thromboxane-a2 and Uterine-Neoplasms

Topics: Contraceptives, Oral; Endometriosis; Epoprostenol; Female; Genital Neoplasms, Female; Humans; Hysterectomy; Placental Insufficiency; Pre-Eclampsia; Pregnancy; Prostaglandins; Thromboxane A2; Time Factors; Uterine Neoplasms; Uterus

An increased risk of cardiovascular disease has been found in postmenopausal women in comparison to premenopausal women. The aim of this study was to investigate platelet function, blood clotting and plasma lipid levels in 12 women with a condition of hypoestrogenism, similar to the postmenopausal status induced by treatment with the GnRH analogue buserelin for uterine leiomyoma. Platelet aggregation in whole blood and platelet-rich plasma (PRP), serum thromboxane (TX) B2 production, fibrinopeptide A (FPA) plasma levels and plasma lipid pattern were measured before and after 13 weeks of buserelin treatment. No changes of platelet aggregability were found either in whole blood or PRP. Serum TXB2 generation increased significantly after 13 weeks of therapy (p less than 0.001). No signs of increased thrombin generation were found, as indicated by unchanged FPA plasma levels. Total cholesterol plasma levels were found increased after 13 weeks, LDL cholesterol levels showed a tendency to increase although not significantly. HDL cholesterol and triglyceride concentrations were unaffected. The changes of arachidonic acid metabolism and lipid pattern suggest that buserelin treatment may induce a condition of increased thrombotic risk even if the lack of enhanced thrombin generation and increased platelet aggregability indicates that no blood clotting activation occurs.

Topics: Adult; Blood Coagulation; Blood Platelets; Buserelin; Female; Gonadal Steroid Hormones; Humans; Leiomyoma; Lipids; Menopause; Middle Aged; Thromboxane A2; Uterine Neoplasms

The release of 6-keto-prostaglandin F1 alpha(6-keto-PGF1 alpha), a metabolite of prostacyclin (PGI2) and thromboxane B2 (TxB2), a metabolite of thromboxane A2 (TxA2), was estimated in endometrial biopsies taken from 12 menorrhagic and 12 healthy women during the luteal phase of the cycle. The releases of 6-keto-PGF1 alpha and TxB2 were normal, but the ratio TxB2/6-keto-PGF1 alpha was inversely related to menstrual blood loss in women with measured menstrual blood loss exceeding 70 ml. In the second part of the study, 24 women with excessive menstrual bleeding (13 with primary menorrhagia, 10 with uterine fibromyomas, one with haemostatic factor VIII deficiency) were treated at random with ibuprofen (600 mg/day and 1200 mg/day) and with a placebo. Ibuprofen 1200 mg/day reduced (P less than 0.01) median blood loss from 146 ml (range 71-374 ml) to 110 ml (30-288 ml) in primary menorrhagia but had no effect on blood loss in women with uterine fibroids and factor VIII deficiency. Blood loss was normal in six women and was not affected by ibuprofen. Thus, our data suggest that there is a PGI2 dominance in the endometrium of patients with menorrhagia. In addition, primary, but neither fibromyoma nor coagulation defect-associated menorrhagia, can be treated by ibuprofen.

Topics: Adult; Clinical Trials as Topic; Double-Blind Method; Endometrium; Epoprostenol; Female; Humans; Ibuprofen; Leiomyoma; Menorrhagia; Middle Aged; Random Allocation; Thromboxane A2; Uterine Neoplasms

