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Biodistribution and Efficacy of Low Temperature-Sensitive Liposome Encapsulated Docetaxel Combined with Mild Hyperthermia in a Mouse Model of Prostate Cancer

To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s11095-016-1971-8 Byline: Ashish Ranjan (1), Compton J. Benjamin (2), Ayele H. Negussie (1), Saurin Chokshi (2), Paul H. Chung (2), Dmitry Volkin (2), Nitin Yeram (2),... Full description

Journal Title: Pharmaceutical Research 2016, Vol.33(10), pp.2459-2469
Main Author: Ranjan, Ashish
Other Authors: Benjamin, Compton , Negussie, Ayele , Chokshi, Saurin , Chung, Paul , Volkin, Dmitry , Yeram, Nitin , Linehan, W. , Dreher, Matthew , Pinto, Peter , Wood, Bradford
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0724-8741 ; E-ISSN: 1573-904X ; DOI: 10.1007/s11095-016-1971-8
Link: http://dx.doi.org/10.1007/s11095-016-1971-8
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recordid: springer_jour10.1007/s11095-016-1971-8
title: Biodistribution and Efficacy of Low Temperature-Sensitive Liposome Encapsulated Docetaxel Combined with Mild Hyperthermia in a Mouse Model of Prostate Cancer
format: Article
creator:
  • Ranjan, Ashish
  • Benjamin, Compton
  • Negussie, Ayele
  • Chokshi, Saurin
  • Chung, Paul
  • Volkin, Dmitry
  • Yeram, Nitin
  • Linehan, W.
  • Dreher, Matthew
  • Pinto, Peter
  • Wood, Bradford
subjects:
  • cancer
  • docetaxel
  • HIFU
  • LTSL
  • prostate
ispartof: Pharmaceutical Research, 2016, Vol.33(10), pp.2459-2469
description: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s11095-016-1971-8 Byline: Ashish Ranjan (1), Compton J. Benjamin (2), Ayele H. Negussie (1), Saurin Chokshi (2), Paul H. Chung (2), Dmitry Volkin (2), Nitin Yeram (2), W. Marston Linehan (2), Matthew R. Dreher (1), Peter A. Pinto (2), Bradford J. Wood (1) Keywords: cancer; docetaxel; HIFU; LTSL; prostate Abstract: Purpose Low temperature sensitive liposome (LTSL) encapsulated docetaxel were combined with mild hyperthermia (40--42[degrees]C) to investigate in vivo biodistribution and efficacy against a castrate resistant prostate cancer. Method Female athymic nude mice with human prostate PC-3 M-luciferase cells grown subcutaneously into the right hind leg were randomized into six groups: saline (+/- heat), free docetaxel (+/- heat), and LTSL docetaxel (+/- heat). Treatment (15 mg docetaxel/kg) was administered via tail vein once tumors reached a size of 200-300 mm.sup.3. Mice tumor volumes and body weights were recorded for up to 60 days. Docetaxel concentrations of harvested tumor and organ/tissue homogenates were determined by LC-MS. Histological evaluation (Mean vessel density, Ki67 proliferation, Caspase-3 apoptosis) of saline, free Docetaxel and LTSL docetaxel (+/- heat n=3--5) was performed to determine molecular mechanism responsible for tumor cell killing. Result LTSL/heat resulted in significantly higher tumor docetaxel concentrations (4.7-fold greater compared to free docetaxel). Adding heat to LTSL Docetaxel or free docetaxel treatment resulted in significantly greater survival and growth delay compared to other treatments (p10% and were not statistically different from each other. Molecular markers such as caspase-3 were upregulated, and Ki67 expression was significantly decreased in the chemo-hyperthermia group. Vessel density was similar post treatment, but the heated group had reduced vessel area, suggesting thermal enhancement in efficacy by reduction in functional perfusion. Conclusion This technique of hyperthermia sensitization and enhanced docetaxel delivery has potential for clinical translation for prostate cancer treatment. Author Affiliation: (1) Center for Interventional Oncology, Radiology & Imaging Sciences, Clinical Center, National Institutes of Health, MSC 1182- building 10- room 1c -341, 10 Center Drive, Beth
language: eng
source:
identifier: ISSN: 0724-8741 ; E-ISSN: 1573-904X ; DOI: 10.1007/s11095-016-1971-8
fulltext: fulltext
issn:
  • 1573-904X
  • 1573904X
  • 0724-8741
  • 07248741
url: Link


