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Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a previous study we observed that expression of mRNA encoding prostaglandin endoperoxide synthase is elevated within ovarian epithelial cells that cover the surface of preovulatory ovine follicles. We report herein that during the process of ovulation these cells undergo degenerative morphological changes typical of apoptosis and are sloughed from the follicular apex. This response was circumvented by blockade of ovulation by indomethacin. The effect of indomethacin was reversed by prostaglandin E2 or F2 alpha. Prostaglandin-induced DNA fragmentation (a hallmark of apoptosis) was verified in primary cultures of sheep ovarian surface epithelial cells. Prostaglandins did not cause apoptosis in a human ovarian cancer cell line of epithelial origin.
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PMID:Prostaglandin-induced apoptosis of ovarian surface epithelial cells. 832 16

The sensitivity of cancer patient macrophages from different anatomical sites to arachidonic acid metabolism was investigated in tumor cell cytotoxicity assays. Alveolar macrophages and peripheral blood monocytes from 13 non-small cell lung cancer patients, peritoneal macrophages and peripheral blood monocytes from 13 ovarian cancer patients, and comparable macrophages from control patients with nonmalignant lung or gynecological diseases were tested. Inhibitors of either the cyclooxygenase pathway or the lipoxygenase pathway together with specific metabolites of each pathway were used to evaluate how these different macrophage populations are regulated by eicosanoids. In addition, metabolic studies were performed to compare directly the arachidonic acid metabolism of macrophages obtained from these different anatomical locations. The results demonstrate that the peripheral blood monocytes from lung cancer and ovarian cancer patients and the peritoneal macrophages from ovarian cancer patients are sensitive to cyclooxygenase inhibition; this was not seen with comparable macrophages from the relevant control patients. Sensitivity to modulation by cyclooxygenase inhibition correlated with increased cyclooxygenase metabolism and with the capacity of prostaglandin to mediate suppression of tumoricidal function in these populations of cancer patient macrophages. In contrast, alveolar macrophages from cancer patients were not sensitive to either cyclooxygenase inhibition or to prostaglandin-mediated suppression. No such differential influences were revealed for the lipoxygenase pathway of arachidonic acid metabolism in any macrophage population tested. Thus, eicosanoids, particularly those of the cyclooxygenase pathway, can be a critical immunoregulatory feature of certain tumor microenvironments.
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PMID:Sensitivity of tumoricidal function in macrophages from different anatomical sites of cancer patients to modulation of arachidonic acid metabolism. 839 24

Three new diterpenoid hexose-glycosides, calyculaglycosides A-C (1-3) were isolated from the Caribbean gorgonian Eunicea sp. Calyculaglycosides A-C are rare diterpene glycosides possessing dilophol (4) aglycones related in biosynthetic origin to the elemene-type glycoside class of potent antiinflammatory agents known as fuscosides. The structures of the new compounds, which were assigned on the basis of spectral studies, were further corroborated by molecular modeling studies. Calyculaglycoside B (2) is an effective topical antiinflammatory agent stronger in potency than the industrial standard indomethacin. Calyculaglycoside B inhibits the synthesis of both prostaglandin PGE(2) and leukotriene LTB(4), suggesting it is a nonselective inhibitor of the 5-lipoxygenase and cyclooxygenase pathways. At concentrations of 10(-4)-10(-5)M, calyculaglycoside B produced LC(50)-level differential responses against a majority of the NCI ovarian cancer lines and several of the renal, prostate, and colon tumor lines.
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PMID:The Calyculaglycosides: Dilophol-Type Diterpene Glycosides Exhibiting Antiinflammatory Activity from the Caribbean Gorgonian Eunicea sp.(1)(,)(2). 1167 25

In ovarian cancer patients the poor nutritional status and cachexia are caused by the metabolic effects of the enlarging tumor masses and bowel obstruction. These patients may have a high resting energy expenditure due to increase in Cori cycle activity, glucose and triglyceride-fatty acid cycling and gluconeogenesis. Biochemical mediators of cachexia include cytokines, such as tumor necrosis factor and interleukin-6, and tumor-produced catabolic factors, such as lipid-mobilizing factor, proteolysis-inducing factor, and anemia-inducing factor. Mechanisms involved in the pathogenesis of obstruction may include extrinsic occlusion of the bowel due to pelvic, mesenteric omental masses, or intestinal motility disorders due to infilor tration of the mesentery or bowel muscle and nerves. The relief of malnutrition and cachexia may be attempted through nutritional support, pharmacological approach (megestrol acetate, cyclooxygenase inhibitors) and palliative treatment of bowel obstruction. Very few agents have been demonstrated to have true anticachectic activity, so future research should be addressed to the identification of drugs able to block the activity of tumor-produced catabolic factors. The decision regarding optimum management of bowel obstruction should be individualized. Krebs' and Goplerud's score (based on age, nutritional status, tumor status, ascites, previous chemotherapy and irradiation) seems to offer reliable eligibility criteria for those patients who can benefit from surgery.
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PMID:Malnutrition and cachexia in ovarian cancer patients: pathophysiology and management. 1171 91

