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At least 19 recordsLinked to original sources
PubMed1998

In vivo and in vitro effects of boron and boronated compounds.

Boron is ubiquitously present in soils and water. Associated with pectin it is essential for vascular plants as a component of cell walls, and it stabilizes cell membranes. It is required for the growth of pollen tubes and is involved in membrane transport, stimulating H(+)-pumping ATPase activity and K+ uptake. However, a high boron concentration in the soils is toxic to plants and some boronated derivatives are used as herbicides. An absolute requirement for boron has not been definitively demonstrated in animals and humans. However, experiments with boron supplementation or deprivation show that boron is involved in calcium and bone metabolism, and its effects are more marked when other nutrients (cholecalciferol, magnesium) are deficient. Boron supplementation increases the serum concentration of 17 beta-estradiol and testosterone but boron excess has toxic effects on reproductive function. Boron may be involved in cerebral function via its effects on the transport across membranes. It affects the synthesis of the extracellular matrix and is beneficial in wound healing. Usual dietary boron consumption in humans is 1-2 mg/day for adults. As boron has been shown to have biological activity, research into the chemistry of boronated compounds has increased. Boronated compounds have been shown to be potent anti-osteoporotic, anti-inflammatory, hypolipemic, anti-coagulant and anti-neoplastic agents both in vitro and in vivo in animals.

Adult↗
PubMed1998

On the possible use of a new boron compound, hydroxysalicylhydroxamato boron(III), and ultrasound in the treatment of female mice bearing the Ehrlich ascites carcinoma cells.

The inhibitory effects of a new boron compound, hydroxy salicylhydroxamato boron (III) (SHB) and ultrasound of frequency 25 KHz (US) on the growth of ascites tumor in female Swiss mice were studied by monitoring the survival and the tumor growth in the treated tumor bearing mice and also the transplantability and the DNA synthesis in the treated tumor (Ehrlich ascites carcinoma) cells. While SHB alone produced a highly significant antitumor activity, US alone produced a small but significant effect. The combination of SHB and US produced significantly greater antitumor activity than SHB alone. The mechanisms of SHB and US actionary are discussed.

Animals↗
PubMed1997

Chemistry and biology of some low molecular weight boron compounds for boron neutron capture therapy.

Boronated DNA targeting agents are especially attractive candidates for BNCT because they may deliver boron-10 to the nuclei of tumor cells. Numerous boron-containing analogs have been synthesized and some have shown promising results in initial biological tests. One of the most challenging tasks in this special field of research remains the finding of suitable targeting strategies for the selective delivery of boron rich DNA-intercalator/alkylator to tumor cells. Synthetic and biological studies of boron compounds suitable for DNA-binding are reviewed. The amino acid p-boronophenylalanine (BPA) is presently of considerable clinical interest. Other boronated amino acids might also be candidates for BNCT either per se, as part of part of tumor-seeking peptides or conjugated to targeting macromolecules. A large number of boronated L- and D-amino acids with varying liphophicility and sterical requirements are now available for evaluation. Recent synthetic and biological studies of aromatic boronoamino acids, carboranylamino acids and carboranyl amines are also reviewed.

Amino Acids↗
PubMed1993

Intracellular distribution of various boron compounds for use in boron neutron capture therapy.

The neutron capture reaction in boron (10B(n, alpha)7Li) generates two short-range particles with high linear energy transfer. The effect of neutron capture therapy depends on the selective localization of 10B atoms in target cells. The determination of the distribution of boron compounds in cancer cells at the subcellular level is required for the understanding of the effect of this treatment. The monomeric sulfhydryl borane (BSH) compound has been used clinically in Japan and preclinically in the U.S.A. Recently, new compounds have been developed: a dimeric sulfhydryl borane (BSSB), a boronophenylalanine (BPA), and two porphyrin complexes (BOPP and VCDP). This study demonstrates that the porphyrin complexes (BOPP and VCDP) are more cytotoxic than the other three compounds to the rat 9L gliosarcoma cell line. Using atomic absorption spectrophotometry to determine boron content for cellular uptake studies of these agents, we found that of the five compounds tested BOPP (25 microM) exposure resulted in the greatest boron uptake averaging 305 ng B/10(6) cells. BSSB (500 microM) was second averaging 93 ng B/10(6) cells, BSH (500 microM) third averaging 62 ng B/10(6) cells, VCDP (25 microM) fourth averaging 58 ng B/10(6) cells, and BPA (500 microM) fifth averaging 7.4 ng B/10(6) cells. Data on the distribution of boron in the nuclei, mitochondria, lysosomes, microsomes, and cytosomes of 9L cells are also presented.

