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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2002-5-20
pubmed:abstractText
Thymidine phosphorylase (TP), an enzyme involved in the reversible conversion of thymidine to thymine, is identical to an angiogenic factor, platelet-derived endothelial cell growth factor (PD-ECGF). Both TP and one of the TP-degradation products of thymidine 2-deoxy-D-ribose (dRib) display endothelial cell chemotactic activity in vitro and angiogenic activity in vivo. Recently, we demonstrated that 2-deoxy-L-ribose (lRib) could abolish the inhibitory effect of dRib on hypoxia-induced apoptosis. This suggested that lRib may be a useful inhibitor of dRib and thereby of TP functions. Therefore, we investigated the ability of lRib to inhibit the range of biological activities of TP and dRib. lRib suppressed both dRib-induced endothelial cell migration in a chemotaxis assay and endothelial tube formation induced by dRib in a collagen gel. lRib could also suppress the biological effects of TP in vivo assays of angiogenesis and tumor growth. Thus, in a corneal assay of angiogenesis, lRib inhibited angiogenesis induced by the implantation of recombinant TP. In a dorsal air sac assay of angiogenesis, lRib inhibited angiogenesis induced by the implantation of KB cells overexpressing TP (KB/TP). In a tumor growth assay, lRib treatment considerably decreased the growth rate of KB/TP cells xenografted into nude mice and also resulted in an increase in the proportion of apoptotic cells in KB/TP tumors. These findings demonstrate that TP and dRib play an important role in angiogenesis and tumor growth, and that these effects can be inhibited by lRib. Thus, lRib is a potentially useful agent for the suppression of TP-dependent angiogenesis and tumor growth.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2834-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12019161-Animals, pubmed-meshheading:12019161-Carcinoma, Squamous Cell, pubmed-meshheading:12019161-Cell Division, pubmed-meshheading:12019161-Chemotaxis, pubmed-meshheading:12019161-Deoxyribose, pubmed-meshheading:12019161-Enzyme Inhibitors, pubmed-meshheading:12019161-Humans, pubmed-meshheading:12019161-Male, pubmed-meshheading:12019161-Mice, pubmed-meshheading:12019161-Mice, Inbred BALB C, pubmed-meshheading:12019161-Mice, Nude, pubmed-meshheading:12019161-Neovascularization, Pathologic, pubmed-meshheading:12019161-Neovascularization, Physiologic, pubmed-meshheading:12019161-Rats, pubmed-meshheading:12019161-Rats, Sprague-Dawley, pubmed-meshheading:12019161-Stereoisomerism, pubmed-meshheading:12019161-Thymidine Phosphorylase, pubmed-meshheading:12019161-Tumor Cells, Cultured
pubmed:year
2002
pubmed:articleTitle
Suppression of thymidine phosphorylase-mediated angiogenesis and tumor growth by 2-deoxy-L-ribose.
pubmed:affiliation
Department of Cancer Chemotherapy, Institute for Cancer Research, Kagoshima University, Faculty of Medicine, Sakuragaoka 8-35-1, Kagoshima 890-8520, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't