共查询到4条相似文献,搜索用时 15 毫秒
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J. Kára N. I. Zimakova E. A. Serebryakova V. Dêdková A. E. Zolotaryov 《Journal of cancer research and clinical oncology》1994,120(11):662-667
New natural and semisynthetic antitumor ether phospholipids PNAE and PNAE(s) [plasmanyl-(N-acyl)ethanolamines] and their selective antitumor activity in vivo have been described previously. We are now presenting the pharmacokinetics, in vivo metabolism and distribution of a [14C]PNAE(s) preparation (1-O-octadecyl-2-oleoyl-sn-glycero-3-phospho-(N-[U-14C]palmitoyl) ethanolamine in the intact or Mc11-tumor-bearing BDF1 mice. Only partial degradation (about 50%–60%) of [14C]PNAE(s) was observed in vivo 24h after i.v. administration, as detected by TLC analysis of phospholipids extracted from the blood, liver, tumor and brain of animals. Pharmacokinetic curves of [14C]PNAE(s) and its metabolites were fitted with a two-compartment model (t
1
2/
=2.5 h,t
1
2/
=61.6 h). After repeated i.v. doses of [14C]PNAE(s) (administered on days 1, 2, 3, 4, and 5) accumulation of [14C]PNAE(s) and lyso-[14C]PNAE(s) in tumor tissue was detected. High levels of [14C]PNAE(s) were also detected in the liver, lung and spleen of animals. After i.v. administration of [14C]PNAE(s) the ether phospholipid was also detected in the brain tissue. The parmacokinetic data indicate that repeated parenteral doses of PNAE(s) are necessary to attain therapeutic concentrations in tumor tissue. The very high accumulation of [14C]PNAE(s) in the liver of animals after repeated i.v. doses, and the absence of toxic side-effects in vivo indicate a possible clinical therapeutic use of PNAE(s), especially in the treatment of tumor metastases in liver as well as in the prophylaxis of liver metastases after surgical removal of primary tumors. 相似文献
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Richard Müller Ronald Gust Günther Bernhardt Christoph Keller Helmut Schönenberger Siegfried Seeber Reinhardt Osieka Alan Eastman Margaretha Jennerwein 《Journal of cancer research and clinical oncology》1990,116(3):237-244
Summary The synthesis of diastereoisomeric [1,2-bis (2-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) complexes,dl-3-PtCl2 andmeso-3-PtCl2, and their evaluation on the hormone-independent, human MDA-MB231 breast cancer cell line, on the cisplatin-sensitive and -resistant L1210 leukemia cell line, on the cisplatinresistant human NIH:OVCAR 3 ovarian cancer cell line, on the P-388 leukemia of the mouse and on the cisplatinsensitive and -resistant Ehrlich ascites tumor of the mouse are described. On all tumor modelsdl-3-PtCl2 produces a marked inhibitory effect. The diastereoisomermeso-3-PtCl2 is less active and more toxic. It is striking thatdl-3-PtCl2 leads to a pronounced inhibition of all cisplatin-resistant tumors. At non-toxic concentrationsdl-3-PtCl2 produces cytocidal effects on the NIH:OV-CAR 3 cell line. Thereforedl-3-PtCl2 is of interest for further evaluation for the therapy of ovarian cancer. 相似文献
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Günther Bernhardt Ronald Gust Herta Reile Hans-Dieter vom Orde Richard Müller Christoph Keller Thilo Spruß Helmut Schönenberger Thomas Burgemeister Albrecht Mannschreck Klaus-Jürgen Range Ulrich Klement 《Journal of cancer research and clinical oncology》1992,118(3):201-208
Summary The enantiomeric [1,2-bis(2-hydroxyphenyl)-ethylenediamine]dichloroplatinum(II) complexes were synthesized and their configuration assessed. A preliminary test in the cisplatin-resistant human NIH:OVCAR-3 ovarian cancer cell line, which was previously characterized by its sensitivity against several therapeutically used drugs, showed that both enantiomers produce cytocidal effects in a concentration of 2.5 M. A difference between the enantiomers became evident from the faster onset of cytocidal activity of theS,S-configurated compound.Dedicated to Professor J. Knabe on the occasion of his 70th birthdayPart I: Müller et al. (1990) 相似文献