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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism of human interleukin (IL)-1 beta-mediated cytolysis was studied in a human melanoma cell line, A375.6. Purified recombinant human IL-1 beta produced 50% cytocidal activity at 50 pg/ml. A variety of compounds were tested for their ability to interfere with A375.6 lysis. Compounds were added simultaneously with IL-1 beta (100 pg/ml), and tumor cytolysis was measured after 72 hr of culture by release of 125I from DNA of A375.6 cells labeled with [125I]-dUrd. A variety of anti-inflammatory/immunosuppressive agents (including auranofin, chloroquine, cyclosporin A, d-penicillamine) and several cyclooxygenase/lipoxygenase inhibitors (AA-861, BW755c, and indomethacin) lacked protective activity. Similarly, phospholipase inhibitors (mepacrine and 4-bromophenacyl bromide), putrescine, inhibitors of lysosomal activity (chloroquine and NH4Cl), calcium channel blockers (nifedipine and verapamil), calmodulin inhibitors (W-7 and calmidazolium), and inhibitors of ADP ribosylation (nicotinamide and 3-aminobenzamide) were inactive. In contrast, corticosteroids (dexamethasone, hydrocortisone, and paramethasone acetate), tilorone, and protein kinase C inhibitors (1-[5-isoquinolinyl-sulfonyl]-2-methylpiperazine and staurosporine) significantly inhibited IL-1 beta-mediated A375.6 cytolysis. These compounds also interfered with tumor necrosis factor-mediated lysis of A375.6, suggesting common mechanisms of tumor cytotoxicity by these monokines. This model may be useful for delineating intracellular biochemical events integral to IL-1 action.
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PMID:Potent inhibition of interleukin 1 beta-mediated human melanoma (A375.6) lysis by corticosteroids, staurosporine, and tilorone. 262 25

Blood platelets are implicated in a series of cellular recognition and adhesion phenomena (adhesion to the subendothelial matrix and platelet aggregation) which are key events in the processes of haemostasis and thrombosis. Platelet aggregation is a model of homotypic cellular adhesion. It is mediated by the binding of bifunctional molecules of fibrinogen to the plasma membrane of adjacent platelets, following stimulation of the platelets by agonists such as ADP, thrombin or collagen, with the fibrinogen serving as an intercellular glue. The platelet receptor for fibrinogen is a macromolecular complex, GPIIb-IIIa, made of two transmembrane glycoproteins, GPIIb (Mr = 142,000) and GPIIIa (Mr = 99,000), assembled into a heterodimer whose conformation depends upon the binding of calcium (Ca2+) to GPIIb. Furthermore, the GPIIb-IIIa complex represents the prototype, and one of the most studied, among a large family of membrane receptors, the integrins, all implicated in various adhesion processes. Binding of fibrinogen to GPIIb-IIIa occurs through interactions between peptide sequences within the receptor and particular adhesive sites within the ligand: thus, GPIIIa can bind to a tetrapeptide sequence of the A alpha chain of fibrinogen, whereas a dodecapeptide of the gamma chain can be preferentially bound to GPIIb. On a physiopathological point of view, qualitative or quantitative defects of GPIIb-IIIa are associated with a rare haemorrhagic syndrome, Glanzmann' thrombasthenia. Its central role in platelet aggregation and thrombogenesis, together with a potential role in tumor cell-platelet interactions and in metastasis, make GPIIb-IIIa, nowadays, an important pharmacological target.
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PMID:[The platelet fibrinogen receptor: a model for the analysis of cellular adhesion mechanisms and their modification in pathology]. 269 68

To elucidate the correlation of platelet aggregating activity of tumor cells and their metastatic potentials, we established a highly and a low metastatic clone with a different platelet aggregating activity from murine fibrosarcoma (Meth A). The parental Meth A cell and its low metastatic clone (ML-01) showed a typical platelet aggregation pattern with a certain lag time, while a highly metastatic clone (MH-02) showed a biphasic aggregation with no lag time in which the first reversible aggregation was caused by ADP released from MH-02, since it was eliminated by apyrase treatment. The highly metastatic potential, however, was not solely due to the platelet aggregating activity because the administration of PGI2-analogue TEI-8153A did not completely inhibit their pulmonary metastasis. In fact, MH-02 attached more preferentially to type IV collagen or endothelial cell than ML-01 in vitro. These results suggest that MH-02 exerts its high metastatic property through the mechanisms involving multiple factors such as the increased platelet aggregating potential or enhanced adhesiveness.
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PMID:[Blood coagulation and metastasis]. 273 22

