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Immune Responses Associated with Killer-Lymphocyte Population in Oral Cancer and their Therapeutic Significance

Research Project

Project/Area Number 61440083
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field 外科・放射線系歯学
Research InstitutionThe University of Tokushima

Principal Investigator

SATO Mitsunobu  University of Tokushima School of Dentistry, Second Department of Oral and Maxillofacial Surgery, Professor, 歯学部, 教授 (00028763)

Co-Investigator(Kenkyū-buntansha) TAKEGAWA Yoshihiro  University of Tokushima School of Medical Sciences, Professor, 医療短期大学部, 教授 (40035754)
YANAGAWA Tetsuo  University of Tokushima School of Dentistry, Second Department of Oral and Maxil, 歯学部付属病院, 講師 (40136263)
YOSHIDA Hideo  University of Tokushima School of Dentistry, Second Department of Oral and Maxil, 歯学部, 助教授 (30116131)
林 良夫  徳島大学, 歯学部附属病院, 講師 (00127854)
Project Period (FY) 1986 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥25,100,000 (Direct Cost: ¥25,100,000)
Fiscal Year 1989: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1988: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1987: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1986: ¥17,000,000 (Direct Cost: ¥17,000,000)
KeywordsOral cancer / Immune response / Killer lymphocyte / NK cells / LAK cells / Subsets of peripheral blood lymphocyte / Phenotype of cancer cells / Therapy of Oral cancer / Killerリンパ球 / 末梢リンパ球亜群 / ADCC / 唾液腺癌細胞 / リンパ球亜群 / 単クローン抗体 / Killer リンパ球
Research Abstract

1. In this study, we have confirmed that the change of the peripheral K-lymphocyte population in oral cancer patients is intimately associated with clinical tumor status and clinical outcome; e.g., the treated, disease-free group showed increased K-lymphocyte counts as compared with the untreated group. In addition, absolute counts of K-lymphocyte in the patients having recurrent tumor or distant metastatis were significantly lower than those in the treated, disease-free patients. Moreover, accumulated data have suggested that the K-lymphocytes seem to be villous, small-to- medium-sized lymphocytes with CD3^+4^-8^- phenotype.
2. The relationship between cell subsets carrying differentiation antigens associated with NK cells (Leu 7, Leu 11a and M1) and clinical tumor status in patients with squamous cell head and neck cancer was examined, Consequently, the percentages of Leu 7^+ cells (p<0.001) and Leu 11a^+ cells (p<0.000001) from 45 patients were significantly higher than those of 25 n … More ormal controls, whereas NK cell activity in the patients was significantly decreased in comparison with that in the controls (p<0.0001). The Leu 7/Leu 11a ratios in 23 patients with regional lymph node metastasis were significantly higher than those in the negative-node group (n=22, p<0.01). There was significant correlation between each of the following pairs: percentages of Leu 7^+ and Leu 11a^+ cells (p<0.01), percentages of Leu 7^+ and M1^+ cells (p<0.05) in patients, and: percentages of Leu 11a^+ and M1^+ cells (p<0.05) in controls. These findings indicate that deficient NK cell activity exists in paripheral blood of the patients and considerable difference between the patients with various clinical tumor status and normal controls exists with regard to NK cell phenotype.
3. It has been found that the levels of immunoglobulin A circulating immune complexes (IgA-CIC)in the sera of 31 patients with oral cancer are significantly higher than those in 21 normal controls and are associated with clinial tumor status and clinical outcome.
4. In this study, we have investigated on the phenotype of human salivary gland adenocarcinoma cell line HSG and generated an iminunoglobulin G2a mouse monoclonal antibody (MAb) 5B/10 which reacts with a subset of human salivary gland tumors, by using HSG cells as immunogen. In addition, we have established the in vitro and in vivo experimental systems which arrow to examine the antitumor effects mediated by MAb 5B/10 in human salivary gland adenocarcinoma (HSG)-bearing nude mice, and the antibody- dependent cell-mediated cytotoxicity (ADCC) against HSG cells using MAb 5B/10 and human peripheral blood mononuclear cells as effector cells, or the effects on the ADCC systems of biological response modifiers, antitumor drugs or irradiation. Less

