Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high grade gliomas, recurrent cancers of the head and neck region and either primary or metastatic melanoma. Neutron sources for BNCT currently have been limited to specially modified nuclear reactors, which are or until the recent Japanese natural disaster, were available in Japan, the United States, Finland and several other European countries, Argentina and Taiwan. Accelerators producing epithermal neutron beams also could be used for BNCT and these are being developed in several countries. It is anticipated that the first Japanese accelerator will be available for therapeutic use in 2013. The major hurdle for the design and synthesis of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations in the range of 20 μg/g. This would be sufficient to deliver therapeutic doses of radiation with minimal normal tissue toxicity. Two boron drugs have been used clinically, a dihydroxyboryl derivative of phenylalanine, referred to as boronophenylalanine or “BPA”, and sodium borocaptate or “BSH” (Na2B12H11SH). In this report we will provide an overview of other boron delivery agents that currently are under evaluation, neutron sources in use or under development for BNCT, clinical dosimetry, treatment planning, and finally a summary of previous and on-going clinical studies for high grade gliomas and recurrent tumors of the head and neck region. Promising results have been obtained with both groups of patients but these outcomes must be more rigorously evaluated in larger, possibly randomized clinical trials. Finally, we will summarize the critical issues that must be addressed if BNCT is to become a more widely established clinical modality for the treatment of those malignancies for which there currently are no good treatment options.

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Purpose: Survivin, a member of the inhibitor of apoptosis protein family, is an attractive target for cancer therapy. We have now investigated the effect of YM155, a small-molecule inhibitor of survivin expression, on the sensitivity of human non^small cell lung cancer (NSCLC) cell lines to g-radiation.Experimental Design: The radiosensitizing effect of YM155 was evaluated on the basis of cell death, clonogenic survival, and progression of tumor xenografts. Radiation-induced DNA damage was evaluated on the basis of histone H2AX phosphorylation and foci formation. Results: YM155 induced down-regulation of survivin expression in NSCLC cells in a concentration-and time-dependent manner. A clonogenic survival assay revealed thatYM155 increased the sensitivity of NSCLC cells to g-radiation in vitro. The combination of YM155 and g-radiation induced synergistic increases both in the number of apoptotic cells and in the activity of caspase-3. Immunofluorescence analysis of histone g-H2AX also showed that YM155 delayed the repair of radiation-induced double-strand breaks in nuclear DNA. Finally, combination therapy with YM155 and g-radiation delayed the growth of NSCLC tumor xenografts in nude mice to a greater extent than did either treatment modality alone. Conclusions: These results suggest thatYM155 sensitizes NSCLC cells to radiation both in vitro and in vivo, and that this effect of YM155 is likely attributable, at least in part, to the inhibition of DNA repair and enhancement of apoptosis that result from the down-regulation of survivin expression. Combined treatment withYM155 and radiation warrants investigation in clinical trials as a potential anticancer strategy.

We report elastic, quasielastic (fdE), and inelastic neutron-scattering studies of the instantaneous and dynamic spin Suctuations in as-grown and doped La2Cu04. Four samples have been studied: (A) as-grown La2Cu04 with Tn 195 K, (8) oxygenated La2Cu04 with Tjv=100 K, (C) LatCup. psLippsOg, and (D) La~.p7Srp. p3Cupp5Lipps04. A11 crystals exhibit variable-rangehopping conductivity behavior. At room temperature each sample exhibits two-dimensional (2D) antiferromagnetie instantaneous correlations in the CuO2 sheets with the correlation length varying from -200 A in crystal A to -14 A in crystal D. The integrated intensity and therefore the effective moment is, however, constant to within the experimental error. In samples A and 8 the 20 correlation length becomes sullciently large with decreasing temperature that the interplanar coupling is able to derive a transition to 30 long-range order. The spin dynamics have been studied in detail in crystals A and 8 and quite unusual behavior is observed. In contrast to previously studied planar antiferromagnets, there is no signi6cant E~O component for temperatures~Tã nd instead the 20 response function is highly inelastic. The effective dispersion of the spin excitations is 0.4 eV k This large energy scale for the spin fluctuations gives credence to models of the superconductivity in doped LatCuO& in which the pairing is magnetic in origin. I. H4i. RODUi-l IONThe discovery of superconductivity in doped La2Cu04 by Bednorz and Muller' has stimulated an enormous number of experimental and theoretical studies of this and related materials. It is broadly viewed that in order to understand the novel high-temperature superconductivity, it will be necessary to elucidate fully the behavior across the phase diagram as a function of temperature, doping, etc.It is already known that the phase diagram is remarkably rich with competing or attendant phases and phase transitions including a tetragonal-orthorhombic structural transition, 2 5 three&imensional (3D) antiferromagnetic ordering, s 7 a crossover from a 3D Niel to a 2D quantum spin Quid states and possibly a low-temperature 3D spinglass state, " an insulator-metal transition, ' and, of course, the superconducting transition. 'In any model for the superconductivity, the spindegrees of freedom of the Cu2+ ions are essential and, indeed, in many models, the magnetism is the progenitor of the high-temperature superconductivity. ' t3 It is therefore essential that the microscopic static and dynamic spin fluctuations in both pure and doped La2Cu04 be elucidated in detail. Such experiments can only be done properly utilizing large, high quality homogeneous single crystals and thus these measurements place great demands on crystal-growth techniques. ' 's In this paper we report the results of a detailed neutron scattering study of the spin Buctuations in four crystals: (A) as-grown La2Cu04, (B) oxygenated La2Cu04, (C) La2CuppsLip I-04, and (D) Lap.97Srp.p3Cup. 95Llp.p504 The 6rst two crystals were grown at Nippon Telegraph and Tele hone...

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We retrospectively review outcomes of applying boron neutron capture therapy (BNCT) to unresectable advanced or recurrent head and neck cancers. Patients who were treated with BNCT for either local recurrent or newly diagnosed unresectable head or neck cancers between December 2001 and September 2007 were included. Clinicopathological characteristics and clinical outcomes were retrieved from hospital records. Either a combination of borocaptate sodium and boronophenylalanine (BPA) or BPA alone were used as boron compounds. In all the treatment cases, the dose constraint was set to deliver a dose <10–12 Gy-eq to the skin or oral mucosa. There was a patient cohort of 62, with a median follow-up of 18.7 months (range, 0.7–40.8). A total of 87 BNCT procedures were performed. The overall response rate was 58% within 6 months after BNCT. The median survival time was 10.1 months from the time of BNCT. The 1- and 2-year overall survival (OS) rates were 43.1% and 24.2%, respectively. The major acute Grade 3 or 4 toxicities were hyperamylasemia (38.6%), fatigue (6.5%), mucositis/stomatitis (9.7%) and pain (9.7%), all of which were manageable. Three patients died of treatment-related toxicity. Three patients experienced carotid artery hemorrhage, two of whom had coexistent infection of the carotid artery. This study confirmed the feasibility of our dose-estimation method and that controlled trials are warranted.