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3. Cardiac arrhythmia catheter ablation procedures guided by x-ray imaging: N-acetylcysteine protection against radiation-induced cellular damage (CARAPACE study): study design

Author

Catto, Valentina, Stronati, Giulia, Porro, Benedetta, Fiorelli, Susanna, Ricci, Veronica, Vavassori, Chiara, Russo, Eleonora, Guerra, Federico, Gasperetti, Alessio, Ribatti, Valentina, Sicuso, Rita, Dello Russo, Antonio, Veglia, Fabrizio, Tondo, Claudio, Cavalca, Viviana, Colombo, Gualtiero I., Tremoli, Elena, and Casella, Michela

Published
2021
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4. Digital PCR for high sensitivity viral detection in false-negative SARS-CoV-2 patients

Author

Poggio, Paolo, Songia, Paola, Vavassori, Chiara, Ricci, Veronica, Banfi, Cristina, Barbieri, Silvia Stella, Garoffolo, Gloria, Myasoedova, Veronika A., Piacentini, Luca, Raucci, Angela, Scopece, Alessandro, Sommariva, Elena, Vinci, Maria Cristina, Carcione, Davide, Biondi, Maria Luisa, Mancini, Maria Elisabetta, Formenti, Alberto, Andreini, Daniele, Assanelli, Emilio M., Agostoni, Piergiuseppe, Camera, Marina, Colombo, Gualtiero I., and Pesce, Maurizio

Published
2021
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6. Impact of Sacubitril/Valsartan on Circulating microRNA in Patients with Heart Failure

Author

Brioschi, M, D'Alessandra, Y, Mapelli, M, Mattavelli, I, Salvioni, E, Eligini, S, Mallia, A, Ricci, V, Gianazza, E, Ghilardi, S, Agostoni, P, Banfi, C, Brioschi, Maura, D'Alessandra, Yuri, Mapelli, Massimo, Mattavelli, Irene, Salvioni, Elisabetta, Eligini, Sonia, Mallia, Alice, Ricci, Veronica, Gianazza, Erica, Ghilardi, Stefania, Agostoni, Piergiuseppe, Banfi, Cristina, Brioschi, M, D'Alessandra, Y, Mapelli, M, Mattavelli, I, Salvioni, E, Eligini, S, Mallia, A, Ricci, V, Gianazza, E, Ghilardi, S, Agostoni, P, Banfi, C, Brioschi, Maura, D'Alessandra, Yuri, Mapelli, Massimo, Mattavelli, Irene, Salvioni, Elisabetta, Eligini, Sonia, Mallia, Alice, Ricci, Veronica, Gianazza, Erica, Ghilardi, Stefania, Agostoni, Piergiuseppe, and Banfi, Cristina

Abstract

Sacubitril/Valsartan, used for the treatment of heart failure (HF), is a combination of two drugs, an angiotensin receptor inhibitor, and a neprilysin inhibitor, which activates vasoactive peptides. Even though its beneficial effects on cardiac functions have been demonstrated, the mechanisms underpinning these effects remain poorly understood. To achieve more mechanistic insights, we analyzed the profiles of circulating miRNAs in plasma from patients with stable HF with reduced ejection function (HFrEF) and treated with Sacubitril/Valsartan for six months. miRNAs are short (22–24 nt) non-coding RNAs, which are not only emerging as sensitive and stable biomarkers for various diseases but also participate in the regulation of several biological processes. We found that in patients with high levels of miRNAs, specifically miR-29b-3p, miR-221-3p, and miR-503-5p, Sacubitril/Valsartan significantly reduced their levels at follow-up. We also found a significant negative correlation of miR-29b-3p, miR-221-3p, and miR-503-5p with VO2 at peak exercise, whose levels decrease with HF severity. Furthermore, from a functional point of view, miR-29b-3p, miR-221-3p, and miR-503-5p all target Phosphoinositide-3-Kinase Regulatory Subunit 1, which encodes regulatory subunit 1 of phosphoinositide-3-kinase. Our findings support that an additional mechanism through which Sacubitril/Valsartan exerts its functions is the modulation of miRNAs with potentially relevant roles in HFrEF pathophysiology.

Published
2023

7. Impact of Sacubitril/Valsartan on Circulating microRNA in Patients with Heart Failure

Author

Brioschi, Maura, primary, D’Alessandra, Yuri, additional, Mapelli, Massimo, additional, Mattavelli, Irene, additional, Salvioni, Elisabetta, additional, Eligini, Sonia, additional, Mallia, Alice, additional, Ricci, Veronica, additional, Gianazza, Erica, additional, Ghilardi, Stefania, additional, Agostoni, Piergiuseppe, additional, and Banfi, Cristina, additional

Published
2023
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8. Inhibition of SARS-CoV-2 3CLpro by chemically modified tyrosinase from Agaricus bisporusElectronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d4md00289j

Author

Aguilera-Rodriguez, David, Ortega-Alarcon, David, Vazquez-Calvo, Angela, Ricci, Veronica, Abian, Olga, Velazquez-Campoy, Adrian, Alcami, Antonio, and Palomo, Jose M.