The cellular ATP content and the phosphorylation potential, defined as the ATP, ADP and inorganic phosphate (Pi) ratios, of exponentially growing Ehrlich ascites tumour cells were compared with cells at the plateau phase of growth. These phosphorus compounds were measured using 31P-NMR-spectroscopy immediately after removal of the cell material from the host and in their ascites fluid reflecting in vivo growth conditions. Reaching the plateau phase of growth, the ATP content and the phosphorylation potential decreased. Upon addition of glucose, the phosphorylation potential immediately increased. We concluded that the reduced phosphorylation potential was due to a limited availability of glucose in spite of the nearly normal blood glucose concentration found. An increasing diffusion distance from the host to all parts of the tumor is a possible reason for that.
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PMID:31P-NMR-spectroscopy measurements of energy metabolism of in vivo growing ascites tumours following addition of glucose. 273 18

We studied the effects on platelet function of cells isolated from freshly dissociated human tumor tissues (11 breast carcinomas, 9 colon carcinomas and 1 lymph node metastasis from melanoma) obtained at surgery as compared with cultured human tumor cells: namely, human melanoma 1402 cell line derived from a primary tumor and two lines derived from lymph node metastases (ME 7110/2 and Me 665/1) as well as a human hepatoma cell line (Hep G2). The three melanoma cell lines activated platelets by producing ADP, as evidenced by the inhibitory effect of apyrase and by the direct measurement of the agonist in the supernatants of tumor cell suspensions; this production was much greater by the cells derived from metastases than by the cells derived from the primary tumor. On the other hand, aggregation induced by Hep G2 hepatoma cells was unaffected by apyrase and was inhibited by hirudin or concanavalin A, suggesting that the cells aggregate platelets by producing thrombin, probably through tissue factor activity of the cells themselves. Cells isolated from 16 of the 21 human tumor tissues possessed a potent platelet-aggregating effect, which was not inhibited by apyrase, hirudin or concanavalin A, but was virtually abolished by the cysteine protease inhibitors iodoacetic acid or p-hydroxymercuri-phenylsulfonate. Collectively, our data demonstrate that cells isolated from freshly dissociated tumor tissues activate platelets through tumor-associated cysteine proteinases rather than by the ADP- or thrombin-dependent mechanisms characteristic of cultured human tumor cell lines.
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PMID:Mechanisms of platelet activation by cultured human cancer cells and cells freshly isolated from tumor tissues. 276 27

The properties of the adenylate cyclase from forskolin-resistant mutants of Y1 adrenocortical tumor cells was compared with the properties of the enzyme from parental Y1 cells in order to localize the site of mutation. In parental Y1 cells, forskolin stimulated adenylate cyclase activity with kinetics suggestive of an interaction at two sites; in mutant cells, forskolin resistance was characterized by a decrease in enzymatic activity at both sites. Forskolin potentiated the enzyme's responses to NaF and guanyl-5'-yl imidodiphosphate (Gpp(NH)p) in parent and mutant clones, and the mutant enzyme showed the same requirements for Mg2+ and Mn2+ as did the parent enzyme. The adenylate cyclase associated with forskolin-resistant mutants was insensitive to ACTH and was less responsive to Gpp(NH)p than was the parent enzyme. In parental Y1 cells and in the forskolin-resistant mutants, cholera toxin catalyzed the transfer of [32P]ADP-ribose from [32P]NAD+ into three membrane proteins associated with the alpha subunit of Gs; however, the amount of labeled ADP-ribose incorporated into mutant membranes was reduced by as much as 70%. Both parent and mutant membranes were labeled by pertussis toxin to the same extent. The insensitivity of the mutant adenylate cyclase to ACTH and Gpp(NH)p and the selective resistance of the mutant membranes to cholera toxin-catalyzed ADP-ribosylation suggest that a specific defect associated with Gs is involved in the mutation to forskolin resistance in Y1 cells.
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PMID:Forskolin-resistant Y1 mutants harbor defects associated with the guanyl nucleotide-binding regulatory protein, Gs. 282 64

Y1 adrenal tumor cells are resistant to the steroidogenic effect of A-II though they possess specific A-II binding sites. The number of these binding sites is lower in Y1 cells than in bovine adrenal cells, but the affinity is similar in the two models. Moreover, Y1 cells are shown to contain a high level of cytosolic protein kinase C whose properties appear similar to those observed in bovine adrenal cells. However, the activation of protein kinase C by a phorbol ester (PMA) or diacylglycerol (OAG) does not induce steroidogenesis in Y1 cells. On the other hand, A-II, without any effect on adenylate cyclase in basal conditions, reduces the ACTH-induced cAMP production in Y1 cells. This inhibitory effect of A-II is not blocked by phosphodiesterase inhibitor but is completely abolished after 24 hours of pretreatment of intact cells with pertussis toxin. This inhibition is probably mediated by the inhibitory guanine nucleotide regulatory protein (Gi) since the labeled 41 KD-ADP ribosylated protein disappeared after 24 hours of pretreatment of intact cells with pertussis toxin. Moreover, the accumulation of inositol phosphates under A-II stimulation was low, which suggests that the coupling of A-II receptors with phospholipase C is reduced in Y1 cells. The Y1 cell line is probably a good model to study the post membrane events in A-II action.
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PMID:Angiotensin II (A-II) steroidogenic refractoriness in Y-1 cells in the presence of A-II receptors negatively coupled to adenylate cyclase. 282 18

