SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
The influence of rotational magnetic field on Walker's carcinosarcoma growth was studied. The antitumor effect of the field was established. In some cases, tumor growth was inhibited by more than 80-90%. The antitumor effect was related to induction value, duration of daily exposure and period of time between transplantation and start of treatment.
In vivo studies with L-[13N]glutamate in the Walker 256 carcinosarcoma implanted under the renal capsule of female Sprague-Dawley rats demonstrate that uptake of glutamate and the rate of incorporation of the nitrogen label from this amino acid into metabolites is slower in the tumor than in nontumorous kidney tissue. Glutamate dehydrogenase, glutaminase, and alanine aminotransferase activities are significantly lower within the tumor than within the adjoining kidney. However, the tumor expresses high levels of aspartate aminotransferase, attesting to the importance of this enzyme in the metabolism of glutamate. Indeed, high performance liquid chromatographic analysis showed that the principal metabolic fate of label derived from L-[13N]glutamate in the tumor is incorporation into aspartate. Measurement of specific activity ratios of glutamate to aspartate shows that the transfer of nitrogen from glutamate to aspartate is rapid and that equilibration of label among components of the aspartate aminotransferase reaction is attained within minutes after tumor uptake. Analyses of the nontumorous portion of the implanted kidney also showed that aspartate is the major recipient of glutamate nitrogen. However, high performance liquid chromatographic analyses of deproteinized tissue revealed that glutamine and ammonia are also significant 13N-labeled metabolites formed from L-[13N]glutamate within the kidney. Proportionately lower amounts of these labeled metabolites were found in the tumor.
The pharmacokinetics of fluorescein, hematoporphyrin and a derivative of hematoporphyrin was studied microspectrofluorometrically on rats with transplanted carcinosarcoma. It was shown that in the rats in contrast to intact animals the tissue concentration of fluorescein exhibits a general tendency towards an increase, that of hematoporphyrin towards a decrease and that of hematoporphyrin derivative towards an increase in all parenchymatous organs and a decrease in the skin and mucosae of the hollow organs. At the equally short period of the maximal accumulation of luminophores, the tumour tissue differs from the normal one by a pronounced delay of excretion only of hematoporphyrin derivative.
It has been shown that the local radiation therapy, and also radiation therapy modified by the short-term hyperglycemia really increase the life-span of rats with Walker 256 carcinosarcoma. At the same time the metastatic process also increases, especially after the modified radiation therapy. The total irradiation of experimental animals in a dose of 50 sGy before the modified radiation therapy considerably decreases the frequency of metastatic process. A conclusion is drawn that the total irradiation has a prophylactic influence on metastases under conditions of modified radiation therapy.
In a series of experiments the alpha-glycerophosphate dehydrogenase and succinate dehydrogenase (SDH) activities were daily determined simultaneously by the cytochemical method in peripheral blood lymphocytes of normal rats and those with the Walker carcinosarcoma. Using an original algorithm a hierarchy of biorhythms was singled out by a computer according to individual changes in the dehydrogenase activity for each rat. The mean level of succinate dehydrogenase activity was higher than that of alpha-glycerophosphate dehydrogenase. A set of discovered biorhythms and their representation were identical in the both enzymes. The tumor transplantation caused changes in the phase coordination of investigated dehydrogenases in all rhythms and promoted an increase of the succinate dehydrogenase amplitude as compared with the alpha-glycerophosphate dehydrogenase amplitude in certain rhythms. It is concluded that biorhythmological parameters of these enzymes may be used for characterization of the tumor-bearing host.
The intravenous injection of ferromagnetic particles (FMP) was studied for its effect on the growth of Walker 256 carcinosarcoma in Wistar rats. The injection of FMP in a dose of 750 mg/kg increased the organism resistance to the tumour development against a background of phagocytic reaction activation in neutrophils. The injection of FMP in a dose up to 2 g/kg inhibited the phagocytic reactions of neutrophils and accelerated the tumour growth. The data obtained evidence that depending on the FMP dose the total reactivity of the organism may either increase or decrease, thus changing, respectively, its resistance to the development of the tumour process.
