dinoprost and Ovarian-Neoplasms

The aim of the study is to evaluate oxidant-antioxidant balance as well as lysosomal and anti-protease activities in ovarian cancer since it has been emphasized that the crucial inducing factor of carcinogenesis may be reactive oxygen/nitrogen species or, more precisely, oxidative stress-induced inflammation. The study involved 15 women with ovarian cancer, aged 59.9 ± 7.8 years, and 9 healthy women aged 56.3 ± 4.3 years (controls). The study material was venous blood collected from fasting subjects. In erythrocytes, the activities of superoxide dismutase, glutathione peroxidase, and catalase, as well as concentrations of conjugated dienes (CDs) and thiobarbituric acid reactive substances (TBARS), were investigated. CD, TBARS, and vitamins A and E plasma concentrations were also determined. Moreover, total antioxidant capacity and concentrations of 4-hydroxynonenal adducts and 8-iso-prostaglandin F2α, as well as activities of acid phosphatase, arylsulfatase, cathepsin D, and α

Topics: Aged; Catalase; Cathepsin D; Dinoprost; Female; Glutathione Peroxidase; Humans; Lysosomes; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Ovarian Neoplasms; Oxidative Stress; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vitamin A; Vitamin E

To evaluate 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-isoprostane levels in the peritoneal fluid (PF) of women with endometriosis.. One hundred and ten women with laparoscopically and histopathologically confirmed endometriosis and, as reference groups, 119 patients with simple serous (n=78) and dermoid (n=41) ovarian cysts were studied. Peritoneal fluid 8-OHdG and 8-isoprostane concentrations were evaluated by enzyme-linked immunosorbent assays.. 8-OHdG and 8-isoprostane levels in peritoneal fluid were significantly higher in patients with endometriosis compared with the reference groups. Higher PF 8-OHdG and 8-isoprostane concentrations were observed in patients with advanced stages of endometriosis. A statistically significant positive correlation was found between 8-OHdG and 8-isoprostane levels in peritoneal fluid.. Endometriosis induces greater oxidative stress and frequent DNA mutations in peritoneal fluid than nonendometriotic ovarian cysts. The most severe oxidative stress occurs in the peritoneal cavity of women with more advanced stages of the disease.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Adult; Ascitic Fluid; Biomarkers; Cysts; Deoxyguanosine; Dermoid Cyst; Dinoprost; Endometriosis; Female; Humans; Middle Aged; Mutation; Ovarian Cysts; Ovarian Neoplasms; Oxidative Stress; Peritoneum; Severity of Illness Index; Up-Regulation; Young Adult

Suppression of Bcl-2 expression can overcome cellular resistance to apoptosis induced by the adenovirus type 5 gene E1A in models of ovarian and breast cancer. Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, is known to downregulate Bcl-2 expression. We hypothesized that celecoxib would enhance E1A-induced apoptosis by suppressing Bcl-2 through suppressing COX-2 expression. If successful, this strategy could represent a means of overcoming resistance to E1A gene therapy.. We first established the cytotoxicity of celecoxib in two COX-2-overexpressing E1A-transfected breast cancer cell lines (MDA-MB-231 and MDA-MB-435) and in two low-COX-2-expressing E1A-transfected cell lines (MCF-7 (breast cancer) and SKOV3.ip1 (ovarian cancer)). We next tested whether higher sensitivity to celecoxib among these cell lines resulted from increased apoptosis by flow cytometry and western blotting. We further investigated whether suppression of Bcl-2 by celecoxib was involved in the apoptosis resulting from celecoxib treatment, and we explored whether the celecoxib-induced apoptosis in these cells depends on a COX-2 downstream pathway.. The two COX-2-overexpressing cell lines MDA-MB-231-E1A and MDA-MB-435-E1A were more sensitive to celecoxib than the corresponding control cells, but the two low-COX-2-expressing cell lines MCF-7-E1A and SKOV3.ip1-E1A were no more sensitive than control cells to celecoxib. Therefore, we used the MDA-MB-231-E1A and MDA-MB-435-E1A cells for all further experiments. In both cell lines, sub-G1 fraction was increased, or cleavage of PARP and caspase-9 were increased after 5 days of exposure to 40 microM celecoxib. However, Bcl-2 was suppressed only in the MDA-MB-435-E1A cells and not in the MDA-MB-231-E1A cells. Restoring Bcl-2 expression in the MDA-MB-435-E1A stable transfectants did not affect their sensitivity to celecoxib. However, adding prostaglandin E2 (PGE2) or PGF2alpha blunted the sensitivity to celecoxib of both E1A stable transfectants.. We speculate that one mechanism by which celecoxib enhances E1A-induced apoptosis in cells that express high levels of COX-2 is through blocking PGE2 or PGF2alpha.

Topics: Adenovirus E1A Proteins; Apoptosis; Blotting, Western; Breast Neoplasms; Celecoxib; Cell Survival; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dinoprost; Dinoprostone; Female; Flow Cytometry; Humans; Ovarian Neoplasms; Proto-Oncogene Proteins c-bcl-2; Pyrazoles; Sulfonamides; Transfection; Tumor Cells, Cultured

Malignant ascites is a major source of morbidity and mortality in ovarian cancer patients. It functions as a permissive reactive tumor-host microenvironment and provides sustenance for the floating tumor cells through a plethora of survival/metastasis-associated molecules. Using a syngeneic, immunocompetent model of peritoneal ovarian carcinomatosis in SP(-/-) mice, we investigated the molecular mechanisms implicated in the interplay between host secreted protein acidic and rich in cysteine (SPARC) and ascitic fluid prosurvival/prometastasis factors that result in the significantly augmented levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP). Ascitic fluid-enhanced ID8 invasiveness was mediated through VEGF via a positive feedback loop with MMP-2 and MMP-9 and through activation of alpha(v) and beta(1) integrins. Host SPARC down-regulated the VEGF-MMP axis at the transcriptional and posttranscriptional levels. In vitro, SPARC attenuated the basal as well as VEGF-induced integrin activation in tumor cells. SPARC inhibited the VEGF- and integrin-mediated ID8 proliferation in vitro and significantly suppressed their tumorigenicity in vivo. Relative to SP(+/+), SP(-/-) ascitic fluid contained significantly higher levels of bioactive lipids and exerted stronger chemotactic, proinvasive, and mitogenic effects on ID8 cells in vitro. SP(-/-) ascites also contained high levels of interleukin-6, macrophage chemoattractant protein-1, and 8-isoprostane (prostaglandin F(2)alpha) that were positively correlated with extensive infiltration of SP(-/-) ovarian tumors and ascites with macrophages. In summary, our findings strongly suggest that host SPARC normalizes the microenvironment of ovarian cancer malignant ascites through down-regulation of the VEGF-integrin-MMP axis, decreases the levels and activity of bioactive lipids, and ameliorates downstream inflammation.

Topics: Animals; Ascitic Fluid; Carcinoma; Cell Adhesion; Cell Proliferation; Cell Survival; Chemokine CCL2; Dinoprost; Female; Inflammation; Integrins; Interleukin-6; Metalloendopeptidases; Mice; Mice, Mutant Strains; Osteonectin; Ovarian Neoplasms; Peritoneal Neoplasms; Tissue Inhibitor of Metalloproteinases; Vascular Endothelial Growth Factor A

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

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