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3. Emerging Role of Immunomonitoring to Predict the Clinical Outcome of Patients With Malignant Pleural Mesothelioma Treated With Radical Radiation Therapy

Author

Cangemi, M., Montico, M., Trovo, M., Minatel, E., Di Gregorio, E., Corona, G., Giordari, F., Comaro, E., Colizzi, F., Baboci, L., Steffan, A., Revelant, A., and Muraro, E.

Subjects
Cancer Research, Radiation, Oncology, Radiology, Nuclear Medicine and imaging
Abstract

The present study aimed at evaluating the baseline immune profile and the immunomodulating effects of radical hemithoracic radiation therapy (RT) in patients affected by malignant pleural mesothelioma (MPM) to identify potential predictive biomarkers of therapy response, toxicity development, and eligibility for further immunotherapeutic treatments.Blood samples were collected from 55 patients with MPM, enrolled in a phase 3 trial comparing radical hemithoracic RT (interventional arm, n = 28) with local palliative RT (control arm, n = 27). Immunomonitoring was performed before RT, at the end of treatment, and 1 month after therapy, characterizing natural killer cells, B and T lymphocytes, activated CD4 and CD8 T cells, interferon-γ- and tumor necrosis factor-α-producing T helper (Th) 1 cells, regulatory T cells, and Th17 and Th22 lymphocytes, through flow cytometry. Serum levels of interleukin (IL)-6, -8, -10 and mesothelin were quantified through Enzyme-Linked Immunosorbent Assay (ELISA) assays at the same time points. Variations in the immune parameters were investigated by Friedman test and Wilcoxon signed rank post hoc test with Bonferroni correction for multiple testing, while the prognostic effect of immune biomarkers was evaluated through Kaplan-Meier method and Spearman's correlation analysis.Major immune variations were noticed after radical RT compared with palliative treatment, in particular an improvement in activated T cells and in interferon-γ-producing Th1 cells after RT. In the interventional arm, baseline high levels of Th22 and IL-10 and an increase in T cells were associated with an improved survival, whereas a fold increase in serum mesothelin correlated with the development of severe toxicity. An improvement of immunosuppressive regulatory T cells was observed in both arms of treatment.The immunomonitoring performed in patients with MPM revealed potential prognostic biomarkers for radical hemithoracic RT treatment and identified specific immune signatures induced by RT immunomodulation, which could suggest a synergistic effect with an immunotherapeutic treatment.

Published
2022

4. Betulinic acid and its spray dried microparticle formulation: In vitro PDT effect against ovarian carcinoma cell line and in vivo plasma and tumor disposition

Author

Serain, A, Morosi, L, Ceruti, T, Matteo, C, Meroni, M, Minatel, E, Zucchetti, M, Salvador, M, Serain, Alessandra F., Morosi, Lavinia, Ceruti, Tommaso, Matteo, Cristina, Meroni, Marina, Minatel, Elaine, Zucchetti, Massimo, Salvador, Marcos J., Serain, A, Morosi, L, Ceruti, T, Matteo, C, Meroni, M, Minatel, E, Zucchetti, M, Salvador, M, Serain, Alessandra F., Morosi, Lavinia, Ceruti, Tommaso, Matteo, Cristina, Meroni, Marina, Minatel, Elaine, Zucchetti, Massimo, and Salvador, Marcos J.

Abstract

The race against ovarian cancer continue to motivate the research worldwide. It is known that many antitumor drugs have limited penetration into solid tumor tissues due to its microenvironment, thus contributing to their low efficacy. Therapeutic modalities have been exploited to elicit antitumor effects based on microenvironment of tumor, including Photodynamic therapy (PDT). Prospection of natural small molecules and nanotechnology are important tools in the development of new ways of obtaining photoactive compounds that are biocompatible. The Betulinic acid (BA) has shown potential biological effect as bioactive drug, but it has low water solubility. Thus, in the present study, owing to the poor solubility of the BA, its free form (BAF) was compared to a spray dried microparticle betulinic acid/HP-beta-CD formulation (BAC) aiming to assess the BAF and BAC efficacy as a photosensitizer in PDT for application in ovarian cancer. BAF and BAC were submitted to assays in the presence of LED (lambda = 420 nm) under different conditions (2.75 J/cm(2), 5.5 J/cm(2), and 11 J/cm(2)) and in absence of irradiation, after 5 min or 4 h of contact with ovarian carcinoma cells (A2780) or fibroblast murine cells (3T3). Furthermore, HPLC-MS/MS and MALDI-MSI methods were developed and validated in plasma and tumor of mice proving suitable for in vivo studies. The results found a greater photoinduced cytotoxic effect for the BAC at low concentration for A2780 when irradiated with LED with similar results for fluorescence microscopy. The results motivate us to continue the studies with the BA as a potential antitumor bioactive compound.

