1. Efficacy of Gemcitabine on Intracranial Erlich Tumor and its Determinants.
- Author
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Stukov AN, Bespalov VG, Alexandrov VA, Semenov AL, Kireeva GS, Semiglazova TY, Filatova LV, and Baranenko DA
- Subjects
- Animals, Antineoplastic Agents pharmacokinetics, Antineoplastic Agents pharmacology, Blood-Brain Barrier metabolism, Brain Neoplasms pathology, Carcinoma, Ehrlich Tumor pathology, Deoxycytidine administration & dosage, Deoxycytidine pharmacokinetics, Deoxycytidine pharmacology, Dose-Response Relationship, Drug, Male, Mice, Mice, Inbred BALB C, Permeability, Tissue Distribution, Gemcitabine, Antineoplastic Agents administration & dosage, Brain Neoplasms drug therapy, Carcinoma, Ehrlich Tumor drug therapy, Deoxycytidine analogs & derivatives
- Abstract
Gemcitabine is quite effective in the treatment of brain tumors, although this drug has a limited ability to overcome the blood-brain barrier (BBB). Aim of study is to assess the therapeutic efficacy of gemcitabine and other drugs with different permeability of BBB in the model of intracranial tumor. The therapeutic activity of gemcitabine, carmustine, cyclophosphamide and cisplatin was studied in mice with intracranially implanted Ehrlich tumor, and also gemcitabine in various doses - with intramuscularly implanted tumor. On intracranial tumor model gemcitabine (25 mg/kg) increased the life span (ILS) by 60-89% (p<0.001), despite the fact that its permeability of the BBB is about 10%. Therapeutic activity of carmustine, cyclophosphamide and cisplatin (ILS were 44, 22 and 11%, respectively) corresponds with the BBB permeability for these drugs (90, 20 and 8%, respectively). On intramuscular tumor model, gemcitabine showed significant antitumor effect at both 25 and 2.5 mg/kg, indicating a wide range of therapeutic doses of this drug. Pronounced therapeutic effect of gemcitabine on intracranial tumor most likely is due to the small but sufficient concentration of the drug that overcomes the BBB., Competing Interests: The authors declare that there is no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)
- Published
- 2020
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