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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of the blood-brain barrier and of tumor-specific antibodies to concentrate boron selectivity in gliomas for neutron capture therapy is considered experimentally and theoretically. The time-dependent concentration of two anionic boranes, B12 H11 SH2- and B12 H11 SOSB12 H114-, in the blood, brain, and tumor of rats bearing a tumor of gliomatous origin is reported. The rate of clearance of each anionic borane from the blood is correlated with the fraction of non-protein bound anion in the plasma. The use of antibodies to carry therapeutical useful amounts of boron to tumor-specific or tumor-associated antigens on the tumor cell surface will require different numbers of boron atoms bound per antibody depending on several immunological and physical parameters. Calculations using published values of antibody-antigen association constants and of cell surface antigen densities predict that in order to obtain 10mug 10B/g tumor from 10 to over 10,000 boron-10 atoms will have to be bound per tumor antigenic site.
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PMID:Boron neutron capture therapy of cerebral gliomas. II. Utilization of the blood-brain barrier and tumor-specific antigens for the selective concentration of boron in gliomas. 18 Apr 70

This monograph on lynestrenol includes chemical and physical data (synonyms and tradenames), structural and molecular formulae and molecular weight, chemical and physical properties of lynestrenol, and the production, use, occurrence, and analysis of lynestrenol. Production of lynestrenol, which is not known to occur naturally, is by treatment of 19-nortestosterone with ethane-1,2-dithiol and boron trifluoride to give the 3-thioketal, followed by oxidation steps, and concluded by treatment with lithium acetylide. Lynestrenol is used primarily as a component of contraceptive tablets. It has also been used (in combination with mestranol) to control dysfunctional uterine bleeding and endometriosis. Typical analytical methods for determining lynestrenol as a bulk chemical are presented tabularly. Biological data relevant to the evaluation of carcinogenic risk to humans are also presented in brief. Lynestrenol has been tested in mice and rats by oral administration either alone or in combination with mestranol. No increases in any tumor incidences were found. No case reports or human epidemiological studies on lynestrenol alone are available. It is therefore not possible to evaluate this agent's possible carcinogenicity, although as an agent in oral contraceptives it is implicated in their side effects.
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PMID:Lynoestrenol. 29 35

Pure ferritin from male mouse liver produces a single band of monomers (RF = 0.199) with electrophoresis in polyacrylamide gels at pH 9.0. The five sub-bands within this monomeric band appear to represent charge isomers having the same molecular size. Ferritin from BH3 transplantable mouse hepatoma shows two overlapping bands of monomers (RFA = 0.208 and RFB = 0.240); further electrophoretic studies show that these bands represent two subpopulations of molecules differing both in charge and size. Sub-bands are not found in this hepatoma ferritin. The larger tumor ferritin reaches the same end migration position as all liver isoferritins on gradient gels, signifying a very similar or identical molecular size; however, the absence of sub-bands indicates that this hepatoma ferritin differs in charge from the homologous liver proteins. Liver and hepatoma ferritins both produce a single prominent subunit band corresponding to nominal molecular weights of 22 250 and 21 700, with polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and dithiothreitol. With electrophoresis on polyacrylamide gradient slabs containing sodium dodecyl sulfate and dithiothreitol, both liver and hepatoma ferritins now reveal two subunits bands situated at identical positions. The polypeptides of these two closely spaced bands have a nominal molecular weight difference of less than 1000. Neither the hepatoma nor the liver seems to produce the ferritins found in the other tissue. Nevertheless, all these ferritins are composed of the same two types of subunits, albeit in different relative amounts. Observed distinctions in the ferritins from these normal or neoplastic cells must reflect differences in assembly and processing, as well as in the regulated expression of the same ferritin genes.
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PMID:Mouse hepatoma and liver ferritins. Comparative structural studies. 46 27

The phosphorylations of B12H11OH2-,B12H10(OH)2-2-, and B20H17OH4-with POCl3 and (C6H5O)2POCl were investigated and the following derivatives were isolated: B12H11OPO3H3-,B12H11OPO3H2-2-,B12H11OPO(OC6H5)-2-2 minus, B12H11OPO(OC6H5)OH2 minus, b12h10(op2o6h2)2-4 minus, B12H10(OPO3H2)2-2 minus, B12Br10(OPO3H)2-4 minus, B12H10[O-PO(OC6H5)2]2-2 minus, B20H18OP2O6H2-4 minus, B20H18OPO3H2-3 minus. The B-O-P bonds proved very resistant to hydrolysis and the phosphates were administered in the for of Na+ salts at pH 7.2 to rats bearing subcutaneous glioma. The boron concentrations in tumors and the tumor/blood concentration ratios were compared with those of parent hydroxy derivatives. Except when the POH function was blocked by phenyl groups the phosphorylation invariably resulted in a greatly enhanced uptake of the borane into tumors and improved the tumor/blood boron ratio. The phopshate function appears to be one of the most effective handles for the incorporation of boron into brain tumors and the compounds show considerable promise for use in the neutron capture therapy of brain tumors.
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PMID:Synthesis and tumor-uptake study of phosphate esters of polyhedral hydroxyboranes. 112 Oct 3

