Characteristics of the metastatic spread of transplanted tumors under high-altitude conditions

The data on nature of metastatic spreading of transplantable animal tumours of the Tien-Shan mountains at an altitude of 3200 m above sea level are reviewed. It is shown that the adaptation of mice with Ehrlich adenocarcinoma is followed by the primary tumour growth inhibition and a two-fold decrease of frequency of metastatic spreading into regional lymph nodes as compared with the control animals at sea level. In mountains the activity of metastatic spreading into lungs of Lewis lung carcinoma and Walker carcinosarcoma decreases. In experiments with (CBA x C57Bl)F1 mice-hybrids with Lewis lung carcinoma the enhancement of antitumour and antimetastatic effect of the cyclophosphamide is revealed under high-altitude hypoxia influence.     

Pathogenetic aspects of the individualization of diagnosis and prevention of metastasis

Pathogenetic aspects of individualization of prognosis and prevention of metastatic spreading have been studied for many years. The paper presents the results obtained in the course of the study. Prognostic importance of the indices of external respiration, functional activity of macrophages and natural killers, growth-modifying properties of the blood serum and the angiogenic factor content in it is substantiated. The methods of individual antimetastatic therapy with the application of neurotropic drugs and diet restriction as well as with the use of tests of the metastatic cells' sensitivity to different therapeutic influences are suggested.     

Antimetastatic effect of the delta-sleep peptide during stress in mice with Lewis' lung carcinoma

The experiments on C57Bl mice with metastatic Lewis lung carcinoma have shown that peptide delta-sleep (DSIP) lowers the stimulation of metastatic spreading which is observed in combination of the surgical removal of the tumour with the emotional-painful stress. The antimetastatic effect is accompanied by stabilization of neurohumoral indices, by a decrease in the intensity of lipid peroxidation and of the acid cathepsin activity in the blood vessels and in the lung tissue.     

Changes in the total proteolytic activity and inhibitory potential of tumor and lung tissue in mice during growth and metastatic spread of malignant neoplasms

In tumour tissue and in lungs of mice with carcinoma 3LL, melanoma B-16, adenocarcinoma 755 different changes of proteolytic and antitryptic activities have been revealed. An excessive level of the protease activity and/or a decrease of the inhibitory potential activity are the factors of decompensation of the body's protease-inhibitory system and stimulate development of metastatic process.     

The role of the system of proteolytic enzymes and their inhibitors in the pathogenesis of ovarian tumors in Wistar rats and the possibilities for correcting the disorders detected]

The system of proteolytic enzymes and their inhibitors was studied in tissues of ovarian tumours of Wistar rats. It has been revealed that activation of proteolysis enzymes is observed in the genesis of tumour growth against a background of the absence of protease inhibitors. The correction of revealed disturbances by introducing the inhibitors of proteolytic enzymes and hormone preparations has shown that contrical and norcolute are the most effective. The results obtained suggest the further search of preparation normalizing the condition of the given system.     

Elastase activity during growth and metastasis of tumors andthe pharmacological effects in C57Bl/6 mice

The elastase activity in malignant tumour tissues and lungs of C57B1/6 mice has been studied under growth and metastatic spreading of tumours and under some pharmacological influences (tryelin, cyclophosphamide). The highest elastase activity was revealed in mice with carcinoma 3LL, especially in the period of formation and appearance of metastases. Tryelin alone and in combination with cyclophosphamide reduces the elastase activity and inhibits the process of metastatic spreading in lungs.     

Effect of GMDP encapsulated into liposomes on metastatic spread of Lewis lung carcinoma

N-acetylglucosaminyl-N-acetylmuramyl-L-alanyl-D-isoglutamine (GMDP), a new liposome-encapsulated muramyl dipeptide analog, was studied for its effect on the Lewis lung carcinoma metastatic spreading as well as on the adenosine deaminase (ADA) and 5'-nucleotidase (5-N) activity in the alveolar and peritoneal mice macrophages. The drug administration was found to cause a sharp dose-dependent decrease in the lung metastases volume and number as compared to those in mice not treated with GMDP. The antimetastatic effect of GMDP is accompanied by an increase in the functional macrophage activity determined by ADA and 5-N level in these cells.     

