BIOMAGNETISM OF DRUG-SENSITIVE AND DRUG-RESISTANT MALIGNANT TUMORS AFTER INJECTION OF FERROMAGNETIC NANOCOMPOSITE.

Magnetic signals emitted by living organisms, regardless of a biological species, are important biophysical indicators. The study of these indicators is very relevant and promising for the visualization of the tumor process and the development of technologies using artificial intelligence when it comes to malignant neoplasms, particularly resistant to chemotherapy. AIM: To measure magnetic signals from transplantable rat tumors and their counterparts resistant to cytostatics for evaluating the features of the accumulation of iron-containing nanocomposite Ferroplat. MATERIALS AND METHODS: Doxorubicin (Dox)-sensitive and Dox-resistant Walker-256 carcinosarcoma and cisplatin-sensitive and cisplatin-resistant Guerin's carcinoma transplanted in female Wistar rats were studied. The magnetism of tumors, liver and heart was determined using Superconductive Quantum Interference Device (SQUID) - magnetometry in a non-contact (13 mm over the tumor) way using specially designed computer programs. In a group of the experimental animals, a ferromagnetic nanocomposite (Ferroplat) was administered as a single intravenous injection and biomagnetism was assessed in 1 h. RESULTS: The magnetic signals coming from Dox-resistant Walker-256 carcinosarcoma in the exponential growth phase were significantly higher in comparison with sensitive tumor. Intravenous administration of Ferroplat increased biomagnetism by at least an order of magnitude, especially in resistant tumors. At the same time, the magnetic signals of the liver and heart were within the magnetic noise. CONCLUSION: The use of SQUID-magnetometry with ferromagnetic nanoparticles as a contrast agent is a promising approach for visualization of malignant neoplasms with varying sensitivity to chemotherapy.

Biomagnetism of tumor in rats with Guerin's carcinoma after injection of ferromagnetic nanocomposite (Ferroplat): contactless measurement.

AIM: In order to develop fundamentally new technologies for non-invasive and safer diagnosis of cancer, we aimed to detect non-contact magnetic signals from a malignant tumor in animals treated or not-treated with the ferromagnetic nanocomposite Ferroplat. MATERIALS AND METHODS: Guerin's carcinoma was used as a model of tumor growth. The biomagnetism of the tumor was evaluated in the dynamics of its growth. Ten days after tumor transplantation, Ferroplat was administered intravenously to half of the animals with the tumor and to half of the control animals. The magnitude of the magnetic signals was determined 1 h and every two days after administration of the nanocomposite using a Superconducting Quantum Interference Device magnetometer of the original design. RESULTS: We have found that the magnetic signals coming from the tumor are significantly higher compared to control tumor-free animals. Intravenous administration of a ferromagnetic nanocomposite (Ferroplat: Fe3O4 + cisplatinum) led to a significant increase of the magnetic signal, especially in the tumor tissue, and inhibition of Guerin's carcinoma growth. Ferromagnetic nanoparticles (32.7 nm) are retained in malignant cells for a longer time than in normal ones. CONCLUSION: Tumor cells accumulate iron nanoparticles more intensively than normal ones. Nanocomposite Ferroplat can be used for a targeted delivery of cisplatin to malignant cells.

The influence of lactoferrin on elemental homeostasis and activity of metal-containing enzymes in rats with Walker-256 carcinosarcoma.

AIM: To investigate the content of essential elements (EE): copper, zinc, magnesium, iron and calcium and the evaluation of the activity of metal-containing enzymes - ceruloplasmin (CP), myeloperoxidase (MPO) and the content of transferrin (TF) in blood plasma (BP) and tumor tissue (TT) of animals with Walker-256 carcinosarcoma treated with lactoferrin (LF). MATERIALS AND METHODS: The study of the EE content and the activity of the abovementioned enzymes was carried out on rats with Walker-256 carcinosarcoma treated with LF at the doses of 1 and 10 mg/kg of body weight. The quantitative content of EE in BP and TT of animals was determined using the inductively coupled plasma atomic emission spectroscopy (ICP-AES). Determination of CP activity, content of TF and hemochromes was performed using the method of electron paramagnetic resonance (EPR), and MPO - by unified biochemical method. RESULTS: The introduction of LF at the doses of 1 and 10 mg/kg resulted in a decrease in the ratio of Cu/Zn in BP and even more expressed decrease of Ca/Mg ratio in TT. Administration of LF, especially at a dose of 10 mg/kg, affected the increase in CP and MPO activity in BP. It has been shown that administration of LF at a dose of 10 mg/kg led to an increase in oxidative products of destruction of the hemoglobin-hemochrom system in the TT, against the background of lowering the TF content. CONCLUSIONS: The administration of LF, especially at a dose of 10 mg/kg, led to metabolic alterations associated with inhibition of the tumor process. The detected modulating effect of LF on the content of the EE and the activity of the CP and MPO may be a basis for correction of the elemental balance in carcinogenesis.