Abstract

Antiviral compounds are crucial to controlling the SARS-CoV-2 pandemic. Approved drugs have been tested for their efficacy against COVID-19, and new pharmaceuticals are being developed as a complementary tool to vaccines. In this work, a cheap and fast purification method for natural tyrosinase from Agaricus bisporus(AbTyr) fresh mushrooms was developed to evaluate the potential of this enzyme as a therapeutic protein viathe inhibition of SARS-CoV-2 3CLpro protease activity in vitro. AbTyr showed a mild inhibition of 3CLpro. Thus, different variants of this protein were synthesized through chemical modifications, covalently binding different tailor-made glycans and peptides to the amino terminal groups of the protein. These new tyrosinase conjugates were purified and characterized through circular dichroism and fluorescence spectroscopy analyses, and their stability was evaluated under different conditions. Subsequently, all these tyrosinase conjugates were tested for 3CLpro protease inhibition. From them, the conjugate between tyrosinase and a dextran-aspartic acid (6 kDa) polymer showed the highest inhibition, with an IC50of 2.5 μg ml−1and IC90of 5 μg ml−1, with no cytotoxicity activity by polymer insertion. Finally, SARS-CoV-2 virus infection was studied. It was found that this new AbTyr-Dext6000 protein showed an 80% decrease in viral load. These results show the capacity of these tyrosinase bioconjugates as potential therapeutic proteins, opening the possibility of extension and applicability against other different viruses.

Published
2024
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9. Phase I trial of thymidylate synthase poly-epitope peptide (TSPP) vaccine in advanced cancer patients

Author

Cusi, Maria Grazia, Botta, Cirino, Pastina, Pierpaolo, Rossetti, Maria Grazia, Dreassi, Elena, Guidelli, Giacomo Maria, Fioravanti, Antonella, Martino, Elodia Claudia, Gandolfo, Claudia, Pagliuchi, Marco, Basile, Assunta, Carbone, Salvatore Francesco, Ricci, Veronica, Micheli, Lucia, Tassone, Pierfrancesco, Tagliaferri, Pierosandro, Pirtoli, Luigi, and Correale, Pierpaolo

Published
2015
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10. Effects of changing dietary habits on the fecal microbiome as an innovative approach for the development of integrated strategies of prevention and control of global cardiovascular risk in the Salerno area.

Author

Ricci, Veronica and Ricci, Veronica

Abstract

According to the World Health Organization, coronary artery disease (CAD) is the leading cause of morbidity and mortality in the world with an estimated 17.9 million deaths each year. Several risk factors are involved in the onset and progression of this disease and among them, in recent years, dietary habits and gut microbiota composition have been shown to have a relevant impact. There are many scientific evidences showing the protective role of the Mediterranean diet (MD) in cardiovascular disease especially in CAD primary prevention while less is recognized in secondary prevention. Moreover, alterations in the gut microbiota have been reported as factors responsible for several diseases. Because the mechanisms underlying the protective role of MD have not been fully elucidated, recent attention has focused on the modulation of the gut microbiota by MD in a "protective direction" for the cardiovascular system. Aim: The main aim of this study was to improve the knowledge of the mechanisms underlying the beneficial role of MD on the cardiovascular system. In particular, we sought to elucidate the relationship between this dietary pattern and the gut microbiota in CAD patients. Subsequently, in order to carry out a technological transfer from the “Centro Cardiologico Monzino” in Milan to the Check-up Center in Salerno, we conducted the same analysis on a group of healthy subjects or in primary prevention for CVD residing in the Salerno area, who presented a high adherence to DM already at the baseline. Finally, we preliminarily studied the effects of DM on the whole blood transcriptome in CAD patients. Materials and methods: This study is included in a parallel-group, randomized, open-label, interventional trial to assess the effects of the MD compared to a low-fat diet (LFD) on CAD patients. 103 CAD patients have been enrolled and randomized into the two groups (MD vs LFD). Sequencing experiments were performed in order to evaluate diets effects on microbiota compo

Published
2021

14. Differential Role of Circulating microRNAs to Track Progression and Pre-Symptomatic Stage of Chronic Heart Failure: A Pilot Study

Author

D’Alessandra, Yuri, primary, Chiesa, Mattia, additional, Carena, Maria Cristina, additional, Beltrami, Antonio Paolo, additional, Rizzo, Paola, additional, Buzzetti, Marta, additional, Ricci, Veronica, additional, Ferrari, Roberto, additional, Fucili, Alessandro, additional, Livi, Ugolino, additional, Aleksova, Aneta, additional, Pompilio, Giulio, additional, and Colombo, Gualtiero I., additional

