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1. Oxaliplatin plus fluoropyrimidines as adjuvant therapy for colon cancer in older patients: A subgroup analysis from the TOSCA trial

Author

Rosati, G, Lonardi, S, Galli, F, Di Bartolomeo, M, Ronzoni, M, Zampino, M, Banzi, M, Zaniboni, A, Pasini, F, Bozzarelli, S, Garattini, S, Ferrari, D, Montesarchio, V, Mambrini, A, Ciuffreda, L, Pusceddu, V, Carlomagno, C, Bidoli, P, Amoroso, D, Bochicchio, A, Frassineti, L, Corsi, D, Bilancia, D, Pastorino, A, De Stefano, A, Labianca, R, Iaffaioli, R, Nasti, G, Daniele, B, Zagonel, V, Pella, N, Aprile, G, Marchetti, R, Romiti, A, Foa, P, Mosconi, S, Sobrero, A, Cazzaniga, M, Beretta, G, Cortesi, E, Barni, S, Petrelli, F, Allione, P, D'Arco, A, Valmadre, G, Piazza, E, Veltri, E, Ramus, G, Giustini, L, Tumulo, S, Cascinu, S, Granetto, C, Testore, F, Giordano, M, Moroni, M, Di Seri, M, Nuzzo, A, Angelelli, L, Gori, S, Farina, G, Aglietta, M, Franchi, R, Comande, M, Giordani, P, Tonini, G, Bucci, E, Ballestrero, A, Benasso, M, Graiff, C, Bravi, S, Caffo, O, Silva, R, Frontini, L, Rota, S, Cozzi, L, Cantore, M, Maiello, E, Cinieri, S, Silvestris, N, Romito, S, Gebbia, V, Santoro, A, Artioli, F, Mattioli, R, Contu, A, Di Costanzo, F, Leonardi, F, Cavanna, L, Passalacqua, R, Sozzi, P, D'Amico, M, Amadori, D, Turci, D, Ravaioli, A, Pasquini, E, Gambi, A, Faedi, M, Cruciani, G, Bajetta, E, Gianni, L, Ionta, M, Massidda, B, Scartozzi, M, Ciarlo, A, Di Leo, A, Frustaci, S, Rangoni, G, Arizzoia, A, Pavesi, L, Verusio, C, Pinotti, G, Iop, A, De Placido, S, Adamo, V, Ficorella, C, Natale, D, Greco, E, Rulli, E, Poli, D, Porcu, L, Torri, V, Rosati G., Lonardi S., Galli F., Di Bartolomeo M., Ronzoni M., Zampino M. G., Banzi M., Zaniboni A., Pasini F., Bozzarelli S., Garattini S. K., Ferrari D., Montesarchio V., Mambrini A., Ciuffreda L., Pusceddu V., Carlomagno C., Bidoli P., Amoroso D., Bochicchio A. M., Frassineti L., Corsi D., Bilancia D., Pastorino A., De Stefano A., Labianca R., Iaffaioli R. V., Nasti G., Daniele B., Zagonel V., Pella N., Aprile G., Marchetti R. P., Romiti A., Foa P., Mosconi S., Sobrero A., Cazzaniga M., Beretta G. D., Cortesi E., Barni S., Petrelli F., Allione P., D'Arco A. M., Valmadre G., Piazza E., Veltri E., Ramus G. V., Giustini L., Tumulo S., Cascinu S., Granetto C., Testore F., Giordano M., Moroni M., Di Seri M., Nuzzo A., Angelelli L., Gori S., Farina G., Aglietta M., Franchi R., Comande M., Giordani P., Tonini G., Bucci E., Ballestrero A., Benasso M., Graiff C., Bravi S., Caffo O., Silva R. R., Frontini L., Rota S., Cozzi L., Cantore M., Maiello E., Cinieri S., Silvestris N., Romito S., Gebbia V., Santoro A., Artioli F., Mattioli R., Contu A., Di Costanzo F., Leonardi F., Cavanna L., Passalacqua R., Sozzi P., D'Amico M., Amadori D., Turci D., Ravaioli A., Pasquini E., Gambi A., Faedi M., Cruciani G., Bajetta E., Gianni L., Ionta M. T., Massidda B., Scartozzi M., Ciarlo A., Di Leo A., Frustaci S., Rangoni G., Arizzoia A., Pavesi L., Verusio C., Pinotti G., Iop A., De Placido S., Adamo V., Ficorella C., Natale D., Greco E., Rulli E., Poli D., Porcu L., Torri V., Rosati, G, Lonardi, S, Galli, F, Di Bartolomeo, M, Ronzoni, M, Zampino, M, Banzi, M, Zaniboni, A, Pasini, F, Bozzarelli, S, Garattini, S, Ferrari, D, Montesarchio, V, Mambrini, A, Ciuffreda, L, Pusceddu, V, Carlomagno, C, Bidoli, P, Amoroso, D, Bochicchio, A, Frassineti, L, Corsi, D, Bilancia, D, Pastorino, A, De Stefano, A, Labianca, R, Iaffaioli, R, Nasti, G, Daniele, B, Zagonel, V, Pella, N, Aprile, G, Marchetti, R, Romiti, A, Foa, P, Mosconi, S, Sobrero, A, Cazzaniga, M, Beretta, G, Cortesi, E, Barni, S, Petrelli, F, Allione, P, D'Arco, A, Valmadre, G, Piazza, E, Veltri, E, Ramus, G, Giustini, L, Tumulo, S, Cascinu, S, Granetto, C, Testore, F, Giordano, M, Moroni, M, Di Seri, M, Nuzzo, A, Angelelli, L, Gori, S, Farina, G, Aglietta, M, Franchi, R, Comande, M, Giordani, P, Tonini, G, Bucci, E, Ballestrero, A, Benasso, M, Graiff, C, Bravi, S, Caffo, O, Silva, R, Frontini, L, Rota, S, Cozzi, L, Cantore, M, Maiello, E, Cinieri, S, Silvestris, N, Romito, S, Gebbia, V, Santoro, A, Artioli, F, Mattioli, R, Contu, A, Di Costanzo, F, Leonardi, F, Cavanna, L, Passalacqua, R, Sozzi, P, D'Amico, M, Amadori, D, Turci, D, Ravaioli, A, Pasquini, E, Gambi, A, Faedi, M, Cruciani, G, Bajetta, E, Gianni, L, Ionta, M, Massidda, B, Scartozzi, M, Ciarlo, A, Di Leo, A, Frustaci, S, Rangoni, G, Arizzoia, A, Pavesi, L, Verusio, C, Pinotti, G, Iop, A, De Placido, S, Adamo, V, Ficorella, C, Natale, D, Greco, E, Rulli, E, Poli, D, Porcu, L, Torri, V, Rosati G., Lonardi S., Galli F., Di Bartolomeo M., Ronzoni M., Zampino M. G., Banzi M., Zaniboni A., Pasini F., Bozzarelli S., Garattini S. K., Ferrari D., Montesarchio V., Mambrini A., Ciuffreda L., Pusceddu V., Carlomagno C., Bidoli P., Amoroso D., Bochicchio A. M., Frassineti L., Corsi D., Bilancia D., Pastorino A., De Stefano A., Labianca R., Iaffaioli R. V., Nasti G., Daniele B., Zagonel V., Pella N., Aprile G., Marchetti R. P., Romiti A., Foa P., Mosconi S., Sobrero A., Cazzaniga M., Beretta G. D., Cortesi E., Barni S., Petrelli F., Allione P., D'Arco A. M., Valmadre G., Piazza E., Veltri E., Ramus G. V., Giustini L., Tumulo S., Cascinu S., Granetto C., Testore F., Giordano M., Moroni M., Di Seri M., Nuzzo A., Angelelli L., Gori S., Farina G., Aglietta M., Franchi R., Comande M., Giordani P., Tonini G., Bucci E., Ballestrero A., Benasso M., Graiff C., Bravi S., Caffo O., Silva R. R., Frontini L., Rota S., Cozzi L., Cantore M., Maiello E., Cinieri S., Silvestris N., Romito S., Gebbia V., Santoro A., Artioli F., Mattioli R., Contu A., Di Costanzo F., Leonardi F., Cavanna L., Passalacqua R., Sozzi P., D'Amico M., Amadori D., Turci D., Ravaioli A., Pasquini E., Gambi A., Faedi M., Cruciani G., Bajetta E., Gianni L., Ionta M. T., Massidda B., Scartozzi M., Ciarlo A., Di Leo A., Frustaci S., Rangoni G., Arizzoia A., Pavesi L., Verusio C., Pinotti G., Iop A., De Placido S., Adamo V., Ficorella C., Natale D., Greco E., Rulli E., Poli D., Porcu L., and Torri V.

