42 results on '"De Santo I"'
Search Results
2. Prognostic value of intrinsic subtypes in hormone-receptor-positive metastatic breast cancer: systematic review and meta-analysis
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Schettini, F., Martínez-Sáez, O., Falato, C., De Santo, I., Conte, B., Garcia-Fructuoso, I., Gomez-Bravo, R., Seguí, E., Chic, N., Brasó-Maristany, F., Paré, L., Vidal, M., Adamo, B., Muñoz, M., Pascual, T., Ciruelos, E., Perou, C.M., Carey, L.A., and Prat, A.
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- 2023
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3. Eribulin in combination with bevacizumab as second-line treatment for HER2-negative metastatic breast cancer progressing after first-line therapy with paclitaxel and bevacizumab: a multicenter, phase II, single arm trial (GIM11-BERGI)
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De Angelis, C., Bruzzese, D., Bernardo, A., Baldini, E., Leo, L., Fabi, A., Gamucci, T., De Placido, P., Poggio, F., Russo, S., Forestieri, V., Lauria, R., De Santo, I., Michelotti, A., Del Mastro, L., De Laurentiis, M., Giuliano, M., De Placido, S., and Arpino, G.
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- 2021
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4. Corrigendum to ‘Eribulin in combination with bevacizumab as second-line treatment for HER2-negative metastatic breast cancer progressing after first-line therapy with paclitaxel and bevacizumab: a multicenter, phase II, single arm trial (GIM11-BERGI)’: [ESMO Open Volume 6, Issue 2, April 2021, 100054]
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De Angelis, C., Bruzzese, D., Bernardo, A., Baldini, E., Leo, L., Fabi, A., Gamucci, T., De Placido, P., Poggio, F., Russo, S., Forestieri, V., Lauria, R., De Santo, I., Caputo, R., Cianniello, D., Michelotti, A., Del Mastro, L., De Laurentiis, M., Giuliano, M., De Placido, S., and Arpino, G.
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- 2021
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5. The Emerging Role of ESR1 Mutations in Luminal Breast Cancer as a Prognostic and Predictive Biomarker of Response to Endocrine Therapy
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Amelia McCartney, I. Migliaccio, De Santo I, Di Leo A, and Luca Malorni
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0301 basic medicine ,Cancer Research ,Fulvestrant ,biology ,business.industry ,Estrogen receptor ,medicine.disease ,Metastatic breast cancer ,body regions ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Breast cancer ,Oncology ,030220 oncology & carcinogenesis ,medicine ,Cancer research ,biology.protein ,Endocrine system ,Aromatase ,business ,Estrogen receptor alpha ,Tamoxifen ,medicine.drug - Abstract
Mutations in the hotspot ligand-binding domain of the estrogen receptor (ER) gene ESR1 have recently been recognized as mechanisms of endocrine resistance in endocrine receptor-positive metastatic breast cancer (MBC). Accumulating data suggest these mutations develop under the selective pressure of endocrine treatments, and are infrequent in untreated ER-positive breast cancers. In vitro studies show that these mutations confer ligand-independent activity, resistance to estrogen deprivation, and relative resistance to tamoxifen and fulvestrant. Post-hoc retrospective and prospective analyses of ESR1 mutations in patients with MBC have consistently found that these mutations are markers of poor prognosis and predict resistance to aromatase inhibitors (AIs). These results warrant further investigation and prospective validation in dedicated studies. Moreover, studies are ongoing to clarify the activity of novel drugs in the context of metastatic endocrine resistant luminal breast cancer harboring ESR1 mutations. In this review, we summarize the pre-clinical and clinical findings defining the characteristics of ESR1 mutant breast cancer, and highlight the potential clinical developments in this field.
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- 2019
6. Abstract P6-21-13: A phase II single arm trial evaluating the efficacy and safety of eribulin in combination with bevacizumab for second-line treatment of human epidermal growth factor receptor 2 (HER2)–negative metastatic breast cancer (MBC) progressing after first-line therapy with bevacizumab and paclitaxel
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De Placido, S, primary, De Laurentiis, M, additional, Bruzzese, D, additional, Bernardo, A, additional, Baldini, EE, additional, Montesarchio, V, additional, Fabi, A, additional, Gamucci, T, additional, De Placido, P, additional, Russo, S, additional, Lauria, R, additional, De Santo, I, additional, De Angelis, C, additional, Del Mastro, L, additional, Giuliano, M, additional, and Arpino, G, additional
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- 2019
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7. Androgen receptor in triple negative breast cancer: A potential target for the targetless subtype
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Gerratana, L., primary, Basile, D., additional, Buono, G., additional, De Placido, S., additional, Giuliano, M., additional, Minichillo, S., additional, Coinu, A., additional, Martorana, F., additional, De Santo, I., additional, Del Mastro, L., additional, De Laurentiis, M., additional, Puglisi, F., additional, and Arpino, G., additional
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- 2018
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8. Shedding light on azopolymer brush dynamics by fluorescence correlation spectroscopy
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Kollarigowda, R. H., primary, De Santo, I., additional, Rianna, C., additional, Fedele, C., additional, Manikas, A. C., additional, Cavalli, S., additional, and Netti, P. A., additional
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- 2016
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9. Isothermal Oxidation for Wellsite Near-Real-Time Assessment of Organic Matter Concentration of Source Rocks.
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Karoum, R.., additional, Bondabou, K.., additional, De Santo, I.., additional, and Strapoc, D.., additional
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- 2015
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10. Multiplex single particle analysis in microfluidics
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Dannhauser, D., primary, Romeo, G., additional, Causa, F., additional, De Santo, I., additional, and Netti, P. A., additional
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- 2014
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11. Abstract P4-01-21: Head to head comparison of standard echo doppler versus 3D speckle tracking echocardiography for early subclinical cardiotoxicity detection in breast cancer patients treated with anthracycline adjuvant chemotherapy
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Arpino, G, primary, Galderisi, M, additional, De Angelis, C, additional, Milano, M, additional, Gargiulo, P, additional, Santoro, A, additional, De Stefano, F, additional, Muscariello, R, additional, De Santo, I, additional, Lauria, R, additional, De Simone, G, additional, and De Placido, S, additional
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- 2013
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12. Mapping CO2 in Real Time in Hydrocarbon Reservoirs with Downhole Fluid Analysis: First Successful Experience in the East Irish Sea, UK Continental Shelf
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Quayle, B.., additional, James, S.., additional, Quine, M.., additional, De Santo, I.., additional, Jeffreys, P.., additional, and Y. Zuo, Julian, additional
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- 2013
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13. MOLECULAR MOTION IN NANOCHANNELS: SINGLE MOLECULE EVIDENCE AND MULTISCALE SIMULATION
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Netti, A. P., primary, De Santo, I., additional, Panemi, M. S., additional, Pricl, S., additional, D’Amore, Alberto, additional, Acierno, Domenico, additional, and Grassia, Luigi, additional
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- 2008
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14. Strain-oriented strategy for guiding cardioprotection initiation of breast cancer patients experiencing cardiac dysfunction
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O Casciano, F Luciano, Roberta Esposito, Mario Giuliano, Sabino De Placido, Maurizio Galderisi, Ciro Santoro, Patrizio Lancellotti, Irene De Santo, Grazia Arpino, Maria Lembo, Regina Sorrentino, Bruno Trimarco, Santoro, C., Esposito, R., Lembo, M., Sorrentino, R., De Santo, I., Luciano, F., Casciano, Ofelia, Giuliano, M., De Placido, S., Trimarco, B., Lancellotti, P., Arpino, G., and Galderisi, M.
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Ramipril ,medicine.medical_specialty ,Heart Diseases ,Heart disease ,heart failure ,Antineoplastic Agents ,Breast Neoplasms ,030204 cardiovascular system & hematology ,Ventricular Dysfunction, Left ,03 medical and health sciences ,breast cancer ,0302 clinical medicine ,Breast cancer ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,030212 general & internal medicine ,ejection fraction ,Carvedilol ,cancer therapeutics related cardiac dysfunction ,Subclinical infection ,Ejection fraction ,business.industry ,Cancer ,Stroke Volume ,General Medicine ,medicine.disease ,Echocardiography ,Heart failure ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,global longitudinal strain ,medicine.drug - Abstract
Aims This study assessed the impact of the strain-guided therapeutic approach on cancer therapy-related cardiac dysfunction (CTRCD) and rate of cancer therapy (CT) interruption in breast cancer. Methods and results We enrolled 116 consecutive female patients with HER2-positive breast cancer undergoing a standard protocol by EC (epirubicine + cyclophosphamide) followed by paclitaxel + trastuzumab (TRZ). Coronary artery, valvular and congenital heart disease, heart failure, primary cardiomyopathies, permanent or persistent atrial fibrillation, and inadequate echo-imaging were exclusion criteria. Patients underwent an echo-Doppler exam with determination of ejection fraction (EF) and global longitudinal strain (GLS) at baseline and every 3 months during CT. All patients developing subclinical (GLS drop >15%) or overt CTRCD (EF reduction Conclusion These findings highlight the usefulness of ‘strain oriented’ approach in reducing the rate of overt CTRCD and CT interruption by a timely cardioprotective treatment initiation.