Animals↗
PubMedDate not supplied

[A uniform approach to the synthesis of carbohydrate conjugates of polyhedral boron compounds as potential agents for boron neutron capture therapy].

A uniform approach to the synthesis of carbohydrate conjugates with polyhedral boron compounds (PBCs) was developed. Oligosaccharide derivatives with an aglycone moiety amino group can be coupled with PBC carboxyl derivatives using N-methyl-N-(4,6-dimethoxy-1,3,5-triazin-2-yl)morpholinium chloride as a coupling agent. Both N- and O-glycosides differing in the conformational mobility around the glycoside bond were shown to be useful as oligosaccharides with a functional group in the aglycone moiety. This allows the application of this approach to the synthesis of PBC conjugates with a wide range of oligosaccharides. For example, not only oligosaccharides obtained by chemical synthesis but also reducing oligosaccharides isolated from natural sources can be transformed into N-glycosides. The approach was tested by the example of conjugation of the carboxyl derivatives of ortho-carborane and dodecaborate anion with lactose as a model oligosaccharide. Lactose, an easily available disaccharide, is a ligand for lectins expressed on the surface of melanoma cells. The approach suggested is the first example of the synthesis of such conjugates that does not require protective groups for the carbohydrate residue. It is especially important for obtaining dodecaborate-carbohydrate conjugates for which the removal of protective groups is often a non-trivial task.

Animals↗
PubMed1993

Subcellular distribution of various boron compounds and implications for their efficacy in boron neutron capture therapy by Monte Carlo simulations.

Neutron capture therapy has a promising role in cancer treatment since it can achieve selectivity at the cellular level. The effect of this therapy depends on the subcellular localization of boron atoms in the target cell. Five boron compounds were investigated in this study: the monomeric and dimeric sulfhydryl boranes (BSH and BSSB), a boronated phenylalanine (BPA), and two porphyrin complexes (BOPP and VCDP). The study shows that when exponentially growing rat 9L gliosarcoma cells are exposed to an isoeffective concentration of each of the five compounds for 1 h, BOPP produces a much higher intracellular level of boron than the other four compounds; BSSB produces the second highest level, while exposure to BSH, VCDP, and BPA resulted in lower intracellular boron levels. Subcellular fractionation studies showed that most of the boron localized in the cytoplasm of the cells with all five compounds. A significantly higher boron concentration was found in the lysosomes of the cells, but the nuclei contained only minimal concentrations of boron. Computer simulations of neutron capture reactions with boron using a Monte Carlo simulation code indicated that BOPP would yield the highest potential effectiveness, followed by BSSB, BSH, VCDP, and BPA, in that order.

Animals↗
PubMed2006

Impact of intra-arterial administration of boron compounds on dose-volume histograms in boron neutron capture therapy for recurrent head-and-neck tumors.

PURPOSE: To analyze the dose-volume histogram (DVH) of head-and-neck tumors treated with boron neutron capture therapy (BNCT) and to determine the advantage of the intra-arterial (IA) route over the intravenous (IV) route as a drug delivery system for BNCT. METHODS AND MATERIALS: Fifteen BNCTs for 12 patients with recurrent head-and-neck tumors were included in the present study. Eight irradiations were done after IV administration of boronophenylalanine and seven after IA administration. The maximal, mean, and minimal doses given to the gross tumor volume were assessed using a BNCT planning system. RESULTS: The results are reported as median values with the interquartile range. In the IA group, the maximal, mean, and minimal dose given to the gross tumor volume was 68.7 Gy-Eq (range, 38.8-79.9), 45.0 Gy-Eq (range, 25.1-51.0), and 13.8 Gy-Eq (range, 4.8-25.3), respectively. In the IV group, the maximal, mean, and minimal dose given to the gross tumor volume was 24.2 Gy-Eq (range, 21.5-29.9), 16.4 Gy-Eq (range, 14.5-20.2), and 7.8 Gy-Eq (range, 6.8-9.5), respectively. Within 1-3 months after BNCT, the responses were assessed. Of the 6 patients in the IV group, 2 had a partial response, 3 no change, and 1 had progressive disease. Of 4 patients in the IA group, 1 achieved a complete response and 3 a partial response. CONCLUSION: Intra-arterial administration of boronophenylalanine is a promising drug delivery system for head-and-neck BNCT.