Abstract

Background: Previous studies on oxaliplatin and fluoropyrimidines as adjuvant therapy in older patients with stage III colon cancer (CC) produced conflicting results. Patients and methods: We assessed the impact of age on time to tumour recurrence (TTR), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) in 2360 patients with stage III CC (1667 aged <70 years and 693 ≥ 70 years) randomised to receive 3 or 6 months of FOLFOX or CAPOX within the frame of the phase III, TOSCA study. Results: Older patients compared with younger ones presented more frequently an Eastern Cooperative Oncology Group performance status equal to 1 (10.5% vs 3.3%, p < 0.001), a greater number of right-sided tumours (40.9% vs 26.6%, p < 0.001), and were at higher clinical risk (37.2% vs 33.2%, p = 0.062). The treatments were almost identical in the two cohorts (p = 0.965). We found a greater proportion of dose reductions (46.7% vs 41.4%, p = 0.018), treatment interruptions (26.1% vs 19.3%, p < 0.001) and a higher proportion of recurrences (24.2% vs 20.3%, p = 0.033) in the older patients. The multivariable analysis of the TTR did not indicate a statistically significant effect of age (hazard ratio [HR]: 1.19; 95% confidence interval [CI]: 0.98–1.44; p = 0.082). The HR comparing older with younger patients was 1.34 (95% CI: 1.12–1.59; p = 0.001) for DFS, 1.58 (95% CI: 1.26–1.99; p < 0.001) for OS, and 1.28 (95% CI: 0.96–1.70; p = 0.089) for CSS. Conclusions: Worse prognostic factors and reduced treatment compliance have a negative impact on the efficacy of oxaliplatin-based adjuvant therapy in older patients.

Published
2021

3. Abstract OT1-03-03: Phase II, open label, randomized, biomarker study of immune-mediated mechanism of action of neoadjuvant subcutaneous trastuzumab in patients with operable or locally advanced/Inflammatory HER2-positive breast cancer. ImmunHER trial on behalf of the Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC)

Author

Musolino, A, primary, Gori, S, additional, Cavanna, L, additional, Graiff, C, additional, Frassoldati, A, additional, Bria, E, additional, Bisagni, G, additional, Zambelli, A, additional, Partesotti, G, additional, Brandes, A, additional, Bonetti, A, additional, Moscetti, L, additional, Zamagni, C, additional, Rocca, A, additional, Generali, D, additional, Montemurro, F, additional, Gianni, L, additional, Tognetto, M, additional, Maglietta, G, additional, and Todeschini, R, additional

Published
2018
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4. Trattamenti sostenibili per la protezione e il consolidamento di legno e carta

Author

Bergamonti L., Graiff C., Isca C., Predieri G., Lottici P.P., Di Maggio R., Palanti S., Maistrello L., and Montanari M.

Subjects
wood, paper, polyamidoamines, preservation, sustainable treatments, polyamidoamines, paper, preservation, sustainable treatments, wood
Abstract

Nuove poliammidoammine (PAA) funzionalizzate sono state sviluppate per la protezione sostenibile di legno e carta. Esse sono polimeri ecocompatibili, biocompatibili, dotati di un ampio spettro di azione protettiva e attivi a bassa concentrazione. Le PAA sono veicolabili omogeneamente con mezzi acquosi all'interno dei manufatti lignocellulosici dove esercitano soprattutto le azioni deacidificante e biostatica contro batteri, funghi, muffe e insetti. Nel caso di antichi manoscritti possono fissare l'inchiostro ferro-gallico formando complessi insolubili di ferro.

Published
2017
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5. Incidence, characteristics and treatment of fatigue in oncological cancer patients (pts) in italy: a cross-section study

Author

Roila, F., primary, Spina, F., additional, Ripamonti, C., additional, Fumi, G., additional, Antonuzzo, A., additional, Cavanna, L., additional, Gori, S., additional, Mirabile, A., additional, Fabi, A., additional, Marzano, N., additional, Graiff, C., additional, De Sanctis, V., additional, Serpentini, S., additional, Bocci, C., additional, Pino, M.S., additional, Clienti, G., additional, Verusio, C., additional, Lutrino, S.E., additional, Fatigoni, S., additional, and Ballatori, E., additional

Published
2016
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6. Breast cancer 'tailored follow-up' in Italian oncology units: a web-based survey

Author

Natoli, C., Brocco, D., Sperduti, I., Nuzzo, A., Tinari, N., De Tursi, M., Grassadonia, A., Mazzilli, L., Iacobelli, S., Gamucci, T., Vici, P., Study, Group, Adamo, V., Airoldi, M., Amoroso, D., Angelini, F., Angiolini, C., Angiolucci, G., Ardizzoia, A., Baldini, E., Ballardini, P., Barni, S., Barone, C., Battelli, N., Bernardi, D., Bianchetti, S., Bianco, N., Biglia, Nicoletta, Bilancia, D., Biti, G., Boni, C., Bordonaro, R., Botta, M., Bretti, S., Brunello, A., Brunetti, C., Bruno, D., Bucci, E., Buzzoni, R., Cagossi, K., Cappelletti, C., Cappuzzo, F., Cardillo, F., Carroccio, R., Cascinu, S., Cavanna, L., Cianchetti, E., Clerico, M., Contu, A., Corsi, D., Cortesi, L., Cretella, E., Crispino, S., Di Lieto, M., Di Lullo, L., Durini, E., Fabi, A., Failla, G., Fattorusso, S., Ferraù, F., Ferro, A., Ficorella, C., Fogazzi, G., Foglietta, J., Francini, G., Fusco, O., Gennari, A., Ghiani, M., Gianni, L., Giordano, M., Giotta, F., Giuliani, R., Gori, S., Graiff, C., Guarneri, V., Guarneri, D., Guglielmi, F., Landriscina, M., Laudadio, L., Lombardo, M., Longo, F., Macellari, G., Madeddu, C., Magnanini, S., Maiorino, L., Mangiameli, A., Marini, G., Massidda, B., Mattioli, R., Michelotti, A., Molino, A., Montesarchio, V., Morale, A., Murgo, R., Naso, G., Natale, D., Orditura, M., Orrù, S., Pace, R., Palazzo, A., Palma, F., Pancotti, A., Pandoli, G., Papaldo, P., Parisi, A. M., Passalacqua, R., Pellegrino, A., Perrucci, B., Proietti, E., Recchia, F., Riccardi, F., Rispoli, A. I., Rocca, A., Romaniello, I., Rossetti, R., Rossi, D., Rosti, G., Ruggeri, E. M., Russo, A., Savarino, A., Savastano, C., Scognamiglio, G., Scognamiglio, M., Seminara, P., Serrachini, S., Sidoti, V., Silva, R. R., Surace, G., Tomao, S., Tonini, G., Trenta, P., Turazza, M., Valenza, R., Veltri, E., Zampa, G., Zaniboni, A., Zanirato, S., C, Natoli, D, Brocco, I, Sperduti, A, Nuzzo, N, Tinari, M, De Tursi, A, Grassadonia, L, Mazzilli, S, Iacobelli, T, Gamucci, P, Vici, Study Group, 'FOLLOW-UP', and Orditura, Michele

Subjects
Oncology, breast cancer, Follow-up, survey, Medical Oncology, law.invention, Randomized controlled trial, law, Aged, Breast Neoplasms, Female, Follow-Up Studies, Health Care Surveys, Humans, Italy, Middle Aged, Secondary Prevention, Guideline Adherence, Breast Tumors, Medicine and Health Sciences, Web based survey, Multidisciplinary, Pharmaceutics, Surgical Oncology, Cancer Therapy, Medicine, medicine.symptom, Disease staging, Research Article, medicine.medical_specialty, Adjuvant Cancer Chemotherapy, Science, MEDLINE, Asymptomatic, Breast cancer, Drug Therapy, Internal medicine, medicine, Cancer Detection and Diagnosis, Chemotherapy, Modalities, business.industry, Cancers and Neoplasms, medicine.disease, Blood chemistry, Women's Health, Clinical Medicine, business
Abstract

PurposeBreast cancer follow-up procedures after primary treatment are still a controversial issue. Aim of this study was to investigate, through a web-based survey, surveillance methodologies selected by Italian oncologists in everyday clinical practice.MethodsReferents of Italian medical oncology units were invited to participate to the study via e-mail through the SurveyMonkey website. Participants were asked how, in their institution, exams of disease staging and follow-up are planned in asymptomatic women and if surveillance continues beyond the 5th year.ResultsBetween February and May 2013, 125 out of 233 (53.6%) invited referents of Italian medical oncology units agreed to participate in the survey. Ninety-seven (77.6%) referents state that modalities of breast cancer follow-up are planned according to the risk of disease progression at diagnosis and only 12 (9.6%) oncology units apply the minimal follow-up procedures according to international guidelines. Minimal follow-up is never applied in high risk asymptomatic women. Ninety-eight (78.4%) oncology units continue follow-up in all patients beyond 5 years.ConclusionsOur survey shows that 90.4% of participating Italian oncology units declare they do not apply the minimal breast cancer follow-up procedures after primary treatment in asymptomatic women, as suggested by national and international guidelines. Interestingly, about 80.0% of interviewed referents performs the so called "tailored follow-up", high intensity for high risk, low intensity for low risk patients. There is an urgent need of randomized clinical trials able to determine the effectiveness of risk-based follow-up modalities, their ideal frequency and persistence in time.