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- 2019
15. Eribulin in combination with bevacizumab as second-line treatment for HER2-negative metastatic breast cancer progressing after first-line therapy with paclitaxel and bevacizumab: a multicenter, phase II, single arm trial (GIM11-BERGI)
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P. De Placido, A. Michelotti, L. Del Mastro, M. De Laurentiis, L. Leo, Rossella Lauria, A. Fabi, Stefania Russo, Mario Giuliano, I. De Santo, Dario Bruzzese, Elizabeth H. Baldini, Teresa Gamucci, Antonio Bernardo, Valeria Forestieri, C. De Angelis, Grazia Arpino, Francesca Poggio, S. De Placido, De Angelis, C, Bruzzese, D, Bernardo, A, Baldini, E, Leo, L, Fabi, A, Gamucci, T, De Placido, P, Poggio, F, Russo, S, Forestieri, V, Lauria, R, De Santo, I, Michelotti, A, Del Mastro, L, De Laurentiis, M, Giuliano, M, De Placido, S, and Arpino, G
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Oncology ,Cancer Research ,medicine.medical_specialty ,Bevacizumab ,genetic structures ,medicine.medical_treatment ,Phases of clinical research ,Neutropenia ,bevacizumab ,chemistry.chemical_compound ,Internal medicine ,Clinical endpoint ,Medicine ,Adverse effect ,eribulin ,Original Research ,Chemotherapy ,business.industry ,medicine.disease ,Metastatic breast cancer ,chemistry ,metastatic breast cancer ,business ,HER2-negative ,Eribulin ,medicine.drug - Abstract
Background We evaluated the efficacy and safety of the nontaxane microtubule dynamics inhibitor eribulin plus the humanized anti-VEGF monoclonal antibody bevacizumab in a novel second-line chemotherapy scheme in HER2-negative metastatic breast cancer (MBC) patients progressing after first-line paclitaxel and bevacizumab. Patients and methods This is a multicenter, single-arm, Simon's two-stage, phase II study. The primary endpoint was the overall response rate, considered as the sum of partial and complete response based on the best overall response rate (BORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and clinical benefit rate. Results A total of 58 of the 61 patients enrolled in the study were evaluable for efficacy. The BORR was 24.6% (95% CI 14.5-37.3). The clinical benefit rate was 32.8% (95% CI 21.3-46.0). The median PFS was 6.2 months (95% CI 4.0-7.8), and median OS was 14.8 months (95% CI 12.6-22.8). Overall, adverse events (AEs) were clinically manageable and the most common AEs were fatigue, paresthesia, and neutropenia. Quality of life was well preserved in most patients. Conclusions The results of this study suggest that second-line therapy with bevacizumab in combination with eribulin has a meaningful clinical activity and may represent a potential therapeutic option for patients with HER2-negative MBC., Highlights • Bevacizumab + chemotherapy improved progression-free survival in HER2-negative metastatic breast cancer (MBC) patients. • Eribulin monotherapy improved overall survival in patients with anthracycline- and taxane-pretreated MBC. • The GIM11-BERGI trial assessed the efficacy and safety of eribulin + bevacizumab as second-line treatment for HER2-MBC. • Eribulin + bevacizumab showed to be a safe and active treatment after progression to first-line paclitaxel + bevacizumab.
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- 2021
16. Impact of COVID-19 outbreak on cancer immunotherapy in Italy: A survey of young oncologists
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Sara Parola, Diletta Cavallero, Pietro De Placido, Rossella Di Franco, Francesca Zacchi, Giacomo Cartenì, Sabino De Placido, Claudia von Arx, Alice Rossi, Fernanda Picozzi, Pasquale Rescigno, Laura Attademo, Giovannella Palmieri, Carminia Maria Della Corte, Fabiana Vitiello, Anna Russo, Lucia Nappi, Michele Aieta, Alessia Mennitto, Fabiana Napolitano, Marco Messina, Giuseppe Buono, Valeria Merz, Marco De Felice, Stefano De Falco, Immacolata Paciolla, Irene De Santo, Dario Trapani, Antonio M. Grimaldi, Paolo Tarantino, Alessandro Morabito, Tortora Vincenzo, Stefano Pepe, Giuseppe Palmieri, Antonietta Fabbrocini, Diana Giannarelli, Alfonso De Stefano, Sabrina Vari, Cesare Gridelli, Vittorio Riccio, Angelica Petrillo, Martina Pagliuca, Giuseppe Calderoni, Margaret Ottaviano, Vincenza Conteduca, Michela Lia, Giuseppe Santabarbara, Ester Simeone, Valentina Borzillo, Francesca Caputo, Mario Rosanova, Marcello Curvietto, Pasquale Assalone, Brigitta Mucci, Raffaele Conca, Vito Vanella, Francovito Piantedosi, Vincenzo Montesarchio, Erica Pietroluongo, Lucia Festino, Federica Tomei, Vincenzo Di Lauro, Bruno Daniele, Caterina Vivaldi, Andrea Zivi, Veronica Prati, Pasqualina Giordano, Luisa Piccin, Francesco Bloise, Massimiliano Spada, Jole Ventriglia, Davide Bosso, Alessandro Marco Minisini, Massimiliano Salati, Monica Milano, Carlo Messina, Valentina Massa, Mario Giuliano, Claudia Trojanello, Antonella Lucia Marretta, Fortunato Ciardiello, Antonio Avallone, Marianna Tortora, Ilaria Zampiva, Alessia Cavo, Floriana Morgillo, Andrea Sbrana, Piera Federico, Maria Grazia Vitale, Sandro Pignata, Antonia Silvestri, Paola Taveggia, Sara Merler, Paolo A. Ascierto, Michelino De Laurentiis, Ottaviano, Margaret, Curvietto, Marcello, Rescigno, Pasquale, Tortora, Marianna, Palmieri, Giovannella, Giannarelli, Diana, Aieta, Michele, Assalone, Pasquale, Attademo, Laura, Avallone, Antonio, Bloise, Francesco, Bosso, Davide, Borzillo, Valentina, Buono, Giuseppe, Calderoni, Giuseppe, Caputo, Francesca, Cartenì, Giacomo, Cavallero, Diletta, Cavo, Alessia, Ciardiello, Fortunato, Conca, Raffaele, Conteduca, Vincenza, De Falco, Stefano, De Felice, Marco, De Laurentiis, Michelino, De Placido, Pietro, De Placido, Sabino, De Santo, Irene, De Stefano, Alfonso, Della Corte, Carminia Maria, Di Franco, Rossella, Di Lauro, Vincenzo, Fabbrocini, Antonietta, Federico, Piera, Festino, Lucia, Giordano, Pasqualina, Giuliano, Mario, Gridelli, Cesare, Grimaldi, Antonio Maria, Lia, Michela, Marretta, Antonella Lucia, Massa, Valentina, Mennitto, Alessia, Merler, Sara, Merz, Valeria, Messina, Carlo, Messina, Marco, Milano, Monica, Minisini, Alessandro Marco, Montesarchio, Vincenzo, Morabito, Alessandro, Morgillo, Floriana, Mucci, Brigitta, Nappi, Lucia, Napolitano, Fabiana, Paciolla, Immacolata, Pagliuca, Martina, Palmieri, Giuseppe, Parola, Sara, Pepe, Stefano, Petrillo, Angelica, Piantedosi, Francovito, Piccin, Luisa, Picozzi, Fernanda, Pietroluongo, Erica, Pignata, Sandro, Prati, Veronica, Riccio, Vittorio, Rosanova, Mario, Rossi, Alice, Russo, Anna, Salati, Massimiliano, Santabarbara, Giuseppe, Sbrana, Andrea, Simeone, Ester, Silvestri, Antonia, Spada, Massimiliano, Tarantino, Paolo, Taveggia, Paola, Tomei, Federica, Vincenzo, Tortora, Trapani, Dario, Trojanello, Claudia, Vanella, Vito, Vari, Sabrina, Ventriglia, Jole, Vitale, Maria Grazia, Vitiello, Fabiana, Vivaldi, Caterina, von Arx, Claudia, Zacchi, Francesca, Zampiva, Ilaria, Zivi, Andrea, Daniele, Bruno, Ascierto, Paolo Antonio, Ottaviano, M., Curvietto, M., Rescigno, P., Tortora, M., Palmieri, G., Giannarelli, D., Aieta, M., Assalone, P., Attademo, L., Avallone, A., Bloise, F., Bosso, D., Borzillo, V., Buono, G., Calderoni, G., Caputo, F., Carteni, G., Cavallero, D., Cavo, A., Ciardiello, F., Conca, R., Conteduca, V., De Falco, S., De Felice, M., De Laurentiis, M., De Placido, P., De Placido, S., De Santo, I., De Stefano, A., Della Corte, C. M., Di Franco, R., Di Lauro, V., Fabbrocini, A., Federico, P., Festino, L., Giordano, P., Giuliano, M., Gridelli, C., Grimaldi, A. M., Lia, M., Marretta, A. L., Massa, V., Mennitto, A., Merler, S., Merz, V., Messina, C., Messina, M., Milano, M., Minisini, A. M., Montesarchio, V., Morabito, A., Morgillo, F., Mucci, B., Nappi, L., Napolitano, F., Paciolla, I., Pagliuca, M., Parola, S., Pepe, S., Petrillo, A., Piantedosi, F., Piccin, L., Picozzi, F., Pietroluongo, E., Pignata, S., Prati, V., Riccio, V., Rosanova, M., Rossi, A., Russo, A., Salati, M., Santabarbara, G., Sbrana, A., Simeone, E., Silvestri, A., Spada, M., Tarantino, P., Taveggia, P., Tomei, F., Vincenzo, T., Trapani, D., Trojanello, C., Vanella, V., Vari, S., Ventriglia, J., Vitale, M. G., Vitiello, F., Vivaldi, C., Von Arx, C., Zacchi, F., Zampiva, I., Zivi, A., Daniele, B., and Ascierto, P. A.