Published
2020
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17. Cardiac arrhythmia catheter ablation procedures guided by x-ray imaging: N-acetylcysteine protection against radiation-induced cellular damage (CARAPACE study): study design

Author

Catto, Valentina, primary, Stronati, Giulia, additional, Porro, Benedetta, additional, Fiorelli, Susanna, additional, Ricci, Veronica, additional, Vavassori, Chiara, additional, Russo, Eleonora, additional, Guerra, Federico, additional, Gasperetti, Alessio, additional, Ribatti, Valentina, additional, Sicuso, Rita, additional, Dello Russo, Antonio, additional, Veglia, Fabrizio, additional, Tondo, Claudio, additional, Cavalca, Viviana, additional, Colombo, Gualtiero I., additional, Tremoli, Elena, additional, and Casella, Michela, additional

Published
2020
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18. Circulating MicroRNAs as Potential Predictors of Anthracycline-Induced Troponin Elevation in Breast Cancer Patients: Diverging Effects of Doxorubicin and Epirubicin

Author

Gioffré, Sonia, primary, Chiesa, Mattia, additional, Cardinale, Daniela Maria, additional, Ricci, Veronica, additional, Vavassori, Chiara, additional, Cipolla, Carlo Maria, additional, Masson, Serge, additional, Sandri, Maria Teresa, additional, Salvatici, Michela, additional, Ciceri, Fabio, additional, Latini, Roberto, additional, Staszewsky, Lidia Irene, additional, Pompilio, Giulio, additional, Colombo, Gualtiero I., additional, and D’Alessandra, Yuri, additional

Published
2020
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19. Anti-cancer activity of dose-fractioned mPE +/− bevacizumab regimen is paralleled by immune-modulation in advanced squamous NSLC patients

Author

Pastina, Pierpaolo, primary, Nardone, Valerio, additional, Croci, Stefania, additional, Battaglia, Giuseppe, additional, Vanni, Francesca, additional, Bellan, Cristiana, additional, Barbarino, Marcella, additional, Ricci, Veronica, additional, Costantini, Susan, additional, Capone, Francesca, additional, Botta, Cirino, additional, Zarone, Mayra Rachele, additional, Misso, Gabriella, additional, Boccellino, Mariarosaria, additional, Caraglia, Michele, additional, Giordano, Antonio, additional, Paladini, Piero, additional, Tassone, Pierfrancesco, additional, Tagliaferri, Pierosandro, additional, Cusi, Maria Grazia, additional, Pirtoli, Luigi, additional, and Correale, Pierpaolo, additional

Published
2017
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20. Radiotherapy prolongs the survival of advanced non-small-cell lung cancer patients undergone to an immune-modulating treatment with dose-fractioned cisplatin and metronomic etoposide and bevacizumab (mPEBev)

Author

Pastina, Pierpaolo, primary, Nardone, Valerio, additional, Botta, Cirino, additional, Croci, Stefania, additional, Tini, Paolo, additional, Battaglia, Giuseppe, additional, Ricci, Veronica, additional, Cusi, Maria Grazia, additional, Gandolfo, Claudia, additional, Misso, Gabriella, additional, Zappavigna, Silvia, additional, Caraglia, Michele, additional, Giordano, Antonio, additional, Aldinucci, Donatella, additional, Tassone, Pierfrancesco, additional, Tagliaferri, Pierosandro, additional, Pirtoli, Luigi, additional, and Correale, Pierpaolo, additional

Published
2017
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21. P2.03a-053 Immuno-Inflammatory Markers in Advanced NSCLC Patients Undergone Fractioned Cisplatin, Oral Etoposide and Bevacizumab

Author

Pastina, Pierpaolo, primary, Nardone, Valerio, additional, Giuseppe, Battaglia, additional, Botta, Cirino, additional, Tini, Paolo, additional, Bellan, Cristiana, additional, Ricci, Veronica, additional, Barbarino, Marcella, additional, Croci, Stefania, additional, Caraglia, Michele, additional, Giordano, Antonio, additional, Cusi, Maria Grazia, additional, Pirtoli, Luigi, additional, and Correale, Pierpaolo, additional

Published
2017
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22. P2.05-057 Baseline Inflammatory and Immunological Profile Predict the Survival of NSCLC Patients Undergone Palliative Radiotherapy

Author

Pastina, Pierpaolo, primary, Nardone, Valerio, additional, Tini, Paolo, additional, Battaglia, Giuseppe, additional, Croci, Stefania, additional, Botta, Cirino, additional, Bellan, Cristiana, additional, Barbarino, Marcella, additional, Ricci, Veronica, additional, Caraglia, Michele, additional, Giordano, Antonio, additional, Tagliaferri, Pierosandro, additional, Pierfrancesco, Tassone, additional, Pirtoli, Luigi, additional, and Correale, Pierpaolo, additional

Published
2017
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28. Phase Ib study of TSPP (thymidilate synthase poly-epitope peptide) vaccine in combination with GOLFIG chemoimmuno-burst in advanced colon cancer patients: Results from the TSPP/VAC-1/c trial.

