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PubMed1982

Impairment of feeding response to cold exposure of rats bearing Walker 256 carcinosarcoma.

The feeding response to cold exposure of male Sprague-Dawley rats bearing Walker 256 carcinosarcoma has been measured at 5 degrees, 13 degrees, and 17 degrees exposure. The cold-specific feeding response of the host is estimated taking account of the food cost of the tumor and of changes in food intake induced by weight change of host produced by both cold exposure and tumor growth. The cold-specific feeding response to cold exposure is depressed by about 30% by presence of tumor but is only marginally influenced by tumor size. This tumor-induced impairment of feeding response contrasts with the eventual total abolition and tumor size dependency of feeding response of tumour bearers to caloric density of food.

Animals↗
PubMed1982

Phorbol myristate acetate-induced adherence of Walker 256 carcinosarcoma cells.

Treatment of nonadherent Walker 256 carcinosarcoma cells with phorbol myristate acetate (PMA) causes these cells to become adherent to noncellular foreign surfaces such as nylon fibers and plastic culture dishes and to monolayers of endothelial cells. Increased adherence is first observed after a short lag period (5 to 15 min) and is transient. Other tumor-promoting analogs of PMA also induce this response, while inactive analogs of PMA do not. Simultaneous treatment of the cells with 2-deoxyglucose, colchicine, cytochalasin B, and cycloheximide indicates that the adherence response of the cells is an energy-dependent process that requires an intact cytoskeleton but does not require protein synthesis. Inhibitors of phospholipids and arachidonic acid metabolism including indomethacin, nordihydroguaiaretic acid, and p-bromophenacyl bromide greatly inhibit PMA-induced adherence, but acetylsalicylic acid is much less effective. PMA also increases the rate of attachment to plastic dishes of cells which would normally attach, although slowly, and grow as substrate-attached cells. However, PMA treatment has no effect on the subsequent degree of susceptibility of these cells to release from plastic dishes mediated by proteolytic enzymes. These findings suggest (a) that PMA may be useful in delineating the initial events involved in the adherence of cells to cellular and noncellular surfaces and (b) that PMA may stimulate tumor cell adherence in a manner similar to that of chemotactic peptides may be useful in delineating the events associated with chemotactic factor stimulation of these cells.

Animals↗
PubMedDate not supplied

[Metabolic study of sarcoma 45 and Walker carcinosarcoma cells during growth and anticoagulant exposure. An autoradiographic study].

Intensity of DNA, RNA and protein synthesis was estimated autoradiographically in rat tumour cells of sarcoma 45 (S. 45) and Walker carcinosarcoma (WCS). It is shown that the DNA synthesis reduces with tumour growth, the RNA synthesis in growing S.45 increases. The level of nucleic acid synthesis is higher in metastatic cells of WCS than in the initial transplant. DNA, RNA and protein synthesis in neoplastic cells decreases under anticoagulant treatment.

Animals↗
PubMedDate not supplied

[Metabolic study of sarcoma 45 and Walker carcinosarcoma cells during the process of growth and exposure to anticoagulants (an enzyme cytochemical analysis)].

The enzyme activities of lactate dehydrogenase (LDH), succinate dehydrogenase (SDH) and acid phosphatase (AP) in the rat sarcoma 45 (S. 45) cells and Walker carcinosarcoma (WCS) cells were estimated from the histochemical study. No significant changes were found in the histochemical reaction intensity during the tumour growth but at the late stage of WCS growth the LDH activity increased. WCS metastases were distinguished by the elevated enzyme activity of LDH as compared with the tumour. During the anticoagulant treatment the LDH and SDH activity in S. 45 and WCS cells falls, but the AP activity increases.

Acid Phosphatase↗
PubMed1981

Extrahypothalamic mediation of changes in feeding behavior induced by growth of Walker 256 carcinosarcoma in rats.

