“…Radiation, chemotherapy, and BNCT induce DNA strand breaks and reactive oxygen species which react with DNA and other cellular molecules causing cell dysfunction and mortality (Sonis, 2009;Medina et al, 2011a;Faião-Flores et al, 2013). Free radical production is the initial stage of mucositis (Elad et al, 2006;Sonis, 2009).…”
Section: Discussionmentioning
confidence: 99%
“…Histamine reduces oral mucositis in BNCT A Monti Hughes et al radioprotective compounds is of utmost importance in clinical radiotherapy (Medina et al, 2011a). Histamine [2-(4-imidazolyl)-ethylamine] is an important regulator of a range of (patho)physiological conditions, acting through four histamine receptor subtypes (H1R, H2R, H3R, and H4R).…”
Section: Oral Diseasesmentioning
confidence: 99%
“…Histamine [2-(4-imidazolyl)-ethylamine] is an important regulator of a range of (patho)physiological conditions, acting through four histamine receptor subtypes (H1R, H2R, H3R, and H4R). In particular, H4R could be associated with inflammation and immune disorders (Medina et al, 2011a). Medina et al (2011a,b) and Martinel Lamas et al (2013) demonstrated that histamine and JNJ7777120 [1-[(5-Chloro-1H-indol-2-yl)carbonyl-]-4-methylpiperazine], another H4R ligand, prevent gamma radiation-induced toxicity in intestinal mucosa, bone marrow, and salivary glands of mice and rats.…”
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.
“…Radiation, chemotherapy, and BNCT induce DNA strand breaks and reactive oxygen species which react with DNA and other cellular molecules causing cell dysfunction and mortality (Sonis, 2009;Medina et al, 2011a;Faião-Flores et al, 2013). Free radical production is the initial stage of mucositis (Elad et al, 2006;Sonis, 2009).…”
Section: Discussionmentioning
confidence: 99%
“…Histamine reduces oral mucositis in BNCT A Monti Hughes et al radioprotective compounds is of utmost importance in clinical radiotherapy (Medina et al, 2011a). Histamine [2-(4-imidazolyl)-ethylamine] is an important regulator of a range of (patho)physiological conditions, acting through four histamine receptor subtypes (H1R, H2R, H3R, and H4R).…”
Section: Oral Diseasesmentioning
confidence: 99%
“…Histamine [2-(4-imidazolyl)-ethylamine] is an important regulator of a range of (patho)physiological conditions, acting through four histamine receptor subtypes (H1R, H2R, H3R, and H4R). In particular, H4R could be associated with inflammation and immune disorders (Medina et al, 2011a). Medina et al (2011a,b) and Martinel Lamas et al (2013) demonstrated that histamine and JNJ7777120 [1-[(5-Chloro-1H-indol-2-yl)carbonyl-]-4-methylpiperazine], another H4R ligand, prevent gamma radiation-induced toxicity in intestinal mucosa, bone marrow, and salivary glands of mice and rats.…”
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.
“…To make this possible, the precancerous dose-limiting tissue should be protected from severe mucositis. The role of radioprotec-tive compounds is of utmost importance in clinical radiotherapy (Medina et al 2011a). Histamine [2-(4-imidazolyl)-ethylamine] is an important regulator of a range of (patho) physiological conditions, acting through four histamine receptor subtypes (H1R, H2R, H3R, and H4R).…”
Section: Introductionmentioning
confidence: 99%
“…Histamine [2-(4-imidazolyl)-ethylamine] is an important regulator of a range of (patho) physiological conditions, acting through four histamine receptor subtypes (H1R, H2R, H3R, and H4R). In particu-lar, H4R could be associated with inflammation and immune disorders (Medina et al 2011a). Medina et al (2011a, b) and Martinel Lamas et al (2013) demonstrated that histamine prevented gamma radiation-induced toxicity in intestinal mucosa, bone marrow, and salivary glands of mice and rats.…”
Boron neutron capture therapy (BNCT) is based on selective accumulation of B-10 carriers in tumor followed by neutron irradiation. We demonstrated, in 2001, the therapeutic effect of BNCT mediated by BPA (boronophenylalanine) in the hamster cheek pouch model of oral cancer, at the RA-6 nuclear reactor. Between 2007 and 2011, the RA-6 was upgraded, leading to an improvement in the performance of the BNCT beam (B2 configuration). Our aim was to evaluate BPA-BNCT radiotoxicity and tumor control in the hamster cheek pouch model of oral cancer at the new "B2" configuration. We also evaluated, for the first time in the oral cancer model, the radioprotective effect of histamine against mucositis in precancerous tissue as the dose-limiting tissue. Cancerized pouches were exposed to: BPA-BNCT; BPA-BNCT + histamine; BO: Beam only; BO + histamine; CONTROL: cancerized, no-treatment. BNCT induced severe mucositis, with an incidence that was slightly higher than in "B1" experiments (86 vs 67%, respectively). BO induced low/moderate mucositis. Histamine slightly reduced the incidence of severe mucositis induced by BPA-BNCT (75 vs 86%) and prevented mucositis altogether in BO animals. Tumor overall response was significantly higher in BNCT (94-96%) than in control (16%) and BO groups (9-38%), and did not differ significantly from the "B1" results (91%). Histamine did not compromise BNCT therapeutic efficacy. BNCT radiotoxicity and therapeutic effect at the B1 and B2 configurations of RA-6 were consistent. Histamine slightly reduced mucositis in precancerous tissue even in this overly aggressive oral cancer model, without compromising tumor control.
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