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[14C]leucine chloromethylketone interaction with sarcoma 37 cell plasma membrane components.

Leucine chloromethylketone labeling of viable S37 cells was preferential for the plasma membrane fraction. The pattern of radiolabeling of the plasma membrane proteins was time dependent. After 5 min the radiolabel was localized with glutamyl transpeptidase, and subsequently with other physiologically active proteins as a function of time after incubation. Labeling of proteins was temperature dependent and incubation of viable S37 cells with the radiolabeled substrate at 0 degrees C yielded little or no radioactivity localized in the plasma membrane. The molecular weight of one radiolabeled substrate--membrane protein complex was estimated on sodium dodecyl sulfate polyacrylamide gel electrophoresis to be between 100,000-200,000.

Amino Acid Chloromethyl Ketones↗

[Antitumor action of new 2,4-diethyleneimino-6-amino-sym.-triazina derivatives].

In experiments of mice and rats with transplantable tumors (sarcoma 37, sarcoma 45, ascites Ehrlich tumor, etc) the authors studied the antitumor activity of a number of new water-soluble derivatives of 2,4-diethylenimino-6-amino-sym.-triazine differing only in the substituting radical associated with sym.-triazine cycle. All substances under study showed marked antitumor activity. The effect of the structure of the compounds concerned and their physico-chemical properties for antitumor activity are discussed.

Animals↗

[Effects of 4-hydroxypentenal on the noncancerous and the cancerous ectocervix uteri hominis (author's transl)].

PROBLEM: 4-hydroxy-2,3-transpentenal (HPE) represents the 5-C-homologue of a series of hitherto unknown alpha,beta-unsaturated aldehydes. The marked inhibition of DNA-biosynthesis by these chemical compounds, particularly by HPE, suggests blocking of mitosis by HPE due to direct action on the S-phase. It is known that DNA-biosynthesis as well as energy metabolism are generally more disturbed by HPE in animal tumor cells (Ehrlich ascites and solid tumors, NK/Ly sarcoma 37, sarcoma 180, plasmocytoma G, murine Harding-Passey melanoma) than in normal cells (liver, kidney, jejunum, spleen, thymus); for details see BICKIS et al. 1969; RINDLER et al. 1970; KAPFER et al. 1972). After systemic administration of HPE the concentration of the cytotoxic agent in the blood caysed a bituceabke but merely selective inhibition of the metabolism in experimental animal tumors; however, it was not sufficient to produce therapeutic results. The low stability of HPE in the blood and in the peritoneal cavity is to be attributed to its affinity to SH-groups. Therefore the biological tests had to be confined to the local administration of HPE. In this histological study of the action of HPE the substance was administered directly to the human portio vaginalis uteri (ecto- and endocervix) in cases of carcinomatous alterations, in cases of non-carcinomatous affections as well as in normal portions. MATERIAL AND METHODS: In this test 42 women were treated with HPE. 3 patients were observed clinically only, the other 39 cases were investigated also histologically. The histological studies were performed on the extirpated uterus (36 cases), the resected portio (1 case) and only on a conus (2 cases). In 17 of these patients examined histologically the portio was clinically free of pathological symptoms. They suffered from such more or less commonplace gynecological disorders as displacement of the uterus, incontinentia urinae relativa, uterus myomatosus, endometriosis and cystical adnexal tumors. 7 patients suffered from ectopies, 8 from Ca coli uteri, 7 were affected by invasive cancer of the cervix. 8 of the patients were older than 50 years, the others were aged between 25 and 50 years. Mode of HPE administration: 1. Application of a small HPE-soaked linen patch fixed on a Sta Seal impression of the vagina (Sta Seal=dental silicon impression paste). 2. Application by means of a small linen patch in a portio cap. The inner surface of a portio cap corresponding to the vaginal uterus in shape and size was coated with a circular linen patch. The unneeded segment was cut off. After moistening with the aldehyde (HPE) it was fit tightly to the inner surface of the cap and, in situ, to the portio surface as well. In several cases the portio did not fill the cap completely and did not contact the tissue in the region of the os uteri. Consequently, there the aldehyde effect was lower than in the lateral regions of the portio. Therefor 3...

