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1. Riduzione dei CD34+ circolanti nella broncopneumopatia cronica ostruttiva (BPCO)

Author

HUERTAS A, TESTA U, CALABRO' L, ANTONUCCI R, PETRUCCI E, SATTA A, BONSIGNORE G, SERRA P, PALANGE P., MORICI, Giuseppe, VIGNOLA, Antonio Maurizio, BONSIGNORE, Maria Rosaria, HUERTAS A, TESTA U, CALABRO' L, ANTONUCCI R, PETRUCCI E, SATTA A, MORICI G, VIGNOLA AM, BONSIGNORE G, SERRA P, BONSIGNORE MR, and PALANGE P

Published
2004

2. Valsartan for prevention of recurrent atrial

Author

Disertori, M, Latini, R, Maggioni, Ap, Barlera, S, Di Pasquale, G, Franzosi, Mg, Lucci, D, Staszewsky, L, Tognoni, G, Delise, P, Bertocchi, F, Maiocchi, G, Geraci, E, Correale, E, Lombardi, F, Mugelli, A, Urso, R, Scardi, S, Fabbri, G, Bartolomei, B, Barbato, G, Carbonieri, E, Ciricugno, S, Cosmi, F, Pratola, C, Rossi, Mg, Sciarra, L, Zeni, P, Ceseri, M, Atzori, A, Bambi, F, Baviera, M, Bianchini, F, Cfenicia, E, Gianfriddo, M, Lonardo, G, Luise, A, Nota, R, Orlando, Me, Petrolo, R, Pierattini, C, Pierota, V, Ragno, A, Serio, C, Tafi, A, Tellaroli, E, Masson, S, Vago, T, Gramenzi, S, Orso, F, Suliman, I, Nicolis, E, Casola, C, Dall'Osso, D, Gorini, M, Bianchini, E, Cabiddu, S, Cangioli, I, Carnaghi, A, Cipressa, Ml, Cipressa, L, Galbiati, L, Lorimer, A, Priami, P, Moccetti, T, Vaghi, F, Capello, Af, Rossetti, G, Viada, E, Morena, L, Delucchi, M, Reynaud SG, Allemano, P, Massobrio, N, Gavazzi, A, Taddei, F, Mor, Da, Bortolini, F, Lorini, M, Inama, G, Durin, O, Pirelli, S, Spotti, A, Procopio, R, Cuzzucrea, D, Gentile, G, Margonato, A, Bassanelli, G, Tavazzi, L, Buzzi, Mp, Rordorf, R, Gualco, A, Opasich, C, Gronda, E, Genovese, L, Mattioli, R, Donatelli, F, Uriarte, Ja, Rauhe, W, Bertagnolli, C, Canestrini, S, Stefenelli, C, Cioffi, G, Giovanelli, C, Rigatelli, G, Boni, S, Pasini, A, Sitta, N, Sacchetta, A, Borgese, L, Sciascia, R, Targa L, Raviele, A, Madalosso, M, Bertaglia, E, Zoppo, Fc, Capanna, M, Fiorencis, R, Baracca, E, Rossi, R, Rossi, I, Trappolin, R, Morgera, T, Barducci, E, Baldin, Mg, Gobbo, G, Zardo, F, Hrovatin, E, Mos, L, Vriz, O, Sinagra, G, Aleksova, A, Mazzone, C, Fresco, C, Rubartelli, P, Moroni, La, Camerieri, A, Piana, M, Mureddu, R, Bertoli, D, Petacchi, R, Pancaldi, Lg, Gabrieli, L, Urbinati, S, Pedone, C, Di Niro, M, Brunelli, A, Bosi, S, Censi, S, Moruzzi, P, Pastori, P, Modena, Mg, Malavasi, V, Mezzetti, M, Melandri, F, Zuppiroli, A, Fazi, A, Testa, R, Venturini, E, Mazzinghi, F, Cosmi, D, Santoro, Gm, Minneci, C, Galli, M, Paperini, L, Bovenzi, Fm, Cortigiani, L, Cocchieri, M, Severini, D, Arcuri, Gm, Bagliani, G, Bernardinangeli, M, Proietti, G, Bocconcelli, P, Pierantozzi, A, Monti, F, Giamundo, L, Tancredi, P, Rossini, E, Bianchi, C, Bettiol, F, Giovannini, E, Fera, Ms, Santini, M, Bianconi, L, Boccanelli, A, Morosetti, P, Volpe, M, Facciolo, C, Vacri, A, Romanazzi, F, Napoletano, C, Piccioni, Ll, Candelmo, F, De Marco, G, Arnese, Mr, Vetrano, A, Prinzi, D, De Rosa, P, Capuano, V, Torre, S, D'Onofrio, A, Ammendola, E, Chiariello, M, Filardi, Pp, Battista, R, De Fusco, A, Molero, U, Iervoglini, A, Stefanelli, S, Fattore, L, Bosco, B, Liguori, A, Padula, G, De Luca, I, Sorino, M, Colonna, P, D'Agostino, C, Pierfelice, O, Pettinati, G, Muscella, A, De