Source:http://linkedlifedata.com/resource/pubmed/id/18302483
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rdf:type | |
lifeskim:mentions |
umls-concept:C0018956,
umls-concept:C0086022,
umls-concept:C0086418,
umls-concept:C0279038,
umls-concept:C0333873,
umls-concept:C0442335,
umls-concept:C0444782,
umls-concept:C0815304,
umls-concept:C1332710,
umls-concept:C1424622,
umls-concept:C1517499,
umls-concept:C1524108,
umls-concept:C1538698,
umls-concept:C1704939,
umls-concept:C1705099
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pubmed:issue |
3
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pubmed:dateCreated |
2008-2-27
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pubmed:abstractText |
Tumor radiotherapy with large-field irradiation results in an increase in apoptosis of the radiosensitive hematopoietic stem cells (CD34(+)). The aim of this study was to demonstrate the radioprotective potential of MDR1 overexpression in human CD34(+) cells using a lentiviral self-inactivating vector. Transduced human undifferentiated CD34(+) cells were irradiated with 0-8 Gy and held in liquid culture under myeloid-specific maturation conditions. After 12 days, MDR1 expression was determined by the rhodamine efflux assay. The proportion of MDR1-positive cells in cells from four human donors increased with increasing radiation dose (up to a 14-fold increase at 8 Gy). Determination of expression of myeloid-specific surface marker proteins revealed that myeloid differentiation was not affected by transduction and MDR1 overexpression. Irradiation after myeloid differentiation also led to an increase of MDR1-positive cells with escalating radiation doses (e.g. 12.5-16% from 0-8 Gy). Most importantly, fractionated irradiation (3 x 2 Gy; 24-h intervals) of MDR1-transduced CD34(+) cells resulted in an increase in MDR1-positive cells (e.g. 3-8% from 0-3 x 2 Gy). Our results clearly support a radioprotective effect of lentiviral MDR1 overexpression in human CD34(+) cells. Thus enhancing repopulation by surviving stem cells may increase the radiation tolerance of the hematopoietic system, which will contribute to widening the therapeutic index in radiotherapy.
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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 |
Mar
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pubmed:issn |
0033-7587
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
169
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
301-10
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pubmed:meshHeading |
pubmed-meshheading:18302483-Cell Survival,
pubmed-meshheading:18302483-Cells, Cultured,
pubmed-meshheading:18302483-Dose-Response Relationship, Radiation,
pubmed-meshheading:18302483-Genetic Vectors,
pubmed-meshheading:18302483-Hematopoietic Stem Cells,
pubmed-meshheading:18302483-Humans,
pubmed-meshheading:18302483-Lentivirus,
pubmed-meshheading:18302483-P-Glycoprotein,
pubmed-meshheading:18302483-Radiation Dosage,
pubmed-meshheading:18302483-Radiation Protection,
pubmed-meshheading:18302483-Radiation Tolerance,
pubmed-meshheading:18302483-Receptors, Complement 3b,
pubmed-meshheading:18302483-Recombinant Proteins,
pubmed-meshheading:18302483-Transfection
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pubmed:year |
2008
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pubmed:articleTitle |
MDR1 gene transfer using a lentiviral SIN vector confers radioprotection to human CD34+ hematopoietic progenitor cells.
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pubmed:affiliation |
Department of Radiation Oncology, Mannheim Medical Centre, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. patrick.maier@radonk.ma.uni-heidelberg.de
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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