Gestational choriocarcinoma metastasizes rapidly, in which process the vasoactive prostanoids may be significant. We therefore compared the urinary excretion of prostacyclin and thromboxane A2 (TxA2) metabolites in 19 women with gestational choriocarcinoma and 20 healthy age-matched women by assessing spot urine samples for 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and 2,3-dinor-6-keto-prostaglandin F1 alpha (2,3-dinor-6-keto-PGF1 alpha) (degradation products of prostacyclin) as well as for thromboxane B2 (TxB2) and 2,3-dinor-TxB2 (degradation products of TxA2) by high-pressure liquid chromatography, followed by radioimmunoassay; the data were related to urinary creatinine concentration. The urinary output of 6-keto-PGF1 alpha [29.56 +/- 7.0 versus 25.08 +/- 3.91 ng/mmol creatinine (SE)] in patients with choriocarcinoma was normal, but that of 2,3-dinor-6-keto-PGF1 alpha in cancer patients was higher than in controls (24.44 +/- 5.20 versus 14.84 +/- 1.94, P less than 0.02), as was that of TxB2 (22.72 +/- 4.69 versus 9.69 +/- 1.52, P less than 0.001) and 2,3-dinor-TxB2 (114.21 +/- 30.81 versus 51.81 +/- 10.40, P less than 0.01). The ratio of net prostacyclin output (6-keto-PGF1 alpha plus 2,3-dinor-6-keto-PGF1 alpha) to the net TxA2 output (TxB2 plus 2,3-dinor-TxB2) in cancer patients [0.52 +/- 0.1 (SE)] was lower (P less than 0.03) than in the controls (0.83 +/- 0.1), and in an inverse relation (r = -0.54, P less than 0.05) to the scoring index of poor prognosis for the disease. We conclude that the prostanoid excess in gestational trophoblastic disease, as evidenced for the first time in this study, may originate from choriocarcinoma cells, or may be a paraneoplastic phenomenon, and we conclude also that TxA2 excess may contribute to the tumor growth and/or formation of metastases.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Biomarkers, Tumor; Choriocarcinoma; Epoprostenol; Female; Humans; Pregnancy; Reference Values; Thromboxane A2; Thromboxane B2; Uterine Neoplasms

To study the role of prostacyclin (PGI2) and thromboxane A2 (TxA2) in uterine tumors, pieces of endometrial cancer (n = 12) and leiomyomas (n = 12) were incubated in vitro, and the productions of 6-keto-prostaglandin F1a (6-keto-PGF1a, a hydration product of PGI2) and thromboxane B2 (TxB2, a hydration product of TxA2), measured by radioimmunoassay, were compared to those of corresponding healthy tissues. The production of 6-keto-PGF1a by endometrial cancer (20.8; 15.1-85.0 ng/mg protein/min, median and interquartile range), by healthy endometrium (25.5; 10.0-55.0), by healthy myometrium (34.9; 25.0-59.9) and by leiomyoma (20.3; 10.2-45.1) was similar. The production of TxB2 was increased by endometrial cancer (55.5; 10.5-155.2, p less than 0.02) in comparison with endometrium (9.8; 4.3-35.1), myometrium (3.8; 2.1-8.0) and leiomyoma (1.9; 1.0-3.8). The 6-keto-PGF1a/TxB2 ratio in endometrial cancer (0.9; 0.3-1.5) was smaller (p less than 0.02) than that in healthy endometrium (3.3; 1.9-4.8). Thus, TxA2 may be a factor in endometrial cancer.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Aged, 80 and over; Epoprostenol; Female; Humans; In Vitro Techniques; Leiomyoma; Middle Aged; Thromboxane A2; Thromboxane B2; Uterine Neoplasms

To explore the relationships between the antioxidant selenium and pro-aggregatory thromboxane A2 in patients with gynaecological cancer, we measured the serum concentrations of selenium and the production of thromboxane B2 (TxB2, a stable metabolite of thromboxane A2) by the aggregating platelets in patients with endometrial (n = 35), ovarian (n = 30) and cervical cancer (n = 25), and in 32 control women. The selenium concentration in endometrial (1.14 +/- 0.04 mumol/l; mean +/- SE), ovarian (0.96 +/- 0.04 mumol/l) and cervical cancer (0.97 +/- 0.06 mumol/l) was significantly lower than in control subjects (1.26 +/- 0.03 mumol/l). The release of TxB2 into serum during spontaneous clotting of the blood was significantly increased in ovarian cancer (229.2 +/- 15.9 ng/ml), decreased in endometrial cancer (142.6 +/- 12.4 ng/ml) and normal in cervical cancer (185.9 +/- 14.8 ng/ml) as compared with control subjects (185.9 +/- 11.9 ng/ml). The levels of selenium and TxB2 did not correlate with each other in the whole series or in any subgroup. Thus, selenium does not seem to be an important determinant in the biosynthesis of TxB2 in patients with gynaecological malignancy.