Adult↗

[The antitumor effect of an extract of human umbilical cord].

The study was concerned with the evaluation of effect of the extract of a human fetal organ, the umbilical cord, on development and growth of such transplantable tumors as Ehrlich's ascites tumor, sarcoma 37, sarcoma 180 and Zajdela's hepatoma as well as of dimethylbenzanthracene- and benzo(a)pyrene-induced cancer. In a subgroup of animals who had been vaccinated once or twice prior to inoculation of cells, a significant inhibition of growth of tumors of all the histologies except sarcoma 180 was observed alongside with a decrease in tumor incidence and partial resorption of ascitic fluid. Preliminary vaccination of rats interfered with dimethylbenzanthracene- and benzo(a)pyrene-induced carcinogenesis reducing tumor incidence and assuring longer latent period and slower progression of cancer.

Animals↗

[The antineoplastic activity of testiphenon].

The paper describes the antitumor activity of a newly-developed hormonocytostatic drug testiphenon--a complex ether of 5 alpha-dihydrotestosterone and chlorphenacyl (17 beta-[n-di/2-chloroethyl/aminophenylacetate]-5 alpha-androstan-17 beta-ol-3-on). Its antitumor properties were studied in 15 models of transplantable solid tumors and systemic neoplasms of mice and rats such as sarcoma 298, sarcoma 37, sarcoma-180, Lewis lung epidermoid carcinoma, carcinoma of the forestomach-5, large bowel adenocarcinoma, Harding-Passey's melanoma, cervical cancer-5, mammary adenocarcinoma Ca-755, hemoblastosis La, plasmacytoma MOPC-406, Rauscher's erythroblastosis, Walker's carcinosarcoma 256, sarcoma 45, alveolar carcinoma of the mammary gland and DMBA-induced mammary tumors of mice. The spectrum of antitumor activity of testiphenon proved wider than those of its components or other estrogeno-cytostatic drugs--phenestrol and estracyt. The drug is specifically intended for selective action upon target tissues for androgens and tumors developing from the said tissues.

Animals↗

Influence of antitumor drugs of natural origin on the intramuscular and subcutaneous form of five transplantable tumor models.

The influence of six antitumor drugs of natural origin (rubomycin, bruneomycin, olivomycin, mitomycin C, vinblastine, and vincristine) on five transplantable tumor models (sarcoma 37, sarcoma 180, Ehrlich tumor, RL-67 and TAVS) was investigated. Each tumor was transplanted subcutaneously and intramuscularly, bilaterally, on one animal. Marked differences in the sensitivity between subcutaneous and intramuscular form of Ehrlich tumor and more slightly of TAVS were established. The used experimental regimen held out possibilities for saving labor, animals and substances as well as for the study of potential antitumor substances of natural origin at maximum equalized biological conditions.

Animals↗

[Acetylation reaction in mice in the normal state and in tumors].

Studies of peculiarities of acetylation with the use of sulfadimidine showed the distribution of female white non-bred mice into two groups - with high and low activity. In C3H/He mice a relatively high activity of sulfadimidine acetylation was observed, while in C57BL/He mice a low activity of acetylation was noted. The growth of transplanted melanoma B-16 in C57BL/He mice and sarcoma 37 and sarcoma 180 in non-bred mice resulted in an increased activity of sulfadimidine acetylation. The use of w-sodium methylpantothenate (an antagonist of pantothenic acid) failed to show an increased activity of sulfadimidine acetylation and inhibited the tumor growth.

Acetylation↗

[Antitumor activity of fatty acid derivatives isolated from protozoa].