Published
2014

7. Breast cancer 'tailored follow-up' in Italian oncology units: a web-based survey

Author

Natoli, C, Adamo, V, Airoldi, M, Amoroso, D, Angelini, F, Angiolini, C, Angiolucci, G, Ardizzoia, A, Baldini, E, Ballardini, P, Barni, S, Barone, C, Battelli, N, Bernardi, D, Bianchetti, S, Bianco, N, Biglia, N, Bilancia, D, Biti, G, Boni, C, Bordonaro, R, Botta, M, Bretti, S, Brunello, A, Brunetti, C, Bruno, D, Bucci, E, Buzzoni, R, Cagossi, K, Cappelletti, C, Cappuzzo, F, Cardillo, F, Carroccio, R, Cascinu, S, Cavanna, L, Cianchetti, E, Clerico, M, Contu, A, Corsi, D, Cortesi, L, Cretella, E, Crispino, S, Di Lieto, M, Di Lullo, L, Durini, E, Fabi, A, Failla, G, Fattorusso, S, Ferraù, F, Ferro, A, Ficorella, C, Fogazzi, G, Foglietta, J, Francini, G, Fusco, O, Gennari, A, Ghiani, M, Gianni, L, Giordano, M, Giotta, F, Giuliani, R, Gori, S, Graiff, C, Guarneri, V, Guarneri, D, Guglielmi, F, Landriscina, M, Laudadio, L, Lombardo, M, Longo, F, Macellari, G, Madeddu, C, Magnanini, S, Maiorino, L, Mangiameli, A, Marini, G, Massidda, B, Mattioli, R, Michelotti, A, Molino, A, Montesarchio, V, Morale, A, Murgo, R, Naso, Giuseppe, Natale, D, Orditura, M, Orrù, S, Pace, R, Palazzo, Antonella, Palma, F, Pancotti, A, Pandoli, G, Papaldo, P, Parisi, Am, Passalacqua, R, Pellegrino, A, Perrucci, B, Proietti, E, Recchia, F, Riccardi, F, Rispoli, Ai, Rocca, A, Romaniello, I, Rossetti, R, Rossi, D, Rosti, G, Ruggeri, Em, Russo, A, Savarino, A, Savastano, C, Scognamiglio, G, Scognamiglio, M, Seminara, Patrizia, Serrachini, S, Sidoti, V, Silva, Rr, Surace, G, Tomao, Silverio, Tonini, G, Trenta, P, Turazza, M, Valenza, R, Veltri, E, Zampa, G, Zaniboni, A, and Zanirato, S.

Published
2014

8. Impact of use of oral anticancer drugs on activity of Italian oncology practices: results of a survey conducted by the Italian Society of Medical Oncology (AIOM)

Author

Gori, S, DI MAIO, Massimo, Pinto, C, Alabiso, O, Baldini, E, Barbato, E, Beretta, Gd, Bravi, S, Caffo, O, Canobbio, L, Carrozza, F, Cinieri, S, Cruciani, G, Dinota, A, Gebbia, V, Giustini, L, Graiff, C, Molino, A, Muggiano, A, Pandoli, G, Puglisi, F, Tagliaferri, P, Tomao, S, Lunardi, G, Venturini, M, and AIOM Working Group 'Interaction with Regional Sections'

Subjects
Adult, Male, oral anticancer drugs, Administration, Oral, Antineoplastic Agents, Medical Oncology, Pharmacists, Drug Costs, Reimbursement Mechanisms, Physicians, Surveys and Questionnaires, drug dispensation, Humans, Molecular Targeted Therapy, Practice Patterns, Physicians', Societies, Medical, Aged, Oncology Nursing, Health Care Costs, Middle Aged, reimbursement, Italy, Health Care Surveys, Workforce, Female
Abstract

In recent years, the number of oral anticancer drugs used in clinical practice has rapidly increased. The Italian Society of Medical Oncology (AIOM) conducted a survey to describe the impact of the use of oral anticancer drugs on the daily activity of Italian oncology practices.A survey questionnaire was distributed to the coordinators of the regional sections of AIOM. A 6-month period was considered, from January 1, 2010 to June 30, 2010. The survey addressed (1) quantitative aspects of the use of oral anticancer drugs; (2) practical aspects in the management of patients treated with these drugs; (3) issues related to treatment costs and reimbursement procedures.Thirty-six questionnaires were received from institutions distributed throughout the Italian territory. Oral anticancer drugs (both chemotherapy and molecularly targeted agents) accounted for a significant proportion (17%) of prescribed treatments. Among the responding institutions, there were different dispensation procedures of oral drugs to patients: drugs were dispensed by the pharmacist (57%) or directly by the medical oncologist (23%) or nurse (20%). The medical oncologist played a major role in the communication with patients (73% alone and a further 24% in cooperation with other professional figures) and was the point of reference in the event of side effects in 97% of cases. In most cases, the reimbursement of drug costs was separated ("File F" procedure) from the flat fare received by the hospital for outpatient visits or day-hospital access.Optimal organization of oral anticancer treatment warrants the cooperation and integration of multiple professional figures. At least three figures are involved in patient management in the hospital: the medical oncologist, the nurse, and the hospital pharmacist. Oral anticancer treatments are associated with specific reimbursement issues: in the majority of cases, the cost of the drug is reimbursed separately from the cost of patient access.

Published
2013

9. An international expanded-access programme of everolimus: Addressing safety and efficacy in patients with metastatic renal cell carcinoma who progress after initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy

Author

Grünwald, V, Karakiewicz, P, Bavbek, S, Miller, K, Machiels, J, Lee, S, Larkin, J, Bono, P, Rha, S, Castellano, D, Blank, C, Knox, J, Hawkins, R, Anak, O, Rosamilia, M, Booth, J, Pirotta, N, Bodrogi, I, Romedi, M, Ferrandini, S, Rondinon, M, Pittman, K, Goldstein, D, Shapiro, J, Troon, S, Yip, D, Mainwaring, P, Zigeuner, R, Loidl, W, Greil, R, Schmidinger, M, De Grève, J, Rottey, S, Vermorken, J, Gil, T, Gennigens, C, Roumeguere, T, Barrios, C, Mathias, C, Assi, H, Hotte, S, Spadafora, S, Wood, L, Zalewski, P, Mackensie, M, Bjarnason, G, Lalancette, A, Chan, A, Higgins, B, North, S, Soulieres, D, Asselah, J, Sperlich, C, Miller, W, Yadav, S, El Maraghi, R, Godoy, J, Prausová, J, Katolicka, J, Petruzelka, L, Kiss, I, Lapela, M, Bergmann, L, Beck, J, Jäger, E, Kindler, M, Overkamp, F, Wirth, M, Hölzer, W, Gschwend, J, Stenzl, A, Gauler, T, Niederwieser, D, Marschner, N, Lück, A, Tessen, H, Eichelberg, C, Steiner, T, Goebell, P, Kettner, E, Bakhshandeh Bath, A, Wilhelm, M, Schmitz, S, Jacob, A, Bierer, S, Kube, U, Staehler, M, Engel, E, Frambach, M, Schellenberger, U, Albers, P, Simon, J, Gleissler, M, Klotz, T, Repp, R, Kröning, H, Westermann, J, Rebmann, U, Brehmer, B, Niederle, N, Grund, C, Verpoort, K, Fonara, P, Rassweiler, J, Bamias, A, Fountzilas, G, Razis, E, Mouratidou, D, Georgoulias, V, Samantas, E, Mangel, L, Szanto, J, Berger, R, Pe'Er, A, Sella, A, Ben Yosef, R, Nechushtan, H, Crinò, L, Bracarda, S, Ciuffreda, L, Graiff, C, Falcone, A, Roselli, M, Sternberg, C, Santoro, A, Ruggeri, E, Bearz, A, Venturini, M, Aglietta, M, Amadori, D, Di Costanzo, F, Bari, M, Gebbia, N, Conte, P, Bonetti, A, Bordonaro, R, Cascinu, S, Contu, A, Cruciani, G, Gasparro, D, Nardi, M, Lelli, G, Lo Re, G, Boccardo, F, Lorusso, V, Maiello, E, Manente, P, Passalacqua, R, Piantedosi, F, Porta, C, Sacco, C, Tondini, C, De Placido, S, Carteni, G, Dogliotto, L, Rosti, G, Milella, M, Roila, F, Amoroso, D, Farina, G, Al Khatib, H, Kim, T, Ahn, J, Lim, H, Chung, I, Kim, J, Chung, J, Ghosn, M, Shameseddine, A, Lugo, R, Cabrera, P, Osanto, S, Groenewegen, G, van den Eertwegh, F, van Herpen, C, Oosting, S, Soetekouw, P, Lilleby, W, Klepp, O, Guren, T, Alcedo, J, Karlov, P, Nosov, D, Roman, L, Rusakov, I, Bazarbashi, S, Toh, C, Mardiak, J, del Muro Solans, F, Ray, J, Mollins, J, Martinez, I, Gonzalez, B, Santasusana, M, Piqueras, M, Fuentes, J, Larriba, J, Caro, R, Garcia, A, Aparicio, L, Lopez, N, Aragon, V, Morales, C, Figueiras, M, Ibanez, J, Billalabeitia, G, Estrada, E, Arranz, J, Sorrosal, J, Lozano, A, de Villena, M, Espinosa, E, Lopez, R, Perez, J, Laurell, A, Stierner, U, Cwikiel, M, Borner, M, Dietrich, P, Rothermundt, C, Pu, Y, Chang, Y, Ou, Y, Chuang, C, Liao, Y, Srimuninnimit, V, Sriuranpong, V, Buyukberber, S, Yalcin, B, Goker, E, Yalcin, S, Geldart, T, Wagstaff, J, Nicholson, S, Chowdhury, S, Bahl, A, Jones, R, Azzabi, A, Chao, D, Fife, K, Mead, G, Nathan, P, Pandha, H, Hajdenberg, J, Gabrail, N, Nimeh, N, Logan, T, Flaig, T, Schraeder, R, Rini, B, O'Rourke, M, Alemany, C, Kessinger, A, Amin, A, Arriaga, M, Rodriguez, J, Gauler, Thomas (Beitragende*r), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, and Laboratory of Molecular and Medical Oncology