Inhibition of cyclooygenase-2 (COX-2) catalytic activity has proven successful in restricting the growth of epithelial-derived cancers in vivo. Whether COX-2 inhibitor therapy would be beneficial in the prevention and/or treatment of ovarian cancer, the most lethal gynecological malignancy worldwide, is not known. Most patients with ovarian cancer undergo cytoreductive therapy. Because many of the cytotoxic drugs used to treat ovarian cancer induce COX-2 expression, samples from patients that had not undergone cytoreductive therapy were specifically chosen for COX isoform expression analysis. A majority of specimens exhibited elevated levels of COX-1, not COX-2, mRNA, and protein compared with normal ovarian tissue. Focal regions within the tumor expressing high COX-1 also had elevated levels of pro-angiogenic proteins. Selective inhibition of COX-1, not COX-2, inhibited arachidonic acid-stimulated vascular endothelial growth factor production, which could be reversed by cotreatment with prostaglandin E(2). Thus, COX-1 may contribute to carcinoma development in the ovary through stimulation of neovascularization. Clinical studies testing the efficacy of COX inhibition as adjuvant therapy for ovarian cancer may see more beneficial effects with adjuvant therapy with either a COX-1 selective or nonselective cyclooxygenase inhibitor as compared with a COX-2 selective drug.
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PMID:Cyclooxygenase-1 is overexpressed and promotes angiogenic growth factor production in ovarian cancer. 1261 1

The pre-ovulatory surge of gonadotrophins triggers a marked and obligatory increase in follicular prostaglandin synthesis prior to ovulation, and the cyclooxygenase (COX) enzyme is a key rate-limiting step in the biosynthesis of prostaglandins. In the early 1990s, the pre-ovulatory rise in follicular prostaglandin synthesis was shown to result from the selective induction of a novel COX isoform, now referred to as COX-2. Differences in the time-course of COX-2 induction in species with a short versus a long ovulatory process suggest that the enzyme could be a molecular determinant that sets the alarm of the mammalian ovulatory clock. Some of the fine molecular mechanisms involved in the transcriptional activation of the COX-2 gene in granulosa cells have also been elucidated. The binding of trans-activating upstream stimulatory factors (USF) to a consensus E-box cis-element in the proximal region of the promoter was shown to play a predominant role in COX-2 transcription. Studies showed that COX-2 expression could also serve as a valuable marker for follicular commitment to ovulation during hyperstimulatory cycles. This paper presents a comprehensive review of the events that led to the characterization of COX-2 in pre-ovulatory follicles, updates current concepts on the control of COX-2 expression in pre-ovulatory follicles, and addresses the consequences of COX-2 inhibition to women fertility and potential implications of COX-2 expression in ovarian cancer.
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PMID:Cyclooxygenase-2 and its role in ovulation: a 2004 account. 1520 95

Ovarian cancer G-protein-coupled receptor 1 (OGR1) and GPR4 have recently been identified as proton-sensing or extracellular pH-responsive G-protein-coupled receptors stimulating inositol phosphate production and cAMP accumulation, respectively. In the present study, we found that OGR1 and GPR4 mRNAs were expressed in human aortic smooth muscle cells (AoSMCs). Acidic extracellular pH induced inositol phosphate production, a transient increase in intracellular Ca(2+) concentration ([Ca(2+)](i)), and cAMP accumulation in these cells. When small interfering RNAs (siRNAs) targeted for OGR1 and GPR4 were transfected to the cells, the acid-induced inositol phosphate production and [Ca(2+)](i) increase were markedly inhibited by the OGR1 siRNA but not by the GPR4 siRNA. Unexpectedly, the acid-induced cAMP accumulation was also largely inhibited by OGR1 siRNA but only slightly by GPR4 siRNA. Acidic extracellular pH also stimulated prostaglandin I2 (PGI(2)) production, which was again inhibited by OGR1 siRNA. The specific inhibitors for extracellular signal-regulated kinase kinase and cyclooxygenase attenuated the acid-induced PGI(2) production and cAMP accumulation without changes in the inositol phosphate production. A specific inhibitor of phospholipase C also inhibited the acid-induced cAMP accumulation. In conclusion, OGR1 is a major receptor involved in the extracellular acid-induced stimulation of PGI(2) production and cAMP accumulation in AoSMCs. The cAMP accumulation may occur through OGR1-mediated stimulation of the phospholipase C/cyclooxygenase/PGI(2) pathway.
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PMID:Prostaglandin I(2) production and cAMP accumulation in response to acidic extracellular pH through OGR1 in human aortic smooth muscle cells. 1608 74