Water-soluble monoethers of sucrose and fatty acids were obtained from Trypanosoma lewisi and Astasia longa. The maximum tolerated dose of the preparations on their single intraperitoneal administration was more than 25 g/kg. The doses of 10--40 mg/kg were used repeatedly in therapy. Carcinoma 755, Lewis carcinoma, sarcoma 45, sarcoma 37 and sarcoma 180 were sensitive to the preparations. The preparations were inactive against experimental leukemia.

Animals↗

Subcellular distribution of inorganic pyrophosphatase activity in various normal and neoplastic cell types.

Inorganic pyrophosphatase (PPiase) activity was measured in cell fractions of rat, mouse, and human erythrocytes; normal rat liver; Novikoff hepatoma; Morris 3924A hepatoma; and mouse Ehrlich and Sarcoma 37 ascites tumors. Despite high intracellular activities, when precautions were taken to maintain cell integrity, only negligible activities were found on the surface of intact erythrocytes, Novikoff ascites hepatoma, Ehrlich carcinoma, and Sarcoma 37 cells. Suspensions of intact Ehrlich and Sarcoma 37 cells exhibited low PPiase activity, but this was only about 1 to 2% of the intracellular activity and was completely accounted for by activity present in the suspension medium. It is considered to be due to extrusion of the intracellular enzyme. Systematic fractionation of subcellular components revealed that 92% of the total PPiase activity of rat liver and 97.5% of that of Hepatoma 3924A were in the cytosol. The soluble activity consisted of a major form, accompanied by very low activities of two minor forms, all of which migrate toward the anode on electrophoresis. About 4.5% of the liver activity was present in the mitochondria in two forms, one remaining at the origin and one migrating toward the cathode. The same cytosolic isozymes were present in Hepatoma 3924A, and the cathodic form was present in mitochondria but in much reduced amount. No evidence was obtained for specific isozymes in nuclei or microsomes. Only negligible PPiase activities were found in cell membranes isolated by sucrose gradient centrifugation. These results discount the occurrence of PPiase activity as an ectoenzyme or in the plasma membrane of these cells and point to the cytosol as the major and mitochondria as a minor locus of intracellular PPiase activity.

Animals↗

[Cytostatic action of N-ethyl-13-dihydrorubomycin on the cells of various tumor strains].

The cytostatic effect of rubomycin and N-ethyl-13-dihydrorubomycin, its semisynthetic derivative, was studied with a radiometric method based on measuring the intensity of labeled thymidine incorporation into the tumor cells of NK/Ly, sarcoma 37 and leukemia P-388 and a method for total determination of nucleic acids in the cell hydrolysates of these tumor strains. Spectrophotometric determination of the total content of DNA and RNA in the tumor cells of NK/Ly showed that the inhibitory effect of the derivative was 6 times higher than that of rubomycin. Radiometric estimation of their cytostatic activity and the studies with the cells of ascitic sarcoma 37 and leukemia P-388 demonstrated that the inhibitory effect of N-ethyl-13-dihydrorubomycin was lower than that of rubomycin.

Animals↗

[Interaction of sarcolysine with beta-adrenoreceptors in tumor cells].

The sites of specific binding of 3H-L-dihydroalprenolol (3H-DHA) were identified on the surface of ascites sarcoma 37 cells, using competitive displacement and binding of the beta-adrenergic antagonists, 3H-DHA and L-propranolol. These binding sites possessed the properties of beta-adrenergic receptors coupled with adenylate cyclase. Analysis of 3H-DHA binding by the Scatchard method revealed the presence of beta-adrenergic receptors of two types, i. e., with a high (Kd = 0.9-1.0 nM) and low (Kd = 15-20 nM) affinity for 3H-DHA. The number of high affinity receptors was (5.0-7.5) X 10(3); that of low affinity receptors was (20-30) X 10(3) on a per cell basis. Sarcolysine at concentrations of 1-10 microM displaced receptor-bound 3H-DHA, competed with the ligand for the common binding sites and caused, similar to isoproterenol, a short-term elevation of the intracellular cAMP content. Sarcolysine within the same concentration range (2.5-25 microM) caused non-competitive inhibition of the cAMP phosphodiesterase (PDE2) activity of plasma membranes isolated from ascites sarcoma 37 cells. The data obtained point to the functional coupling between beta-adrenergic receptors, adenylate cyclase and membraneous PDE2 of tumour cells as well as to its possible role in the antitumour effect of sarcolysine.

