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Publications [#210126] of Mark W. Dewhirst

Papers Published

  1. PS Yarmolenko, Y Zhao, C Landon, I Spasojevic, F Yuan, D Needham, BL Viglianti, MW Dewhirst, Comparative effects of thermosensitive doxorubicin-containing liposomes and hyperthermia in human and murine tumours., International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, vol. 26 no. 5 (2010), pp. 485-98, ISSN 1464-5157 [doi]
    (last updated on 2012/10/26)

    Abstract:
    OBJECTIVE: 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.

    Keywords:
    Animals • Carcinoma, Squamous Cell • Cell Division • Cell Line, Tumor • Combined Modality Therapy • Doxorubicin • Female • Humans • Hydrogen-Ion Concentration • Hyperthermia, Induced* • Liposomes • Mice • Mice, Inbred BALB C • Mice, Nude • Treatment Outcome • administration & dosage • drug effects • drug therapy • therapeutic use* • therapy* • toxicity


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