Human tumor necrosis factor alpha (TNF) inhibits tumor growth, but its effects on tumor and skeletal muscle protein metabolism in vivo have not been adequately studied. Walker 256 carcinosarcoma growth rate was followed over an 11-day period in Sprague-Dawley rats. Tumor-bearing rats received either saline or 50 micrograms of TNF (Genentech, Inc.) s.c. on day 8 of tumor growth. This single dose of TNF reduced tumor protein growth during a 2-day posttreatment period from 27.6 +/- 4.4 to 10.5 +/- 3.7%/day (mean +/- SE; P less than 0.01). The rate of in vivo incorporation of L-[1-14C]leucine into skeletal muscle protein was significantly increased (P less than 0.05) from 5.1 +/- 0.2%/day in the saline-treated tumor-bearing rats to 7.7 +/- 1.3%/day in the TNF-treated tumor-bearing rats. The latter value was not statistically different from the 9.2 +/- 0.9%/day observed in the tumor-free control animals. TNF administration significantly increased both the total and individual acid-soluble skeletal muscle amino acid concentrations in tumor-bearing rats by an average of 86 +/- 7%, compared to values in saline-treated tumor-bearing rats. Similarly, acid-soluble skeletal muscle 3-methyl-histidine concentrations increased from 66 +/- 14 to 113 +/- 19 pmol/g protein (P less than 0.05). Tumor protein synthesis in the TNF-treated group was 50% greater than in the saline-treated group, whether expressed as %/day (72.7 +/- 9.1 versus 47.9 +/- 4.8; P less than 0.05) or was micrograms/g tumor/min (58.7 +/- 7.7 versus 40.7 +/- 4.5; P less than 0.05). In contrast, estimated tumor protein degradation rates were increased by over 200% in the TNF-treated rats, compared to the values in the saline-treated rats [62.1 +/- 10.7 versus 20.3 +/- 6.0%/day (P less than 0.01) and 50.0 +/- 8.9 versus 17.5 +/- 5.4 micrograms/g tumor/min (P less than 0.01)]. Thus, TNF appears to stimulate tumor protein degradation more than protein synthesis, explaining the overall decrease in tumor growth.
Bone is a major source of transforming growth factor-beta (TGF-beta), and a preferred target organ for metastasis of the rat Walker carcinosarcoma 256 (W256). Since chemotactic mechanisms may contribute to metastatic site specificity, we have tested the hypothesis that TGF-beta is a chemoattractant for these cancer cells. Purified platelet-derived TGF-beta elicited dose-dependent migration of W256 cells in the Boyden chamber assay with half-maximal responses (ED50) elicited by 0.12 +/- 0.01 ng TGF-beta/ml. Checkerboard analysis confirmed dependence of the response upon a concentration gradient. Conditioned media from organ cultures of bone contained TGF-beta and chemotactic activity in proportion to the extent of bone resorption. The chemotactic activity in conditioned bone culture medium and that of the purified platelet-derived TGF-beta were both inhibited after incubation with anti-TGF-beta 1. We conclude that TGF-beta, released from resorbing bone, can influence the migratory behavior of the osteotropic W256 cell line.
Cell membranes of carcinosarcoma-256 ascites cells were isolated by the Zn++ method. Neutral sugars, sialic acid, fucose and N-Acetylhexosamines were determined in the cell membrane fraction. Cells were agglutinated by wheat germ agglutinin, Concanavalin A, and the lectins from Phaseolus vulgaris and Glycine max. No agglutination was observed with peanut lectin (Arachis hypogaea). Gel electrophoresis under dissociating conditions revealed more than 40 bands in the membrane fraction after silver staining. Only 2 bands were evident with PAS staining.
