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著作: Yamagishi Naoko/[近藤 茂忠]/[増田 清士]/[西田 憲生]/[桑野 由紀]/Dang T Duyen/Dang H Long/[二川 健]/[六反 一仁]/Chronic inhibition of tumor cell-derived VEGF enhances the malignant phenotype of colorectal cancer cells/[BMC Cancer]

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EID
283539
EOID
1094543
Map
0
LastModified
2023年11月28日(火) 16:23:46
Operator
三木 ちひろ
Avail
TRUE
Censor
0
Owner
西田 憲生
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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
著者 必須
  1. (英) Yamagishi Naoko
    役割 任意
    貢献度 任意
    学籍番号 推奨
  2. 近藤 茂忠
    役割 任意
    貢献度 任意
    学籍番号 推奨
  3. 増田 清士
    役割 任意
    貢献度 任意
    学籍番号 推奨
  4. 西田 憲生([徳島大学.大学院医歯薬学研究部.医学域.先端医学教育研究プロジェクト]/[徳島大学.大学院医歯薬学研究部.医学域.医科学部門.社会医学系.医療教育学])
    役割 任意
    貢献度 任意
    学籍番号 推奨
  5. 桑野 由紀([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.生理系.遺伝情報医学])
    役割 任意
    貢献度 任意
    学籍番号 推奨
  6. (英) Dang T Duyen
    役割 任意
    貢献度 任意
    学籍番号 推奨
  7. (英) Dang H Long
    役割 任意
    貢献度 任意
    学籍番号 推奨
  8. 二川 健([徳島大学.大学院医歯薬学研究部.医学域.栄養科学部門.医科栄養学系.生体栄養学])
    役割 任意
    貢献度 任意
    学籍番号 推奨
  9. 六反 一仁
    役割 任意
    貢献度 任意
    学籍番号 推奨
題名 必須

(英) Chronic inhibition of tumor cell-derived VEGF enhances the malignant phenotype of colorectal cancer cells

副題 任意
要約 任意

(英) Vascular endothelial growth factor-a (VEGF)-targeted therapies have become an important treatment for a number of human malignancies. The VEGF inhibitors are actually effective in several types of cancers, however, the benefits are transiently, and the vast majority of patients who initially respond to the therapies will develop resistance. One of possible mechanisms for the acquired resistance may be the direct effect(s) of VEGF inhibitors on tumor cells expressing VEGF receptors (VEGFR). Thus, we investigated here the direct effect of chronic VEGF inhibition on phenotype changes in human colorectal cancer (CRC) cells. To chronically inhibit cancer cell-derived VEGF, human CRC cell lines (HCT116 and RKO) were chronically exposed (2 months) to an anti-VEGF monoclonal antibody (mAb) or were disrupted the Vegf gene (VEGF-KO). Effects of VEGF family members were blocked by treatment with a VEGF receptor tyrosine kinase inhibitor (VEGFR-TKI). Hypoxia-induced apoptosis under VEGF inhibited conditions was measured by TUNEL assay. Spheroid formation ability was assessed using a 3-D spheroid cell culture system. Chronic inhibition of secreted/extracellular VEGF by an anti-VEGF mAb redundantly increased VEGF family member (PlGF, VEGFR1 and VEGFR2), induced a resistance to hypoxia-induced apoptosis, and increased spheroid formation ability. This apoptotic resistance was partially abrogated by a VEGFR-TKI, which blocked the compensate pathway consisted of VEGF family members, or by knockdown of Vegf mRNA, which inhibited intracellular function(s) of all Vegf gene products. Interestingly, chronic and complete depletion of all Vegf gene products by Vegf gene knockout further augmented these phenotypes in the compensate pathway-independent manner. These accelerated phenotypes were significantly suppressed by knockdown of hypoxia-inducible factor-1α that was up-regulated in the VEGF-KO cell lines. Our findings suggest that chronic inhibition of tumor cell-derived VEGF accelerates tumor cell malignant phenotypes.

キーワード 推奨
  1. 分散分析(analysis of variance)
  2. (英) Antibodies, Monoclonal
  3. アポトーシス(apoptosis)
  4. (英) Enzyme Inhibitors
  5. (英) Gene Knockdown Techniques
  6. (英) HCT116 Cells
  7. (英) Humans
  8. (英) Hypoxia-Inducible Factor 1
  9. (英) Phenotype
  10. (英) Pregnancy Proteins
  11. (英) Spheroids, Cellular
  12. (英) Vascular Endothelial Growth Factor A
  13. (英) Vascular Endothelial Growth Factor Receptor-1
  14. (英) Vascular Endothelial Growth Factor Receptor-2
発行所 推奨
誌名 必須 BMC Cancer([BioMed Central Ltd.])
(eISSN: 1471-2407)
ISSN 任意 1471-2407
ISSN: 1471-2407 (eISSN: 1471-2407)
Title: BMC cancer
Title(ISO): BMC Cancer
Publisher: BioMed Central
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
必須 13
必須 ---
必須 229 229
都市 任意
年月日 必須 2013年 3月 初日
URL 任意
DOI 任意 10.1186/1471-2407-13-229    (→Scopusで検索)
PMID 任意 23651517    (→Scopusで検索)
CRID 任意
WOS 任意 000319210500001
Scopus 任意 2-s2.0-84877039223
評価値 任意
被引用数 任意
指導教員 推奨
備考 任意
  1. (英) Article.ELocationID: 10.1186/1471-2407-13-229

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

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

  4. (英) OtherID: PMC3658959