thromboxane-b2 and Uterine-Neoplasms

In order to investigate the production of eicosanoids in human endometrium, myometrium, leiomyoma, adenomyosis, normal ovary, non-endometrial cyst and endometrial cyst, slices of each tissue were incubated. 6-Keto-prostaglandin (PG) F1 alpha, thromboxane (TX) B2, PGF2 alpha and PGE2 concentrations in the incubation medium were measured by direct RIA. 6-Keto-PGF1 alpha production of adenomyosis was significantly higher than that of endometrium, myometrium and leiomyoma, especially in the menstrual phase. The production of eicosanoids in endometrial cyst was significantly higher than that of non-endometrial cyst and normal ovary. These results suggest that endometriosis is associated with increased eicosanoid production in vivo.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Cysts; Dinoprost; Dinoprostone; Eicosanoids; Endometriosis; Female; Humans; Leiomyoma; Middle Aged; Myometrium; Ovary; Thromboxane B2; 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

In order to investigate whether prostanoids are involved in the pathophysiology of endometriosis, prostaglandin and leukotriene concentrations in peritoneal fluid were measured in adenomyosis, ovarian chocolate cyst and uterine leiomyoma. In the secretory phase, there was no significant difference in 6-keto PGF1 alpha concentration in peritoneal fluid between the adenomyosis group and the leiomyoma group. TXB2 concentration did not significantly differ in the three study groups. Leukotriene C4 level in the adenomyosis group was significantly higher than that of leiomyoma in the secretory phase. Leukotriene B4 could not be detected by our assay system. Our results suggest that leukotriene C4 is possibly involved in the pathophysiology of endometriosis.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Ascitic Fluid; Endometriosis; Female; Genital Diseases, Female; Humans; Leukotriene B4; Prostaglandins; SRS-A; Thromboxane B2; Uterine Neoplasms

The biochemical responses to 8-week supplementary treatment with selenium and/or vitamin E were evaluated in 41 patients with gynaecological cancer during cytotoxic chemotherapy, in Finland, a selenium-deficient country. After the control course of 1-day treatment with cytostat agents, 11 patients received a combination of selenium and vitamin E (sodium selenate, 200 micrograms/day + vitamin E, 300 mg/day), 11 received selenium (sodium selenate, 200 micrograms/day) and seven received vitamin E (300 mg/day) as supplementary therapy, while 12 patients had no supplementary drugs. Sodium selenate alone and combined with vitamin E significantly increased the serum selenium levels, but the activity of serum glutathione peroxidase (GSH-Px) increased significantly only in the selenium- and vitamin E-treated patients with low initial GSH-Px activity. The cytotoxic chemotherapy did not change the activity of GSH-Px, while the concentrations of lipid peroxides decreased. Sodium selenate alone or with vitamin E did not modify this decrease. Sodium selenate alone significantly decreased the capacity of the platelets to produce thromboxane A2; it increased high-density lipoprotein cholesterol levels and prevented the cytotoxic-chemotherapy-associated increase of creatine kinase. Selenium supplementation might thus be beneficial during cytotoxic chemotherapy in ovarian cancer patients with low selenium levels.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cholesterol, HDL; Drug Therapy, Combination; Female; Glutathione Peroxidase; Humans; Lipid Peroxides; Ovarian Neoplasms; Selenium; Thromboxane B2; Uterine Neoplasms; Vitamin E

Peripheral plasma prostaglandins (PGs) were assayed in 10 cases of gynecologic malignancies. In addition, fluctuations of PG levels during chemotherapeutically-induced gastrointestinal toxicity as well as those caused by a bolus infusion of steroid hormone were investigated. As a result, the level of PGE2 in most cases of gynecologic malignancies was seen above or around the upper limit of that in healthy women. During chemotherapy, the levels of PGF2 alpha and thromboxane B2 (TxB2) increased significantly compared to baseline levels (P less than 0.05). A bolus infusion of steroid hormone did not bring about any noticeable change in any of the levels of PGF2 alpha, TxB2, PGE2 or 6K. It may be inferred from these findings that PGs are synthesized in tumor tissue itself and released into plasma. Also, the finding that the levels of peripheral plasma PGs increased during chemotherapy suggested that such an increase in PG release could be one of the factors causing gastrointestinal toxicity. Based on the fact that there were no changes in levels of peripheral plasma PGs due to the administration of steroid hormone, however, we failed to support the proposal that steroid hormone suppresses the release of PG.

Topics: 6-Ketoprostaglandin F1 alpha; Antineoplastic Combined Chemotherapy Protocols; Dinoprost; Dinoprostone; Female; Humans; Hydrocortisone; Nausea; Ovarian Neoplasms; Prostaglandins; Prostaglandins E; Prostaglandins F; Radioimmunoassay; Thromboxane B2; Uterine Neoplasms; Vomiting

Fatty acid composition and arachidonic acid metabolites in ascitic fluids of patients with ovarian cancer were compared to those in the peritoneal fluids of patients with benign gynecologic conditions. Substantial amounts of PGE2, PGF2 alpha, TXB2, and leukotriene B4 were detected in the fluids of the both patient groups. In the group of the cancer patients the concentrations of TXB2 were slightly smaller than those in the control group. In the percentage amounts of the eicosanoid precursor fatty acids there could not be detected differences between these two groups. However, in the peritoneal fluids of the cancer patients the percentage amount of palmitoleic acid (16:1) was significantly higher than that in the control group.

Topics: Arachidonic Acid; Arachidonic Acids; Ascitic Fluid; Dinoprost; Dinoprostone; Fatty Acids; Fatty Acids, Monounsaturated; Female; Humans; Leiomyoma; Leukotriene B4; Ovarian Neoplasms; Palmitic Acids; Prostaglandins E; Prostaglandins F; Radioimmunoassay; SRS-A; 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