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Ultrastructural and cytochemical studies on cancer and apoptosis in bone.

Research Project

Project/Area Number 09557164
Research Category

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

Allocation TypeSingle-year Grants
Section展開研究
Research Field Surgical dentistry
Research InstitutionNIIGATA UNIVERSITY

Principal Investigator

SHINGAKI Susumu (2000)  Faculty of Dentistry Associate Professor, 歯学部, 助教授 (30134943)

中島 民雄 (1997-1999)  新潟大学, 歯学部, 教授 (10014010)

Co-Investigator(Kenkyū-buntansha) ITO Masahiro  Niigata University Faculty of Dentistry Assistant, 歯学部, 助手 (40313522)
TAKADA Masahito  Niigata University Faculty of Dentistry Assistant, 歯学部, 助手 (10251828)
新垣 晋 (新垣 普)  新潟大学, 歯学部, 助教授 (30134943)
野村 務  新潟大学, 歯学部附属病院, 助手 (20228365)
Project Period (FY) 1997 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1997: ¥5,400,000 (Direct Cost: ¥5,400,000)
Keywordsbone metastasis / bone invasion / osteoclasts / bisphosphonates / apoptosis / ALPase / immunohistochemistry / morphology / 癌骨浸潤 / 細胞外基質 / 血管 / 骨芽細胞 / マクロファージ / Bisphosphonate / VEGF / ODF / 微細構造学 / PTHrP / PTH / PTHrPレセプター / Bisphosphewate / oc / ocマウス / 腫瘍細胞 / 骨転移
Research Abstract

We examined the mechanisms of bone metastasis and bone invasion. The tumor mass was surrounded by a membrane consisting of fibroblastic cells. These cells were positive for ALP ase. TRAPase-positive cells were localized close to the ALP ase-positive cells and numerous osteoclasts were observed on the neighboring bone surfaces. It seems that PTHrP secreted by the tumor cells appears to stimulate differentiation of osteoclasts and bone resorption in a paracrine manner through PTH/PTHrP receptor-immunopositive osteoblastic cells. In bone metastatic, breast cancer cells produced VEGF and induced many CD31-positive blood vessels in bone. TRAPase-positive osteoclasts directly contacted to RANKL-positive cells. It seems that VEGF of the tumor cells induce growth of cancer and osteoclasts progenitor, and stimulate differentiation and activation of osteoclasts via RANKL of osteoblastic cells. Furthermore, we found that bisphosphonate inhibited the number of osteoclasts and blood vessels in bone metastatic area. We investigated the mechanism which a mutant ALPase induced bone disease in vitro. The mutant ALPase gene resulted in protein synthesis but not ER-to-Golgi apparatus trafficking. Then, osteoclasts apoptosis were studied in the tibia of rats treated with a bisphosphonate. They became devoid of ruffled borders and detached from bone surface, and showed formation of many vesicles and degradation of Golgi apparatus and DNA fragmentation. The majority of them are eliminated by macrophages, but there are some that escape into blood vessels. Furthermore, we found that bisphosphonates directly affect osteoclasts without mediating its deposition to the bone matrix.

Report

(5 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (56 results)

All Other

All Publications (56 results)

