Neuroepithelial tumor cells were cultured in vitro. The biopsy material was taken from 93 children at removal of the
brain tumors during neurosurgical operations. The individual features of the cells sensitivity of primary cultures in respect to protocol-approved
chemotherapy drugs and changes in the
Interleukin-6 (Il-6) level in the culture medium after the application of
chemotherapy were established. The initial level of
Il-6 exceeded 600.0 pg/ml in the cultural medium with histologically verified pilomyxoid
astrocytoma cells, and ranged from 100.0 to 200.0 pg/ml in the medium at cultivation of
ganglioneuroblastoma and
pilocytic astrocytoma. A decrease in the
Il-6 level in the medium culture of primary
tumors cells was observed after the application of chemotherapeutic agents on the cells of pilomyxoid
astrocytoma,
astrocytomas, and pilocytic desmoplastic/nodular
medulloblastoma. The production of
Il-6 increased after application of
cytostatic drugs on the cells of oligoastrocytomas. A decrease in
Il-6 level after application of
Cisplatin and
Methotrexate and a 5-10 fold increase in the level of
Il-6 after application of
Etoposide,
Carboplatin,
Cytarabine, and
Gemcitabine were registered in the medium with
ganglioneuroblastoma. To improve the cytotoxic action of chemotherapeutic agents, the combined application of
cytostatics with
heterocyclic compounds was carried out. A computer modeling of
ligand-
protein complexes of
carbamide using the Dock 6.4 and USF Chimera program packages was performed with molecular mechanics method. Special attention was drawn to the ability of several
isoxazole heterocycles and isothiazolyl to inhibit the
tyrosine kinase. It was proved in vitro that the joint application of chemotherapeutic agents and
heterocyclic compounds could reduce the concentration of the
cytostatic factor by 10 or more times, having maintained the maximum cytotoxic effect. It was assumed that the target amplification of cytotoxic action of chemotherapeutic agents had prospects for reducing toxic side effects of
chemotherapy in vivo, which would be carried out only after the preclinical studies.