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 seven patients suffering from inoperable pancreatic cancer and in 14 patients with inoperable colonic cancer the half-life (T/2) of prostaglandin (PG)I2 in plasma in vitro has been determined before and at various intervals after irradiation. No significant difference of PGI2-T/2 could be observed either before irradiation, at the end of the irradiation period or 3 and 6 weeks after the last irradiation. Thus irradiation does not appear to interfere with the degradation of PGI2-T/2 in plasma. In patients with inoperable pancreatic and colonic cancer the PGI2-T/2 was not significantly different to that of the PGI2-T/2 of controls. Thus, a shortening of PGI2-T/2 is not a common feature in tumour patients. Hyperaggregation promoting seeding of metastases is not influenced by irradiation via the particular parameter of the PG-system.
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PMID:The influence of irradiation on the biological half-life of prostacyclin in plasma of patients with gastrointestinal cancer. 331 3

For suppression of primary tumor growth and metastatic spread, aspirin and theophylline, either alone or combined, were given daily to inbred female BN rats after sc implantation of a syngeneic nonimmunogenic tumor. Treatment with 200 mg aspirin/kg (body wt) resulted in a statistically significant regression of tumor growth as well as of the number of metastases in the lungs. Aspirin given in a lower dose (20 mg/kg) did not show significant difference from the vehicle group. Theophylline (75 mg/kg) significantly increased primary tumor growth as well as lung metastases. Inhibition of in vitro platelet aggregation, determined in whole blood taken from non-tumor-bearing animals treated with the same therapeutic regimen, was most pronounced in those groups in which tumor growth and spread were significantly retarded. However, this positive correlation between inhibition of tumor spread and platelet aggregation was not associated with a favorable balance of prostacyclin and thromboxane A2 in these animals.
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PMID:Reductive effect of aspirin treatment on primary tumor growth and metastasis of implanted fibrosarcoma in rats. 351 10

Nutritional antioxidants support prostacyclin synthesis by preventing lipid hydroperoxide-mediated inhibition of prostacyclin synthetase. Recent preliminary clinical studies indicate that supplementary antioxidants exert antithrombotic effects in vivo that are most likely attributable to enhanced prostacyclin production. Optimal antioxidant nutrition may thus have preventive and therapeutic value for disorders in which inappropriate platelet aggregation plays an etiologic role, including MI, stroke, atherogenesis, pre-eclampsia, and the vascular complications of diabetes. In light of evidence that platelet aggregation encourages the implantation of hematogenous tumor metastases, supplemental antioxidants should also impede tumor dissemination--an effect which will be complemented by the immunostimulant actions of these nutrients. By exerting anticarcinogenic, immunostimulant and anti-metastatic effects, nutritional antioxidants should act to inhibit neoplasia at each stage of its development.
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PMID:An antithrombotic role for nutritional antioxidants: implications for tumor metastasis and other pathologies. 352 Feb 53

Prostaglandins are secreted by a variety of animal and human tumours. A higher prostaglandin production is sometimes associated with a decreased tendency to metastasis, though there are features of the metastatic cascade where prostaglandins might be expected to facilitate dissemintion. Prostaglandins may aid metastases through the mediation of proteolytic enzyme production, by prostaglandin-induced neovascularization or by subversion of the immune response. Inhibitors of platelet aggregation such as prostacyclin on thromboxane A2 synthetase inhibitors may be useful in the prevention of metastatic spread of cancer.
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PMID:Role of postaglandins in metastatic dissemination of cancer. Minireview on cancer research. 619 28

Prostaglandins are secreted by a variety of animal and human tumours. A higher prostaglandin production is sometimes associated with a decreased tendency to metastasis, though there are features of the metastatic cascade where prostaglandins might be expected to facilitate dissemination. Prostaglandins may aid metastases through the mediation of proteolytic enzyme production, by prostaglandin-induced neovascularization or by subversion of the immune response. Inhibitors of platelet aggregation such as prostacyclin on thromboxane A2 synthetase inhibitors may be useful in the prevention of metastatic spread of cancer.
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PMID:Role of prostaglandins in metastatic dissemination of cancer. Minireview on cancer research. 619 29

