Analysis of the mechanisms for cytotoxic effects in the perforin/granzyme B system

• Project/Area Number: 14571221
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Iwate Medical University School of Medicine
• Principal Investigator: SATO Nobuhiro Iwate Med. Univ. School of Med., Dept. of Surgery, Lecturer, 医学部, 講師 (10244914)
• Co-Investigator(Kenkyū-buntansha): MAESAWA Chihaya Iwate Med. Univ. School of Med., Dept. of Pathl, Lecturer, 医学部, 講師 (10326647)
• Project Period (FY): 2002 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000); Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
• Keywords: perform / granzyme B / bioineratction analysis / maspin / sensor chip / 生体内分子 / パーフォリン / CTL / リン脂質膜 / リ脂質膜

Research Abstract

We developed a new assay for cytotoxic effects of perforin/ granzyme B systems, by using Bio Sensor Chip. The assay utilized the surface plasmon resonance technology for the analysis Biomolecular interaction analysis. The assay is rapid and sensitive method, and moreover, allows precise quantitative membranous injury. We also examined inhibitory effects of seine protease inhibitor (Serpin) family to cellular injury. Maspin is a candidate for intra cellular molecule to inhibit granzyme B system. We are now examining for the inhibitor effects by using the RNAi method.

Research Products

• [Publications] Sato N, Koeda K, Ikeda K, Kimura Y, Aoki K, Iwaya T, Akiyama Y, Ishida K, Saito K, Endo S.: "Randomized study of the benefits of preoperative corticosteroid administration on the postoperative morbidity and cytokine response in patients undergoing surgery."Ann Surg.. 236(2). 184-190 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sato N, Endo S, Kimura Y, Ikeda K, Aoki K, Iwaya T, Akiyama Y, Noda Y, Saito K.: "Influence of a human protease inhibitor on surgical stress induced immunosuppression."Dig Surg.. 19(4). 300-305 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Maesawa C, Iijima S, Sato N, Yoshinori N, Suzuki M, Tarusawa M, Ishida K, Tamura G, Saito K, Masuda T.: "Esophageal extraskeletal Ewing's sarcoma."Hum Pathol.. 33(1). 130-132 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tarusawa M, Yashima A, Endo M, Maesawa C.: "Quantitative assessment of minimal residual disease in childhood lymphoid malignancies using an allele-specific oligonucleotide real-time quantitative polymerase chain reaction."Int J Hematol.. 75(2). 166-173 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Iijima S, Maesawa C, Sato N, Ikeda K, Inaba T, Akiyama Y, Ishida K, Saito K, Masuda T.: "Gastrointestinal stromal tumour of the oesophagus : significance of immunohistochemical and genetic analyses of the c-kit gene."Gastroenterol Hepatol.. 14(4). 445-448 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Wada K, Maesawa C, Satoh T, Akasaka T, Masuda T.: "A case of primary cutaneous CD30+ T-cell lymphoproliferative disorder with features of granulomatous slack skin disease."Br J Dermatol.. 147(5). 998-1002 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Maesawa C, Inaba T, Sato H, Iijima S, Ishida K, Terashima M, Sato R, Suzuki M, Yashima A, Ogasawara S, Oikawa H, Sato N, Saito K, Masuda T.: "A rapid biosensor chip assay for measuring of telomerase activity using surface plasmon resonance."Nucleic Acids Res.. 31(2). E4-E4 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yashima A, Maesawa C, Uchiyama M, Tarusawa M, Satoh T, Satoh M, Enomoto S, Sugawara K, Numaoka H, Murai K, Utsugisawa T, Ishida Y, Masuda T.: "Quantitative assessment of contaminating tumor cells in autologous peripheral blood stem cells of B-cell non-Hodgkin lymphomas using immunoglobulin heavy chain gene allele-specific oligonucleotide real-time quantitative-polymerase chain reaction."Leuk Res.. 27(10). 925-934 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nakatani K, Hagihara S, Sando S, Sakamoto S, Yamaguchi K, Maesawa C, Saito I.: "Induction of a remarkable conformational change in a human telomeric sequence by the binding of naphthyridine dimer : inhibition of the elongation of a telomeric repeat by telomerase."J Am Chem Soc.. 125(3). 