Source:http://linkedlifedata.com/resource/pubmed/id/15447990
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
18 Pt 1
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| pubmed:dateCreated |
2004-9-27
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| pubmed:abstractText |
We reported induction of broad-spectrum chemoresistance by acidic and basic fibroblast growth factors and chemosensitization by their nonspecific inhibitor suramin at nontoxic and subtherapeutic doses. This study evaluated whether low-dose suramin enhances paclitaxel activity in chemotherapy-naïve and paclitaxel-pretreated human MCF7 breast xenograft tumors in mice. Suramin, 10 mg/kg, and/or paclitaxel, 15 mg/kg, were administered intravenously, twice weekly for 2 to 3 weeks. In addition to conventional end points [tumor size change, median survival time (MST)], we also used clinically relevant end points [partial (PR) and complete response rates (CR); progressive disease (PD); stable disease (SD); time to tumor progression (TTP)]. In chemotherapy-naïve mice, the control and suramin groups showed identical TTP (3 days) and MST (21 days). Single-agent paclitaxel produced 47% PR and 24% CR, and prolonged both TTP and MST to 73 days. The addition of suramin further improved the total response rate to 100% with a dramatically greater 63% CR, shortened the time to attain PR and CR, and prolonged TTP and MST to > or =136 days. In the paclitaxel-pretreated group, single-agent paclitaxel resulted in 67% SD and 33% PD, whereas the combination produced 50% PR and 50% SD. Suramin also significantly enhanced the apoptotic effect of paclitaxel in tumors. In conclusion, suramin improved the activity of paclitaxel in both chemotherapy-naïve and paclitaxel-pretreated animals, without enhancing host toxicity (< or =10% body weight loss in all groups). These data have led to the initiation of phase I/II trials of paclitaxel and low-dose suramin combination in advanced metastatic breast cancer patients.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
1078-0432
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
10
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
6058-65
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:15447990-Animals,
pubmed-meshheading:15447990-Antineoplastic Agents,
pubmed-meshheading:15447990-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:15447990-Antineoplastic Combined Chemotherapy Protocols,
pubmed-meshheading:15447990-Apoptosis,
pubmed-meshheading:15447990-Body Weight,
pubmed-meshheading:15447990-Breast Neoplasms,
pubmed-meshheading:15447990-Cell Line, Tumor,
pubmed-meshheading:15447990-Cell Survival,
pubmed-meshheading:15447990-Disease Progression,
pubmed-meshheading:15447990-Drug Synergism,
pubmed-meshheading:15447990-Female,
pubmed-meshheading:15447990-Humans,
pubmed-meshheading:15447990-Mice,
pubmed-meshheading:15447990-Mice, Nude,
pubmed-meshheading:15447990-Neoplasm Transplantation,
pubmed-meshheading:15447990-Paclitaxel,
pubmed-meshheading:15447990-Suramin,
pubmed-meshheading:15447990-Time Factors,
pubmed-meshheading:15447990-Treatment Outcome
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| pubmed:year |
2004
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| pubmed:articleTitle |
Low-dose suramin enhanced paclitaxel activity in chemotherapy-naive and paclitaxel-pretreated human breast xenograft tumors.
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| pubmed:affiliation |
College of Pharmacy and James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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