The enzymatic machinery for the production of prostanoids and the receptors responsible for detecting their presence are widely distributed in the body. One pair of prostanoids, prostacyclin and thromboxane A(2), are particularly important in the control of haemodynamics and haemostasis. Prostacyclin achieves its antiplatelet effect by acting as a physiological antagonist, but displays some selectivity towards thromboxane A(2)-mediated platelet activation, possibly by virtue of the inability of thromboxane A(2) receptors to couple directly to G(i) proteins, and because platelet-derived endoperoxides can act as substrates for prostacyclin synthesis in endothelial cells. At low concentrations, prostaglandin E(2) can synergize with thromboxane A(2) by acting on the EP(3) subtype of prostaglandin E(2) receptor, resulting in opposition to the protective function of prostacyclin. In contrast, high concentrations of prostaglandin E(2) act on the prostacyclin receptor, and possibly the prostaglandin D(2) receptor, to turn off platelet activation. Integration of prostanoid signalling in the vascular system is similarly complex, and interpretation of data is further complicated by the regional distribution of prostanoid receptors in different vascular beds, and the poor selectivity of agonists and antagonists.

Blood Platelets↗

PubMedDate not supplied

Probable cure of metastatic testicular tumors treated with sequential therapy.

This clinical trial explores the possibility of inducing long-term unmaintained complete remissions in testicular cancer using sequential multimodality therapy. We designed a prospective study using a combination of vinblastine and bleomycin for three courses followed by cis-dichlorodiammineplatinum(II), actinomycin D, and vincristine until a surgically proven complete remission was achieved. One to three additional consolidation courses were given following surgery, and then all therapy was stopped. Eleven of 15 patients completing therapy have achieved complete remission, with seven patients remaining free of disease without maintenance therapy for 15-36 months (average, > 27 months). We conclude that patients with disseminated nonseminomatous testicular cancer should be treated for cure with intensive primary therapy. Prolonged disease-free status can be achieved without maintenance therapy, and the value of maintenance therapy needs further study.

Adolescent↗