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Query: UMLS:C1261473 (sarcoma)
 25,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Disturbances in the functional properties of tumor mitochondria have been studied during the course of induction of haemorrhage brought about by endotoxin in the murine Crocker sarcoma (S 180). Extensive impairment of function was already present in mitochondria isolated from control tumors, as shown by low respiratory control ratios. The existing mitochondrial damage intensified promptly in response to injection of endotoxin long before the onset of haemorrhage at 4 h. The nature of the additional damage took two forms, depending on the duration of exposure to endotoxin; first, at 30 min, a true uncoupling of oxidative phosphorylation was seen, largely reversible in vitro by pre-treatment of the isolated organelles with bovine serum albumin (BSA). Second, at 1 h and later, oxygen utilisation in the presence of succinate, ADP and inorganic phosphate (Pi) was depressed. The pre-addition of BSA consistently lowered respiration rates with succinate and Pi in all preparations. The extent of endogenous inhibition of the adenine nucleotide translocase appeared unaltered by endotoxin in vivo.
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PMID:Early mitochondrial damage in the induction of haemorrhagic necrosis in the Crocker sarcoma (S 180) by endotoxin. 38 16

The reduction in DNA, RNA, amino acid, and total protein in muscle tissue of tumor-bearing rats may influence muscle function. The effects of MCA-sarcoma tumor burden on muscle performance and adenine nucleotides was evaluated in three fiber types of skeletal muscle. Twenty-one days after MCA-sarcoma tumor inoculation, the gastrocnemius-soleus muscle group of Fischer 344 rats was stimulated using an in situ preparation; tetanic stimulation for 10 min at 7.5, 15, or 30 tetani per min (TPM) or 60 TPM for 5 min (n = 6 control and six tumor-bearing rats/group). ATP, ADP, AMP, IMP, phosphocreatine, and creatine content in white and red gastrocnemius muscle and soleus muscle was measured. There were no differences among controls and tumor-bearing rats in force output; however, ATP content in the soleus muscle of tumor-bearing rats was significantly reduced after 30 TPM for 10 min or 60 TPM for 5 min. The performance of skeletal muscle, over a wide range of stimulation frequency, in tumor-bearing rats does not appear to be influenced by changes in adenine nucleotide content.
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PMID:Muscle performance and adenine-nucleotides status in MCA-sarcoma tumor-bearing rats. 140 56

In BALB/c 3T3 cells pretreated with platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) (primed-competent cells), insulin-like growth factors I and II (IGF-I and IGF-II) bind to their own receptors (IGF-IR and IGF-IIR) and stimulate calcium influx and DNA synthesis by a mechanism involving a 40-kDa pertussis toxin substrate. In contrast, these IGFs do not act on unprimed quiescent cells. In this study, the 40-kDa pertussis toxin substrate was identified as Gi-2 alpha using anti-G protein antibodies. We analyzed the quality of signal transduction from IGF-II to Gi-2 alpha. There was no difference in the amount of Gi-2 alpha between quiescent and primed-competent cells, and both of these cells had similar Kd values and numbers of IGF-II-binding sites. Whereas IGF-II did not alter pertussis toxin-catalyzed ADP-ribosylation of Gi-2 alpha in quiescent cells, IGF-II reduced the pertussis toxin substrate activity by 35-50% via the IGF-IIR in primed-competent cells. The action of IGF-II lasted for up to 3 h when IGF-II was present in the medium, and it disappeared when IGF-II was removed. These results suggest that the signaling pathway triggered by IGF-II is uncoupled between the IGF-IIR and Gi-2 alpha in quiescent cells and that PDGF and EGF restore the IGF-IIR-Gi-2 coupling. This study also indicates that low concentrations of IGF-I reduce the pertussis toxin substrate activity of Gi-2 alpha in primed-competent cells in a time course slower than that of IGF-II, but not at all in quiescent cells. However, both of these cells had similar Kd values and numbers of IGF-I binding sites. Therefore, the IGF-I signaling pathway may also be uncoupled between the IGF-IR and Gi-2 alpha in quiescent cells and restored by PDGF and EGF. In BALB/c 3T3 cells transfected with temperature-sensitive Kirsten sarcoma virus bearing the v-Ki-ras gene (ts cells), a 40-kDa pertussis toxin substrate was also identified as Gi-2 alpha. In nonpermissive ts cells, IGF-II was without effect on the pertussis toxin substrate activity of Gi-2 alpha or on calcium influx.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of transmembrane signal transduction of insulin-like growth factor II by competence type growth factors or viral ras p21. 198 36

