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)

In a patient who had undergone surgery for a medullary carcinoma of the thyroid, and with multiple hepatic metastases and severe diarrhoea, prostaglandins PGE1, PGE2, and PGF2alpha measured in peripheral venous blood and hepatic venous blood were normal in level and closely comparable, i.e. without gradient. Arachidonic acid, a PGs precursor, labelled with Iodine 131 was not taken up in the plaques of hypofixation seen with bengal rose and technetium sulphate. Finally, aspirin and indomethacin failed to relieve the diarrhoea. It is suggested that PGs were not secreted by the hepatic metastases and could not therefore be considered responsible for the diarrhoea.
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PMID:[Proof of the absence of prostaglandin secretion by a medullary carcinoma of the thyroid with functional diarrhea]. 121 94

The report summarizes the work of our laboratory aimed at improving the understanding of the angiogenic response of adult tissues, an event that transforms a micro-embolus of neoplastic cells into a growing metastasis. Attention has been focused on tumor-induced angiogenesis. The following aspects of the subject are discussed: (a) relationship between size of vascular network and tumor growth rate or tumor cell population; (b) angiogenic capacity of tumors and role that prostaglandin E1 may have as an angiogenesis factor; (c) relationship between acquisition of angiogenic capacity and neoplastic transformation of a cell population; (d) modification of tissue composition at the onset of angiogenesis; (e) behaviour of copper ions and copper carriers in the course of the angiogenic response; (f) the influence of gangliosides on endothelial cell motility, survival and growth in vitro; (g) modulation of the angiogenic response by gangliosides (GM1, GT1b) in vivo.
Cancer Metastasis Rev 1990 Nov
PMID:Gangliosides, copper ions and angiogenic capacity of adult tissues. 170 87

Previous studies from our laboratory have shown that intravenous (iv) infusion of pharmacologic doses of prostaglandin E1 (PGE1) inhibits "spontaneous" metastases in mice bearing Lewis Lung carcinoma (LLC). This study was done to determine the effect of iv PGE1 on "artificial" metastases. Male hybrid mice (20 g) underwent iv catheterization and were begun on continuous infusions of either PGE1 at 10 micrograms/kg/min or 0.9% NaCl (NS). After 2 days, each mouse received an iv injection of 10(5) viable LLC cells and was continued on the infusion regimens. Pulmonary metastatic nodules were enumerated and measured 12 days after injection. The iv infusion of PGE1 increased the metastatic rate 6-fold, the number of metastases greater than or equal to 2 mm in diameter 7-fold, and the number of metastases greater than or equal to 3 mm in diameter 14-fold. Thus, PGE1 demonstrates differential effects on tumor metastases, acting as a promotor of artificial metastases, in contrast to its antimetastatic effect on an intact primary tumor. When the promotional effect of iv PGE1 on artificial metastases is evaluated in light of our previous studies, it can be concluded that the inhibitory effect of PGE1 on spontaneous metastases from an intact tumor is secondary to the effect of PGE1 at the level of the primary tumor, and not in the circulation or at the target organ of metastases (lung).
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PMID:Differential role of prostaglandin E1 on tumor metastasis. 233 19

The role of prostaglandins and their synthesis inhibitors in malignant disease is undefined. The following studies were done to determine the effects of continuous intravenous prostaglandin E1 (PGE1) or a prostaglandin synthesis inhibitor, indomethacin, on tumor growth and metastasis in mice bearing Lewis lung carcinoma. Male B6D2F1 mice underwent tumor implantation in the right axilla on day 0. After 10 days of tumor growth, mice underwent intravenous (IV) catheterization and were infused with either PGE1 at 3 micrograms/kg/minute (PG-LOW), PGE1 at 6 micrograms/kg/minute (PG-HIGH), indomethacin (INDO) at 1 microgram/kg/minute, or normal saline (NS). After 10 days of infusion, tumor volume, tumor weight, and the number of metastases greater than 2 mm in diameter were significantly decreased, and tumor doubling time was significantly prolonged in the PG-HIGH group compared to NS controls. None of the other experimental groups showed differences in these parameters. A second experiment with a similar experimental design was done infusing PGE1 at 6 micrograms/kg/minute and at 12 micrograms/kg/minute to determine the maximum dose response of IV PGE1. Again a decrease in tumor volume, tumor weight, and metastatic rates were identified when compared to saline control, but there were no significant difference between the two doses of PGE1.
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PMID:Inhibition of tumor growth and metastasis by chronic intravenous infusion of prostaglandin E1. 236 3

