Toric anti-self-dual 4-manifolds via complex geometry

Using the twistor correspondence, this article gives a one-to-one correspondence between germs of toric anti-self-dual conformal classes and certain holomorphic data determined by the induced action on twistor space. Recovering the metric from the holomorphic data leads to the classical problem of prescribing the Cech coboundary of 0-cochains on an elliptic curve covered by two annuli. The classes admitting Kahler representatives are described; each such class contains a circle of Kahler metrics. This gives new local examples of scalar-flat Kahler surfaces and generalises work of Joyce who considered the case where the distribution orthogonal to the torus action is integrable.Comment: 25 pages, 2 figures, v2 corrected some misprints, v3 corrected more misprints, published version (minus one typo

Early clinical experience of boron neutron capture therapy for glioblastoma multiforme

Boron neutron capture therapy (BNCT) is a binary treatment modality that can selectively irradiate tumor tissue. BNCT uses drugs containing a stable isotope of boron. {sup 10}B, to sensitize tumor cells to irradiation by low energy (thermal) neutrons. The interaction of the {sup 10}B with a thermal neutron (neutron capture) causes the {sup 10}B nucleus to split, releasing an alpha particle and a lithium nucleus. These products of the {sup 10}B(n, {alpha}){sup 7}Li reaction are very damaging to cells but have a combined path length in tissue of approximately 14 {mu}m, or roughly the diameter of one or two cells. Thus, most of the ionizing energy imparted to tissue is localized to {sup 10}B-loaded cells

Toric anti-self-dual Einstein metrics via complex geometry

Using the twistor correspondence, we give a classification of toric anti-self-dual Einstein metrics: each such metric is essentially determined by an odd holomorphic function. This explains how the Einstein metrics fit into the classification of general toric anti-self-dual metrics given in an earlier paper (math.DG/0602423). The results complement the work of Calderbank-Pedersen (math.DG/0105263), who describe where the Einstein metrics appear amongst the Joyce spaces, leading to a different classification. Taking the twistor transform of our result gives a new proof of their theorem.Comment: v2. Published version. Additional references. 14 page

Carborane-containing metalloporphyrins for BNCT

For BNCT of malignant brain tumors, it is crucial that there be relatively high boron concentrations in tumor compared with normal tissues within the neutron-irradiated treatment volume. Fairchild and Bond estimated that major advances in BNCT should be possible if ratios of {sup 10}B concentrations in tumor to those in normal tissue (e.g. brain and blood) were at least 5: 1. Given that the only current boron carrier being tested clinically in the U.S., p-boronophenyl-alanine[BPA], yields tumor blood and tumor brain ratios of about 3:1, the criteria for new boronated compounds should be to at least match these ratios and maintain tumor boron concentrations greater than 30 {mu}g B/g. Although previously tested boronated porphyrins have not only matched but surpassed these ratios, it was at a cost of greater toxicity. Chemical and hematological assays of blood analytes; showed marked thrombocytopenia, a decrease to about one-tenth the normal concentration of platelets circulating in the blood, in addition to abnormalities in concentrations of circulating enzymes, that indicated liver toxicity. The physical appearance and behavior of the affected mice were different from those of mice injected with solvent only. Although thrombocytopenia and other toxic effects had disappeared after a few days, previously tested porphyrins would not be safe to infuse into patients for BNCT of potentially hemorrhagic malignant tumors in the brain such as glioblastoma multiforme and metastatic melanoma. We synthesized a different boronated porphyrin, tetracarboranylphenylporphyrin, [TCP] and inserted nickel, copper, or manganese into its coordination center. Biological studies of NiTCP in mice and of CuTCP in rats show that these compounds elicit little or no toxicity when given at potentially therapeutic doses

BPA uptake in rat tissues after partial hepatectomy

In boron neutron capture therapy (BNCT), boron given as boronophenylalanine (BPA) accumulates transiently not only in tumors but also in normal tissues. Average boron concentrations in transplanted 9L gliosarcoma tumors of 20 rats were 2.5 to 3.7 times concentrations found in blood. Although boron levels in a variety of tissues were also higher than blood the concentrations were less than the lowest found in the tumor. Further note than although BPA is a structural analogue of phenylalanine (Phe), the pathway of BPA uptake into regenerating liver may not be linked to Phe uptake mechanisms

Boron neutron capture therapy of ocular melanoma and intracranial glioma using p-boronophenylalanine