Simian virus 40 (SV40) large tumor antigen (T antigen) binds to two contiguous sites at the SV40 origin of replication. Of these two sites, I and II, only site II is critical for replication. We have studied the interaction between T antigen and these sites by two methods--nitrocellulose filter binding and DNase I protection. We show that T antigen binds with high occupancy to site I at 0 degrees C, 25 degrees C, and 37 degrees C but to site II only at 0 degrees C and 25 degrees C. At 37 degrees C, the temperature essential for the initiation of SV40 DNA replication in vitro, ATP is required for the interaction of T antigen and site II. ATP can be replaced efficiently by adenosine 5'-[beta,gamma-imido]triphosphate and ADP, suggesting that hydrolysis of the nucleotide is not essential for the binding of T antigen to site II. The binding to the region critical for replication can occur in the presence of a variety of nucleoside triphosphates; dATP supports binding at a concentration 1/30th that of ATP, while dGTP and rGTP were inactive at all concentrations tested.
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PMID:ATP stimulates the binding of simian virus 40 (SV40) large tumor antigen to the SV40 origin of replication. 282 77

When the cytosol of Ehrlich ascites tumor cells was fractionated by chromatofocusing in the pH range of 9 to 6, two active peaks (I and II) of tRNA nucleotidyltransferase were obtained. Fraction I was a multiple complex with a high molecular weight (M.W. greater than 300K) and fraction II comprised components derived from fraction I. Fraction II was separated into tRNA nucleotidyltransferase (M.W., ca. 46,000) and nucleosidediphosphate kinase (M.W., ca. 74,000) by subsequent Sephacryl S-200 chromatography. The two enzymes appeared to be associated loosely with each other. Using the above fraction II or a mixture of the purified tRNA nucleotidyltransferase and nucleosidediphosphate kinase, it was possible to effectively synthesize the 3'-terminal -pCpCpA of tRNA in a reaction mixture containing [3H]-CDP plus XTP or [3H]ADP plus XTP as substrate. Among the XTPs investigated, dTTP was most effective. In addition, it was found that [3H]AMP + XTP also serves as a substrate. [14C]CMP plus XTP, however, was not utilized. From the antagonism of cold CDP against [3H]CTP, and that of cold ADP and AMP against [3H]ATP with the purified tRNA nucleotidyltransferase, the affinity of CDP to the enzyme was estimated to be 1/100 of that of CTP, while the affinities of ADP and AMP to the enzyme were 3 and 30 times higher, respectively, than that of ATP, suggesting that the subsite which binds ATP also binds ADP or AMP. The tRNA nucleotidyltransferase, which had bound ADP or AMP, could not completely synthesize the 3'-terminus of tRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Possible regulation by nucleosidediphosphate kinase involvement of the synthesis of tRNA 3'-terminal -pCpCpA in mammalian cells. 283 Feb 45

Toxic shock syndrome toxin-1 (TSST-1) is a 22-kDa exotoxin produced by most Staphylococcus aureus strains responsible for toxic shock syndrome. TSST-1 is a mitogen for human T cells. The mechanism of T cell activation by TSST-1 was investigated. TSST-1 induced IL-2R expression, IL-2 synthesis, and proliferation in T cells in a monocyte-dependent fashion. Neither IL-1 nor IL-2, alone or in combination, substituted for monocytes in supporting TSST-1-induced mitogenesis. We investigated the mechanism by which TSST-1 induces initogenesis. TSST-1 failed to induce ADP-ribosylation of T cell membrane proteins. However, the toxin induced transient translocation of protein kinase C from cytosol to plasma membranes and also induced the mobilization of cellular Ca2+ stores in both PBMC and the Jurkat human tumor T cell line, suggesting that TSST-1 triggered inositol phospholipid turnover. This was directly demonstrated to be the case in both cellular preparations studied. TSST-1 induced the increased synthesis of the inositol phospholipid phosphatidyl inositol, phosphatidyl inositol-4 phosphate, and phosphoinositol inositol-4,5-bisphosphate, and induced the breakdown of inositol phospholipid as evidence by the accumulation of phosphatidic acid and inositol phosphates. We conclude that the action of TSST-1 involves the induction of inositol phospholipid turnover, protein kinase C activation, and mobilization of cellular Ca2+ stores. This effect is similar to that of mitogenic lectins and of anti-CD3 antibodies.
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PMID:Toxic shock syndrome toxin-1 induces inositol phospholipid turnover, protein kinase C translocation, and calcium mobilization in human T cells. 283 Mar 36


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