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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1-2
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pubmed:dateCreated |
2007-6-11
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pubmed:abstractText |
To enhance the efficacy of ganciclovir/herpes simplex virus thymidine kinase (GCV/HSV-TK) suicide gene therapy for nasopharyngeal cancer KB, we developed long-circulating liposome-encapsulated GCV, and evaluated cytotoxicity in vitro and in vivo. PEGylated liposome-encapsulated GCV (PEG-GCV-lipo) was prepared by the freeze-thawing method. In vitro experiments demonstrated that GCV from liposomes was gradually released over a period of 3 days. The in vitro cytotoxicity of PEG-GCV-lipo was similar to that of GCV solution in human cervical carcinoma HeLa cells expressing HSV-TK. Pharmacokinetics studies in mice showed that, compared with GCV solution, intravenous and intraperitoneal injection of PEG-GCV-lipo (10 mg/kg) led to long circulation in plasma; the area under the curve was 36-fold or 32-fold higher than that of GCV solution, respectively. In GCV/HSV-TK suicide gene therapy, the HSV-TK gene complexed with nanoparticle vector was directly injected into KB xenografts, and PEG-GCV-lipo or GCV solution was injected intravenously in mice once a day (25 mg/kg/day every 2nd day, 4 times). PEG-GCV-lipo was significantly 3-fold more effective than GCV solution in inhibiting tumor growth and produced durable complete tumor remissions on day 11 after injection. These findings demonstrate that long-circulating liposome-encapsulated GCV is a new approach to drug carriers to enhance the efficacy of suicide gene therapy.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1873-4995
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
16
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pubmed:volume |
120
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
104-10
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pubmed:meshHeading |
pubmed-meshheading:17509714-Animals,
pubmed-meshheading:17509714-Antineoplastic Agents,
pubmed-meshheading:17509714-Antiviral Agents,
pubmed-meshheading:17509714-Cell Survival,
pubmed-meshheading:17509714-Chemistry, Pharmaceutical,
pubmed-meshheading:17509714-Cytomegalovirus,
pubmed-meshheading:17509714-Delayed-Action Preparations,
pubmed-meshheading:17509714-Dose-Response Relationship, Drug,
pubmed-meshheading:17509714-Drug Compounding,
pubmed-meshheading:17509714-Ganciclovir,
pubmed-meshheading:17509714-Gene Therapy,
pubmed-meshheading:17509714-Genes, Transgenic, Suicide,
pubmed-meshheading:17509714-HeLa Cells,
pubmed-meshheading:17509714-Humans,
pubmed-meshheading:17509714-Inhibitory Concentration 50,
pubmed-meshheading:17509714-Injections, Intraperitoneal,
pubmed-meshheading:17509714-Injections, Intravenous,
pubmed-meshheading:17509714-Liposomes,
pubmed-meshheading:17509714-Male,
pubmed-meshheading:17509714-Mice,
pubmed-meshheading:17509714-Mice, Inbred BALB C,
pubmed-meshheading:17509714-Mice, Nude,
pubmed-meshheading:17509714-Nasopharyngeal Neoplasms,
pubmed-meshheading:17509714-Particle Size,
pubmed-meshheading:17509714-Polyethylene Glycols,
pubmed-meshheading:17509714-Simplexvirus,
pubmed-meshheading:17509714-Solubility,
pubmed-meshheading:17509714-Technology, Pharmaceutical,
pubmed-meshheading:17509714-Thymidine Kinase,
pubmed-meshheading:17509714-Transfection,
pubmed-meshheading:17509714-Xenograft Model Antitumor Assays
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pubmed:year |
2007
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pubmed:articleTitle |
Long-circulating liposome-encapsulated ganciclovir enhances the efficacy of HSV-TK suicide gene therapy.
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pubmed:affiliation |
Institute of Medicinal Chemistry, Hoshi University, Ebara, Shinagawa-ku, Tokyo, Japan.
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pubmed:publicationType |
Journal Article
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