Lorenzi, E, Falco, M, Giannattasio, C, Baldi, N, Clemente, Ma, D'Alessandro, B, Truncellito, L, Arabia, F, Ciconte, Va, Perticone, F, Ruberto, C, Buffon, A, Tomaselli, C, De Rosa, F, Mazza, S, Zampaglione, G, Pirozzi, Am, Butera, A, Levato, M, Musacchio, D, Polimeni, Rm, Lacquaniti, V, Pulitanò, G, Ruggeri, A, Provenzano, A, Cuccurullo, O, Musolino, M, Marrari, A, Anastasio, L, Schiavello, M, Comito, Mg, Gulizia, Mm, Francese GM, Vasquez, L, Coppolino, C, Casale, A, D'Urso, G, Oliva, G, Giordano, U, Andolina, S, Sanfilippo, N, Ingrillì, F, Accardo, S, Grasso, S, Buffa, L, Bambi, Serra E., Baviera, M., Bianchini, F., Fenicia, E., Gianfriddo, M., Lonardo, G., Luise, A., Nota, R., Orlando, M. E., Petrolo, R., Pierattini, C., Pierota, V., Ragno, A., Serio, C., Tafi, A., Tellaroli, E., Masson, Core Laboratories — S., Latini, R., Vago (Biomarkers), T., Staszewsky, L., Gramenzi (Echocardiography), S., Orso, F., Suliman (Electrocardiography), I., Nicolis, Database Management and Statistics — E., Casola, C., Barlera, S., Dall'Osso, D., Gorini, M., Lucci, D., Regulatory, Administrative, Bianchini, and Secretariat — E., Cabiddu, S., Cangioli, I., Carnaghi, A., Cipressa, M. L., Cipressa, L., Galbiati, L., Lorimer, A., Priami, P., Moccetti, Participating Centers and Investigators — Switzerland: Lugano (T., Rossi, M. G., Vaghi), F., Capello), Italy: Piemonte: Asti (A. F. L., Rossetti, Cuneo (G., Viada, E., Morena), L., Delucchi, Saluzzo (M., Reynaud, S. G., Allemano), P., Massobrio), Torino Valdese (N., Gavazzi, Lombardia: Bergamo (A., Taddei), F., Mor), Brescia (D. A., Bortolini, Chiari (F., Lorini), M., Inama, Crema (G., Durin), O., Pirelli, Cremona (S., Spotti, A., Procopio), R., Cuzzucrea, Giussano (D., Gentile), G., Margonato, Milano San Raffaele (A., Bassanelli), G., Tavazzi, Pavia San Matteo (L., Buzzi, M. P., Rordorf), R., Gualco, Pavia Fondazione Salvatore Maugeri (A., Opasich), C., Gronda, Rozzano (E., Genovese), L., Mattioli, Sesto San Giovanni (R., Donatelli), F., Salerno Uriarte), Varese (J. A., Rauhe), P. A. Bolzano: Bolzano (W., Bertagnolli, P. A. Trento: Cles (C., Canestrini), S., Stefenelli, Trento Villa Bianca (C., Cioffi), G., Disertori, Trento Santa Chiara (M., Zeni, P., Giovanelli), C., Rigatelli, Veneto: Bovolone (G., Boni, S., Pasini), A., Sitta), Conegliano Santa Maria dei Battuti (N., Sacchetta, Conegliano Veneto De Gironcoli (A., Borgese, L., Sciascia), R., Targa), Este (L., Raviele, Mestre (A., Madalosso), M., Bertaglia, Mirano (E., Zoppo), F. C., Capanna, Porto Viro (M., Fiorencis), R., Baracca), Rovigo (E., Rossi, San Bonifacio (R., Carbonieri, E., Rossi), I., Trappolin), Villafranca di Verona (R., Morgera, Friuli Venezia Giulia: Monfalcone (T., Barducci), E., Baldin, Palmanova (M. G., Gobbo), G., Zardo, Pordenone (F., Hrovatin), E., Mos, San Daniele del Friuli (L., Vriz), O., Sinagra, Trieste Az. Ospedaliera-Universitaria Ospedali Riuniti (G., Aleksova), A., Scardi, Trieste Az. Servizi Sanitari n. 1 Triestina (S., Mazzone), C., Fresco), Udine (C., Rubartelli, Liguria: Genova-Sampierdarena (P., Moroni), L. A., Camerieri), Genova-Voltri (A., Piana), Imperia (M., Mureddu), Pietra Ligure (R., Bertoli, Sarzana-Loc. S. Caterina (D., Petacchi), R., Pancaldi, Emilia Romagna: Bentivoglio (L. G., Gabrieli), L., Urbinati, Bologna Bellaria (S., Pedone), C., Di Pasquale, Bologna Maggiore (G., Di Niro, M., Brunelli), A., Bosi, Cotignola (S., Censi), S., Pratola), Ferrara (C., Moruzzi, Fidenza (P., Pastori), P., Modena, Modena (M. G., Malavasi), V., Mezzetti), Rimini (M., Melandri), Sassuolo (F., Zuppiroli, Toscana: Bagno a Ripoli (A., Fazi), A., Testa, Cecina (R., Venturini, E., Mazzinghi), F., Cosmi, Cortona (F., Cosmi), D., Santoro, Firenze Nuovo Osp. S Giovanni di Dio (G. M., Minneci), C., Galli, Livorno (M., Paperini), L., Bovenzi, Lucca (F. M., Cortigiani), L., Cocchieri, Umbria: Città di Castello (M., Severini, D., Arcuri), G. M., Bagliani), Foligno (G., Bernardinangeli, Terni (M., Proietti, G., Proietti), G., Bocconcelli, Marche: Pesaro (P., Pierantozzi), A., Monti, Lazio: Albano Laziale (F., Giamundo), L., Tancredi, Formia (P., Rossini), E., Bianchi), Roma Centro Traumatologico Ortopedico (C., Roma San Camillo, Bettiol), Cardiologia Riabilitativa e Preventiva (F., Giovannini, Cardiologia I (E., Fera), M. S., Santini, Roma San Filippo Neri (M., Bianconi), L., Boccanelli, Roma San Giovanni (A., Morosetti), P., Volpe, Roma Sant'Andrea (M., Facciolo), C., Vacri, Abruzzo: Penne (A., Romanazzi), F., Napoletano, Teramo (C., Piccioni), L. L., Candelmo), Campania: Avellino (F., De Marco, Aversa (G., Arnese), M. R., Vetrano), Caserta (A., Prinzi, Giugliano in Campania (D., De Rosa), P., Capuano, Mercato San Severino (V., Torre), S., D'Onofrio, Napoli Azienda Ospedaliera Monaldi (A., Ammendola), E., Chiariello, Napoli Policlinico Universitario Federico II (M., Perrone Filardi), P., Battista, Piedimonte Matese (R., De Fusco), A., Molero), Pozzuoli (U., Iervoglini, San Felice a Cancello (A., Stefanelli), S., Fattore, Santa Maria Capua Vetere (L., Bosco), B., Liguori, Vallo della Lucania (A., Padula), G., De Luca, Puglia: Bari Ospedale Consorziale Policlinico (I., Sorino, M., Colonna), P., D'Agostino, Bari-Carbonara (C., Pierfelice), O., Pettinati, Casarano (G., Muscella), A., De Lorenzi, Scorrano (E., Falco), M., Giannattasio), Taranto Villa Verde (C., Baldi), Taranto Santissima Annunziata (N., Clemente), Basilicata: Matera (M. A., D'Alessandro, Policoro (B., Truncellito), L., Arabia, Calabria: Catanzaro Pugliese (F., Ciconte), V. A., Perticone, Catanzaro Germaneto (F., Ruberto), C., Buffon, Cosenza Santissima Annunziata (A., Tomaselli), C., De Rosa, Cosenza Mariano Santo (F., Mazza), S., Zampaglione, Crotone (G., Pirozzi), A. M., Butera, Lamezia Terme (A., Levato), M., Musacchio), Paola (D., Polimeni, Polistena (R. M., Lacquaniti), V., Pulitanò, Reggio Calabria (G., Ruggeri), A., Provenzano), Rogliano (A., Cuccurullo), San Marco Argentano (O., Musolino, Scilla (M., Marrari), A., Anastasio, Soriano Calabro (L., Schiavello), M., Comito), Vibo Valentia (M. G. A., Gulizia, Sicilia: Catania (M. M., Francese), G. M., Vasquez, Milazzo (L., Coppolino), C., Casale, Nicosia (A., D'Urso), G., Oliva, Palermo Civico e Benfratelli (G., Giordano, U., Andolina), S., Sanfilippo, Palermo Villa Sofia (N., Ingrillì), F., Accardo), Palermo Buccheri La Ferla (S., Grasso, Palermo Cervello (S., Buffa), L., and Sardegna: Cagliari Brotzu, (E. Serra).

