Prostacyclin and thromboxanes. Implications for their role in tumor cell metastasis

Survival of mice with NC carcinoma is unchanged by drugs that are thought to inhibit thromboxane synthesis or increase prostacyclin formation

“…However, we found no effect of the drug on the serum or tumour prostanoid content or host survival, although nafazatromtreated mice tended to have smaller tumours. The lack of effect on survi'Val is consistent with the failure of nafazatrom to sffect serum or tumour prostanoids, but again we do not know if this explains the difference from the results of Honn et al (1983) since they did not measure prostanoids.…”

“…Nafazatrom is reported to inhibit lipoxygenase activity and increase PGI2 production, and was found by Honn et al (1983) to reduce the formation of lung metastases in mice injected with B-16a melanoma cells. However, we found no effect of the drug on the serum or tumour prostanoid content or host survival, although nafazatromtreated mice tended to have smaller tumours.…”

“…Platelet aggregation is thought to be important in the haematogenous spread of some tumours, and Honn (1982) and his colleagues (Honn et al, 1981(Honn et al, , 1983 suggested that circulating tumour cells, or vesicles shed from the primary tumour cells, disrupt the balance between PGI2 and TXA2 in favour of platelet aggregation. Experiments with intravenously injected B-16a melanoma cells showed that thromboxane synthesis inhibitors, PGI2, or nafazatrom (which has various actions including an increase of PGI2 formation), are antimetastatic (Honn, 1982;Honn et al, 1983). A thromboxane synthesis inhibitor also reduced spontaneous metastasis from Lewis lung carcinoma (Honn, 1982 Drugs that inhibit cyclo-oxygenase usually reduce the size of NC tumours, and prolong host survival when given alone or with the cytotoxic drugs methotrexate and melphalan (Bennett et al, 1979(Bennett et al, , 1982.…”

Urinary excretion of prostacyclin and thromboxane degradation products in patients with ovarian malignancy: effect of cytostatic treatment

“…It is generally thought that PGI2 or its dominance over TxA2 should prevent metastasis (Honn et al, , 1983b, but this theory has also been disputed (Stamford et al, 1986). The picture may be partly unclear due to difficulties in assessing PGI2 and TxA2 production in vivo.…”

Effect of n-3 fatty acids on spontaneous and experimental metastasis of rat mammary tumour 13762

“…Thromboxane A2 has highly potent vasoconstricting and platelet-aggregatory effects, actions that are important in development of metastasis (Honn et al, 1983;Gasic et al, 1973;Karmali et al, 1986;Mehta et al, 1987). When n-3 fatty acids are included in the diet, eicosapentaenoic acid and docosahexaenoic acid compete with arachidonic acid and inhibit the production of thromboxane A2 by tumour cells and platelets.…”