A5040436989- Glycosylation and Glycoproteins Research
- Cell Adhesion Molecules Research
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Angiogenesis and VEGF in Cancer
- Cellular transport and secretion
- Cancer, Hypoxia, and Metabolism
- Retinoids in leukemia and cellular processes
- Cancer Research and Treatments
- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- Lipid Membrane Structure and Behavior
- Nanoplatforms for cancer theranostics
- Amino Acid Enzymes and Metabolism
- Neuropeptides and Animal Physiology
- Multiple Myeloma Research and Treatments
- Axon Guidance and Neuronal Signaling
- Biochemical and Structural Characterization
- Platelet Disorders and Treatments
- Nanoparticle-Based Drug Delivery
- Immune Cell Function and Interaction
- Bioactive natural compounds
- Biotin and Related Studies
- CAR-T cell therapy research
- Lung Cancer Research Studies
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2016-2025
Vita-Salute San Raffaele University
2016-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2016-2025
IRCCS Ospedale San Raffaele
2023
San Raffaele University of Rome
1996-2016
Molecular Oncology (United States)
2010
The San Raffaele Telethon Institute for Gene Therapy
2002-2008
University of Turin
1997
Platelet microparticles from patients with systemic sclerosis prompt endothelial cell activation, neutrophil recruitment, and lung fibrosis.
Cyclic and linear peptides containing the Asn-Gly-Arg (NGR) motif have proven useful for delivering various anti-tumor compounds viral particles to tumor vessels. We investigated role of cyclic constraints on structure tumor-homing properties NGR using necrosis factor-α (TNF) derivatives disulfide-bridged (CNGRC-TNF) (GNGRG-TNF) domains. Experiments carried out in animal models showed that both GNGRG CNGRC can target TNF tumors. However, activity CNGRC-TNF was >10-fold higher than GNGRG-TNF....
Abstract Purpose: Subnanogram doses of NGR-tumor necrosis factor (TNF), a TNF-α derivative able to target tumor neovessels, can enhance the antitumor activity doxorubicin and melphalan in murine models. We have examined NGR-TNF combination with various chemotherapeutic drugs acting via different mechanisms, including, besides melphalan, cisplatin, paclitaxel, gemcitabine. Experimental Design: Chemotherapeutic were tested alone (0.1 ng) lymphoma, fibrosarcoma, mammary adenocarcinoma Different...
Despite the impressive results obtained in animal models, clinical use of tumor necrosis factor-alpha (TNF) as an anticancer drug is limited by severe toxicity. We have shown previously that targeted delivery TNF to aminopeptidase N (CD13), a marker angiogenic vessels, improved therapeutic index this cytokine tumor-bearing mice. To assess whether vascular-targeting approach could be extended other markers blood work, we fused with ACDCRGDCFCG peptide, ligand alpha(V) integrins recombinant...
Abstract Because of its immunomodulatory and anticancer activities, IFNγ has been used as an drug in several clinical studies, unfortunately with modest results. Attempts to increase the response by increasing dose or repeated continuous injection often resulted lower efficacy, likely due counterregulatory effects. We show here that targeted delivery low doses CD13, a marker angiogenic vessels, can overcome major mechanisms delay tumor growth two murine models respond poorly IFNγ. Tumor...
Various NGR-containing peptides have been exploited for targeted delivery of drugs to CD13-positive tumor neovasculature. Recent studies shown that compounds containing this motif can rapidly deamidate and generate isoaspartate-glycine-arginine (isoDGR), a ligand alphavbeta3-integrin be also drug tumors. We investigated the role NGR isoDGR peptide scaffolds on their biochemical biological properties. Peptides cyclic CNGRC sequence could bind endothelial cells more efficiently than those...
Abstract Colloidal gold (Au), a well-tolerated nanomaterial, is currently exploited for several applications in nanomedicine. We show that nanoparticles tagged with novel tumor-homing peptide containing Asn-Gly-Arg (NGR), ligand of CD13 expressed by the tumor neovasculature, can be as carriers cytokine delivery to tumors. Biochemical and functional studies showed NGR molecular scaffold/linker used functionalization critical recognition. Using fibrosarcoma-bearing mice, NGR-tagged nanodrugs...
Abstract Background The αvβ6- and αvβ8-integrins, two cell-adhesion receptors upregulated in many solid tumors, can promote the activation of transforming growth factor-β (TGFβ), a potent immunosuppressive cytokine, by interacting with RGD sequence latency-associated peptide (LAP)/TGFβ complex. We have previously described chromogranin A-derived peptide, called “peptide 5a ”, which recognizes RGD-binding site both αvβ6 αvβ8 high affinity selectivity, efficiently accumulates or αvβ8-positive...
Abstract Asparagine deamidation in peptides or fibronectin fragments containing the asparagine-glycine-arginine sequence generates isoaspartate-glycine-arginine (isoDGR), a new αvβ3 integrin-binding motif. Because is expressed angiogenic vessels, we hypothesized that isoDGR-containing could be exploited as ligands for targeted delivery of drugs to tumor neovasculature. We found cyclic CisoDGRC peptide coupled fluorescent nanoparticles (quantum dots) bind integrin and colocalize with...
Although several functions have been suggested for chromogranin A, a glycoprotein secreted by many neuroendocrine cells, the physiological role of this protein and its proteolytic fragments has not established. We found that mixtures A can inhibit fibroblast adhesion. The anti-adhesive activity was converted into pro-adhesive limited trypsin treatment. Pro-adhesive effects were observed also with recombinant N-terminal corresponding to residues 1-78 1-115 synthetic peptide encompassing 7-57....