Subjects
Nephrology, Oncology, Male, Cancer Research, mTOR inhibitor, Settore MED/06 - Oncologia Medica, Medizin, Advanced kidney cancer, RAD001, REACT, 0302 clinical medicine, Renal cell carcinoma, Receptors, 80 and over, Treatment Failure, Neoplasm Metastasis, Aged, 80 and over, 0303 health sciences, Vascular Endothelial Growth Factor, Sirolimus, Young Adult, Antineoplastic Agents, Humans, Aged, Immunosuppressive Agents, Protein Kinase Inhibitors, Receptors, Vascular Endothelial Growth Factor, Kidney Neoplasms, Adult, Carcinoma, Renal Cell, Middle Aged, Female, 3. Good health, 030220 oncology & carcinogenesis, Safety, medicine.drug, medicine.medical_specialty, SECOND LINE THERPAY, Second-line therapy, Everolimus, 03 medical and health sciences, Internal medicine, medicine, Adverse effect, 030304 developmental biology, business.industry, Carcinoma, Renal Cell, medicine.disease, Surgery, Clinical trial, Expanded access, business, Kidney cancer
Abstract

BACKGROUND AND OBJECTIVES: The RECORD-1 trial established the clinical benefit of everolimus in patients with metastatic renal cell carcinoma (mRCC) after failure of initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy. The REACT (RAD001 Expanded Access Clinical Trial in RCC) study was initiated to address an unmet medical need by providing everolimus prior to commercial availability, and also to further assess the safety and efficacy of everolimus in patients with VEGFr-TKI-refractory mRCC. PATIENTS AND METHODS: REACT (Clinicaltrials.gov: NCT00655252) was a global, open-label, expanded-access programme in patients with mRCC who were intolerant of, or who had progressed on or after stopping treatment with, any available VEGFr-TKI therapy. Patients received everolimus 10mg once daily, with dose and schedule modifications allowed for toxicity. Patients were closely monitored for the development of serious and grades 3/4 adverse events (AEs). Response was assessed by RECIST every 3months for the first year and every 6months thereafter. RESULTS: A total of 1367 patients were enroled. Safety findings and tumour responses were consistent with those observed in RECORD-1, with no new safety issues identified. The most commonly reported serious AEs were dyspnoea (5.0%), pneumonia (4.7%) and anaemia (4.1%), and the most commonly reported grades 3/4 AEs were anaemia (13.4%), fatigue (6.7%) and dyspnoea (6.5%). Best overall response was stable disease in 51.6% and partial response in 1.7% of patients. Median everolimus treatment duration was 14weeks. CONCLUSION: Everolimus is well tolerated in patients with mRCC and demonstrates a favourable risk-benefit ratio.

Published
2012

10. Characteristics and Prognostic Factors in 455 Elderly Pts Over 70 with Metastatic Renal Cell Carcinoma (Mrcc) Treated with Target Therapies (Tt) in the Community Setting: an Italian Survey

Author

Fraccon, A.P., primary, Pasini, F., additional, Basso, U., additional, Larussa, F., additional, Valduga, F., additional, Re, G. Lo, additional, Graiff, C., additional, Rosti, G., additional, Bearz, A., additional, Sartori, D., additional, Abeni, C., additional, Grillone, F., additional, Vicario, G., additional, Pegoraro, C., additional, Bassan, F., additional, Da Corte, D., additional, Modonesi, C., additional, Segati, R., additional, Medici, M., additional, and Barile, C., additional

Published
2014
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13. Evaluation of an unconventional cancer treatment (the Di Bella multitherapy): results of phase II trials in Italy

Author

Raschetti, R, Bruzzi, P, Greco, D, Maggini, M, Menniti Ippolito, F, Spila Alegiani, S, Traversa, G, Benagiano, G, Caffari, B, Chiarotti, F, Da Cas, R, De Mei, B, Di Giovambattista, G, Modigliani, S, Popoli, P, Ruggeri, P, Tomino, C, Gamucci, T, Amadori, D, Buiatti, E, Ciranni, E, Cognetti, F, Colucci, G, Conte, Pf, Di Bella, G, Iacobelli, S, Mandelli, F, Marubini, E, Massotti, M, Monfardini, S, Oleari, F, Sannazzari, Gl, Tomatis, L, Veronesi, U, Cellerino, R, Antognoli, S, Berardi, R, Bracci, R, Lippe, P, Pulita, F, Di Vito, F, Martinod, D, Musi, M, Veronesi, A, Lazzarini, R, Attolico, V, Giotta, F, Longo, M, Maiello, E, Tura, S, Gherlinzoni, F, Tani, M, Amor, H, Borona, P, Giradi, F, Graiff, C, Broccia, G, Corona, Mg, Desogus, A, Mascia, V, Pasqualucci, S, Failla, G, Aiello, Rm, Cordio, S, Finocchiaro, P, Melena, E, Tursi, De, Scognamiglio, Mt, Tinati, N, Maltoni, M, Nanni, O, Scardovi, F, Serra, P, Rosso, R, Boccardo, F, Bapr, A, Coli, T, Grimaldi, M, Cascinalli, N, Ascani, L, Bajetta, E, Bidoli, P, Cassata, A, De Candis, D, Giannessi, W, Procopio, G, Di Donato, S, Boiardi, A, Cerri, D, Eoli, M, Silvani, A, Colleoni, M, Rotmensz, N, Morfadini, S, Comella, G, De Matteis, A, Gravina, A, Gridelli, C, Perrone, F, Salzano, Mr, Sandomenico, C, Battista, C, Iodice, G, Fico, R, Nicchia, A, Lise, M, De Salvo GL, Di lenardo, E, Iadicicco, F, Agostara, Bb, Cafarelli, I, Tonato, M, Radicchi, F, Sorbolini, S, Taschini, O, Carmignani, A, Del Mastro, L, Gennari, A, Orlandini, C, Manzione, L, Dinota, A, Lombardi, G, Gasparini, G, Arena, Mg, Fanelli, M, Modafferi, F, Fazi, P, Mauro, F, Martelli, M, Ricci, C, Vignetti, M, D’Alessio, A, Giannarelli, D, Magnani, E, Rellecati, P, Ruggeri, Em, Zeuli, Borgognone, M, Chio', Adriano, Gasco, A, Ragona, R, Sacco, M, Soffietti, Riccardo, Tessa, M, Pileri, A, Galligoini, E, Lucenti, A, Moltreer, F, Paolazzi, F, Bianco, Ar, Labianca, R, Rossi Ferrini PL, Simonetti, G, and Sobrero, A.

Subjects
Papers
Published
1999

17. Synthesis of the first chiral phosphorous chelate aminophosphino-carbene complex and its applications in stereoselective addition reactions

Author

Maiorana, S, Papagni, A, Licandro, E, Perdicchia, D, Baldoli, C, Graiff, C, Tiripicchio, A, PAPAGNI, ANTONIO, Tiripicchio, A., Maiorana, S, Papagni, A, Licandro, E, Perdicchia, D, Baldoli, C, Graiff, C, Tiripicchio, A, PAPAGNI, ANTONIO, and Tiripicchio, A.

Abstract

The first phosphorous chelate chiral aminophosphinomethyl carbene complex 5 has been synthesized. Its conjugated base represents a new chiral cr-unsubstituted amide enolate equivalent for stereoselective addition reactions. The structure of the major diastereoisomer of the aldol addition complex between 5 and pO(2)N-C6H4-CHO, solved by X-ray diffraction, shows that the (S)-enantiomer of the conjugated base of 5 reacts preferentially with the re face of the carbonyl function. (C) 1999 Elsevier Science S.A. All rights reserved

Published
1999

18. The anion of the pentacarbonyl[(trans-2,6-dimethylmorpholino)-(methyl)carbene]chromium complex in the reactions with nitroalkenes

Author

Licandro, E, Maiorana, S, Capella, L, Manzotti, R, Papagni, A, Pryce, M, Graiff, C, Tiripicchio, A, Licandro, E, Maiorana, S, Capella, L, Manzotti, R, Papagni, A, Pryce, M, Graiff, C, and Tiripicchio, A

Abstract

The diastereoselective Michael addition of the title anion to alpha-hydrogen- and alpha-methyl-substituted conjugated nitroalkenes leads to new gamma-nitrocarbene complexes and gamma-hydroximoamides, respectively. The gamma-nitrocarbene complexes can be quantitatively oxidized to gamma-nitrobutyric acid derivatives (precursors of GABA derivatives); the gamma-hydroximoamides are formed as a result of an unexpected intramolecular transfer of an oxygen atom from the nitro group to the carbene atom, with elimination of the pentacarbonyl-chromium(0) group, which is recovered in high yield as the PyCr(CO)(5) complex

Published
1998

19. 838P - Characteristics and Prognostic Factors in 455 Elderly Pts Over 70 with Metastatic Renal Cell Carcinoma (Mrcc) Treated with Target Therapies (Tt) in the Community Setting: an Italian Survey

Author

Fraccon, A.P., Pasini, F., Basso, U., Larussa, F., Valduga, F., Re, G. Lo, Graiff, C., Rosti, G., Bearz, A., Sartori, D., Abeni, C., Grillone, F., Vicario, G., Pegoraro, C., Bassan, F., Da Corte, D., Modonesi, C., Segati, R., Medici, M., and Barile, C.