Scutellaria barbata D. Don (Lamiaceae) (SB) is a perennial herb, which is natively distributed throughout Korea and southern China. This herb is known in traditional Chinese medicine as Ban-Zhi-Lian and in traditional Korean medicine as Banjiryun. SB has been used as an antiinflammatory and antitumor agent. The SB showed strong growth-inhibitory activity and cancer chemopreventive activity in assays representing three major stages of carcinogenesis. The SB was found to act as an antimutagen; it mediated antiinflammatory effects; inhibited cyclooxygenase and hydroperoxidase functions (antipromotion activity). In addition, SB inhibited the development of preneoplastic lesions in carcinogen-treated mouse mammary glands in culture and inhibited tumorigenesis in a mouse skin cancer model. On the other hand, an inhibitory effect of SB on the growth of gynecological cancer cell lines such as HeLa cell and human ovary cancer (HOC) was shown. When HOC cells were treated with SB, the expression of cyclooxygenase-2 was inhibited. These data suggest that SB merits investigation as a potential cancer chemopreventive agent in humans, especially in gynecological cancers.
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PMID:Chemoprevention of Scutellaria bardata on human cancer cells and tumorigenesis in skin cancer. 1712 38

Menopausal ovaries undergo morphological changes, known as ovarian aging, which are implicated in the high incidence of ovarian cancer occurring during the perimenopausal and immediate postmenopausal periods. The germ cell-deficient Wv mice recapitulate these postmenopausal alterations in ovarian morphology and develop tubular adenomas. We demonstrate that a reduction of cyclooxygenase 2 gene dosage rescued the ovarian aging phenotype of the Wv mice, whereas homozygous deletion was accompanied by a compensatory increase in ovarian cyclooxygenase 1 expression and prostaglandin E(2) synthesis. Cyclooxygenase inhibitors also reduced the tumor phenotype in a preliminary study. These findings suggest that increased cyclooxygenase activity contributes to the preneoplastic morphological changes of the ovarian surface epithelium, which can be reversed by a reduction of gene dosage achieved by either genetic or pharmacological approaches.
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PMID:A reduction of cyclooxygenase 2 gene dosage counters the ovarian morphological aging and tumor phenotype in Wv mice. 1739 71

The study objective was to determine whether tumor vascularity correlates with patient survival, to compare newer semiautomated methods of angiogenesis assessment to older methods, and to determine if advanced image analysis methods can offer useful patient outcome data in serous ovarian cancer. Using the specific endothelial marker CD34, microvessel determinations were quantified in 132 serous ovarian tumors by manual counting at final magnifications of x 200 and x 400 in the most highly vascular areas. Computer-assisted image analysis microvessel counts, endothelial area estimates, and minimum spanning tree (MST) analysis of capillary architecture, which involves assessment of intercapillary distances, were correlated with traditional manual techniques.Manual, semiautomated, and advanced image analysis methods were found to be highly reproducible and express strong correlation with one another. Univariate cyclooxygenase analysis revealed angiogenesis parameters to be highly significant predictors for overall survival (OS) and disease-free survival. Multivariate cyclooxygenase analysis revealed maximum MST (P = 0.009), length MST (P = 0.005), 1 nearest neighbor (P <or= 0.01) and mean microvessel density (x 400) (P = 0.0001) to be significant predictors for OS, and mean endothelial area (P <or= 0.01) and stage (P = 0.001) significant predictors for disease-free survival. Despite showing prognostic significance on univariate analysis, most clinicopathologic parameters did not retain independent significance on multivariate analysis. Microvessel determination is an independent prognostic indicator for survival in patients with serous ovarian carcinoma. Computer-assisted image analysis is a highly reproducible method of assessment capable of accurately evaluating tumor vascularity. Minimum spanning tree analysis of capillary architecture was found to be the strongest prognosticator for OS, suggesting this to be a promising marker.
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PMID:Prognostic value of measurements of angiogenesis in serous carcinoma of the ovary. 1788 89


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