Antitumor and genotoxic effects of lactoferrin in Walker-256 tumor-bearing rats.

AIM: To investigate the influence of exogenous lactoferrin (LF) on tumor growth, energy and lipid metabolism of Walker-256 carcinosarcoma and to assess genotoxic effects of LF. MATERIALS AND METHODS: The study was performed on Walker-256 tumor-bearing rats. Total lipids and phospholipids were determined by thin-layer chromatography. Comet assay was used to investigate the genotoxic effects of LF. RESULTS: Daily i.p. administrations of exogenous LF at concentrations of 1 mg/kg and 10 mg/kg starting from the 4th day after tumor transplantation suppressed growth of Walker-256 carcinosarcoma by almost 44%. After treatment with recombinant LF in both doses, the phospholipid composition of Walker-256 carcinosarcoma cells was changed (3-fold increase of phosphatidylethanolamine, 3.4-fold increase of phosphatidylcholine, and 1.8-fold increase of sphingomyelin, while the cardiolipin content decreased by 67%. Exogenous LF was not genotoxic for bone marrow cells (as assessed by the ratio of PCE/NCE, number of micronuclei) and peripheral blood lymphocytes (percentage of DNA in the tail of a comet) in Walker-256 carcinosarcoma-bearing rats. CONCLUSION: Exogenous LF caused the inhibition of Walker-256 carcinosarcoma growth and a decrease in the microviscosity of plasma cell membranes, and exerted no genotoxicity toward bone marrow cells and peripheral blood of experimental animals.

Influence of ferromagnetic nanocomposite (Ferroplat) on human breast cancer cells of different malignancy degrees: pro/antioxidant balance and energy metabolism.

AIM: To study the effect of Ferroplat (FrP) on the indexes of pro/antioxidant balance and energy metabolism in breast cancer cells of different malignancy degree and different sensitivity to drug therapy. MATERIALS AND METHODS: The study was carried out on breast cancer cells of low (T47D, MCF-7) and high malignancy degree (MCF-7/DDP (cisplatin-resistant), MDA-MB-231, MDA-MB-468) using cell culture techniques, immunocytochemical, biochemical, biophysical methods, flow cytometry and polarography. RESULTS: We established that the addition of FrP to the culture medium reduces the activity of glucose-6-phosphate dehydrogenase (G6PDH), superoxide dismutase (SOD) and the level of non-protein thiols by 32-41% (p < 0.05). At the same time, there was an increase of the total level of ROS and the rate of NO generation by inducible NO synthase by 1.7-2.5 times (p < 0.05). This testifies that FrP disturbs the antioxidant balance in cells, resulting in their death. Also, the use of FrP led to a decrease in the rate of oxygen absorption in MCF-7 and T47D cells by 26% and 25%, respectively (p < 0.05). In cells of high malignancy degree this index decreased by 38-40% under the influence of FrP. Incubation of MCF-7 and T47D cells with the indicated agent also reduced the content of phospholipid cardiolipin by 15-16% (p < 0.05), and in MDA-MB-231, MCF-7/DDP, MDA-MB-468 cells - by 29%, 30% and 32%, respectively. In addition, the effect of FrP caused a decrease in the levels of Mg2+ and lactate in MCF-7 and T47D cells by 21-29% and 14-24%, respectively, whereas in MDA-MB-231, MDA-MB-468, MCF-7/DDP cells - by 34-38% and 32-35%, respectively. In this case, the agent raised the level of glucose in the cells of low malignancy degree by 20-23% (p < 0.05), and in the cells of high malignancy degree and with the phenotype of drug resistance - by 31-36%. However, the nanocomposite did not affect the activity of lactate dehydrogenase in all studied breast cancer cells. CONCLUSION: The study has shown that FrP has an effect on the pro/antioxidant balance and energy metabolism of cancer cells. In addition, the denoted effect of FrP was more pronounced in the breast cancer cells with a high malignancy degree and the phenotype of drug resistance.

