Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1,5-Dihydro-7-(1-piperidinyl)-imidazo[2,1-b]quinazolin-2(3H)-one dihydrochloride hydrate (DN-9693), a new c-AMP: phosphodiesterase inhibitor was examined for its inhibitory effects on platelet aggregation induced by metastasizing tumor cells and on blood-borne metastases of these tumors. 1-3 microM of DN-9693 completely inhibited platelet aggregation induced by B16 melanoma subline BL6 and Lewis lung carcinoma (3LL) cells. Platelets prepared from mice intravenously or orally administered with DN-9693 failed to aggregate after the addition of BL6 cells. Intravenous injection of DN-9693 was effective in protecting the mice inoculated with 1 X 10(6) BL6 cells against acute pulmonary embolic death. Either intravenous or oral administration of DN-9693 (1-10 mg/kg) sufficiently suppressed thrombus formation and subsequent pulmonary metastasis caused by intravenously inoculated BL6 or 3LL cells. Spontaneous pulmonary metastasis of 3LL was also inhibited by DN-9693. Continuous administration of DN-9693 during and after surgical excision of the primary tumors was the most effective treatment against the development of pulmonary metastases of 3LL.
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PMID:Effects of DN-9693, a new metastasis inhibitor, on murine hematogenous metastasis. 301 18

Evidence is steadily mounting that the proto-oncogenes, whose products organize and start the programs that drive normal eukaryotic cells through their chromosome replication/mitosis cycles, are transiently stimulated by sequential signals from a multi-purpose, receptor-operated mechanism (consisting of internal surges of Ca2+ and bursts of protein kinase C activity resulting from phosphatidylinositol 4,5-bisphosphate breakdown and the opening of membrane Ca2+ channels induced by receptor-associated tyrosine-protein kinase activity) and bursts of cyclic AMP-dependent kinase activity. The bypassing or subversion of the receptor-operated Ca2+/phospholipid breakdown/protein kinase C signalling mechanism is probably the basis of the freeing of cell proliferation from external controls that characterizes all neoplastic transformations.
Cancer Metastasis Rev 1987
PMID:Calcium, cyclic AMP and protein kinase C--partners in mitogenesis. 303 May 78

A diagnostic and therapeutic strategy for the management of patients with Zollinger-Ellison syndrome has been developed, based on the review of a large personal experience and the most recent literature. The mainstay of a modern ZES management is the eradication of tumoral processes whenever feasible. Diagnosis is centred upon gastric acid and gastrin secretion measurements both in basal conditions and on secretin stimulation. Recognition of other endocrine involvement and familial inheritance is of the utmost importance in distinguishing sporadic ZES patients from those who have the condition known as multiple endocrine neoplasia type I. Blood calcium and phosphorus levels, parathyroid hormone concentration, combined if necessary with urinary cyclic AMP excretion measurement, should be performed routinely once ZES diagnosis is established or highly suspected. Localization of the tumour is the next essential step, and this has been considerably facilitated by the recent development in imaging techniques: it involves computerized axial tomography and selective abdominal angiography, a combination of which allows tumour detection in 60-70% of sporadic gastrinoma patients, with a maximal sensitivity for well-developed hepatic metastases. In sporadic ZES exploratory laparotomy is legitimate when preoperative localization of the tumour has failed; this laparotomy will allow further detection and then eradication of gastrinomas in a significant number of patients. Control of gastric acid secretion is mandatory throughout the work-up period; modern antisecretory agents are efficacious in most cases; total gastrectomy, when control of acid hypersecretion has failed, is now exceptional. Eradication of the tumour should be attempted in cases of sporadic ZES in the absence of recognizable liver involvement. The chance of a definite cure provided by surgery when performed by an experienced surgeon varies from 20% to 60% in pancreatic and ectopic gastrinomas respectively. In ZES patients with MEN I, exploratory laparotomy is seldom indicated (other than for symptomatic associated endocrine secretion), as the chance of a definite cure by surgery is very rare. Parathyroid surgery is often indicated and should take place before any form of abdominal surgery. In cases of hepatic metastases, chemotherapy with streptozocin and fluorouracil is indicated and soon, perhaps, chemo-embolization.
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PMID:Diagnosis and treatment of Zollinger-Ellison syndrome. 304 57

