[Features of cytogenetic changes in the human lymphoma U-937 cells after induction of apoptosis by tumor necrosis factor].

A comparative analysis of the frequency of cytogenetic abnormalities in cell population U-937 in control conditions and after exposure to tumor necrosis factor has been performed. We have found that in such treatment there is a maximum effect after 48 h, which is expressed in the stimulation of apoptosis and the accumulation of cells with micronuclei and binuclear cells. The induction of premature chromosome condensation is an early marker of the TNF influence. Changing the composition of the population by the number of chromosomes in the cell may lead to the emergence of a subline with new properties compared to the parental cell population.

[Antiviral activity of extracts of transgenic cichory and lettuce plants with the human interferon alpha-2b gene].

Biological activity of protein extracts from transgenic plants of chicory Cichorium intybus L. and lettuce Lactuca sativa L. with human interferon alpha2b gene was investigated against vesicular stomatitis virus. It was shown that the extracts from the hairy roots of chicory and lettuce transformed by A. rhizogenes possess the antiviral activity 1620...5400 IU/g weight, and the extracts from leaves of the plants transformed by A. tumefaciens--till 9375 IU/g weight. Dependence of plant extract biological activity on the transformation vector was shown.

[Cytological features of the development of multi-organ failure induced by exposure of the body to tumor necrosis factor]. / Tsitologicheskie osobennosti razvitiia poliorgannoi nedostatochnosti pri deistvii na organizm faktora nekroza opukholi.

Morphologic analysis of the changes in the internal organs after i.v. injection of 20 micrograms per mice of tumor necrosis factor (TNF) revealed the development of signs of multiorgan failure (interstitial and intraalveolar edema in the lung, acute fatty liver, tubular necrosis in kidney, brain edema) during first 24 h. The microvascular endothelial cells played a particular role in the state development. Results of investigation proved that endothelial cells were one of the major cellular targets for TNF action in vivo.

[The action of tumor necrosis factor on the microvascular endothelium and its role in the morphological changes in the internal organs]. / Deistvie faktora nekroza opukholi na éndotelii mikrososudov i rol' ego v morfologicheskikh izmeneniiakh vnutrennikh organov.

Tumor necrosis factor exerts the systemic influence on endothelial cells in vivo. Structural changes in endotheliocytes lead to specific damage in the organs. Interstitial and alveolar edema develops in lung. Kupffer cell activation, change of sinusoid endothelial cell porosity, lipid dystrophia of hepatocytes are revealed in liver, damage of glomerular and peritubular capillaries, dystrophic changes of tubular epithelial cells are found out in kidney. The data obtained indicate that endothelial cells in microvessels are one of major cellular targets for action of tumor necrosis factor.

[Tumor cell proteins, detected using antibodies to the S- and N-terminal fragments of the fos proto-oncogene product]. / Belki opukholevykh kletok, vyiavliaemye s pomoshch'iu antitel k S- i N-kontsevym fragmentam produkta protoonkogena fos.

Antibodies to c-fos oncoprotein were produced in rabbits by immunization with synthetic peptides, corresponding to the sequences 6-15 of N-end and 371-380 of C-end of c-fos oncoprotein. C-fos expression was tested with immunoprecipitation and immunoblotting in various transformed cell lines with antibodies to N- and C-decapeptides. It was shown that antibodies to C-terminal decapeptide revealed a c-fos gene product and also some fos-related antigens FRAs 36 kD, 46 kD, 75 kD and 90 kD in rat pheochromocytoma PC-12 cells and mouse carcinoma cell lines MAC-3 and LL. In some cell lines 46 kD FRA was expressed in the absence of p62 c-fos. Besides, different clones of the same cell line cultivated in identical conditions revealed differences in the 46 kD FRA expression. Antibodies to sequence 6-15 of N-end revealed only c-fos products and no FRAs were detected. Therefore FRAs have homology with the c-fos product in the C-terminal region and differ from it in the N-terminal region.

[Modifying effects of recombinant tumor necrosis factor on the metastatic potential of tumor cells]. / Modifitsiruiushchee vliianie rekombinantnogo faktora nekroza opukholei na metastaticheskii potential opukholevykh kletok.

Cells of the Lewis lung carcinoma (3LL), B16 melanoma and Ehrlich carcinoma pre-treated in vitro by a recombinant tumour necrosis factor (rTNF) were studied for their spontaneous and experimental metastatic spreading. The rTNF (1000 u/ml) was determined to stimulate a metastatic potential of the Lewis carcinoma cells after their treatment with the factor for 6 h and, vice versa, to inhibit it after 96 h prolonged treatment. The efficacy of the stimulating effect of rTNF on a metastatic spreading depends on the peculiarities of the studied cells.

[Recombinant tumor necrosis factor promotes the formation of hematogenic metastases to the lungs of C57Bl/6 mice]. / Rekombinantnyi faktor nekroza opukholei sposobstvuet formirovaniiu gematogennykh metastazov v legkikh myshei C57Bl/6.