Published
2009

5. Recombinant transmembrane CD59 (CD59-TM) confers complement resistance to GPI-anchored protein defective melanoma cells

Author

De Nardo, C, Fonsatti, E, Sigalotti, L, Calabro', L, Colizzi, F, Cortini, E, Coral, S, Altomonte, M, and Maio, M

Subjects
Glycosylphosphatidylinositols, Drug Resistance, Tumor Cells, Cultured, Socio-culturale, Gene Expression, Humans, Protein Isoforms, CD59 Antigens, Complement System Proteins, Melanoma, Recombinant Proteins
Abstract

Protectin (CD59) is a glycosylphosphatidylinositol (GPI)-anchored cell membrane glycoprotein, broadly expressed on melanocytic cells, that represents the main restriction factor of complement (C)-mediated lysis of human melanoma cells. Levels of CD59 expression may impair the clinical efficacy of C-activating monoclonal antibodies (mAb); thus, we investigated the molecular mechanisms underlying the lack of CD59 expression in selected melanoma cells. Serological and biochemical analyses showed that MeWo melanoma cells expressed CD59 neither at cell surface nor at cytoplasmic levels; however, no critical mutations were identified in their CD59 mRNA. Consistently, MeWo CD59 cDNA (MeWo-CD59) was appropriately translated when transfected into the CD59-positive Mel 100 melanoma cells, and into the CD59-negative Nalm-6 pre-B leukemia cells that acquired resistance to C. In contrast, transfection of MeWo cells with CD59 cDNA from Mel 275 melanoma cells did not induce CD59 expression; however, their transfection with the CD59-TM chimeric construct, obtained by replacing the GPI-anchoring signal of MeWo-CD59 with the transmembrane tail of the human low-density lipoprotein receptor, induced the expression of a C-protective transmembrane form of CD59. These data, together with the absent expression of additional GPI-anchored proteins (i.e., CD55), suggest that defects in the biosynthesis and/or processing of GPI-anchored proteins underlie the lack of CD59 expression in MeWo cells. Further unveiling of the molecular mechanism that turns off CD59 expression in human melanoma cells will help to set-up more effective therapeutic strategies utilizing C-activating mAb in melanoma patients.

Published
2002

12. Bioimmunotherapeutic targets on angiogenetic blood vessels in solid malignangies

Author

Michele Maio, Altomonte, M., Calabro, L., and Fonsatti, E.

