Tumor-specific blood serum factors as determinants of tumor growth.

In the present review, we focus on the importance of blood serum factors for tumor growth in vivo. Data from mice experiments indicate the existence of serum factors, which increase the mitotic index of Ehrlich carcinoma cells from 15 to 80%. The impaired production of these factors increases the life span of tumor-bearing animals from 14-20 days to 90 days. Blocking the production of tumor-specific factors causes the complete regression of already developed Ehrlich carcinoma. These serum factors do not affect the malignant carcinoma cells in vitro. We identified serpins as tumor-specific serum factors. Experimental evidence suggests that serpins are not only essential for tumor growth. Serpins are also involved in the regeneration of normal tissues, such - as adipose tissue, recurrence after cosmetic operations (liposuction), inhibiting rejection after liver transplantation, protection of parasitic flat worms living in host tissues and organs etc. We conclude that the inhibition ofserum factors may represent attractive novel strategies for the prevention and treatment of relapsed cancers.

[The cross resistance to cytostatics of leukemia P388 cells with induced resistance to doxorubicin]. / Perekrestnaia rezistentnost' k tsitostatikam kletok leikoza P388 s indutsirovannoi ustoichivost'iu k doksorubitsinu.

Using BDF1 mice it has been shown that P388 leukemia tumor cells with induced resistance to doxorubicin (P388/DX) were cross-resistant to daunomycin, carminomycin, actinomycin D, vincristine and mitomycin C. It has been shown that P388/DX leukemia tumor cells were sensitive to bleocina, bleomycitina, cyclophosphamide, 5 fluorouracil. It has been discussed the ways of cross-resistance of P388/DX leukemia tumor cells to cytostatic drugs.

[The characteristics of Ehrlich carcinoma recurrence and metastasis]. / Nekotorye osobennosti retsidivirovaniia i metastazirovaniia kartsinomy Erlikha.

It was shown that surgical removal of Ehrlich carcinoma growing i. m. in male mice F1 (CBA C57Bl/6) does not entail longer survival in comparison with intact tumor-bearing mice (59.4 and 62.2 days, respectively). Postoperative relapses appear in 40-60% of the animals, metastases in 100% of animals. Metastases were not observed in intact tumor bearing mice. The second-challenge tumor was not observed in operated mice despite metastatic growth and recurrences of the same tumor. We suggest that metastatic growth depends on the tumor cell features and that this process is controlled by host organism.

[The effect of ascitic fluid globulins on the growth of leukemia P388/DOX and Ehrlich's carcinoma in mice]. / Vliianie globulinov astsitnoi zhidkosti na rost leikoza P388/DKS i kartsinomy Erlikha u myshei.

The study was performed to investigate the effect of ascitic fluid globulins of tumor on tumor growth and life span of mice. The globulins are shown to shorten the life span of Ehrlich tumor mice from 86.8 to 61.8 days, to increase 3-5-fold the growth rate of Ehrlich carcinoma and P388/DOX tumor. It was found that globulins of ascitic fluids and serum globulins of tumor have equal effects of tumor growth. It is proposed to use globulins of ascitic fluid to study the globulin role in tumor growth.

[The effect of ascitic fluid on the growth of Ehrlich tumor and Lewis carcinoma]. / Vliianie astsitnoi zhidkosti na rost opukholi Erlikha i kartsinomy L'iuis.

In the study of the effect of ascitic fluid and dialysate of Ehrlich ascites tumor cells (m.m. less than 15 kDa) on the growth of Ehrlich and Lewis carcinoma it was found that the ascitic fluid significantly decreased the size of Ehrlich tumor (by more than 50% on day 9-25 after the tumor cell inoculation). It also reduced Lewis carcinoma tumor volume by more than 30% during 3 weeks after the tumor cells inoculation. Dialysate of Ehrlich tumor cells significantly inhibited the growth of Ehrlich tumor too. It is suggested that this test-system simulates inhibition of a small tumor by a big tumor in vivo.

