Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have developed neutron-capture therapy (NCT) for cutaneous malignant melanoma using a melanoma-seeking 10B-dopa, analogue, 10B1-para-boronophenylalanine (10B1-BPA). In order to explore the feasibility of applying NCT further to ocular melanoma, we investigated the boron concentrations in ocular melanomas and normal ocular tissues by 10B1-BPA administration to three patients, because success of NCT depends mainly upon selective boron accumulation in melanoma. In the first and second ocular melanoma patients, to whom 10B1-BPA fructose complex (total dose of 10B1-BPA: 170 mg/kg body weight) was administered orally in two divided doses, the boron concentrations in blood, vitreous body, sclera and retina choroidea were lower than that in melanoma examined. In the third conjunctival melanoma patient, to whom 10B1-BPA fructose complex (dose of 10B1-BPA: 85 mg/kg body weight) was administered by intravenous drip infusion, the average boron concentration in four melanoma samples was 17.7 ppm, which was estimated to be within the range necessary for melanoma eradication by thermal neutron irradiation. Boron uptake by lens, vitreous body, retina choroidea and sclera was much lower than that by melanoma. It was suggested that such a superficial ocular melanoma as iris melanoma can be destroyed by NCT, although vision may be affected--mainly due to cataract formation.
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PMID:Selective boron accumulation in human ocular melanoma vs surrounding eye components after 10B1-p-boronophenylalanine administration. Prerequisite for clinical trial of neutron-capture therapy. 791 64

Sodium borocaptate (BSH) and boronophenylalanine (BPA) are two drugs that have been used clinically for boron neutron capture therapy (BNCT) of brain tumors. We previously have reported that hyperosmotic mannitol-induced disruption of the blood-brain barrier (BBB-D), followed by intracarotid (i.c.) administration of BPA or BSH, either individually or in combination, significantly enhanced tumor boron delivery and the efficacy of BNCT in F98 glioma bearing rats. The purpose of the present study was to determine the short-term neuropathologic consequences of this treatment and the long-term effects on motor and cognitive function, as well as the neuropathologic sequelae 1 year following neutron capture irradiation. BBB-D was carried out in non-tumor bearing Fischer rats by infusing a 25% solution of mannitol i.c. followed by i.c. injection of BPA or BSH, either individually or in combination, immediately thereafter. Animals were euthanized 2 days after compound administration, and their brains were processed for neuropathologic examination, which revealed sporadic, mild, focal neuronal degeneration, hemorrhage, and necrosis. To assess the long-term effects of such treatment followed by neutron capture irradiation, non-tumor bearing rats were subjected to BBB-D after which they were injected i.c. with BPA (25 mg B/kg body weight (b.w)) or BSH (30 mg B/kg b.w.) either individually or in combination (BPA 12.5 mg and BSH 14 mg B/kg b.w.). Two and a half hours later they were irradiated at the Medical Research Reactor, Brookhaven National Laboratory, Upton, NY, with the same physical radiation doses (5.79, 8.10 or 10.06 Gy), delivered to the brain, as those that previously had been used for our therapy experiments. The animals tolerated this procedure well, after which they were returned to Columbus, Ohio where their clinical status was monitored weekly. After 1 year, motor function was assessed using a sensitive and reliable locomotor rating scale for open field testing in rats and cognitive function was evaluated by their performance in the Morris water maze, the results of which were similar to those obtained with age matched controls. After functional evaluation, the rats were euthanized, their brains were removed, and then processed for neuropathologic examination. Subtle histopathologic changes were seen in the choroid plexuses of irradiated animals that had received BPA, BSH or saline. Radiation related ocular changes consisting of keratitis, blepharitis, conjunctivitis and cataract formation were seen with similar frequency in most rats in each treatment group. Based on these observations, and the previously reported significant therapeutic gain associated with BBB-D and i.c. injection of BSH and BPA, the present observations establish its safety in rats and suggest that further studies in large animals and humans are warranted.
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PMID:Boron neutron capture therapy of brain tumors: functional and neuropathologic effects of blood-brain barrier disruption and intracarotid injection of sodium borocaptate and boronophenylalanine. 1110 Aug 16