National Institute of Tumors

Napoli, Italy

National Institute of Tumors

Napoli, Italy
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D'Esposito V.,University of Naples Federico II | Liguoro D.,University of Naples Federico II | Ambrosio M.R.,University of Naples Federico II | Collina F.,National Institute of Tumors | And 12 more authors.
Oncotarget | Year: 2016

Growing evidence indicates that adiposity is associated with raised cancer incidence, morbidity and mortality. In a subset of tumors, cancer cell growth and/ or metastasis predominantly occur in adipocyte-rich microenvironment. Indeed, adipocytes represent the most abundant cell types surrounding breast cancer cells. We have studied the mechanisms by which peritumoral human adipose tissue contributes to Triple Negative Breast Cancer (TNBC) cell invasiveness and dissemination. Co-culture with human adipocytes enhanced MDA-MB231 cancer cell invasiveness. Adipocytes cultured in high glucose were 2-fold more active in promoting cell invasion and motility compared to those cultured in low glucose. This effect is induced, at least in part, by the CC-chemokine ligand 5 (CCL5). Indeed, CCL5 inhibition by specific peptides and antibodies reduced adipocyte-induced breast cancer cell migration and invasion. CCL5 immuno-detection in peritumoral adipose tissue of women with TNBC correlated with lymph node (p-value = 0.04) and distant metastases (p-value = 0.001). A positive trend was also observed between CCL5 expression and glycaemia. Finally, Kaplan-Meier curves showed a negative correlation between CCL5 staining in the peritumoral adipose tissue and overall survival of patients (p-value = 0.039). Thus, inhibition of CCL5 in adipose microenvironment may represent a novel approach for the therapy of highly malignant TNBC.

Burastero S.E.,San Raffaele Scientific Institute | Frigerio B.,National Institute of Tumors | Lopalco L.,San Raffaele Scientific Institute | Sironi F.,San Raffaele Scientific Institute | And 7 more authors.
PLoS ONE | Year: 2011

To penetrate susceptible cells, HIV-1 sequentially interacts with two highly conserved cellular receptors, CD4 and a chemokine receptor like CCR5 or CXCR4. Monoclonal antibodies (MAbs) directed against such receptors are currently under clinical investigation as potential preventive or therapeutic agents. We immunized Balb/c mice with molecular complexes of the native, trimeric HIV-1 envelope (Env) bound to a soluble form of the human CD4 receptor. Sera from immunized mice were found to contain gp120-CD4 complex-enhanced antibodies and showed broad-spectrum HIV-1-inhibitory activity. A proportion of MAbs derived from these mice preferentially recognized complex-enhanced epitopes. In particular, a CD4-specific MAb designated DB81 (IgG1K) was found to preferentially bind to a complex-enhanced epitope on the D2 domain of human CD4. MAb DB81 also recognized chimpanzee CD4, but not baboon or macaque CD4, which exhibit sequence divergence in the D2 domain. Functionally, MAb DB81 displayed broad HIV-1-inhibitory activity, but it did not exert suppressive effects on T-cell activation in vitro. The variable regions of the heavy and light chains of MAb DB81 were sequenced. Due to its broad-spectrum anti-HIV-1 activity and lack of immunosuppressive effects, a humanized derivative of MAb DB81 could provide a useful complement to current preventive or therapeutic strategies against HIV-1. © 2011 Burastero et al.

Berger M.,Regina Margherita Childrens Hospital | Grignani G.,Institute for Cancer Research and Treatment | Giostra A.,Mauriziano Umberto 1 Hospital | Ferrari S.,Rizzoli Orthopaedic Institute | And 10 more authors.
Annals of Oncology | Year: 2012