Effects of ATP and some other nucleotides (AMP, ADP, CTP, GTP, UTP and dATP) on reparative DNA synthesis and repair patch ligation in bleomycin-pretreated permeable mouse sarcoma cells were studied. Reparative DNA synthesis was significantly stimulated by 2.5 mM ATP, ADP or dATP. The stimulation was observed on both DNA polymerase alpha- and beta-dependent reparative DNA synthesis. ATP concentration required for repair patch ligation was much lower than that required for the stimulation of reparative DNA synthesis. An apparent Km value for ATP of the repair patch ligation was about 40 microM. ADP supported repair patch ligation after being converted into ATP by adenylate kinase in permeable cells.
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PMID:Effects of ATP and other nucleotides on DNA repair synthesis in bleomycin-pretreated permeable mouse sarcoma cells. 244 62

DNA repair in bleomycin-pretreated, permeable mouse sarcoma (SR-C3H/He) cells requires ATP for at least two steps, the repair DNA synthesis step and the repair patch ligation step. ADP can apparently replace ATP in both steps. Maximal, 1.5-2 fold stimulation of repair DNA synthesis was observed with 5-10 mM ADP as well as 2.5-5 mM ATP. Repair patch ligation in the presence of 2.5 mM ADP occurred at almost the same high efficiency as it did in the presence of ATP. The ADP effect on DNA repair patch ligation was attributed to ATP formed from ADP by adenylate kinase in permeable cells, however the ADP effect on repair DNA synthesis could not be attributed solely to the formation of ATP in the same manner.
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PMID:ADP effects on bleomycin-induced DNA repair synthesis and adenylate kinase activity in permeable mouse sarcoma cells. 247 Mar 76

Phosphatidylinositol (PtdIns) kinase activities from non-transformed and polyoma-middle-T-transformed murine fibroblasts were examined. Both normal and transformed 3T3 fibroblasts have two PtdIns kinases, which can be separated by anion-exchange chromatography. One of these activities (Type I) has a Km for ATP of 10 microM, is resistant to inhibition by adenosine, AMP or ADP, and is inhibited by non-ionic detergents. The other activity (Type II) has a somewhat higher Km for ATP (35 microM) and is inhibited competitively by ADP, AMP and adenosine at concentrations suggesting regulation of this activity by the energy charge of the cell. The Type II PtdIns kinase is activated by non-ionic detergents. We have previously reported the specific association of a PtdIns kinase activity with polyoma-middle-T immunoprecipitates [Whitman, Kaplan, Schaffhausen, Cantley & Roberts (1985) Nature (London) 315, 239-242; Kaplan, Whitman, Schaffhausen, Raptis, Garcea, Pallas, Roberts & Cantley (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 3624-3628]. Comparison of the immunoprecipitated PtdIns kinase with the activities identified by ion-exchange chromatography indicates that it is the Type I enzyme which specifically associates with the middle-T/pp60c-src complex. This PtdIns kinase activity is separable from both middle T and pp60c-src. Type I PtdIns kinase also associates with pp60v-src immunoprecipitates from Rous-sarcoma-virus-transformed cells. Furthermore, this PtdIns kinase appears to co-precipitate with partially purified platelet derived growth factor (PDGF) receptor. The amount of this activity found in anti-phosphotyrosine immunoprecipitates or in wheat-germ-lectin-agarose precipitates is increased 50-fold by stimulation of quiescent Balb/C 3T3 fibroblasts with PDGF. These results suggest that the Type I PtdIns kinase is regulated by agents which affect cell growth and transformation, whereas the Type II PtdIns kinase may be regulated by the local [ATP]/[ADP] ratio.
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PMID:Evidence for two distinct phosphatidylinositol kinases in fibroblasts. Implications for cellular regulation. 282 54

Products of phosphatidylinositol (PI) turnover have recently been implicated as regulators of cell growth and differentiation. Transformation of cells in culture by infection with certain viruses (Rous sarcoma virus, Kirsten sarcoma virus, and polyoma virus) or by transfection with the oncogenes carried by these viruses affect the steady-state level of intermediates in the PI turnover pathway. In addition, immunoprecipitates of the transforming gene products of Rous sarcoma virus and polyoma virus contain activities of certain enzymes in the PI turnover pathway. We have previously reported that polyoma middle T immunoprecipitates can catalyze phosphorylation of PI to phosphatidylinositol-4-phosphate (PIP). This activity is not intrinsic to middle T or pp60c-src but is due to a cellular enzyme that specifically associates with the middle T/pp60c-src complex. The PI kinase is found in immunoprecipitates of the middle t protein from polyoma viruses that are capable of cell transformation but does not associate with mutants of middle t defective in transformation, suggesting that this association may be important for transformation. Two PI kinases from fibroblasts (type I and type II) that are separable by anion exchange chromatography have been partially purified and characterized. These enzymes differ in their Km for ATP as well as their Ki for adenosine and ADP. Only the type I PI kinase specifically associates with the transformation-competent mutants of middle T.
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PMID:Phosphatidylinositol kinases and cell transformation. 282 83

