Document Detail


Comparative effects of thermosensitive doxorubicin-containing liposomes and hyperthermia in human and murine tumours.
MedLine Citation:
PMID:  20597627     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: In previous reports, laboratory-made lysolecithin-containing thermosensitive liposome encapsulating doxorubicin (LTSL-DOX) showed potent anticancer effects in FaDu human squamous cell carcinoma. To further study the spectrum of LTSL-DOX activity, the efficacy of its commercial formulation was re-examined in FaDu and compared in HCT116, PC3, SKOV-3 and 4T07 cancer cell lines. Factors that may influence differences in HT-LTSL-DOX efficacy were also examined.
METHODS: Anticancer effect was measured using standard growth delay methods. We measured doubling time and clonogenic survival after doxorubicin exposure in vitro, and interstitial pH and drug concentrations in vivo.
RESULTS: In all five tumour types, HT-LTSL-DOX increased median tumour growth time compared with untreated controls (p < 0.0006) and HT alone (p < 0.01), and compared with LTSL-DOX alone in FaDu, PC-3 and HCT-116 (p < 0.0006). HT-LTSL-DOX yielded significantly higher drug concentrations than LTSL-DOX (p < 0.0001). FaDu was most sensitive (p < 0.0014) to doxorubicin (IC(50) = 90 nM) in vitro, compared to the other cell lines (IC(50) = 129-168 nM). Of the parameters tested for correlation with efficacy, only the correlation of in vitro doubling time and in vivo median growth time was significant (Pearson r = 0.98, p = 0.0035). Slower-growing SKOV-3 and PC-3 had the greatest numbers of complete regressions and longest tumour growth delays, which are clinically important parameters.
CONCLUSIONS: These results strongly suggest that variations in anti-tumour effect of HT-LTSL-DOX are primarily related to in vitro doubling time. In the clinic, the rate of tumour progression must be considered in design of treatment regimens involving HT-LTSL-DOX.
Authors:
Pavel S Yarmolenko; Yulin Zhao; Chelsea Landon; Ivan Spasojevic; Fan Yuan; David Needham; Benjamin L Viglianti; Mark W Dewhirst
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group     Volume:  26     ISSN:  1464-5157     ISO Abbreviation:  Int J Hyperthermia     Publication Date:  2010  
Date Detail:
Created Date:  2010-07-05     Completed Date:  2010-10-04     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  8508395     Medline TA:  Int J Hyperthermia     Country:  England    
Other Details:
Languages:  eng     Pagination:  485-98     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Carcinoma, Squamous Cell / drug therapy,  therapy*
Cell Division / drug effects
Cell Line, Tumor
Combined Modality Therapy
Doxorubicin / administration & dosage,  therapeutic use*,  toxicity
Female
Humans
Hydrogen-Ion Concentration
Hyperthermia, Induced*
Liposomes / therapeutic use*
Mice
Mice, Inbred BALB C
Mice, Nude
Treatment Outcome
Grant Support
ID/Acronym/Agency:
CA42745/CA/NCI NIH HHS; GM40162/GM/NIGMS NIH HHS; P01 CA042745/CA/NCI NIH HHS; P01 CA042745-23/CA/NCI NIH HHS; R01 CA040355/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Liposomes; 80168379AG/Doxorubicin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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