Subjects
Vascular Endothelial Growth Factor A, Angiogenesis, Morphogenesis, Vascular Cell Adhesion Molecule-1, Angiogenesis Inhibitors, Antineoplastic Agents, Receptors, Cell Surface, Endothelial Growth Factors, Matrix Metalloproteinase Inhibitors, NO, Antigens, CD, Neoplasms, Humans, Medicine, Receptors, Growth Factor, Receptors, Vitronectin, Inverse correlation, VEGFMMPalpha v beta 3 integrinendostatinCD31CD105tumorendothelial cellsangiogenesisreview, Lymphokines, Neovascularization, Pathologic, Vascular Endothelial Growth Factors, business.industry, Physiological Angiogenesis, Endoglin, Tumor blood supply, Proteolytic enzymes, Antibodies, Monoclonal, Receptor Protein-Tyrosine Kinases, Peptide Fragments, Endostatins, Platelet Endothelial Cell Adhesion Molecule-1, Endothelial stem cell, Receptors, Vascular Endothelial Growth Factor, Cancer research, Collagen, Wound healing, business
Abstract

Physiological angiogenesis is a tightly regulated process that occurs mainly during reproduction, development and wound healing. Although angiogenesis is a continuous process, different consecutive steps can be identified, including: i) release of pro-angiogenetic factors; ii) release of proteolytic enzymes; iii) endothelial cell migration, morphogenesis and proliferation. Angiogenesis is also a hallmark of malignant diseases, and an inverse correlation between tumor vascularity and survival was demonstrated. Thus, strategies aimed at interfering with tumor blood supply by targeting tumor vasculature, presently represent promising new approaches for the treatment of solid malignancies. In fact, at least 30 angiogenetic inhibitors, utilized alone or in combination with other therapeutic agents, are currently being tested in clinical trials in humans. In this paper, we will review current knowledges on selected molecules expressed by endothelial cells and involved in distinct steps of the angiogenetic process, that represent potential targets for bioimmunotherapeutic approaches in human malignancies.

13. Italian Cohort of Nivolumab Expanded Access Program in Squamous Non-Small Cell Lung Cancer: Results from a Real-World Population

Author

Paolo Bidoli, Daniele Turci, Hector Soto Parra, Domenico Galetta, Fabiana Vitiello, Teresa Gamucci, Paola Antonelli, Filippo de Marinis, Giuseppe Lo Russo, Angelo Delmonte, Enrico Cortesi, Francesco Grossi, Luana Calabrò, Andrea Ardizzoni, Alessandro Morabito, Diana Giannarelli, Antonio Chella, Federico Cappuzzo, Lucio Crinò, Marcello Tiseo, Crino L., Bidoli P., Delmonte A., Grossi F., De Marinis F., Ardizzoni A., Vitiello F., Lo Russo G., Parra H.S., Cortesi E., Cappuzzo F., Calabro L., Tiseo M., Turci D., Gamucci T., Antonelli P., Morabito A., Chella A., Giannarelli D., Galetta D., Crinò, L, Bidoli, P, Delmonte, A, Grossi, F, De Marinis, F, Ardizzoni, A, Vitiello, F, Lo Russo, G, Parra, H, Cortesi, E, Cappuzzo, F, Calabrò, L, Tiseo, M, Turci, D, Gamucci, T, Antonelli, P, Morabito, A, Chella, A, Giannarelli, D, and Galetta, D

Subjects
Compassionate Use Trials, Male, 0301 basic medicine, Oncology, real-world, Cancer Research, Lung Neoplasms, Squamous non‐small cell lung cancer, Cohort Studies, Efficacy, Antineoplastic Agents, Immunological, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, 80 and over, Medicine, squamous non-small cell lung cancer, Non-Small-Cell Lung, Aged, 80 and over, education.field_of_study, Lung Cancer, Expanded access program, Immunotherapy, Nivolumab, Real‐world, Treatment beyond disease progression, Adult, Aged, Drug Administration Schedule, Female, Humans, Italy, Middle Aged, Safety, Treatment Outcome, Immunological, expanded access program, Docetaxel, 030220 oncology & carcinogenesis, Cohort, treatment beyond disease progression, medicine.drug, medicine.medical_specialty, Population, Antineoplastic Agents, 03 medical and health sciences, Internal medicine, Adverse effect, education, business.industry, Carcinoma, Clinical trial, 030104 developmental biology, Expanded access, immunotherapy, business
Abstract