Adult↗
PubMed1999

Boron neutron capture therapy (BNCT): implications of neutron beam and boron compound characteristics.

The potential efficacy of boron neutron capture therapy (BNCT) for malignant glioma is a significant function of epithermal-neutron beam biophysical characteristics as well as boron compound biodistribution characteristics. Monte Carlo analyses were performed to evaluate the relative significance of these factors on theoretical tumor control using a standard model. The existing, well-characterized epithermal-neutron sources at the Brookhaven Medical Research Reactor (BMRR), the Petten High Flux Reactor (HFR), and the Finnish Research Reactor (FiR-1) were compared. Results for a realistic accelerator design by the E. O. Lawrence Berkeley National Laboratory (LBL) are also compared. Also the characteristics of the compound p-Boronophenylaline Fructose (BPA-F) and a hypothetical next-generation compound were used in a comparison of the BMRR and a hypothetical improved reactor. All components of dose induced by an external epithermal-neutron beam fall off quite rapidly with depth in tissue. Delivery of dose to greater depths is limited by the healthy-tissue tolerance and a reduction in the hydrogen-recoil and incident gamma dose allow for longer irradiation and greater dose at a depth. Dose at depth can also be increased with a beam that has higher neutron energy (without too high a recoil dose) and a more forward peaked angular distribution. Of the existing facilities, the FiR-1 beam has the better quality (lower hydrogen-recoil and incident gamma dose) and a penetrating neutron spectrum and was found to deliver a higher value of Tumor Control Probability (TCP) than other existing beams at shallow depth. The greater forwardness and penetration of the HFR the FiR-1 at greater depths. The hypothetical reactor and accelerator beams outperform at both shallow and greater depths. In all cases, the hypothetical compound provides a significant improvement in efficacy but it is shown that the full benefit of improved compound is not realized until the neutron beam is fully optimized.

Biophysics↗
PubMed2002

Antineoplastic effect of new boron compounds against leukemic cell lines and cells from leukemic patients.

Three new boron compounds, dihydroxy (oxybiguanido) boron (iii) hydrochloride monohydrate (HB), guanidine biboric acid adduct (GB) and hydroxosalicyl hydroxomato boron (iii) (SHB) were studied to observe their antineoplastic effect, if any. Leukemic cells isolated from acute lymphatic leukaemia (ALL) patients and chronic myeloid leukaemia patients (CML) and myeloid leukemia cell lines (HL 60 and U-937) showed cell growth inhibition after treatment with the boron compounds. MTT assay showed that the growth of metabolically active cells was inhibited by treatment with these drugs. The molecular mechanism by which SHB induced apoptosis in immature blast cells was also investigated by ladder formation in gel electrophoresis.

Acute Disease↗
PubMed2007

Analysis of boron distribution in vivo for boron neutron capture therapy using two different boron compounds by secondary ion mass spectrometry.

The efficiency of boron neutron capture therapy (BNCT) for malignant gliomas depends on the selective and absolute accumulation of (10)B atoms in tumor tissues. Only two boron compounds, BPA and BSH, currently can be used clinically. However, the detailed distributions of these compounds have not been determined. Here we used secondary ion mass spectrometry (SIMS) to determine the histological distribution of (10)B atoms derived from the boron compounds BSH and BPA. C6 tumor-bearing rats were given 500 mg/kg of BPA or 100 mg/kg of BSH intraperitoneally; 2.5 h later, their brains were sectioned and subjected to SIMS. In the main tumor mass, BPA accumulated heterogeneously, while BSH accumulated homogeneously. In the peritumoral area, both BPA and BSH accumulated measurably. Interestingly, in this area, BSH accumulated distinctively in a diffuse manner even 800 microm distant from the interface between the main tumor and normal brain. In the contralateral brain, BPA accumulated measurably, while BSH did not. In conclusion, both BPA and BSH each have advantages and disadvantages. These compounds are considered to be essential as boron delivery agents independently for clinical BNCT. There is some rationale for the simultaneous use of both compounds in clinical BNCT for malignant gliomas.