Rats were randomized into splenectomised and sham-splenectomised groups (n = 15 in each). W256 carcinosarcoma cells were implanted in the subcutis of each animal 10 days after splenic operation. T cell subsets of peripheral blood were evaluated serially before and after the operation. The growth rate of implanted tumor and diameter of local tumor in the splenectomised were larger than those of the sham-splenectomised. Simultaneously T cell subsets of peripheral blood presented severe reduction of pan-T and T h/i cells and slight increase of T s/c cells in the splenectomised, all of which still remained at the lower level after tumor inoculation, as compared with the non-tumor and tumor growth in sham-splenectomised (P less than 0.01). From these data, it is evident that splenectomy results in the reduction of T h/i cells and a relative increase of T s/c cells, which shows a close correlation with the rapid growth of the tumor following splenectomy.
An examination of eighteen thiols and thio ethers revealed that the simultaneous administration of several of these with cis-platinum (CDDP) at 7.5 mg/kg (25 mumols/kg) iv, as a single injection to rats bearing the Walker 256 carcinosarcoma led to significant reduction in the nephrotoxicity typically found with cis-platinum, and no apparent interference in its anti-neoplastic action towards this tumor. The thiols and thiol ethers were administered at a twenty-fold molar excess to the CDDP and were combined with the CDDP immediately prior to administration. The most effective compounds in suppression nephrotoxicity were D-, and L-methionine, methyl and ethyl L-methioninate, and N-acetyl-D, L-methionine.
The passage of circulating tumor cells across vessel walls is an important step in cancer metastasis and is promoted by endothelial injury. Because Walker carcinosarcoma 256 (W256) cells generate oxygen-derived free radicals after cellular activation, the authors tested the hypothesis that these cancer cells can damage endothelial monolayers by producing such reactive oxygen species. To confirm that oxygen-derived radicals can damage endothelial cells, 3H-2-deoxyglucose-labeled human endothelial cell monolayers were exposed to xanthine oxidase in the presence of 0.2 mmol/l xanthine. 3H-2-deoxyglucose release was observed after the addition of xanthine oxidase in concentrations ranging from 6.5 x 10(-3) to 52 x 10(-3) units/ml. The extent of damage correlated with xanthine oxidase-dependent chemiluminescence (r = 0.91). Chemiluminescence assays in the presence of 5 x 10(-5) M luminol confirmed activation of the W256 cells by 1 x 10(-6) M chemotactic peptide fMLP. When fMLP-activated activated W256 cells were incubated with endothelial monolayers, concentrations of 2 x 10(6) to 6 x 10(6) W256 cells/ml were found to cause a 27% increase in the specific release of 2-deoxyglucose after a 90-minute incubation. A small but significant increase in 3H-2-deoxyglucose release also was observed in the absence of fMLP. Detection of 3H-2-deoxyglucose release in the presence of activated or unactivated tumor cells was dependent on preincubating the endothelial cell monolayer with 1 mM buthionine sulfoximine, an inhibitor of glutathione synthesis. Under these conditions, the specific release of 3H-2-deoxyglucose was increased from nondetectable levels to 21%, in the presence of 6.5 x 10(-3) units of the oxidase. Cultured W256 cells promoted isotope release from endothelial cell monolayers when activated with phorbol myristate acetate. Catalase (1000 units/ml) inhibited the tumor cell-induced release of 3H-2-deoxyglucose by 84% whereas superoxide dismutase, even at concentrations of 1 mg/ml, had no effect. A requirement for cell contact was shown because addition of cell-free supernatants from fMLP activated tumor cells did not cause 3H-2-deoxyglucose release and because pretreatment of W256 cells with 1 microM cytochalasin B inhibited their ability to promote isotope release even while increasing tumor cell-generated chemiluminescence threefold. Electron microscopy revealed that fewer cytochalasin B-treated W256 cells were attached to the endothelial cell monolayer than in untreated controls. It is concluded that the W256 tumor cells can damage endothelial cells directly via a mechanism involving production of reactive oxygen species.
In the series of experiments alpha-glycerophosphate dehydrogenase activity was daily determined at the same time by cytochemical method in the peripheral lymphocyte of normal rats and those with Walker carcinosarcoma. Using an original algorithm a hierarchy of biorhythms was singled out on a computer according to the individual changes in alpha-glycerophosphate dehydrogenase activity in each rat. It was shown that tumor development resulted in the reduction of the mean level of alpha-glycerophosphate dehydrogenase activity and considerable changes in diverse rhythms. Particular attention is paid to the phase changes, which can reveal changes in phase coordination of glycerophosphate shuttle cycle components.