Modifying effects of recombinant tumor necrosis factor on the metastatic potential of tumor cells

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.     

The role of cyclic nucleotides in the development of resistance to metastases after treatment with immunomodulators

It is shown that zymosan, prodigiosan, tiloron and levamisol have a different effect on the level of cyclic nucleotides and the cAMP/cGMP correlation in the lungs, thymus and spleen of mice during metastatic spreading of the Lewis carcinoma. A more pronounced antimetastatic effect after administration of immunomodulators is accompanied by a more considerable increase in the cAMP/cAMP coefficient in immunocompetent organs. There exists a close negative correlation between the increase in the cAMP/cGMP coefficient in the thymus and spleen, on the one hand, and inhibition of the metastatic spreading in the lungs under the effect of levamisol and zymosan, on the other.     

Changes in the RNA content of the blood plasma in rats with Ehrlich ascitic cancer

The RNA content in the blood plasma of tumour-bearing animals correlates with the tumour growth stage. The development of Ehrlich carcinoma in rats is followed by the RNA increase in the blood plasma, while spontaneous regression of the tumour is accompanied by a decrease of the RNA content in the blood plasma of rats with Ehrlich carcinoma almost to the normal level. The fractional spectrum of the blood plasma RNA in the tumour bearing rats is similar to that of the cell-free ascitic fluid of rats.     

Metastasis and stress reactions in the surgical resection of tumors

Complex investigations of brain mediator systems, catecholamine metabolism, II-oxycorticosteroid level in blood plasma, histochemical study of hormonogenesis in adrenal medulla and adrenal cortex in C57N1 mice with metastatic Lewis (3LL) carcinoma showed that metastatic stimulation initiated by the removal of a tumour caused an intensive prolonged stress reaction which differed from the reaction to a surgical trauma without removing a tumour. It is supposed that neuroendocrinal stress reactions could to a considerable extent determine this metastatic stimulation.     

Effect of preparations from the vitreous body having anti-angiogenic properties on the metastatic spread of Lewis lung carcinoma

Preparations extracted from the vitreous body were studied for their effect on the activity of angiogenesis and metastatic spreading. A semipurified extract and a protein preparation with molecular weight 12,000 exerted an inhibitory effect on metastasis growth of Lewis carcinoma after removal of the primary tumour. Application of these preparations has also led to an inhibition of the capillary network growth which developed subcutaneously in the site of the organic glass plate implanting, which was considered as an inhibition of the angiogenesis activity. Such an effect was not observed with the use of hyaluronate, extracted from the vitreous body.     

Immunosuppressive activity of the blood serum of patients with cancer of the corpus uteri

In 40 patients with endometrial carcinoma of I-IV stage reaction of suppression of migration and adhesion of leukocytes (RSML and RSAL) in response to antigen prepared from the same tumour and in the presence of autoserum of blood of these patients, was studied. The index of antibody-forming cells (IAFC) and percentage of rosette-producing cells (RPC) in mice spleen after their infusion before immunization by sheep erythrocytes blood serum of the mentioned patients were also investigated. It was ascertained, that in all cases with using of autoserum of patients with endometrial carcinoma, especially on late stages, significant diminution of positive RSML and RSAL and decrease of IAFC and RPC take place. It was concluded that blood serum of patients with endometrial carcinoma gives evidence of immunosuppressive activity at late stages of the process.     

Inhibition of the metastasis of Lewis lung carcinoma in mice by the administration of spasmolytin, midantan and L-DOPA

Different combinations and doses of neurotropic drugs of the central action (spasmolytine, midantane, L-DOPA) coupled with the surgical removal of the lung Lewis carcinoma were studied for their effect on the metastatic spreading in C57BL/6 mice. It has been established that the long-term use of spasmolytine and midantane before and after the operation inhibits the metastatic process, that is expressed in the total volume reduction of lung metastases, lack of metastases in a number of mice and augmentation of the average life. Such method of drug application is more effective in the metastatic growth inhibition as against their application only in the pre- or postoperation periods as well as with the use of the other neurotropic drug combinations.     