The intravenous injection of the recombinant tumour necrosis factor (rTNF) to the C57BL/6 mice at a dose of 10(4) U 1.4 and 24 hours before or 4 hours after the intravenous inoculation of the LL (Lewis carcinoma) or MM-4 (B-16 melanoma) cells was found to be accompanied by a significant increase in the number of hematogenic metastases in the lungs of animals. The above rTNF effect could be considerably inhibited by the single heparin injection.

[The modifying action of tumor necrosis factor on angiogenesis]. / Modifitsiruiushchee deistvie faktora nekroza opukholei na angiogenez.

It has been shown that capillary formation in chorion-allantois membranes of chicken embryos under the influence of tumour necrosis factor (TNF) on neovascularization process depends on the dose applied and that the character of this influence may be different. Little TNF doses (0.025-0.25 ng) inhibit angiogenesis induced by the angiogenic factor received from the Lewis carcinoma. An increase of the TNF dose stimulates angiogenesis. The further rise of the dose produces a destructive effect on capillaries. The dose-dependent effect of the TNF must be considered in different model systems as well as in clinical practice.

[The cellular sensitivity of the primary tumor and its metastases in breast cancer patients to cytostatics, interferon and tumor necrosis factor]. / Issledovanie chuvstvitel'nosti kletok pervichnoi opukholi i metastazov u bol'nykh rakom molochnoi zhelezy k tsitostatikam, interferonu i faktoru nekroza opukholei.

Samples of tumor tissue obtained from 47 patients with primary and metastatic breast cancer were implanted under the renal capsule of mice (SRCA-test) to assess individual sensitivity of these malignancies to cytostatics, recombinant interferon (rIFN) and--in some cases--to tumor necrosis factor (TNF). Primary tumor was shown to respond to cytostatics and rIFN in as few as 33.3 and 26.7% of cases, respectively. Xenografts of metastases displayed higher rates of response to all the drugs studied, viz. 64.2, 86.7 and 90% for cytostatics, rIFN and TNF, respectively.

[Expression of oncogenes in transplantable tumors and rodent cell lines]. / Ekspressiia onkogenov v nekotorykh transplantiruemykh opuliakh i kletochnykh liniiakh gryzunov.

The expression of 8 oncogenes in transplanted rodent tumours and cell lines was tested. In 6 cases the synthesis of myc-, fos-, ras-oncogene RNA was observed. The transcription of these oncogenes was observed nonspecifically in tumours of different histological types. No difference in the set of the oncogenes expressed and the size of their transcripts was noticed between transplanted tumours and the cell lines obtained from them. The expression of myb-, sis-, Blym-, erb-B- and abl-was not observed in tested cells.

[Antiproliferative activity of difluoromethylornithine and the factors decreasing its effectiveness in malignant growth]. / Izuchenie antiproliferativnoi aktivnosti diftormetilornitina i nekotorykh faktorov, snizhaiushchikh ego éffektivnost' pri zlokachestvennom roste.

The inhibitory effect of difluoromethylornithine (DFMO) synthesized by the authors on the activity of the ornithine decarboxylase (ODC) and proliferation of microbial and mammalian cells in vitro was studied. The in vivo growth of ascite plasmocytoma of solid melanoma B-16 cells in mice was also effectively inhibited by DFMO. But the antiproliferative activity of DFMO in solid tumours was substantially lower. Such a decrease in the antitumour activity may be associated with polyamines released from necrotic areas of solid tumours. As the tumour cells "catch" the vitally important metabolites, their effect inside solid tumours is turned against the tumour cells themselves. The second reason of the decrease in the DFMO activity is adsorption of polyamines on the erythrocyte surface.

[Preparation and characteristics of a cell line from transplantable Svec's leukemia]. / Poluchenie i kharakteristika kletochnoi linii iz transplantiruemogo leikoza Shvetsa.

The procedure for obtaining the CL-C5 suspension cell line from the transplantable rat leukemia (erythromyelosis) is described. Cytochemical and biochemical features of CL-C5 blast cells are established to be typical of T-cells at the differentiation stage, corresponding to thymocytes. The results obtained permit considering CL-C5 cell line as that having phenotypical indications of lymphocytes and retrovirus production lost due to the selection in the cell population.

[Influence of interferon on the toxic effect and antitumor activity of vinblastine in the combined therapy of metastatic Lewis carcinoma]. / Vliianie interferona na toksicheskii éffekt i protivoopukholevuiu aktivnost' vinblastina pri kombinirovannoi terapii metastaziruiushchei kartsinomy L'iuis.

Antitumour and antimetastatic effects of the combination of vinblastine (VLB) and L-cell interferon were examined. It is shown that mice with 3LL carcinoma are more sensitive to common toxic effect of VLB than intact animals. Interferon (IF) decreases the toxic effect of VLB in tumour-bearing mice, and thus provides a possibility to increase the total therapeutic dose of the cytostatic. The combination of VLB and IF showed a synergistic inhibitory effect on the development of carcinoma metastases and significantly increases the survival rate of the tumour-bearing mice. Neither synergistic nor additive antitumour effects of the combined therapy were observed on the primary tumour. IF suppresses the primary tumour growth more significantly when given by intratumoural injection. At the same time the inhibition of metastase development was more efficient with intraperitoneal injection of IF.