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Cytological and cytochemical properties of ten ascites tumors.

1. The cytological and cytochemical properties of the Ehrlich tetraploid and hyperdiploid, TA3 tetraploid and diploid, Krebs 2B, sarcoma 37, MC1M, 6C3HED and DBA lymphoma, and lymphoma #1 ascites tumors at a fixed interval after transplantation are described. 2. No qualitative differences were observed in the cytochemical properties of the nucleus, nucleolus, parachromatin, parachromatin bodies, large lipide globules, lipochondria, mitochondria, and cytoplasm of the tumor cells of the 10 neoplasms. 3. Quantitative differences were noted in the cells of the 10 neoplasms. These were reflected by variation in nuclear and cytoplasmic diameter, nucleolar mode, mitotic index, incidence of gross abnormalities of mitosis, karyorrhexis, multinucleated cells, accessory micronuclei, cell clumping, and in the number and size of the large lipide globules and lipochondria of the cells.

Animals↗

Correlation of tubulin-binding and antitumor activities of podophyllotoxin analogs.

The tubulin-binding affinities of podophyllotoxin and 12 related compounds have been compared with the effectiveness of these drugs in three assays of antitumor activity: (1) The mastocytoma assay of inhibited tumor cell growth in vitro; (2) the 37 sarcoma assay of tumor remission in vivo; and (3) the Stentor regeneration inhibition assay which detects a requirement for microtubule polymerization. The results indicate that there is a positive Spearman rank correlation coefficient between the inhibition constant for the binding of colchicine to tubulin in the presence of these compounds and the effectiveness of the compounds in the three assays of tumor growth inhibition. It is suggested that tubulin-binding assays may be a useful step in the screening of podophyllotoxin-like compounds suspected of disrupting mitosis by binding to microtubule protein.

Animals↗

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.

Alkaloids↗

[Universal approaches to the control of tissue radiosensitivity during radiation therapy of malignant tumors].

Approaches to the problem of the control over tissue radiosusceptibility, united by the common purpose--a need for selective increase of the intact tissues tolerance to overcome tumor hypoxia, are discussed. Such universal approaches include an application of radiation characterized by high linear wastes of radiation energy, methods of increased oxygenation of tumors, the use of electron sink compounds, and irradiation under conditions of hypoxia--hypoxiradiotherapy. The experiments conducted by the author and his collaborators with local irradiation of a number of transplantable mice tumors under general hypoxia, produced by inhalation of oxygen poor gaseous mixtures (5% O2+95% N2), have shown not only a selective protection of normal tissues, but also greater regression of tumors. The mechanism of the observed phenomenon is being suggested, and some prospects of hypoxiradiotherapy in the oncological clinic are discussed.

Animals↗

[Immunohistochemical studies of recessive oncogene p53 and N-myc oncogene expression in 7, 12 dimethylbenz (a) anthracene-induced rat ovarian tumors].

In the present study, the expressions of p53 and N-myc gene were analyzed immunohistochemically in rat ovarian tumors induced by 7,12 dimethylbenz (a) anthracene (DMBA). 1) p53 could be seen in the nucleolei of tumor cells. The positive rates were: adenomas 17%, adenocarcinomas 37%, sarcomas 0%, mixed müllerian tumor 0% and epidermal cysts 100%. Neither the serial-allografted tumor nor DMBA-OC-1 was positive. 2) N-myc could be seen in the cytoplasm and perinuclear cytoplasm of tumor cells. The positive rates were: adenomas 33%, adenocarcinomas 77%, sarcomas 100%, mixed müllerian tumors 100% and epidermal cysts 100%. Both the serial-allografted tumor and DMBA-OC-1 were positive. 3) The positive rates in both p53 and p21 were: adenocarcinoma 20% and epidermal cysts 100%. The positive rates in both N-myc and p21 at the were: adenoma 17%, adenocarcinoma 50%, sarcoma 33%. Both the serial-allografted tumor and DMBA-OC-1 were positive. Only two cases were positive for p53, N-myc and p21. p53 was detected in most of the adenomas. 4) The positive rate for both N-myc and p21 was higher than that for both p53 and p21. This was similar to other reports. The results suggested that p53 plays a role in precancerous tumor as a recessive oncogene. It was supposed that tumors with N-myc gene expression were had malignant growth characteristics.