Author

Correale, Pierpaolo, primary, Pastina, Pierpaolo, additional, Botta, Cirino, additional, Rossetti, Maria Grazia, additional, Apollinari, Serena, additional, Bestoso, Elena, additional, Fioravanti, Antonella, additional, Guidelli, Giacomo, additional, Chellini, Federico, additional, Mantovani, Giovanni, additional, Gori Savellini, Gianni, additional, Carbone, Salvatore Francesco, additional, Ricci, Veronica, additional, Basile, Assunta, additional, Pagliuchi, Marco, additional, Tagliaferri, Pierosandro, additional, Pirtoli, Luigi, additional, and Cusi, Maria Grazia, additional

Published
2012
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32. Dose/dense metronomic chemotherapy with fractioned cisplatin and oral daily etoposide enhances the anti-angiogenic effects of bevacizumab in advanced non-small-cell-lung cancer patients

Author

Correale, Pierpaolo, primary, Remondo, Cinzia, additional, Carbone, Salvatore Francesco, additional, Ricci, Veronica, additional, Migali, Cristina, additional, Martellucci, Ignazio, additional, Licchetta, Antonella, additional, Addeo, Raffaele, additional, Volterrani, Luca, additional, Gotti, Giuseppe, additional, Rotundo, Maria Saveria, additional, Tassone, Pierfrancesco, additional, Sperlongano, Pasquale, additional, Abbruzzese, Alberto, additional, Caraglia, Michele, additional, Tagliaferri, Pierosandro, additional, and Francini, Guido, additional

Published
2010
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34. Dose/dense metronomic chemotherapy with fractioned cisplatin and oral daily etoposide enhances the anti-angiogenic effects of bevacizumab and has strong antitumor activity in advanced non-small-cell-lung cancer patients.

Author

Correale, Pierpaolo, Remondo, Cinzia, Carbone, Salvatore Francesco, Ricci, Veronica, Migali, Cristina, Martellucci, Ignazio, Licchetta, Antonella, Addeo, Rafaele, Volterrani, Luca, Gotti, Giuseppe, Rotundo, Maria Saveria, Tassone, Pierfrancesco, Sperlongano, Pasquale, Abbruzzese, Alberto, Caraglia, Michele, Tagliaferri, Pierosandro, and Francini, Guido

Published
2010
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35. Diabetes Induces a Transcriptional Signature in Bone Marrow–Derived CD34 + Hematopoietic Stem Cells Predictive of Their Progeny Dysfunction.

Author

D'Alessandra, Yuri, Chiesa, Mattia, Vigorelli, Vera, Ricci, Veronica, Rurali, Erica, Raucci, Angela, Colombo, Gualtiero Ivanoe, Pompilio, Giulio, Vinci, Maria Cristina, and Balestrieri, Maria Luisa

Subjects
HEMATOPOIETIC stem cells, CORONARY artery bypass, BLOOD cells, HEMATOPOIETIC system, LYMPHOCYTE transformation, GENES, CHEMOTAXIS, HEMATOPOIESIS
Abstract

Hematopoietic stem/progenitor cells (HSPCs) participate in cardiovascular (CV) homeostasis and generate different types of blood cells including lymphoid and myeloid cells. Diabetes mellitus (DM) is characterized by chronic increase of pro-inflammatory mediators, which play an important role in the development of CV disease, and increased susceptibility to infections. Here, we aimed to evaluate the impact of DM on the transcriptional profile of HSPCs derived from bone marrow (BM). Total RNA of BM-derived CD34+ stem cells purified from sternal biopsies of patients undergoing coronary bypass surgery with or without DM (CAD and CAD-DM patients) was sequenced. The results evidenced 10566 expressed genes whose 79% were protein-coding genes, and 21% non-coding RNA. We identified 139 differentially expressed genes (p-value < 0.05 and |log2 FC| > 0.5) between the two comparing groups of CAD and CAD-DM patients. Gene Set Enrichment Analysis (GSEA), based on Gene Ontology biological processes (GO-BP) terms, led to the identification of fourteen overrepresented biological categories in CAD-DM samples. Most of the biological processes were related to lymphocyte activation, chemotaxis, peptidase activity, and innate immune response. Specifically, HSPCs from CAD-DM patients displayed reduced expression of genes coding for proteins regulating antibacterial and antivirus host defense as well as macrophage differentiation and lymphocyte emigration, proliferation, and differentiation. However, within the same biological processes, a consistent number of inflammatory genes coding for chemokines and cytokines were up-regulated. Our findings suggest that DM induces transcriptional alterations in HSPCs, which are potentially responsible of progeny dysfunction. [ABSTRACT FROM AUTHOR]

Published
2021
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36. Differential Role of Circulating microRNAs to Track Progression and Pre-Symptomatic Stage of Chronic Heart Failure: A Pilot Study.