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Male ,Cancer Research ,Immune checkpoint inhibitors ,Programmed Cell Death 1 Receptor ,Practice Patterns ,Medical Oncology ,B7-H1 Antigen ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Drug Prescription ,Neoplasms ,Surveys and Questionnaires ,Pandemic ,Prevalence ,Surveys and Questionnaire ,Infection control ,Immunology and Allergy ,CTLA-4 Antigen ,030212 general & internal medicine ,Viral ,Practice Patterns, Physicians' ,RC254-282 ,Clinical/Translational Cancer Immunotherapy ,Oncologists ,Geography ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,antineoplastic protocols ,Immunological ,Oncology ,Italy ,030220 oncology & carcinogenesis ,Molecular Medicine ,Female ,immunotherapy ,Coronavirus Infections ,Human ,healthcare economics and organizations ,Adult ,Telemedicine ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Pneumonia, Viral ,Immunology ,Antineoplastic Agents ,lung neoplasms ,Drug Prescriptions ,Time-to-Treatment ,03 medical and health sciences ,Betacoronavirus ,medicine ,melanoma ,COVID-19 ,Humans ,Infection Control ,Pandemics ,SARS-CoV-2 ,Medical prescription ,Pharmacology ,Physicians' ,Betacoronaviru ,Coronavirus Infection ,Cancer ,Outbreak ,Pneumonia ,medicine.disease ,lung neoplasm ,antineoplastic protocol ,Family medicine ,healthcare economics and organization ,Oncologist ,Neoplasm - Abstract
BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has overwhelmed the health systems worldwide. Data regarding the impact of COVID-19 on cancer patients (CPs) undergoing or candidate for immune checkpoint inhibitors (ICIs) are lacking. We depicted the practice and adaptations in the management of patients with solid tumors eligible or receiving ICIs during the COVID-19 pandemic, with a special focus on Campania region.MethodsThis survey (25 questions), promoted by the young section of SCITO (Società Campana di ImmunoTerapia Oncologica) Group, was circulated among Italian young oncologists practicing in regions variously affected by the pandemic: high (group 1), medium (group 2) and low (group 3) prevalence of SARS-CoV-2–positive patients. For Campania region, the physician responders were split into those working in cancer centers (CC), university hospitals (UH) and general hospitals (GH). Percentages of agreement, among High (H) versus Medium (M) and versus Low (L) group for Italy and among CC, UH and GH for Campania region, were compared by using Fisher’s exact tests for dichotomous answers and χ2 test for trends relative to the questions with 3 or more options.ResultsThis is the first Italian study to investigate the COVID-19 impact on cancer immunotherapy, unique in its type and very clear in the results. The COVID-19 pandemic seemed not to affect the standard practice in the prescription and delivery of ICIs in Italy. Telemedicine was widely used. There was high consensus to interrupt immunotherapy in SARS-CoV-2–positive patients and to adopt ICIs with longer schedule interval. The majority of the responders tended not to delay the start of ICIs; there were no changes in supportive treatments, but some of the physicians opted for delaying surgeries (if part of patients’ planned treatment approach). The results from responders in Campania did not differ significantly from the national ones.ConclusionOur study highlights the efforts of Italian oncologists to maintain high standards of care for CPs treated with ICIs, regardless the regional prevalence of COVID-19, suggesting the adoption of similar solutions. Research on patients treated with ICIs and experiencing COVID-19 will clarify the safety profile to continue the treatments, thus informing on the most appropriate clinical conducts.
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- 2020
17. Unexpected ovarian activity in premenopausal breast cancer survivors treated with exemestane and GnRH analogues
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Giovanni Nazzaro, Alessandro Conforti, Rossella Lauria, Francesca Di Rella, Roberta Caputo, Irene De Santo, Sabino De Placido, Grazia Arpino, Roberta Vallone, Michelino De Laurentiis, Mario Giuliano, Mariavittoria Locci, Pasquale De Rosa, Giuseppe De Placido, Francesco Schettini, Carlo Alviggi, Conforti, A., Schettini, F., Vallone, R., Di Rella, F., De Rosa, P., De Santo, I., Giuliano, M., Arpino, G., Lauria, R., De Placido, S., Caputo, R., De Laurentiis, M., Nazzaro, G., De Placido, G., Locci, M., and Alviggi, C.
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Oncology ,Adult ,medicine.medical_specialty ,Antineoplastic Agents, Hormonal ,medicine.medical_treatment ,MEDLINE ,Breast Neoplasms ,Gonadotropin-Releasing Hormone ,Premenstrual Syndrome ,chemistry.chemical_compound ,Text mining ,Exemestane ,Cancer Survivors ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Ovarian Function Tests ,Chemotherapy ,Estradiol ,business.industry ,Ovary ,Androstadienes ,Tamoxifen ,chemistry ,Chemotherapy, Adjuvant ,Premenopausal breast cancer ,Surgery ,Female ,Uterine Hemorrhage ,Drug Monitoring ,business - Published
- 2019
18. CDK 4/6 inhibitors as single agent in advanced solid tumors
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Francesco Schettini, Irene De Santo, Carmen G. Rea, Pietro De Placido, Luigi Formisano, Mario Giuliano, Grazia Arpino, Michelino De Laurentiis, Fabio Puglisi, Sabino De Placido, Lucia Del Mastro, Schettini, F, De Santo, I, Rea, Cg, De Placido, P, Formisano, L, Giuliano, M, Arpino, G, De Laurentiis, M, Puglisi, F, De Placido, S, and Del Mastro, L.
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0301 basic medicine ,Cancer Research ,Review ,Palbociclib ,Cell cycle ,lcsh:RC254-282 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Breast cancer ,Cyclin-dependent kinase ,Ribociclib ,Solid tumors ,Medicine ,Rhabdomyosarcoma ,Abemaciclib ,neoplasms ,Cyclin-dependent kinases ,Oncology ,biology ,business.industry ,abemaciclib, cell cycle, cyclin-dependent kinases, palbociclib, ribociclib, solid tumors ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Metastatic breast cancer ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,biology.protein ,business - Abstract
Cyclin-dependent kinases (CDK) 4/6 inhibitors, namely abemaciclib, palbociclib, and ribociclib, interfere with cell cycle progression, induce cell senescence and might promote cancer cell disruption by a cytotoxic T cells-mediated effect. Phase III randomized clinical trials have proven that CDK4/6 inhibitors (CDK4/6i) in combination with several endocrine agents improve treatment efficacy over endocrine agents alone for hormone receptor positive (HR+) HER2 negative (HER2-) metastatic breast cancer (MBC). Based on such results, these combinations have been approved for clinical use. Preclinical studies in cell cultures and mouse models proved that CDK4/6i are active against a broad spectrum of solid tumors other than breast cancer, including liposarcoma, rhabdomyosarcoma, non-small cell lung cancer, glioblastoma multiforme, esophageal cancer, and melanoma. The role of CDK4/6i in monotherapy in several solid tumors is currently under evaluation in phase I, II, and III trials. Nowadays, abemaciclib is the only of the three inhibitors that has received approval as single agent therapy for pretreated HR+ HER2- MBC. Here we review biological, preclinical and clinical data on the role of CDK4/6 inhibitors as single agents in advanced solid tumors.
