徳島大学 教育・研究者情報データベース(EDB)

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著作: [上原 久典]/Kim Sun-Jin/Karashima Takashi/Shepherd L. David/Fan Dominic/Tsan Rachel/Killion J. Jerald/Logothetis Christopher/Mathew Paul/Fidler J Isaiah/Effects of blocking platelet-derived growth factor-receptor signaling in a mouse model of experimental prostate cancer bone metastases/[Journal of the National Cancer Institute]

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EID
88541
EOID
694116
Map
0
LastModified
2013年7月9日(火) 11:38:02
Operator
三木 ちひろ
Avail
TRUE
Censor
0
Owner
上原 久典
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種別 必須 学術論文(審査論文)
言語 必須 英語
招待 推奨
審査 推奨
カテゴリ 推奨
共著種別 推奨
学究種別 推奨
組織 推奨
  1. 徳島大学.大学院ヘルスバイオサイエンス研究部.再生修復医歯学部門.生体防御腫瘍医学講座(2004年4月1日〜2015年3月31日)
著者 必須
  1. 上原 久典([徳島大学.病院.中央診療施設等.病理部])
    役割 任意
    貢献度 任意
    学籍番号 推奨
  2. (英) Kim Sun-Jin
    役割 任意
    貢献度 任意
    学籍番号 推奨
  3. (英) Karashima Takashi
    役割 任意
    貢献度 任意
    学籍番号 推奨
  4. (英) Shepherd L. David
    役割 任意
    貢献度 任意
    学籍番号 推奨
  5. (英) Fan Dominic
    役割 任意
    貢献度 任意
    学籍番号 推奨
  6. (英) Tsan Rachel
    役割 任意
    貢献度 任意
    学籍番号 推奨
  7. (英) Killion J. Jerald
    役割 任意
    貢献度 任意
    学籍番号 推奨
  8. (英) Logothetis Christopher
    役割 任意
    貢献度 任意
    学籍番号 推奨
  9. (英) Mathew Paul
    役割 任意
    貢献度 任意
    学籍番号 推奨
  10. (英) Fidler J Isaiah
    役割 任意
    貢献度 任意
    学籍番号 推奨
題名 必須

(英) Effects of blocking platelet-derived growth factor-receptor signaling in a mouse model of experimental prostate cancer bone metastases

副題 任意
要約 任意

(英) Expression of platelet-derived growth factor (PDGF) and activation (by autophosphorylation) of its receptor (PDGF-R), a tyrosine kinase, are associated with the growth of metastatic prostate tumor cells in the bone parenchyma. The tyrosine kinase inhibitor STI571 blocks the PDGF signaling pathway by inhibiting PDGF-R autophosphorylation. We examined the effects of STI571, given alone or with paclitaxel (Taxol), on tumor growth in a mouse model of prostate cancer metastasis. Human prostate cancer PC-3MM2 cells were injected into the tibias of male nude mice. Three days later the mice (20 per group) were randomly assigned to 5 weeks of treatment with oral and injected water (control), daily oral STI571, weekly injected paclitaxel, or STI571 plus paclitaxel. Lesions in bone and the surrounding muscles were then harvested and analyzed by histology, western blotting (for PDGF-R phosphorylation), immunohistochemistry (for expression of proangiogenic molecules), and double immunofluorescence (to identify endothelial cells and apoptotic tumor cells). Growth of bone lesions was monitored by digital radiography. Bone lesions from control mice were used to establish short-term cell cultures for analysis of PDGF-R phosphorylation. All statistical tests were two-sided. PC-3MM2 cells cultured from bone lesions and treated in vitro with STI571 had less phosphorylated PDGF-R than untreated cells. In control mice, bone lesions expressed high levels of PDGF and activated (i.e., phosphorylated) PDGF-R, whereas lesions in the adjacent musculature did not. Activated PDGF-R was present on the surface of endothelial cells within the bone lesions but not in endothelial cells of uninjected bone. Mice treated with STI571 or STI571 plus paclitaxel had a lower tumor incidence, smaller tumors, and less bone lysis and lymph node metastasis than mice treated with water or paclitaxel alone (P<.001 for all). Mice treated with STI571 or STI571 plus paclitaxel had less phosphorylated PDGF-R on tumor cells and tumor-associated endothelial cells, less tumor cell proliferation, statistically significantly more apoptotic tumor cells (all P<.001), and fewer tumor-associated endothelial cells (P<.001) than control mice. Endothelial cells appear to express phosphorylated PDGF-R when they are exposed to tumor cells that express PDGF. Using STI571 to inhibit PDGF-R phosphorylation may, especially in combination with paclitaxel, produce substantial therapeutic effects against prostate cancer bone metastasis.

キーワード 推奨
  1. (英) Administration, Oral
  2. (英) Animals
  3. (英) Antineoplastic Agents
  4. (英) Antineoplastic Agents, Phytogenic
  5. (英) Antineoplastic Combined Chemotherapy Protocols
  6. アポトーシス(apoptosis)
  7. (英) Blotting, Western
  8. (英) Bone Neoplasms
  9. 細胞分裂(cell division)
  10. (英) Disease Models, Animal
  11. (英) Enzyme Inhibitors
  12. (英) Fluorescent Antibody Technique
  13. (英) Gene Expression Regulation, Neoplastic
  14. (英) Humans
  15. 免疫組織化学(immunohistochemistry)
  16. (英) In Situ Nick-End Labeling
  17. (英) Male
  18. (英) Mice
  19. (英) Mice, Nude
  20. (英) Microcirculation
  21. (英) Neoplasms, Experimental
  22. (英) Paclitaxel
  23. リン酸化(phosphorylation)
  24. (英) Piperazines
  25. (英) Platelet-Derived Growth Factor
  26. (英) Prostatic Neoplasms
  27. (英) Protein-Tyrosine Kinases
  28. (英) Pyrimidines
  29. (英) Radiographic Image Enhancement
  30. (英) Receptors, Platelet-Derived Growth Factor
  31. シグナル伝達(signal transduction)
  32. (英) Tumor Cells, Cultured
発行所 推奨
誌名 必須 Journal of the National Cancer Institute(National Cancer Institute (U.S.))
(pISSN: 0027-8874, eISSN: 1460-2105)
ISSN 任意 0027-8874
ISSN: 0027-8874 (pISSN: 0027-8874, eISSN: 1460-2105)
Title: Journal of the National Cancer Institute
Title(ISO): J Natl Cancer Inst
Supplier: Oxford University Press
Publisher: Oxford University Press
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
必須 95
必須 6
必須 458 470
都市 任意
年月日 必須 2003年 3月 9日
URL 任意 http://jncicancerspectrum.oxfordjournals.org/cgi/reprint/jnci;95/6/458.pdf
DOI 任意 10.1093/jnci/95.6.458    (→Scopusで検索)
PMID 任意 12644539    (→Scopusで検索)
NAID 任意
WOS 任意 000181559700010
Scopus 任意
評価値 任意
被引用数 任意
指導教員 推奨
備考 任意
  1. (英) Article.Affiliation: Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.

  2. (英) Article.PublicationTypeList.PublicationType: Journal Article

  3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't

  4. (英) Article.PublicationTypeList.PublicationType: Research Support, U.S. Gov't, P.H.S.