The data presented suggest that F1 and F10 cells display an inverse relationship between their levels of metastasis and prostaglandin D2 production. Prostaglandin D2 was able to reduce in vitro aggregation of platelets from C57 black mice. Other prostaglandins that decreased platelet aggregation such as prostacyclin also reduced the metastatic rate. Prostaglandin D2 also reduced macrophage cytotoxicity for B16 target cells in vitro. Interferons stimulated prostaglandin D2 synthesis in F10 cells and reduced lung metastasis. F10 metastasis was not blocked by interferon to the same extent by in vivo treatment as it had been in vitro, suggesting that interferons and other modulators of cell function have broader activity in vivo than simply increasing the level of prostaglandins being produced by metastatic cells. Metastasis can therefore be viewed as being modulated in vivo by several mechanisms that may include platelet aggregation and elimination of metastasized cells by host defenses such as macrophages. Prostaglandins and other naturally occurring modulators of host resistance, such as interferons, appear to affect the metastatic rate of tumor cells. Although prostaglandin D2 is not a common major AA product of most cells and therefore may not operate in all cell systems, the B16 cells may provide a system to address the importance of these mediators and mechanisms in the metastatic process.
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PMID:Prostaglandins and metastasis. 620 37

The interaction between metastasizing tumor cells and the hemostatic system of the host has been implicated in successful tumor cell dissemination. Prostacyclin (PGI2) decreases metastasis from tail vein injected B16 amelanotic melanoma (B16a) cells when administered 15 min prior to tumor cells. This effect is potentiated by a phosphodiesterase inhibitor. Initial trapping of 125I Udr labelled tumor cells in pulmonary vascular beds is unaltered by PGI2 but retention time is decreased. PGI2 decreases retention time even when administered 60 min post tumor cells. Structurally unrelated thromboxane (TX) synthetase inhibitors and a TXA2 receptor antagonist also reduce metastasis from tail vein injected B16a cells. Furthermore, one inhibitor, 1-(7-carboxyheptyl)imidazole, when injected intraperitoneally reduced spontaneous metastasis from subcutaneous B16a and Lewis lung carcinoma tumors. These results suggest that selective manipulation of PGI2 and TXA2 can reduce the hematogenous spread of tumor cells.
Clin Exp Metastasis
PMID:Inhibition of tumor cell metastasis by modulation of the vascular prostacyclin/thromboxane A2 system. 624 6

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

Our clinical study to prevent relapse and metastases in several sarcomas and malignant lymphomas of the head and neck region with a long-term treatment with mopidamole was initiated in 1972 because the pyrimido-pyrimidine derivative was shown to inhibit platelet aggregation in vivo and to increase significantly the circulation time of intravenously injected, 32P-labelled Ehrlich ascites tumour cells in mouse blood. The aggregation of platelets to circulating tumour cells and their subsequent adhesion to vascular endothelium in turn appeared to be part of the early stages of the metastatic process. It seems, however, that other related mechanisms are also involved in the clinical results obtained. Mopidamole, as other related derivatives, probably inhibits platelet aggregation by inhibition of PDE-induced decomposition of cAMP and may stimulate the synthesis and/or release of prostacyclin from the vessel wall which in turn activates adenylate cyclase involved in cAMP synthesis. The latter mechanism was definitely shown only for the related pyrimido-pyrimidine derivative dipyridamole, the methyl-xanthine derivative pentoxifylline and the methyl-pyrazoline derivative nafazatrom. The increase of cAMP levels by mopidamole results in an inhibition of 3H-thymidine incorporation into human neoplastic cells and a direct inhibition of its mitotic rate. The adding of mopidamole to a culture of a human promyelocytic leukemic cell line promotes a reverse transformation of the malignant cells to normal which appears to be a permanent phenotypic change. Furthermore, mopidamole was shown to diminish significantly spontaneous lung metastases in syngenic Wilms' tumor (nephroblastoma) of the rat, the C1300-neuroblastoma of the mouse and the HM-Kim mammary carcinoma of the rat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Modification of metastasis formation by inhibition of platelet aggregation. Experimental and clinical results]. 636 51

Tumor metastasis is mediated in part by platelet activation. Since prostacyclin regulates platelet activity, we examined stabilization of bioactivity of exogenous prostacyclin in plasma of patients with malignant bone tumors. Bioactivity of prostacyclin (platelet aggregation inhibition) incubated in patient plasma was found to be significantly less compared to that in normal plasma. In addition, the duration of bioactivity of prostacyclin was considerably less in plasma of patients with bone tumors. These preliminary data indicate decreased prostacyclin activity in plasma of patients with malignant bone tumors, which may be a mechanism of platelet-tumor cell aggregate formation and subsequent evolution of metastasis.
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PMID:Decreased stabilization of prostacyclin activity in patients with bone tumors. 637 3


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