Coagulation system and platelets play an important role in the stage of lodgement of tumor cells. We examined abilities of human and hamster pancreatic cancer cell lines to aggregate platelets in vitro, and investigated the effect of prostaglandin E1, I2, on artificial liver metastases of pancreatic cancer in Syrian golden hamster. Platelet aggregating activities were found in five out of six human pancreatic cancer cell line and thromboplastin likes activity in five cell lines. Diisopropanolnitrosamine induced hamster pancreatic cancer cells (HPK-1) were able to aggregate platelets both in vitro and in vivo and these activities were inhibited by prostaglandin I2. Hamster was inoculated intraportally with 1 X 10(6) HPK-1 cells. After two weeks autopsy of these hamsters revealed multiple metastatic nodules on liver surface. In this model we administered prostaglandin E1, I2 into the portal vein five minutes before cell inoculation. Number of liver surface nodules were significantly decreased to 33.1 + 7.0, 11.0 + 9.6 in hamster given 100g PGE1 PGI2 before cell inoculation, compared with control group of hamsters (62.0 + 6.6 PH9.3, 66.1 + 13.9 PH7.4). But administration of prostaglandin after cell injection was not effective. In all cases none of extrahepatic metastases were noted. Inhibitory action of PGE1 PGI2 on liver metastasis is suspected to be related to inhibition of platelet aggregation.
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PMID:[Inhibitory effect of anti-platelet prostaglandin on liver metastasis of hamster pancreatic cancer]. 250 99

The metastatic murine mammary tumor cell line 410.4 and its nonmetastatic counterpart tumor line 410 were examined for the presence of prostaglandin E2 (PGE2) binding using a 3H-PGE2 ligand binding assay. Inhibition of endogenous prostaglandin synthesis with indomethacin was shown to increase markedly binding of 3H-PGE2. Equilibrium binding data for tumor 410.4 show that specific binding is saturable, reversible by unlabeled PGE2, temperature-dependent and specific. PGE1, PGE2 or 16-16-dimethyl PGE2 compete well with 3H-PGE2 for binding. PGD2 partially inhibits 3H-PGE2 binding, whereas PGA2 does not compete. Scatchard analysis of equilibrium binding data reveals a high affinity (Kd = 3.9 X 10(-9) M) and an average of 33,785 binding sites/cell. In contrast, binding of 3H-PGE2 to nonmetastatic line 410 has a slightly lower affinity (Kd = 8.8 X 10(-9) M) and an average of 368,857 binding sites/cell. 3H-PGE binding to line 410 cells is comparatively nonspecific as PGD2 is nearly as effective as PGE1, PGE2 and an analogue of PGE2 in competing with 3H-PGE2 and PGA2 also inhibits 3H-PGE2 binding.
Invasion Metastasis 1988
PMID:Heterogeneity of prostaglandin E2 binding in murine mammary tumor cells differing in metastatic potential. 342 34

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

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

Neuroblastoma, one of the commonest malignant childhood tumors, arises from the adrenal glands and/or sympathetic ganglia, and metastases into lymph nodes, bone marrow, bones, etc. Patients with advanced stages of neuroblastoma are poorly responsive to current combined chemo-radiotherapy. However, neuroblastoma is known to maturate into benign ganglioneuroma spontaneously or induced by certain chemicals. In our previous studies, adenosine 3', 5'-monophosphate (cAMP) was found to play an important role in this maturational process. It was also demonstrated that long-term continuous infusion of dibutyryl cAMP and papaverine caused significant growth-inhibition and tumor differentiation of C 1300 neuroblastoma in mice. These results prompted us to apply intra-aortic PGE1 infusion to two cases of abdominal neuroblastomas with stages III and IV.PGE1 infusion (0.25-3.0 ng/kg/min, over the period of 3 to 32 weeks), combined with oral papaverine and conventional chemotherapy, was effective in decreasing tumor size and promoting tumor maturation in the infused area. However, distant osseous metastases occurred in both cases, during and after the PGE1 administration. Similar modalities should be further evaluated in order to potentiate anti-metastatic effect on neuroblastoma cells.
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PMID:[Intra-aortic prostaglandin E1 infusion in the treatment of advanced neuroblastoma]. 631 Nov 12

The blood supply in the central portions of solid Yoshida sarcoma tumors is poor, but these portions contain viable cells capable of tumor growth when transplanted into new hosts. Attempts were made to increase penetration into these portions in rats by an injection of prostaglandin E1 together with lissamine green dye (used as a marker of drug penetration). The lissamine green dye defined the regions which could not readily be reached by blood-borne substances. Next, mitomycin C in place of lissamine green was administered together with prostaglandin E1. The growth of Yoshida sarcoma cells transplanted subcutaneously was suppressed significantly in the rats given mitomycin C with prostaglandin E1 compared with that in the rats given mitomycin C alone. The effect was greater when prostaglandin E1 was administered by an intraarterial route than by an intravenous route (P less than 0.01). Five patients with hepatic metastases from colorectal carcinoma were treated with a one-shot infusion of mitomycin C together with prostaglandin E1. Two patients showed objective evidence of improvement.
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PMID:Enhancement of the cytocidal effect of mitomycin C by means of simultaneous administration of prostaglandin E1. 640 85


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