Previous studies showed that chromogranin A (CgA), a glycoprotein stored and co-released with various hormones by neuroendocrine cells neurons, can modulate cell adhesion. We have investigated the structure-activity relationships of CgA using fibroblasts coronary artery smooth muscle in adhesion assays. recombinant fragment 1–78 peptide 7–57 containing reduced alkylated cysteines (Cys17 Cys38) induced after adsorption onto solid phases at 50–100 nm. Peptides lacking disulfide loop region,...
NGR-TNF is a derivative of TNF-alpha, consisting TNF fused to CNGRCG, tumor vasculature-targeting peptide. Previous studies showed that can exert synergistic antitumor effects with doxorubicin and other chemotherapeutic drugs in murine models. In this study, we have investigated the role endogenous IFN-gamma on activity combination doxorubicin. The study was carried out using B16F1 melanoma TS/A mammary adenocarcinoma implanted subcutaneously (a) immunocompetent mice, (b) athymic nude (c)...
A new cyclic peptide containing the isoDGR motif that, after coupling to albumin, selectively binds αvβ3, an integrin overexpressed in tumor vasculature. IsoDGR-tagged albumin vessels and can be exploited as a carrier for preparation of vasculature-selective nanomedicines, such gold nanoparticles (Au) carrying necrosis factor α (TNF), potent vascular damaging agent.
Abstract The clinical use of interleukin‐12 (IL12), a cytokine endowed with potent immunotherapeutic anticancer activity, is limited by systemic toxicity. hypothesis addressed that gold nanoparticles tagged tumor‐homing peptide containing isoDGR, an αvβ3‐integrin binding motif, can be exploited for delivering IL12 to tumors and improving its therapeutic index. To this aim, nanospheres are functionalized the head‐to‐tail cyclized‐peptide CGisoDGRG (Iso1) murine IL12. resulting nanodrug...
The clinical use of doxorubicin (Doxo), a widely used anticancer chemotherapeutic drug, is limited by dose-dependent cardiotoxicity. We have investigated whether chromogranin A (CgA), cardioregulatory protein released in the blood neuroendocrine system and heart itself, may contribute to regulation cardiotoxic antitumor activities Doxo. effects physiologic dose full-length recombinant CgA on Doxo-induced cardiotoxicity activity were rats using vivo ex models murine melanoma, fibrosarcoma,...
Angiogenesis has been postulated to be critical for the pathogenesis of multiple myeloma, a neoplastic disease characterized by abnormal proliferation malignant plasma cells in bone marrow (BM). Cleavage N- and C-terminal regions circulating chromogranin A (CgA, CHGA), classically an antiangiogenic protein, can activate latent proangiogenic sites, respectively. In this study, we investigated distribution CgA-derived polypeptides myeloma patients subsequent implications progression. We show...
Vasostatins (VS) are vasoinhibitory peptides derived from the N‐terminal domain of chromogranin A, a secretory protein present in electron‐dense granules many neuroendocrine cells. In this work we describe method for production Escherichia coli large amounts recombinant vasostatins, corresponding to A residues 1–78 (VS‐I), and 1–115 (VS‐2), use these materials structure characterisation. The masses both products were close expected values, by SDS/PAGE mass spectrometry analysis. However,...
Abstract High-dose endothelial-monocyte activating polypeptide II (EMAP-II), a tumor-derived antiangiogenic cytokine, can sensitize tumor vasculature to the damaging activity of high-dose necrosis factor (TNF)-α. However, this combination cannot be used for systemic treatment patients because prohibitive toxicity. We have found that limitation overcome by combining TNF-targeting strategy with use ultra low-dose EMAP-II. Coadministration 0.1 ng EMAP-II and CNGRCG-TNF (NGR-TNF), peptide-TNF...
NGR (asparagine-glycine-arginine) is a tumor vasculature-homing peptide motif widely used for the functionalization of drugs, nanomaterials and imaging compounds cancer treatment diagnosis. Unfortunately, this has strong propensity to undergo rapid deamidation. This reaction, which converts into isoDGR, associated with receptor switching from CD13 integrins, potentially important manufacturing, pharmacological toxicological implications. It found that glycine N-methylation NGR-tagged...
Abstract Background Gold nanospheres tagged with peptides containing iso DGR ( Asp-Gly-Arg), an αvβ3 integrin binding motif, represent efficient carriers for delivering pro-inflammatory cytokines to the tumor vasculature. We prepared bi- or trifunctional nanoparticles bearing necrosis factor-α (TNF) and/or interleukin-12 (IL12) plus a peptide isoDGR, and we tested their anti-cancer effects, alone in combination doxorubicin, tumor-bearing mice. Results In vitro biochemical studies showed that...
Chromogranin A is a protein contained in the secretory granules of many neuroendocrine cells. The linear antigenic sites human chromogranin were studied by examining cross‐reaction polyclonal and monoclonal anti‐chromogranin antibodies with native synthetic peptides encompassing most sequence. residues 1–20, 47–67, 107–158, 254–297, 331–375, 395–419 found to be poorly or not antigenic, while 25–46, 163–210, 231–253, 298–314 68–106, 222–230, 315–330, 376–394 contain weak strong sites,...
Abstract NGR-TNF is a derivative of TNF-α that targets tumor blood vessels and enhances penetration chemotherapeutic drugs. Because this property, being tested in combination with chemotherapy various phase II III clinical trials. Here we report chromogranin A (CgA), protein present variable amounts the normal subjects cancer patients, inhibits synergism doxorubicin melphalan mouse models lymphoma melanoma. Pathophysiologically relevant levels circulating CgA blocked NGR-TNF–induced drug by...