Published
2014
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27. Disparity in the 'time to patient access' to new anti-cancer drugs in Italian regions. Results of a survey conducted by the Italian Society of Medical Oncology (AIOM)

Author

Gori, S, DI MAIO, Massimo, Pinto, C, Alabiso, O, Baldini, E, Barbato, E, Beretta, Gd, Bravi, S, Caffo, O, Canobbio, L, Carrozza, F, Cinieri, S, Cruciani, G, Dinota, A, Gebbia, V, Giustini, L, Graiff, C, Molino, A, Muggiano, A, Pandoli, G, Puglisi, F, Tagliaferri, P, Tomao, S, Venturini, M, and AIOM Working Group Interactions with Regional Sections

Subjects
Cancer Research, Time Factors, Italy, Oncology, Health Care Surveys, Humans, Antineoplastic Agents, General Medicine, disparity, time to patient access, anticancer drugs, Medical Oncology, Health Services Accessibility, Societies, Medical
Abstract

Aims and background In 2009, the Italian Society of Medical Oncology (AIOM) conducted a survey to describe the impact of regional pharmaceutical formularies on the disparity of access to eight new drugs among cancer patients treated in Italian regions. The survey documented some regional restrictions for some anti-cancer drugs. In the study, we analyzed the “time to patient access” to new anti-cancer drugs in Italian regions. Methods In March 2010, we analyzed the availability of 17 new anti-cancer drugs at a regional level, specifically the coherence of regional authorizations compared with national authorizations approved by the Italian Medicines Agency (AIFA). In the regions with pharmaceutical formularies, we analyzed the characteristics of technical-scientific committees for the evaluation of inclusion of hospital drugs in these formularies. We also analyzed the time from EMA (CMPH) authorization to AIFA marketing authorization, the time from AIFA marketing authorization to patient availability, and the total time from EMA (CMPH) authorization to patient availability of the drugs in all Italian regions, for 11 of these drugs. Results Some drugs were included in all the regional pharmaceutical formularies, without restrictions, whereas other drugs were not included in one and others were not included in more than one formulary. Median time from EMA to AIFA was 11.2 months (range, 2.9–17.1). Median time from AIFA to patient availability was 1.4 months (range, 0.0–50.5) in regions with drug formularies versus 0.0 months in regions without drugs formularies. Median total time from EMA to patient availability was longer in regions with formularies (13.3 months; range, 2.9–65.3) than in regions without formularies (11.2 months; range, 2.9–24.0), where drugs are immediately available after AIFA marketing authorization. Moreover, the interval was very long (range, 2.9–65.3) for some drugs in regions with formularies. Conclusions The analysis confirmed that the presence of multiple hierarchical levels of drug evaluation can create disparity in drug availability for Italian citizens.

28. Oxaliplatin plus fluoropyrimidines as adjuvant therapy for colon cancer in older patients: A subgroup analysis from the TOSCA trial

Author

Gerardo Rosati, Sara Lonardi, Fabio Galli, Maria Di Bartolomeo, Monica Ronzoni, Maria G. Zampino, Maria Banzi, Alberto Zaniboni, Felice Pasini, Silvia Bozzarelli, Silvio K. Garattini, Daris Ferrari, Vincenzo Montesarchio, Andrea Mambrini, Libero Ciuffreda, Francesca Galli, Valeria Pusceddu, Chiara Carlomagno, Paolo Bidoli, Domenico Amoroso, Anna M. Bochicchio, Luca Frassineti, Domenico Corsi, Domenico Bilancia, Alessandro Pastorino, Alfonso De Stefano, Roberto Labianca, D. Bilancia, G. Rosati, V. Montesarchio, R.V. Iaffaioli, G. Nasti, B. Daniele, V. Zagonel, S. Lonardi, N. Pella, G. Aprile, F. Pasini, Roma P. Marchetti, A. Romiti, L. Ciuffreda, D. Ferrari, P. Foa, A. Zaniboni, R. Labianca, S. Mosconi, A. Sobrero, P. Bidoli, M. Cazzaniga, G.D. Beretta, D.C. Corsi, E. Cortesi, S. Barni, F. Petrelli, P. Allione, A.M. D'Arco, G. Valmadre, E. Piazza, E. Veltri, G. Vietti Ramus, L. Giustini, S. Tumulo, S. Cascinu, C. Granetto, F. Testore, M. Giordano, M. Moroni, M. Di Seri, A. Nuzzo, L. Angelelli, S. Gori, G. Farina, M. Aglietta, R. Franchi, M. Comandé, P. Giordani, G. Tonini, E. Bucci, A. Ballestrero, M. Benasso, C. Graiff, S. Bravi, O. Caffo, R.R. Silva, L. Frontini, S. Rota, L. Cozzi, M. Cantore, E. Maiello, S. Cinieri, N. Silvestris, S. Romito, V. Gebbia, M. Banzi, A. Santoro, F. Artioli, R. Mattioli, A. Contu, F. Di Costanzo, F. Leonardi, L. Cavanna, R. Passalacqua, D. Amoroso, P. Sozzi, M. D'Amico, D. Amadori, L. Frassineti, D. Turci, A. Ravaioli, E. Pasquini, A. Gambi, M. Faedi, G. Cruciani, E. Bajetta, M. Di Bartolomeo, L. Gianni, M. Ronzoni, M.T. Ionta, B. Massidda, M. Scartozzi, M.G. Zampino, A.M. Bochicchio, A. Ciarlo, A. Di Leo, S. Frustaci, G. Rangoni, A. Arizzoia, L. Pavesi, C. Verusio, G. Pinotti, A. Iop, S. De Placido, C. Carlomagno, V. Adamo, C. Ficorella, D. Natale, E. Greco, E. Rulli, F. Galli, D. Poli, L. Porcu, V. Torri, Rosati, G, Lonardi, S, Galli, F, Di Bartolomeo, M, Ronzoni, M, Zampino, M, Banzi, M, Zaniboni, A, Pasini, F, Bozzarelli, S, Garattini, S, Ferrari, D, Montesarchio, V, Mambrini, A, Ciuffreda, L, Pusceddu, V, Carlomagno, C, Bidoli, P, Amoroso, D, Bochicchio, A, Frassineti, L, Corsi, D, Bilancia, D, Pastorino, A, De Stefano, A, Labianca, R, Iaffaioli, R, Nasti, G, Daniele, B, Zagonel, V, Pella, N, Aprile, G, Marchetti, R, Romiti, A, Foa, P, Mosconi, S, Sobrero, A, Cazzaniga, M, Beretta, G, Cortesi, E, Barni, S, Petrelli, F, Allione, P, D'Arco, A, Valmadre, G, Piazza, E, Veltri, E, Ramus, G, Giustini, L, Tumulo, S, Cascinu, S, Granetto, C, Testore, F, Giordano, M, Moroni, M, Di Seri, M, Nuzzo, A, Angelelli, L, Gori, S, Farina, G, Aglietta, M, Franchi, R, Comande, M, Giordani, P, Tonini, G, Bucci, E, Ballestrero, A, Benasso, M, Graiff, C, Bravi, S, Caffo, O, Silva, R, Frontini, L, Rota, S, Cozzi, L, Cantore, M, Maiello, E, Cinieri, S, Silvestris, N, Romito, S, Gebbia, V, Santoro, A, Artioli, F, Mattioli, R, Contu, A, Di Costanzo, F, Leonardi, F, Cavanna, L, Passalacqua, R, Sozzi, P, D'Amico, M, Amadori, D, Turci, D, Ravaioli, A, Pasquini, E, Gambi, A, Faedi, M, Cruciani, G, Bajetta, E, Gianni, L, Ionta, M, Massidda, B, Scartozzi, M, Ciarlo, A, Di Leo, A, Frustaci, S, Rangoni, G, Arizzoia, A, Pavesi, L, Verusio, C, Pinotti, G, Iop, A, De Placido, S, Adamo, V, Ficorella, C, Natale, D, Greco, E, Rulli, E, Poli, D, Porcu, L, Torri, V, Rosati, G., Lonardi, S., Galli, F., Di Bartolomeo, M., Ronzoni, M., Zampino, M. G., Banzi, M., Zaniboni, A., Pasini, F., Bozzarelli, S., Garattini, S. K., Ferrari, D., Montesarchio, V., Mambrini, A., Ciuffreda, L., Pusceddu, V., Carlomagno, C., Bidoli, P., Amoroso, D., Bochicchio, A. M., Frassineti, L., Corsi, D., Bilancia, D., Pastorino, A., De Stefano, A., Labianca, R., Iaffaioli, R. V., Nasti, G., Daniele, B., Zagonel, V., Pella, N., Aprile, G., Marchetti, R. P., Romiti, A., Foa, P., Mosconi, S., Sobrero, A., Cazzaniga, M., Beretta, G. D., Cortesi, E., Barni, S., Petrelli, F., Allione, P., D'Arco, A. M., Valmadre, G., Piazza, E., Veltri, E., Ramus, G. V., Giustini, L., Tumulo, S., Cascinu, S., Granetto, C., Testore, F., Giordano, M., Moroni, M., Di Seri, M., Nuzzo, A., Angelelli, L., Gori, S., Farina, G., Aglietta, M., Franchi, R., Comande, M., Giordani, P., Tonini, G., Bucci, E., Ballestrero, A., Benasso, M., Graiff, C., Bravi, S., Caffo, O., Silva, R. R., Frontini, L., Rota, S., Cozzi, L., Cantore, M., Maiello, E., Cinieri, S., Silvestris, N., Romito, S., Gebbia, V., Santoro, A., Artioli, F., Mattioli, R., Contu, A., Di Costanzo, F., Leonardi, F., Cavanna, L., Passalacqua, R., Sozzi, P., D'Amico, M., Amadori, D., Turci, D., Ravaioli, A., Pasquini, E., Gambi, A., Faedi, M., Cruciani, G., Bajetta, E., Gianni, L., Ionta, M. T., Massidda, B., Scartozzi, M., Ciarlo, A., Di Leo, A., Frustaci, S., Rangoni, G., Arizzoia, A., Pavesi, L., Verusio, C., Pinotti, G., Iop, A., De Placido, S., Adamo, V., Ficorella, C., Natale, D., Greco, E., Rulli, E., Poli, D., Porcu, L., Torri, V., and Corsi, D. C.