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- 2018
19. Androgen receptor in triple negative breast cancer: A potential target for the targetless subtype
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Giuseppe Buono, Lorenzo Gerratana, Debora Basile, Grazia Arpino, S. Minichillo, L. Del Mastro, Mario Giuliano, M. De Laurentiis, Fabio Puglisi, Federica Martorana, A. Coinu, I. De Santo, S. De Placido, Gerratana, L, Basile, D, Buono, G, De Placido, S, Giuliano, M, Minichillo, S, Coinu, A, Martorana, F, De Santo, I, Del Mastro, L, De Laurentiis, M, Puglisi, F, and Arpino, G
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0301 basic medicine ,Bicalutamide ,Triple Negative Breast Neoplasms ,Antiandrogen therapy ,Disease ,Antiandrogen therapy, Epithelial-to-Mesenchymal Transition, Luminal androgen receptor positive, Triple negative breast cancer, Oncology ,Radiology, Nuclear Medicine and Imaging ,Luminal androgen receptor positive ,Androgen ,03 medical and health sciences ,chemistry.chemical_compound ,Basal (phylogenetics) ,0302 clinical medicine ,Nuclear Medicine and Imaging ,Receptors ,Epithelial-to-Mesenchymal Transition ,medicine ,Animals ,Humans ,Enzalutamide ,Radiology, Nuclear Medicine and imaging ,Triple negative breast cancer ,Epithelial–mesenchymal transition ,Triple-negative breast cancer ,business.industry ,Androgen Antagonists ,General Medicine ,Androgen receptor ,030104 developmental biology ,Oncology ,chemistry ,Receptors, Androgen ,030220 oncology & carcinogenesis ,Cancer research ,Female ,Signal transduction ,Radiology ,business ,medicine.drug - Abstract
Triple negative breast cancer (TNBC) represents the 15-20% of all breast cancers (BC) and is characterized by a very aggressive behavior. Recent data suggest that TNBC is not a single disease, but it is rather an umbrella for different ontology-profiles such as basal like 1 and 2, mesenchymal, and the luminal androgen receptor (LAR). The LAR subtype is characterized by the expression of the Androgen Receptor (AR) and its downstream effects. Notwithstanding the role of the AR in several signaling pathways, its impact on a biological and clinical standpoint is still controversial. The LAR subtype has been associated with better prognosis, less chemotherapy responsiveness and lower pathologic complete response after neoadjuvant treatment. Clinical evidence suggests a role for anti-androgen therapies such as bicalutamide, enzalutamide and abiraterone, offering an interesting chemo-free alternative for chemo-unresponsive patients, and therefore potentially shifting current treatment strategies.
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- 2018
20. Shedding light on azopolymer brush dynamics by fluorescence correlation spectroscopy
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I. De Santo, Ravichandran H. Kollarigowda, Paolo A. Netti, Chiara Fedele, Silvia Cavalli, Carmela Rianna, Anastasios C. Manikas, Kollarigowda, Rh, De Santo, I, Rianna, Carmela, Fedele, Chiara, Manikas, Ac, Cavalli, S, and Netti, PAOLO ANTONIO
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chemistry.chemical_classification ,Materials science ,Confocal ,Fluorescence correlation spectroscopy ,02 engineering and technology ,General Chemistry ,Polymer ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Polymer brush ,Photochemistry ,01 natural sciences ,0104 chemical sciences ,law.invention ,chemistry.chemical_compound ,chemistry ,Azobenzene ,Methacrylic acid ,Confocal microscopy ,law ,Polymer chemistry ,Side chain ,0210 nano-technology - Abstract
Understanding the response to illumination at a molecular level as well as characterising polymer brush dynamics are key features that guide the engineering of new light-stimuli responsive materials. Here, we report on the use of a confocal microscopy technique that was exploited to discern how a single molecular event such as the photoinduced isomerisation of azobenzene can affect an entire polymeric material at a macroscopic level leading to photodriven mass-migration. For this reason, a set of polymer brushes, containing azobenzene (Disperse Red 1, DR) on the side chains of poly(methacrylic acid), was synthesised and the influence of DR on the polymer brush dynamics was investigated for the first time by Fluorescence Correlation Spectroscopy (FCS). Briefly, two dynamics were observed, a short one coming from the isomerisation of DR and a long one related to the brush main chain. Interestingly, photoinduced polymer aggregation in the confocal volume was observed.
- Published
- 2016
21. A Closed Form for Fluorescence Correlation Spectroscopy Experiments in Submicrometer Structures
- Author
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Filippo Causa, Ilaria De Santo, Paolo A. Netti, Luigi Sanguigno, Sanguigno, L., De Santo, I., Causa, Filippo, and Netti, PAOLO ANTONIO
- Subjects
Models, Molecular ,Low concentration ,Diffusion Coefficient ,Autocorrelation function ,Fluorescence spectrometry ,Experimental data ,Fluorescence correlation spectroscopy ,Submicrometer structure ,Analytical Chemistry ,Microstructured material ,Diffusion ,Fluorescent probe ,Time dependent ,Optics ,Detection volume ,Fluorescence Correlation Spectroscopy ,Transport process ,Limit (mathematics) ,Diffusion (business) ,Boundary effect ,Constrained model ,Fluorescent Dyes ,Lateral confinement ,Closed form ,business.industry ,Chemistry ,Autocorrelation ,Small compartment ,Fluorescence ,Computational physics ,In-channel ,Spectrometry, Fluorescence ,Volume (thermodynamics) ,Fluorescent molecule ,business ,Fabry–Pérot interferometer - Abstract
Fluorescence correlation spectroscopy (FCS) is a powerful technique for measuring low concentrations of fluorescent molecules and their diffusion coefficients in an open detection volume. However, in several practical cases, when FCS measurements are carried out in small compartments like microchannels, neglecting boundary effects could lead to erroneous results. Here, a close form solution is proposed to explicitly account for the presence of walls located at a distance comparable with the characteristic detection volume lengths. We derive a one-dimensional diffusion constrained model and then generalize the solution to the two- and the three-dimensional constrained cases. We further indicate within which limits the standard autocorrelation function (ACF) model gives reliable results in microconfinement. Our model relies just on the assumption of elastic hits at the system walls and succeeds in describing the ACF of fluorescent probes confined along one direction. Through the analysis of FCS experimental data, we are able to predict the correct shape of the ACF in channels of micrometric and submicrometric width and measure the extent of lateral confinement. In addition, it permits the investigation of microstructured material features such as cages and cavities having dimensions on the micrometric range. On the basis of the proposed model, we also show in which conditions confinement could generate an apparent time dependent probe mobility, thus allowing a proper interpretation of the transport process taking place in submicrometric compartments.
- Published
- 2010
22. Subdiffusive molecular motion in nanochannels observed by fluorescence correlation spectroscopy
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Ilaria De Santo, Filippo Causa, Paolo A. Netti, De Santo, I., Causa, Filippo, and Netti, PAOLO ANTONIO
- Subjects
Flexible molecule ,Diffusion Coefficient ,Nano channel ,Fluorescence spectrometry ,Analytical chemistry ,Rhodamine 6G ,Fluorescence correlation spectroscopy ,Glass channel ,Analytical Chemistry ,Nanocomposites ,Polyethylene Glycols ,Surface interaction ,Rhodamine ,Diffusion ,Molecular motion ,chemistry.chemical_compound ,Fluorescence Correlation Spectroscopy ,Molecule ,Diffusion (business) ,Particle Size ,Fluorescent Dyes ,Nano-device ,Square-root dependence ,chemistry.chemical_classification ,Desorption time ,Key parameter ,Molecule size ,Rhodamines ,Diffusion model ,Biomolecule ,Nanometric ,Dextrans ,Single molecule level ,Time dependence ,Order of magnitude ,Kinetics ,Molecule diffusion ,Spectrometry, Fluorescence ,chemistry ,Chemical physics ,Channel height ,Adsorption ,Diffusion time - Abstract
The influence of confinement on biomolecule motion in glass channels of nanometric height has been investigated with fluorescence correlation spectroscopy (FCS). We measured intrachannel molecule diffusion time and concentration based on a single-component diffusion model as a function of molecule size to channel height (r(g)/h). Poly(ethylene glycol) (PEG) of 20 kDa and dextran of 40 kDa showed a reduction of their diffusion coefficients of almost 1 order of magnitude when nanochannel height approached probe diameter, whereas rhodamine 6G (Rh6G) was shown to be almost unaffected from confinement. Subdiffusive motion has been proven for flexible molecules in nanochannels, and deviations toward a square root dependence of mobility with time for confinement up to molecule size r(g)/h approximately 0.5 were registered. Diffusion coefficient time dependence has been evaluated and described with a model that accounts for diffusion time increase due to molecule rearrangements related to molecule flexibility and surface interactions dynamics. The evaluation of the subdiffusive mode and the key parameters extracted at the single-molecule level of partitioning, intrachannel diffusion time, desorption time, and binding probability at surfaces can be exploited for the engineering of bioanalytic nanodevices.