Published
2021

6. Predictive Value of Dosimetric Measures on Lung Toxicity in Randomized Trial of Radical RT with Intact Lung in Malignant Pleural Mesothelioma

Author

Revelant, A., primary, Trovo, M., additional, Polesel, J., additional, Baresic, T., additional, Barresi, L., additional, Bearz, A., additional, Drigo, A., additional, Del Conte, A., additional, Fontana, P., additional, Fanetti, G., additional, Caroli, A., additional, Franchin, G., additional, and Minatel, E., additional

Published
2019
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7. EP-1143 Regional nodal failure after primary treatment for differentiated thyroid cancer.

Author

Fanetti, G., primary, Borsatti, E., additional, Baresic, T., additional, Bampo, C., additional, Esposito, A., additional, Mazzone, S., additional, Mazzon, C., additional, Minatel, E., additional, Revelant, A., additional, Pisu, S., additional, Nappo, A., additional, Casanova Fuga, E., additional, Burello, M., additional, Giacomarra, V., additional, Franchin, G., additional, and Gobitti, C., additional

Published
2019
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8. OC-0500 Radical Hemi-thoracic Radiotherapy vs. Palliative Radiotherapy for Malignant Pleural Mesothelioma.

Author

Minatel, E., primary, Trovo, M., additional, Polesel, J., additional, Furlan, C., additional, Revelant, A., additional, Drigo, A., additional, Barresi, L., additional, Bearz, A., additional, Del Conte, A., additional, Follador, A., additional, Zuccon, U., additional, Dicorato, A., additional, Fontana, P., additional, and Franchin, G., additional

Published
2019
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9. PO-164 Regional nodal failure after primary treatment for differentiated thyroid cancer

Author

Fanetti, G., primary, Borsatti, E., additional, Baresic, T., additional, Bampo, C., additional, Esposito, A., additional, Mazzone, S., additional, Mazzon, C., additional, Minatel, E., additional, Revelant, A., additional, Pisu, S., additional, Nappo, A., additional, Fuga, E. Casanova, additional, Burello, M., additional, Giacomarra, V., additional, Franchin, G., additional, and Gobitti, C., additional

Published
2019
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10. PO-063 Induction chemotherapy followed by radiotherapy for organ preservation in Oropharyngeal Cancer

Author

Fanetti, G., primary, Gobitti, C., additional, Minatel, E., additional, Revelant, A., additional, Avanzo, M., additional, Pirrone, G., additional, Polesel, J., additional, Vaccher, E., additional, Schioppa, O., additional, Martellotta, F., additional, Giuseppe, G., additional, Lupato, V., additional, Baresic, T., additional, Bampo, C., additional, Vittorio, G., additional, Borsatti, E., additional, Sartor, G., additional, and Franchin, G., additional

Published
2019
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14. Stereotactic body radiation therapy and intensity modulated radiation therapy induce different plasmatic cytokine changes in non-small cell lung cancer patients: a pilot study

Author

Trovo, M., primary, Giaj-Levra, N., additional, Furlan, C., additional, Bortolin, M. T., additional, Muraro, E., additional, Polesel, J., additional, Minatel, E., additional, Tedeschi, R., additional, Filippi, A. R., additional, Alongi, F., additional, and Ricardi, U., additional

Published
2015
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20. Extended Pleurectomy/Decortication or Surgical Biopsy in the Era of High Doses of Radiation Therapy for Malignant Pleural Mesothelioma

Author

Trovo, M., primary, Minatel, E., additional, Bearz, A., additional, Del Conte, A., additional, Baresic, T., additional, Franchin, G., additional, Gobitti, C., additional, Abu Rumeileh, I., additional, Crestani, A., additional, Drigo, A., additional, Barresi, L., additional, Fontana, P., additional, Pagan, V., additional, and Trovo, M.G., additional

Published
2014
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26. ARCON: accelerated radiotherapy with carbogen and nicotinamide in head and neck squamous cell carcinomas. The experience of the Cooperative Group of Radiotherapy of the European Organization for Research and Treatment of Cancer (EORTC)

Author

UCL, Bernier, J, Denekamp, J, Rojas, A, Minatel, E, Horiot, JC., Hamers, H, Antognoni, P, Dahl, O, Richaud, P, Van Glabbeke, Martine, Pierart, M, UCL, Bernier, J, Denekamp, J, Rojas, A, Minatel, E, Horiot, JC., Hamers, H, Antognoni, P, Dahl, O, Richaud, P, Van Glabbeke, Martine, and Pierart, M