Antitumor resistance formation in animals in early neonatal period.

Immunization of new-born mice during the first three days after birth enhances immunity in adult life, and it remains high throughout the entire life course. The antitumor resistance is raised so high in order to produce cancerogenesis blockade caused by 20-methylcholanthrene injection to adult animals even one year after vaccination. The dynamics of growth of new-borns shows that immediately after birth the animal growth proceeds very quickly, following an exponential law. The same occurs in rats and even in human beings. Vaccination of animals during fast growth phase ensures an antitumor effect, while vaccination after fast growth phase leads to antitumor immunity breakdown. It was assumed fetal lymphocytes do not attain full sexual maturity and their cytotoxic properties start developing only after birth. This hypothesis is in full agreement with our results. Vaccination of new-borns during fast growth phase leads to a significant increase of immature lymphocytes of those clones which are sensitive to an injected antigen. Upon vaccination termination, these lymphocytes attain complete maturation and remain in tissues, thereby ensuring a prolonged and high immunity. Our earlier experiments clearly demonstrated the increase in lymphocytes number in animals which had been exposed to early postnatal immunization. The kinetic analysis showed that full tumor destruction would be only possible if the rate of tumor cells destruction by cytotoxic lymphocytes is greater than the rate of tumor cells reproduction, as the tumor is incapable to make up for loss of its own cells. Immunization during fast growth phase does allow maximum increase in the number of cytotoxic lymphocytes and, thereby, enhance an entire cell immunity - unattainable after full lymphocyte maturation.

[Ultrastructural organization of carcinoma Lewis (3LL) cells during cisplatin resistance formation].

The electron-microscopic analysis of the morphological status of 3LL (Lewis) carcinoma tumour cells in the process of cisplatin resistant phenotype formation has been performed. It was shown that selection of tumour cells forming cell clones characterized by more complicated nuclear and cytoplasm organization took place. The tumour cells had the diffused nuclear chromatin; nuclear envelope had the numerous pores with expanded diaphragms. The prominent nucleoli consisted of the active centres surrounded by considerable areas of the condensed nucleolar chromatin. Cell cytoplasm contained the well-developed Goldgi complex and the numerous well-structured myelinoid formations in the form of dense-wrapped concentric membrane structures. The obtained data can morphologically confirm the hypothesis of Gately D.P. and Howel S.B., 1993, thain the process of resistant phenotype formation the tumour cells can create the cellular mechanisms to remove the drug from the cell and to correct the damages of the cellular nucleus and cytoplasm.

Modifying effects of 5-azacytidine on metal-containing proteins profile in Guerin carcinoma with different sensitivity to cytostatics.

AIM: To assess the influence of the treatment with 5-azacytidine (5-aza) on the profile of metal-containing proteins and factors of their regulation in Guerin carcinoma cells in vivo. MATERIALS AND METHODS: The study was conducted on Wistar rats transplanted with wild-type Guerin carcinoma (Guerin/WT) and its strains resistant to cisplatin (Guerin/CP) or doxorubicin (Guerin/Dox). Animals were distributed in 6 groups treated with 5-aza and control animals without treatment. 5-Aza was injected by i.v. route (1 injection in 4 days at a dose of 2 mg/kg starting from the 4th day after tumor transplantation, 4 injections in total). Ferritin levels in blood serum and tumor tissue were measured by ELISA, transferrin and free iron complexes - by low-temperature EPR, miRNA-200b, -133a and -320a levels and promoter methylation - by real-time quantitative reverse transcription polymerase chain reaction. RESULTS: The study has shown that 5-aza treatment caused demethylation of promoter regions of fth1 and tfr1 genes in all studied Guerin carcinoma strains. 5-Aza treatment resulted in a significant decrease of ferritin levels in tumor tissue (by 32.1% in Guerin/WT strain, by 29.8% in Guerin/Dox and by 69.1% in Guerin/CP). These events were accompanied by 3.5-fold and 2-fold increase of free iron complexes levels in tumor tissue of doxorubicin and cisplatin resistant strains, respectively. Also, 5-aza treatment resulted in significantly elevated levels of miR-200b, -133a, 320a expression in tumor tissue. After 5-aza treatment, ferritin levels in blood serum of animals with Guerin/Dox were increased by 23.9%, while in Guerin/Wt and Guerin/CP they were decreased by 17 and 16%, respectively. CONCLUSION: Alterations of epigenetic regulation upon in vivo treatment with 5-aza change the levels of metal-containing proteins due to DNA demethylation and altered miRNA expression profiles in Guerin carcinoma cells.

