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

It is shown that cyclic nucleotides can have a variety of effects on cell division, cell shape, cell adhesion, and cell movement, depending on the cells selected and the conditions under which they are used. For example, while CHO cells elongate under the influence of exogenous dibutyryl CAMP, Y-1 adrenal tumor cells round up and polyoma-transformed 3T3 cells show no change in shape. The totality of experience with cyclic nucleotides suggests that where they have been used by cells as control elements involving the four processes listed above, they are superimposed on basic cellular processes that progress in their absence--that is, they must be acting indirectly. In attempting to understand the inhibitory action of methyl xanthines on egg development, we were forced to abandon the idea that they acted through cyclic nucleotides. We found that methyl xanthines inhibited the activation of glutathione reductase and that glutathione oxidizing agents act as mitotic inhibitors. Further, we found that tubulin polymerizability, NAD-kinase activity, and a mitotic apparatus associated Ca+2-ATP-ase were all inhibited by oxidation of some of their sulfhydryls and were activated by reduction of the resulting disulfides. These results are discussed in terms of reported cycles and activations of glutathione reductase (GR) in cells and reports that mixed disulfides of glutathione and proteins can act as substrates for GR. Using the fact that a CAMP-dependent protein kinase has been reported to be activated by glutathione, we have suggested potential sites where sulfhydryl control processes and cyclic nucleotide control processes and cyclic nucleotide control processes may interact in certain restricted cases.
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PMID:Cyclic nucleotides, thioldisulfide status of proteins, and cellular control processes. 18 78

Steroidogenesis by Y-1 adrenal tumor cells in culture is stimulated by ATP, adenyl-5'-yl imidodiphosphate (App(NH)), adenosine 5'(beta, alpha-methylene)triphosphate (App(CH2)p), ADP, AMP, NAD, FAD, and adenosine but not by adenine or other nucleoside triphosphates. ATP, App(NH)p, App(CH2)p, and adenosine are active in the micromolar range. Like adrenocorticotropic hormone (ACTH), the onset of stimulation is immediate and occurs to the same extent. Also active are 2'- and 5'-deoxyadenosine and 2-chloroadenosine whereas adenine xyloside, L-riboside, or arabinoside have very low activity. Stimulation is accompanied by rounding of the cells. Dipyridamole, an inhibitor of adenosine transport, increased the response to low concentrations of adenosine, suggesting that adenosine acts externally. Stimulation of steroidogenesis by adenosine or phosphorylated adenosine compounds fails to occur in the presence of crystalline adenosine deaminase, and the effect of the enzyme on adenosine, ATP, or NAD stimulation is reversed by the competitive inhibitor erythro-9-[3-(nonane-2-ol)]adenine. This suggests that the enzyme acts specifically on adenosine and a requirement for the conversion of the above compounds to adenosine seems probable. The inhibition of cAMP effects by adenosine deaminase suggests that some of its effects are also mediated by conversion to adenosine. Similar stimulation is seen in I-10 Leydig tumor cells, but an ACTH-resistant mutant of Y-1 cells, called OS-3, is relatively resistant to adenosine. Adenosine and 2-chloroadenosine stimulate adenylate cyclase in membranes from Y-1 and I-10 cells at concentrations slightly greater than are effective for steroidogenesis. Other nucleosides are ineffective. Like the NH2-terminal 24 residues of adrenocorticotropic hormone (1-24 ACTH), the adenosine effect in Y-1 membranes is rapid and is on the Vmax intercept (versus ATP) and not on the Km. In contrast to steroidogenesis, adenosine is only a partial agonist for adenylate cyclase. It effect occurs in the presence of ITP, GTP, or guanyl-5'-yl imidodiphosphate (Gpp(NH)p). Theophylline inhibits adenosine-stimulated steroidogenesis. Inhibition of adenylate cyclase occurs in the same concentration range but is of the mixed type.
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PMID:Activation of steroidogenesis and adenylate cyclase by adenosine in adrenal and Leydig tumor cells. 18 24