  • [Publications] Ito, M.: "Bisphosphonate acts on osteoclasts independent of ruffled borders in osteosclerotic (oc/oc) mice."Bone.. 28(in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 伊藤将広: "Bisphosphonatesの作用機序"THE BONE.. 7(in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fukushi-Irie, M.: "Possible interference between tissue-non-specific alkaline phosphatase with an Arg54→Cys substitution and a counterpart with an Asp277→Ala substituion found in a compound heterozygote associated with severe hypophosphatasia."Biochem. Journal.. 348. 633-642 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 伊藤将広: "破骨細胞の細胞死"THE BONE.. 14. 3-6 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 網塚憲生: "骨転移に関わる細胞群"ホルモンと臨床. 7. 585-594 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ito, M.: "Ultrastructural and cytochemical studies on cell death of osteoclasts induced by bisphosphonate treatment."Bone.. 25. 447-452 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 伊藤将広: "骨腫瘍と骨組織"Quintessence.. 18. 183-190 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 織田公光: "低ホスファターゼ症"Niigata Dental Journal.. 29. 35-36 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ono, Y.: "Clinicopathologic significance of laminin-5 gamma2 chain expression in squamous cell carcinoma of the tongue. immunohistochemical analysis of 67 lesion."Cancer.. 85. 2315-2321 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ito, M.: "Ultrastructural and cytochemical studies on cell death of osteoclasts."Niigata Dental Journal.. 28. 87-88 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mahmood, J. U.: "Heterogeneity of squamous cell carcinomas of the head and neck in relation to clinicopathological parameters."Br. J. Oral. Maxillofac. Surg.. 36. 446-452 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hiraga, T.: "Morphology of bone metastasis."Eur. J. Cancer.. 34. 230-239 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Naito, Y.: "Effects of UFT on metastatic potentials of hamster squamous cell carcinoma (O-1N)."Oral Oncology.. 34. 326-331 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ono, Y.: "Vascular invasion of O-1N, hamster squamous cell carcinoma with high potential of lymph node metastasis. ultrastructural comparision between lymphatics and blood vessels."Path. Int.. 8. 254-264 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 網塚憲生: "骨と軟骨組織におけるアポトーシス"現代医療. 29. 171-180 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shingaki, S.: "Impact of clinicopathologic parameters on survival of patients with tongue carcinoma."Asian J. Oral Maxillofac. Surg.. 9. 107-116 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 中島民雄: "癌の転移"Niigata Dental Journal.. 27. 1-12 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ito, M., et al.: "Bisphosphonate acts on osteoclasts independent of ruffled borders in osteosclerotic(oc/oc)mice."Bone.. 28, (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ito, M., et al.: "Mechanism of action of bisphosphonates."THE BONE.. 7, (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fukushi-Irie, M.: "Possible interference between tissue-non-specific alkaline phosphatase with an Arg54 -->Cys substitution and a counterpart with an Asp277 -->Ala substitution found in a compound heterozygote associated with severe hypophosphatasia."Biochme.Journal.. 348. 633-642 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ito, M., et al.: "Apoptosis of osteoclasts."THE BONE.. 14. 3-6 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Amizuka, N., et al.: "Cellular involvement in bone metastasis."Hormone to Rinsho.. 7. 585-594 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ito, M., et al.: "Ultrastructural and cytochemical studies on cell death of osteoclasts induced by bisphosphonate treatment."Bone.. 25. 447-452 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ito, M., et al.: "Tumor and bone"Quinitessence.. 18. 183-190 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Oda, K., et al.: "Hypophosphatasia."Niitgata Dental Journal.. 29. 35-36 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ono, Y., et al.: "Clinicopathologic significance of laminin-5 gamma2 chain expression in squamous cell carcinoma of the tongue. immunohistochemical analysis of 67 lesion."Cancer.. 85. 2315-2321 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ito, M., et al.: "Ultrastructural and and cytochemical studies on cell death of osteoclasts."Niigata dental Journal.. 28. 87-88 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mahmood, J.U., et al.: "Heterogeneity of squamous cell carcinomas of the head and neck in relation to clinicopathological parameters."Br.J.Oral Maxillofac.Surg.. 36. 446-452 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hiraga, T., et al.: "Morphology of bone metastasis."Eur.J.Cancer.. 34. 230-239 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Naito, Y., et al.: "Effects of UFT on metastatic potentials of hamster squamous cell carcinoma(O-1N)"Oral Oncology.. 34. 326-331 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ono, Y., et al.: "Vascular invasion of O-1N, hamster squamous cell carcinoma with high potential of lymph node metastasis. ultrastructural comparison between lymphatics and blood vessels."Path.Int.. 8. 254-264 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Amizuka, N., et al.: "Apoptosis in bone."Gendai-iryo.. 29. 171-180 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shingaki, S., et al.: "Impact of clinicopathologic parameters on survival of patients with tongue carcinoma."Asian J.Oral Maxillofac.Surg.. 9. 107-116 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakajima, T., et al.: "Metastasis of cancer."Niigata dental Journal.. 27. 1-12 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ito.M., et al.: "Bisphosphonate acts on osteoclasts independent of ruffled borders in osteosclerotic (oc/oc) mice."Bone.. 28(in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 佐藤将広: "Bisphosphonatesの作用機序"THE BONE.. 7(in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fukushi-Irie.M. et al: "Possible interference between tissue-non-specific alkaline phosphatase with an Arg54→Cys substitution and a counterpart with an Asp277→Ala substitution found in a compound heterozygote associated with severe hypophosphatasia."Biochem.Journal.. 348. 633-642 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 佐藤将広: "破骨細胞の細胞死"THE BONE.. 14. 3-6 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 網塚憲生: "骨転移に関わる細胞群"ホルモンと臨床. 7. 585-594 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakajima, T., et al.: "The postoperative maxillary cyst."Oral. Maxillofac. Surg.. 137-147 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shingaki, S., et al.: "Impact of Lymph node metastasis on the pattern of treatment failure and survival in oral carcinomas."Oral Oncology.. Vol. 6. 391-394 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shingaki, S., et al.: "The impact of extranodal spread of lymph node metastases in patients with oral cancer."Int. J. Oral. Maxillofac. Surg.. in press.