The technique of boron neutron capture therapy in the treatment of cerebral gliomas depends upon the selective loading of the tumor with a 10B-enriched compound and subsequent irradiation of the brain with low-energy neutrons. The charged particles produced in the 10B (n,alpha) 7Li reaction have ranges in tissue of less than 10 mum so that the dose distribution closely follows the 10B distribution even to the cellular level. The effectiveness of this therapy procedure is dependent not only on the 10B compound but on the spectral characteristics of the neutron source as well. Hence, an optimization of these characteristics will increase the chances of therapeutic success. Transport calculations using a neutral particle transport code have been made to determine the dose-depth distributions within a simple head phantom for five different incident neutron beams. Comparison of these beams to determine their relative therapeutic efficacy was made by the use of a maximum useable depth criterion. In particular, with presently available compounds, the MIT reactor (MITR) therapy beam (a) is not inferior to a pure thermal neutron beam, (b) would be marginally improved if its gamma-ray contamination were eliminated, (c) is superior to a partially 10B-filtered MITR beam, and (d) produces a maximum useable depth which is strongly dependent upon the tumor-to-blood ratio of 10B concentrations and weakly dependent upon the absolute 10B concentration in tumor. A pure epithermal neutron beam with a mean energy of 37 eV is shown to have close to the optimal characteristics for boron neutron capture therapy. Futhermore, these optimal characteristics can be approximated by a judiciously D2O moderated and 10B-filtered 252Cf neutron source. This tailored 252Cf source would have at least a 1.5 cm greater maximum useable depth than the MITR therapy beam for realistic 10B concentrations. However, at least one gram of 252Cf would be needed to make this a practical therapy source. If the moderated 252Cf source is not 10B filtered, the resultant neutron beam has characteristics similar to those of the MITR beam with no gamma-ray contamination. For usch a beam, 100 mg of 252Cf would produce a flux of 2.4 X 10(8) neutrons/(cm2 sec), which is an intensity suitable for therapy applications.
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PMID:Boron neutron capture therapy for the treatment of cerebral gliomas. I. Theoretical evaluation of the efficacy of various neutron beams. 118 17

Recent interest in the production of epithermal neutrons for use in boron neutron capture therapy (BNCT) has promoted an investigation into the feasibility of generating such neutrons with a high current proton accelerator. Energetic protons (2.5 MeV) on a 7Li target produce a spectrum of neutrons with maximum energy of roughly 800 keV. A number of combinations of D2O moderator, lead reflector, 6Li thermal neutron filtration, and D2O/6Li shielding will result in a useful epithermal flux of 1.6 x 10(8) n/s at the patient position. The neutron beam is capable of delivering 3000 RBE-cGy to a tumor at a depth of 7.5 cm in a total treatment time of 60-93 min (depending on RBE values used and based on a 24-cm diameter x 19-cm length D2O moderator). Treatment of deeper tumors with therapeutic advantage would also be possible. Maximum advantage depths (RBE weighted) of 8.2-9.2 (again depending on RBE values and precise moderator configuration) are obtained in a right-circular cylindrical phantom composed of brain-equivalent material with an advantage ratio of 4.7-6.3. A tandem cascade accelerator (TCA), designed and constructed at Science Research Laboratory (SRL) in Somerville MA, can provide the required proton beam parameters for BNCT of deep-seated tumors. An optimized configuration of materials required to shift the accelerator neutron spectrum down to therapeutically useful energies has been designed using Monte Carlo simulation in the Whitaker College Biomedical Imaging and Computation Laboratory at MIT. Actual construction of the moderator/reflector assembly is currently underway.
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PMID:Accelerator-based epithermal neutron beam design for neutron capture therapy. 132 92

A fluorine-18 labeled analogue of D-talose, 2-deoxy-2-[18F]fluoro-D-talose ([18F]FDT), was synthesized via nucleophilic fluorination with [18F]fluoride ion and its biodistributions in animals were examined. Radiofluorination of benzyl 3,5,6-tri-O-benzyl-2-O-(trifluoromethanesulfonyl)-alpha-D-galac tof uranoside (5) with aminopolyether supported potassium [18F]fluoride (K18F/Kry222) in acetonitrile followed by deprotection of the [18F]fluorinated intermediate (6) with boron tribromide in CH2Cl2 gave [18F]FDT in an average radiochemical yield of 29% with a radiochemical purity greater than 98%. Biodistribution studies of [18F]FDT in mice bearing fibrosarcoma showed the highest uptake of radioactivity in the liver (34.9% dose/g), followed by the kidney (15.9%dose/g), the small intestine (12.9%dose/g) and fibrosarcoma (5.7%dose/g), at 30 min after i.v. administration. Although the radioactivity in the kidney and small intestine decreased with time, the uptake in the liver and the tumor slightly increased until 120 min. The high liver uptake of [18F]FDT was also observed in normal rats and this uptake was strongly inhibited by co-administration of D-galactose. These preliminary results suggest that [18F]FDT might be metabolized through the galactose metabolic pathway as analogously observed with 2-deoxy-2-[18F]fluoro-D-galactose which is an isomer with respect to carbon-2 of [18F]FDT, and that it may be another candidate for studying liver function by positron emission tomography.
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PMID:Synthesis and biodistribution of a fluorine-18 labeled analogue of D-talose: 2-deoxy-2-[18F]fluoro-D-talose. 132 21