Author

D'Alessandra, Yuri, Chiesa, Mattia, Carena, Maria Cristina, Beltrami, Antonio Paolo, Rizzo, Paola, Buzzetti, Marta, Ricci, Veronica, Ferrari, Roberto, Fucili, Alessandro, Livi, Ugolino, Aleksova, Aneta, Pompilio, Giulio, and Colombo, Gualtiero I.

Subjects
HEART failure, MICRORNA, PILOT projects, ANALYSIS of covariance, REGRESSION analysis
Abstract

(1)Background: Chronic heart failure (CHF) contributes to the overall burden of cardiovascular disease. Early identification of at-risk individuals may facilitate the targeting of precision therapies. Plasma microRNAs are promising circulating biomarkers for their implications with cardiac pathologies. In this pilot study, we investigate the possible exploitability of circulating micro-RNAs (miRNAs) to track chronic heart failure (CHF) occurrence, and progression from NYHA class I to IV. (2)Methods: We screened 367 microRNAs using TaqMan microRNA Arrays in plasma samples from healthy controls (HC) and CHF NYHA-class I-to-IV patients (5/group). Validation was performed by singleplex assays on 10 HC and 61 CHF subjects. Differences in the expression of validated microRNAs were evaluated through analysis of covariance (ANCOVA). Associations between N-terminal pro-BNP (NT-proBNP), left ventricular end-diastolic volume (LVEDV) or peak oxygen uptake (VO2 peak) and plasma microRNA were assessed by multivariable linear regression analysis. (3)Results: Twelve microRNAs showed higher expression in CHF patients vs. HC. Seven microRNAs were associated with NT-proBNP concentration; of these, miR-423-5p was also an independent predictor of LVEDV. Moreover, miR-499-5p was a predictor of the VO2 peak. Finally, a cluster of 5 miRNAs discriminated New York Heart Association (NYHA) class-I from HC subjects. (4)Conclusions: Our data suggest that circulating miRNAs have the potential to serve as pathophysiology-based markers of HF status and progression, and as indicators of pre-symptomatic individuals. [ABSTRACT FROM AUTHOR]

Published
2020
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37. Immuno-Inflammatory Markers in Advanced NSCLC Patients Undergone Fractioned Cisplatin, Oral Etoposide and Bevacizumab

Author

Pastina, Pierpaolo, Nardone, Valerio, Giuseppe, Battaglia, Botta, Cirino, Tini, Paolo, CRISTIANA BELLAN, Ricci, Veronica, Barbarino, Marcella, Croci, Stefania, Caraglia, Michele, Giordano, Antonio, Cusi, Maria Grazia, Pirtoli, Luigi, Correale, Pierpaolo, Pastina, Pierpaolo, Nardone, Valerio, Giuseppe, Battaglia, Botta, Cirino, Tini, Paolo, Bellan, Cristiana, Ricci, Veronica, Barbarino, Marcella, Croci, Stefania, Caraglia, Michele, Giordano, Antonio, Grazia Cusi, Maria, Pirtoli, Luigi, and Correale, Pierpaolo

Subjects
Immuno-inflammatry, chemoimmunotherapy, markers, chemoimmunotherapy, nsclc, Immuno-inflammatry, markers, nsclc
Abstract

These results suggest that both systemic Inflammatory status and treatment-related immunomodulation may affect the outcome of these patients a finding that highlight a possible involvement of immunesystem in ultimate antitumor effect of this regimen, and offer a solid rationale to test our metronomic regimen in a module of sequential combination with anti-PD-1/PDL-1 inhibitors.

