Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activation of protein kinase C involves its translocation from a cytosol fraction to a membrane fraction. Effects of interferon-gamma (IFN-gamma) on the epidermal protein kinase C were investigated. The treatment of recombinant human IFN-gamma on intact human epidermis resulted in the translocation of protein kinase C from a cytosol to a membrane fraction. The human IFN-gamma had no translocation effect on pig epidermal protein kinase C. Tumor promoter, 12-o-tetradecanoylphorbol-13-acetate (TPA), and a membrane-permeable diacylglycerol analogue, 1-oleoyl-2-acetylglycerol (OAG), both of which are well-known activators of protein kinase C, translocated the epidermal protein kinase C. The IFN-gamma had no direct effect on the epidermal protein kinase C; the addition of the IFN-gamma to partially-purified pig epidermal protein kinase C had no effect on its activity. The effect of the IFN-gamma on human epidermal protein kinase C appears to be through the species specific IFN-gamma receptors. It has been reported that the epidermal beta-adrenergic adenylate cyclase response is decreased following the TPA- (and OAG-) induced activation of protein kinase C. Human recombinant IFN-gamma, however, had no effect on the beta-adrenergic response of the human epidermis. Our results indicate that IFN-gamma affects intact keratinocytes in vitro, resulting in the activation of protein kinase C, which might be related to the physiological effect of IFN-gamma on keratinocyte.
 ...
PMID:Translocation of protein kinase C from cytosol to membrane fractions in human epidermal keratinocytes by recombinant human interferon-gamma. 215 6

Permanent clonal cell lines from newborn mouse striatum have been established after transfer of the simian virus 40 large tumor oncogene by means of a retroviral vector. Some of the lines obtained displayed properties of bipotential and plastic glio-neuronal precursors. Depending on the culture conditions, these cells express either the glial fibrillary acidic protein or neurofilaments. In addition, the cells can display adrenergic, D1 and D2 dopaminergic, muscarinic, and 5-hydroxytryptamine type 2 serotoninergic receptors, which are coupled either to the adenylate cyclase or to the phosphatidylinositol signaling pathways. The panel of receptors for neurotransmitters exhibited by these lines closely resembles that of primary striatal neurons. Results suggest that plastic common precursors of astrocytes and neurons persist in the striatum at a late developmental stage. As these permanent cell lines constitute an unlimited source of homogenous cell material, we suggest that they should be useful for molecular and pharmacological studies on the mechanisms and regulation of signal transduction as well as the commitment, plasticity, and differentiation of neural cells.
 ...
PMID:Immortalization of bipotential and plastic glio-neuronal precursor cells. 215 1

Cloned Lewis lung carcinoma (LLC) variants were used in an in vitro migration model for dissemination, to determine if prostaglandin E2 (PGE2) produced by nonmetastatic LLC cells could directly stimulate dissemination of metastatic LLC cells and to identify an intracellular mechanism for such an effect. The migration of metastatic LLC clones was stimulated not only by exogenous PGE2 but also by nonmetastatic LLC cells, by their production of a migration-stimulatory factor which was sensitive to indomethacin and anti-PGE2 antibodies. Nonmetastatic LLC clones were unresponsive to migration stimulation by PGE2. The results of in vivo metastasis studies were consistent with those of in vitro migration studies. In vivo lung metastasis was increased by PGE2, as well as by nonmetastatic cells when they were either admixed with the metastatic LLC inoculum, irradiated and injected adjacent to the metastatic LLC tumor, or localized in chambers and implanted s.c. into mice given injections of metastatic LLC cells. Indomethacin blocked metastasis stimulation by nonmetastatic cells. The in vitro PGE2 stimulation of metastatic LLC cells appeared to be linked to a cyclic AMP (cAMP) response, since migration could also be stimulated by dibutyryl-cyclic AMP and blockage of a cAMP response with nicotinic acid ablated the PGE2 stimulation of migration. In vivo metastasis could be stimulated by elevation of cAMP with aminophylline. The differential responsiveness of metastatic versus nonmetastatic LLC cells to PGE2 could not be due to PGE2-adenylate cyclase coupling, since PGE2 increased the cAMP levels in cultures of both metastatic and nonmetastatic LLC cells. There was, however, a difference in the cyclic AMP-dependent protein kinase (PKA) response to PGE2, with PKA activity of metastatic LLC being stimulated by PGE2 and by the adenylate cyclase-stimulator forskolin, whereas PKA of nonmetastatic LLC was not stimulated by these cAMP elevators, suggesting a dysfunction in the cAMP-PKA coupling.
 ...
PMID:Association of a functional prostaglandin E2-protein kinase A coupling with responsiveness of metastatic Lewis lung carcinoma variants to prostaglandin E2 and to prostaglandin E2-producing nonmetastatic Lewis lung carcinoma variants. 215 67