- Published
- 2010
23. Immune-Based Therapy in Triple-Negative Breast Cancer: From Molecular Biology to Clinical Practice.
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Carlino F, Diana A, Piccolo A, Ventriglia A, Bruno V, De Santo I, Letizia O, De Vita F, Daniele B, Ciardiello F, and Orditura M
- Abstract
Triple-negative breast cancer (TNBC) has been considered for many years an orphan disease in terms of therapeutic options, with conventional chemotherapy (CT) still representing the mainstay of treatment in the majority of patients. Although breast cancer (BC) has been historically considered a "cold tumor", exciting progress in the genomic field leading to the characterization of the molecular portrait and the immune profile of TNBC has opened the door to novel therapeutic strategies, including Immune Checkpoint Inhibitors (ICIs), Poly ADP-Ribose Polymerase (PARP) inhibitors and Antibody Drug Conjugates (ADCs). In particular, compared to standard CT, the immune-based approach has been demonstrated to improve progression-free survival (PFS) and overall survival (OS) in metastatic PD-L1-positive TNBC and the pathological complete response rate in the early setting, regardless of PD-L1 expression. To date, PD-L1 has been widely used as a predictor of the response to ICIs; however, many patients do not benefit from the addition of immunotherapy. Therefore, PD-L1 is not a reliable predictive biomarker of the response, and its accuracy remains controversial due to the lack of a consensus about the assay, the antibody, and the scoring system to adopt, as well as the spatial and temporal heterogeneity of the PD-L1 status. In the precision medicine era, there is an urgent need to identify more sensitive biomarkers in the BC immune oncology field other than just PD-L1 expression. Through the characterization of the tumor microenvironment (TME), the analysis of peripheral blood and the evaluation of immune gene signatures, novel potential biomarkers have been explored, such as the Tumor Mutational Burden (TMB), Microsatellite Instability/Mismatch Repair Deficiency (MSI/dMMR) status, genomic and epigenomic alterations and tumor-infiltrating lymphocytes (TILs). This review aims to summarize the recent knowledge on BC immunograms and on the biomarkers proposed to support ICI-based therapy in TNBC, as well as to provide an overview of the potential strategies to enhance the immune response in order to overcome the mechanisms of resistance.
- Published
- 2022
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24. A Dose-finding Study of Metronomic Oral Vinorelbine in Combination With Oral Cyclophosphamide and Bevacizumab in Patients With Advanced Breast Cancer.
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Sanna G, Pestrin M, Moretti E, Biagioni C, De Santo I, Gabellini S, Galardi F, McCartney A, and Biganzoli L
- Subjects
- Administration, Metronomic, Administration, Oral, Adult, Aged, Breast Neoplasms pathology, Carcinoma pathology, Dose-Response Relationship, Drug, Drug Therapy, Combination, Endothelial Cells, Female, Humans, Middle Aged, Neoplastic Cells, Circulating, Pilot Projects, Prospective Studies, Antineoplastic Agents administration & dosage, Bevacizumab administration & dosage, Breast Neoplasms drug therapy, Carcinoma drug therapy, Cyclophosphamide administration & dosage, Vinorelbine administration & dosage
- Abstract
Background: Metronomic chemotherapy can induce disease control in patients with metastatic breast cancer (MBC) and has better safety profiles than conventional chemotherapy. Evidence suggests that cytotoxics can be anti-angiogenic in pre-clinical models and may have synergistic effects when combined with anti-vascular endothelial growth factor therapies., Patients and Methods: Patients pretreated with ≥ 1 prior line of therapy for MBC received oral cyclophosphamide 50 mg daily in combination with oral vinorelbine at escalating doses of 20 mg (V20), 30 mg (V30), and 40 mg (V40) 3 times per week, and intravenous bevacizumab 15 mg/kg every 3 weeks. Patients with human epidermal growth factor receptor 2-positive disease were given the same regimen plus standard trastuzumab. Doses were escalated when 3 patients completed 3 treatment cycles of V20 and V30, without experiencing dose-limiting toxicities. The recommended dose was then tested in a further 6 patients. Circulating tumour cells and circulating endothelial cells (CEC) were measured in 30 mL of whole blood samples at baseline, after cycle 1, and at the disease progression., Results: Fifteen patients were recruited from June 2013 to October 2015. The median age was 61 years (range, 29-72 years); 80% had estrogen receptor-positive and 33% had human epidermal growth factor receptor 2-positive disease. At least 67% had visceral metastases, and 80% had received ≥ 2 lines of prior treatment. No dose-limiting toxicities were observed at the 3 dose-levels, making V40 the recommended dose. Overall 8 (53%) patients developed grade 2 adverse events (arthralgia, n = 3 [20%]; asthenia, n = 2 [13%]; diarrhea, n = 2 [13%]; leukopenia, n = 2 [13%]). Bevacizumab was associated with grade 3 hypertension (n = 3 [20%]). Stable disease as best response was observed in 11 (73.3%) patients. The clinical benefit rate was 66.6% (10/15 patients). The median time to progression was 6.9 months. At baseline, CECs were more commonly detectable than circulating tumor cells; however, no statistical correlation was found between CEC kinetics and response., Conclusion: A metronomic vinorelbine dose of 40 mg combined with cyclophosphamide and bevacizumab is a promising treatment regimen in pretreated patients with MBC., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2021
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25. Impact of COVID-19 outbreak on cancer immunotherapy in Italy: a survey of young oncologists.
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Ottaviano M, Curvietto M, Rescigno P, Tortora M, Palmieri G, Giannarelli D, Aieta M, Assalone P, Attademo L, Avallone A, Bloise F, Bosso D, Borzillo V, Buono G, Calderoni G, Caputo F, Cartenì G, Cavallero D, Cavo A, Ciardiello F, Conca R, Conteduca V, De Falco S, De Felice M, De Laurentiis M, De Placido P, De Placido S, De Santo I, De Stefano A, Della Corte CM, Di Franco R, Di Lauro V, Fabbrocini A, Federico P, Festino L, Giordano P, Giuliano M, Gridelli C, Grimaldi AM, Lia M, Marretta AL, Massa V, Mennitto A, Merler S, Merz V, Messina C, Messina M, Milano M, Minisini AM, Montesarchio V, Morabito A, Morgillo F, Mucci B, Nappi L, Napolitano F, Paciolla I, Pagliuca M, Palmieri G, Parola S, Pepe S, Petrillo A, Piantedosi F, Piccin L, Picozzi F, Pietroluongo E, Pignata S, Prati V, Riccio V, Rosanova M, Rossi A, Russo A, Salati M, Santabarbara G, Sbrana A, Simeone E, Silvestri A, Spada M, Tarantino P, Taveggia P, Tomei F, Vincenzo T, Trapani D, Trojanello C, Vanella V, Vari S, Ventriglia J, Vitale MG, Vitiello F, Vivaldi C, von Arx C, Zacchi F, Zampiva I, Zivi A, Daniele B, and Ascierto PA
- Subjects
- Adult, Antineoplastic Agents, Immunological adverse effects, B7-H1 Antigen antagonists & inhibitors, B7-H1 Antigen immunology, Betacoronavirus pathogenicity, COVID-19, CTLA-4 Antigen antagonists & inhibitors, CTLA-4 Antigen immunology, Coronavirus Infections immunology, Coronavirus Infections prevention & control, Coronavirus Infections transmission, Drug Prescriptions statistics & numerical data, Female, Geography, Humans, Infection Control standards, Italy epidemiology, Male, Medical Oncology standards, Neoplasms immunology, Oncologists statistics & numerical data, Pandemics prevention & control, Pneumonia, Viral immunology, Pneumonia, Viral prevention & control, Pneumonia, Viral transmission, Practice Patterns, Physicians' standards, Practice Patterns, Physicians' statistics & numerical data, Prevalence, Programmed Cell Death 1 Receptor antagonists & inhibitors, Programmed Cell Death 1 Receptor immunology, SARS-CoV-2, Surveys and Questionnaires statistics & numerical data, Time-to-Treatment, Antineoplastic Agents, Immunological administration & dosage, Betacoronavirus immunology, Coronavirus Infections epidemiology, Medical Oncology statistics & numerical data, Neoplasms drug therapy, Pneumonia, Viral epidemiology
- Abstract
Background: The coronavirus disease 2019 (COVID-19) pandemic has overwhelmed the health systems worldwide. Data regarding the impact of COVID-19 on cancer patients (CPs) undergoing or candidate for immune checkpoint inhibitors (ICIs) are lacking. We depicted the practice and adaptations in the management of patients with solid tumors eligible or receiving ICIs during the COVID-19 pandemic, with a special focus on Campania region., Methods: This survey (25 questions), promoted by the young section of SCITO (Società Campana di ImmunoTerapia Oncologica) Group, was circulated among Italian young oncologists practicing in regions variously affected by the pandemic: high (group 1), medium (group 2) and low (group 3) prevalence of SARS-CoV-2-positive patients. For Campania region, the physician responders were split into those working in cancer centers (CC), university hospitals (UH) and general hospitals (GH). Percentages of agreement, among High (H) versus Medium (M) and versus Low (L) group for Italy and among CC, UH and GH for Campania region, were compared by using Fisher's exact tests for dichotomous answers and χ
2 test for trends relative to the questions with 3 or more options., Results: This is the first Italian study to investigate the COVID-19 impact on cancer immunotherapy, unique in its type and very clear in the results. The COVID-19 pandemic seemed not to affect the standard practice in the prescription and delivery of ICIs in Italy. Telemedicine was widely used. There was high consensus to interrupt immunotherapy in SARS-CoV-2-positive patients and to adopt ICIs with longer schedule interval. The majority of the responders tended not to delay the start of ICIs; there were no changes in supportive treatments, but some of the physicians opted for delaying surgeries (if part of patients' planned treatment approach). The results from responders in Campania did not differ significantly from the national ones., Conclusion: Our study highlights the efforts of Italian oncologists to maintain high standards of care for CPs treated with ICIs, regardless the regional prevalence of COVID-19, suggesting the adoption of similar solutions. Research on patients treated with ICIs and experiencing COVID-19 will clarify the safety profile to continue the treatments, thus informing on the most appropriate clinical conducts., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2020
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26. Plasma Thymidine Kinase Activity as a Biomarker in Patients with Luminal Metastatic Breast Cancer Treated with Palbociclib within the TREnd Trial.