Adenylyl Cyclases↗

[Oxygen status of transplantable murine tumors and its change during radiotherapy].

The degree of oxygenation in sarcoma 37, Lewis' carcinoma and melanoma B-16 of mice has been shown to depend on a tumor type (the most marked degree in sarcoma 37), it decreases from the periphery and with tumor growth. In single and fractionated irradiation the oxygen tension increases considerably in large size tumors and in the central zones of small size tumors. In melanoma B-16 reoxygenation is insignificant. It is assumed that the oxygen status plays an important role in the radiation response of large size tumors only.

Animals↗

[A clinical analysis of 153 uterine sarcomas].

OBJECTIVE: To evaluate the prognostic factors and treatment methods of 153 uterine sarcomas. METHODS: 153 cases of the uterine sarcoma were eligible for this retrospective study. Of the 153 cases, 48 were leiomyosarcomas, 47 mixed mesodermal sarcomas, 37 endometrial stromal sarcomas, 8 carcinosarcomas, 4 sarcoma botryoides, 1 fibrosarcoma, and 8 malignant lymphomas. 81 cases were in stage I, 11 stage II, 33 stage III and 11 stage IV. 38 cases were treated by surgery alone, 24 by surgery combined with radiation therapy, 50 by surgery plus chemotherapy, 23 by surgery plus radiation therapy and chemotherapy, 4 by radiation therapy alone, 3 by chemotherapy alone, and 11 by radiation therapy plus chemotherapy. RESULTS: The overall 5-year survival rate was 49.0%, and that of leiomyosarcomas, mixed mesodermal sarcomas and endometrial stromal sarcomas was 46.9%, 34.1% and 69.3% respectively (P < 0.01). The 5-year survival rate of lesions limited to the uterus (stage I + II), and that of pelvic cavity invasion (stage III) and distant metastases was 59.6%, 25.6% and 10.0% respectively (P < 0.01. When the uterus was smaller than a 3 months pregnant uterus, the 5-year survival rate was 49.9%. When the uterus size larger than a 3 months pregnant uterus, the survival rate was 18.8% (P < 0.05). Premenopausals surviving 5-year accounted for 56.3% and post-menopausal 28.9% (P < 0.01). CONCLUSIONS: The prognosis of uterine sarcoma is significantly associated with histologic type, clinical and surgico-pathological stage, uterine size and pre- or post-menopausal status. Radiation or chemotherapy alone is palliative. Postsurgical adjuvant radiotherapy significantly decreased vaginal and pelvic recurrences rates. A combination of surgery, radiotherapy and chemotherapy can reduce pelvic recurrence as well as enhance survivals.

Adolescent↗

[Blood flow in normal and tumor tissue during hyperthermia].

The authors reported the results of measurements of the blood flow in subcutaneous fat and 3 types of tumors (sarcoma 37, Lewis carcinoma, melanoma B16) by a thermoelectric method during local hyperthermia of mouse limbs. In the first minutes of exposure the blood flow rate increased reaching a plateau in 25-35 min. Changes in the blood flow grew with raising the temperature of heating, and they were more noticeable for normal tissues than for tumorous ones. The blood flow enhancement varied in different tumors: the highest in sarcoma 37, and the lowest in melanoma B16. In some tumors after prolonged heating (over 30 min.) and at high temperature (44 degrees C) a maximum increase in the blood flow was followed by its weakening.

