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[恶性肿瘤中三磷酸胸苷合成的研究。II. 热疗、维生素K及细胞毒性药物的作用(作者译)]

[Studies on the thymidine-triphosphate synthesis in malignant tumors. II. Effect of hyperthermia, Vitamin K and Cytotoxic agents (author's transl)].

作者信息

Kummer D

出版信息

Z Krebsforsch Klin Onkol Cancer Res Clin Oncol. 1977 Jan 21;88(2):145-56. doi: 10.1007/BF00284122.

Abstract

Measurements of the deoxyribonucleoside triphosphate (dNTP) contents, the [14C] thymidine and deoxyuridine incorporation and the "key enzymes" of the thymidine triphosphate (dTTP) synthesis, thymidine kinase and ribonucleotide reductase, in diploid Ehrlich-ascites carcinoma, under the application of hyperthermia, vitamin K and cytocidal agents show: The effect of hyperthermia and menadion (the basic substance of the K vitamins) on the above parameters of dNTP synthesis can explain the labile effects of hyperthemia and vitamin K therapy on cancer growth. Alterations of the dNTP concentrations and demonstrable or absent inhibition of the ribonucleotide reduction with application of fluoruracil, amethopterine, cytosine arabinoside, hydroxyurea, trisethylen iminobenzochinone and daunomycin confirm and supplement our knowledge of the cytostatic action mechanism of these substances. They show moreover by the example of fluoruracil and amethopterine medication that the dTTP concentration estimation after in-vitro incubation of tumour cells with the addition of FU or methotrexat is a better measurement of the therapeutic in-vivo responsiveness of malignant tumours than the previously performed test methods.

摘要

在对二倍体艾氏腹水癌应用热疗、维生素K和细胞杀伤剂的情况下,对脱氧核糖核苷三磷酸(dNTP)含量、[14C]胸苷和脱氧尿苷掺入量以及胸苷三磷酸(dTTP)合成的“关键酶”——胸苷激酶和核糖核苷酸还原酶进行测量,结果显示:热疗和甲萘醌(维生素K类的基本物质)对上述dNTP合成参数的影响,可以解释热疗和维生素K疗法对癌症生长的不稳定作用。应用氟尿嘧啶、氨甲蝶呤、阿糖胞苷、羟基脲、三乙烯亚胺苯醌和柔红霉素后,dNTP浓度的改变以及核糖核苷酸还原的可证实或不存在的抑制作用,证实并补充了我们对这些物质细胞生长抑制作用机制的认识。此外,以氟尿嘧啶和氨甲蝶呤用药为例,它们表明在肿瘤细胞与氟尿嘧啶(FU)或甲氨蝶呤一起进行体外孵育后,对dTTP浓度的估计,比以前执行的测试方法,是一种更好的测量恶性肿瘤体内治疗反应性的方法。

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