Boron analogues of carbamoylcholine and thiocholine and esters of these analogues were prepared. These compounds were fairly stable toward hydrolysis and demonstrated moderate anti-inflammatory and hypolipidemic activities in mice. The hypolipidemic activity of the compounds at a dose of 8 mg/kg/day was equivalent in reducing lipid levels in serum to those of clofibrate at 150 mg/kg/day and lovastatin at 8 mg/kg/day. The compounds demonstrated significant cytotoxic activity against the growth of murine and human tumor cells; all were active against the growth of human HeLa-S3 uterine suspended cells, and some were active against murine L1210 lymphoid leukemia, human Tmolt3 leukemia cells, colorectal adenocarcinoma, KB nasopharynx, osteosarcoma, and glioma. These studies demonstrated that antimetabolite analogues of acetylcholine exhibit the same types of pharmacological activity as other boron-substituted betaine and amino acids. Furthermore, a strong positive correlation exists between hypolipidemic activity and cytotoxicity for these new choline derivatives, as has previously been demonstrated for other boron-containing amino acids, amides, esters, and peptides.
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PMID:Synthesis, cytotoxicity, hypolipidemic and anti-inflammatory activities of amine-boranes and esters of boron analogues of choline and thiocholine. 140 80

The successful treatment of cancer by boron neutron-capture therapy (BNCT) requires the selective concentration of boron-10 within malignant tumors. The potential of liposomes to deliver boron-rich compounds to tumors has been assessed by the examination of the biodistribution of boron delivered by liposomes in tumor-bearing mice. Small unilamellar vesicles with mean diameters of 70 nm or less, composed of a pure synthetic phospholipid (distearoyl phosphatidylcholine) and cholesterol, have been found to stably encapsulate high concentrations of water-soluble ionic boron compounds. The hydrolytically stable borane anions B10H10(2-), B12H11SH2-, B20H17OH4-, B20H19(3-), and the normal form and photoisomer of B20H18(2-) were encapsulated in liposomes as their soluble sodium salts. The tissue concentration of boron in tumor-bearing mice was measured at several time points over 48 h after i.v. injection of emulsions of liposomes containing the borane anions. Although the boron compounds used do not exhibit an affinity for tumors and are normally rapidly cleared from the body, liposomes were observed to selectively deliver the borane anions to tumors. The highest tumor concentrations achieved reached the therapeutic range (greater than 15 micrograms of boron per g of tumor) while maintaining high tumor-boron/blood-boron ratios (greater than 3). The most favorable results were obtained with the two isomers of B20H18(2-). These boron compounds have the capability to react with intracellular components after they have been deposited within tumor cells by the liposome, thereby preventing the borane ion from being released into blood.
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PMID:Model studies directed toward the boron neutron-capture therapy of cancer: boron delivery to murine tumors with liposomes. 140

Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when a stable isotope, boron-10 (10B), is irradiated with low-energy thermal neutrons (nth) to yield (4He) alpha-particles and 7Li nuclei (10B+nth-->[11B]-->4He+7Li+2.31 MeV). The success of BNCT as a tumoricidal modality is dependent on the delivery of a sufficient quantity of 10B and nth to individual cancer cells to sustain a lethal 10B(n, alpha) 7Li reaction. The current review covered the radiobiologic considerations on which BNCT is based, including a brief discussion of microdosimetry and normal tissue tolerance. The development of tumor-localizing boron compounds was discussed, including the sulfhydryl-containing polyhedral borane, sodium borocaptate (Na2B12H11SH), and boronophenylalanine (BPA), both of which are currently being used clinically in Japan as capture agents for malignant brain tumors and melanomas, respectively. Compounds currently under evaluation, such as boronated porphyrins, nucleosides, liposomes, and monoclonal antibodies (MoAbs), were also considered. Nuclear reactors have been used as the exclusive source of neutrons for BNCT. The use of low-energy (0.025 eV) thermal neutrons and higher-energy (1-10,000 eV) epithermal beams, beam optimization, and possible alternative neutron sources (accelerators) were also discussed. Clinical studies performed in the United States during the 1950s and 1960s for the treatment of malignant brain tumors were reviewed. Current studies in Japan and future studies in Europe and the United States concerning the treatment of glioblastomas and melanomas by BNCT were discussed, as were critical issues that must be addressed if BNCT is ever to be a useful therapeutic modality.
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PMID:Boron neutron capture therapy for cancer. Realities and prospects. 145 Oct 84


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