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In vitro and in vivo effect of doxorubicin combined with liposome-encapsulated muramyl tripeptide on canine monocyte activation.

Chemotherapeutic agents have been shown to enhance the antitumor activity of biological response modifiers and cytokines in rodents and humans. The purpose of this study was 2-fold: (a) to determine whether doxorubicin (DOX) would enhance or interfere with the effect of muramyl dipeptide and lipopol... Full description

Journal Title: Cancer research September 1, 1993, Vol.53(17), pp.3986-3991
Main Author: Shi, F
Other Authors: Macewen, E G , Kurzman, I D
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0008-5472
Link: http://search.proquest.com/docview/75919221/?pq-origsite=primo
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title: In vitro and in vivo effect of doxorubicin combined with liposome-encapsulated muramyl tripeptide on canine monocyte activation.
format: Article
creator:
  • Shi, F
  • Macewen, E G
  • Kurzman, I D
subjects:
  • Acetylmuramyl-Alanyl-Isoglutamine–Administration & Dosage
  • Animals–Analogs & Derivatives
  • Antibodies, Monoclonal–Pharmacology
  • Dogs–Administration & Dosage
  • Doxorubicin–Pharmacology
  • Drug Carriers–Metabolism
  • Fibrosarcoma–Drug Effects
  • In Vitro Techniques–Administration & Dosage
  • Leukocyte Count–Pharmacology
  • Lipopolysaccharides–Drug Effects
  • Liposomes–Metabolism
  • Monocytes–Metabolism
  • Time Factors–Metabolism
  • Tumor Cells, Cultured–Metabolism
  • Tumor Necrosis Factor-Alpha–Metabolism
  • Antibodies, Monoclonal
  • Drug Carriers
  • Lipopolysaccharides
  • Liposomes
  • Tumor Necrosis Factor-Alpha
  • Acetylmuramyl-Alanyl-Isoglutamine
  • Muramylnac-Ala-Isogln-Lys-Tripeptide
  • Doxorubicin
ispartof: Cancer research, September 1, 1993, Vol.53(17), pp.3986-3991
description: Chemotherapeutic agents have been shown to enhance the antitumor activity of biological response modifiers and cytokines in rodents and humans. The purpose of this study was 2-fold: (a) to determine whether doxorubicin (DOX) would enhance or interfere with the effect of muramyl dipeptide and lipopolysaccharide on canine monocyte activation as measured by an in vitro WEHI-164 cell cytotoxicity assay; and (b) to evaluate the in vivo effect of DOX alone and combined with liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) on monocyte activation and serum tumor necrosis factor activity. The in vitro results showed that increasing concentrations of DOX for either 1 or 24 h incubation did not directly enhance or inhibit spontaneous or activated monocyte supernatant-mediated cytotoxicity. The in vivo study showed that monocyte supernatant-mediated cytotoxicity was increased on day 3 and significantly elevated on day 7 (P = 0.016) post-DOX (30 mg/m2, single injection) administration. When DOX was given in combination with L-MTP-PE (2 mg/m2, twice weekly for 3 weeks), monocyte-mediated cytotoxicity was enhanced on days 3 through 10 with a significant increase on day 10 (P < 0.001). In vivo monocyte supernatant-mediated cytotoxicity was significantly elevated in dogs receiving L-MTP-PE alone at 2 h after day 0, 7, and 14 treatment, and this response was further enhanced by DOX. Serum tumor necrosis factor activity at 2 h post-L-MTP-PE was enhanced and sustained for a longer period of time in dogs that also received DOX. We conclude that DOX administered with L-MTP-PE will enhance canine monocyte activation induced by DOX or L-MTP-PE alone, and suggest that DOX may be combined with L-MTP-PE early in the treatment of cancer patients.
language: eng
source:
identifier: ISSN: 0008-5472
fulltext: fulltext
issn:
  • 00085472
  • 0008-5472
url: Link