Sarcoma cells growing in tissue culture have morphological and growth characteristics different than normal fibroblasts. Several of the morphological characteristics of normal fibroblasts are regained when the cells are incubated with dibutyryl-cyclic AMP or butyryl-cyclic AMP (0.1-1 mM), or cyclic AMP (3 mM) plus theophylline (1 mM), but not with ATP, ADP, AMP, adenine, or adenosine (1-7 mM). The cell bodies become elongated; distinct narrow processes are formed. With prolonged incubation, the cells show less tendency to pile up or become polygonal. Further, L-929 and Rous sarcomatransformed hamster cells orient in parallel arrays characteristic of contact inhibition. The cells retain their altered morphology as long as the butyryl-cyclic AMP is present, but revert after its removal. Experiments with cycloheximide, puromycin, and actinomycin D indicate that protein Synthesis, but not RNA synthesis, is required for the response. Microtubular proteins may be involved. No response is observed with normal fibroblasts or with various epithelial cells. The data suggest that cyclic AMP may be an important factor in the determination of morphology of normal fibroblasts and this function may be lost or altered during transformation.
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PMID:Restoration of several morphological characteristics of normal fibroblasts in sarcoma cells treated with adenosine-3':5'-cyclic monphosphate and its derivatives. 432 9

We have demonstrated the usefulness of several angiotensin analogs as substrates for a number of tyrosyl protein kinases of viral or cellular origin. Results of initial rate studies with pp60src at varying substrate concentrations indicated that the mechanism was sequential; Michaelis constants for ATP and peptide were 7 microM and 0.24 microM respectively and Vmax was 1.0 nmol/min/mg. The end-product ADP and the ATP analog, AMP-PNP, were competitive inhibitors at varying ATP concentrations and noncompetitive inhibitors at varying peptide concentrations. A dead-end analog of angiotensin II, [delta Phe4]-angiotensin II, was a noncompetitive inhibitor at varying ATP concentrations but induced substrate inhibition at varying peptide concentrations. The kinetic data allowed us to conclude that the reaction proceeded via an Ordered Bi Bi mechanism with ATP as the first binding substrate. The available evidence allowed us to conclude that while pp60src contained essential histidine and lysine residues in its active site, the kinase reaction does not involve a phosphoryl enzyme intermediate. Phosphorylation of the angiotensin peptides in vitro also has allowed us to demonstrate the presence of at least two tyrosyl protein kinases in the cytoplasm of normal rat liver cells. These kinases appear to be novel in that they are present in normal cells and are not stimulated by growth factors. Also, results of preliminary experiments indicate that these kinases are not immunologically related to the transforming gene products of Rous and Fujinami sarcoma viruses (unpublished observations). The identification of these new kinases represents another application of the angiotensin peptides as substrates for tyrosyl kinases (13). The results obtained do not exclude the possibility that there exist in rat liver other tyrosyl kinases that do not phosphorylate these particular peptide substrates. No attempt has been made to characterize tyrosyl kinases associated with the plasma membrane fraction. Although they represent only a small fraction of the total activity of liver cells, the plasma membrane kinases have a relatively high specific activity. These kinases may be identical with growth factor receptor kinases previously identified in liver cell membranes (5). The most abundant tyrosyl kinase in rat liver cytoplasm has a molecular weight of 75,000 daltons and was found in cytosol and microsomal salt-wash fraction. The observation that the purified 75 Kd enzyme phosphorylates a 75 Kd protein on tyrosine residues suggests that the enzyme may possess autophosphorylating activity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Properties and mechanism of action of viral and cellular tyrosyl protein kinases. 608 13

The Harvey sarcoma virus-transformed derivative of normal rat kidney cells contains a very large membrane-associated NAD+ pyrophosphatase activity. Exogenous NAD+ was metabolized into NMN, demonstrating that the enzyme was located, at least in part, on the external surface of the cell. This external location of the pyrophosphatase was used to evaluate possible extrusion of NAD+ during treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG); i.e., extruded NAD+ would be degraded to NMN. NAD+ levels quickly decreased following MNNG addition. The nicotinamide moiety of degraded NAD+ was accounted for as nicotinamide in the culture medium, and no NMN was detectable. Thus, NAD+ was not extruded during MNNG treatment. Additional studies were done to determine which enzyme system was responsible for the rapid fall in NAD+ in these cells. MNNG treatment increased (ADP-rib)n synthetase activity; moreover, this increase in activity was sufficient to account for the loss in intracellular NAD+. Also, the decrease in NAD+ during treatment with MNNG was prevented by 3-aminobenzamide, an agent which inhibited (ADP-rib)n synthetase but not NAD+ glycohydrolase or pyrophosphatase. MNNG had no effect on NAD+ glycohydrolase or pyrophosphatase activities. The results are consistent with the proposal that NAD+ is not extruded but rather is rapidly metabolized by the nuclear (ADP-rib)n synthetase during MNNG treatment.
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PMID:A pyrophosphatase which degrades NAD+ is located on the external surface of cultured fibroblasts: evidence that NAD+ is not extruded during treatment with N-methyl-N'-nitro-N-nitrosoguanidine. 614 96


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