Linked Life Data

15466213

Source:http://linkedlifedata.com/resource/pubmed/id/15466213

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2004-10-6
pubmed:abstractText
NGR-TNF is a derivative of TNF-alpha, consisting of TNF fused to CNGRCG, a tumor vasculature-targeting peptide. Previous studies showed that NGR-TNF can exert synergistic antitumor effects with doxorubicin and with other chemotherapeutic drugs in murine models. In this study, we have investigated the role of endogenous IFN-gamma on the antitumor activity of NGR-TNF in combination with doxorubicin. The study was carried out using murine B16F1 melanoma and TS/A mammary adenocarcinoma implanted subcutaneously in (a) immunocompetent mice, (b) athymic nude mice, and (c) IFN-gamma-knockout mice. Synergism between NGR-TNF and doxorubicin was observed in immunocompetent mice but not in nude or IFN-gamma-knockout mice. Preadministration of a neutralizing anti-IFN-gamma antibody to immunocompetent mice inhibited the NGR-TNF/doxorubicin synergism, whereas administration of IFN-gamma to nude and to IFN-gamma-knockout mice restored the synergistic activity. The synergism in nude mice was restored also by transfecting tumor cells with the IFN-gamma cDNA. Administration of NGR-TNF in combination with IFN-gamma to nude mice, but not of NGR-TNF alone, doubled the penetration of doxorubicin in TS/A tumors. These findings point to a crucial role for locally produced IFN-gamma in tumor vascular targeting with NGR-TNF and doxorubicin. Finally, addition of IFN-gamma to the treatment of immunocompetent mice with NGR-TNF/doxorubicin induced only modest improvement in response, suggesting that exogenous IFN-gamma can improve the therapeutic activity of these drugs only in case of suboptimal production of endogenous IFN-gamma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
64
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7150-5
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15466213-Adenocarcinoma, pubmed-meshheading:15466213-Animals, pubmed-meshheading:15466213-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:15466213-Cell Line, Tumor, pubmed-meshheading:15466213-Doxorubicin, pubmed-meshheading:15466213-Drug Synergism, pubmed-meshheading:15466213-Female, pubmed-meshheading:15466213-Interferon-gamma, pubmed-meshheading:15466213-Mammary Neoplasms, Experimental, pubmed-meshheading:15466213-Melanoma, Experimental, pubmed-meshheading:15466213-Mice, pubmed-meshheading:15466213-Mice, Inbred BALB C, pubmed-meshheading:15466213-Mice, Knockout, pubmed-meshheading:15466213-Mice, Nude, pubmed-meshheading:15466213-Neovascularization, Pathologic, pubmed-meshheading:15466213-T-Lymphocytes, pubmed-meshheading:15466213-Tumor Necrosis Factor-alpha
pubmed:year
2004
pubmed:articleTitle
Crucial role for interferon gamma in the synergism between tumor vasculature-targeted tumor necrosis factor alpha (NGR-TNF) and doxorubicin.
pubmed:affiliation
Department of Biological and Technological Research and Cancer Immunotherapy and Gene Therapy Program, San Raffaele H Scientific Institute, Milan, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't