6-ketoprostaglandin-f1-alpha 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

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

Tissue contents of prostaglandins (PG) PGE2, PGE2a and 6-keto-PGF1a (degradation product of PGI2) were determined in specimens of advanced human ovarian cancer (n = 11). The PG levels (ng/mg tissue protein) varied widley: PGE2 17-515; PGF2a 2-43 and 6-keto-PGF1a 5-105. Tumors of patients without response to chemotherapy contained more PGE2, PGF2a and 6-keto-PGF1a than did tumors responding to chemotherapy. PG production was investigated in two ovarian carcinoma-derived cell lines. The ability of these cells to synthesize PG varied depending on the cell density. An increase of cell number was associated with a decrease of PG yield. PG formation was inhibited by indomethacin in a concentration-dependent manner. The present study suggests that ovarian carcinoma cells form PG in vivo and vitro.

Topics: 6-Ketoprostaglandin F1 alpha; Adenocarcinoma; Animals; Cell Line; Dinoprost; Dinoprostone; Female; Humans; Mice; Mice, Nude; Ovarian Neoplasms; Prostaglandins; Prostaglandins E; Prostaglandins F

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