Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2005-8-16
pubmed:abstractText
Recombinant human erythropoietin (rHuEPO) is widely used for correction of hemoglobin level in cancer patients. However, apart from hematopoiesis, rHuEPO reportedly has an effect on endothelial cells. We describe here how rHuEPOalpha can modulate tumor vasculature in human squamous cell (A431) and colorectal carcinoma (HT25) xenograft models. In vivo rHuEPO treatment of xenografts at human-equivalent dose significantly increased the proliferation index of the tumor-associated endothelial cells and the size of CD31-positive intratumoral blood vessels, whereas the pericyte coverage became fragmented. Moreover, rHuEPO administration resulted in decreased expression of vascular endothelial growth factor both by cancer cells and tumor stroma, measured by quantitative PCR. Due to the morphologic alterations in tumoral microvessels, DNA-binding agents (Hoechst and Doxorubicin) labeled significantly larger areas in the tumor mass. Furthermore, rHuEPO treatment led to a significantly improved efficacy of 5-fluorouracil (5-FU) chemotherapy in the case of both tumor xenografts. Meanwhile, rHuEPO had no effect on the in vitro proliferation of erythropoietin receptor-positive tumor cells, and did not interfere with the effects of 5-FU either. These data reveal a new effect of rHuEPO administration: remodeling tumoral microvessels, suppressing vascular endothelial growth factor expression, thereby augmenting antitumor effects of a cancer drug, 5-FU, even in erythropoietin receptor-positive human cancer xenografts.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7186-93
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:16103069-Animals, pubmed-meshheading:16103069-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:16103069-Carcinoma, Squamous Cell, pubmed-meshheading:16103069-Cell Line, Tumor, pubmed-meshheading:16103069-Colorectal Neoplasms, pubmed-meshheading:16103069-Drug Synergism, pubmed-meshheading:16103069-Erythropoietin, pubmed-meshheading:16103069-Female, pubmed-meshheading:16103069-Fluorouracil, pubmed-meshheading:16103069-Humans, pubmed-meshheading:16103069-Mice, pubmed-meshheading:16103069-Mice, SCID, pubmed-meshheading:16103069-Neovascularization, Pathologic, pubmed-meshheading:16103069-Pericytes, pubmed-meshheading:16103069-RNA, Messenger, pubmed-meshheading:16103069-Receptors, Erythropoietin, pubmed-meshheading:16103069-Recombinant Proteins, pubmed-meshheading:16103069-Xenograft Model Antitumor Assays
pubmed:year
2005
pubmed:articleTitle
Recombinant human erythropoietin alpha targets intratumoral blood vessels, improving chemotherapy in human xenograft models.
pubmed:affiliation
Department of Tumor Progression and Central Laboratory, National Institute of Oncology, Budapest, Hungary.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't