    • Related Report
      1999 Annual Research Report
  • [Publications] Ito, M., et al.: "Ultrastructural and Cytochemical Studies on Cell Death of Osteoclasts Induced by Bisphosphonate Treatment."Bone. Vol.25. 447-452 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 伊藤将広: "腫瘍と骨組織"ザ・クインテッセンス. Vol.18. 183-190 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nomura.T: "Clinical evaluation of vascularized fibula grefts for waedihalar reconstruction in b cases." Asian J.Dral Maxillofac.Surg.9. 31-38 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Izumi.K: "A denosquamous carcinoma of the tongue: Report of a case with histochemical immunokistochemical and ultrastructural study and veview of the literature." Dral Surg Dral Med Dral Parhol. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Shingaki.S: "Impact of clinicopathologic perometers on surviral of patieets with tonque cavcinoma." Asian J.Dral Maxillofac Surg. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Mahmood.Ju.: "Heteropeueity of squamous cell carcinomas of the head and ueck in relation to clinicepathelogical pavametsrs." Brit.J.Oral.Maxilofac.Surg.(in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Suzuki.K: "Carcinomes detected of ten tooth extraction: clinical and radioqraphic analysis of 32 cases." Ind.J.Oral Maxillofac.Surg.(in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Hamamoto.Y: "Iuduction of odontogenic tumars from epithelial rests of Malassos by lecal adwinistration of N-wathyln trosouvea." Arch.Dral.Biol.(in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Hiraga T: "EFFECTS OF BISPHOSPHONATE (PAMIDRONATE) ON BONE-RESORPTION RESULTING FROM METASTASIS OF A SQUAMOUS-CELL CARCINOMA REPORT OF AN AUTOPSY CASE AND EVALUATION OF BONE-RESORBING ACTIVITY IN AN EXPERIMENTAL ANIMAL-MODEL" J.Oral Maxillofac Surg.54. 1327-1333 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Chujuou T: "Differential expression of laminin and matrix maeitalloproteinases in the mesastatic and non-metastatic cells isolated from quamous cell carcination(O-1N)" Oral Med Pathol. 2. 81-87 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shingaki S: "Impact of clinicopathologic parametoers on survival of patients with tongue carcinoma" Asian J.Oral Maxillofac Surg. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Hiraga T: "Morphology of bone metastasis" Eur.J.Cancer. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Ono Y: "Vascular invasion of O-1N hamster squamous cell carcinoma with high potential of lymph nede metastasis: ultrastractural comparision between lymphatics and blood vessels" Paeh.Int.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] 中島民雄: "癌の転移" 新潟歯学会誌. 27. 1012 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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