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Arrest of human lung tumor xenograft growth in severe combined immunodeficient mice using doxorubicin encapsulated in sterically stabilized liposomes.

Incorporation of polyethylene glycol-derivatized phospholipids into liposomes results in carriers that can enhance the therapeutic efficacy of encapsulated drugs by imparting the ability to evade the reticuloendothelial system and remain in the circulation for prolonged periods. In this study, doxor... Full description

Journal Title: Cancer research September 1, 1993, Vol.53(17), pp.3964-3967
Main Author: Williams, S S
Other Authors: Alosco, T R , Mayhew, E , Lasic, D D , Martin, F J , Bankert, R B
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0008-5472
Link: http://search.proquest.com/docview/75914053/?pq-origsite=primo
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title: Arrest of human lung tumor xenograft growth in severe combined immunodeficient mice using doxorubicin encapsulated in sterically stabilized liposomes.
format: Article
creator:
  • Williams, S S
  • Alosco, T R
  • Mayhew, E
  • Lasic, D D
  • Martin, F J
  • Bankert, R B
subjects:
  • Animals–Drug Therapy
  • Carcinoma, Squamous Cell–Administration & Dosage
  • Dose-Response Relationship, Drug–Adverse Effects
  • Doxorubicin–Drug Therapy
  • Drug Administration Schedule–Drug Therapy
  • Drug Carriers–Drug Therapy
  • Humans–Drug Therapy
  • Liposomes–Drug Therapy
  • Lung Neoplasms–Drug Therapy
  • Mice–Drug Therapy
  • Mice, Scid–Drug Therapy
  • Neoplasm Transplantation–Drug Therapy
  • Transplantation, Heterologous–Drug Therapy
  • Drug Carriers
  • Liposomes
  • Doxorubicin
ispartof: Cancer research, September 1, 1993, Vol.53(17), pp.3964-3967
description: Incorporation of polyethylene glycol-derivatized phospholipids into liposomes results in carriers that can enhance the therapeutic efficacy of encapsulated drugs by imparting the ability to evade the reticuloendothelial system and remain in the circulation for prolonged periods. In this study, doxorubicin encapsulated in these sterically stabilized liposomes (S-DOX) is shown to completely arrest the growth of human lung tumor xenografts in severe combined immunodeficient (scid) mice. Doxorubicin administered at equivalent doses as free drug or encapsulated into conventional liposomes was ineffective at completely arresting the growth of this human tumor, although a decrease in tumor growth rate compared to untreated controls was observed. Scid mice were found to be significantly more susceptible to the toxic effects of doxorubicin than were immunocompetent C.B-17 control mice, a characteristic that is likely to result from the deficit in DNA repair mechanisms previously identified in scid mice. However, doxorubicin toxicity in scid mice could be minimized while maintaining the antitumor activity of doxorubicin encapsulated in sterically stabilized liposomes by administering the drug in multiple weekly injections at low doses. This report provides the first evidence that antitumor drugs delivered in sterically stabilized liposomes are more effective at arresting the growth of human tumors than are conventional delivery systems. In addition, the scid mouse is presented as a viable model in which to study novel chemotherapeutic approaches to the treatment of human cancer.
language: eng
source:
identifier: ISSN: 0008-5472
fulltext: fulltext
issn:
  • 00085472
  • 0008-5472
url: Link


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titleArrest of human lung tumor xenograft growth in severe combined immunodeficient mice using doxorubicin encapsulated in sterically stabilized liposomes.
creatorWilliams, S S ; Alosco, T R ; Mayhew, E ; Lasic, D D ; Martin, F J ; Bankert, R B
contributorWilliams, S S (correspondence author) ; Williams, S S (record owner)
ispartofCancer research, September 1, 1993, Vol.53(17), pp.3964-3967
identifierISSN: 0008-5472
subjectAnimals–Drug Therapy ; Carcinoma, Squamous Cell–Administration & Dosage ; Dose-Response Relationship, Drug–Adverse Effects ; Doxorubicin–Drug Therapy ; Drug Administration Schedule–Drug Therapy ; Drug Carriers–Drug Therapy ; Humans–Drug Therapy ; Liposomes–Drug Therapy ; Lung Neoplasms–Drug Therapy ; Mice–Drug Therapy ; Mice, Scid–Drug Therapy ; Neoplasm Transplantation–Drug Therapy ; Transplantation, Heterologous–Drug Therapy ; Drug Carriers ; Liposomes ; Doxorubicin
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descriptionIncorporation of polyethylene glycol-derivatized phospholipids into liposomes results in carriers that can enhance the therapeutic efficacy of encapsulated drugs by imparting the ability to evade the reticuloendothelial system and remain in the circulation for prolonged periods. In this study, doxorubicin encapsulated in these sterically stabilized liposomes (S-DOX) is shown to completely arrest the growth of human lung tumor xenografts in severe combined immunodeficient (scid) mice. Doxorubicin administered at equivalent doses as free drug or encapsulated into conventional liposomes was ineffective at completely arresting the growth of this human tumor, although a decrease in tumor growth rate compared to untreated controls was observed. Scid mice were found to be significantly more susceptible to the toxic effects of doxorubicin than were immunocompetent C.B-17 control mice, a characteristic that is likely to result from the deficit in DNA repair mechanisms previously identified in scid mice. However, doxorubicin toxicity in scid mice could be minimized while maintaining the antitumor activity of doxorubicin encapsulated in sterically stabilized liposomes by administering the drug in multiple weekly injections at low doses. This report provides the first evidence that antitumor drugs delivered in sterically stabilized liposomes are more effective at arresting the growth of human tumors than are conventional delivery systems. In addition, the scid mouse is presented as a viable model in which to study novel chemotherapeutic approaches to the treatment of human cancer.
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titleArrest of human lung tumor xenograft growth in severe combined immunodeficient mice using doxorubicin encapsulated in sterically stabilized liposomes.
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