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McCartney A, Bonechi M, De Luca F, Biagioni C, Curigliano G, Moretti E, Minisini AM, Bergqvist M, Benelli M, Migliaccio I, Galardi F, Risi E, De Santo I, Romagnoli D, Biganzoli L, Di Leo A, and Malorni L
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers, Tumor blood, Breast Neoplasms blood, Breast Neoplasms pathology, Cell Line, Tumor, Cyclin-Dependent Kinase 4 antagonists & inhibitors, Cyclin-Dependent Kinase 4 blood, Cyclin-Dependent Kinase 6 antagonists & inhibitors, Cyclin-Dependent Kinase 6 blood, Drug Resistance, Neoplasm, Female, Humans, Middle Aged, Neoplasm Metastasis, Protein Kinase Inhibitors therapeutic use, Receptors, Estrogen metabolism, Survival Rate, Thymidine Kinase blood, Treatment Switching, Breast Neoplasms drug therapy, Breast Neoplasms enzymology, Piperazines therapeutic use, Pyridines therapeutic use
- Abstract
Purpose: Thymidine kinase 1 (TK1) is downstream to the CDK4/6 pathway, and TK activity (TKa) measured in blood is a dynamic marker of outcome in patients with advanced breast cancer (ABC). This study explores TK1 as a biomarker of palbociclib response, both in vitro and in patients with ABC., Experimental Design: Modulation of TK1 levels and activity by palbociclib were studied in seven estrogen receptor-positive breast cancer cell lines: sensitive (PDS) and with palbociclib acquired resistance (PDR). TKa was assayed in plasma obtained at baseline (T0), after one cycle (T1), and at disease progression on palbociclib (T2) in patients enrolled in the "To Reverse ENDocrine Resistance" (TREnd) trial ( n = 46)., Results: Among E2F-dependent genes, TK1 was significantly downregulated after short-term palbociclib. Early TKa reduction by palbociclib occurred in PDS but not in PDR cells. In patients, median TKa (mTKa) at T0 was 75 DiviTum units per liter (Du/L), with baseline TKa not proving prognostic. At T1, mTKa decreased to 35 Du/L, with a minority of patients ( n = 8) showing an increase-correlating with a worse outcome than those with decreased/stable TKa ( n = 33; mPFS 3.0 vs 9.0 months; P = 0.002). At T2, mTKa was 251 Du/L; patients with TKa above the median had worse outcomes on post-study treatment compared with those with lower TKa (2.9 vs 8.7 months; P = 0.05)., Conclusions: TK is a dynamic marker of resistance to palbociclib which may lead to early identification of patients in whom treatment escalation may be feasible. In addition, TKa may stratify prognosis in patients with acquired resistance to palbociclib., (©2020 American Association for Cancer Research.)
- Published
- 2020
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27. Strain-oriented strategy for guiding cardioprotection initiation of breast cancer patients experiencing cardiac dysfunction.
- Author
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Santoro C, Esposito R, Lembo M, Sorrentino R, De Santo I, Luciano F, Casciano O, Giuliano M, De Placido S, Trimarco B, Lancellotti P, Arpino G, and Galderisi M
- Subjects
- Echocardiography, Female, Humans, Stroke Volume, Antineoplastic Agents adverse effects, Breast Neoplasms diagnostic imaging, Breast Neoplasms drug therapy, Heart Diseases, Ventricular Dysfunction, Left
- Abstract
Aims: This study assessed the impact of the strain-guided therapeutic approach on cancer therapy-related cardiac dysfunction (CTRCD) and rate of cancer therapy (CT) interruption in breast cancer., Methods and Results: We enrolled 116 consecutive female patients with HER2-positive breast cancer undergoing a standard protocol by EC (epirubicine + cyclophosphamide) followed by paclitaxel + trastuzumab (TRZ). Coronary artery, valvular and congenital heart disease, heart failure, primary cardiomyopathies, permanent or persistent atrial fibrillation, and inadequate echo-imaging were exclusion criteria. Patients underwent an echo-Doppler exam with determination of ejection fraction (EF) and global longitudinal strain (GLS) at baseline and every 3 months during CT. All patients developing subclinical (GLS drop >15%) or overt CTRCD (EF reduction <50%) initiated cardiac treatment (ramipril+ carvedilol). In the 99.1% (115/116) of patients successfully completing CT, GLS and EF were significantly reduced and E/e' ratio increased at therapy completion. Combined subclinical and overt CTRCD was diagnosed in 27 patients (23.3%), 8 at the end of EC and 19 during TRZ courses. Of these, 4 (3.4%) developed subsequent overt CTRCD and interrupted CT. By cardiac treatment, complete EF recovery was observed in two of these patients and partial recovery in one. These patients with EF recovery re-started and successfully completed CT. The remaining patient, not showing EF increase, permanently stopped CT. The other 23 patients with subclinical CTRCD continued and completed CT., Conclusion: These findings highlight the usefulness of 'strain oriented' approach in reducing the rate of overt CTRCD and CT interruption by a timely cardioprotective treatment initiation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2019
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28. Cyclin-Dependent Kinase 4/6 Inhibitors in Neoadjuvant Endocrine Therapy of Hormone Receptor-Positive Breast Cancer.
- Author
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Rossi L, McCartney A, Risi E, De Santo I, Migliaccio I, Malorni L, Biganzoli L, and Di Leo A
- Subjects
- Breast Neoplasms metabolism, Breast Neoplasms pathology, Female, Humans, Neoplasms, Hormone-Dependent metabolism, Neoplasms, Hormone-Dependent pathology, Prognosis, Receptor, ErbB-2 metabolism, Receptors, Estrogen metabolism, Receptors, Progesterone metabolism, Breast Neoplasms drug therapy, Cyclin-Dependent Kinase 4 antagonists & inhibitors, Cyclin-Dependent Kinase 6 antagonists & inhibitors, Molecular Targeted Therapy, Neoadjuvant Therapy, Neoplasms, Hormone-Dependent drug therapy, Protein Kinase Inhibitors therapeutic use
- Abstract
The landscape of therapeutic options for the treatment of hormone receptor (HR)-positive (HR
+ ) HER2- breast cancer (BC) has been profoundly changed by the introduction of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors into the metastatic setting. Currently all CDK4/6 inhibitors are approved only in the metastatic setting by Food and Drug Administration (FDA) and European Medicine Agency (EMA), whereas their role in the neoadjuvant setting is still at an investigational stage. Exploitation of novel agents such as CDK4/6 inhibitors to improve the efficacy of neoadjuvant endocrine therapy (ET) or to overcome de novo resistance to ET is an area of research under active evaluation. We present a review of the currently available data and ongoing clinical trials that are evaluating the role of CDK4/6 inhibitors in neoadjuvant therapy of HR+ HER2- early BC, and also illustrate translational aspects, such as the potential biomarkers of response to these new therapeutic agents., (Copyright © 2019 Elsevier Inc. All rights reserved.)- Published
- 2019
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29. The Emerging Role of ESR1 Mutations in Luminal Breast Cancer as a Prognostic and Predictive Biomarker of Response to Endocrine Therapy.
- Author
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De Santo I, McCartney A, Migliaccio I, Di Leo A, and Malorni L
- Abstract
Mutations in the hotspot ligand-binding domain of the estrogen receptor (ER) gene ESR1 have recently been recognized as mechanisms of endocrine resistance in endocrine receptor-positive metastatic breast cancer (MBC). Accumulating data suggest these mutations develop under the selective pressure of endocrine treatments, and are infrequent in untreated ER-positive breast cancers. In vitro studies show that these mutations confer ligand-independent activity, resistance to estrogen deprivation, and relative resistance to tamoxifen and fulvestrant. Post-hoc retrospective and prospective analyses of ESR1 mutations in patients with MBC have consistently found that these mutations are markers of poor prognosis and predict resistance to aromatase inhibitors (AIs). These results warrant further investigation and prospective validation in dedicated studies. Moreover, studies are ongoing to clarify the activity of novel drugs in the context of metastatic endocrine resistant luminal breast cancer harboring ESR1 mutations. In this review, we summarize the pre-clinical and clinical findings defining the characteristics of ESR1 mutant breast cancer, and highlight the potential clinical developments in this field.