Report

(5 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • 1987 Annual Research Report
  • 1986 Annual Research Report
  • Research Products

    (58 results)

All Other

All Publications (58 results)

  • [Publications] Hideo Yoshida: "Effect of dibutyryl cyclic AMP on morphologic features and biological markers of a human salivary gland adenocarcinoma cell line in culture" Cancer. 57. 1011-1018 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yoshio Hayashi: "Monoclonal antibody analysis of peripheral blood lymphocyte subpopulations in squamous cell head and neck cancer" The Cancer Journal. 1. 25-29 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Tetsuo Yanagawa: "Immunohistochemical demonstration of carcinoembryonic antigen(CEA)on tissue sections from squamous cell head and neck cancer and plasma CEA levels of the patient" International Journal of Oral and Maxillofacial Surgery. 15. 296-306 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mitsuru Urata: "Immunoglobulin A circulating immune complexes in oral squamous cell cancer" The Cancer Journal. 1. 68-71 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Tetsuo Yanagawa: "An adenoid squamous carcinoma-forming cell line established from an oral keratinizing squamous cell carcinoma expressing carcinoembryonic antigen" The American Journal of Pathology. 124. 496-509 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yoshio Hayashi: "Phenotypic and functional characterization of peripheral natural killer cell population in squamous cell head and neck cancer" The Cancer Journal. 1. 353-357 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Hideo Yoshida: "Generation and characterization of a monoclonal antibody against a neoplastic human salivary intercalated human salivary intercalated duct cell line" The Cancer Journal. 1. 269-276 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mitsunobu Sato: "5-azacytidine induction of stable myoepithelial and acinar cells from a human salivary intercalated duct cell clone" Cancer Research. 47. 4453-4459 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Masayuki Azuma: "The relation of ras oncogene product p21 expression to clinicopathological status criteria and clinical outcome in squamous cell head and neck cancer" The Cancer Journal. 1. 357-380 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mitsunobu Sato: "Monoclonal antibody to the streptococcal preparation OK-432 localization and analysis of interaction bertween OK-432 and macrophages or NK cells in human salivary adenocarcinoma-bearing nude mice given OK-432" Journal of Biological Response Modifiers. 7. 212-228 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Hideo Yoshida: "Enhancement of cis-diamminedichloroplatinum and mitomycin C-induced sister chromatid exchanges by dibutyryl cyclic AMP in a human salivary gland adenocarcinoma cell line in culture" Cancer. 61. 1741-1748 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Masayuki Azuma: "Effect of retinoic acid on morphological features and biological markers of a neoplastic human salivary intercalated duct cell line in culture" Cancer Research. 48. 7219-7225 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ryoji Kaji: "Monoclonal antibody to a human salivary gland adenocarcinoma cell line:Augmentation of antibody dependent cell-mediated cytotoxicity activity by streptococcal preparation OK-432 in human salivary gland adenocarcinoma-bearing nude mice given the antibody" Journal of Biological Response Modifiers. 8. 488-500 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mitsunobu Sato: "Induction of bone formation in an adenoid cystic carcinoma of the maxillary sinus by adoptive immunotherapy involving intraarterial injection of lymphokine-activated killer cells and recombinant interleukin 2 in combination with radiotherapy" Journal of Biological Response Modifiers(in press). (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mitsunobu Sato(Editors:Y.Kawade & S.Kobayashi): "The Biology of the Interferon System 1988.Proceeding of the 1988 Annual Meeting of ISIR.Effect of interferon α,β or γ on the neoplastic human salivary intercalated duct cell line" c/o Inter Group Corp., 389-394(6) (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mitsunobu Sato(Editors:B.Berkarda & H.