During conventional radiotherapy, the dose that can be delivered to the tumor is limited by the tolerance of the surrounding normal tissue within the treatment volume. Boron Neutron Capture Therapy (BNCT) represents a promising modality for selective tumor irradiation. The key to effective BNCT is selective localization of {sup 10}B in the tumor. We have shown that the synthetic amino acid p-boronophenylalanine (BPA) will selectively deliver boron to melanomas and other tumors such as gliosarcomas and mammary carcinomas. Systemically delivered BPA may have general utility as a boron delivery agent for BNCT. In this paper, BNCT with BPA is used in treatment of experimentally induced gliosarcoma in rats and nonpigmented melanoma in rabbits. The tissue distribution of boron is described, as is response to the BNCT. 6 refs., 4 figs., 1 tab

Uptake of [sup 10]B in gliosarcomas following the injection of gluthathione monoethyl ester and sulfhydryl borane

The sulfhydryl borane Na[sub 2][sup 10]B[sub 12]H[sub 11]SH (BSH) was developed as a capture agent for BNCT about 20 years ago and is the compound currently used clinically in Japan for BNCT of malignant brain tumors. Tumor [sup 10]B concentrations following the infusion of the oxidized BSH, a disulfide dimer (Na[sub 4][sup 10]B[sub 24]H[sub 22]S[sub 2]), are nearly twice those obtained following administration of equal amounts of boron as BSH. Also, the rate of decrease of tumor [sup 10]B concentration is slower after dimer infusion than after BSH infusion. When BNCT was administered to rats bearing intracerebral gliosarcomas, the animals infused with dimer had a significant longer median survival time. Dimer, on the other hand, induces a moderately severe, but reversible, hepatotoxicity which may complicate its use in humans. Intracellular glutathione plays an important role in defense against radical-mediated tissue injury. Glutathione monoesters have been reported to have a protective effective on cisplatin toxicity and on radical-induced acute pancreatitis. We investigated the possibility of reducing dimer-induced hepatotoxicity by pre-administration of GSH-ME. The results indicate that not only does the pre-administration of GSH-ME markedly reduce dimer-induced hepatotoxicity, but also results in nearly a doubling of tumor boron concentration. Furthermore, GSH-ME markedly increases tumor boron uptake and retention following administration of BSH

Major compound-dependent variations of sup 10 B(n. alpha. ) sup 7 Li RBE for the 9L RAT gliosarcoma in vitro and in vivo

Relative biological effectiveness (RBE) values for the high linear-energy-transfer (LET) radiations produced during born neutron capture therapy (BNCT) were determined using the 9L rat gliosarcorna both in vitro and as an intracerebral tumor. In the absence of {sup 10}B, the combined effect of the recoiling protons from the {sup 14}N(n,p){sup 14}C and the {sup 1}H(n,n{prime})p reactions, compared to an iso-effect endpoint produced by 250 kVp x-rays, yielded RBEs for these high-LET protons of 4.4 in vitro and 3.8 in an in vivo/in vitro assay. RBEs for the {sup 10}B(n,{alpha}){sup 7}Li reaction were calculated from cell survival data following reactor irradiation in the presence or in the absence of the either of the amino acid, p-boronophenylalanine (BPA) or the sulfhydryl dodecaborane dimer (BSSB). With BPA, RBE values ranged from 3.5 to 11.4, while under the same set of conditions with BSSB, RBE values ranged from 1.1 to 4.3. In vitro, higher RBEs for the {sup 10}B(n,{alpha}){sup 7}Li reaction using BPA than with BSSB suggest a difference in distribution of {sup 10}B relative to the nucleus

Spatially fractionated microirradiation of normal CNS and gliosarcomas of the rat with synchrotron photons: Cell and tissue lesions; Raeumlich fraktionierte Mikrobestrahlung von normalem ZNS und Gliosarkomen der Ratte mit Synchrotron-Photonen: Zell- und Gewebelaesionen

Rats were implanted intracerebrally with 9L gliosarcoma cells were used to experimentally determine the curative effectiveness of synchrotron radiation produced by the National Synchrotron Radiation Source. Radiation was delivered in beams with each ray 25 micrometers thick and arranged in an array of 4 mm corners. All experimental animals receiving the gliosarcoma cells and not treated died within four weeks. Treated animals surviving 113 days were sacrificed and their brains were examined histologically