Animals↗
PubMedDate not supplied

On the inhibitory activities of a new boron compound and ultrasound against the mouse ascites tumour.

The inhibitory effects of a new boron compound, dihydroxy (oxybiguanido) boron (III) hydrochloride monohydrate (HB), and ultrasound (US) of a frequency 25 kHz on the growth of ascites tumour in female Swiss mice were studied by monitoring the survival, weight of tumour-associated material, tumour cell count, serum alkaline phosphatase activity and the haematological parameters of the treated animals. 5-Fluorouracil (5-FU), a well-known anticancer agent, was used as positive control. While HB exhibited a very significant antitumour action, US alone produced a small but significant inhibitory effect. The combination of US with HB or 5-FU produced an extra antitumour action as compared to the actions of these chemicals used singly. The mechanisms of action of the new boron compound (HB) and US are discussed.

Alkaline Phosphatase↗
PubMed1990

In vitro determination of uptake, retention, distribution, biological efficacy, and toxicity of boronated compounds for neutron capture therapy: a comparison of porphyrins with sulfhydryl boron hydrides.

A major problem remaining in the evaluation of boronated compounds for neutron capture therapy (NCT) is the need to know the intra- or extracellular microdistribution of boron. This is a consequence of the short range of the 10B(n,alpha)7Li reaction products (approximately 10 microns), such that biological efficacy is dependent upon intracellular distribution. In particular, if boron location is predominantly extracellular, a significant reduction in efficacy would be expected. The in vitro procedure described here was developed mainly to provide information regarding the intra- and extracellular location and concentration of boron. However, use of the technique also allows the measurement of compound uptake and retention (binding) and the determination of biological efficacy by the evaluation of survival curves obtained following irradiation with thermal neutrons. Comparison is made to results obtained with boric acid (H3(10)BO3) and to results calculated for various boron distributions. Concomitantly, an indication of compound toxicity can be obtained from the plating efficiency of unirradiated control cells. Currently, most investigators utilize in vivo systems for testing and evaluating boron uptake from various carrier molecules. Given the large number of boron compounds being synthesized and needing evaluation as to their usefulness for NCT, the in vitro technique described here is simple and advantageous for initial compound screening. In addition to sparing animal lives, it is both time and cost effective and utilizes much smaller quantities of test compound than are required for an in vivo assay. A boronated porphyrin (BOPP) evaluated by the above procedure shows an uptake and retention approximately 20 times that of sulfhydryl boron hydride monomer (BSH); the latter compound is currently being used clinically for NCT in Japan and is anticipated for use in clinical trials in the United States. If the advantages demonstrated by BOPP in these in vitro studies are validated in animal experiments, BOPP should be considered for clinical application.

Animals↗
PubMed1994

Fourier transform infrared (FTIR) spectrometry for the assay of polyhedral boron compounds in plasma and pharmaceutical formulations.

The determination of polyhedral boron compounds such as sodium borocaptate directly in blood plasma is described using FTIR with computed nonlinear background subtraction of the water absorption band. The procedure can be performed in less than 15 min to a sensitivity level of 5 ppm boron (as a signal/noise ratio of 2.5), which is satisfactory in the clinical application of such compounds in neutron capture therapy of cancer. For boron compounds with suitable organic solubility, extraction from plasma into carbon tetrachloride is described as an alternative approach not requiring computed subtraction and capable of achieving a sensitivity level of 1 ppm. Both the boron and the lipid content of liposome formulations containing the polyhedral boron compounds can be measured simultaneously by FTIR. After extraction into CHCl3:CH3OH (1:1) or dispersion in ethanol, the extracts are evaporated to dryness and redissolved in carbon tetrachloride for FTIR assay.

Boron Compounds↗
PubMedDate not supplied

Preparation and characterization of liposomal systems entrapping the boronated compound o-carboranylpropylamine.

Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when the stable isotope, Boron-10, is irradiated with low-energy thermal neutrons to yield ionizing Helium and Lithium ions that are highly damaging and usually lethal to cells. The successful treatment of cancer by BNCT requires the selective concentration of Boron-10 within malignant tumours. Liposomes have been used as therapeutic compound delivery vehicles for in vivo application, including several anticancer agents. The ability of the boron-containing compound, o-carboranylpropylamine chloride, to accumulate within unilamellar liposomes in response to a transmembrane pH gradient is evaluated. Characterization of the systems obtained is performed for conventional and polyethylene glycol (PEG)-modified (stealth) liposomes, in terms of lipid and CPA contents, vesicle size and stability in detergent solutions. Results demonstrate that CPA loading and vesicle stability can be controlled by the experimental procedure. The loading of CPA into liposomes with average diameters of 100 nm is estimated at 13000 molecules per vesicle for the most stable systems. CPA toxicity to normal human peripheral blood lymphocytes and to adherent glioblastoma multiforme SK-MG-1 cells in vitro is observed to decrease as a result of the entrapment of CPA in liposomes.

