thromboxane-b2 and Ovarian-Neoplasms

The production of the antiaggregatory prostacyclin (PG1(2) ) and proaggregatory thromboxane A2 (TxA2) were studied in 19 patients with residual ovarian cancer. The plasma 6-keto-PGF1 alpha (a metabolite of PG1(2) ) in cancer patients (146.7 +/- 14.7 pg/ml, mean +/- SE) was higher (P less than 0.02) than that in the controls (85.3 +/- 9.2 pg/ml, n = 17). Also the releases of TxB2 (a metabolite of TxA2) during spontaneous clotting of the blood samples were greater (P less than 0.05) in the patients (253.4 +/- 30.1 ng/ml) than controls (183.2 +/- 19.8 ng/ml). The combined administration of doxorubicin, cyclophosphamide and cis-platinum temporarily decreased the plasma 6-keto-PGF1 alpha levels but caused no changes in TxB2 generation. Prostaglandin synthesis inhibitors (acetylsalicyclic acid or indomethacin) during cytostatic infusion did not prevent the occurrence of the acute side effects of cytostatics, but they inhibited the TxB2 generation. Thus our data suggest that residual ovarian cancer is accompanied by increased production of PG1(2) and TxA2, and that prostaglandins have no role in the acute side effects of cancer chemotherapy.

Topics: 6-Ketoprostaglandin F1 alpha; Antineoplastic Combined Chemotherapy Protocols; Aspirin; Epoprostenol; Female; Humans; Indomethacin; Ovarian Neoplasms; Thromboxane A2; Thromboxane B2; Thromboxanes

To study the relationship between cyclooxygenase-2 (COX-2) protein expression, prostaglandins levels assay and ovarian carcinoma biologic behavior in ovarian carcinoma tissue.. The levels of COX-2 protein, prostaglandin (PG) E(2), 6-keto-PGF(1 alpha) and thromboxane (TX) B(2) in 54 biopsy specimens from patients with ovarian serous tumor which included three groups: 33 samples of ovarian serous carcinomas; 10 samples of borderline ovarian serous tumors and 11 samples of benign ovarian serous tumors and 10 samples of normal ovarian tissues were detected by western blot analysis and radioimmunoassay to investigate their clinical significance.. (1) The levels of COX-2 protein expression (82%, 27/33) and relative quantity (20.08 +/- 3.53) in ovarian serous tumor tissues were statistically higher than those in benign ovarian serous tumor tissues and in normal ovary tissues [0 and (15.04 +/- 0.12), 0 and (15.33 +/- 0.60), P < 0.05]. The level of COX-2 protein expression in borderline ovarian serous tumor tissues (90%, 9/10) and relative quantity (20.61 +/- 3.03) were statistically higher than those in benign ovarian serous tumor and normal ovary tissues (P < 0.05). The levels of COX-2 protein expression and relative quantity were found no significant differences in different clinical stages (I to II and III to IV), different histological grades, with or without ascites and lymphatic metastasis. (2) The levels of PGE(2), 6-keto-PGF(1 alpha) and TXB(2) in ovarian serous carcinoma tissues were statistically higher than in borderline ovarian serous tumor, benign ovarian serous tumor or normal ovarian tissues (P < 0.05). No significant differences of the levels were found among borderline tissues, benign tissues or normal ovarian tissues (P > 0.05). PGE(2), 6-keto-PGF(1 alpha) and TXB(2) were found no significant differences in different clinical stages (I to II and III to IV), different histological grades, with or without ascites and lymphatic metastasis. (3) COX-2 expression was correlated with PGE(2), 6-keto-PGF(1 alpha) and TXB(2) (P < 0.01).. (1) Our data suggest that COX-2 overexpression leads to increased PGE(2), 6-keto-PGF(1 alpha) and TXB(2) biosynthesis, which may be mechanisms underlying the contribution of COX-2 to the development of ovarian serous carcinoma. (2) PGE(2), 6-keto-PGF(1 alpha) and TXB(2) may be helpful parameters of diagnosis and differentiate diagnosis in ovarian serous carcinoma.

Topics: 6-Ketoprostaglandin F1 alpha; Cyclooxygenase 2; Dinoprostone; Female; Humans; Isoenzymes; Membrane Proteins; Neoplasm Staging; Ovarian Neoplasms; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Thromboxane B2

We studied the effect of ovarian cancer and its chemotherapy on the urinary excretion of prostacyclin (PGI2) and thromboxane A2 (TxA2) hydration and metabolic products. In six patients we measured 6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha (PGI2 products) and thromboxane B2 (TxB2) and 2,3-dinor-TxB2 (TxA2 products) by HPLC followed by radioimmunoassay before, during and after the combined infusion of cisplatin, 4'epi-adriamycin and cyclophosphamide. Before the first cytostatic infusion, the urinary excretion of prostanoids was on average 4.4-5.8 times higher than in patients with ovarian endometriosis (n = 19). The infusion of cytostatics led to a 50-120% rise in the excretion of prostanoids during the first post-infusion 9 hours, but in the subsequent 10 hours their output was 25-45% below the initial value and remained low for at least 2 weeks. Following repetitive courses of cytostatics (2-4 per patient), prostanoid excretion tended to normalise. These data suggest that ovarian cancer is associated with increased production of PGI2 and TxA2, and that cytostatics suppress this production. This may be of biological significance in tumour behaviour and in the effect of cytostatics.