Two morphologically distinct types of polarization and locomotion are found in Walker carcinosarcoma cells. Spontaneously polarized cells are characterized by formation of ruffles and spikes, cells polarized in the presence of microtubule-disassembling drugs by blebbing at the leading edge. Polarization and locomotion are closely correlated. Both can be stimulated by the microtubule-disassembling agents colchicine, nocodazole and vinblastine and suppressed by taxol or cytochalasin B. The results suggest that both microfilaments and microtubules may be involved in regulating polarization and chemokinesis, and that shape changes elicited by microtubule-disassembling agents depend on microfilaments.
Walker 256 rat carcinosarcoma cells growing as solid subcutaneous or intramuscular tumors depressed hepatic microsomal mixed-function oxygenase activity to less than 20% of control activity, but the same tumor cells growing as free ascites cells in the peritoneal cavity did not. Necrosis of the core area of solid tumors was observed. Tumor cells may release a substance that depresses hepatic microsomal mixed-function oxygenase activity only upon their death.
The peptide N-formyl-Met-Leu-Phe stimulates chemotaxis and metastasis in rat Walker carcinosarcoma cells by a receptor-mediated pathway. Since oxygen radical generation follows chemotactic stimulation in leukocytes, we looked for similar responses in the Walker tumor. Upon incubation with 10(-6) M N-formyl-Met-Leu-Phe, Walker cells elicited chemiluminescence in the presence of 5 X 10(-5) M luminol. The response peaked within 2 min and was maintained for greater than 20 min; it was dose dependent with a 50% maximal effective dose (ED50) value of 4.5 X 10(-8) comparable to the 50% maximal effective dose value for chemotaxis. The responses were significantly reduced but not abolished in the absence of calcium in the external medium and were elicited by the ionophore A23187. The lipoxygenase inhibitor nordihydroguaiaretic acid had almost no effect in decreasing the response, while flurbiprofen, a cyclooxygenase inhibitor was very effective at 10(-6) M. Evidence for the generation of oxygen radicals included: (a) marked inhibition of light emission in the absence of oxygen; (b) inhibition in the presence of superoxide dismutase, catalase, and mannitol; and (c) dose-dependent reduction of acetylated cytochrome c. We postulate that activation of circulating tumor cells may facilitate metastasis by the release of toxic oxygen species.
The pharmacokinetics of phthorafur-2-14C (Ph) was investigated after its intravenous injection to rats with Walker carcinosarcoma. The blood plasma level of Ph-2-14C and its metabolites proved to decrease in to a three-phase process. The content of the agent in the tissues decreased in the following sequence: the kidney, small intestine, tumour, stomach, muscle, heart, liver, lungs, spleen, brain and fat. The tumour was observed to contain Ph-2-14C and endogenous metabolite 5-phthoruracil-2-14C. Excretion of the agent continued for 48 hrs, 52.2% of the administered dose being eliminated via the urinary tract, 30% as 14CO2, and 0.8% in feces.
Specific glucocorticoid hormone receptors with Kass = 1.23 X 10(8) M-1 and the content of binding sites 5.59 X 10(-13) moles per mg of protein were found in liver cytosol of intact rats. During growth of Walker carcinosarcoma concentration of binding sites decreased approximately by 40%, whereas the affinity of receptors to the hormone did not mainly altered. At the same time, a considerable decrease was noticed in the content of free binding sites not bound with endogenous corticosteroids. After thermoactivation about 50% of 3H-dexamethasone receptor complexes acquired the ability to bind DNA, while in the same experimental conditions only about 20% of the complexes were activated in cytosol of tumor-bearing rats. With growing of the tumor thermal inactivation of the hormone-receptor complexes was not practically altered both in presence and in absence of molybdate ions. In a solution with low ion strength at 25 degrees a half-life dissociation of 3H-dexamethasone-receptor complexes was equal to 0.042 and 0.084 min-1, respectively, in cytosols of healthy and tumor-bearing rats.