Feeding efficiency (amount of food ingested per unit of feeding activity) was chronically depressed in male Sprague-Dawley rats recovered from the acute aphagia or hypophagia of lateral hypothalamic damage. The extent of depression varied with the severity of the acute feeding response to hypothalamic damage. Growth of Walker 256 carcinosarcoma in intact rats increased feeding efficiency. Chronic lateral hypothalamic damage did not significantly attenuate tumor-induced increase in feeding efficiency but lowered the initial and maximum efficiency levels. Growth of the tumor-bearing host was depressed by residual lateral hypothalamic damage, but this depression was not related to the severity of the acute feeding response to damage.

Animals↗
PubMedDate not supplied

Influence of the "Corynebacterium parvum" vaccine and stilbostat on intratesticular development of Walker 256 carcinosarcoma in hyper- or hypothyroidized Wistar rats.

This work studies the effect of nonspecific antitumoral immunity produced by the "Corynebacterium Parvum" vaccine (C.P.) and Stilbostal on the development of Walker 256 carcinosarcoma intratesticularly grafted to hyper- or hypothyroidized Wistar rats. The thyroid hormone level was altered by administration of thyroxin, Alkiron or surgical thyroidectomy. The C.P. vaccine was given in a mixture with tumoral cells suspension and the treatment with the Stilbostat drug was started 5 days from grafting. The results show that C.P. administered in a mixture with tumoral cells suspension causes marked inhibition of the development of the primary tumor and metastasis, an effect which is not significantly influenced by the thyroid hormone level. The antitumoral effect of the Stilbostat drug is enhanced by administration of C.P. in tumoral cells suspension. The greatest effect produced by Stilbostal was noted in the hyperthyroidized lots in which the tumor was administered in a mixture with C.P.

Animals↗
PubMedDate not supplied

Influence of BCG on the development of 256 Walker carcinosarcoma inoculated intratesticularly in the rat, in relation to thyroid status alerations.

The effect of nonspecific antitumoral immunity caused by BCG on intratesticular development of 256 Walker carcinosarcoma has been studied on male hyper- or hypothyroidectomized rats. Thyroid hormones level was altered by administration of T4. Alkiron or thyroidectomy. The time and route of BCG administration differed from one lot to another. Authors' results show that administration of BCG before or concomitantly with the graft stimulates tumor development, whereas administration of BCG mixed with a suspension of tumoral cells causes marked inhibition in the development of primary tumor and metastasis, an inhibition which is not influenced by the thyroid hormones level. In vitro proliferation of the tumoral cells as well as histopathologic examination of the tumors suggest the involvement of a complex process in achieving the nonspecific antitumoral immunity.

Animals↗
PubMed1994

Antitumor activity of a medium-chain triglyceride solution of the angiogenesis inhibitor TNP-470 (AGM-1470) when administered via the hepatic artery to rats bearing Walker 256 carcinosarcoma in the liver.

The antitumor effect of an angiogenesis inhibitor, TNP-470 (AGM-1470, 6-0-(N-chloroacetylcarbamoyl)-fumagillol), administered via the hepatic artery in a medium-chain triglyceride (MCT) solution, in which TNP-470 is very stable, was examined in rats bearing Walker 256 carcinosarcoma in the liver. The MCT solution containing 0.1 mg of TNP-470 completely suppressed tumor growth after a single arterial injection, and the solutions containing 0.5 approximately 5 mg of TNP-470 caused tumor regression function. These antitumor effects lasted for at least 2 weeks. Moreover, the administration of the MCT solution containing 5 mg of TNP-470 also caused remarkable regression of well-developed enlarged tumors 2 weeks after inoculation, indicating potential in the treatment of unresectable hepatic cancer. When the MCT solution containing radiolabeled TNP-470 was injected via the hepatic artery, the initial radioactivity in the tumor was 22 times that in the normal part of the liver and 5.7 times that in the tumor when an aqueous solution of radiolabeled TNP-470 was injected. Also, in the case of the MCT solution, the radioactivity in the tumor was maintained at a relatively high level for over 2 weeks after injection. These results indicate that the remarkable antitumor effect resulted from the selective delivery and prolonged retention of TNP-470 at the tumor site.