38. Phase Ib study of TSPP (thymidilate synthase poly-epitope peptide) vaccine in combination with GOLFIG chemoimmunoburst in advanced colon cancer patients: Results from the TSPP/VAC-1/c trial

Author

Correale, Pierpaolo, Pastina, Pierpaolo, Botta, Cirino, Rossetti, Maria Grazia, Apollinari, Serena, Bestoso, Elena, Fioravanti, Antonella, Guidelli, Giacomo, Chellini, Federico, Mantovani, Giovanni, Gianni Gori Savellini, Carbone, Salvatore Francesco, Ricci, Veronica, Basile, Assunta, Pagliuchi, Marco, Tagliaferri, Pierosandro, Pirtoli, Luigi, and Cusi, Maria Grazia

40. Circulating MicroRNAs as Potential Predictors of Anthracycline-Induced Troponin Elevation in Breast Cancer Patients: Diverging Effects of Doxorubicin and Epirubicin

Author

Maria Teresa Sandri, Giulio Pompilio, Carlo M. Cipolla, Yuri D'Alessandra, Michela Salvatici, Mattia Chiesa, Chiara Vavassori, Veronica Ricci, Roberto Latini, Lidia Staszewsky, Gualtiero I. Colombo, Daniela Cardinale, Serge Masson, Fabio Ciceri, Sonia Gioffré, Gioffré, Sonia, Chiesa, Mattia, Maria Cardinale, Daniela, Ricci, Veronica, Vavassori, Chiara, Maria Cipolla, Carlo, Masson, Serge, Teresa Sandri, Maria, Salvatici, Michela, Ciceri, Fabio, Latini, Roberto, Irene Staszewsky, Lidia, Pompilio, Giulio, Colombo, Gualtiero I., and D’Alessandra, Yuri

Subjects
Oncology, Drug, medicine.medical_specialty, Anthracycline, media_common.quotation_subject, lcsh:Medicine, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, medicine, Doxorubicin, health care economics and organizations, media_common, anthracyclines, Cardiotoxicity, biology, microRNA, business.industry, lcsh:R, biomarkers, General Medicine, medicine.disease, Troponin, Circulating MicroRNA, 030220 oncology & carcinogenesis, biology.protein, business, medicine.drug, Epirubicin
Abstract

Anthracyclines are anti-neoplastic drugs presenting cardiotoxicity as a side effect. Cardiac troponins (cTn) and echocardiography are currently used to assess cardiac damage and dysfunction, but early biomarkers identifying patients in need of preventive treatments remain a partially met need. Circulating microRNAs (miRNAs) represent good candidates, so we investigated their possible roles as predictors of troponin elevation upon anthracycline treatment. Eighty-eight female breast cancer patients administered with doxorubicin (DOX) or epirubicin (EPI) were divided into four groups basing on drug type and cTn positive (cTn+) or negative (cTn&minus, ) levels: DOX cTn&minus, DOX cTn+, EPI cTn&minus, and EPI cTn+. Blood was collected at baseline, during treatment, and at follow-up. We identified plasma miRNAs of interest by OpenArray screening and single assay validation. Our results showed miR-122-5p, miR-499a-5p and miR-885-5p dysregulation in DOX patients at T0, identifying a signature separating, with good accuracy, DOX cTn&minus, from DOX cTn+. No miRNAs showed differential expression in EPI subjects. Conversely, an anthracycline-mediated modulation (regardless of cTn) was observed for miR-34a-5p, -122-5p and -885-5p. Our study indicates specific circulating miRNAs as possible prediction markers for cardiac troponin perturbation upon anthracycline treatment. Indeed, our findings hint at the possible future use of plasma miRNAs to predict the cardiac responsiveness of patients to different anticancer agents.

Published
2020

41. Anti-cancer activity of dose-fractioned mPE +/- bevacizumab regimen is paralleled by immune-modulation in advanced squamous NSLC patients

Author

Cristiana Bellan, Stefania Croci, Veronica Ricci, Maria Grazia Cusi, Valerio Nardone, Susan Costantini, Piero Paladini, Pierpaolo Correale, Francesca Vanni, Michele Caraglia, Gabriella Misso, Pierfrancesco Tassone, Luigi Pirtoli, Pierpaolo Pastina, Mariarosaria Boccellino, Giuseppe Battaglia, Francesca Capone, Mayra Rachele Zarone, Marcella Barbarino, Pierosandro Tagliaferri, Cirino Botta, Antonio Giordano, Pastina, Pierpaolo, Nardone, Valerio, Croci, Stefania, Battaglia, Giuseppe, Vanni, Francesca, Bellan, Cristiana, Barbarino, Marcella, Ricci, Veronica, Costantini, Susan, Capone, Francesca, Botta, Cirino, Zarone, Mayra Rachele, Misso, Gabriella, Boccellino, Mariarosaria, Caraglia, Michele, Giordano, Antonio, Paladini, Piero, Tassone, Pierfrancesco, Tagliaferri, Pierosandro, Cusi, Maria Grazia, Pirtoli, Luigi, Correale, Pierpaolo, Pastina P., Nardone V., Croci S., Battaglia G., Vanni F., Bellan C., Barbarino M., Ricci V., Costantini S., Capone F., Botta C., Zarone M.R., Misso G., Boccellino M., Caraglia M., Giordano A., Paladini P., Tassone P., Tagliaferri P., Cusi M.G., Pirtoli L., and Correale P.