Antitumor resistance activation in mice: can the immunological memory cells enhance resistance?

Immunization of adult animals with the Ehrlich ascytic cancer cells homogenate three months prior to an experiment, did not affect either tumor transplantation or the progress of cancerogenesis induced by injection of 20-methylcholanthrene oil solution into the femoral muscle. All consequences of adult animal vaccination disappeared in 30-40 days following antigen administration. Quite different consequences were observed after immunization of the newborn mice. The same antigen (Ehrlich cancer cells homogenate) injected to newborn mice on days 1 and 3 after birth in a dose that failed to develop tolerance not only significantly increased the ascytic tumor transplantation threshold (by nearly 200 times for sarcoma 37 cells and by nearly 400 times for Ehrlich cancer cells) in adult animals but also led to almost 50% inhibition of cancerogenesis (induced by injection of 20-methylcholanthrene oil solution in the femoral muscle of mature mouse) after three and even after 12 months following immunization. The MTT-analysis did not reveal any noticeable differences in the number and activity of the cytotoxic lymphocytes in populations of splenocytes obtained from the intact mice (control) and from the adult animals which had been exposed to postnatal immunization (experiment).However, after a new vaccination such differences were found. In the populations of splenocytes obtained from control animals, the cytotoxic activity measured on day 10 after vaccination had increased 2.86-fold mainly at the expense of an increased number of effector cells. In the populations of splenocytes obtained from the experimental group of animals the activation was much greater (25.8-fold), being accomplished not only at the expense of an increased number of the effector cells, as observed in the control group, but also at the expense of their higher activity. The kinetic analysis of a mechanism of effector cells/target cells interaction has led to derive equations for estimation of the limiting rates of such interaction and of the equilibrium constants for interacting cells. Analysis of a generally accepted mechanism of the cytotoxic lymphocytes formation, with an account of the kinetic analysis data, has shown that a major reason of low antitumor resistance of animal organism is the negligible population of resting cells--the precursors of antitumor cytotoxic lymphocytes. Newborn mice vaccination does not produce any increase in the number of resting cells of the necessary type. This circumstance explains both, increase of the ascytic tumor transplantation threshold and increase of the resistance to 20-methylcholanthrene action in adulthood. Adult animal immunization does not possess such action. Analysis of the problem leads to the conclusion that the system of organism's antitumor resistance becomes effective only in those cases when, owing to antigen activation of resting cells, the concentration of cytotoxic lymphocytes rises to such an extent that the rate of tumor cell destruction becomes greater than the rate of target cells reproduction.

Metabolic changes during development of Walker-256 carcinosarcoma resistance to doxorubicin.

AIM: To study indices of energy metabolism, content of K(+) and Mg(++) both in peripheral blood and in Walker-256 carcinosarcoma during development of resistance to doxorubicin. METHODS: Resistance of Walker-256 carcinosarcoma to doxorubicin has been developed through 12 subsequent transplantations of tumor after the chemotherapy. Parental strain was inhibited by drug by 65%, while transitional resistant substrains - by 30% and 2%, respectively. Determination of biochemical indices in blood serum and homogenates of tumor tissue, level of potassium, magnesium, lactate, glucose, activities of lactate dehydrogenase and glucose-6-phosphate dehydrogenase was performed with the help of biochemical and immune-enzyme analyzer GBG ChemWell 2990 (USA) using standard kits. Polarography was used to determine indices of mitochondrial oxidative phosphorylation. Study of mitochondrial membrane potential was carried out on flow cytometer Beckman Coulter Epics XL using dye JC-1. RESULTS: It has been determined that development of drug resistance causes the decrease of K(+), Mg(++), glucose content in blood serum and increase of these indices in tumor tissue. At the same time, gradual tumor's loss of sensitivity is characterized by decrease of glycolysis activity in it and activation of mitochondrial oxidative phosphorylation and pentose phosphate pathway of glucose degradation, which causes more intensive formation of NADPH. CONCLUSION: Development of drug resistance of tumor causes certain metabolic changes in organism and tumor. Further study of such changes will make possible to determine tumor and extratumor markers of resistance.

Pharmacological effect of aminoferrocene in mice with L1210 leukemia.