Background Nivolumab has shown a survival benefit compared with docetaxel as second-line treatment for patients with previously treated advanced squamous non-small cell lung cancer (NSCLC) in a randomized phase III trial. The experiences of patients and physicians in routine clinical practice are often different from those in a controlled clinical trial setting. We present data from the entire Italian cohort of patients with squamous NSCLC enrolled in a worldwide nivolumab NSCLC expanded access program. Patients and Methods Patients with pretreated advanced squamous NSCLC received nivolumab 3 mg/kg every 2 weeks for up to 24 months. Safety was monitored throughout; efficacy data collected included objective tumor response, date of progression, and survival information. Results The Italian cohort comprised 371 patients who received at least one dose of nivolumab. In the overall population, the objective response rate (ORR) was 18%, the disease control rate (DCR) was 47%, and median overall survival (OS) was 7.9 months (95% confidence interval 6.2–9.6). In subgroup analyses, ORR, DCR, and median OS were, respectively, 17%, 48%, and 9.1 months in patients previously treated with two or more lines of therapy (n = 209) and 8%, 40%, and 10.0 months in patients treated beyond disease progression (n = 65). In the overall population, the rate of any-grade and grade 3–4 adverse events was 29% and 6%, respectively. Treatment-related adverse events led to treatment discontinuation in 14 patients (5%). There were no treatment-related deaths. Conclusion To date, this report represents the most extensive clinical experience with nivolumab in advanced squamous NSCLC in current practice outside the controlled clinical trial setting. These data suggest that the efficacy and safety profiles of nivolumab in a broad, real-world setting are consistent with those obtained in clinical trials. Implications for Practice Nivolumab is approved in the U.S. and Europe for the treatment of advanced non-small cell lung cancer (NSCLC) after failure of prior platinum-based chemotherapy. In this cohort of Italian patients with previously treated, advanced squamous NSCLC treated in a real-world setting as part of the nivolumab expanded access program, the efficacy and safety of nivolumab was consistent with that previously reported in nivolumab clinical trials.

Published
2019
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14. Nivolumab in never-smokers with advanced squamous non-small cell lung cancer: Results from the Italian cohort of an expanded access program

Author

Marina Chiara Garassino, Annamaria Catino, Luana Calabrò, Francesca Ambrosio, Carmelo Bengala, Alessandro Follador, Fabiana Vitiello, Floriana Morgillo, Lucio Crinò, Paola Bordi, Enrico Mini, Giuseppe Lo Russo, Enrico Vasile, Andrea Ardizzoni, Antonio Santo, Federico Cappuzzo, Alessandro Scoppola, Giuseppe Altavilla, Diana Giannarelli, Enrico Cortesi, Natale Tedde, Fausto Barbieri, Garassino, M. C., Crino, L., Catino, A., Ardizzoni, A., Cortesi, E., Cappuzzo, F., Bordi, P., Calabro, L., Barbieri, F., Santo, A., Altavilla, G., Ambrosio, F., Mini, E., Vasile, E., Morgillo, F., Scoppola, A., Bengala, C., Follador, A., Tedde, N., Giannarelli, D., Lo Russo, G., Vitiello, F., Garassino, Marina Chiara, Crinò, Lucio, Catino, Annamaria, Ardizzoni, Andrea, Cortesi, Enrico, Cappuzzo, Federico, Bordi, Paola, Calabrò, Luana, Barbieri, Fausto, Santo, Antonio, Altavilla, Giuseppe, Ambrosio, Francesca, Mini, Enrico, Vasile, Enrico, Morgillo, Floriana, Scoppola, Alessandro, Bengala, Carmelo, Follador, Alessandro, Tedde, Natale, Giannarelli, Diana, Lo Russo, Giuseppe, and Vitiello, Fabiana