The parathyroid hormone (PTH)-like activity, defined by the stimulation of cAMP production in MC3T3E1 cells, in the extract of a pancreatic cancer associated with humoral hypercalcemia of malignancy (HHM) was eluted in two peaks (I and II) by reverse phase HPLC. Both peaks dose-dependently inhibited the binding of human (h) PTH(1-34) to canine renal membrane in an essentially similar fashion to hPTH(1-34) or PTH-related protein (rP). In the renal membrane, neither of these peaks stimulated adenylate cyclase (AC) but rather dose-dependently inhibited AC activity stimulated by hPTH(1-34), PTH-rP(1-34) or forskolin. In rat renal cortical slices, however, both peaks could exhibit their own stimulatory effect and did not inhibit PTH or forskolin-stimulated cAMP production. It has been concluded that a factor which inhibits AC activity, probably reflecting the direct action at catalytic site, can occasionally be produced with PTH-like factor. Although PTH-like and AC-inhibiting activities were very close on reverse phase HPLC, currently the interrelation between these two activities is not clear. It may be important to be aware of the presence of such a factor in the evaluation of the bioassay data employing a broken cell preparation, which is often used to assess the PTH-like activity of tumor products.
 ...
PMID:Inhibition of renal membrane adenylate cyclase by extract of pancreatic cancer associated with humoral hypercalcemia of malignancy. 216 91

It was found that repeated transplantation of ACATOL strain cells resulted in a loss of their sensitivity to growth-stimulating effect of pentagastrin. The effect of gastrin receptor antagonist proglumide, on ACATOL cells growth was inconstant. ACATOL tumor was sensitive to VIP and glucagon in vitro (as shown by adenylate cyclase activity assay), that makes the model promising for selecting potent hormone drugs against colorectal cancer.
 ...
PMID:[The hormonal sensitivity of a transplantable adenocarcinoma of the large intestine]. 222 62

Little notice has been paid in the surgical literature to problems with psychoeffective lithium, which by interfering with adenylate cyclase affects thyroid and parathyroid function, causing hypercalcemia, hyperparathyroidism, and hypothyroidism. Seven patients with lithiumogenic hyperparathyroidism occurring after years of lithium therapy underwent treatment and manifested osteoporosis (n = 2), hypertension (n = 2), nephrolithiasis (n = 1), coma (n = 1), rising hypercalcemia (n = 1), goitrous myxedema (n = 4), nephrogenic diabetes insipidus (n = 2), renal failure (n = 2), and hyperlipidemia (n = 1). Disease-directed parathyroidectomy (without morbidity) was curative. Unique laboratory findings included normal serum phosphorus and reduced urinary calcium and cyclic adenosine monophosphate values. Three separate cases of thyroid carcinoma after long-term lithium therapy were also treated, being preceded by myxedema (n = 2) and concurrent with hyperparathyroidism (n = 1). There has been only one previous report of lithium-associated thyroid carcinoma. All patients taking lithium should undergo surveillance for thyroid and parathyroid dysfunction and neoplasia, and appropriate surgical and medical treatment should be considered in each situation. Although hyperparathyroidism may be reversible with lithium discontinuance, such therapy may be obligatory for patient well-being, thus dictating parathyroidectomy.
 ...
PMID:Lithiumogenic disorders of the thyroid and parathyroid glands as surgical disease. 224 24

5'-(N-Ethyl)carboxamidoadenosine (NECA), an analog of adenosine, transiently stimulated a rat tumor mast cell (RBL-2H3 cells) to cause a release of inositol phosphates and an increase in levels of Ca2+ in the cytosol. It failed, however, to stimulate a sustained uptake of 45Ca2+ or secretion. The effects of other agents that act on P1- or P2-purinergic receptors suggested that NECA and other adenosine agonists acted via a novel subtype of adenosine membrane receptor. Although the order of potency of agonists was characteristic of A2-adenosine receptors, there was no indication of the involvement of adenylate cyclase, and antagonists such as isobutylmethylxanthine, 8-phenyltheophylline, and 8-p-sulfophenyltheophylline inhibited the responses to either NECA or antigen. The fact that stimulation of inositol phospholipid hydrolysis by NECA in washed, permeabilized RBL-2H3 cells was blocked by pertussis toxin as well as by cholera toxin suggested instead that the NECA-sensitive receptor activated phospholipase C via a G-protein. In contrast to NECA, antigen stimulation resulted in a pertussis toxin-resistant, sustained hydrolysis of inositol phospholipids, increases in free intracellular Ca2+, accelerated influx of 45Ca2+, and secretion from RBL-2H3 cells. In combination with NECA, all responses to antigen were markedly enhanced, and the enhancement was selectively blocked by pertussis toxin. The ability of antigen, but not NECA, to provoke secretion may be dependent primarily on the sustained activation of a cholera toxin-sensitive Ca2+ influx pathway that serves to amplify stimulatory signals for secretion. These studies also suggested that phospholipase C could be activated through different G-proteins via different receptors within the same cell.
 ...
PMID:Activation of phospholipase C via adenosine receptors provides synergistic signals for secretion in antigen-stimulated RBL-2H3 cells. Evidence for a novel adenosine receptor. 229 18