Adipose Tissue↗

The effect of plasmacytomas on serum immunoglobulin levels of BALB/c mice.

The effect of tumor growth on serum immunoglobulin levels and on the immune response to sheep erythrocytes (SRBC) was studied in BALB/c mice bearing MOPC-315 (IgA), MOPC-460 (IgA), MOPC-173 (IgG2a) and MOPC-104E (IgM) to gain insight into the immunologic competence of the plasmacytoma-bearing host. The initial increase of myeloma protein coincided with the first appearance of the tumor and increased as the tumor progressed. However, at the time of death there was little correlation between spleen weights, tumor size, and myeloma-protein levels. The mean serum concentration of the myeloma proteins reached a higher level in the mice bearing tumors transplanted i.p. compared to those with tumors transferred subcutaneously (s.c.). Non-myeloma immunoglobulin levels in the serum were reduced: IgM was significantly lowered in the presence of MOPC-315 injected i.p. and MOPC-460 injected s.c. and the IgG2 levels were depressed in mice injected i.p. with MOPC-315 and MOPC-104E. The only significant reduction of IgA levels was seen when MOPC-173 was transplanted i.p. The decreases observed in immunoglobulin levels correlated with plasmacytoma growth. They were specific for myeloma and were not due to tumor growth per se since the levels of all immunoglobulins tested increased in the presence of Sarcoma 37, a pleomorphic neoplasm. The primary plaque-forming cell (PFC) response of tumor-bearing animals after the injection of 0.5 ml of 10% SRBC was either similar or enhanced compared to the controls. However, with a lower SRBC dosage (0.5 ml of 2% SRBC) the indirect PFC were reduced with mice bearing MOPC-104E and MOPC-173. Tumor sizes did not seem to correlate with reduction of the PFC response. MOPC-460-bearing mice had a comparable number of PFC per spleen to those of the controls, but reduced numbers when calculated per 10 spleen cells. Consistently, hemagglutination titers were reduced in all tumor-bearing animals. The number of direct and indirect PFC per spleen was increased in mice bearing Sarcoma 37, compared to the controls. The possible implications of these findings are discussed.

Animals↗

Similarity of host responses elicited by polysaccharides of animal and plant origin and by bacterial endotoxins.

Ten polysaccharides, isolated from various animal and plant sources, were selected for comparison with 2 bacterial polysaccharides, typical of Gram-negative endotoxins. The tissue sources were: mouse (kidney, liver, lung, stomach, Sarcoma 37, and Carcinoma 241-6); rabbit skin and chick embryo skin; and tangerine and Bryonia root. The bacterial endotoxins were those of S. typhosa and Serr. marcescens. Their relative potency was determined in inducing the following host effects: fever, tolerance to pyrogenic action, leucocytic changes, the Shwartzman reaction, damage to Sarcoma 37, dermal hemorrhagic-necrosis by epinephrine, enhancement of antibody production, and lethality. Some of the polysaccharides were consistently active in all the host reactions studied; except for pyrogenic activity at high dosage, the other polysaccharides were consistently negative throughout. The mouse tissue polysaccharides elicited all the effects studied; in some instances their potency approached those of the bacterial polysaccharides. It is pointed out that elicitation of the above array of biological phenomena, hitherto considered characteristic of bacterial endotoxins, can be obtained with polysaccharides from animal and plant tissues.

Animals↗

[Radiosensitizing effect of interferon synthesis inducers].

The preinjection of inductors of leukocytic interferon synthesis of rapid (poly I.poly C, dextransulfate) and slow (tyloron) types to mice bearing inoculated solid sarcoma 37 considerably increases the efficiency of X-irradiation of tumors: the coefficient of tumor growth inhibition (kappa *) exceeds 1.0, and the number of animals with the completely regressed tumors increases. The effectiveness of the procedure depends on the time of the injection of the preparations and modes of irradiation.

Animals↗