The application of the principles of basic sciences in anesthesiology not only has succeeded in allaying man's pain on Earth, but also within this decade has provided him with a controlled safe environment for successive journeys into outer space and to the moon and soon to planets beyond. These same principles have made possible his exploration of the ocean floors in artifical atmospheres and pressures and his escape, without breathing devices, from depths of 300 feet. The science of anesthesia has contributed immeasurably to the active treatment of paralytic poliomyelitis and to resuscitation. Furthermore, it has introduced needless jet injection for drug and vaccine therapy in epidemics and with increasing rapidity to diabetcs. This accumulating body of knowledge within the past 13 decades has contributed to the development of modern surgery, obstetrics, and dentistry, and provided techniques for the control of pain from metastatic cancer, from trauma, from arthritis, and during postoperative convalescence. The anesthesiologist shares with the surgeon and clinical pathologist the responsibility for the safe use of fluid and blood replacement therapy; and with the internist, psychiatrist, and general practitioner the proper sequential medication of analgesics, anesthetics, ataractics, cortisone, antihypertensive and antihistaminic agents, and prompt reversal of many undesirable depressions during emergence. A new concept is the reversal of many narcotic states with cyclic AMP. Major advances in anesthesia have been developed on every continent. The fact that there are at least 30 anesthetic techniques and 62 agents in worldwide use reemphasizes our present lack of an ideal single anesthetic agent and technique. Iti is encouraging to note that the science of anesthesiology has made more progress during the past three decades than in all of the previous century. The great preponderance of that progress has been largely confined to Canada, the United States, the British Commonwealth, Western Europe, and a few of the metropolitan areas in South America. Happily, the significant progress in the last decade has added monitors and other safeguards, understanding, tecyniques, agents, and pioneer investigators, in increasing proportions for a world that will double its population in the present half-century. Surely, there is no more important field toward the direction of world scientific effort for human betterment than in this broad area of universal agreement.
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PMID:Delivery of anesthesia services throughout the world. 444 13

Because tumor-induced platelet aggregation appears to play a role in the development of certain experimental tumor metastases, we examined the mechanism(s) of tumor-induced platelet aggregation as well as the effect of various anti-platelets agents. Two mechanisms for tumor-induced platelets aggregation have been previously described: (1) a mechanism which requires complement, a stable plasma factor, divalent cation and a sialo-lipo-protein vesicular component of the tumor membrane for platelet aggregation; and (2) a mechanism which operates via the generation of thrombin and requires a phospholipid component of the tumor membrane. We now report a new mechanism of tumor-induced platelet aggregation which is shared by three different tumors: a spontaneously metastatic human melanoma, HM29, a murine melanoma, B16F10, and a carcinogen-induced metastatic murine colon carcinoma, CT26. These tumors do not require cell-surface sialic acid or serum complement as does the first mechanism. They do not require cell-surface phospholipid, as do the tumors representing the other two mechanism. They do not aggregate platelets via the generation of thrombin as do tumors representing the second mechanism. These tumors are unique in that they require a trypsin-sensitive surface protein for activity. The ability of the thrombin-generating tumors to aggregate platelets is uniquely sensitive to two highly specific, synthetic thrombin-competitive inhibitors: DAPA and No. 805. The other two groups of tumors are at least 10 times more sensitive to inhibition of platelet aggregation by elevation of cyclic AMP levels (prostacyclin, 6-keto-PGE1, dibutyryl cyclic AMP) and at least 10 times more sensitive to inhibition of prostaglandin synthesis (indomethacin, ibuprofen). Thus, tumor-induced platelet aggregation is heterogeneous with respect to mechanism of action as well as inhibition by anti-platelet pharmacologic agents. Sensitivity to anti-platelet agents correlates with the mechanism by which tumor cells aggregate platelets.
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PMID:A new mechanism for tumor induced platelet aggregation. Comparison with mechanisms shared by other tumor with possible pharmacologic strategy toward prevention of metastases. 629 77

Hypercalcemia, hypercalciuria, and hyperphosphaturia were present in female dogs with adenocarcinomas derived from apocrine glands of the anal sac (CA). Remission of hypercalcemia accompanied tumor excision in all six dogs undergoing surgery, whereas tumor recurrence or growth of metastases was associated with a return of hypercalcemia. Preoperatively, the plasma concentrations of immunoreactive parathyroid hormone in all dogs were undetectable or in the low normal range. Plasma concentrations of 13,14-dihydro-15-keto-prostaglandin E2 (PGE2M) and serum 1,25-dihydroxyvitamin D were not significantly different from control dogs. Urinary cyclic AMP and hydroxyproline were increased in dogs with CA. No immunoreactive parathyroid hormone was detected in extracts from tumor tissue, and parathyroid glands from dogs with CA had ultrastructural characteristics of secretory inactivity. Lumbar vertebrae from hypercalcemic dogs had decreased trabecular bone volume and increased osteoclastic bone resorption compared with age-matched control dogs. After tumor excision, serum total calcium returned to the normal range, whereas immunoreactive parathyroid hormone increased 2- to 20-fold and 1,25-dihydroxyvitamin D decreased 2- to 8-fold. Postoperative hypocalcemia was not observed. These results indicate that CA produces a hypercalcemic factor other than immunoreactive parathyroid hormone or prostaglandin E2 that increases osteoclastic osteolysis distant from the tumor and results in hypercalcemia, hypercalciuria, and hyperphosphaturia.
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PMID:Hypercalcemia in dogs with adenocarcinoma derived from apocrine glands of the anal sac. Biochemical and histomorphometric investigations. 630 May 51