-P.Kuemmerle): "Progress in Antimicrobial and Anticancer chemotherapy.Proceedings of the 15th International Congress of Chemotherapy.Expression of interferons in NK cells or macrophages capturing the streptococcal preparation OK-432 present in nude mouse-grown thmor with administration." ecomed, 174-176(3) (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Hideo Yoshida: "Effect of dibutyryl cyclic AMP on morphologic features and biological markers of a human salivary gland adenocarcinoma cell line in culture" Cancer. 57(5). 1011-1018 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yoshio Hayashi: "Monoclonal antibody analysis of peripheral blood lymphocyte subpopulations in squamous cell head and neck cancer" The Cancer Journal, 1(1), 25-29, 1986.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Tetsuo Yanagawa: "Immunohistochemical demonstration of carcinoembryonic antigen (CEA) on tissue sections from squamous cell head and neck cancer and plasma CEA levels of the patient" International Journal of Oral and Maxillofacial Surgery, 15(3), 296-306, 1986.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mitsuru Urata: "Immunoglobulin A circulating immune complexes in oral squamous cell cancer" The Cancer Journal, 1(2), 68-71, 1986.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Tetsuo Yanagawa: "An adenoid squamous carcinomaforming cell line established from an oral keratinizing squamous cell carcinoma expressing carcinoembryonic antigen" The American Journal of Pathology, 124(3), 496-509, 1986.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yoshio Hayashi: "Phenotypic and functional characterization of peripheral natural killer cell population in squamous cell head and neck cancer" The Cancer Journal, 1(8), 353-357, 1987.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Hideo Yoshida: "Generation and characterization of a monoclonal antibody against a neoplastic human salivary intercalated duct cell line" The Cancer Journal, 1(6), 269-276, 1987.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mitsunobu Sato: "5-azacytidine induction of stable myoepithelial and acinar cells from a human salivary intercalated duct cell clone" Cancer Research, 47(16), 4453-4459, 1987.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Masayuki Azuma: "The relation of ras oncogene product p21 expression to clinicopathological status criteria and clinical outcome in squamous cell head and neck cancer" The Cancer Journal, 1(9), 375-380, 1987.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mitsunobu Sato: "Monoclonal antibody to the streptococcal preparation OK-432 localization and analysis of interaction between OK-432 and macrophages or NK cells in human salivary adenocarcinoma-bearing nude mice given OK-432" Journal of Biological Response Modifiers, 7(2), 212-228, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Hideo Yoshida: "Enhancement of cis-diamminedichloroplatinum and mitomycin C-induced sister chromatid exchanges by dibutyryl cyclic AMP in a human salivary gland adenocarcinoma cell line in culture" Cancer, 61(9), 1741-1748, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Masayuki Azuma: "Effect of retinoic acid on morphological features and biological markers of a neoplastic human salivary intercalated duct cell line in culture" Cancer Research, 48(24), 7219-7225, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ryoji Kaji: "Monoclonal antibody to a human salivary gland adenocarcinoma cell line: Augmentation of antibody-dependent cell-mediated cytotoxicity activity by streptococcal preparation OK-432 in human salivary gland adenocarcinoma-bearing nude mice given the antibody" Journal of Biological Response Modifiers, 8(5), 488-500, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mitsunobu Sato: "Induction of bone formation in an adenoid cystic carcinoma of the maxillary sinus by adoptive immunotherapy involving intraarterial injection of lymphokine-activated killer cells and recombinant interleukin 2 in combination with radiotherapy" Journal of Biological Response Modifiers (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mitsunobu Sato (Editors: Y. Kawade & S. Kobayashi): "The Biology of the interferon System 1988. Proceeding of the 1988 Annual Meeting of ISIR. Effect of interferon alpha, beta or gamma on the proliferation and differentiation of a neoplastic human salivary intercalated duct cell line" c/o Inter Group Corp.389-394(6) (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mitsunobu Sato (Editors: B. Berkarda & H.