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, Colorectal cancer, Leucovorin, Efficacy, Older patient, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Stage (cooking), Aged, 80 and over, Colonic Neoplasm, Prognostic factor, Middle Aged, Prognosis, Colon cancer, Survival Rate, Oxaliplatin, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Colonic Neoplasms, Female, Fluorouracil, medicine.drug, Human, Compliance, Adult, medicine.medical_specialty, Prognosi, Adjuvant chemotherapy, Older patients, Prognostic factors, Subgroup analysis, Follow-Up Studie, 03 medical and health sciences, Internal medicine, Post-hoc analysis, medicine, Adjuvant therapy, Humans, Capecitabine, Cancer staging, Aged, Antineoplastic Combined Chemotherapy Protocol, business.industry, medicine.disease, 030104 developmental biology, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract

Background: Previous studies on oxaliplatin and fluoropyrimidines as adjuvant therapy in older patients with stage III colon cancer (CC) produced conflicting results. Patients and methods: We assessed the impact of age on time to tumour recurrence (TTR), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) in 2360 patients with stage III CC (1667 aged

Published
2021

29. A 2A Adenosine Receptor Antagonists: Are Triazolotriazine and Purine Scaffolds Interchangeable?

Author

Andrea Spinaci, Catia Lambertucci, Michela Buccioni, Diego Dal Ben, Claudia Graiff, Maria Cristina Barbalace, Silvana Hrelia, Cristina Angeloni, Seyed Khosrow Tayebati, Massimo Ubaldi, Alessio Masi, Karl-Norbert Klotz, Rosaria Volpini, Gabriella Marucci, and Spinaci A, Lambertucci C, Buccioni M, Dal Ben D, Graiff C, Barbalace MC, Hrelia S, Angeloni C, Tayebati SK, Ubaldi M, Masi A, Klotz KN, Volpini R, Marucci G.

Subjects
A2A adenosine receptor antagonist, molecular modeling, Organic Chemistry, Pharmaceutical Science, anti-Parkinson agent, anti-inflammatory agent, Analytical Chemistry, A2A adenosine receptor antagonists, purine derivatives, triazolotriazine derivatives, anti-Parkinson agents, anti-inflammatory agents, triazolotriazine derivative, Chemistry (miscellaneous), purine derivative, Drug Discovery, Molecular Medicine, ddc:610, Physical and Theoretical Chemistry
Abstract

The A\(_{2A}\) adenosine receptor (A\(_{2A}\)AR) is one of the four subtypes activated by nucleoside adenosine, and the molecules able to selectively counteract its action are attractive tools for neurodegenerative disorders. In order to find novel A\(_{2A}\)AR ligands, two series of compounds based on purine and triazolotriazine scaffolds were synthesized and tested at ARs. Compound 13 was also tested in an in vitro model of neuroinflammation. Some compounds were found to possess high affinity for A\(_{2A}\)AR, and it was observed that compound 13 exerted anti-inflammatory properties in microglial cells. Molecular modeling studies results were in good agreement with the binding affinity data and underlined that triazolotriazine and purine scaffolds are interchangeable only when 5- and 2-positions of the triazolotriazine moiety (corresponding to the purine 2- and 8-positions) are substituted.

Published
2022

30. Synthesis of the first chiral phosphorous chelate aminophosphino-carbene complex and its applications in stereoselective addition reactions

Author

Antonio Tiripicchio, Emanuela Licandro, Dario Perdicchia, Stefano Maiorana, Claudia Graiff, Antonio Papagni, Clara Baldoli, Maiorana, S, Papagni, A, Licandro, E, Perdicchia, D, Baldoli, C, Graiff, C, and Tiripicchio, A

Subjects
Addition reaction, Chemistry, Stereochemistry, carbene complexe, Diastereomer, intramolecular phosphorous coordination, Conjugated system, Inorganic Chemistry, chemistry.chemical_compound, Aldol reaction, Amide, Polymer chemistry, Materials Chemistry, Stereoselectivity, Chelation, diastereoselective aldol addition, Physical and Theoretical Chemistry, Carbene
Abstract

The first phosphorous chelate chiral aminophosphinomethyl carbene complex 5 has been synthesized. Its conjugated base represents a new chiral cr-unsubstituted amide enolate equivalent for stereoselective addition reactions. The structure of the major diastereoisomer of the aldol addition complex between 5 and pO(2)N-C6H4-CHO, solved by X-ray diffraction, shows that the (S)-enantiomer of the conjugated base of 5 reacts preferentially with the re face of the carbonyl function. (C) 1999 Elsevier Science S.A. All rights reserved

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31. Mechanochemical preparation of strongly emissive monosubstituted triarylphosphane gold(i) compounds activated by hydrogen bonding driven aggregations.

Author

Luciani L, Sargentoni N, Graiff C, Monge M, Rodríguez-Castillo M, López-de-Luzuriaga JM, and Galassi R

Abstract

Gold(i) triarylphosphane compounds are a well-known class of coordination compounds displaying from mild to strong emissive properties. Mechanochemical approaches to the preparation, spectroscopic characterization, X-ray diffraction structural determination, and photophysical studies of green emissive neutral linear monophosphane or neutral pseudo-T-shaped or cationic bis-phosphane gold(i) compounds, are herein discussed. The mechanochemical approach to the preparation of gold(i) derivatives was particularly successful for ligands bearing the carboxylic group, while the preparation with esterified ligands yields better results with solvent-mediated methods. The introduction of carboxyl or ester substituents in one aryl group favors the ligand-centered emissions. The analysis of the origin of the emissions was elucidated on the basis of DFT calculations, addressing the emissive behavior to ligand-centered excited states, strongly affected by supramolecular reversible hydrogen bonding aggregation. The study indicates that the ligand with the carboxylic group is particularly suitable for the mechanochemical preparation of emissive gold(i) complexes for material science applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Published
2023
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32. Rapid Prototyping of 3D-Printed AgNPs- and Nano-TiO 2 -Embedded Hydrogels as Novel Devices with Multiresponsive Antimicrobial Capability in Wound Healing.

Author

Remaggi G, Bergamonti L, Graiff C, Ossiprandi MC, and Elviri L

Abstract

Two antimicrobial agents such as silver nanoparticles (AgNPs) and titanium dioxide (TiO 2 ) have been formulated with natural polysaccharides (chitosan or alginate) to develop innovative inks for the rapid, customizable, and extremely accurate manufacturing of 3D-printed scaffolds useful as dressings in the treatment of infected skin wounds. Suitable chemical-physical properties for the applicability of these innovative devices were demonstrated through the evaluation of water content (88-93%), mechanical strength (Young's modulus 0.23-0.6 MPa), elasticity, and morphology. The antimicrobial tests performed against Staphylococcus aureus and Pseudomonas aeruginosa demonstrated the antimicrobial activities against Gram+ and Gram- bacteria of AgNPs and TiO 2 agents embedded in the chitosan (CH) or alginate (ALG) macroporous 3D hydrogels (AgNPs MIC starting from 5 µg/mL). The biocompatibility of chitosan was widely demonstrated using cell viability tests and was higher than that observed for alginate. Constructs containing AgNPs at 10 µg/mL concentration level did not significantly alter cell viability as well as the presence of titanium dioxide; cytotoxicity towards human fibroblasts was observed starting with an AgNPs concentration of 100 µg/mL. In conclusions, the 3D-printed dressings developed here are cheap, highly defined, easy to manufacture and further apply in personalized antimicrobial medicine applications.

