Therapeutic effect of boron neutron capture therapy (BNCT) on field cancerized tissue: Inhibition of DNA synthesis and lag in the development of second primary tumors in precancerous tissue around treated tumors in DMBA-induced carcinogenesis in the hamster cheek pouch oral cancer model

Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential

“…1), ranging from approximately 4-15 ppm, would be an asset. Additionally, the fact that precancerous tissue boron values are, overall, higher than normal pouch tissue values, would make it potentially possible to achieve a therapeutic effect in precancerous tissue in terms of inhibition of tumor development without significant damage to normal pouch tissue (Heber et al 2007;Monti Hughes et al 2009). …”

“…We then demonstrated the therapeutic efficacy of BNCT mediated by BPA and/or GB-10 to treat experimental oral cancer in an experimental model in the hamster cheek pouch with no normal tissue radiotoxicity and without exceeding the radiotolerance of precancerous tissue (Kreimann et al 2001b;Trivillin et al 2004Trivillin et al , 2006Heber et al 2007;Pozzi et al 2009;Monti Hughes et al 2009). We also demonstrated the feasibility of treating spontaneous squamous cell carcinomas in felines with BNCT (Rao et al 2004;Trivillin et al 2008) and the efficacy of BNCT to inhibit the development of tumors from precancerous tissue (Monti ).…”

Boron neutron capture therapy for oral precancer: proof of principle in an experimental animal model

“…It is known that tissues with a faster rate of basal cell proliferation are more liable to develop mucositis (Sonis et al , ). Thus, the reduction in DNA synthesis induced by BNCT previously described in hamster cheek pouch field‐cancerized tissue (Heber et al , ) would make the tissue exposed to the second application of BNCT less or, at worst, equally liable to develop mucositis than if the total dose is delivered in a single application. These effects must be interpreted in the context of low and high LET radiation dose components of BNCT (Hopewell et al , ).…”

“…As previously described, the histological analysis of field‐cancerized tissue induced by the 6‐week protocol confirmed the existence of the same histological categories that are known to exist in the tissue with PMD induced by the classical 12‐week protocol, that is, NUMF (no unusual microscopic features): an epithelium with no apparent lesions, but with subepithelial fibrosis; hyperplasia; dysplasia. These areas coexist with tumours (Heber et al , , ). Experiments were carried out in accordance with the guidelines laid down by the National Institute of Health (NIH) in the USA regarding the care and use of animals for experimental procedures and in accordance with local laws and regulations.…”

Histamine reduces boron neutron capture therapy‐induced mucositis in an oral precancer model

“…We previously demonstrated BNCT therapeutic efficacy to treat oral cancer in this experimental model employing boron compounds approved for their use in humans (Kreimann et al , ; Trivillin et al , ) and novel boron compounds (Heber et al , ). Despite therapeutic success, the inhibition of tumor development from field‐cancerized tissue remained an unresolved challenge (Heber et al , ). The relevance of field cancerization in head and neck cancer lies in the frequent occurrence of second primary tumors after treatment (Jaiswal et al , ; Monti‐Hughes et al , ).…”