AIM: To study the cytostatic and some biological effects of aminoferrocene using mice with L1210 lymphoid leukemia. MATERIALS AND METHODS: Experiments were performed on BDF1 male mice (DBA/2, female × C57Bl/6, male) with transplantable L1210 lymphoid leukemia. Determination of antitumor activity of Benzyl-Fc Boron (Bn), it was injected intraperitoneally 6 times daily, starting on day 2 after L1210 leukemia cell transplantation. Doses of Bn such as 26; 260 and 2600 µg/kg were used. The determination of intracellular content of cardiolipin, thiols, reactive oxygen species (ROS) and also analysis of Annexin V positivity and mitochondrial transmembrane potential (JC-1 staining) were performed with use of flow cytometry. The levels of "free iron" complexes, transferrin active forms and the rate of NO generation were measured by EPR-specroscopy. RESULTS: Six daily injections of Bn at a dose of 26 µg/kg resulted in an increased survival of mice with L1210 leukemia by 28% (p < 0.05). Bn led to an increase of apoptotic cells number and ROS amount in leukemia cells. Besides, Bn caused a decrease of cardiolipin and nonprotein thiol compounds content. The membrane electrochemical potential of cell mitochondria was decreased also after Bn administration. Studies using EPR-spectroscopy revealed a significant increase in a level of "free iron", content of transferrin active species and generation rate of NO by inducible NO-synthase in L1210 cells after aminoferrocene administration. CONCLUSION: Our data indicate that Benzyl-Fc Boron can be promising candidate for realizing a new strategy of anticancer therapy with the use of ROS-inducing agents.

Prevention of myelosuppression by combined treatment with enterosorbent and granulocyte colony-stimulating factor.

UNLABELLED: Hematotoxicity and its complication are the prominent limiting factors for rational treatment of malignancies. Granulocyte colony-stimulating factor (G-CSF) is used to increase granulocyte production. It has been shown previously that enterosorption causes prominent myeloprotective activity also. Still, no trial was performed to combine both of them. AIM: To study the influence of combination of enterosorption and pharmaceutical analogue of naturally occurring G-CSF (filgrastim) on bone marrow protection and the growth of grafted tumor in a case of injection of melphalan (Mel). MATERIALS AND METHODS: Mel injections were used for promotion of bone marrow suppression in rats. Carbon granulated enterosorbent C2 (IEPOR) was used for providing of enteral sorption detoxifying therapy. Filgrastim was used to increase white blood cells (WBC) count. RESULTS: The simultaneous usage of enterosorption and filgrastim had maximum effectiveness for restoring of all types of blood cells. WBC count was higher by 138.3% compared with the Mel group. The increase of platelets count by 98.5% was also observed. In the group (Mel + C2 + filgrastim) the absolute neutrophils count was twofold higher, in comparison with rats of Mel group. CONCLUSION: Simultaneous administration of G-CSF-analogue and carbonic enterosorbent C2 is a perspective approach for bone marrow protection, when the cytostatic drug melphalan is used. Such combination demonstrates prominent positive impact on restoring of all types of blood cells and had no influence on the antitumor efficacy.

The SEIRA spectroscopy data of nucleic acids and phospholipids from sensitive- and drug-resistant rat tumours.

It is known that tumour progression towards drug resistance is one of the main factors resulting in the failure of cancer treatment. As tumour progression is based on the genetic instability, the study of the structure of nucleic acid from tumour cells is of great importance both for basic knowledge and for biomedical application. We applied surface enhanced infrared absorption spectroscopy (SEIRA) of nucleic acids on gold substrate and essentially increased the sensitivity of IR spectroscopy. We observed numerous changes in infrared spectra of DNA from sensitive and resistant cells that reflect drastic changes in molecular structure of DNA from tumour cells. The DNA from resistant cancer cells could be characterised as rigid structure, the structure of DNA from sensitive cancer strain seems to be flexible and after application of anticancer drugs drastically changes and approaches to the structure of helix forms. The molecular structure of lipids from resistant and sensitive cancers after application of anti-tumour drugs is also modified. Thus, we observed a disordering in the lipid chain packing from resistant cells after application of cisplatin and, in some cases, formation of phospholipid-Pt complex.

The influence of glucose, succinate, pH of the medium and higher temperature on the cytotoxic activity of the preparation Ukrain.