Boron Compounds↗
PubMed1996

Radiobiological evidence suggesting heterogeneous microdistribution of boron compounds in tumors: its relation to quiescent cell population and tumor cure in neutron capture therapy.

PURPOSE: The heterogeneous microdistribution of boron compounds in tumors and its significance on tumor cure were examined by a radiobiological procedure. The role of quiescent (Q) cells in tumor was especially investigated. METHODS AND MATERIALS: 10B-enriched paraboronophenylalanine (BPA) and mercaptoundecahydrododecaborate (BSH) were administered to SCCVII tumor bearing C3H/He mice by intragastric and i.v. injections, respectively. The continued effects of these boron compounds with thermal irradiations were studied by using colony formation and tumor control assays. Their effects on Q cells were also analyzed by the combined method of micronucleus frequency assay and an identification of proliferating (P) cells by BUdR and anti-BUdR monoclonal antibody. RESULTS: 10B-concentration after BPA (1,500 mg/kg) and BSH (75 mg/kg) administration were 11 ppm at 3 h and 10.5 ppm at 30 min, respectively. Cell survival decreased exponentially with an increment of neutron fluence (phi). The exponential parts of the curves were: -InSF = -0.052+ 13.0x10(13)phi, -InSF = -0.032+7.68X10(-13)phi, and -InSF = -0.0005+2.68x10(-13)phi for BPA-BNCT, BSH-BNCT, and NCT alone, respectively. Fifty percent tumor control was obtained at the influence of 10.2 x 10(12) n/cm2 in BPA-BNCT. On the other hand, 11.4 x 10(12) n/cm2 of neutrons had to be delivered in BSH-BNCT. The normal nuclear division fraction defined as the cell fraction that did not express micronuclei at first mitosis after treatment was investigated. The surviving cell fraction and the normal nuclear division fraction were regarded as equal in NCT alone. However, the normal nuclear division factor following BPA-BNCT was greater than the surviving cell fraction, and the difference increased with an increase in neutron fluence. In Q cells, BSH-BNCT yielded higher micronucleus frequency than BPA-BNCT and NCT alone. The frequencies in Q cells following BPA-BNCT and NCT alone were almost same as that in total cell population after NCT alone. CONCLUSIONS: Our data suggested that BPA distributed in tumors hetergeneously. Q cells especially might not accumulate BPA. To decrease the possible disadvantage of BPA-BNCT, the combination of BPA and BSH or other neutron capture element that emit particles with longer ranges, for example, gadolinium, would have to be investigated.

Animals↗
PubMed2006

Polyhedral boron compounds as potential diagnostic and therapeutic antitumor agents.

The use of polyhedral boron hydrides for cancer treatment is traditionally connected with boron neutron capture therapy. More recently, polyhedral borate anions were proposed as carriers of radionuclide label for targeted radionuclide therapy and diagnostics of cancer. Some metal derivatives of carboranes were found to demonstrate significant antitumor activity themselves. This review is designed to highlight the recent work concerning various fields of potential application of polyhedral boron compounds in anticancer diagnostics and therapy.

Animals↗
PubMedDate not supplied

A new boron compound (guanidine biboric acid adduct) as an antitumour agent against Ehrlich ascites carcinoma in mice.

The inhibitory effects of a new boron compound of guanidine biboric acid adduct (GB) and guanidium chloride (L1) on the growth of ascites tumour in female Swiss mice were studied by monitoring the survival, tumour weight, tumour cell count, transplantability of Ehrlich ascites cells, precursor incorporation and the haematological parameters of the treated mice. 5-Fluorouracil, a known anticancer drug, was used as a positive control. The most important parameter was the survival time, which increased significantly when tumour-bearing mice were treated with the boron compound. Haematological parameters of the treated animals showed minimum toxic effects when boron was coupled with guanidine.

Animals↗