Nineteen outpatients with malignant melanoma and squamous cell carcinoma of the head and neck, who had surgical resection for complete removal of the tumor and no demonstrable metastases following surgery, were administered Levamisole (p.o., 150 mg per day, two days per week) and maintained on this dose for at least six months. Of this group, drug therapy was discontinued in four patients because of severe "flu-like" syndromes leaving a group of 15 patients for detailed analysis. T-lymphocyte percentages and levels, cAMP levels in the lymphocytes and a battery of skin tests for recall antigens were evaluated following surgery and at various intervals during immunotherapy. Patients who responded well to the treatment showed increased levels of T-lymphocytes and increased cAMP levels, whereas non-responders had low T-cell levels and low cAMP levels. Also positive skin test reactions were observed in most patients who responded well to immunotherapy, although this was the least reliable indicator of patient response. Eight of the nine patients in the melanoma group have responded well clinically, whereas five of the six squamous cell carcinoma patients have developed recurrences.
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PMID:Immunocompetence of cancer patients treated with Levamisole. 18 94

The studies are presented which demonstrate that smooth endoplasmic membrane of normal liver has a single apparent binding site for cAMP with a KD of 0.6 X 10(-8) M. In contrast to this, however, cyclic AMP binding to the intracellular membrane of hepatoma 7800 exhibit two binding sites; the binding constant of one site on the tumor membrane is comparable to that of the normal liver whereas the value of the second intrinsic association constant differ by a factor of 10. It is suggested that there may be an association between abnormal cyclic nucleotide metabolism and the intracellular membrane modulation of the expression of genetic information in normal and neoplastic cells.
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PMID:Cyclin nucleotide binding sites of the smooth endoplasmic reticulum from normal and neoplastic liver in the rat. 18 1

Protein kinase activity has been studied in four human adrenocortical tumors and compared to the one of the normal human adrenal. In two cases where the lack of action of ACTH was related to an anomaly of ACTH receptor, the protein kinase activity was normal. In the other two cases the ACTH receptor was normal, but the protein kinase activity was different from that of the normal adrenal. In one of these cases where the steroidogenesis response of isolated tumor cells to ACTH and DcAMP was higher than in normal adrenal, basal and cAMP stimulated protein kinase activities were significantly higher than those of the normal adrenal, but the activation constants of both nucleotides were similar to those of the normal gland. In the other case, the basal and the cAMP stimulated protein kinase activities were significantly lower, as well as the activation constant of cAMP. However, the binding affinity of 3H-cAMP was normal. Normal adrenal cytosol contains three protein kinases, as resolved by DEAE-cellulose, two of which designated I and II, are cAMP-dependent. The DEAE-cellulose chromatography of the last tumor showed a loss of isoenzyme II. In addition, the protein kinase eluted at the same molarity as that of isoenzyme I of the normal adrenal was not activated by cAMP. Therefore, the lack of response to ACTH of some adrenocortical human tumors may be attributed either to an anomaly of the ACTH receptor or to some defect of the cAMP-dependent protein kinase.
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PMID:Adenosine 3'5'-cyclic monophosphate dependent protein kinase in human adrenocortical tumors. 19 Feb 57

Some of the regulatory mechanisms of cyclic adenosine monophosphate (AMP) production in human brain tumors were investigated by assessing both cyclic AMP levels and adenyl cyclase activity. A large disparity was found between the levels of cyclic AMP of normal brain and brain-tumor tissue. Cyclic AMP levels were much lower in brain tumors (25.8 pmoles (picomoles)/mg protein) than in normal brain (98.8 pmoles/mg protein). These studies also show that the abnormally low levels of cyclic AMP in tumors parallel those of adenyl cyclase. The mean adenyl cyclase activity of brain tissue was found to be 111.0 pmoles of cyclic AMP/min/mg protein, while that of the tumor was only 23.0 pmoles/min/mg protein. Levels of cyclic AMP and adenyl cyclase activity were inversely related to the degree of malignancy. Attempts to stimulate adenyl cyclase in homogenates of human brain and brain tumors resulted in a similar response in both tissues. Norepinephrone was the most effective stimulant and produced a two- to threefold increase in cyclic AMP production, while histamine had no effect. It is concluded that one of the factors governing tumor growth may be a defect in the adenyl cyclase system.
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PMID:Cyclic AMP and adenyl cyclase in brain tumors. 19 76

