thromboxane-a2 and Ovarian-Neoplasms

Ovarian cancer is the most lethal gynecologic malignancy among women. Due to the heterogeneity and complexity of the disease, as well as the insidious onset of symptoms, timely diagnosis remains extremely challenging. Despite recent advances in chemotherapy regimens for ovarian cancer patients, many still suffer from recurrence and ultimately succumb to the disease; thus, there is an urgent need for the identification of novel therapeutic targets. Within this rapidly evolving field, the role of platelets in the ovarian cancer tumor microenvironment has garnered increased attention. It is well-established that platelets and tumor cells exhibit bidirectional communication in which platelets enhance tumor cell invasion, extravasation, and protection from host system defenses, while tumor cells serve as platelet agonists, increasing platelet adhesion, aggregation, and degranulation. This mini-review focuses on the platelet-tumor cell relationship in ovarian cancer, specifically highlighting the essential role of bioactive lipid mediators at this interface.

Topics: Animals; Blood Platelets; Female; Humans; Neoplasm Invasiveness; Ovarian Neoplasms; Thromboxane A2

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

We studied the effect of intraperitoneal recombinant interleukin 2 (rIL-2) on the production of prostacyclin (PGI2) and thromboxane A2 (TxA2) in six patients with metastatic ovarian malignancy. Time-span urine samples collected before and after 17 intraperitoneal instillations of IL-2 (6 x 10(5) IU m-2) were assessed for 2,3-dinor-6-keto-prostaglandin F1 alpha (dinor-6-keto; a metabolite reflecting the in vivo product of PGI2) and 2,3-dinor-thromboxane B2 (dinor-TxB2; a metabolite reflecting the production of TxA2). Analysis was by high-pressure liquid chromatography, followed by radioimmunoassay. Recombinant IL-2 administration was accompanied by a significant rise (85%; P < 0.02) in the output of dinor-6-keto within the first 2 h, and this elevation persisted for up to 6 h. Moreover, output of dinor-TxB2 also rose; this rise (30%) was significant (P < 0.02) 6 h after the instillation. These effects may, in some yet unknown manner, prove significant in the anti-cancer action of rIL-2.

Topics: Epoprostenol; Female; Humans; Injections, Intraperitoneal; Interleukin-2; Ovarian Neoplasms; Recombinant Proteins; Thromboxane A2

To study the production of antiaggregatory prostacyclin (PGI2) and proaggregatory thromboxane (TxA2) by ovarian tumors, we incubated pieces of benign and malignant ovarian tissue in vitro, and measured by radioimmunoassay the release of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) (a hydration product of PGI2) and thromboxane B2 (TxB2) (a hydration product of TxA2). Healthy ovary (n = 10) produced both 6-keto-PGF1 alpha [mean, 8.9; 95% confidence interval (CI) from 5.4 to 15.2 ng/mg protein/min] and TxB2 (mean, 1.9 ng/mg protein/min; 95% CI from 1.0 to 3.7 ng/mg protein/min). The production of 6-keto-PGF1 alpha (mean, 12.2; 95% CI from 7.7 to 19.3 ng/mg protein/min) and that of TxB2 (mean, 4.8; 95% CI from 2.1 to 11.9 ng/mg protein/min) by benign cystic tumors (n = 12) was normal. Ovarian anaplastic cancer and adenocarcinoma (n = 12) produced 6-keto-PGF1 alpha on average 11.6-fold (95% CI from 5.2 to 26.0) 6-keto-PGF1 alpha and TxB2 on average 30.0-fold (95% CI from 13.5 to 66.7) over production by healthy ovaries, and the ratio of 6-keto-PGF1 alpha to TxB2 shifted to the dominance of TxB2. Similarly ovarian metastases of breast cancer, tubal cancer, and colon cancer produced increasingly 6-keto-PGF1 alpha (mean, 20.7 ng/mg protein/min) and TxB2 (5.1 ng/mg protein/min). The dominance of TxA2 in human ovarian cancer may contribute to the aggressing growth and spreading of this tumor.

Topics: Epoprostenol; Female; Humans; Ovarian Neoplasms; Thromboxane A2

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

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