[The modelling of the growth of Ehrlich carcinoma and teratoma T-36 with ascitic fluid and tumor-cell dialysate]. / Modelirovanie rosta kartsinomy Erlikha i teratomy T-36 astsitnoi zhidkost'iu i dializatom opukholevykh kletok.

The study of the effect of ascitic fluid and dialysate of Ehrlich ascites tumor cells (M.m. less than 15 kDa) on the growth of Ehrlich carcinoma and teratoma T-36 has shown that both the ascitic fluid and dialysate can protect tumor cells in vivo. The number of animals with tumors increased from 0% in control animals to 60 and 20%, respectively, in experimental ones after transplantation i.m. of 20 x 10(3) Ehrlich tumor cells into mice. Compared to control, ascitic fluid and dialysate of Ehrlich ascites tumor cells increased the rate of tumor growth to 195 and 153%, respectively. It is suggested that this test-system simulates the effect of tumor humoral factors in vivo.

[Mouse serum inhibition of cytotoxicity of goat antibodies against mouse thymocytes]. / Ingibirovanie tsitotoksichnosti koz'ikh antitel protiv timotsitov myshi syvorotkoi myshei.

It is shown that the serum of Balb/c, C57Bl/6 and F1(C57Bl/6 x CBA) mice inhibits cytotoxicity of goat antithymocyte antibodies. The addition of the serum into the incubation medium increases the proportion of alive cells from -5% up to 95%. Cytotoxicity was also inhibited by the globulin fraction of the mice serum. It is suggested that normal mice serum contains factors which block cytotoxicity of antibodies against antigen host determinants.

[Effect of Triton X-100 on accumulation and therapeutic effect of doxorubicin in mice with leukemia P-388 with induced resistance to cytostatic agents]. / Vliianie tritona X-100 na nakoplenie i lechebnoe deistvie doksorubitsina u myshei s leikozom P-388 s indutsirovannoi rezistentnost'iu k tsitostatiku.

Using P 388 and P 388/Dx tumour-bearing mice BDF1 it has been studied effect Tritton X-100 on accumulation and therapeutic action of doxorubicin (Dx). It has been shown that LD50 of Tritton X-100 is 153.6 mg/kg and MTD is 80 mg/kg body weight of animals. It has been shown that Tritton X-100 in dose 40 mg/kg body weight increases initial level of Dx in P 388/Dx cells to 215% and doesn't change accumulation of Dx in P 388 cells. It has been shown that Tritton X-100 doesn't influence the therapeutic effect of Dx in P 388 and P 388/Dx tumour-bearing mice.

[Changes in glutathione-S-transferase activity during induction of resistance of leukemia P 388 and Ehrlich ascitic tumor cells to doxorubicin]. / Izmenenie aktivnosti glutation-S-transferaz pri induktsii rezistentnosti kletok leikoza P 388 i astsitnoi opukholi Erlikha k doksorubitsinu.

We have studied by uridine short term test the level of resistance of murine leukemia cell lines P 388/Dx and ELD/Dx carcinoma cells with induced resistance to doxorubicin, P 388/Fp + Dx cells with induced resistance to combination of finoptOFF++ and doxorubicin in vivo. It was shown that the level of resistance was 6 fold for P 388/Dx cells, 4.5 fold for ELD/Dx cells and 2 fold for P 388/Fp + Dx cells. It was shown that the P 388/Dx cells and P 388/Fr + Dx cells had a 3.5 and 4.4 fold increase level of glutathione-S-transferase activity than P 388 cells. No increase in the activity of glutathione-S-transferase was detected in ELD/Dx cells. We conclude that increase of cellular glutathione-S-transferase activity is not associated with the development of resistance to doxorubicin.

[The effect of finoptin on the metabolism and pharmacological action of cyclophosphane in vivo and in vitro]. / Vliianie finoptina na metabolizm i farmakologicheskoe deistvie tsiklofosfana in vivo i in vitro.