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titleIn vitro and in vivo effect of doxorubicin combined with liposome-encapsulated muramyl tripeptide on canine monocyte activation.
creatorShi, F ; Macewen, E G ; Kurzman, I D
contributorShi, F (correspondence author) ; Shi, F (record owner)
ispartofCancer research, September 1, 1993, Vol.53(17), pp.3986-3991
identifierISSN: 0008-5472
subjectAcetylmuramyl-Alanyl-Isoglutamine–Administration & Dosage ; Animals–Analogs & Derivatives ; Antibodies, Monoclonal–Pharmacology ; Dogs–Administration & Dosage ; Doxorubicin–Pharmacology ; Drug Carriers–Metabolism ; Fibrosarcoma–Drug Effects ; In Vitro Techniques–Administration & Dosage ; Leukocyte Count–Pharmacology ; Lipopolysaccharides–Drug Effects ; Liposomes–Metabolism ; Monocytes–Metabolism ; Time Factors–Metabolism ; Tumor Cells, Cultured–Metabolism ; Tumor Necrosis Factor-Alpha–Metabolism ; Antibodies, Monoclonal ; Drug Carriers ; Lipopolysaccharides ; Liposomes ; Tumor Necrosis Factor-Alpha ; Acetylmuramyl-Alanyl-Isoglutamine ; Muramylnac-Ala-Isogln-Lys-Tripeptide ; Doxorubicin
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descriptionChemotherapeutic agents have been shown to enhance the antitumor activity of biological response modifiers and cytokines in rodents and humans. The purpose of this study was 2-fold: (a) to determine whether doxorubicin (DOX) would enhance or interfere with the effect of muramyl dipeptide and lipopolysaccharide on canine monocyte activation as measured by an in vitro WEHI-164 cell cytotoxicity assay; and (b) to evaluate the in vivo effect of DOX alone and combined with liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) on monocyte activation and serum tumor necrosis factor activity. The in vitro results showed that increasing concentrations of DOX for either 1 or 24 h incubation did not directly enhance or inhibit spontaneous or activated monocyte supernatant-mediated cytotoxicity. The in vivo study showed that monocyte supernatant-mediated cytotoxicity was increased on day 3 and significantly elevated on day 7 (P = 0.016) post-DOX (30 mg/m2, single injection) administration. When DOX was given in combination with L-MTP-PE (2 mg/m2, twice weekly for 3 weeks), monocyte-mediated cytotoxicity was enhanced on days 3 through 10 with a significant increase on day 10 (P < 0.001). In vivo monocyte supernatant-mediated cytotoxicity was significantly elevated in dogs receiving L-MTP-PE alone at 2 h after day 0, 7, and 14 treatment, and this response was further enhanced by DOX. Serum tumor necrosis factor activity at 2 h post-L-MTP-PE was enhanced and sustained for a longer period of time in dogs that also received DOX. We conclude that DOX administered with L-MTP-PE will enhance canine monocyte activation induced by DOX or L-MTP-PE alone, and suggest that DOX may be combined with L-MTP-PE early in the treatment of cancer patients.
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titleIn vitro and in vivo effect of doxorubicin combined with liposome-encapsulated muramyl tripeptide on canine monocyte activation.
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0Acetylmuramyl-Alanyl-Isoglutamine–Administration & Dosage
1Animals–Analogs & Derivatives
2Antibodies, Monoclonal–Pharmacology
3Dogs–Administration & Dosage
4Doxorubicin–Pharmacology
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10Liposomes–Metabolism
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12Time Factors–Metabolism
13Tumor Cells, Cultured–Metabolism
14Tumor Necrosis Factor-Alpha–Metabolism
15Antibodies, Monoclonal
16Drug Carriers
17Lipopolysaccharides
18Liposomes
19Tumor Necrosis Factor-Alpha
20Acetylmuramyl-Alanyl-Isoglutamine
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titleIn vitro and in vivo effect of doxorubicin combined with liposome-encapsulated muramyl tripeptide on canine monocyte activation.
authorShi, F ; Macewen, E G ; Kurzman, I D
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1Animals–Analogs & Derivatives
2Antibodies, Monoclonal–Pharmacology
3Dogs–Administration & Dosage
4Doxorubicin–Pharmacology
5Drug Carriers–Metabolism
6Fibrosarcoma–Drug Effects
7In Vitro Techniques–Administration & Dosage
8Leukocyte Count–Pharmacology
9Lipopolysaccharides–Drug Effects
10Liposomes–Metabolism
11Monocytes–Metabolism
12Time Factors–Metabolism
13Tumor Cells, Cultured–Metabolism
14Tumor Necrosis Factor-Alpha–Metabolism
15Antibodies, Monoclonal
16Drug Carriers
17Lipopolysaccharides
18Liposomes
19Tumor Necrosis Factor-Alpha
20Acetylmuramyl-Alanyl-Isoglutamine
21Muramylnac-Ala-Isogln-Lys-Tripeptide
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