Flavio Curnis

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The clinical use of tumor necrosis factor alpha (TNF) as an anticancer drug is limited to local treatments because of its dose-limiting systemic toxicity. We show here that murine TNF fused with CNGRC peptide (NGR-TNF), an aminopeptidase N (CD13) ligand that targets activated blood vessels in tumors, is 12-15 times more efficient than murine TNF in(More)
The NGR peptide motif is an aminopeptidase N (CD13) ligand that targets angiogenic blood vessels. NGR-containing peptides have proven useful for delivering cytotoxic drugs, proapoptotic peptides, and tumor necrosis factor-alpha(TNF) to tumor vasculature. Given that CD13 is not only expressed in the angiogenic endothelium but also in other cell types, the(More)
Drug delivery and penetration into neoplastic cells distant from tumor vessels are critical for the effectiveness of solid-tumor chemotherapy. We have found that targeted delivery to tumor vessels of picogram doses of TNF-alpha (TNF), a cytokine able to alter endothelial barrier function and tumor interstitial pressure, enhances the penetration of(More)
Despite the impressive results obtained in animal models, the clinical use of tumor necrosis factor-alpha (TNF) as an anticancer drug is limited by severe toxicity. We have shown previously that targeted delivery of TNF to aminopeptidase N (CD13), a marker of angiogenic vessels, improved the therapeutic index of this cytokine in tumor-bearing mice. To(More)
Isoaspartate formation in extracellular matrix proteins, by aspartate isomerization or asparagine deamidation, is generally viewed as a degradation reaction occurring in vivo during tissue aging. For instance, non-enzymatic isoaspartate formation at RGD-integrin binding sites causes loss of cell adhesion sites, which in turn can be enzymatically "repaired"(More)
We have investigated the role of p55 and p75 tumor necrosis factor receptors 1 and 2 (TNFR1 and TNFR2, respectively) in TNF-induced alteration of endothelial permeability in vitro and in vivo. Stimulation of TNFR1 with an agonist antibody or a receptor-selective TNF mutein increased the flux of (125)I-albumin through endothelial cell monolayers. An(More)
Previous studies showed that chromogranin A (CgA), a glycoprotein stored and co-released with various hormones by neuroendocrine cells and neurons, can modulate cell adhesion. We have investigated the structure-activity relationships of CgA using fibroblasts and coronary artery smooth muscle cells in adhesion assays. A recombinant CgA fragment 1-78 and a(More)
A growing body of evidence suggests that peptides containing the Asn-Gly-Arg (NGR) motif can selectively recognize tumor neovasculature and can be used, therefore, for ligand-directed targeted delivery of various drugs and particles to tumors or to other tissues with an angiogenesis component. The neovasculature binding properties of these peptides rely on(More)
PURPOSE Subnanogram doses of NGR-tumor necrosis factor (TNF), a TNF-alpha derivative able to target tumor neovessels, can enhance the antitumor activity of doxorubicin and melphalan in murine models. We have examined the antitumor activity of NGR-TNF in combination with various chemotherapeutic drugs acting via different mechanisms, including, besides(More)
AIMS High chromogranin-A (CgA) levels were observed in patients with heart failure but its source remained uncertain. We evaluated whether CgA is produced by myocardium and might affect myocardial function. METHODS AND RESULTS We measured plasma CgA levels and performed immunohistochemistry with anti-CgA antibodies on myocardial biopsies in 40 patients(More)