662-666 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Uchiyama M, Maesawa C, Yashima A, Itabashi T, Ishida Y, Masuda T.: "Consensus primers for detecting monoclonal immunoglobulin heavy chain rearrangement in B-cell lymphomas."J Clin Pathol.. 56(10). 778-779 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Uchiyama M, Maesawa C, Yashima A, Itabashi T, Satoh T, Ishida Y, Masuda T.: "Development of immunoglobulin variable heavy-chain gene consensus probes with conjugated 3'-minor groove binder groups for monitoring minimal residual disease in childhood acute lymphoblastic leukemia."J Clin Pathol.. 56(12). 952-955 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Akiyama Y, Maesawa C, Ogasawara S, Terashima M, Masuda T.: "Cell-type-specific repression of the maspin gene is disrupted frequently by demethylation at the promoter region in gastric intestinal metaplasia and cancer cells."Am J Pathol.. 163(5). 1911-1919 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Uchiyama M, Maesawa C, Yashima A, Tarusawa M, Satoh S, Ishida Y, Ito S, Murai K, Enomoto S, Utsugisawa T, Motoyoshi K, Masuda T.: "Development of consensus fluorogenically labeled probes of the immunoglobulin heavy-chain gene for detecting minimal residual disease in B-cell non-Hodgkin lymphomas."Cancer Sci.. 94(10). 877-885 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ogasawara S, Maesawa C, Yamamoto M, Akiyama Y, Wada K, Fujisawa K, Higuchi T, Tomisawa Y, Sato N, Endo S, Saito K, Masuda T.: "Disruption of cell-type-specific methylation at the Maspin gene promoter is frequently involved in undifferentiated thyroid cancers."Oncogene.. 23(5). 1117-1124 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Wada K, Maesawa C, Akasaka T, Masuda T.: "Aberrant expression of the maspin gene associated with epigenetic modification in melanoma cells."J Invest Dermatol.. 122(3). 805-811 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Oyama M, Terashima M, Takagane A, Maesawa C.: "Prognostic significance of peritoneal minimal residual disease in detecting mRNA in gastric cancer using quantitative real-time reverse transcriotive-polymerase chain reaction of carcinoembryonic antigen."Br J Surg.. 91(4). 435-443 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Itabashi T, Maesawa C, Uchiyama M, Higuchi T, Masuda T.: "Quantitative detection of mutant alleles of the K-ras gene with minor groove binder-conjugated fluorogenic DNA probes."Int J Oncol.. 24(3). 687-696 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Satoh H, Nakamura M, Satoh M, Nakajima T, Izumoto H, Maesawa C, Kawazoe K, Masuda T, Hiramori K.: "Expression and localization of Tumor Necrosis Factor-alpha and its converting enzyme in human abdominal aortic aneurysm."Clin Sci (Lond).. 106(3). 301-306 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Akiyama Y, Maesawa C, Wada K, Fujisawa K, Itabashi T, Noda Y, Honda T, Sato N, Ishida K, Takagane A, Saito K, Masuda T.: "Human PinX1, a potent telomerase inhibitor, is not involved in human gastrointestinal tract carcinoma."Oncol Rep.. 11(4). 871-874 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sato N, Koeda K, Ikeda K, Kimura Y, Aoki K, Iwaya R, Akiyama Y, Ishida K, Saito K, Endo S.: "Randomized study of the benefits of preoperative corticosteroid administration on the postoperative morbidity and cytokine response in patients undergoing surgery for esophageal cancer."Ann Surg.. 235(2). 184-190 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sato N, Endo S, Kimura Y, Ikeda K, Aoki K, Iwaya T, Akiyama Y, Noda Y, Saito K.: "Influence of a human protease inhibitor on surgical stress induced immunosuppression."Dig Surg. 19(4). 300-305 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Maesawa C, Iijina S, Sato N, Yoshinori N, Suzuki M, Tanisawa M, Ishida K, Tamura G, Saito K, Masuda T.: "Esophageal extraskeletal Ewing's sarcoma."Hum Pathol.. 33(1). 