9,10-Dimethyl-1,2-benzanthracene↗

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.

Animals↗

[Tomizine--a new inhibitor of folate metabolism enzymes possessing an antitumor activity].

In the experiments on enzymic systems functioning in the metabolism of folic acid and on transplantable tumors in animals the preparation thomizine (chlorohydrate 4-methoxy-6-aminopyrimido (4,5-b) (1,4) thiazine) was worked out. Thomizine, as well as the known antimetabolite of folic acid-methotrexate, suppresses the activity of dihydrofolate reductase, but contrary to it suppresses FAP enzymic system, inhibiting aminopterin in the organism. Thomizine differes from methotrexate by another spectrum of antitumor effect, selective suppression of the tumor tissue growth, compared with the normal in vitro, it does not inhibit leucopoiesis, shows less toxicity and insignificant cumulative properties.

Aminopterin↗

[Effects of hyperbaric oxygenation on tumor growth].

The study failed to show a stimulating effect of hyperbaric oxygen on growth and metastatic spreading of sarcoma 37 transplanted subcutaneously or intravenously to female SHR mice, melanoma B16 intramuscularly transplanted to female C57/Bl mice and methylcholanthrene-induced tumors in female albino noninbred rats. An insignificant inhibitory effect of hyperbaric oxygen on transplantable tumor growth and development of inducible ones in experimental animals was observed.

Animals↗

[Localization of metronidazole in the organs of tumor-bearing animals using electron paramagnetic resonance].

The low-temperature ESR-spectroscopy was used to study the irradiated organs and blood of tumor-bearing animals before and after the administration of metronidazole. The ESR signals of metronidazole anion-radicals were registered in tissues of the animals injected with metronidazole: the intensity of these signals correspondent with the tissues preparation content.

Animals↗

[Effect of metronidazole and local irradiation of the tumor on paramagnetic metal complexes of the liver and tumor tissues].

A study was made of changes in the intensity of the ESR signals in tissues of sarcoma-37 and liver of mice after radiation of the tumor, administration of metronidazole, and after the combined effect of the two factors. The most pronounced changes in the ESR signals were induced by metronidazole. An appreciable increase in the content of nitrosyl complexes in the tumor was noted after the combined effect of metronidazole and radiation which was indicative of the radiation-induced formation of a large number of metronidazole anion-radicals in the tumor.

Animals↗

[Action of khanerol on the superhelical DNA structure of S-37 cells].

The damaging effects on the structure of a supramolecular DNA complex of sarcoma-37 cells in mice following the use of the therapeutic doses of khanerol were found. Capillary elastoviscosimetry and nucleoid sedimentation procedure showed that the damage of the supramolecular DNA complex structure becomes apparent already after 4 hours, and increases by 24 hour. In studies of the binding of khanerol with DNA by Cd and Tmelt. the procedure showed direct interaction of khanerol with DNA. The role of conformational changes of the supramolecular DNA complex in the cytotoxic action of antitumour agents is discussed.

Animals↗

[Disordered DNA repair in tumor cells as affected by sarcolysine].

Sarcolysine-induced damaging and reparative processes in the primary structure of tumour cell DNA have been studied. The presence of low sarcolysine concentrations (1 mkM) in the cell culture during the first two hours of incubation caused suturing of DNA molecules. The increase of the incubation time from 4 to 18 hours and the rise in the drug concentration (by 10.20 times and more) resulted in intensive accumulation of one-strand breaks. However, we have not observed the appearance of high-molecular DNA, which is the evidence of the completion of the reparative process. The impulse treatment with sarcolysine (1 hour, 10 mkM) with subsequent drug removal caused the irreversible damage of DNA reparative processes at the stage of short fragments' suturing.

Animals↗

[Microangiographic signs of blood vessel rearrangement during tumor growth].

In the experiment performed in mice with a subcutaneously implanted sarcoma-37 on the chin, rearrangement of the blood vessels has been followed by means of micro-roentgenography. In the process of the implanted tumour growth, the blood vessels undergo a profound functional-anatomical rearrangement, which develops, beginning from the first hours, in two ways: at the expense of the peripheral vessels rearrangement in the recepient and at the expense of real tumorous vessels development ensuaring vascular trophic of the tumour.

Angiography↗