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PURPOSE: To determine if lucanthone crossed the blood-brain barrier in experimental animals; and to determine accelerated tumor regression of human brain metastases treated jointly with lucanthone and whole brain radiation. METHODS AND MATERIALS: The organ distribution of 3H lucanthone in mice and 125I lucanthone in rats was determined to learn if lucanthone crossed the blood-brain barrier. Size determinations were made of patients' brain metastases from magnetic resonance images or by computed tomography before and after treatment with 30 Gy whole brain radiation alone or with lucanthone. RESULTS: The time course of lucanthone's distribution in brain was identical to that in muscle and heart after intraperitoneal or intravenous administration in experimental animals. Lucanthone, therefore, readily crossed the blood-brain barrier in experimental animals. CONCLUSION: Compared with radiation alone, the tumor regression in patients with brain metastases treated with lucanthone and radiation was accelerated, approaching significance using a permutation test at p = 0.0536. 相似文献
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The problem of semantic clustering of subject-oriented natural language texts is discussed. Based on the theory of Formal Concept Analysis, an approach is proposed to determine the measure of semantic affinity of texts. 相似文献
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The dependence of the final macrogeometry and microgeometry of the machined hole surface on the surface quality of the blank
in broaching is investigated by simulation. 相似文献
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The ability to calculate the field of a set of arbitrarily charged and arbitrarily arranged rectangular areas was considered.
The result was verified by calculating the recorded field on a magnetic tape. 相似文献
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TJ Stout D Tondi M Rinaldi D Barlocco P Pecorari DV Santi ID Kuntz RM Stroud BK Shoichet MP Costi 《Canadian Metallurgical Quarterly》1999,38(5):1607-1617
Thymidylate synthase is an attractive target for antiproliferative drug design because of its key role in the synthesis of DNA. As such, the enzyme has been widely targeted for anticancer applications. In principle, TS should also be a good target for drugs used to fight infectious disease. In practice, TS is highly conserved across species, and it has proven to be difficult to develop inhibitors that are selective for microbial TS enzymes over the human enzyme. Using the structure of TS from Lactobacillus casei in complex with the nonsubstrate analogue phenolphthalein, inhibitors were designed to take advantage of features of the bacterial enzyme that differ from those of the human enzyme. Upon synthesis and testing, these inhibitors were found to be up to 40-fold selective for the bacterial enzyme over the human enzyme. The crystal structures of two of these inhibitors in complex with TS suggested the design of further compounds. Subsequent synthesis and testing showed that these second-round compounds inhibit the bacterial enzyme at sub-micromolar concentrations, while the human enzyme was not inhibited at detectable levels (selectivities of 100-1000-fold or greater). Although these inhibitors share chemical similarities, X-ray crystal structures reveal that the analogues bind to the enzyme in substantially different orientations. Site-directed mutagenesis experiments suggest that the individual inhibitors may adopt multiple configurations in their complexes with TS. 相似文献
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A. M. Mikhailov 《Journal of Mining Science》2001,37(5):482-485
A numerical method is developed for solving three-dimensional problem on the stress state around an arbitrary crack in the infinite medium. 相似文献
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