Subjects
Oncology, Male, Cancer Research, Lung Neoplasms, medicine.medical_treatment, never-smokers, carcinoma, Health Services Accessibility, Cohort Studies, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, 80 and over, Medicine, 030212 general & internal medicine, squamous non-small cell lung cancer, RC254-282, Aged, 80 and over, never-smoker, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, General Medicine, Middle Aged, Prognosis, expanded access program, italian, nivolumab, Survival Rate, Nivolumab, 030220 oncology & carcinogenesis, Cohort, Carcinoma, Squamous Cell, Disease Progression, Female, Case-Control Studie, Human, Cohort study, Expanded access program, italian, never-smokers, nivolumab, squamous non-small cell lung cancer, adult, aged, aged, 80 and over, carcinoma, non-small-cell lung, squamous cell, case-control studies, cohort studies, disease progression, female, follow-up studies, humans, lung neoplasms, male, middle aged, nivolumab, non-smokers, Prognosis, survival rate, health services accessibility, Adult, medicine.medical_specialty, Italian, Prognosi, Follow-Up Studie, 03 medical and health sciences, Internal medicine, Humans, Survival rate, Aged, squamous cell, Expanded access program, business.industry, Case-control study, Immunotherapy, Non-Smokers, Lung Neoplasm, non-small-cell lung, Non-Smoker, Expanded access, Case-Control Studies, Squamous non-small cell lung cancer, Cohort Studie, business, Follow-Up Studies
Abstract

Objectives: Never-smokers may be a distinct subgroup among patients with advanced non-small cell lung cancer, appearing to benefit less from immunotherapy than smokers. We report results from never-smokers enrolled in the Italian cohort of the nivolumab expanded access program in pre-treated patients with advanced squamous non-small cell lung cancer. Materials and methods: Nivolumab (3 mg/kg every 2 weeks for ≤24 months) was available on physician request. Efficacy data included objective tumor response, date of progression, and survival information. Safety was monitored. Results: Overall, 371 patients received at least one dose of nivolumab, including 31 never-smokers (8%). Objective response rate, disease-control rate, and median overall survival were 23%, 45%, and 12.1 months (95% confidence interval: 3.7–20.4), respectively, in never-smokers, and 18%, 47%, and 7.9 months (95% confidence interval: 6.2–9.6), respectively, in the overall expanded access program population. Any-grade and grade 3–4 treatment-related adverse events were reported in 12 (39%) and 3 (10%) never-smokers, respectively, and in 109 (29%) and 21 (6%) patients, respectively, in the overall expanded access program population. Grade 3–4 treatment-related adverse events in non-smokers were increased transaminases (n = 2; 6%) and diarrhea (n = 1; 3%). Treatment-related adverse events led to treatment discontinuation in 4 non-smokers (17%) and in 26 patients (9%) overall. Conclusion: Pre-treated never-smokers with advanced squamous non-small cell lung cancer in this Italian expanded access program demonstrated efficacy and safety that were consistent with those in the overall expanded access program population and clinical trials. These results suggest that a proportion of never-smoker patients with squamous non-small cell lung cancer may be responsive to immunotherapy. Other factors, such as the tumor mutational load and the status of programmed death-ligand 1, anaplastic lymphoma kinase, and epidermal growth factor receptor, might play a potential key role.

Published
2018

15. Circulating haemopoietic and endothelial progenitor cells are decreased in COPD

Author

Paolo Palange, Morici G, R. Antonucci, Alice Huertas, Eleonora Petrucci, Elvira Pelosi, A Satta, Maria R. Bonsignore, Ugo Testa, L. Calabrò, M A Vignola, Luca Pasquini, PALANGE P, TESTA U, HUERTAS A, CALABRO' L, ANTONUCCI R, PETRUCCI E, PELOSI E, PASQUINI L, SATTA A, MORICI G, VIGNOLA MA, and BONSIGNORE MR

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Angiogenesis, CD34, Antigens, CD34, cd34, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Settore BIO/09 - Fisiologia, chronic obstructive pulmonary disease, immunology, Pulmonary Disease, Chronic Obstructive, cd34+ cells, cd34+cells, chemistry.chemical_compound, antigens, blood, stem cells, Internal medicine, growth factors, middle aged, Medicine, Progenitor cell, humans, CD34+ cells, chronic obstructive pulmonary disease, exercise, growth factors, hypoxia, cell count, pulmonary disease, COPD, chronic obstructive, exercise, hypoxia, business.industry, aged, endothelial cells, hematopoietic stem cells, Hypoxia (medical), medicine.disease, Endothelial stem cell, Vascular endothelial growth factor, Endocrinology, chemistry, Hepatocyte growth factor, medicine.symptom, business, medicine.drug
Abstract