The effects of recombinant human interleukin-1 alpha (IL-1) on procollagen gene expression were examined in the clonal mouse osteoblastic cell line MC3T3-E1. Cells were grown in Dulbecco's Modified Eagle's Medium containing 10% fetal calf serum and 50 micrograms/ml ascorbic acid. Collagen synthesis was assessed as [3H]proline incorporation into collagenase-digestible protein (CDP). Procollagen mRNA levels were determined by Northern blot analysis using a 32P-labeled alpha 1(I) cDNA. Transcription rates were determined by nuclear run-off assay. IL-1 at 1-1000 pg/ml caused a concentration-dependent inhibition of CDP, which was maximally reduced by 75-80%, and a parallel reduction of procollagen alpha 1(I) mRNA levels. The effects of IL-1 were mimicked by the tumor promoter phorbol 12-myristate 13-acetate (PMA) at 1-100 nM, which inhibited CDP and reduced procollagen alpha 1(I) mRNA levels to a similar extent. The effects of IL-1 and PMA were independent of prostaglandin production, since indomethacin did not alter the inhibitory effect of either agent on CDP. Neither IL-1 (up to 10 ng/ml) nor PMA (100 nM) affected adenylate cyclase activity, while forskolin (10 microM), PTH (10 nM) and prostaglandin E2 (1 microM) stimulated adenylate cyclase activity 3- to 5-fold. However, forskolin (10 microM) and (Bu)2cAMP (100 microM) failed to alter CDP or procollagen alpha 1(I) mRNA levels. IL-1 (1 ng/ml) and PMA (100 nM) reduced transcription of the alpha 1(I) procollagen gene by 70% and 80%, respectively, while alpha 2(I) transcription was decreased by 59% and 53%. Neither IL-1 nor PMA affected transcription of the beta-actin or beta-tubulin genes.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Interleukin-1 alpha and phorbol ester inhibit collagen synthesis in osteoblastic MC3T3-E1 cells by a transcriptional mechanism. 232 98

Metastasis is a multistep phenomenon in which platelets appear to play an important role. This study examined several compounds for their effects on experimental hepatic metastasis and on human pancreatic tumor cell-platelet interactions. Prostacyclin (PGI2) and forskolin (stimulators of platelet adenylate cyclase) and ketoconazole (inhibitor of lipoxygenese and thromboxane synthetase) were used in order to investigate their effects on hepatic metastases from a human pancreatic tumor cell (RWP-2) in the nude mouse. The tumor cells were injected intrasplenically and the animals were divided into control, prostacyclin (PGI2 200 micrograms), forskolin (150 micrograms), and ketoconazole (180 micrograms) groups. All three drugs were administered intraperitoneally 30 minutes before and 24 hours after the tumor cell injections. Statistically significant differences were observed between control and treated groups in tumor surface area (P less than 0.001), percentage of liver surface area occupied by tumor (P less than 0.001), and number of tumor colonies (P less than 0.004 for prostacyclin, P less than 0.005 for forskolin, and P less than 0.001 for ketoconazole). These agents also strongly inhibited RWP-2-induced platelet aggregation in human platelet-rich plasma.
 ...
PMID:Inhibition of hepatic metastasis from a human pancreatic adenocarcinoma (RWP-2) in the nude mouse by prostacyclin, forskolin, and ketoconazole. 240 57

Beta-adrenergic stimulation of cellular cyclic AMP accumulation was characterized in normal anterior pituitary cells in vitro. In the presence of isobutylmethylxanthine, the order of potency of catecholamine agonists, as well as the antagonism by propranolol and not phentolamine, aided in classifying the receptor as beta-adrenergic. Furthermore, this agonist effect was rapidly desensitized. Tumor promoters, which directly activate protein kinase C, enhanced the cyclic AMP levels achieved with beta-adrenergic agonists (1.5-fold average at 10 min). This acute effect occurred over 10-1000 nM phorbol dibutyrate or phorbol myristate acetate. Finally, 3H-phorbol dibutyrate binding to unstimulated anterior pituitary cells was predominantly associated with the cytosol (79%) versus membrane (21%) fractions. Thus, an acute role for protein kinase C in promoting beta-adrenergic receptor activation of adenylate cyclase activity is suggested for anterior pituitary cells.
 ...
PMID:Beta-adrenergic stimulation of anterior pituitary cyclic AMP is enhanced by tumor promoters. 242 24


<< Previous 1 2 3 4 5 6 7 8 9 10