Alanine Transaminase↗
PubMed1978

[The heparin-dependent inhibition of the accumulation of 131J-fibrinogen in the solid form of Walker-256-carcinosarcoma of the rat (author's transl)].

The intravenous injection of 131J-fibrinogen results in a selective accumulation of radioactivity in the solid Walker-256-carcinosarcoma of the rat. An effective anticoagulation with heparin beginning before administration of the radio-iodinated fibrinogen and continued up to the end of the experiment inhibits the enrichment of radioactivity. It is supposed that the radioactivity in the tumor is correlated to the deposition of 131J-fibrin. A clotting process in tumor transforms both fibrinogen and 131J-fibrinogen to fibrin resp. 131J-fibrin. This conversion is thrombin-dependent might be blocked by heparin. The tumor growth is not influenced by the presence of heparin.

Animals↗
PubMed1975

Temperature and blood flow measurements in and around 7,12-dimethylbenz(a)anthracene-induced tumor and Walker 256 carcinosarcomas in rats.

By means of an implanted transmitter, a circadian rhythm of temperature was found both in 7,12-dimethylbenz(a)anthracene-induced tumors and in Walker 256 carcinosarcomas. There was no significant difference in the temperatures of the two tumors. The temperature was lowest in periods of rest, and the temperature difference between light and dark periods was about 1 degree. Both tumors were found to have a higher temperature than that of s.c. tissue. External temperature measurements of the skin covering the 7,12-dimethylbenz(a)anthracene-induced tumor by thermistor probe and by thermography showed a temperature 1-2 degrees below the temperature of surrounding skin areas. In the 7,12-dimethylbenz(a)anthracene-induced tumors the blood flow was low, which should correspond to a relatively small heat production, although the temperature was relatively high. Blood flow in skin overlying tumor was high, presumably a perifocal hyperemic reaction, although the temperature was relatively low in this area. Thus tissue temperatures was not indicative of blood flow.

9,10-Dimethyl-1,2-benzanthracene↗
PubMedDate not supplied

[Activity of the pyruvate dehydrogenase complex in Walker-256 carcinosarcoma].

Pyruvate dehydrogenase complex activity in the coarsely purified enzyme fractions (supernatant and mitochondrial extract) isolated from Walker-256 carcinosarcoma is shown to be much lower than the complex activity in the rat brain. Acetoin was not found in the incubation medium containing pyruvate dehydrogenase tumour complex. The rate of the reaction of nonoxidative formation of acetaldehyde by pyruvate dehydrogenase complex of the tumour was approximately five times lower than the rate of reaction catalyzed by the complex from the rat brain. It is shown that in the presence of adenine nucleotides AMP, ADP or ATP (0.5 mM) in the medium pyruvate: NAD+ oxidoreductase activity of the tumour complex is inhibited by 40-56% as compared to the control and reaction of nonoxidative decarboxylation of pyruvate is approximately 2 times activated. It is supposed that the accumulation of nonoxidative reaction products may be an essential factor for development and functioning of the tumour.

Adenosine Diphosphate↗
PubMed1993

Enhanced therapeutic effect against liver W256 carcinosarcoma with temperature-sensitive liposomal adriamycin administered into the hepatic artery.