Effect of induced hyperglycemia on the metastasis of RL-67 lung carcinoma

The effect of multiple artificial hyperglycemia treatments on metastatic spreading and tumour growth depending on the stage of the tumour development is studied in experiments on mice with transplanted subcutaneous lung cancer LC-67. Intensification of the metastatic spreading and of the primary tumour growth under hyperglycemia treatment of early and advanced diseases is detected. Artificial hyperglycemia does not influence the tumour progress at the terminal stage of the disease.     

Effect of cryodestruction of Lewis lung carcinoma in mice on the development of metastases

The effect of the primary tumour cryodestruction on a degree of metastatic spreading in the lungs was investigated in experiments with C57B1/6 mice with Lewis carcinoma of the lungs. It is found that after the tumour cryosurgery there was a less quantity of metastases as compared with operated animals (surgical removal of the tumour or amputation of the limb with the tumour) or with untreated animals. A regular correlation is observed between the degree of metastatic spreading and the efficiency of the primary tumour treatment. The relapse after cryosurgery or surgical removal of the tumour led to an increase in the quantity of pulmonary metastases.     

Lipid metabolic disorders in rats with a transplanted Pliss lymphosarcoma

Changes in biosynthesis of cholesterol and free fatty acids from 2-14C-acetate in the host liver and tumour tissue as well as concentrations of various classes of lipids in blood were determined in rats bearing the transplanted Pliss lymphosarcoma. The transplantation of the tumour stimulates cholesterol biosynthesis de novo in the liver, but produces no changes in the fatty acid synthesis. Tumour growth is accompanied by a progressive increase in the content of triglycerides and beta-lipoproteins with a parallel drop in the alpha-cholesterol level in the animal blood. The concentration of total cholesterol is of phasic character depending on the stage of tumour growth. The possible mechanisms determining such alterations in lipids metabolism are discussed.     

The characteristics of the incorporation of the 14C-glucose label into the total lipids of the organs and tissues of Wistar rats with Guérin's carcinoma under differing nutritional conditions

Peculiarities of 14C-glucose label incorporation into total lipids (TL) of organs, tissues, blood serum and tumors in rats with the Guérin carcinoma under different nutrition conditions have been studied. It is determined that after recycling 14C-glucose is used in TL synthesis of organs, tissues, tumor which may be again involved in the process of metabolism, that evidences for the function of the synthesis mechanism and mobilization of TL. With an increase of tumor mass the specific activity of label in TL of organs and tissues decreases. In contrast to organs and tissues, the tumor involves 14C-glucose into synthesis of own TL independent of nutrition conditions, their level does not decrease in starvation.     

Plasminogen activators in malignant tissues and lungs of mice during metastatic spreading and administration of various pharmacological agents

The method of fibrin plates and electrophoresis in PAAG was used to study the activity and forms of plasminogen activators (PA) in extracts of normal tissues (muscle, lungs) as well as of the malignant tumours and the lungs of mice during metastatic spreading and under certain drugs (trielin and cyclophosphane). It was stated that determination of the specific activity level of plasminogen activator in a target organ (lungs) may be used as one of the indices during evaluation of the antimetastatic effect.     

Pathogenetic aspects of metastasis

The results of studies on the pathogenic mechanisms of metastatic spreading which determine sedimentation of tumour cells, their extravasation and development in the extravascular space and affect the growth of metastatic germs are summarized. It is shown that the hypothalamo-pituitary-adrenal and sympathoadrenal systems, the system of natural resistance represented by macrophages, the prekallikrein-kinin system and the interferon system modulate the metastatic process and mechanisms of antitumoral resistance. In the course of the tumour growth the activity of these systems undergoes pathologic changes which, on the one hand, are the result of the tumour growth and, on the other hand, affect the mechanisms of metastatic spreading of tumours and the factors of its regulation. The possibility of finding the ways for inhibiting metastatic tumour spreading by means of the studying the pathogenetic mechanisms of the metastasis development is discussed.