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Development of screening system for searching cellular differentiation-inducing agents by utlizing human salivary cancer cells

Research Project

Project/Area Number 05557084
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 病態科学系歯学(含放射線系歯学)
Research InstitutionThe University of Tokushima

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) AZUMA Masayuki  School of Dentistry, Second Department of Oral and Maxillofacial Surgery, Instru, 歯学部・付属病院, 講師 (20144983)
YOSHIDA Hideo  School of Dentistry, Second Department of Oral and Maxillofacial Surgery, Associ, 歯学部, 助教授 (30116131)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 1994: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1993: ¥8,000,000 (Direct Cost: ¥8,000,000)
KeywordsHuman salivary cancer cells / Cellular differentiation-inducing agents / Screening system / Salivary adenoid squamous carcinoma-forming cells / DNA hypomethylation / Apoptosis / Anti-tumor agents / 口腔小唾液腺由来腺様扁平上皮癌細胞 / 造腫瘍性ヒト腺房細胞癌細胞 / 分化誘導剤
Research Abstract

1.Neuron-like cells (HSG-AZAll) with ample neurofilament bundles and endoplasmic reticulum as well as alpha-and beta-chain of tubulin were isolated from human salivary cancer cell line HSG treated with 5-azactidine. This HSG-AZAll cells were found to from neurites and express synaptophysin and neuron-specific enolase in response to dibutyryl cyclic AMP.This indicated that HSG-AZAll cells might be useful for searching cellular differentiation-inducing agents which work via cAMP signal transduction. 2.We have found that the treatment of HSG cells with 5-fluorodeoxyuridine monophosphate results in the differentiation into myoepithelial cells and induciton of apoptosis. 3.We have found that the cultivation of HSG-AZA3 cells with an acinar cell phenotype, which were induced by treatment of HSG cells with 5-azacytidine, in the presence of 3,4-dihydro-6-[3,4-dimethoxybenzoyl)-1-piperazinyl]-2 (1H) -quinolnone (vesnarinone) results in the differentiation into chondrocytes.In addition, it has b … More een found that the treatment of HSG-AZA3 cells with 22-oxa-1alpha, 25-dihydroxyvitamin D_3 causes the differentiation into osteoblasts. 4.We have found that the treatment of HSG cells with etoposide, an inhibitor of DNA topoisomerase II,results in the induction of cells with a smooth muscle cell phenotype, such as expression of alpha-smooth muscle actin and myofilaments, as well as in the induction of apoptosis. 5.When adenoid squamous carcinoma-forming cells (TYS) , derived from human minor salivary gland present in the oral cavity, was treated with 5-fluorouracil or vesnarinone, it has been found that the induction of apoptosis and differentiation into acinar cells occurs in the treated cells. 6.The treatment with 22-oxa-1alpha, 25 (OH) _2D_3 of HSG-AZA3 cells grown as xenografts in nude mice resulted in the marked growth inhibition of tumors, in which bone formation and bone remodeling were detected. 7.When TYS nude mouse tumors were treated with vesnarinone, significant suppression of tumor growth as well as differentiation into both keratinocytes and acinar cells were detected in the treated tumors. Less

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (39 results)

All Other

All Publications (39 results)

