A Monti Hughes1, Ecc Pozzi2, S I Thorp3, P Curotto2, V A Medina4,5,6, D J Martinel Lamas4,5, E S Rivera4, M A Garabalino1, R O Farías7, S J Gonzalez6,7, E M Heber1, M E Itoiz1,8, R F Aromando8, D W Nigg9, V A Trivillin1,6, A E Schwint1,6. 1. Department of Radiobiology, National Atomic Energy Commission, San Martin, Province Buenos Aires, Argentina. 2. Department of Research and Production Reactors, National Atomic Energy Commission, Ezeiza, Province Buenos Aires, Argentina. 3. Department of Instrumentation and Control, National Atomic Energy Commission, Ezeiza, Province Buenos Aires, Argentina. 4. Radioisotopes Laboratory, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina. 5. Laboratory of Cellular and Molecular Biology, School of Medical Sciences, Institute for Biomedical Research (BIOMED CONICET-UCA), Pontifical Catholic University of Argentina (UCA), Buenos Aires, Argentina. 6. National Research Council (CONICET), Buenos Aires, Argentina. 7. Department of Technology and Applications of Accelerators, National Atomic Energy Commission, San Martin, Province Buenos Aires, Argentina. 8. Department of Oral Pathology, Faculty of Dentistry, University of Buenos Aires, Buenos Aires, Argentina. 9. Idaho National Laboratory, Idaho Falls, ID, USA.
Abstract
OBJECTIVES: Searching for more effective and selective therapies for head and neck cancer, we demonstrated the therapeutic effect of boron neutron capture therapy (BNCT) to treat oral cancer and inhibit long-term tumor development from field-cancerized tissue in the hamster cheek pouch model. However, BNCT-induced mucositis in field-cancerized tissue was dose limiting. In a clinical scenario, oral mucositis affects patients' treatment and quality of life. Our aim was to evaluate different radioprotectors, seeking to reduce the incidence of BNCT-induced severe mucositis in field-cancerized tissue. MATERIALS AND METHODS: Cancerized pouches treated with BNCT mediated by boronophenylalanine at 5 Gy were treated as follows: control: saline solution; Hishigh : histamine 5 mg kg(-1) ; Hislow : histamine 1 mg kg(-1) ; and JNJ7777120: 10 mg kg(-1). RESULTS: Hislow reduced the incidence of severe mucositis in field-cancerized tissue to 17% vs CONTROL: 55%; Hishigh : 67%; JNJ7777120: 57%. Hislow was non-toxic and did not compromise the long-term therapeutic effect of BNCT or alter gross boron concentration. CONCLUSION: Histamine reduces BNCT-induced mucositis in experimental oral precancer without jeopardizing therapeutic efficacy. The fact that both histamine and boronophenylalanine are approved for use in humans bridges the gap between experimental work and potential clinical application to reduce BNCT-induced radiotoxicity in patients with head and neck cancer.
OBJECTIVES: Searching for more effective and selective therapies for head and neck cancer, we demonstrated the therapeutic effect of boron neutron capture therapy (BNCT) to treat oral cancer and inhibit long-term tumor development from field-cancerized tissue in the hamster cheek pouch model. However, BNCT-induced mucositis in field-cancerized tissue was dose limiting. In a clinical scenario, oral mucositis affects patients' treatment and quality of life. Our aim was to evaluate different radioprotectors, seeking to reduce the incidence of BNCT-induced severe mucositis in field-cancerized tissue. MATERIALS AND METHODS: Cancerized pouches treated with BNCT mediated by boronophenylalanine at 5 Gy were treated as follows: control: saline solution; Hishigh : histamine 5 mg kg(-1) ; Hislow : histamine 1 mg kg(-1) ; and JNJ7777120: 10 mg kg(-1). RESULTS: Hislow reduced the incidence of severe mucositis in field-cancerized tissue to 17% vs CONTROL: 55%; Hishigh : 67%; JNJ7777120: 57%. Hislow was non-toxic and did not compromise the long-term therapeutic effect of BNCT or alter gross boron concentration. CONCLUSION:Histamine reduces BNCT-induced mucositis in experimental oral precancer without jeopardizing therapeutic efficacy. The fact that both histamine and boronophenylalanine are approved for use in humans bridges the gap between experimental work and potential clinical application to reduce BNCT-induced radiotoxicity in patients with head and neck cancer.
Authors: Marcela A Garabalino; Nahuel Olaiz; Agustina Portu; Gisela Saint Martin; Silvia I Thorp; Emiliano C C Pozzi; Paula Curotto; María E Itoiz; Andrea Monti Hughes; Lucas L Colombo; David W Nigg; Verónica A Trivillin; Guillermo Marshall; Amanda E Schwint Journal: Radiat Environ Biophys Date: 2019-05-23 Impact factor: 1.925
Authors: Andrea Monti Hughes; Juan Longhino; Esteban Boggio; Vanina A Medina; Diego J Martinel Lamas; Marcela A Garabalino; Elisa M Heber; Emiliano C C Pozzi; María E Itoiz; Romina F Aromando; David W Nigg; Verónica A Trivillin; Amanda E Schwint Journal: Radiat Environ Biophys Date: 2017-09-04 Impact factor: 1.925
Authors: Verónica A Trivillin; Emiliano C C Pozzi; Lucas L Colombo; Silvia I Thorp; Marcela A Garabalino; Andrea Monti Hughes; Sara J González; Rubén O Farías; Paula Curotto; Gustavo A Santa Cruz; Daniel G Carando; Amanda E Schwint Journal: Radiat Environ Biophys Date: 2017-08-08 Impact factor: 1.925