Subjects
0301 basic medicine, Oncology, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pathology, Bevacizumab, medicine.medical_treatment, Squamous-NSCLC (sqNSCLC), 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Progression-free survival, Radical surgery, Etoposide, Chemotherapy, business.industry, Metronomic chemotherapy, Cancer, medicine.disease, Metronomic Chemotherapy, Regimen, 030104 developmental biology, 030220 oncology & carcinogenesis, Original Article, Cisplatin, business, medicine.drug
Abstract

Background: Results from the BEVA2007 trial, suggest that the metronomic chemotherapy regimen with dose-fractioned cisplatin and oral etoposide (mPE) +/− bevacizumab, a monoclonal antibody to the vascular endothelial growth factor (VEGF), shows anti-angiogenic and immunological effects and is a safe and active treatment for metastatic non-small cell lung cancer (mNSCLC) patients. We carried out a retrospective analysis aimed to evaluate the antitumor effects of this treatment in a subset of patients with squamous histology. Methods: Retrospective analysis was carried out in a subset of 31 patients with squamous histology enrolled in the study between September 2007 and September 2015. All of the patients received chemotherapy with cisplatin (30 mg/sqm, days 1–3q21) and oral etoposide (50 mg, days 1–15q21) (mPE) and 14 of them also received bevacizumab 5 mg/kg on the day 3q21 (mPEBev regimen). Results: This treatment showed a disease control rate of 71% with a mean progression free survival (PFS) and overall survival (OS) of 13.6 and 17 months respectively. After 4 treatment courses, 6 patients showing a remarkable tumor shrinkage, underwent to radical surgery, attaining a significant advantage in term of survival (P=0.04). Kaplan-Meier and log-rank test identified the longest survival in patients presenting low baseline levels in neutrophil-to-lymphocyte ratio (NLR) (P=0.05), interleukin (IL) 17A (P=0.036), regulatory-T-cells (T reg s) (P=0.020), and activated CD83+ dendritic cells (DCs) (P=0.03). Conclusions: These results suggest that the mPE +/− bevacizumab regimen is feasible and should be tested in comparative trials in advanced squamous-NSCLC (sqNSCLC). Moreover, its immune-biological effects strongly suggest the investigation in sequential combinations with immune check-point inhibitors.

Published
2017

42. Radiotherapy prolongs the survival of advanced non-smallcell lung cancer patients undergone to an immune-modulating treatment with dose-fractioned cisplatin and metronomic etoposide and bevacizumab (mPEBev)

Author

Paolo Tini, Cirino Botta, Donatella Aldinucci, Silvia Zappavigna, Michele Caraglia, Gabriella Misso, Giuseppe Battaglia, Antonio Giordano, Pierfrancesco Tassone, Pierosandro Tagliaferri, Pierpaolo Pastina, Claudia Gandolfo, Luigi Pirtoli, Pierpaolo Correale, Maria Grazia Cusi, Stefania Croci, Veronica Ricci, Valerio Nardone, Pastina P., Nardone V., Botta C., Croci S., Tini P., Battaglia G., Ricci V., Cusi M.G., Gandolfo C., Misso G., Zappavigna S., Caraglia M., Giordano A., Aldinucci D., Tassone P., Tagliaferri P., Pirtoli L., Correale P., Pastina, Pierpaolo, Nardone, Valerio, Botta, Cirino, Croci, Stefania, Tini, Paolo, Battaglia, Giuseppe, Ricci, Veronica, Cusi, Maria Grazia, Gandolfo, Claudia, Misso, Gabriella, Zappavigna, Silvia, Caraglia, Michele, Giordano, Antonio, Aldinucci, Donatella, Tassone, Pierfrancesco, Tagliaferri, Pierosandro, Pirtoli, Luigi, and Correale, Pierpaolo

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Retrospective analysi, Bevacizumab, medicine.medical_treatment, Retrospective analysis, NSCLC, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, Lung cancer, Etoposide, Cisplatin, business.industry, Metronomic chemotherapy, Abscopal effect, medicine.disease, Metronomic Chemotherapy, Immune-modulation, Surgery, Radiation therapy, Regimen, 030104 developmental biology, 030220 oncology & carcinogenesis, immune-modulation, metronomic chemotherapy, radiation therapy, retrospective analysis, business, medicine.drug, Research Paper
Abstract