  • [Publications] Mitsunobu Sato: "5-azacytidine induction of neuron-like cells from a neoplastic human salivary intercalated duct cell line and effect of dibutyryl cyclic adenosine 3':5'-monophosphate on proliferation and phenotype of the induced cells" Cancer Journal. 6. 26-36 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masayuki Azuma: "Role of plasminogen activators,metalloproteinases and tissue inhibitor of metalloproteinase-1 in the metastatic process of human salivary gland adenocarcinoma cells" International Journal of Cancer. 54. 669-676 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hideo Yoshida: "Emergence of a smooth muscle cell phenotype and apoptosis by treatment with etoposide,an inhibitor of DNA topoisomerase II,in a neoplastic human salivary intercalated duct cell line" Cancer Journal. 6. 220-228 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masayuki Azuma: "Effects of media conditioned by a non-metastasizing human salivary gland adenocarcinoma cell clone and metastasizing clones from salivary gland and various other tissues on the proliferation,migration and protease production of bovine aortic endothelial cells in vitro" Cancer Letters. 73. 85-93 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 佐藤光信: "唾液腺腫瘍の分化誘導療法" 癌と化学療法. 20. 1028-1036 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 佐藤光信: "固形がんの分化誘導療法" Biotherapy. 7. 1671-1681 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masayuki Azuma: "Enhanced proteolytic activity is responsible for the aberrant morphogenetic development of SV40-immortalized normal human salivary gland cells grown on basement membrane component" Laborarory Investigation. 70. 217-227 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masayuki Azuma: "Identification of EGF as an angiogenic factor present in conditioned medium from human salivary gland adenocarcinoma cell lines with varying degrees of metastastic potential" Cancer Letters. 84. 189-198 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masayuki Azuma: "Morphogenesis of normal human salivary gland cells in vitro" Hitology and Histopathology. 9. 781-790 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 東雅之: "SV40不死化正常ヒト唾液腺細胞における野生型P53の発現" 日本口腔科学会雑誌. 43. 580-589 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsunobu Sato: "Induction of differentiation and apoptosis, and Le^Y antigen expression by treatment with 3,4-dihydro-6-〔4-(3,4-dimethoxybenzoy1)-1-piperaziny1〕-2(1H)-quinolinone(vesnarinone)in a human salivary cancer cell line" Acta Histochem.Cytochem. (in press). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsunobu Sato: "Characteristics of antitumor activity of 3,4-dihydro-6-〔4-(3,4-dimethoxybenzoyl)-1-piperazinyl〕-2(1H)-quinolinone(vesnarinone)against a human adenoid squamous carcinomaforming cell line grown in athymic nude mice" Cancer Letters. (in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 佐藤光信(穂積本男、斉藤政樹、佐藤光信編): "「癌細胞の分化誘導とアポトーシス」-癌分化誘導療法-IV、臨床編 2.固形癌唾液線癌と扁平上皮癌" 共立出版(印刷中), (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsunobu Sato: "5-azacytidine induction of neuron-like cells from a neoplastic human salivary intercalated duct cell line and effect of dibutyryl cyclic adenosine 3' : 5'-monophosphate on proliferation and phenotype of the induced cells" Cancer Journal. 6. 26-36 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masayuki Azuma: "Role of plasminogen activators, metalloproteinases and tissue inhibitor of metalloproteinase-1 in the metastatic process of human salivary gland adenocarcinoma cells" International Journal of Cancer. 54. 669-676 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hideo Yoshida: "Emergence of a smooth muscle cell phenotype and apoptosis by treatment with etoposide, an inhibitor of DNA topoisomerase II,in a neoplastic human salivary intercalated duct cell line" Cancer Journal. 6. 220-228 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masayuki Azuma: "Effects of media conditioned by a non-metastasizing human salivary gland adenocarcinoma cell clone and metastasizing clones from salivary gland and various other tissues on the prolifertion, migration and protease production of bovine aortic endothelial cells in vitro" Cancer Letters. 73. 85-93 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsunobu Sato: "Differentiation therapy for salivary gland tumors" Jpn J Cancer Chemother. 20. 1028-1036 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsunobu Sato: "Differentiation therapy for solid tumors" Biotherapy. 7. 1671-1681 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masayuki Azuma: "Enhanced proteolytic activity is responsible for the aberrant morphogenetic development of SV40-immortalized normal human salivary gland cells grown on basement membrane component" Laboratory Investigation. 