130-132 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tarusawa M, Yashima A, Endo M, Maesawa C.: "Quantitative assessment of minimal residual disease in childhood lymphoid malignancies using an allele-specific oligonucleotide real-time quantitative polymerase chain reaction."Int J Hematol.. 75(2). 166-173 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Iijima S, Maesawa C, Sato N, Ikeda K, Inaba T, Akiyama Y, Ishida K, Saito K, Masuda T.: "Gastrointestinal stromal tumour of the oesophagus: significance of immunohistochemical and genetic analyses of the c-kit gene."Eur J Gastroenterol Hepatol.. 14(4). 445-448 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Wada K, Maesawa C, Satoh T, Akasaka T, Masuda T.: "A case of primary cutaneous CD30+ T-cell lyimphoproliferative disorder with features of granulomatous slack skin disease."Br J Dermatol.. 147(5). 998-1002 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Maesawa C, Inaba T, Sato H, Iijima S, Ishida K, Terashima M, Sato R, Suzuki M, Yashima A, Ogasawara S, Oikawa H, Sato N, Saito K, Masuda T.: "A rapid biosensor chip assay for measuring of telomerase activity using surface plasmon resonance."Nucleic Acids Res.. 31(2). E4-E4 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yashima A, Maesawa C, Uchiyama M, Tarusawa M, Satoh T, Satoh M, Enomoto S, Sugawara K, Numaoka H, Murai K, Utsugisawa T, Ishida Y, Masuda T.: "Quantitative assessment of contaminating tumor cells in autologous peripheral blood stem cells of B-cell non-Hodgkin lymphomas using immunoglobulin heavy chain gene allele-specific oligonucleotide real-time quantitative-polymerase chain reaction."Leuk Res.. 27(10). 925-934 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nakatani K, Hagihara S, Sando S, Sakamoto S, Yamaguchi K, Maesawa C, Saito I.: "Induction of a remarkable conformational change in a human telomeric sequence by the binding of naphthyridine dimer inhibition of the elongation of a telomeric repeat by telomerase."J Am Chem Soc.. 125(3). 662-666 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Uchiyama M, Maesawa C, Yashima A, Itabashi T, Ishida Y Masuda T.: "Consensus primers for detecting monoclonal immunoglobulin heavy chain rearrangement in B-cell lymphomas."J Chin Pathol.. 56(10). 778-779 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Uchiyama M, Maesawa C, Yashima A, Itabashi T, Satoh T, Ishida Y, Masuda T.: "Development of immunoglobulin variable heavy-chain gene consensus probes with conjugated 3'-minor groove binder groups for monitoring minimal residual disease in childhood acute lymphoblastic leukemia."J Chin Pathol.. 56(12). 952-955 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Akiyama Y, Maesawa C, Ogasawara S, Terashima M, Masuda T.: "Cell-type-specific repression of the maspin gene is disrupted frequently by demethylation at the promoter region in gastric intestinal metaplasia and cancer cells."Am J Pathol.. 163(5). 1911-1919 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Uchiyama M, Maesawa C, Yashima A, Tarusawa N, Satoh S< Ishida Y, Ito S, Murai K, Enomoto S, Utsugisawa T, Motoyoshi K, Masuda T.: "Development of consensus fluorogenically labeled probes of the immunoglobulin heavy-chain gene for detecting minimal residual disease in B-cell non-Hodgkin lymphomas."Cancer Sci.. 94(10). 877-885 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ogasawara S, Maesawa C, Yamamoto M, Akiyama Y, Wada K, Fujisawa K, Higuchi T, Tomisawa Y, Sato N, Endo S, Saito K, Masuda T.: "Disruption of cell-type-specific methylation at the Maspin gene promoter is frequently involved in undifferentiated thyroid cancers."Oncogene.. 23(5). 1117-1124 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Wada K, Maesawa C, Akasaka T, Masuda T.: "Aberrant expression of the maspin gene associated with epigenetic modification in melanoma cells."J Invest Dermatol.. 112(3). 