-P. Kuemmerle): "Progress in Antimicrobial and Anticancer Chemotherapy. Proceedings of the 15th International congress of Chemotherapy. Expression of interferons in NK cells or macrophages capturing the streptococcal preparation OK-432 present in nude mouse-grown tumor with administration" ecomed. 174-176(3) (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ryoji kaji: "Monoclnal antibody to a human salivary adenocarcinoma cell line:Augmentation of antibody-dependent cell-mediated cytotoxicity(ADCC)activity by streptococcal preparation OK-432 in human salivary adenocarcinoma-bearing nude mice given the antibody" Journal of Biological Response Modifiers. 8. 488-500 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Masayuki Azuma: "Induction of cells with a chondrocyte-like phenotype by treatment with 1alpha,25-dihydroxyvitamin D_3 in a human salivary acinar cell line" Cancer Research. 49. 5435-5442 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 竹川佳宏: "歯槽歯肉癌の集学治療" 日本放射線腫瘍学会誌. 1. 111-118 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Kazunori Miyamoto: "Establishment of a transformed human epithelial cell line with a sebaceous cell phenotype and effect of epidermal growth factor and dibutyryl cyclic adenosine 3′:5′-monophosphate on the cellular phenotype" The Cancer Journal. 3. 414-422 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Mitsunobu Sato: "Induction of bone formation in an adenoid cystic carcinoma of the maxillary sinus by adoptive immunotherapy involving intraarterial injection of lymphokine-activated killer cells and recombinant interleukin 2 in combination with radiotherapy" Journal of Biological Response Modifiers. (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] Mitsunobu,Sato: J.Biol.Response Mod.7. 212-228 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Hideo,Yoshida: Cancer. 61. 1741-1748 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Masayuki,Azuma: Cancer Research. 48. 2898-2903 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Masayuki,Azuma: Cancer,Research. 48. 7219-7225 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 梁川哲雄: 癌と化学療法. 15. 3159-3161 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Ryoji,Kaji: J.Biol.Response Mod.(1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Mitsunobu Sato Editor:Y.kawade: "Proceeding of the 1988 Annual Meeting of ISIR.Effect of interferon α,βorγon the prolifiration and differentiation of a neoplastic human salivary intercalated duct cell line." C/O Inter Group Corp., (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Yoshio Hayashi: The Cancer Journal. 1. 353-357 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Mitsunobu Sato: Cancer Research. 47. 4453-4459 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Yoshio Hayashi: Cancer. 60. 1000-1008 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Hideo Yoshida: The Cancer Journal. 1. 269-273 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Mitsunobu Sato: J. Biol. Response Mod.(1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Hideo Yoshida: Cancer. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Mitsunobu Sato Editor: B. Berkarda: "Progress in antimicrobial and anticancer chemotherapy. Anticancer section-Expression of interferons in NK cells or macrophages capturing the streptococcal preparation OK-432 present in nude mouse-grown tumor with OK-432 administration" Ecomed, 874 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Mitsuru Urata: The Cancer Jouranl. 1. 68-72 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Tetsuo Yanagawa: The American Journal of Pathology. 124. 496-509 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Mitsunobu Sato: The Cancer Jouranl. 1. 161-168 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Yoshio Hayashi: Cancer.

    • Related Report
      1986 Annual Research Report
  • [Publications] Hideo Yoshida: The Cancer Journal.

    • Related Report
      1986 Annual Research Report
  • [Publications] Mitsunobu Sato: Cancer Research.

    • Related Report
      1986 Annual Research Report
  • [Publications] Mitsunobu Sato Editor:Takashi Hashino: "Immunopharmacological aspects of OK-432 in humans-Effect of immunotherapy with a streptococcal preparation,OK-432 on the peripheral killer lymphocyte population in patients with head and neck cancer" Excerpta Medica, 238(78-88) (1986)

    • Related Report
      1986 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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