Abstract:
:The aim of the present study was to potentiate the cytotoxic effects of melphalan through pharmacological and physical modulators. The combination of the cytotoxic agent with ethacrynic acid, a glutathione-S-transferase pi (GST pi) inhibitor, or topotecan, a topoisomerase I inhibitor, or mild hyperthermia was investigated. The selected cell lines exhibited variable levels of expression of GST pi, DNA topoisomerase I and heat-shock proteins. Mild hyperthermia (42 degrees C) alone potentiated melphalan cytotoxicity, especially in the two cell lines exhibiting low basal levels of HSP70 expression. The combination of the GST inhibitor with melphalan resulted in a potentiation of drug cytotoxicity only in JR8 cells, one of the two cell lines which expressed high levels of GST pi mRNA and which were the less responsive to ethacrinic acid alone. A synergistic interaction between topotecan and melphalan was observed only in the cell lines expressing low levels of topoisomerase I even if all cell lines exhibited a comparable sensitivity to this agent. The results support an involvement of GST and DNA topoisomerase in cell defense and response to the alkylating agent. However, the variable potentiation of the cytotoxic effects of melphalan achieved in different cell systems suggests that factors other than the level of expression of the modulation target are responsible of such potentiation.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Supino R,Caserini C,Orlandi L,Zaffaroni N,Silvestrini R,Vaglini M,Zunino Fdoi
10.1097/00001813-199607000-00017subject
Has Abstractpub_date
1996-07-01 00:00:00pages
604-12issue
5eissn
0959-4973issn
1473-5741journal_volume
7pub_type
杂志文章abstract::C-reactive protein (CRP) is an independent prognostic factor for renal cell carcinoma (RCC). The aim of the present study was to investigate the overall prognostic impact of CRP in patients with metastatic RCC treated with sorafenib. Between April 2008 and December 2014, 40 consecutive patients with metastatic RCC wer...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2002-04-01 00:00:00
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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doi:10.1097/00001813-199605000-00006
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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