ACTH stimulates the incorporation of 14C-leucine into proteins of adrenal tumor cells in culture. This stimulation though about 20% over controls is statistically significant. Cyclic AMP did not reproduce the stimulation observed with ACTH.
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PMID:[Stimulation by ACTH of protein synthesis in cultured adrenal cells. Absence of an effect by cyclin AMP]. 19 54

Cell division is induced in stationary cultures of BALB/c-3T3 mouse embryo cells without renewal of medium by addition of the tumor promoter, phorbol myristate acetate (PMA), or bovine serum. The addition of dbcAMP (10(-3) M) or other inhibitors of cAMP phosphodiesterase, papaverine (6.7 X 10(-6) M), Persantin (5 X 10(-5) M) or RO-20-1724 (10(-4) M), prevents cell replication induced by PMA or serum. In contrast, ouabain (10(-4) M) and N,N'-dicyclohexylcarbodiimide (10(-5) M), inhibitors of Na+-K+-ATPase activity, block the PMA-stimulated effect but do not inhibit serum-stimulated cell division. Several stages in the cell cycle are sensitive to dbcAMP addition. One is early in the G1 phase at the time of reinitiation of the cell cycle from a stationary (Go) phase, a second is associated with the G1-S transition, and a third with passage of cells from a post-S phase to mitosis. Based on observations of early morphological changes, responses of plasma membrane enzymes and effects of enzyme inhibitors, the stimulation of cell division in BALB/c-3T3 cells by PMA or serum appears to involve several membrane functions which may act in a cooperative manner.
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PMID:Induction of cell division in BALB/c-3T3 cells by phorbol myristate acetate or bovine serum: effects of inhibitors of cyclic AMP phosphodiesterase and Na+-K+-ATPase. 19 94

ACTH, 8-Br-cAMP, and serum deprivation arrested Y-1 functional mouse adrenal tumor cells in the G1 phase of the cell cycle. Though ACTH and 8-Br-cAMP treated cells were larger with increased macromolecular synthetic rates compared to cells arrested in G1 by serum removal, a similar 8- to 10-hours lag to initiation of DNA synthesis was observed after either ACTH or 8-Br-cAMP removal or after serum addition. After the 8- to 10-hour lag period, cells entered S phase exponentially. ACTH or 8-Br-cAMP opposed serum induced DNA synthesis initiation only when added prior to S. Once commitment to DNA synthesis occurred, ACTH or 8-Br-cAMP addition did not inhibit DNA synthesis although 8-Br-cAMP induced a secondary block in G2. Though ACTH and 8-Br-cAMP inhibited serum induced initiation of DNA synthesis and did not affect serum induced cellular hypertrophy, both substances increased the steroidogenic capacity of the cell. ACTH and 8-Br-cAMP thus appear to specifically oppose the stimulatory effects of serum on initiation of DNA synthesis while inducing the differentiated function of the cell.
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PMID:Hormonal regulation of initiation of DNA synthesis and of differentiated function in Y-1 adrenal cortical cells. 19 11

Immunofluorescent localization of prostaglandin-E (PGE), cyclic AMP (CAMP), and cyclic GMP (cGMP) was studied in tumor tissues from 40 patients with a variety of solid tumors. Representative normal tissues served as controls. Rabbit antisera specific for PGE or the cyclic nucleotides were used, and the reactions observed were correlated with the degree and type of lymphocytic reaction at the tumor margins. Strong PGE immunofluorescence was detected in tumor cells in 27 of 42 malignancies; by contrast nine of 13 normal tissues showed weak PGE reactions, cAMP was detected in 30 of the 42 malignancies; cGMP was noted in only seven of the 42 malignant tissues and in none of the normal tissues studied. The most common malignant tumor profile (17/42) was that of positive PGE and cAMP and negative cGMP staining. Tumors showing strong staining with anti-PGE or cAMP demonstrated a distinct trend towards heavier lymphocytic infiltration with a predominance of T cells at their margins, although this association did not reach statistical significance in the present material.
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PMID:Direct immunochemical detection of prostaglandin-E and cyclic nucleotides in human malignant tumors. 19 1


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