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101.
Synthesis and immunosuppressive activity of 2-substituted 2-aminopropane-1,3-diols and 2-aminoethanols 总被引:14,自引:0,他引:14
Kiuchi M Adachi K Kohara T Minoguchi M Hanano T Aoki Y Mishina T Arita M Nakao N Ohtsuki M Hoshino Y Teshima K Chiba K Sasaki S Fujita T 《Journal of medicinal chemistry》2000,43(15):2946-2961
A series of 2-substituted 2-aminopropane-1,3-diols was synthesized and evaluated for their lymphocyte-decreasing effect and immunosuppressive effect on rat skin allograft. A phenyl ring was introduced into the alkyl chain of the lead compound 3, which is an immunosuppressive agent structurally simplified from myriocin (1, ISP-I) via compound 2. The potency of the various compounds was dependent upon the position of the phenyl ring within the alkyl side chain. The most suitable length between the quaternary carbon atom and the phenyl ring was two carbon atoms. 2-Substituted 2-aminoethanols were successively synthesized and evaluated for their T-cell-decreasing effect and immunosuppressive effect using a popliteal lymph node gain assay in rats. The absolute configuration at the quaternary carbon affected the activity, and the (pro-S)-hydroxymethyl group of compound 6 was essential for potent immunosuppressive activity. Favorable substituents for the (pro-R)-hydroxymethyl group of 6 were hydroxyalkyl (hydroxyethyl and hydroxypropyl) or lower alkyl (methyl and ethyl) groups. 2-Amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol hydrochloride (6, FTY720) was found to possess considerable activity and is expected to be useful as an immunosuppressive drug for organ transplantation. 相似文献
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Between September 1980 to December 1983, 70 consecutive patients were entered into two randomly allocated trials in order to investigate the effectiveness of different time-dose radiotherapy schemes (i.e., 30 Gy/ten fractions/two weeks versus 50 Gy/20 fractions/four weeks) and the prognostic factors on the palliation for patients with brain metastases from lung carcinoma. The most important factors for predicting poor prognosis in this series, which were shown by stepwise proportional hazard (Cox) model, were lactate dehydrogenase (LDH) and general performance status. In normal LDH group, the most important factors for predicting poor prognosis were multiplicity of brain metastases (p less than 0.001), treatment methods (p less than 0.0005) and age (p less than 0.0053). In high LDH group any items were not shown for meeting of the 0.05 significant level. 相似文献
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A dual stainless steel applicator (CADO-E I type) was developed for intracavitary radiotherapy of endometrial carcinoma using remotely controlled afterloader (RALS). An inverted pear-shaped isodose curve was obtained by means of this metallic applicator and Co-60 source with a stepwise movement. Reference point X was defined as 2 cm below the fundus and 2 cm lateral to the center line of the uterus to specify the dose absorbed to the uterine corpus with our endometrial applicator. Since cancer residua resulting from cold spots in dose distribution were recognized at the uterine fundus by histopathological investigation of serial sections in the hysterectomy specimens, we intend to develop an applicator with three metallic tubes (CADO-E II type). 相似文献
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S Teshima Y Shimosato K Kishi S Hirohashi Y Tome T Ise T Kakizoe K Matsumoto 《Japanese journal of cancer research》1986,77(5):428-431
The presence of testosterone in yolk sac tumor of the infant testis was investigated immunohistochemically. All 16 cases tested were positive for the hormone. The antigen-positive tumor cells were primitive mesenchymal cells and columnar cells forming small ducts, which resembled Leydig cells and Sertoli cells, respectively. These cells accounted for about 1 to 20% of tumor cells and were intermingled with typical yolk sac structures. In contrast, no yolk sac tumor of adult testis was definitely positive for the antigen. In view of its distinctive histological and immunohistochemical features and clinical behavior, yolk sac tumor in the infant testis is most likely a separate and specific entity, composed of a mixture of germ cell and sex cord stroma derivatives. 相似文献
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One hundred forty previously untreated cases of T1N0M0 glottic carcinoma underwent therapy at our department from November 1977 through May 1984. Ninety-six of them were treated with the open-field technique of 4 MVX-ray using parallel opposed fields in bandage up to April 1982 (group I). The remaining 44 cases were treated with the wedge-filtered technique in a plastic shell in order to improve the dose distribution and immobilization during radiotherapy starting in May 1982 (group II). The two-year disease-free survival rates were 85% and 91%, respectively. Thus, better results were achieved by improved treatment techniques. 相似文献
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