Linked Life Data

18823375

Source:http://linkedlifedata.com/resource/pubmed/id/18823375

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2008-11-28
pubmed:abstractText
The therapeutic effect of concurrent chemoradiotherapy with TS-1 has been confirmed in various solid tumors; however, the detailed mechanism of action has not yet been fully elucidated. In the present study, we identified hypoxia-inducible factor-1 (HIF-1) as one of the targets of TS-1 in chemoradiotherapy. In growth delay assays using a tumor xenograft of non-small-cell lung carcinoma, H441, TS-1 treatment enhanced the therapeutic effect of single gamma-ray radiotherapy (14 Gy) and significantly delayed tumor growth by 1.58-fold compared to radiotherapy alone (P < 0.01). An optical in vivo imaging experiment using a HIF-1-dependent 5HRE-luc reporter gene revealed that TS-1 treatment suppressed radiation-induced activation of HIF-1 in the tumor xenografts. The suppression led to apoptosis of endothelial cells resulting in both a significant decrease in microvessel density (P < 0.05; vs radiation therapy alone) and a significant increase in apoptosis of tumor cells (P < 0.01; vs radiation therapy alone) in tumor xenografts. All of these results indicate that TS-1 enhances radiation-induced apoptosis of endothelial cells by suppressing HIF-1 activity, resulting in an increase in radiosensitivity of the tumor cells. Our findings strengthen the importance of both HIF-1 and its downstream gene, such as vascular endothelial cell growth factor, as therapeutic targets to enhance the effect of radiotherapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1349-7006
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
99
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2327-35
pubmed:meshHeading
pubmed-meshheading:18823375-Animals, pubmed-meshheading:18823375-Antimetabolites, Antineoplastic, pubmed-meshheading:18823375-Apoptosis, pubmed-meshheading:18823375-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:18823375-Cell Line, Tumor, pubmed-meshheading:18823375-Combined Modality Therapy, pubmed-meshheading:18823375-Drug Combinations, pubmed-meshheading:18823375-Endothelial Cells, pubmed-meshheading:18823375-Humans, pubmed-meshheading:18823375-Hypoxia-Inducible Factor 1, pubmed-meshheading:18823375-Immunohistochemistry, pubmed-meshheading:18823375-Lung Neoplasms, pubmed-meshheading:18823375-Mice, pubmed-meshheading:18823375-Mice, Inbred BALB C, pubmed-meshheading:18823375-Oxonic Acid, pubmed-meshheading:18823375-Tegafur, pubmed-meshheading:18823375-Vascular Endothelial Growth Factor A
pubmed:year
2008
pubmed:articleTitle
TS-1 enhances the effect of radiotherapy by suppressing radiation-induced hypoxia-inducible factor-1 activation and inducing endothelial cell apoptosis.
pubmed:affiliation
Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't