Source:http://linkedlifedata.com/resource/pubmed/id/17683514
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
2007-8-31
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pubmed:abstractText |
A major problem in high-dose chemotherapy with autologous hematopoietic stem cell transplantation is insufficient function of reconstituted bone marrow that limits the efficacy of post-transplantation chemotherapy. Because transduction of hematopoietic stem cells with the multidrug resistance 1 (MDR1) gene might circumvent this problem, we conducted a pilot study of MDR1 gene therapy against metastatic breast cancer. Peripheral blood stem cells were harvested, and one-third of the cells were transduced with MDR1 retrovirus. After the reconstitution of bone marrow function, the patients received high-dose chemotherapy with transplantation of both MDR1-transduced and unprocessed peripheral blood stem cells. The patients then received docetaxel chemotherapy. Two patients received transplantation of the MDR1-transduced cells in 2001. Peripheral blood MDR1-transduced leukocytes were 3-5% of the total cells after transplantation, but decreased gradually. During docetaxel chemotherapy, an increase in the rate of MDR1-transduced leukocytes (up to 10%) was observed. Comparison of docetaxel-induced granulocytopenia in the two patients suggested a bone marrow-protective effect of the MDR1-transduced cells. No serious side-effect was observed, and the patients were in complete remission for more than 3 years. The MDR1-transduced cells gradually decreased and disappeared almost entirely by the end of 2004. Results of linear amplification-mediated polymerase chain reaction of the MDR1-transduced leukocytes suggested no sign of abnormal amplification of the transduced cells. A third patient received transplantation of the MDR1-transduced cells in 2004. These results suggest the feasibility of our MDR1 gene therapy against metastatic breast cancer, and follow-up is ongoing.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1347-9032
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pubmed:author |
pubmed-author:AibaKeisukeK,
pubmed-author:HatakeKiyohikoK,
pubmed-author:IshikawaEtsukoE,
pubmed-author:ItoYoshinoriY,
pubmed-author:KobayashiTakayukiT,
pubmed-author:MinowaSayuriS,
pubmed-author:MitsuhashiJunkoJ,
pubmed-author:NakaneMinoruM,
pubmed-author:ShibataHarumiH,
pubmed-author:SugimotoYoshikazuY,
pubmed-author:SuzukiRiekoR,
pubmed-author:TakahashiShunjiS,
pubmed-author:TsukaharaSatomiS,
pubmed-author:TsuruoTakashiT
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pubmed:issnType |
Print
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pubmed:volume |
98
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1609-16
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pubmed:meshHeading |
pubmed-meshheading:17683514-Adult,
pubmed-meshheading:17683514-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:17683514-Breast Neoplasms,
pubmed-meshheading:17683514-Combined Modality Therapy,
pubmed-meshheading:17683514-Female,
pubmed-meshheading:17683514-Gene Therapy,
pubmed-meshheading:17683514-Genetic Vectors,
pubmed-meshheading:17683514-Hematopoietic Stem Cell Transplantation,
pubmed-meshheading:17683514-Hematopoietic Stem Cells,
pubmed-meshheading:17683514-Humans,
pubmed-meshheading:17683514-Middle Aged,
pubmed-meshheading:17683514-P-Glycoprotein,
pubmed-meshheading:17683514-Paclitaxel,
pubmed-meshheading:17683514-Pilot Projects,
pubmed-meshheading:17683514-Retroviridae,
pubmed-meshheading:17683514-Transduction, Genetic
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pubmed:year |
2007
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pubmed:articleTitle |
Pilot study of MDR1 gene transfer into hematopoietic stem cells and chemoprotection in metastatic breast cancer patients.
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pubmed:affiliation |
Division of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo 135-8500, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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