Abstract:
BACKGROUND/AIM:Anthracyclines have been proven able to reduce the activity of vinca alkaloids by induction of cell-cycle arrest. The present study aims at identifying the critical initiation steps of signal transduction which transduce the inhibitory effects on the cytotoxicity of vinca alkaloids. MATERIALS AND METHODS:Several new cytostatic drug classes were evaluated together with vincristine in tumor cell lines and patients' tumor cells. RNA interference was used for molecular analyses. RESULTS:Inhibition of vincristine was observed by all cytostatic drugs, which induced cell-cycle arrest. Knockdown of proteins of the DNA damage response ascribed the inhibitory effect to a common pathway involving Chk-1, p53 and p21. Upstream of Chk-1 signal transduction depended on both ATM and ATR for all drugs except methotrexate. CONCLUSION:We have identified critical signaling steps of the DNA damage response system activated by cytostatic drugs, which reduce the anti-tumor activity of vinca alkaloids. The obtained results encourage the development of novel therapeutic strategies to prevent pathway interactions based on the molecular understanding of drug action and drug-drug interactions.
journal_name
Anticancer Resjournal_title
Anticancer researchauthors
Ehrhardt H,Pfeiffer S,Schrembs D,Wachter F,Grunert M,Jeremias Isubject
Has Abstractpub_date
2013-12-01 00:00:00pages
5273-87issue
12eissn
0250-7005issn
1791-7530pii
33/12/5273journal_volume
33pub_type
杂志文章abstract:BACKGROUND:The p16 tumour suppressor gene is known to be involved in regulation of the cell cycle. p16 expression in sequential histological stages of oral squamous cell carcinoma (OSCC) formation was investigated using an experimental model of induced oral carcinogenesis in Syrian golden hamsters. MATERIALS AND METHO...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
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journal_title:Anticancer research
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journal_title:Anticancer research
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journal_title:Anticancer research
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journal_title:Anticancer research
pub_type: 杂志文章
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1997-11-01 00:00:00
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journal_title:Anticancer research
pub_type: 临床试验,杂志文章
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更新日期:2000-05-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2000-09-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章,评审
doi:
更新日期:2009-03-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2008-03-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章,评审
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更新日期:1982-09-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1997-03-01 00:00:00
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pub_type: 杂志文章
doi:
更新日期:2005-01-01 00:00:00
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journal_title:Anticancer research
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doi:
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更新日期:2010-10-01 00:00:00
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doi:
更新日期:2001-11-01 00:00:00
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doi:
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更新日期:2015-06-01 00:00:00
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journal_title:Anticancer research
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pub_type: 临床试验,杂志文章
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更新日期:2006-05-01 00:00:00
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更新日期:2016-04-01 00:00:00
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