Phynoptin (Ph) and cyclophosphamide (CP) gave rise to a type I spectral changes with liver microsomal fraction. KS were 15 microM and 2150 microM, respectively. Ph increases the concentration of NBP product(s) of CP and acrolein in the blood plasma of animals. Ph increases a toxicity of CP. LD50 was 388.0 +/- 13.9 mg/kg for CP and LD50 was 342.8 +/- 16.9 mg/kg for CP in combination with Ph. Ph changes a therapeutic action of CP in mice with hemocytoblastosis La. Pharmacokinetic interactions have been demonstrated between calcium antagonists Ph and CP.

[Comparative accumulation of the Hoechst 33258 fluorescent probe in leukemia P388 cells sensitive and resistant to doxorubicin]. / Issledovanie sravnitel'nogo nakopleniia fliuorestsentnogo zonda Khekhst 33258 v kletkakh leikoza P 388, chuvstvitel'nykh i ustoichivykh k doksorubitsinu.

The authors studied accumulation of the fluorescent probe Hoechst 33258 in leukemia P 388 sensitive (P 388/0) and resistant to doxorubicin (P 388/DOX) cells. It was shown that intensity of fluorescence of the dye increased after binding with nuclear DNA during 25 min for both lines of the cells. Intensity of fluorescence was 40% greater in sensitive than resistant cells. If Triton X-100 was added no difference between two lines of the cell was observed. When doxorubicin was added to the cells with dye, the intensity of fluorescence decreased. It was suggested to use Hoechst 33258 for assessment extent doxorubicin accumulation in nuclei of the cells.

[Modification of doxorubicin action with artificial hyperglycemia]. / Modifikatsiia deistviia doksorubitsina iskusstvennoi giperglikemiei.

Approximately a 1.6-fold increase in the antitumor action of doxorubicin used in combination with artificial hyperglycemia was shown on mice C57B1/6 with hemocytoblastosis La. Artificial hyperglycemia was found to change the doxorubicin pharmacokinetics in the experimental animals evident from increased in antibiotic half-life to 42.3 min against 26.5 min in the controls, the apparent initial concentration of doxorubicin being increased 1.6 times. Accumulation of doxorubicin in the bone marrow cells of the mice did not change with artificial hyperglycemia. It was suggested that the increase in the therapeutic effect of doxorubicin used in combination with artificial hyperglycemia was associated with changes in drug pharmacokinetics.

[The effect of finoptin on doxorubicin accumulation in leukemia P-388 cells with induced resistance to the combination of finoptin and doxorubicin]. / Vliianie finoptina na nakoplenie doksorubitsina v kletkakh leikoza P-388 s indutsirovannoi ustoichivost'iu k kombinatsii finoptina s doksorubitsinom.

Using hybrid mice BDF1 doxorubicin (Dx) accumulation has been determined in leukemia P388 cells (P388/0), P388 cells with induced resistance to Dx (P388/Dx) and P388 cells with induced resistance to the finoptin (Fp) + Dx combination (P388/Fp + Dx). It has been shown that Fp doesn't affect Dx accumulation in or elimination from leukemia cells P388/0 or P388/Fp + Dx. The resistance of P388/Fp + Dx cells to the Fp + Dx combination develops during 6 passages. It can be concluded that Fp application doesn't abolish the problem of tumor cells' resistance to cytostatics.

[Possible mechanism of the alteration in the therapeutic action of cyclophosphane in mice with hemocytoblastosis La against a background of artificial hyperglycemia]. / Vozmozhnyi mekhanizm izmeneniia lechebnogo deistviia tsiklofosfana u myshei s gemotsitoblastozom La na fone iskusstvennoi giperglikemii.

The concentration of reactive cyclophosphamide metabolites (CP) and the time of their circulation in blood plasma of mice increase during artificial hyperglycemia (HG). Intensification of the antitumor CP activity against a background of HG in C57Bl/6 mice with hemocytoblastosis La may be a result of changes in the drug pharmacokinetics. An inhibitory action of HG on the CP-metabolizing system of the liver monooxygenases is shown.