[Cyclic hydroxamic acids as chemosensitizers in cytostatic therapy].

In experimental animals with tumors it was studied antitumor activity of spirocyclic hydroxamic acids which could be classified as targeted agents as their target was enzyme histonedeacetylase, which was involved in the neoplastic process. The results showed that the hydroxamic acids were chemosensitizers for anticancer agents increasing their efficacy and enabling the researchers to reduce significantly the therapeutic dose. Also it was showed that hydroxamic acid, containing nitrogen mustard, was effective in the action on tumors with phenotype and genotype of multidrug resistance.

[Antileukemic activity and development of resistance to cisplatin (CPT) and platinum (IV)-nitroxyl complex VS118].

Treatment with low doses (1/10 of LD50) of cisplatin and platinum (IV)-nitroxyl complex VS118 [e-ammin-d-(4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl)-a,f-bi s(acetate)-b,c-dichlorplatinum (IV)] was followed by a synergistic therapeutic effect (a 100% cure of animals) as compared with monotherapy with either drug. There was no synergistic increase in toxicity. The rates of resistance development decreased in the following order: P388/cPt+VS118, P388/cPt, P388/VS118. Resistant strains P388/cPt+VS18 and P388/VS118 were highly sensitive to doxorubicin, etoposide and cyclophoshamide. Further research in cPt+VS 118 combinations should be continued.

[Inhibitory effect of the radiosensitizer AK-2123 on experimental liver metastasis and active transport of calcium ions]. / Ingibiruiushchii éffekt radiosensibilizatora AK-2123 na éksperimental'nye metastazy v pecheni i aktivnyi transport ionov kal'tsiia.

Radiosensitizer AK-2123, a triazol, has been shown to significantly inhibit the development of hepatic metastases induced in syngeneic mice by intrasplenic injections with cels of bowel adenocarcinoma. The antimetastatic effect was produced by use of a very low dose of the drug. A therapeutic dose of AK-2123 has been shown to inhibit active transport of calcium ions across sarcoplasmic reticular cells effected by Ca(2+)-dependent Mg(2+)-activated ATPase. It is suggested that the antimetastatic effect of AK-2123 is determined by at least partial inhibition of active transport of calcium.

[Changes in biological properties of malignant melanoma B-16 after transplantation to (CBA x C57Bl/6)F1 mice]. / Izmenenie biologicheskikh svoistv zlokachestvennoi melanomy B-16 pri transplantatsii mysham (CBA x C57Bl/6)F1.

The primary tumour properties are studied for their effect on the recurrent tumour growth and metastatic spreading after chemotherapy. Serial transplantation of the B16 melanoma to (CBA X C57Bl/6)F1 mice induced gradual changes in tumour malignancy. With an increase of the generation number the metastatic activity of hybrid mice rises and chemotherapeutic sensitivity lowers. The thirty-first and the fifty-fourth tumour generations after the chemotherapy metastasize earlier and the number of metastases increases more rapidly as compared with the recurrence of the primary tumour. The metastatic potential of recurrent tumours increases with the number of generations in hybrid mice.

[Growth characteristics of adenocarcinoma 755 recurrences in C57Bl/6 and (DBA/2 X C57Bl/6) F1 mouse strains]. / Osobennosti rosta retsidivov adenokartsinomy 755 u myshei linii C57Bl/6 i (DBA/2 X C57Bl/6) F1.

Peculiarities of growth and recurrences of the adenocarcinoma 755 are studied in C57Bl/6 mice and hybrids (DBA/2 X +C57Bl/6)F1 after chemotherapy with cyclophosphamide and 6-mercaptopurine (6-MP). The growth rate of tumours was practically identical in the both mice strains. Growth rate of recurrences was slower in examined lines than in corresponding tumours. The obtained results showed that the antitumour effect of the drugs, in particularly of 6-MP, and the growth rate of the first and that of the second recurrences clearly depended on the tumour host strain.