Cells of ascitic forms of Ehrlich's carcinoma and sarcoma 37 transplanted into C57BI/6 mice were used to study the influence of glucose, succinate, and pH of the medium on the cytotoxic activity of the preparation Ukrain. Viability of cells was estimated by the method of intravital staining with tripan blue after the incubation of cell suspension in the presence of the preparation (1.05 x 10(-5) mol and 1.69 x 10(-4) mol). It was established that glucose (5 mmol) reduces the cytotoxic activity of Ukrain, while succinate (5 mmol) increases it. The activity of the preparation was practically absent at pH 6.1-6.7 of the incubation medium and was at a maximum at pH 7.3-8.0. A temperature of 41.5 degrees C has no influence on the effectiveness of Ukrain.

Study of acute toxicity of Ukrain in rats after intravenous injection.

The acute toxicity of i.v. Ukrain injection in rats was studied. The interrelation between toxicity (death of animals) and dosage was determined by nonlinear regression method. White blood count (WBC) in peripheral blood, weight of animals, and weight of major organs were determined in animals during all stages of investigation. Morphological studies of toxic changes in 40 different organs of rats were performed on macro- and microscopic levels.

[Oxygen metabolic characteristics in the tumor process]. / Osobennosti kislorodnogo obmena pri opukholevom protsesse.

The data available in literature and results of the authors, own investigations on the oxygen metabolism during the appearance and development of the tumour process are presented. The important role of biological oxidation disorders in cell malignancy is discussed. The appearance and development of malignant tumours occur against a background of tissues hypoxia. Severe hypoxia and anoxia are observed constantly in the tumour tissue. Some mechanisms of hypoxia development and cell respiration reduction in malignant tumours are considered. Necessity of methods and drugs searching (antihypoxic agents and antioxidants) for correction of oxygen homeostasis disturbances and increase of antitumour resistance of the organism is substantiated.

[The effect of the combined use of cryosurgery and hyperthermia on an experimental tumor process]. / Vliianie kombinirovannogo primeneniia kriokhirurgii i gipertermii na opukholevyi protsess v éksperimente.

The antitumour efficacy of a single cryosurgery use in combination with hyperthermia was studied in 165 mice with the Lewis carcinoma, sarcoma 180 and 169 rats with Guérin's carcinoma and sarcoma 45. A considerable decrease in the recurrence frequency was observed irrespective of the histological type of the primary tumour. The haemostasis-associated expressed hypoxia has been established to arise in tumour tissues after cryodestruction. A day after the cryodestruction a shift to alkaline pH in the tumour tissue has been observed along with hypoxia. The above conditions possibly specify the high antitumour efficacy of a combined use of the cryosurgery and hyperthermia.

[Effect of solcoseryl on oxygen metabolism and growth of experimental tumors]. / Vliianie solkoserila na kislorodnyi obmen i techenie opukholevogo protsessa v éksperimente.

Antihypoxant and antitumour properties of solcoseryl were studied on intact and tumour-bearing rats and mice. By the polarographic method it is found that solcoseryl increases the oxygen metabolism only in animal hypoxic tissues and improves, probably, energy production of their mitochondria. On many tumour strains it is shown that the injections of solcoseryl decelerate the growth of some tumours, inhibit the metastatic process and produce no toxic effect on the animals.

[The combined use of cryosurgery and solcoseryl in treating malignant neoplasms]. / Kombinirovannoe ispol'zovanie kriokhirurgii i solkoserila pri lechenii zlokachestvennykh novoobrazovanii.

Antitumour efficacy of a combined use of cryosurgery and solcoseryl in mice with Lewis carcinoma was studied. Solcoseryl improves results of cryosurgery. An increase in antitumour effect with a combined use of cryodestruction and solcoseryl is supposed to be followed by the rise of oxygen tension in tissues. Solcoseryl injection followed by cryosurgery of cancer of mouth cavity mucosa in patients considerably accelerates the wound surface regeneration. Thus solcoseryl increases the treatment efficacy of the cryosurgical method.

[Use of WOBE-MUGOS E for prevention and correction of experimental doxorubicin side-effects]. / Ispol'zovanie VOBE-MUGOS E dlia profilaktiki i korrektsii pobochnykh reaktsii doksorubitsina gidrokhlorida v éksperimente.

Examined in treating rats with Guerin's carcinoma with doxorubicin was the possibility that the polyenzymic drug preparation wobe-mugos E had hepatoprotective, cardioprotective and myeloprotective effects. In intramuscular administration wobe-mugos E has not been found to stimulate the tumour growth, it exhibited a manifest hepatoprotective and myeloprotective actions with respect to adverse reactions of doxorubicin but failed to diminish cardiotoxicity of the latter. The protective effect of the above polyenzymic drug was of a dose-dependent character.