These results indicate that BPA-mediated BNCT can exert a curative effect on human oral SCC xenografts in nude mice, if an optimal 10B concentration in tumors is achieved and that the disintegration of blood vessels in tumor stroma may contribute to tumor remission by BNCT.

No abstract

Current oncolytic viruses exert only limited antitumor activity on their own. There is a need to increase their oncolytic capability. We evaluated the effect of a differentiating reagent, hexamethylene bisacetamide (HMBA), on the antitumor activity of a g 1 34.5-deficient herpes simplex virus type 1 (HSV-1) R849 for human oral squamous cell carcinoma (SCC) cells. Hexamethylene bisacetamide increased the viral yield, especially at a low input multiplicity of infection (MOI), and the transcription of immediate early genes of HSV-1. Hexamethylene bisacetamide treatment promoted the cytopathic effect of R849 and increased the proportion of dead cells. Hexamethylene bisacetamide produced more apoptotic cells in R849-infected cells as compared with parental HSV-1(F)-infected cells. The growth of oral SCC xenografts in nude mice was markedly suppressed by treatment with R849 in combination with HMBA, and the survival of the co-treated animals was significantly prolonged as compared with that of animals treated with R849 only. Herpes simplex virus type 1 mRNA was expressed in tumors and trigeminal neurons, but not in brain, lung, liver, and kidney. These results indicate that HMBA enhances the antitumor activity of R849 through the expression of immediate early genes without increasing its toxicity. Hexamethylene bisacetamide can be used as an enhancing agent for oncolytic therapy with HSV-1 mutants.

Boron neutron capture therapy (BNCT) is a tumor-cell targeted radiotherapy. When 10 B absorbs thermal neutrons, the alpha and 7 Li particles generated by the 10 B(n, α) 7 Li reaction are high LET particles, and carry high kinetic energy (2.34 MeV) , and have short ranges (4 9 micron-meters) of approximately one-cell diameter, resulting in a large RBE and selective destruction of tumor cells containing 10 B. We have, for the first time in the world, used BNCT to treat 11 patients with recurrent head and neck malignancies (HNM) after a standard primary therapy since 2001. The 11 patients were composed of 6 squamous cell carcinomas, 3 salivary gland tumors and 2 sarcomas. The results of BNCT were as follows.(1) Regression rates (volume %) were CR : 2 cases, >90% : 5 cases, 73% : 1case, 54% : 1 case, PD : 1 case, NE (not evaluated) : 1 case. The response rate was 82%. (2)Improvement of QOL was recognized, such as disappearance of tumor ulceration and covering with normal skin : relief of severe pain, bleeding, trismus and dyspnea : improvement of PS (from 4 to 2) allowing the patients to return to work and elongate his survival period. (3)Survival periods after BNCT were 1 38 months (mean : 8.5 months) . The survival rate was 36% (4 cases) . (4) There are a few side-effects such as transient mucositis and alopecia less than Grade-2.These results indicate that BNCT represents a new and promising treatment approach even for a huge or far-advanced HNM.Key words：head and neck malignancies，boron neutron capture therapy(BNCT) ，boronophenylalanine (BPA) ，borocaptate sodium(BSH)