805-811 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Oyama M, Terashima M, Takagane A, Maesawa C.: "Prognostic significance of peritoneal minimal residual disease in detecting mRNA in gastric cancer using quantitative real-time reverse transcriotive-polymerase chain reaction of carcinoembryonic antigen."Br J Surg.. 91(4). 435-443 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Itabashi T, Maesawa C, Uchiyama M, Higuchi T, Masuda T.: "Quantitative detection of mutant alleles of the K-ras gene with minor groove binder-conjugated fluorogenic DNA probes."Int J Oncol.. 24(3). 687-696 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Satoh H, Nakamura M, Satoh M, Nakajima T, Izumoto H, Maesawa C, Kawazoc K, Masuda T, Hiramori K.: "Expression and localization of Tumor Necrosis Factor-alpha and its converting enzyme in human abdominal aortic aneurysm."Clin Sci (Lond).. 106(3). 301-306 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Akiyama Y, Maesawa C, Wada K, Fujisawa K, Itabashi T, Noda Y, Honda T, Sato N, Ishida K, Takagane A, Saito K, Masuda T.: "Human PinX1, a potent telomerase inhibitor, is not involved in human gastrointestinal tract carcinoma."Oncol Re. 11(4). 871-874 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Akiyama Y, Maesawa C, Wada K, Fujisawa K, Itabashi T, Noda Y, Honda T, Sato N, Ishida K, Takagane A, Saito K, Masuda T: "Human PinX1, a potent telomerase inhibitor, is not involved in human gastrointestinal tract carcinoma."Oncol Rep. 11・4. 871-874 (2004)
• [Publications] Ogasawara S, Maesawa C, Yamamoto M, Akiyama Y, Wada K, Fujisawa K, Higuchi T, Tomisawa Y. Soto N, E: "Disruption of cell-type-specific methylation at the Maspin gene promoter is frequently involved in undifferentiated thyroid cancers."Oncogene. 23・5. 1117-1124 (2004)
• [Publications] Yamada Y, Endo S, Nakae H, Makabe H, Sato N, Wakabayashi G, Kitamura M, Inada K, Sato S: "Examination of soluble Fas (sFas) and soluble Fas ligand (sFasL) in patients with burns."Burns. 29・8. 799-802 (2003)
• [Publications] Akiyama Y, Maesawa C, Ogasawara S, Terashima M, Masuda T: "Cell-type-specific repression of the maspin gene is disrupted frequently by demethylation at the promoter region in gastric intestinal metaplasia and cancer cells."Am J Pathol. 165・5. 1911-1919 (2003)
• [Publications] Uchiyama M, Maesawa C, Yashima A, Tarusawa M.Satoh S, Ishida Y, Ito S, Murai K, Enomoto S, Utsugisawa T, Motoyoshi K, Masuda T: "Development of consensus fluorogenically labeled probes of the immunoglobulin heavy-chain gene for detecting minimal residual disease in B-cell non-Hodgkin lymphomas."Cancer Sci. 94・10. 875-885 (2003)
• [Publications] Iijima S, Maesawa C, Sato N, et al.: "Gastrointestinal stromal tumour of the oesphagus : significance of immunohistochemical and genetic analyses of the c-kit gene"Eur J Gastroterol Hepatol. 14. 445-448 (2002)
• [Publications] Tarusawa M, Yashima A, Endo M, Maesawa C.: "Quantitative assessment of minimal residual disease in childhood lymphoid malignancies using an allele-specific oligonucleotide real-time quantitative polymerase chain reaction"Int J Hematol. 75. 166-173 (2002)
• [Publications] Sato N, Koeda K, Ikeda K, Kimura Y., et al.: "Randomized study of the benefit of preoperative corticosteroid administration on the postoperative morbidity and cytokine response in patients undergoing surgery for esophageal cancer"Ann Surg. 236. 184-190 (2002)
• [Publications] Nakatani K, Hagihara S, Sando S, Sakamoto S, Yamaguchi K, Maesawa C, Saito I.: "Induction of a remarkable conformational change in a human telomeric sequence by the binding of naphthyridine dimer : inhibition of the elongation of a telomeric repeat by telomerase"J Am Chem Soc. 125. 662-666 (2003)
• [Publications] Maesawa C, Inaba T, Sato H, Iijima S, Ishida K, Terashima M, Sato R, et al.: "A rapid biosensor chip assay for measuring of telomerase activity using surface plasmon resonance"Nucleic Acids Res. 31. E4-4 (2003)
• [Publications] Sato N, Endo S, Kimura Y, Ikeda K, et al.: "Influence of a human protease inhibitor on surgical stress induced immunosuppression"Dig Surg. 19. 300-305 (2002)