio Techniques. 33. 1068-1076 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hashizume K.: "Candidate host marker for peritoneal dissemination"Anticancer Research. 22. 1781-1786 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saimura M.: "Tumor suppression through angiogenesis inhibition by SUIT-2 pancreatic cancer cells genetically engineered to secrete NK4"Clinical Cancer Research. 8. 3234-3249 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saimura M.: "Intraperitoneal injection of adenovirus-mediated NK4 gene suppresses peritoneal dissemination of pancreatic cancer cell line AsPC-1 in nude mice"Cancer Gene Therapy. 9. 799-806 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sasazuki T.: "Identification of a novel transcriptional activator, BSAC, by a functional cloning to inhibit tumor necrosis factor-induced cell death"The Journal of Biological Chemistry. 32. 28853-28860 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Onishi H.: "Dysfunction and short-lived subsets in monocyte-derived dendritic cells from patients with advanced cancer"Clinical Immunology. 105. 286-295 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kojima M.: "Association of enhanced cyclooxygenase-2 expression with possible local immunosuppression in human colorectal carcinomas"Annals of Surgical Oncology. 8. 458-465 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sasaki N.: "Nuclear factor kappa B/p65(RelA) is constitutive activation in human gastric carcinoma"Clinical Cancer Research. 7. 4136-4142 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sato N.: "Telomerase activity of cultured human pancreatic carcinoma cell lines correlates with their potential for migration and invasion"Cancer. 91. 496-504 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masaki I.: "Recombinant Sendai virus-mediated gene transfer to vasculature: a new class of efficient gene transfer vector to the vascular system"The FASEB Journal. 15. 1294-1296 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sonoda H.: "Small-diameter compliant arterial graft prothesis: Design concept of coaxial double tubular graft and its fabrication"Journal of Biomedical Material Research. 55. 266-276 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohya S.: "Thermoresponsive artificial extracellular matrix for tissue engineering hyaluronic acid bioconjugated with poly (N-isopropylacrylamide) grafts"Biomacromolecules. 2. 856-863 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Gohda M.: "Terminally alkylated heparin. 2. Potent antiproliferative agent for vascular smooth muscle cells"Biomacromolecules. 2. 1178-1183 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zhang H: "PSK-mediated NF-kB inhibition augments docetaxel-induced apoptosis in human pancreatic cancer cells NOR-P1"Oncogene. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Onishi H: "A large quantity of CD3-/CD19-/CD16-lymphocytes in malignant pleural effusion from a patient with recurrent cholangio cell carcinoma"Immunological Inveastigations. 31(2). 121-135 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakamura K: "Simulated microgravity culture system for a 3-D carcinoma tissue model"Bio Techniques. 33. 1068-1076 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hashizume K: "Candidate host marker for peritoneal dissemination"Anticancer Research. 22. 1781-1786 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Saimura M: "Tumor suppression through angiogenesis inhibition by SUIT-2 pancreatic cancer cells genetically engineered to secrete NK4"Clinical Cancer Research. 8. 3243-3249 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Saimura M: "Intraperitoneal injection of adenovirus-mediated NK4 gene suppresses peritoneal dissemination of pancreatic cancer cell line AsPC-1 in nude mice"Cancer Gene Therapy. 9. 799-806 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sasazuki T: "Identification of a novel transcriptional activator, BSAC, by a functional cloning to inhibit tumor necrosis factor-induced cell death"The Journal of Biological Chemistry. 32. 28853-28860 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Onishi H: "Dysfunctional and short-lived subsets in monocyte-derived dendritic cells from patients with advanced cancer"Clinical Immunology. 105. 286-295 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 片野光男: "免疫学を基盤とした重症感染症制御"日本臨床麻酔学会雑誌. 22. 115-123 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 森崎 隆: "癌におけるNF-kB活性化の臨床的意義;炎症における発癌と癌悪性化への関与"放射線生物研究. 37. 453-464 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Onishi H: "A large quantity of CD3-/CD19-/CD16-lymphocytes in malignant pleural effusion from a patient with recurrent cholangio cell carcinoma"Immunological Investigations. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Hashizume K: "Candidate host marker for peritoneal dissemination"Anticancer Research. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Kuwahara A: "Expression of melanoma antigen-encoding gene-1 predicts lymph node involvement in early gastric carcinomas"Digestive Diseases and Sciences. 46. 262-267 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kojima M: "Association of enhanced cyclooxygenase-2 expression with possible local immunosuppression in human colorectal carcinomas"Annals of Surgical Oncology. 8. 458-465 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sasaki N: "Nuclear factor kappa B/p65(RelA) is constitutive activation in human gastric carcinoma"Clinical Cancer Research. 7. 4136-4142 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sato N: "Telomerase activity of cultured human pancreatic carcinoma cell lines correlates with their potential for migration and invasion"Cancer. 91. 496-504 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sato N: "Instability of chromosome 8 as an indicator of aggressive tumor phenotype in pancreatic cancer"Journal of Surgical Oncology. 76. 181-187 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Maehara N: "NK4, a four-kringle antagonist of HGF, inhibits spreading and invasion of human pancreatic cancer cells"British Journal of Cancer. 84. 864-873 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Beppu K: "Hepatocyte growth factor production by peripheral blood mononuclear cells of recurrent cancer patients"Anticancer Research. 21. 2195-2200 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 片野光男: "胸腹腔内免疫監視機構システムの再構築による癌性胸腹膜炎治療"がん集学的治療研究財団 第21回一般研究助成研究報告書. 46(印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] 片野光男: "人工ハイブリッド免疫装置の開発と癌病態治療への応用"W'Waves(日本癌病態治療研究会誌). 7. 86-89 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masaki I: "Recombinant Sendai virus-mediated gene transfer to vasculature : a new class of efficient gene transfer vector to the vascular system"The FASEB Journal. 15. 1294-1296 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sonoda H: "Small-diameter compliant arterial graft prosthesis : Design concept of coaxial double tubular graft and its fabrication"Journal of Biomedical Material Research. 55. 266-276 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohya S: "Thermoresponsive artificial extracellular matrix for tissue engineering hyaluronic acid bioconjugated with poly (N-isopropylacrylamide) grafts"Biomacromolecules. 2. 856-863 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Gohda M: "Terminally alkylated heparin. 2. Potent antiproliferative agent for vascular smooth muscle cells"Biomacromolecules. 2. 1178-1183 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 片野光男: "外科領域における癌免疫療法-その理論と実際-"ライフサイエンス・メディカ. 167 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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