Linked Life Data

18575762

Source:http://linkedlifedata.com/resource/pubmed/id/18575762

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-6-25
pubmed:abstractText
Overexpression of the transcription factor Sp1 may play a critical role in human gastric cancer angiogenesis. In the present studies, we determined whether targeting Sp1 has a therapeutic benefit. Treatment with mithramycin A (MIT) suppressed the expression of Sp1 and its downstream target genes in both human gastric cancer cell culture and tumors growing in nude mice. The molecular responses were accompanied by a significant inhibition of gastric cancer angiogenesis, growth and metastasis. Conversely, treatment with bevacizumab (BVZ), a neutralizing antibody against VEGF A, suppressed human gastric cancer growth in nude mice in a dose-dependent manner. Gene expression analyses revealed that treatment with low dose of BVZ substantially upregulated the expression of Sp1 and its downstream target genes, including VEGF and EGFR, in tumor tissues, whereas it did not have this effect on gastric cancer cells in culture. Combined treatment with BVZ and MIT produced synergistic tumor suppression, which was consistent with suppression of the expression of Sp1 and its downstream target genes. Thus, treatment with BVZ may block VEGF function but activate the pathway of its expression via positive feedback. Collectively, Sp1 is an important regulator of the expression of multiple angiogenic factors and functional status of Sp1 signaling pathway may profoundly affect the angiogenic phenotype of and effectiveness of antiangiogenic strategies for human gastric cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1019-6439
pubmed:author
pubmed:issnType
Print
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
161-7
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:18575762-Angiogenesis Inhibitors, pubmed-meshheading:18575762-Animals, pubmed-meshheading:18575762-Antibodies, Monoclonal, pubmed-meshheading:18575762-Antibodies, Monoclonal, Humanized, pubmed-meshheading:18575762-Cell Line, Tumor, pubmed-meshheading:18575762-Disease Models, Animal, pubmed-meshheading:18575762-Drug Synergism, pubmed-meshheading:18575762-Female, pubmed-meshheading:18575762-Humans, pubmed-meshheading:18575762-Mice, pubmed-meshheading:18575762-Mice, Nude, pubmed-meshheading:18575762-Neoplasm Metastasis, pubmed-meshheading:18575762-Neovascularization, Pathologic, pubmed-meshheading:18575762-Plicamycin, pubmed-meshheading:18575762-Sp1 Transcription Factor, pubmed-meshheading:18575762-Stomach Neoplasms, pubmed-meshheading:18575762-Transcription, Genetic, pubmed-meshheading:18575762-Vascular Endothelial Growth Factor A
pubmed:year
2008
pubmed:articleTitle
Targeted inhibition of Sp1-mediated transcription for antiangiogenic therapy of metastatic human gastric cancer in orthotopic nude mouse models.
pubmed:affiliation
The Key Laboratory of Antibody Technology of State Ministry of Health, Nanjing Medical University, Nanjing 210029, P.R. China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural