Linked Life Data

15363970

Source:http://linkedlifedata.com/resource/pubmed/id/15363970

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2004-9-14
pubmed:abstractText
Pancreatic adenocarcinoma is a leading cause of cancer death in the United States and represents a challenging chemotherapeutic problem. The pharmacological control of angiogenesis might represent a novel approach to the management of pancreas cancer, since the pathological development of vascular supply is a critical step for tumor growth and may affect its prognosis. In order to test this hypothesis, SU5416 ([3-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-1,3-dihydro-indol-2-one]) a selective inhibitor of the vascular endothelial growth factor receptor-2 tyrosine kinase, and gemcitabine (2', 2'-difluorodeoxycytidine) were tested on endothelial (HUVEC) and pancreatic tumor cells (MIA PaCa-2) in vitro and in vivo alone and in simultaneous association. SU5416 inhibited HUVEC cells stimulated to proliferate by vascular endothelial growth factor but not MIA PaCa-2 cells; the drug concentration that decreased cell growth by 50% (IC50) was 0.14 microM. Furthermore, SU5416 reduced the development of microvessels from placental explants (IC50, 0.23 microM). Gemcitabine inhibited the growth of both HUVEC and MIA PaCa-2 cells with an IC50 of 0.08 and 0.1 microM, respectively. A synergistic effect (combination index <1 and dose reduction index >1) on anti-proliferative and pro-apoptotic activity was calculated with the simultaneous combination of the two drugs on endothelial cells. A marked in vivo antitumor effect on MIA PaCa-2 xenografts was observed with SU5416 at a protracted schedules, as well as with gemcitabine; furthermore, the combination between the two drugs resulted in an almost complete suppression of tumor growth and relapse. In conclusion, the present results provide the evidence of an effective anti-endothelial/antitumor activity of protracted administration of SU5416 on human pancreas cancer xenografts, which is comparable with the one obtained by gemcitabine; moreover, the synergistic combination between these drugs on endothelial cells and the promising association in pancreatic cancer xenografts could be used in future studies and translated into the clinical setting.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
498
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9-18
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15363970-Angiogenesis Inhibitors, pubmed-meshheading:15363970-Animals, pubmed-meshheading:15363970-Antimetabolites, Antineoplastic, pubmed-meshheading:15363970-Apoptosis, pubmed-meshheading:15363970-Cell Division, pubmed-meshheading:15363970-Cell Line, pubmed-meshheading:15363970-Cell Line, Tumor, pubmed-meshheading:15363970-Deoxycytidine, pubmed-meshheading:15363970-Dose-Response Relationship, Drug, pubmed-meshheading:15363970-Drug Synergism, pubmed-meshheading:15363970-Endothelial Cells, pubmed-meshheading:15363970-Female, pubmed-meshheading:15363970-Humans, pubmed-meshheading:15363970-Immunohistochemistry, pubmed-meshheading:15363970-Indoles, pubmed-meshheading:15363970-Male, pubmed-meshheading:15363970-Mice, pubmed-meshheading:15363970-Mice, Nude, pubmed-meshheading:15363970-Neovascularization, Pathologic, pubmed-meshheading:15363970-Pancreatic Neoplasms, pubmed-meshheading:15363970-Placenta, pubmed-meshheading:15363970-Pregnancy, pubmed-meshheading:15363970-Protein Kinase Inhibitors, pubmed-meshheading:15363970-Pyrroles, pubmed-meshheading:15363970-Time Factors, pubmed-meshheading:15363970-Tissue Culture Techniques, pubmed-meshheading:15363970-Vascular Endothelial Growth Factor A, pubmed-meshheading:15363970-Vascular Endothelial Growth Factor Receptor-2, pubmed-meshheading:15363970-Xenograft Model Antitumor Assays
pubmed:year
2004
pubmed:articleTitle
Antiangiogenic versus cytotoxic therapeutic approaches to human pancreas cancer: an experimental study with a vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor and gemcitabine.
pubmed:affiliation
Division of Pharmacology and Chemotherapy, Department of Oncology, Transplants and Advanced Technologies in Medicine, University of Pisa, Via Roma, 55, I-56126 Pisa, Italy.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't