Abstract

Background: Since there is increasing evidence that both acute (perfusion-limited) and chronic (diffusion-limited) hypoxia, and tumor repopulation may prejudice the outcome of radiotherapy, the combination of carbogen (95% oxygen-5% carbon dioxide) and nicotinamide with accelerated radiotherapy (ARCON) should reduce the impact of these factors of radioresistance. Aim: This clinical study was aimed at determining the feasibility, as well as the qualitative and quantitative toxic effects of a therapeutic approach based on ARCON, and assessing the tumor response rates that can be achieved with this regime in patients with locally advanced tumors of the head and neck. Methods: A phase I/II study conducted between 1993 and 1996 by the Co-operative Group of Radiotherapy of the EORTC included three consecutive steps: accelerated fractionation (AF) combined with carbogen (11 analyzable patients), AF combined with the daily administration of nicotinamide (n = 10), and AF with both carbogen and nicotinamide (n = 17). Radiotherapy was based on an accelerated regime (72 Gy in 5.5 weeks). Nicotinamide was delivered 90 min before the first irradiation session, at a daily dose of 6 g. Carbogen breathing started 5 min before irradiation and lasted throughout the entire radiotherapy sessions. Results: No significant different in loco-regional toxicity was found among the three study steps, when carbogen and nicotinamide, either alone or in combination, were combined with AF. The feasibility of the ARCON protocol, as proposed in the present EORTC study, appears to be significantly impaired when nicotinamide is added, at a daily dose of 6 g, to AF and carbogen, in an unselected group of patients. More than 20% of patients experienced grade 2 or 3 emesis. It also demonstrates, in unselected groups of patients, no significant difference in tumor response and local control when carbogen and nicotinamide, either alone or in combination, are added to accelerated radiotherapy. The percentag

Published
2000

28. Post-operative adjuvant therapy for non-small-cell lung cancer

Author

Johnson, D., Arriagada, R., Barthelemy, N., Bonner, James, Bonomi, P., Enami, B., Minatel, E., Park, Kyungok, Quoix, Elisabeth, Van Houtte, Paul, Johnson, D., Arriagada, R., Barthelemy, N., Bonner, James, Bonomi, P., Enami, B., Minatel, E., Park, Kyungok, Quoix, Elisabeth, and Van Houtte, Paul

Abstract

SCOPUS: cp.j, info:eu-repo/semantics/published

Published
1997

37. Radiotherapy (RT) versus rt enhanced by cisplatin (DDP) in stage III non-small cell lung cancer (NSCLC): Randomized trial

Author

Minatel, E., primary, Trovo, M.G., additional, Franchin, G., additional, Gobitti, C., additional, Innocente, R., additional, Veronesi, A., additional, Crivellari, D., additional, Nascimben, O., additional, Boccieri, M.G., additional, Bolzicco, G., additional, Mazza, F., additional, Pizzi, G., additional, Torretta, A., additional, and Monfardini, S., additional

Published
1991
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40. Combined radiotherapy and chemotherapy versus radiotherapy alone in locally advanced epidermoid bronchogenic carcinoma. A randomized study.

Author

Trovó, Mauro G., Minatel, Emilio, Veronesi, Andrea, Roncadin, Mario, de Paoli, Antonino, Franchin, Giovanni, Magri, Donatella M., Tirelli, Umberto, Carbone, Antonino, Grigoletto, Eligio, Trovò, M G, Minatel, E, Veronesi, A, Roncadin, M, De Paoli, A, Franchin, G, Magri, D M, Tirelli, U, Carbone, A, and Grigoletto, E

Published
1990
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46. Maxillary sinus carcinoma: a retrospective study

Author

CARLO GOBITTI, Barzan L, Franchin G, De Paoli A, Frustaci S, Caruso G, Sacilotto C, Minatel E, Comoretto R, and Grigoletto E

Subjects
Male, Radiotherapy, High-Energy, Maxillary Sinus Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Squamous Cell, Humans, Female, Middle Aged, Combined Modality Therapy, Paranasal Sinus Neoplasms, Retrospective Studies

48. Radiation therapy for recalcitrant pyoderma gangrenosum

Author

Rumeileh, I. A., Furlan, C., Minatel, E., and Maurizio Mascarin

Subjects
Adult, Drug Substitution, Brachytherapy, Drug Resistance, Antibodies, Monoclonal, Immunoglobulins, Intravenous, Dose-Response Relationship, Radiation, Combined Modality Therapy, Infliximab, Pyoderma Gangrenosum, Radiotherapy, High-Energy, Cicatrix, Treatment Outcome, Autonomic Nervous System Diseases, Cyclosporine, Humans, Female, Spondylitis, Ankylosing, Cyclophosphamide, Immunosuppressive Agents
Abstract

Pyoderma gangrenosum is a rare neutrophilic dermatosis, often associated with underlying systemic diseases. Treatment usually consists of topics and sometimes systemic immunosuppression. We present the case of a 32-year-old female patient undergoing radiation therapy for extensive recalcitrant pyoderma gangrenosum in which immunosuppressive measures were ineffective to control the disease. Treatment outcome was favourable with only mild side effects in the irradiated areas. Localized radiation therapy hence is a potential effective palliation for refractory cases of pyoderma gangrenosum, or patients unfit to undergo aggressive systemic immunosuppression.

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