Published
2023
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33. A 2A Adenosine Receptor Antagonists: Are Triazolotriazine and Purine Scaffolds Interchangeable?

Author

Spinaci A, Lambertucci C, Buccioni M, Dal Ben D, Graiff C, Barbalace MC, Hrelia S, Angeloni C, Tayebati SK, Ubaldi M, Masi A, Klotz KN, Volpini R, and Marucci G

Subjects
Purines chemistry, Receptor, Adenosine A2A metabolism, Structure-Activity Relationship, Adenosine A2 Receptor Antagonists chemistry, Adenosine A2 Receptor Antagonists pharmacology, Purinergic P1 Receptor Antagonists pharmacology
Abstract

The A 2A adenosine receptor (A 2A AR) is one of the four subtypes activated by nucleoside adenosine, and the molecules able to selectively counteract its action are attractive tools for neurodegenerative disorders. In order to find novel A 2A AR ligands, two series of compounds based on purine and triazolotriazine scaffolds were synthesized and tested at ARs. Compound 13 was also tested in an in vitro model of neuroinflammation. Some compounds were found to possess high affinity for A 2A AR, and it was observed that compound 13 exerted anti-inflammatory properties in microglial cells. Molecular modeling studies results were in good agreement with the binding affinity data and underlined that triazolotriazine and purine scaffolds are interchangeable only when 5- and 2-positions of the triazolotriazine moiety (corresponding to the purine 2- and 8-positions) are substituted.

Published
2022
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34. Synthesis and characterization of bipyridine cobalt(ii) complex modified graphite screen printed electrode: an electrochemical sensor for simultaneous detection of acetaminophen and naproxen.

Author

Kondori T, Tajik S, Akbarzadeh-T N, Beitollahi H, Graiff C, Jang HW, and Shokouhimehr M

Abstract

The new Co(ii) compound [Co(5,5'-dmbpy) 2 (NCS) 2 ] (a1) was prepared by reacting Co(NO 3 ) 2 ·6H 2 O, 5,5'-dimethyl-2,2'-bipyridine ligand, and Na(SCN). The nano-scale size of [Co(5,5'-dmbpy) 2 (NCS) 2 ] (a1) was synthesized using sonochemical process. The size of the nanoparticles (a2) was ∼13 ± 2 nm. We have also provided a new platform of electrochemical sensing for simultaneous detection of acetaminophen and naproxen using (a2) surface modified graphite screen printed electrode (SPE) in 0.1 M phosphate buffer solution (PBS, pH 7.0). In contrast to bare SPE, the modified SPE could significantly improve the electrooxidation activity of acetaminophen along with the rise in the current of an anodic peak. The peak currents acquired using differential pulse voltammetry (DPV) raised linearly with the raising of acetaminophen concentration and the sensor had a detection range over the concentration range of 0.009-325.0 μM, with a detection limit of 5.0 nM (S/N = 3). In the case of naproxen peak, currents of naproxen oxidation at the modified SPE were linearly dependent on the naproxen amounts in the range of 1.0-500.0 μM. The detection limit (S/N = 3) was calculated to be 0.03 μM. The DPV responses show that the peaks of acetaminophen and naproxen oxidation were vividly separated from one other with a potential difference of 410 mV between them. The low detection limit, high sensitivity, and stability made the relevant electrode applicable for the analysis of acetaminophen and naproxen in real samples. Further, its practical applicability was reliable and desirable in the analysis of pharmaceutical compounds and biological fluids. The benefits of using this modified electrode for the determination of analytes are compared with other works in the manuscript., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

Published
2021
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35. Three-Dimensional (3D) Printed Silver Nanoparticles/Alginate/Nanocrystalline Cellulose Hydrogels: Study of the Antimicrobial and Cytotoxicity Efficacy.

Author

Bergonzi C, Remaggi G, Graiff C, Bergamonti L, Potenza M, Ossiprandi MC, Zanotti I, Bernini F, Bettini R, and Elviri L

Abstract

Here, a formulation of silver nanoparticles (AgNPs) and two natural polymers such as alginate (ALG) and nanocrystalline cellulose (CNC) was developed for the 3D printing of scaffolds with large surface area, improved mechanical resistance and sustained capabilities to promote antimicrobial and cytotoxic effects. Mechanical resistance, water content, morphological characterization and silver distribution of the scaffolds were provided. As for applications, a comparable antimicrobial potency against S. aureus and P. aeruginosa was demonstrated by in vitro tests as function of the AgNP concentration in the scaffold (Minimal Inhibitory Concentration value: 10 mg/mL). By reusing the 3D system the antimicrobial efficacy was demonstrated over at least three applications. The cytotoxicity effects caused by administration of AgNPs to hepatocellular carcinoma (HepG2) cell culture through ALG and ALG/CNC scaffold were discussed as a function of time and dose. Finally, the liquid chromatography-mass spectrometry (LC-MS) technique was used for targeted analysis of pro-apoptotic initiation and executioner caspases, anti-apoptotic and proliferative proteins and the hepatocyte growth factor, and provided insights about molecular mechanisms involved in cell death induction.

Published
2020
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36. Correction: Quality of life under extended continuous versus intermittent adjuvant letrozole in lymph node-positive, early breast cancer patients: the SOLE randomised phase 3 trial.

Author

Ribi K, Luo W, Colleoni M, Karlsson P, Chirgwin J, Aebi S, Jerusalem G, Neven P, Di Lauro V, Gomez HL, Ruhstaller T, Abdi E, Biganzoli L, Müller B, Barbeaux A, Graas MP, Rabaglio M, Francis PA, Foukakis T, Pagani O, Graiff C, Vorobiof D, Maibach R, Di Leo A, Gelber RD, Goldhirsch A, Coates AS, Regan MM, and Bernhard J

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020
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37. Quality of life under extended continuous versus intermittent adjuvant letrozole in lymph node-positive, early breast cancer patients: the SOLE randomised phase 3 trial.

Author

Ribi K, Luo W, Colleoni M, Karlsson P, Chirgwin J, Aebi S, Jerusalem G, Neven P, Di Lauro V, Gomez HL, Ruhstaller T, Abdi E, Biganzoli L, Müller B, Barbeaux A, Graas MP, Rabaglio M, Francis PA, Foukakis T, Pagani O, Graiff C, Vorobiof D, Maibach R, Di Leo A, Gelber RD, Goldhirsch A, Coates AS, Regan MM, and Bernhard J

Subjects
Adult, Aged, Breast Neoplasms pathology, Disease-Free Survival, Drug Administration Schedule, Drug-Related Side Effects and Adverse Reactions classification, Drug-Related Side Effects and Adverse Reactions pathology, Female, Humans, Letrozole adverse effects, Lymph Nodes pathology, Lymphatic Metastasis, Middle Aged, Neoplasm Staging, Quality of Life, Breast Neoplasms drug therapy, Chemotherapy, Adjuvant adverse effects, Letrozole administration & dosage, Lymph Nodes drug effects
Abstract

Background: In the phase III SOLE trial, the extended use of intermittent versus continuous letrozole for 5 years did not improve disease-free survival in postmenopausal women with hormone receptor-positive breast cancer. Intermittent therapy with 3-month breaks may be beneficial for patients' quality of life (QoL)., Methods: In the SOLE QoL sub-study, 956 patients completed the Breast Cancer Prevention Trial (BCPT) symptom and further QoL scales up to 24 months after randomisation. Differences in change of QoL from baseline between the two administration schedules were tested at 12 and 24 months using repeated measures mixed-models. The primary outcome was change in hot flushes at 12 months., Results: There was no difference in hot flushes at 12 months between the two schedules, but patients receiving intermittent letrozole reported significantly more improvement at 24 months. They also indicated less worsening in vaginal problems, musculoskeletal pain, sleep disturbance, physical well-being and mood at 12 months. Overall, 25-30% of patients reported a clinically relevant worsening in key symptoms and global QoL., Conclusion: Less symptom worsening was observed during the first year of extended treatment with the intermittent administration. For women experiencing an increased symptom burden of extended adjuvant endocrine therapy, an intermittent administration is a safe alternative., Clinical Trial Information: Clinical trial information: NCT00651456.

Published
2019
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38. Structural and Luminescent Properties of Homoleptic Silver(I), Gold(I), and Palladium(II) Complexes with n NHC- tz NHC Heteroditopic Carbene Ligands.