The antitumor activity of Adriamycin encapsulated in temperature-sensitive liposomes combined with local hyperthermia (HT) was tested in rats bearing well-developed liver W256 carcinosarcoma tumors. Two h after rats received Adriamycin encapsulated in temperature-sensitive liposomes via either the hepatic artery (i.a.) or the femoral vein (i.v.) or free Adriamycin i.a., liver HT was applied at 42 degrees C for 6 min. In animals treated with liposomal Adriamycin i.a., HT resulted in a 38% reduction in the tumor volume ratio and a 2.2-fold increase in the life span of the animals. In animals treated with liposomal Adriamycin i.v. or free Adriamycin i.a., HT did not alter the tumor volume ratio or life span of the animals. Administration i.a. of liposomal Adriamycin markedly increased the tumor drug levels (4-14-fold), reduced the systemic distribution of the drug, and slowed the drug decrease from both the tumor and liver compared with animals treated i.v.. Liver HT in animals treated with liposomal Adriamycin i.a. further increased tumor drug levels by 1.5-2.6-fold, further slowed the drug decrease from the tumor, and resulted in a dissociation of the parallel decrease of drug and lipid from the tumor. This latter effect was not observed in the other groups. These pharmacological findings combined with the lack of beneficial effect from HT in animals treated with free Adriamycin i.a. or liposomal Adriamycin i.v. suggest that i.a. administration of Adriamycin encapsulated in temperature-sensitive liposomes results in a significant retention of intact liposomes in the tumor vasculature that are able to release the encapsulated drug into the tumor cell compartment upon raising the temperature to the phase transition level.

Animals↗
PubMed1977

Pathogenesis of anemia in rats with Walker 256 carcinosarcoma.

The purpose of this study was to further clarify the pathophysiology of anemia in malignancy. To accomplish this end a total of 210 normal or splenectomized rats with or without the solid form of Walker 256 carcinosarcoma was studied. In vivo studies demonstrated that in stage I cancer (tumor weight less than 10% of body weight) a slightly shortened red cell survival resulted in a mild degree of anemia. With increasing tumor size, 51Cr red cells mass decreased further, in spite of extramedullary erythropoiesis and a slightly increased incorporation transferrin-bound iron into red cells. Splenectomized rats with stage II cancer developed a more profound degree of anemia associated with a significantly decreased incorporation of 59Fe into red cells. Marrow cell culture studies demonstrated that heme synthesis in response to erythropoietin in stage I cancer was not significantly different from normal, but in rats with stage II cancer (tumor weight greater than 10% of body weight) heme synthesis in response to erythropoietin was markedly decreased. In vitro studies demonstrated that plasma erythropoietin levels were appropriately increased in most rats with transplanted malignancy. These studies indicate that bone marrow heme synthesis in response to erythropoietin is impaired in rats with the anemia of advanced malignancy.

Anemia↗
PubMedDate not supplied

Endocrine implications in experimental tumoral metastasis. III. The influence of the thyroid status on the metastasis of 256 Walker carcinosarcoma intratesticularly grafted and on the in vitro proliferation of the tumoral cells.

The influence of thyroid status modifications on the metastasis of 256 Walker carcinosarcoma intratesticularly grafted to rats was examined. Inhibition of metastasization and of the secondary tumoral growth was noticed in animals chronically treated with thyroxine, while hypothyroidization realized either by surgery or by administration of synthetical antithyroid drugs enhanced metastasization and growth of the secondary tumors. The primary tumoral development was not significantly influenced by the thyroid status modifications. The variations of the thyroid hormonal level influenced nonspecifically the proliferation of the in vitro cultivated tumoral cells.

Animals↗
PubMed1976

In vivo studies on the mechanism of action of the tumor inhibitor vernolepin in the Walker 256 carcinosarcoma.

Rats bearing the Walker 256 intramuscular carcinosarcoma were treated intraperitoneally with tritium-labeled vernolepin or with its nontumor-inhibitory methanol adduct. Following treatment with 3H-vernolepin on several different dosage schedules, the tumors were found to contain significantly more radioactivity per gram wet weight than control tissue (muscle from the contralateral limb). After the administration of the nontumor-inhibitory methanol adduct, no such difference was observed. The distribution of radioactivity in various other organs (liver, kidney, spleen, intestine, lung, heat, fat, blood, and brain) was measured following treatment with the parent compound (3H-vernolepin). The implications of these data in terms of the suggested mechanism of action of sesquiterpene lactone tumor inhibitors is discussed.

Animals↗