70. 217-227 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masayuki Azuma: "Identification of EGF as an angiogenic factor present in conditioned medium from human salivary gland adenocarcinoma cell lines with varying degrees of metastastic potential" Cancer Letters. 84. 189-198 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masayuki Azuma: "Morphogenesis of normal human salivary gland cells in vitro" Hitology and Histopathology. 9. 781-790 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masayuki Azuma: "Expression of wild-type p53 in SV40-immortalized normal human salivary gland cells" J Jpn.Stomatol.Soc.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsunobu Sato: "Induction of differentiation and apoptosis, and Le^Y antigen expression by treatment with 3,4-dihydro-6- [4- (3,4-dimethoxybenzoyl) -1-piperazinyl] -2 (1H) -quinolinone (vesnarinone) in a human salivary cancer cell line" Acta Histochem.Cytochem. (in press). (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsunobu Sato: "Characteristics of antitumor activity of 3,4-dihydro-6- [4( 3,4-dimethoxybenzoyl) -1-piperazinyl]-2 (1H) -quinolinone (vesnarinone) against a human adenoid squamous carcinoma-forming cell line grown in athymic nude mice" Cancer Leters. (in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsunobu Sato (Motoo Hozumi, Masaki Saito, Mitsunobu Sato eds): KYORITSU SHUPPAN CO., LTD,Tokyo, Japan. Induction of Differentiation and Apoptosis in Cancer Cells-Differentiation Therapy for Cancer-IV.Clinical Part.2.Solid Tumors.Salivary Gland Cancer and Squamous Cell Carcinoma (in press), (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masayuki Azuma: "Enhanced proteolytic activity is responsible for the aberrant mcrphogenetic development of SV40-immcrtaliged normal hunsr salivary gland cells grown on baseinent membrane components" Laboratory Investigation. 70. 217-227 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Masayuki Azuma: "Identification of EGF as an angiogenic factor present in canditioned medium from human salivary gland adenocarcinoma cell clones with arying degrees of metastastic potential" Cancer Letters. 84. 189-198 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Masayui Azuma: "Mcrphogenesis of normal human salivary gland cells in vitro" Histology and Histopathology. 9. 781-790 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 東 雅之: "SV40 不死化正常ヒト唾液腺細胞における野生型P53の発現" 日本口腔科学会雑誌. 43. 580-589 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mitsunobu Sato: "Induction of differentiation and apoptosis,and Le antigen expression by treatment with 3,4-dihydro-6-[4-(3,4-dimethoxybenzoy1x1-piperaginyl]-2(1H)-guinolinane(vesnarinone)in a human salivary cancer ceil line" Acta.Histochem.Cytochem.,. (in press). (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mitsunobu Sato: "Characteristics of antitumor activity of 3、4-dihydro-6-[4-3、4-demcthoxybenzoyl)1-piperaginyl]-2(1H)、gainolinone(vesnarinone)agoinst a human adenoid sguamous cavrinomafarming ceil line grown in athymic nudmicc" Cancer Letters. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 佐藤光信: "「癌細胞の分化誘導とアポトーシス」-癌分化誘導療法-癌分化誘導療法-IV.臨床編 .2.固形癌 唾液腺癌と扁平上皮癌" 共立出版(印刷中), (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mitsunobu Sato: "5-azacytidine induction of neuron-like cells from a neoplastic human salivary intercalated duct cell line and effect of dibutyryl cyclic adenosine 3':5' monophosphate on proliferation and phenotype of the induced cells." Cancer Journal. 6. 26-36 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Masayuki Azuma: "Role of plasminogen activators,metalloproteinases and tissue inhibitor of metalloproteinase-1 in the metastatic process of human salivary gland adenocarcinoma cells." International Journal of Cancer. 54. 669-676 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hideo Yoshida: "Emergence of a smooth muscle cell phenotype and apoptosis by treatment with etoposide,an inhibitor of DNA topoisomerase II,in a neoplastic human salivary interealated duct cell line." Cancer Journal. 6. 220-228 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Masayuki Azuma: "Effects of media conditioned by a non-metastasizing human salivary gland adenocarcinoma cell clone and metastasizing clones from salivary gland and various other tissues on the proliferation migration and protease production of bovine aortic endothelial cells in vitro." Cancer Letters. 73. 85-93 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 佐藤光信: "唾液腺腫瘍の分化誘導療法" 癌と化学療法. 20. 1028-1036 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 佐藤光信: "固形がんの分化誘導療法" Biotherapy. 7. 1671-1681 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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