- Published
- 2019
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30. Unexpected ovarian activity in premenopausal breast cancer survivors treated with exemestane and GnRH analogues.
- Author
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Conforti A, Schettini F, Vallone R, Di Rella F, De Rosa P, De Santo I, Giuliano M, Arpino G, Lauria R, De Placido S, Caputo R, De Laurentiis M, Nazzaro G, De Placido G, Locci M, and Alviggi C
- Subjects
- Adult, Antineoplastic Agents, Hormonal administration & dosage, Antineoplastic Agents, Hormonal adverse effects, Cancer Survivors statistics & numerical data, Chemotherapy, Adjuvant adverse effects, Chemotherapy, Adjuvant methods, Female, Humans, Ovary drug effects, Ovary metabolism, Ovary physiopathology, Premenstrual Syndrome diagnosis, Uterine Hemorrhage diagnosis, Androstadienes administration & dosage, Androstadienes adverse effects, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Drug Monitoring methods, Drug Monitoring standards, Estradiol blood, Gonadotropin-Releasing Hormone agonists, Ovarian Function Tests methods, Ovarian Function Tests standards, Tamoxifen administration & dosage, Tamoxifen adverse effects
- Published
- 2019
- Full Text
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31. Mechanisms of Resistance to CDK4/6 Inhibitors: Potential Implications and Biomarkers for Clinical Practice.
- Author
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McCartney A, Migliaccio I, Bonechi M, Biagioni C, Romagnoli D, De Luca F, Galardi F, Risi E, De Santo I, Benelli M, Malorni L, and Di Leo A
- Abstract
The recent arrival of CDK4/6 inhibitor agents, with an approximate doubling of progression-free survival (PFS) associated with their use in hormone receptor-positive, HER2-negative advanced breast cancer (BC), has radically changed the approach to managing this disease. However, resistance to CDK4/6 inhibitors is considered a near-inevitability in most patients. Mechanisms of resistance to these agents are multifactorial, and research in this field is still evolving. Biomarkers with the ability to identify early resistance, or to predict the likelihood of successful treatment using CDK4/6 inhibitors are yet to be identified, and represent an area of unmet clinical need. Here we present selected mechanisms of resistance to CDK4/6 inhibitors, largely focussing on roles of Rb, cyclin E1, and the PIK3CA pathway, with discussion of associated biomarkers which have been investigated and applied in recent pre-clinical and clinical studies. These biological drivers may furthermore influence clinical treatment strategies adopted beyond CDK4/6 resistance.
- Published
- 2019
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32. The optimal duration of adjuvant endocrine therapy in early luminal breast cancer: A concise review.
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Rossi L, McCartney A, De Santo I, Risi E, Moretti E, Malorni L, Biganzoli L, and Di Leo A
- Subjects
- Aromatase Inhibitors administration & dosage, Drug Administration Schedule, Gonadotropin-Releasing Hormone agonists, Humans, Randomized Controlled Trials as Topic, Tamoxifen administration & dosage, Antineoplastic Agents, Hormonal administration & dosage, Breast Neoplasms drug therapy
- Abstract
Patients with luminal early breast cancer are at risk of relapse, even after five years of adjuvant endocrine therapy. To date, no biomarkers have been clinically validated to identify those patients at risk of late recurrence, who might benefit from extended adjuvant endocrine therapy. In recent decades, multiple clinical trials have tested the role of extending adjuvant endocrine therapies in patients with luminal disease. However, the data currently at our disposal are conflicting. This article reviews all the major trials concerning extended adjuvant endocrine regimens, and formulates some general conclusions and hypotheses of future study., (Copyright © 2019. Published by Elsevier Ltd.)
- Published
- 2019
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33. CDK 4/6 Inhibitors as Single Agent in Advanced Solid Tumors.
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Schettini F, De Santo I, Rea CG, De Placido P, Formisano L, Giuliano M, Arpino G, De Laurentiis M, Puglisi F, De Placido S, and Del Mastro L
- Abstract
Cyclin-dependent kinases (CDK) 4/6 inhibitors, namely abemaciclib, palbociclib, and ribociclib, interfere with cell cycle progression, induce cell senescence and might promote cancer cell disruption by a cytotoxic T cells-mediated effect. Phase III randomized clinical trials have proven that CDK4/6 inhibitors (CDK4/6i) in combination with several endocrine agents improve treatment efficacy over endocrine agents alone for hormone receptor positive (HR+) HER2 negative (HER2-) metastatic breast cancer (MBC). Based on such results, these combinations have been approved for clinical use. Preclinical studies in cell cultures and mouse models proved that CDK4/6i are active against a broad spectrum of solid tumors other than breast cancer, including liposarcoma, rhabdomyosarcoma, non-small cell lung cancer, glioblastoma multiforme, esophageal cancer, and melanoma. The role of CDK4/6i in monotherapy in several solid tumors is currently under evaluation in phase I, II, and III trials. Nowadays, abemaciclib is the only of the three inhibitors that has received approval as single agent therapy for pretreated HR+ HER2- MBC. Here we review biological, preclinical and clinical data on the role of CDK4/6 inhibitors as single agents in advanced solid tumors.
- Published
- 2018
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34. Fractional microablative CO2 laser in breast cancer survivors affected by iatrogenic vulvovaginal atrophy after failure of nonestrogenic local treatments: a retrospective study.
- Author
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Pagano T, De Rosa P, Vallone R, Schettini F, Arpino G, Giuliano M, Lauria R, De Santo I, Conforti A, Gallo A, Nazzaro G, De Placido S, Locci M, and De Placido G
- Subjects
- Adult, Atrophy, Female, Humans, Laser Therapy, Middle Aged, Retrospective Studies, Severity of Illness Index, Survivors, Treatment Outcome, Vagina pathology, Vaginal Diseases pathology, Vulva pathology, Breast Neoplasms, Vaginal Diseases surgery
- Abstract
Objective: Vulvovaginal atrophy (VVA) is a condition frequently observed in menopause. Its symptoms can significantly affect the quality of life of patients. Since VVA is related to estrogen deficiency, chemotherapy and hormone therapy for breast cancer (BC) might cause VVA by inducing menopause. Given the lack of effective treatment for VVA in BC survivors, we retrospectively evaluated the efficacy and tolerability of fractional microablative CO2 laser therapy in these patients., Methods: We treated 82 BC survivors with three cycles of CO2 laser after failure of topical nonestrogenic therapy. The severity of symptoms was assessed with a visual analog scale (VAS) at baseline and after completion of laser therapy. Differences in mean VAS scores of each symptom before and after treatment were assessed with multiple t tests for pairwise comparisons. Multivariate analyses were used to adjust the final mean scores for the main confounding factors., Results: Pre versus post-treatment differences in mean VAS scores were significant for sensitivity during sexual intercourse, vaginal dryness, itching/stinging, dyspareunia and dysuria (P < 0.001 for all), bleeding (P = 0.001), probe insertion (P = 0.001), and movement-related pain (P = 0.011). Multivariate analyses confirmed that results were significant, irrespective of patients' age and type of adjuvant therapy., Conclusion: This study shows that CO2 laser treatment is effective and safe in BC patients with iatrogenic menopause. However, the optimal number of cycles to administer and the need for retreatment remain to be defined. Prospective trials are needed to compare CO2 laser therapy with therapeutic alternatives.
- Published
- 2018
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35. Correction: Rheometry-on-a-chip: measuring the relaxation time of a viscoelastic liquid through particle migration in microchannel flows.
- Author
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Del Giudice F, D'Avino G, Greco F, De Santo I, Netti PA, and Maffettone PL
- Published
- 2016
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36. Hindered Brownian diffusion in a square-shaped geometry.
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Gentile FS, De Santo I, D'Avino G, Rossi L, Romeo G, Greco F, Netti PA, and Maffettone PL
- Subjects
- Diffusion, Image Processing, Computer-Assisted, Microscopy, Confocal, Computer Simulation, Models, Chemical, Polystyrenes chemistry
- Abstract
We study the spatial dependence of the mobility of microparticles diffusing close to an edge of a square microtube. Confocal particle tracking is used to measure the local diffusion coefficients of fluorescent latex 1.1μm particles suspended in an aqueous solution in a borosilicate square capillary of 50μm section side. Observations are made for a set of planes obtained by confocal sectioning of the capillary volume. The translational diffusion coefficients parallel to the axis channel and perpendicular to one of the walls are measured as a function of the distance from both the two channel walls concurring in an edge. A complete 3D spatial map of the colloid diffusion coefficients is thus obtained. Near the corner, the diffusion is hindered up to about 40% as compared to its bulk value. The three translational diffusion coefficients pertaining to the motions along the channel axis and within the channel cross-section turn out to be different from each other and differently affected by the confinement, i.e., we are in the presence of an anisotropic diffusion. The hindered diffusion phenomenon is also examined by finite element numerical simulations, and the numerical predictions fairly agree with the measured diffusion coefficients., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
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37. Rheometry-on-a-chip: measuring the relaxation time of a viscoelastic liquid through particle migration in microchannel flows.
