Abstract:
:Our objectives were to study the biological activity of a novel gemcitabine-cardiolipin conjugate (NEO6002) and compare that with gemcitabine. Cytotoxicity in vitro was determined against several gemcitabine-sensitive parental and gemcitabine-resistant cancer cell lines using the sulforhodamine B assay. The in vivo toxicity was examined by changes in body weight and hematologic indices of conventional mice. Immunodeficient SCID mice bearing P388 and BxPC-3 tumor xenografts were used to evaluate the in-vivo therapeutic efficacy. Both NEO6002 and gemcitabine showed pro-apoptotic and cytotoxic effects against all gemcitabine-sensitive cell lines tested. Unlike gemcitabine, the cytotoxicity of NEO6002 was independent of nucleoside transporter (NT) inhibitors, indicating a different internalization route of NEO6002. The conjugate demonstrated a favorable activity not only in ARAC-8C, a NT-deficient gemcitabine-resistant human leukemia cell line, but also in several other gemcitabine-resistant cell lines. At the in-vivo level, a comparative toxicity study showed a significant body weight loss and a decrease in white blood cell counts in gemcitabine-treated mice, whereas the influence of NEO6002 was mild. Treatment of NEO6002 at 27 micromol/kg increased the median survival of CD2F1 mice bearing P388 cells by up to 73%, while at the same doses and schedule of gemcitabine resulted in toxic deaths of all treated mice. At a dose of 18 micromol/kg, NEO6002 inhibited the growth of BxPC-3 xenografts by 52%, while only 32% of tumor inhibition was achieved with gemcitabine. We conclude that NEO6002 may be an effective chemotherapeutic agent with improved tolerability and can potentially circumvent NT-deficient, gemcitabine-resistant tumors.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Chen P,Chien PY,Khan AR,Sheikh S,Ali SM,Ahmad MU,Ahmad Idoi
10.1097/01.cad.0000185182.80227.48subject
Has Abstractpub_date
2006-01-01 00:00:00pages
53-61issue
1eissn
0959-4973issn
1473-5741pii
00001813-200601000-00007journal_volume
17pub_type
杂志文章abstract::The sap of Euphorbia peplus, commonly know as 'petty spurge', 'radium weed' or 'milkweed' has been used for centuries as a traditional treatment for skin conditions, including warts, corns and cancers of the skin. Documentation of its use by medical professionals to treat basal cell carcinoma (BCC) dates from the earl...
journal_title:Anti-cancer drugs
pub_type:
doi:10.1097/CAD.0b013e3280149ec5
更新日期:2007-03-01 00:00:00
abstract::Targeting of cytotoxic agents represents a modern approach to the treatment of various cancers, that improves the efficacy and reduces peripheral toxicity. Recently we developed a powerful cytotoxic analog of luteinizing hormone-releasing hormone (LHRH), AN-207, designed to be targeted to tumors that express LHRH rece...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200101000-00010
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abstract::Our study aimed to further investigate the roles and molecular mechanisms of lncRNA taurine upregulated gene 1 (TUG1) in the development and progression of PC. RT-qPCR assay was carried out to measure expression of TUG1, miR-496, together with β-catenin, cyclin D1 and c-myc. Protein levels of β-catenin, cyclin D1 and ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000882
更新日期:2020-07-01 00:00:00
abstract::We have previously reported the cytotoxic effects of chalcone A1, derived from 1-naphthaldehyde, in leukemia cell lines. On the basis of these findings, the main aim of this study was to elucidate some of the molecular mechanisms involved in apoptosis induced by chalcone A1 toward K562 and Jurkat cells. In both cell l...
journal_title:Anti-cancer drugs
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abstract::Gallbladder carcinoma is the most common malignancy of the biliary tract and is associated with a very poor outcome. The aim of the present study was to investigate the effects of oxymatrine (OM) on gallbladder cancer cells and the possible mechanism of its effects. The effects of OM on the proliferation of gallbladde...
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: 杂志文章
doi:10.1097/CAD.0b013e3283607f4f
更新日期:2013-07-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/CAD.0b013e328334d8f9
更新日期:2010-03-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e3282a213ce
更新日期:2007-11-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32835679d3
更新日期:2012-11-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200410000-00010
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000198
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journal_title:Anti-cancer drugs
pub_type: 杂志文章,随机对照试验
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更新日期:2015-06-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
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abstract::Multi-targeted antifolate (MTA) is an anti-metabolite with useful activity in the treatment of non-operable patients presenting with non-small cell lung cancer. Its good efficacy and tolerability profile as first-line therapy was demonstrated in phase II studies of MTA as monotherapy. The use of MTA as second-line the...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:
更新日期:2001-07-01 00:00:00
abstract::The objective of this study was to determine the safety and efficacy of intravesical novantrone in refractory superficial bladder cancer. The eligibility criteria included proven carcinoma in situ or superficial transitional cell carcinoma of the bladder at stage Ta or T1 that was proven refractory to or in relapse af...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
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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
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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: 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
pub_type: 杂志文章
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
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abstract::DNA has been one of the major targets of cancer chemotherapy. A variety of anti-neoplastic agents can cause different types of DNA lesions, including base alterations, single- or double-strand DNA breaks, DNA-DNA cross-links and DNA-protein cross-links. The exact processes by which these DNA lesions lead to cell death...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
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