Linked Life Data

15067350

Source:http://linkedlifedata.com/resource/pubmed/id/15067350

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-4-6
pubmed:abstractText
Chemotherapy is an established treatment modality for bone sarcomas such as osteosarcoma (OS). However, the use of chemotherapy in high-grade soft tissue sarcomas remains controversial, with the most active chemotherapeutic agent, doxorubicin (DOX), reported to have a response rate of, at best only 34% and most studies reporting lower response rates. Apo2L/TRAIL is a member of the tumour necrosis factor (TNF) family of cytokines and induces death of tumour cells, but not normal cells. Its potent apoptotic activity is mediated through cell surface death domain-containing receptors, DR4/TRAIL-R1 and DR5/TRAIL-R2. We investigated the efficacy of Apo2L/TRAIL as a single agent, and in combination with clinically relevant chemotherapeutic drugs, in fresh isolates of primary malignant cells obtained from biopsy material. The data presented here demonstrate that, in a range of primary bone related tumours, as well as soft tissue sarcomas, chemotherapeutic agents were only moderately effective, in terms of induction of cell death. Apo2L/TRAIL alone had little or no effect on any bone-related tumour or sarcoma in culture. In contrast, the combination of Apo2L/TRAIL and chemotherapeutic drugs produced a significant increase in tumour cell death, with DOX and Apo2L/TRAIL proving to be the most effective combination. These data suggest the potential for Apo2L/TRAIL to increase the effectiveness of chemotherapeutic drugs in bone and soft tissue sarcomas, while perhaps concurrently allowing a reduction in the exposure to drugs such as DOX, and a consequent reduction in toxicity. The synergistic action between these two different classes of agents has yet to be tested in vivo but may prove clinically relevant in the treatment of this refractive class of malignancies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1019-6439
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1263-70
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15067350-Adolescent, pubmed-meshheading:15067350-Adult, pubmed-meshheading:15067350-Aged, pubmed-meshheading:15067350-Aged, 80 and over, pubmed-meshheading:15067350-Apoptosis Regulatory Proteins, pubmed-meshheading:15067350-Bone Neoplasms, pubmed-meshheading:15067350-Child, pubmed-meshheading:15067350-Combined Modality Therapy, pubmed-meshheading:15067350-Doxorubicin, pubmed-meshheading:15067350-Drug Resistance, Neoplasm, pubmed-meshheading:15067350-Female, pubmed-meshheading:15067350-Giant Cell Tumor of Bone, pubmed-meshheading:15067350-Humans, pubmed-meshheading:15067350-Male, pubmed-meshheading:15067350-Membrane Glycoproteins, pubmed-meshheading:15067350-Middle Aged, pubmed-meshheading:15067350-Osteosarcoma, pubmed-meshheading:15067350-Sarcoma, pubmed-meshheading:15067350-TNF-Related Apoptosis-Inducing Ligand, pubmed-meshheading:15067350-Transfection, pubmed-meshheading:15067350-Tumor Cells, Cultured, pubmed-meshheading:15067350-Tumor Necrosis Factor-alpha
pubmed:year
2004
pubmed:articleTitle
Sensitivity of fresh isolates of soft tissue sarcoma, osteosarcoma and giant cell tumour cells to Apo2L/TRAIL and doxorubicin.
pubmed:affiliation
Department of Orthopaedics, Royal Adelaide Hospital, Adelaide University, Hanson Institute, Adelaide, South Australia, Australia.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't