The in vitro sensitivities to differentiating agents of a murine neuroblastoma cell line (N18) and a selected variant cell line (N18-LM5) were examined. In addition, the sensitivities to differentiating agents of cells from spontaneous metastases produced by N18 cells were examined. When N18 cells (1 X 10(5) cells/mouse) were injected into the lateral tail vein of syngeneic A/J mice, only a few metastatic nodules formed in the liver and lung, while similar injection of N18-LM5 cells produced larger numbers of metastatic nodules. Exposure of N18 cells to differentiating agents, such as dibutyryl cyclic 3':5'-AMP (db-cAMP), prostaglandin E1, and dexamethasone, resulted in induction of differentiation in terms of neurite extension. N18-LM5 cells responded to differentiating agents to a greater extent than N18 cells, and most of the cells extended neurites when they were exposed to 1 mM db-cAMP for 3 days. On the other hand, not all cell lines from spontaneous metastases produced by N18 cells responded to db-cAMP. These results suggest that the colonizing potential of neuroblastoma cells is not necessarily correlated with loss of responsiveness to differentiating agents and that various spontaneous metastases show heterogeneity in responsiveness to differentiating agents.
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PMID:Differences in inducibility of morphological differentiation of parental cells, selected variant cells and cells from spontaneous metastases of mouse neuroblastoma cells. 630 60

A case of humoral non-parathyroid hypercalcemia in a breast cancer patient is discussed. Bone metastases developed 23 months after the first clinical evidence of increased serum calcium levels and did not appear to be etiologically involved in this case of hypercalcemia. Serum levels of I-PTH and PGE2 were normal, as were urinary c-AMP levels. Furthermore, no significant response to corticosteroid therapy was observed. However, the correlation between the activity of metastatic disease and calcemia suggests that this cancer produced humoral factor(s) with calcium-mobilizing activity.
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PMID:Humoral nonparathyroid hypercalcemia without evidence of bone involvement. 630 87

Metastasis is a complex process whereby tumour cells from a primary neoplastic growth disseminate throughout the body and establish secondary tumour foci in distant organs. Biochemical traits associated with, or essential for, the expression of the metastatic phenotype have not yet been identified. In the course of examining stimulation of the B16 murine melanoma adenylate cyclase by melanocyte-stimulating hormone (MSH) and by the diterpene forskolin, we noted that tumour cell clones isolated from common parent cell populations differed widely in their responses to these agonists. We report here that the accumulation of cyclic AMP induced by MSH or forskolin shows a strong positive correlation with the ability of B16 melanoma clones to form pulmonary tumour colonies when injected intravenously (i.v.) into syngeneic mice ('experimental metastasis'). In parallel in vitro analyses of cyclic AMP metabolism and in vivo assays of experimental metastasis using replicate cell preparations, highly metastatic tumour cell clones consistently show greater than a 30-fold increase in cellular cyclic AMP when exposed to MSH or forskolin. By contrast, clones with limited metastatic abilities respond to the same agonists with only a two- to threefold increase in cellular cyclic AMP. These data suggest that cyclic AMP metabolism is linked with biochemical pathways that are responsible for the formation of experimental metastasis by the B16 melanoma.
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PMID:Experimental metastasis correlates with cyclic AMP accumulation in B16 melanoma clones. 632 99

Prostaglandin E1 (PGE) and d, 1-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (RO 20-1724, an experimental cyclic nucleotide phosphodiesterase inhibitor) cause cell death and cyclic AMP-mediated differentiation of murine neuroblastoma (NB) (cell line C-1300) cells in vitro. We report, for the first time, that these agents can be used in vivo to cause regression of NBs in A/Jax mice. These drugs were also able to slow the growth of primary tumors, prevent metastases, and cause morphological differentiation of tumors. The similarity of the response of human and mouse NB cells to differentiating drugs indicate that these agents have the potential to replace or support conventional chemotherapy in treatment individualized to NB. The mouse model of NB provides an excellent means to study the effectiveness of alternative drug therapy in vivo.
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PMID:Regression and differentiation of neuroblastoma tumors in mice treated with differentiating agents--prostaglandin E1 and a phosphodiesterase inhibitor, RO 20-1724. 689 Dec 84


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