Abstract:
:Thalidomide is considered to be a potent antiangiogenic and immunomodulatory drug for cancer therapy. Earlier clinical studies have found that patients responding to this drug often had high plasma levels of basic fibroblast growth factor (bFGF). This cytokine is a proangiogenic factor overexpressed in many tumors and is also a regulator of limb development; hence, it might be a target of thalidomide. Using U-87 MG cell lines, we found that thalidomide, especially when encapsulated in a liposome, down-regulated the transcription and translation of the FGF-2 gene by interacting with G-rich regions present in the promoter and the internal ribosome entry site of its transcript at concentrations much lower than therapeutic serum concentrations. Thalidomide treatment also dramatically suppressed the anchorage-independent growth of U-87 MG and other glioma cells by over a thousand fold without affecting its anchorage-dependent growth, which may be accomplished by knocking down endogenous bFGF expression in these cells. Accordingly, the addition of recombinant bFGF partially restored the anchorage-independent growth of these cells. Our data suggest that by targeting the G-rich regions of bFGF, thalidomide (at 0.1 microg/mL) can reduce cellular bFGF levels and affect tumor anchorage-independent growth, the hallmark of tumorigenicity. Our results are promising for future clinical investigations using low doses of thalidomide.
journal_name
Mol Cancer Therjournal_title
Molecular cancer therapeuticsauthors
Mei SC,Wu RTdoi
10.1158/1535-7163.MCT-07-2398subject
Has Abstractpub_date
2008-08-01 00:00:00pages
2405-14issue
8eissn
1535-7163issn
1538-8514pii
1535-7163.MCT-07-2398journal_volume
7pub_type
杂志文章abstract::Breast cancer exhibits a propensity to metastasize to bone, resulting in debilitating skeletal complications associated with significant morbidity and poor prognosis. The cross-talk between metastatic cancer cells and bone is critical to the development and progression of bone metastases. We have shown the involvement...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-06-0678
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pub_type: 杂志文章
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-07-0487
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更新日期:2020-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-12-0644-T
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pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-11-0152
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pub_type: 杂志文章
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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更新日期:2021-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-12-1007
更新日期:2013-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:2019-02-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-07-0132
更新日期:2007-08-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-09-0280
更新日期:2009-07-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-07-2409
更新日期:2008-07-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-08-1056
更新日期:2009-05-01 00:00:00
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pub_type: 杂志文章
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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更新日期:2005-01-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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更新日期:2008-04-01 00:00:00
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更新日期:2012-02-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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更新日期:2003-06-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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