Circulating CD34+ cells are haemopoietic progenitors that may play a role in tissue repair. No data are available on circulating progenitors in chronic obstructive pulmonary disease (COPD). Circulating CD34+ cells were studied in 18 patients with moderate-to-severe COPD (age: mean+/-sd 68+/-8 yrs; forced expiratory volume in one second: 48+/-12% predicted) and 12 controls, at rest and after endurance exercise. Plasma concentrations of haematopoietic growth factors (FMS-like tyrosine kinase 3 (Flt3) ligand, kit ligand), markers of hypoxia (vascular endothelial growth factor (VEGF)) and stimulators of angiogenesis (VEGF, hepatocyte growth factor (HGF)) and markers of systemic inflammation (tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8) were measured. Compared with the controls, the COPD patients showed a three-fold reduction in CD34+ cell counts (3.3+/-2.5 versus 10.3+/-4.2 cells.microL-1), and a 50% decrease in AC133+ cells. In the COPD patients, progenitor-derived haemopoietic and endothelial cell colonies were reduced by 30-50%. However, four COPD patients showed progenitor counts in the normal range associated with lower TNF-alpha levels. In the entire sample, CD34+ cell counts correlated with exercise capacity and severity of airflow obstruction. After endurance exercise, progenitor counts were unchanged, while plasma Flt3 ligand and VEGF only increased in the COPD patients. Plasma HGF levels were higher in the COPD patients compared with the controls and correlated inversely with the number of progenitor-derived colonies. In conclusion, circulating CD34+ cells and endothelial progenitors were decreased in chronic obstructive pulmonary disease patients and could be correlated with disease severity.

Published
2006
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16. Targeting of HLA-DR molecules transduces agonistic functional signals in cutaneous melanoma

Author

Luana Calabrò, Maresa Altomonte, Raffaele Tecce, Alberto Visintin, Carlo Pucillo, Ester Fonsatti, Antonio Leonardi, Michele Maio, Altomonte, M., Visintin, A., Tecce, R., Leonardi, Antonio, Calabro, L., Fonsatti, E., Pucillo, C., and Maio, M.

Subjects
Skin Neoplasms, Physiology, medicine.medical_treatment, Clinical Biochemistry, Lymphocyte Activation, Targeted therapy, chemistry.chemical_compound, Monoclonal, Tumor Cells, Cultured, Neoplasm Metastasis, Phosphorylation, Cell Aggregation, Cultured, Blotting, Melanoma, Antibodies, Monoclonal, Protein-Tyrosine Kinases, ntibodies, Tumor Cells, Up-Regulation, Electrophoresis, Polyacrylamide Gel, Western, Cell Division, Intracellular, Signal Transduction, Electrophoresis, Blotting, Western, Human leukocyte antigen, Biology, NO, Antigen, Antigens, Neoplasm, medicine, HLA-DR, melanoma, Humans, Antigens, ntibodies, Monoclonal, Focal Adhesion Kinase 1, Focal Adhesion Protein-Tyrosine Kinases, HLA-DR Antigens, Molecular Weight, Precipitin Tests, Tyrosine, Polyacrylamide Gel, Tyrosine phosphorylation, Cell Biology, medicine.disease, Molecular biology, chemistry, Cutaneous melanoma, Cancer research, Neoplasm
Abstract

The role of human leukocyte antigens (HLA) class II molecules in transducing intracellular signals in immune cells is well established. Solid tumors of different histotype can also express HLA class II antigens; however, their intracellular signaling ability is essentially unknown. Due to the frequent expression of HLA class II molecules in primary and metastatic lesions, cutaneous melanoma was utilized to investigate whether the engagement of HLA-DR molecules transduces functional intracellular signal(s). Triggering of HLA-DR molecules by the anti-HLA-DR monoclonal antibody (mAb) L243 induced a significant (P

Published
2004

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