Author

Monticelli M, Baron M, Tubaro C, Bellemin-Laponnaz S, Graiff C, Bottaro G, Armelao L, and Orian L

Abstract

Novel silver(I), gold(I), and palladium(II) complexes were synthesized with bidentate heteroditopic carbene ligands that combine an imidazol-2-ylidene ( n NHC) with a 1,2,3-triazol-5-ylidene ( tz NHC) connected by a propylene bridge. The silver(I) and gold(I) complexes were dinuclear species, [M 2 ( n NHC- tz NHC) 2 ](PF 6 ) 2 (M = Ag or Au), with the two bidentate ligands bridging the metal centers, whereas in the palladium(II) complex [Pd( n NHC- tz NHC) 2 ](PF 6 ) 2 , the two ligands were chelated on the same metal center. Because of the presence of two different carbene units, isomers were observed for the gold(I) and palladium(II) complexes. The molecular structures of the head-to-tail isomer for gold(I) complexes, with a twisted or folded- syn conformation of the bridge between the carbene units, were determined by X-ray diffraction analysis. The study was completed with a systematic structural investigation through density functional theory (DFT) calculations. For palladium(II) species, the head-to-head form was structurally characterized. The dinuclear gold(I) complexes were emissive in the solid state in the blue region (PLQY up to 8%); time-dependent density functional theory (abbreviated as TD-DFT) calculations disclosed that the absorption bands have metal-to-ligand-charge-transfer character and evidenced that the emission occurs from the T 1 level (phosphorescence)., Competing Interests: The authors declare no competing financial interest.

Published
2019
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39. Hydrogen bonds and π-π inter-actions in two new crystalline phases of methyl-ene blue.

Author

Canossa S, Predieri G, and Graiff C

Abstract

Two unprecedented solid phases involving the 3,7-bis-(di-methyl-amino)-pheno-thia-zin-5-ium cation, i.e. methyl-ene blue ( MB + ), have been obtained and structurally characterized. In the crystals of 3,7-bis-(di-methyl-amino)-pheno-thia-zin-5-ium chloride dihydrate, C 16 H 18 N 3 S + ·Cl - ·2H 2 O ( I ) and 3,7-bis-(di-methyl-amino)-pheno-thia-zinium bis-ulfite, C 16 H 18 N 3 S + ·HSO 4 - ( II ), the cationic dye mol-ecules are planar and disposed in an anti-parallel mode, showing π-π stacking inter-actions, with mean inter-planar distances of 3.326 (4) and 3.550 (3) Å in ( I ) and ( II ), respectively. In compound ( I ), whose phase was found affected by merohedral twinning [BASF = 0.185 (3)], the presence of water mol-ecules allows a network of hydrogen bonds involving MB + as both a donor and an acceptor, whereas in compound ( II ), the homo-inter-action of the anions causes an effective absence of classical hydrogen-bond donors. This substantial difference has important consequences for the stacking geometry and supra-molecular inter-actions of the MB + cations, which are analysed by Hirshfeld fingerprint plots and subsequently discussed.

Published
2018
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40. Assessment of a HER2 scoring system for colorectal cancer: results from a validation study.

Author

Valtorta E, Martino C, Sartore-Bianchi A, Penaullt-Llorca F, Viale G, Risio M, Rugge M, Grigioni W, Bencardino K, Lonardi S, Zagonel V, Leone F, Noe J, Ciardiello F, Pinto C, Labianca R, Mosconi S, Graiff C, Aprile G, Frau B, Garufi C, Loupakis F, Racca P, Tonini G, Lauricella C, Veronese S, Truini M, Siena S, Marsoni S, and Gambacorta M

Subjects
Adult, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Area Under Curve, Biomarkers, Tumor analysis, Colorectal Neoplasms classification, Colorectal Neoplasms drug therapy, Female, Gene Expression Profiling standards, Humans, Immunohistochemistry methods, Lapatinib, Male, Middle Aged, Quinazolines, ROC Curve, Trastuzumab, Colorectal Neoplasms genetics, Gene Expression Profiling methods, In Situ Hybridization, Fluorescence methods, Patient Selection, Receptor, ErbB-2 genetics
Abstract

We sought to develop criteria for ERBB2-positivity (HER2) in colorectal cancer to ensure accurate identification of ERBB2-amplified metastatic colorectal cancer patients suitable for enrollment in a phase II trial of ERBB2-targeted therapy (HERACLES trial). A two-step approach was used. In step 1, a consensus panel of pathologists adapted existing protocols for use in colorectal cancer to test ERBB2 expression and amplification. Collegial revision of an archival test cohort of colorectal cancer samples led to specific recommendations for adapting current breast and gastric cancer criteria for scoring ERBB2 in colorectal cancer. In step 2, from September 2012 to January 2015, colorectal-specific ERBB2 testing protocols and ERBB2 scoring criteria were used to centrally screen for ERBB2-positive KRAS wild-type colorectal cancer patients to be enrolled in the HERACLES trial (clinical validation cohort). In both archival test (N=256) and clinical validation (N=830) cohorts, a clinically sizeable 5% fraction of KRAS wild-type colorectal cancer patients was found to be ERBB2-positive according to the colorectal cancer-specific ERBB2 scoring criteria. ERBB2-positive tumors showed ERBB2 immunostaining consisting of intense membranous ERBB2 protein expression, corresponding to homogenous ERBB2 amplification, in >50% of cells. None of the immunohistochemistry 0 or 1+ cases was amplified. Concordance between SISH and FISH was 100%. In conclusion, we propose specific criteria for defining ERBB2-positivity in colorectal cancer (HERACLES Diagnostic Criteria). In a phase II trial of trastuzumab and lapatinib in a cetuximab-resistant population, HERACLES Diagnostic Criteria shaped the selection of patients and defined ERBB2 as a predictive marker for response to ERBB2-targeted therapy in metastatic colorectal cancer.

Published
2015
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41. Chiral thiahelicene-based alkyl phosphine-borane complexes: synthesis, X-ray characterization, and theoretical and experimental investigations of optical properties.

Author

Dova D, Cauteruccio S, Prager S, Dreuw A, Graiff C, and Licandro E

Abstract

Chiral helical-based phosphanes are challenging and promising ligands, with a great potential for the generation of both organic and organometallic catalysts. We report here the preparation of novel chiral thiahelicene-based alkyl phosphanes, isolated and characterized as air-stable borane adducts, and the investigation of their experimental and theoretical (chir)optical properties. X-ray characterization of a mono- and a disubstituted derivative as a racemic mixture has been performed, which confirms the influence of the number and nature of substituents on the flexibility of the helix. In addition, the absolute configuration inferred from CD spectra of the two enantiomers of a diborane complex has been established from X-ray analysis. State-of-the-art quantum chemical calculations of vibrationally resolved spectra allow, for the first time, for an unambiguous assignment of the experimentally observed peaks in linear absorption and circular dichroism spectra to excited electronic states of this class of thiahelicene phosphorus derivatives.

Published
2015
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42. Adjuvant chemotherapy of pT1a and pT1b breast carcinoma: results from the NEMESI study.

Author

Gori S, Clavarezza M, Siena S, Foglietta J, Tarenzi E, Giordano M, Molino A, Graiff C, Fusco V, Alabiso O, Baldini E, Gamucci T, Altavilla G, Dondi D, and Venturini M

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Antineoplastic Agents therapeutic use, Breast Neoplasms therapy, Chemotherapy, Adjuvant, Female, Humans, Menopause, Middle Aged, Neoplasm Staging, Prognosis, Receptor, ErbB-2 metabolism, Receptors, Estrogen metabolism, Retrospective Studies, Young Adult, Breast Neoplasms drug therapy, Breast Neoplasms pathology
Abstract

Background: The prognosis of pT1a-pT1b breast cancer (BC) used to be considered very good, with a 10-y RFS of 90%. However, some retrospective studies reported a 10-y RFS of 81%-86% and suggested benefit from adjuvant systemic therapy., Methods: To evaluate the variables that determined the choice of adjuvant chemotherapy and the type of chemotherapy delivered in pT1a-pT1b BC, we analysed the small tumours enrolled in the NEMESI study., Results: Out of 1,894 patients with pathological stage I-II BC enrolled in NEMESI, 402 (21.2%) were pT1a-pT1b. Adjuvant chemotherapy was delivered in 127/402 (31.59%). Younger age, grading G3, high proliferative index, ER-negative and HER2-positive status were significantly associated with the decision to administer adjuvant chemotherapy. An anthracycline without taxane regimen was administered in 59.1% of patients, anthracycline with taxane in 24.4%, a CMF-like regimen in 14.2% and taxane in 2.4%. Adjuvant chemotherapy was administered in 88.4% triple-negative and 73.46% HER2-positive pT1a-pT1b BC. Adjuvant trastuzumab was delivered in 30/49 HER2-positive BC (61.2%)., Conclusions: Adjuvant chemotherapy was delivered in 31.59% T1a-pT1b BC treated at 63 Italian oncological centres from January 2008 to June 2008. The choice to deliver chemotherapy was based on biological prognostic factors. Anthracycline-based chemotherapy was administered in 83.5% patients.

Published
2012
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43. Bis(triphenyl-phosphanyl-idene)iminium dichloridotriphenyl-stannate(IV).

Author

De Lorentiis L, Graiff C, and Predieri G

Abstract

The structure of the title compound, [Ph(3)P=N=PPh(3)](+)[Ph(3)SnCl(2)](-) or (C(36)H(30)NP(2))[Sn(C(6)H(5))(3)Cl(2)], obtained as a by product of the reaction between Ph(3)SnCl and [Ph(3)P=N=PPh(3)](+)·HSeO(3) (-), consists of discrete essentially isolated ions. Both the cation and the anion lie on twofold axes which pass through the central N atom in the cation and through the Sn(IV) atom in the anion. In the crystal, the ions inter-act only through a weak inter-action between the Cl atom of the anion and an H atom of a phenyl ring of the cation.

Published
2011
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