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titleBiodistribution and Efficacy of Low Temperature-Sensitive Liposome Encapsulated Docetaxel Combined with Mild Hyperthermia in a Mouse Model of Prostate Cancer
creatorRanjan, Ashish ; Benjamin, Compton ; Negussie, Ayele ; Chokshi, Saurin ; Chung, Paul ; Volkin, Dmitry ; Yeram, Nitin ; Linehan, W. ; Dreher, Matthew ; Pinto, Peter ; Wood, Bradford
ispartofPharmaceutical Research, 2016, Vol.33(10), pp.2459-2469
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subjectcancer ; docetaxel ; HIFU ; LTSL ; prostate
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descriptionTo access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s11095-016-1971-8 Byline: Ashish Ranjan (1), Compton J. Benjamin (2), Ayele H. Negussie (1), Saurin Chokshi (2), Paul H. Chung (2), Dmitry Volkin (2), Nitin Yeram (2), W. Marston Linehan (2), Matthew R. Dreher (1), Peter A. Pinto (2), Bradford J. Wood (1) Keywords: cancer; docetaxel; HIFU; LTSL; prostate Abstract: Purpose Low temperature sensitive liposome (LTSL) encapsulated docetaxel were combined with mild hyperthermia (40--42[degrees]C) to investigate in vivo biodistribution and efficacy against a castrate resistant prostate cancer. Method Female athymic nude mice with human prostate PC-3 M-luciferase cells grown subcutaneously into the right hind leg were randomized into six groups: saline (+/- heat), free docetaxel (+/- heat), and LTSL docetaxel (+/- heat). Treatment (15 mg docetaxel/kg) was administered via tail vein once tumors reached a size of 200-300 mm.sup.3. Mice tumor volumes and body weights were recorded for up to 60 days. Docetaxel concentrations of harvested tumor and organ/tissue homogenates were determined by LC-MS. Histological evaluation (Mean vessel density, Ki67 proliferation, Caspase-3 apoptosis) of saline, free Docetaxel and LTSL docetaxel (+/- heat n=3--5) was performed to determine molecular mechanism responsible for tumor cell killing. Result LTSL/heat resulted in significantly higher tumor docetaxel concentrations (4.7-fold greater compared to free docetaxel). Adding heat to LTSL Docetaxel or free docetaxel treatment resulted in significantly greater survival and growth delay compared to other treatments (p<0.05). Differences in body weight between all Docetaxel treatments were not reduced by >10% and were not statistically different from each other. Molecular markers such as caspase-3 were upregulated, and Ki67 expression was significantly decreased in the chemo-hyperthermia group. Vessel density was similar post treatment, but the heated group had reduced vessel area, suggesting thermal enhancement in efficacy by reduction in functional perfusion. Conclusion This technique of hyperthermia sensitization and enhanced docetaxel delivery has potential for clinical translation for prostate cancer treatment. Author Affiliation: (1) Center for Interventional Oncology, Radiology & Imaging Sciences, Clinical Center, National Institutes of Health, MSC 1182- building 10- room 1c -341, 10 Center Drive, Bethesda, Maryland, 20892, USA (2) Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA Article History: Registration Date: 09/06/2016 Received Date: 04/03/2016 Accepted Date: 09/06/2016 Online Date: 24/06/2016 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s11095-016-1971-8) contains supplementary material, which is available to authorized users.
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