Topics: Adult; Aged; Blood Platelets; Female; Genital Neoplasms, Female; Humans; Middle Aged; Ovarian Neoplasms; Platelet Aggregation; Selenium; Thromboxane A2; Thromboxane B2; Uterine Cervical Neoplasms; Uterine Neoplasms

Plasma levels of thromboxane (TX) A2 and prostacyclin (PGI2), as measured by radioimmunoassay of their respective stable metabolites TXB2 and 6-keto PGF1 alpha, were studied in six molar pregnancies immediately before, immediately following and 24 h after evacuation of the uterus. The mean (SD) levels for TXB2 were 150 (41), 137 (32) and 125 (25) pg/ml respectively, and for 6-keto PGF1 alpha the respective values were 225 (52), 226 (127) and 213 (49) pg/ml. There was no significant difference in the levels of prostanoids between the samples taken at the various time intervals. The concentration of these prostanoids in molar intravesicular fluid was also determined. Their respective mean (SD) pg/ml values were 3682 (760) for TXB2 and 2969 (744) for 6-keto PGF1 alpha. In 15 normal pregnancies of equivalent gestation, the mean amniotic fluid levels of TXB2 and 6-keto PGF1 alpha were 34 (17) and 146 (86) pg/ml respectively. The ability of molar trophoblast to generate the prostanoids from [14C]arachidonic acid in vitro was also demonstrated. Mean (SD) values for TXB2 and 6-keto PGF1 alpha were 12.2 (2.6) and 13.2 (1.8) pg/mg protein/min, respectively. It is likely that the high concentrations of prostanoids in vesicular fluid reflect the synthesizing ability of the villus vesicles. The mole contributes little to the circulatory prostanoids possibly because its villi are deficient in blood circulation.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Epoprostenol; Female; Humans; Hydatidiform Mole; Pregnancy; Thromboxane A2; Thromboxane B2; Thromboxanes; Uterine Neoplasms

Serial measurements of 6-keto-PGF1 alpha (a stable metabolite of prostacyclin), thromboxane B2 (TxB2, a stable metabolite of thromboxane A2), and 13,14-dihydro-15-keto-PGF2 alpha (M-PGF2 alpha, a stable metabolite of prostaglandin F2 alpha) were made from plasma of 9 women with metastatic ovarian or uterine malignancies before and after the combined administration of doxorubicin, cyclophosphamide, 5-fluorouracil, and cis-platinum. Elevated basal levels of TxB2 were detected in all patients, elevated levels of 6-keto-PGF1 alpha in 5 patients and elevated levels of M-PGF2 alpha in 3 patients. The use of chemotherapy was accompanied by a significant increase of 37% (P less than .01) in the M-PGF2 alpha level on the day after treatment and by significant decreases of 30 to 40% (P less than .05) in 6-keto-PGF1 alpha and TxB2 levels, which became apparent immediately after the treatment and persisted for 3 to 5 days. Thus, malignancies may be accompanied by increased production of prostacyclin and thromboxane A2, which can be lowered by cytostatics.

Topics: Aged; Antineoplastic Agents; Drug Therapy, Combination; Epoprostenol; Female; Humans; Middle Aged; Ovarian Neoplasms; Prostaglandins; Prostaglandins F; Thromboxane A2; Thromboxane B2; Thromboxanes; Uterine Neoplasms