// Pierpaolo Pastina 1 , Valerio Nardone 1 , Cirino Botta 2 , Stefania Croci 1 , Paolo Tini 1 , Giuseppe Battaglia 1 , Veronica Ricci 3 , Maria Grazia Cusi 4 , Claudia Gandolfo 4 , Gabriella Misso 5 , Silvia Zappavigna 5 , Michele Caraglia 5,6 , Antonio Giordano 6,7 , Donatella Aldinucci 8 , Pierfrancesco Tassone 2,6 , Pierosandro Tagliaferri 2 , Luigi Pirtoli 1 and Pierpaolo Correale 1,9 1 Radiotherapy Unit, Department of Medicine, Surgery, and Neuroscience, Siena University Hospital, Siena, Italy 2 Medical Oncology Unit, AUO “Mater Domini”, “Magna Graecia” University, Catanzaro, Italy 3 Radiology Unit,Department of Medicine, Surgery, and Neuroscience, Siena University Hospital, Siena, Italy 4 Department of Medical Biotechnology, Microbiology and Virology Unit, University of Siena, Siena, Italy 5 Department of Biochemistry, Biophysics and General Pathology, University of Campania “L. Vanvitelli”, Naples, Italy 6 Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, PA, USA 7 Department of Medicine, Surgery, and Neuroscience, University of Siena and Istituto Toscano Tumori (ITT), Siena, Italy 8 Department of Experimental Oncology 2, CRO Aviano National Cancer Institute, Aviano, Italy 9 Medical Oncology Unit, Metropolitan Hospital “Bianchi-Melacrino-Morelli, Reggio Calabria, Italy Correspondence to: Pierpaolo Correale, email: // Michele Caraglia, email: // Keywords : immune-modulation, radiation therapy, metronomic chemotherapy, NSCLC, retrospective analysis Received : March 21, 2017 Accepted : June 20, 2017 Published : August 24, 2017 Abstract Radiotherapy (RT), together with a direct cytolytic effect on tumor tissue, also elicits systemic immunological events, which sometimes result in the regression of distant metastases (abscopal effect). We have shown the safety and anti-tumor activity of a novel metronomic chemotherapy (mCH) regimen with dose-fractioned cisplatin, oral etoposide and bevacizumab, a mAb against the vasculo-endothelial-growth-factor (mPEBev regimen), in metastatic non-small-cell-lung cancer (mNSCLC). This regimen, designed on the results of translational studies, showed immune-modulating effects that could trigger and empower the immunological effects associated with tumor irradiation. In order to assess this, we carried out a retrospective analysis in a subset of 69 consecutive patients who received the mPEBev regimen within the BEVA2007 trial. Forty-five of these patients, also received palliative RT of one or more metastatic sites. Statistical analysis (a Log-rank test) revealed a much longer median survival in the group of patients who received RT [mCH vs mCH + RT: 12.1 +/-2.5 (95%CI 3.35-8.6) vs 22.12 +/-4.3 (95%CI 11.9-26.087) months; P =0.015] with no difference in progression-free survival. In particular, their survival correlated with the mPEBev regimen ability to induce the percentage of activated dendritic cells (DCs) (CD3-CD11b+CD15-CD83+CD80+) [Fold to baseline value (FBV) ≤1 vs >1: 4+/-5.389 (95%CI,0- 14.56) vs 56+/-23.05 (95%CI,10.8-101.2) months; P :0.049)] and central-memory- T-cells (CD3+CD8+CD45RA-CCR7+) [FBV ≤ 1 vs >1: 8+/-5.96 (95%CI,0-19.68) vs 31+/-12.3 (95%CI,6.94-55.1) months; P :0.045]. These results suggest that tumor irradiation may prolong the survival of NSCLC patients undergone mPEBev regimen presumably by eliciting an immune-mediated effect and provide the rationale for further perspective clinical studies.

Published
2017

43. Single gallbladder and multiple pancreatic metastases from renal cell carcinoma sixteen years after nephrectomy.

Author

Ricci V, Carbone SF, Testi W, Malatesti R, Lo Gatto M, Dell'Avanzato R, Ginanneschi C, and Volterrani L

Subjects
Aged, Female, Gallbladder Neoplasms diagnosis, Gallbladder Neoplasms surgery, Humans, Pancreatic Neoplasms diagnosis, Pancreatic Neoplasms surgery, Time Factors, Carcinoma, Renal Cell secondary, Carcinoma, Renal Cell surgery, Gallbladder Neoplasms secondary, Kidney Neoplasms pathology, Kidney Neoplasms surgery, Neoplasms, Second Primary diagnosis, Neoplasms, Second Primary surgery, Nephrectomy, Pancreatic Neoplasms secondary
Abstract

We describe a case of female patient presenting with acute biliary symptoms and severe haemobilia due to the presence of a large metastasis in the gallbladder wall from renal cell carcinoma treated by radical nephrectomy 16 years before. CT examination also showed the presence of multiple small round metastases from renal carcinoma in the pancreas, subsequently confirmed surgically and pathologically.

Published
2008

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