- Author
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Del Giudice F, D'Avino G, Greco F, De Santo I, Netti PA, and Maffettone PL
- Subjects
- Glycerol chemistry, Microfluidic Analytical Techniques instrumentation, Motion, Particle Size, Polymers chemistry, Rheology instrumentation, Time Factors, Water chemistry, Microfluidic Analytical Techniques methods, Rheology methods, Viscoelastic Substances chemistry
- Abstract
A novel method to estimate the relaxation time of viscoelastic fluids, down to milliseconds, is here proposed. The adopted technique is based on the particle migration phenomenon occurring when the suspending viscoelastic fluid flows in microfluidic channels. The method is applied to measure the fluid relaxation times of two water-glycerol polymer solutions in an ample range of concentrations. A remarkable improvement in the accuracy of the measure of the relaxation time is found, as compared with experimental data obtained from shear or elongational experiments available in the literature. Good agreement with available theoretical predictions is also found. The proposed method is reliable, handy and does not need a calibration curve, opening an effective way to measure relaxation times of viscoelastic fluids otherwise not easily detectable by conventional techniques.
- Published
- 2015
- Full Text
- View/download PDF
38. Exploring doxorubicin localization in eluting TiO2 nanotube arrays through fluorescence correlation spectroscopy analysis.
- Author
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De Santo I, Sanguigno L, Causa F, Monetta T, and Netti PA
- Subjects
- Diffusion, Kinetics, Temperature, Doxorubicin chemistry, Nanotubes chemistry, Spectrometry, Fluorescence methods, Titanium chemistry
- Abstract
Drug elution properties of TiO(2) nanotube arrays have been largely investigated by means of solely macroscopic observations. Controversial elution performances have been reported so far and a clear comprehension of these phenomena is still missing as a consequence of a lack of molecular investigation methods. Here we propose a way to discern drug elution properties of nanotubes through the evaluation of drug localization by Fluorescence Correlation Spectroscopy (FCS) analysis. We verified this method upon doxorubicin elution from differently loaded TiO(2) nanotubes. Diverse elution profiles were obtained from nanotubes filled by soaking and wet vacuum impregnation methods. Impregnated nanotubes controlled drug diffusion up to thirty days, while soaked samples completed elution in seven days. FCS analysis of doxorubicin motion in loaded nanotubes clarified that more than 90% of drugs dwell preferentially in inter-nanotube spaces in soaked samples due to decorrelation in a 2D fashion, while a 97% fraction of molecules showed 1D mobility ascribable to displacements along the nanotube vertical axis of wet vacuum impregnated nanotubes. The diverse drug localizations inferred from FCS measurements, together with distinct drug-surface interaction strengths resulting from diverse drug filling techniques, could explain the variability in elution kinetics.
- Published
- 2012
- Full Text
- View/download PDF
39. Fluorescence lifetimes and quantum yields of rhodamine derivatives: new insights from theory and experiment.
- Author
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Savarese M, Aliberti A, De Santo I, Battista E, Causa F, Netti PA, and Rega N
- Subjects
- Microscopy, Fluorescence, Molecular Structure, Time Factors, Fluorescence, Fluorescent Dyes chemistry, Quantum Theory, Rhodamines chemistry
- Abstract
Although lifetimes and quantum yields of widely used fluorophores are often largely characterized, a systematic approach providing a rationale of their photophysical behavior on a quantitative basis is still a challenging goal. Here we combine methods rooted in the time-dependent density functional theory and fluorescence lifetime imaging microscopy to accurately determine and analyze fluorescence signatures (lifetime, quantum yield, and band peaks) of several commonly used rhodamine and pyronin dyes. We show that the radiative lifetime of rhodamines can be correlated to the charge transfer from the phenyl toward the xanthene moiety occurring upon the S(0) ← S(1) de-excitation, and to the xanthene/phenyl relative orientation assumed in the S(1) minimum structure, which in turn is variable upon the amino and the phenyl substituents. These findings encourage the synergy of experiment and theory as unique tool to design finely tuned fluorescent probes, such those conceived for modern optical sensors.
- Published
- 2012
- Full Text
- View/download PDF
40. Fluorescence correlation spectroscopy in semiadhesive wall proximity.
- Author
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Sanguigno L, De Santo I, Causa F, and Netti PA
- Subjects
- Diffusion, Humans, Cell Adhesion, Cell Membrane, Fluorescent Dyes chemistry, Models, Biological, Nanotubes, Spectrometry, Fluorescence
- Abstract
With examination of diffusion in heterogeneous media through fluorescence correlation spectroscopy, the temporal correlation of the intensity signal shows a long correlation tail and the characteristic diffusion time results are no longer easy to determine. Excluded volume and sticking effects have been proposed to justify such deviations from the standard behavior since all contribute and lead to anomalous diffusion mechanisms . Usually, the anomalous coefficient embodies all the effects of environmental heterogeneity providing too general explanations for the exotic diffusion recorded. Here, we investigated whether the reason of anomalies could be related to a lack of an adequate interpretative model for heterogeneous systems and how the presence of obstacles on the detection volume length scale could affect fluorescence correlation spectroscopy experiments. We report an original modeling of the autocorrelation function where fluorophores experience reflection or adsorption at a wall placed at distances comparable with the detection volume size. We successfully discriminate between steric and adhesion effects through the analysis of long time correlations and evaluate the adhesion strength through the evaluation of probability of being adsorbed and persistence time at the wall on reference data. The proposed model can be readily adopted to gain a better understanding of intracellular and nanoconfined diffusion opening the way for a more rational analysis of the diffusion mechanism in heterogeneous systems and further developing biological and biomedical applications.
- Published
- 2011
- Full Text
- View/download PDF
41. A closed form for fluorescence correlation spectroscopy experiments in submicrometer structures.
- Author
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Sanguigno L, De Santo I, Causa F, and Netti P
- Subjects
- Diffusion, Models, Molecular, Fluorescent Dyes chemistry, Spectrometry, Fluorescence methods
- Abstract
Fluorescence correlation spectroscopy (FCS) is a powerful technique for measuring low concentrations of fluorescent molecules and their diffusion coefficients in an open detection volume. However, in several practical cases, when FCS measurements are carried out in small compartments like microchannels, neglecting boundary effects could lead to erroneous results. Here, a close form solution is proposed to explicitly account for the presence of walls located at a distance comparable with the characteristic detection volume lengths. We derive a one-dimensional diffusion constrained model and then generalize the solution to the two- and the three-dimensional constrained cases. We further indicate within which limits the standard autocorrelation function (ACF) model gives reliable results in microconfinement. Our model relies just on the assumption of elastic hits at the system walls and succeeds in describing the ACF of fluorescent probes confined along one direction. Through the analysis of FCS experimental data, we are able to predict the correct shape of the ACF in channels of micrometric and submicrometric width and measure the extent of lateral confinement. In addition, it permits the investigation of microstructured material features such as cages and cavities having dimensions on the micrometric range. On the basis of the proposed model, we also show in which conditions confinement could generate an apparent time dependent probe mobility, thus allowing a proper interpretation of the transport process taking place in submicrometric compartments.
- Published
- 2010
- Full Text
- View/download PDF
42. Subdiffusive molecular motion in nanochannels observed by fluorescence correlation spectroscopy.
- Author
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De Santo I, Causa F, and Netti PA
- Subjects
- Adsorption, Dextrans chemistry, Diffusion, Fluorescent Dyes chemistry, Kinetics, Particle Size, Polyethylene Glycols chemistry, Rhodamines chemistry, Nanocomposites chemistry, Spectrometry, Fluorescence methods
- Abstract
The influence of confinement on biomolecule motion in glass channels of nanometric height has been investigated with fluorescence correlation spectroscopy (FCS). We measured intrachannel molecule diffusion time and concentration based on a single-component diffusion model as a function of molecule size to channel height (r(g)/h). Poly(ethylene glycol) (PEG) of 20 kDa and dextran of 40 kDa showed a reduction of their diffusion coefficients of almost 1 order of magnitude when nanochannel height approached probe diameter, whereas rhodamine 6G (Rh6G) was shown to be almost unaffected from confinement. Subdiffusive motion has been proven for flexible molecules in nanochannels, and deviations toward a square root dependence of mobility with time for confinement up to molecule size r(g)/h approximately 0.5 were registered. Diffusion coefficient time dependence has been evaluated and described with a model that accounts for diffusion time increase due to molecule rearrangements related to molecule flexibility and surface interactions dynamics. The evaluation of the subdiffusive mode and the key parameters extracted at the single-molecule level of partitioning, intrachannel diffusion time, desorption time, and binding probability at surfaces can be exploited for the engineering of bioanalytic nanodevices.
- Published
- 2010
- Full Text
- View/download PDF
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