Background: Bone metastatic patients with osteosarcoma have a very poor prognosis. Targeted radiation therapy has been pursued as a valid alternative. The primary end point of this study was progression-free survival (PFS) at 4 months. Patients and methods: Twenty-two osteosarcoma patients were treated with Samarium-153 ethylenediaminetetramethylene phosphonic acid (. 153Sm-EDTMP) at various dosages. Administered activities ranged from 150 (3 mCi/kg) to 1140 MBq/kg (30 mCi/kg). Autologous hematopoietic stem cell infusion was carried out on day 14 after the . 153Sm-EDTMP infusion. Results: The median PFS was 61 days (18-436 days) and the median overall survival (OS) was 189 days (31-1175 days). PFS and OS for the entire patient population were 32% [95% confidence interval (CI) 16-50] and 76% (95% CI 52-89) at 4 months, respectively. No statistical differences emerged according to . 153Sm-EDTMP administered or 24-h retained activity. One-month pain palliation was only observed in a minority of subjects and in none at 4 months. Conclusions: Based on our series, the PFS is dramatically short even when higher activity of . 153Sm-EDTMP is administered. This would mean that, even at high level, . 153Sm-EDTMP is itself ineffective against relapsed osteosarcoma or the residual activity is too low to be active on these particular subsets of patients. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Perozziello G.,University of Catanzaro | La Rocca R.,University of Catanzaro | La Rocca R.,Italian Institute of Technology | Cojoc G.,University of Catanzaro | And 14 more authors.
Small | Year: 2012

This study aims to adoptively reduce the major histocompatibility complex class I (MHC-I) molecule surface expression of cancer cells by exposure to microfluid shear stress and a monoclonal antibody. A microfluidic system is developed and tumor cells are injected at different flow rates. The bottom surface of the microfluidic system is biofunctionalized with antibodies (W6/32) specific for the MHC-I molecules with a simple method based on microfluidic protocols. The antibodies promote binding between the bottom surface and the MHC-I molecules on the tumor cell membrane. The cells are injected at an optimized flow rate, then roll on the bottom surface and are subjected to shear stress. The stress is localized and enhanced on the part of the membrane where MHC-I proteins are expressed, since they stick to the antibodies of the system. The localized stress allows a stripping effect and consequent reduction of the MHC-I expression. It is shown that it is possible to specifically treat and recover eukaryotic cells without damaging the biological samples. MHC-I molecule expression on treated and control cell surfaces is measured on tumor and healthy cells. After the cell rolling treatment a clear reduction of MHC-I levels on the tumor cell membrane is observed, whereas no changes are observed on healthy cells (monocytes). The MHC-I reduction is investigated and the possibility that the developed system could induce a loss of these molecules from the tumor cell surface is addressed. The percentage of living tumor cells (viability) that remain after the treatment is measured. The changes induced by the microfluidic system are analyzed by fluorescence-activated cell sorting and confocal microscopy. Cytotoxicity tests show a relevant increased susceptibility of natural killer (NK) cells on microchip-treated tumor cells. The bottom surface of a microfluidic system is biofunctionalized with antibodies specific for major histocompatibility complex class I (MHC-I) molecules. Injected cells roll on this surface and are subjected to shear stress. A reduction of MHC-I expression on tumor cell membranes is observed, as well as an increase in the recognition of tumor target cells by natural killer cells. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Viggiano E.,The Second University of Naples | Passavanti M.B.,The Second University of Naples | Pace M.C.,The Second University of Naples | Sansone P.,The Second University of Naples | And 8 more authors.
Journal of Cellular Physiology | Year: 2012

Glutamine (gln) is the most abundant free amino acid in the blood. It is involved in important metabolic and biochemical processes, like cell proliferation and oxidative stress. Previous studies have demonstrated that gln concentration in human plasma decreases in several conditions such as sepsis, ischemia-reperfusion, trauma, major surgery and burn. The aim of the present work was to compare the acute effects of different types of surgical interventions and of anesthetization on blood gln concentration. Plasma samples from 88 subjects (30 males and 58 females) were collected before and after major or minor surgery and the gln concentration was analyzed with high-performance liquid chromatography. The results showed that plasma gln concentration after surgery was lower than pre-surgery values and that in major surgery the decrease of gln was higher than in minor surgery. No significant effect was shown for sex or type of anesthesia. These results demonstrate the importance of a gln supplementation before a surgical intervention and show that the amount of gln supplementation should also be adjusted based on the type of surgery. © 2011 Wiley Periodicals, Inc.

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