Linked Life Data

12885349

Source:http://linkedlifedata.com/resource/pubmed/id/12885349

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2003-7-29
pubmed:abstractText
Because radiation remains a common postoperative treatment for head and neck cancers, it is critical to determine whether new bone-regenerative approaches are effective for healing craniofacial defects challenged by therapeutic doses of radiation. The objective of this study was to determine whether the deleterious effects of radiotherapy could be overcome by ex vivo gene therapy to heal craniofacial defects. Rat calvarial critical-sized defects were treated with either an inlay calvarial bone graft or syngeneic dermal fibroblasts transduced ex vivo with an adenovirus engineered to express bone morphogenetic protein 7 (BMP-7), a morphogen known to stimulate bone formation. Two weeks postoperatively, either no radiation or a single 12-Gy radiation dose was delivered to the operated area and the tissue was harvested 4 weeks later. None of the inlay bone grafts healed at the wound margins of either the radiated or nonradiated sites. In contrast, bone was successfully regenerated when using an ex vivo gene therapy approach. More bone formed in the nonradiated group as determined by the percentage of defect surface covered (87 +/- 4.1 versus 65 +/- 4.7%; p = 0.003) and percentage of defect area filled by new bone (60 +/- 5.9 versus 32 +/- 2.7%; p = 0.002). Although the effects of radiation on the wound were not completely overcome by the gene therapy approach, bone regeneration was still successful despite the radiation sensitivity of the fibroblasts. These results indicate that BMP-7 ex vivo gene therapy is capable of successfully regenerating bone in rat calvarial defects even after a therapeutic dose of radiation. This approach may represent a new strategy for regenerating skeletal elements lost due to head and neck cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1043-0342
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1107-15
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12885349-Adenoviridae, pubmed-meshheading:12885349-Animals, pubmed-meshheading:12885349-Bone Morphogenetic Protein 7, pubmed-meshheading:12885349-Bone Morphogenetic Proteins, pubmed-meshheading:12885349-Bone Regeneration, pubmed-meshheading:12885349-Bone Transplantation, pubmed-meshheading:12885349-Craniotomy, pubmed-meshheading:12885349-Dermis, pubmed-meshheading:12885349-Dose-Response Relationship, Radiation, pubmed-meshheading:12885349-Fibroblasts, pubmed-meshheading:12885349-Gene Therapy, pubmed-meshheading:12885349-Genetic Vectors, pubmed-meshheading:12885349-Head and Neck Neoplasms, pubmed-meshheading:12885349-Humans, pubmed-meshheading:12885349-Integrases, pubmed-meshheading:12885349-Postoperative Period, pubmed-meshheading:12885349-Radiation Tolerance, pubmed-meshheading:12885349-Radiotherapy, pubmed-meshheading:12885349-Rats, pubmed-meshheading:12885349-Rats, Inbred F344, pubmed-meshheading:12885349-Skull, pubmed-meshheading:12885349-Transduction, Genetic, pubmed-meshheading:12885349-Transforming Growth Factor beta, pubmed-meshheading:12885349-Transplantation, Autologous, pubmed-meshheading:12885349-Viral Proteins
pubmed:year
2003
pubmed:articleTitle
Ex vivo gene therapy for skeletal regeneration in cranial defects compromised by postoperative radiotherapy.
pubmed:affiliation
Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO 63110, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.