Topics: 6-Ketoprostaglandin F1 alpha; Adenocarcinoma; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclophosphamide; Cystadenocarcinoma; Endometriosis; Epirubicin; Female; Humans; Middle Aged; Ovarian Neoplasms; Thromboxane B2

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

The concentrations of prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, thromboxane B2(TxB2), cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in ovarian tumor tissue were measured in 38 post-menopausal women with malignant or benign ovarian tumor and in six women without ovarian neoplasm. PGE2 and TxB2 contents in ovarian cancer tissue were significantly (P less than 0.05) higher than in normal ovarian tissue. The prostanoids were also increased in the cyst fluid of epithelial malignant tumors compared to cyst fluids of benign ovarian tumors. Cyclic AMP concentrations in cancer tissue were lower than in non-malignant ovarian tissue, while the levels of cGMP were similar in all groups studied.

Topics: Aged; Aged, 80 and over; Cyclic AMP; Dinoprostone; Female; Humans; Middle Aged; Nucleotides, Cyclic; Ovarian Neoplasms; Prostaglandins; Prostaglandins E; Thromboxane B2

The five stable metabolites [prostaglandin F2 alpha (PGF2 alpha), prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha)] of arachidonic acid (AA) via the cyclooxygenase pathway were measured by high-resolution gas chromatography-mass spectrometry in M5076 ovarian reticulosarcoma (M5) homogenates at various times after tumor implantation (Days 15, 18, 21, and 24). Vegetating tumor showed an active AA overall metabolism, which significantly increased during tumor growth. Synthesis of selected products (TXB2, PGD2, and PGE2) increased markedly over time (up to 10.6, 3.5, and 0.9 micrograms/g, respectively). The overall metabolic profile was TXB2 much greater than PGD2 greater than PGF2 alpha greater than 6-keto-PGF1 alpha greater than PGE2 on Day 15 and TXB2 much greater than PGD2 much greater than PGF2 alpha greater than 6-keto-PGF1 alpha on Day 24. TXB2 was also by far the most abundant product of in vitro-cultured M5 cells. Chronic treatment of M5-bearing mice with dazmegrel (UK-38,485), a selective thromboxane synthetase inhibitor (100 mg/kg p.o. daily, from Day 7 to killing), resulted in incomplete TXB2 synthesis inhibition, AA metabolism diversion toward the other prostaglandins, and no effects of tumor growth and metastasis. More frequent dazmegrel treatment (100 mg/kg p.o. every 8 h from Day 1 to killing) resulted in complete TXB2 synthetase inhibition, AA metabolism diversion, and increased tumor growth and metastasis. These data do not support the hypothesis of thromboxane synthetase inhibitors reducing tumor growth. However, since TXB2 suppression was accompanied by the production of other products possibly interfering in tumor growth, no conclusions on the effective role of TXA2 in malignancy can be drawn.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Dinoprostone; Female; Gas Chromatography-Mass Spectrometry; Imidazoles; Lymphoma, Non-Hodgkin; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Ovarian Neoplasms; Prostaglandin D2; Prostaglandins; Prostaglandins D; Prostaglandins E; Thromboxane B2; Thromboxane-A Synthase; Thromboxanes

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

Tissue contents of prostaglandin E2 (PGE2), thromboxane B2 (TxB2, a metabolite of proaggregatory thromboxane A2) and 6-keto-PGF1 alpha (a metabolite of antiaggregatory prostacyclin, PGI2) were measured from ovarian cancer (n = 13), borderline malignant, benign ovarian tumor and normal ovary of postmenopausal women. TxB2 contents were significantly (p less than 0.05) increased in metastatic ovarian cancer tissue, compared to local ovarian cancer, borderline malignant, benign tumor or normal ovarian tissues, while in 6-keto-PGF1 alpha production there was no difference between these groups. PGE2 contents were also increased in metastatic ovarian cancer tissue. These data suggest the association between local PG production and advanced ovarian cancer tissue.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Dinoprostone; Epoprostenol; Female; Humans; Middle Aged; Neoplasm Metastasis; Ovarian Neoplasms; Prostaglandins E; Thromboxane B2; Thromboxanes

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