dinoprost and Uterine-Neoplasms

Uterine myomas (UM) are responsible for significant morbidity and have adverse effects on quality of life in women. Reactive oxygen species (ROS) and antioxidant enzymes (AOE), as well as sex steroids play important roles in the reproductive physiology processes. Thus, we aimed to investigate the role of oxidant-antioxidant status in UM by measuring the AOE activities and lipid peroxidation (LPO) levels. This is the first study assessing these parameters together in UM based on also menopausal status and evaluating possible correlations between AOE activities, LPO markers, tumor biomarkers, female reproductive system hormone levels, comprehensively.. The study group consisted of patients who have undergone surgical resection with confirmed pathology of uterine myoma (UM, n = 25) and divided into subgroups; premenopausal (UM. All AOE activities were higher (∼40% for Cu,Zn-SOD, p = 0.003; ∼55% for CAT, p = 0.001; ∼15% for GPx1, p = 0.169) and the LPO levels were lower (∼60% for MDA, p = 0.011 and ∼45% for 8-epi-PGF2α, p = 0.055) in patients with UM vs control. Approximately similar alterations were observed in UM. Decreased LPO levels might be the consequence of compensator high antioxidant enzyme activities against mild oxidative stress in the circulation of patients with UM. The marked negative correlation between erythrocyte Cu,Zn-SOD activity and plasma MDA levels also supported this finding.

Topics: Adult; Antioxidants; Biomarkers, Tumor; Dinoprost; Female; Hormones; Humans; Leiomyoma; Lipid Peroxidation; Middle Aged; Oxidative Stress; Uterine Neoplasms

Oxidative stress is known to be an important contributing factor in many chronic diseases. Spontaneously occurring benign oviduct leiomyomas are common tumors of the Japanese quail (Coturnix coturnix japonica), which makes it a good animal model for screening potential agents for testing in the prevention and treatment of human myoma uteri. Since dietary intake of selenium has been associated with a reduced risk of a variety of human cancers, we investigated the effects of selenium supplementation on the development of leiomyomas in the Japanese quail. Potential mechanisms of action of selenium include its antioxidant properties and modulation of heat shock protein 70 (Hsp70); therefore, we measured levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-isoprostane levels, and Hsp70 expression in tissue specimens obtained from the quails. One hundred and eighty quails (8 mo old) were assigned to 3 treatment groups consisting of 60 birds in each group. Birds were fed either a basal diet containing 0.048 mg Se per kg or the basal diet supplemented with 0.2 mg or 0.4 mg of selenium (Selenomax, yeast-bound l-selenomethionine, 60%) per kg of diet. The animals were sacrificed after 250 days, and the tumors were identified. Selenium supplementation did not affect the number of leiomyomas as compared to control subjects (P > 0.05). However, the tumors in selenium fed birds were smaller than those found in control birds (P = 0.01). Serum Se increased (P = 0.01), whereas MDA and 8-isoprostane, 8-OHdG concentrations decreased (P = 0.01) with selenium supplementation (P = 0.01). Selenium supplementation decreased Hsp70 in the tissue of birds. The results indicate that dietary supplementation with selenium reduces the size of spontaneously occurring leiomyoma of the oviduct in the Japanese quail.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Anticarcinogenic Agents; Antioxidants; Coturnix; Deoxyguanosine; Dietary Supplements; Dinoprost; Female; Genital Neoplasms, Female; HSP70 Heat-Shock Proteins; Incidence; Leiomyoma; Liver; Malondialdehyde; Oviducts; Random Allocation; Selenium; Selenomethionine; Tumor Burden; Uterine Neoplasms; Yeast, Dried

The association between uterine myoma and infertility is still controversial. The anatomical defect of endometrium by uterine fibroids could be a factor for reducing pregnancy rates and increasing miscarriage rates. However, pregnancy and implantation rates were found to be significantly lower in women with intramural myomas (IMMs), when there was no deformity of uterine cavity. This could be due to other biological factors such as increased accumulation of inflammatory cells within fibroid tissue and corresponding endometrium that might impair fertility. Therefore, we tried to investigate the pattern of macrophage (Mvarphi) accumulation in different uterine fibroids and the production of chemokine and prostaglandin (PG) by these tissues.. The selection criteria of uterine fibroids were based on the classification of European Society of Hysteroscopy. Biopsy specimens were collected from respective nodules and autologous endometrium of 20 women with submucosal myoma (SMM), 29 women with IMM and 18 women with subserosal myoma (SSM). CD68 immunoreactive Mvarphis were identified in these tissues by immunohistochemistry. A fraction of corresponding tissues were homogenized, and levels of monocyte chemotactic protein-1 (MCP-1) and PGF(2alpha) were measured by enzyme-linked immunosorbent assay (ELISA).. Mvarphi infiltration in the myoma nodule and corresponding endometrium of women with SMM and IMM was significantly higher than that of women with SSM or control women (P<0.01 and P<0.05, respectively). This tissue accumulation of inflammatory cells was independent of the sizes of the myoma nodules and phases of menstrual cycle. The tissue concentration of MCP-1 corresponded to increased Mvarphi infiltration and was significantly higher in women with SMM and IMM than that in women with SSM (P<0.05 for each). A positive correlation was observed between MCP-1 concentration and accumulated Mvarphi numbers in the endometrium of women with SMM and IMM but not in women with SSM. The tissue levels of PGF2alpha were also significantly higher in the nodule and corresponding endometrium of women with SMM and IMM than that in SSM or control women (P<0.05 for each).. Higher production of MCP-1 could be responsible for the increased accumulation of Mvarphi in women with SMM and IMM. The augmented inflammatory reaction in endometrium and increased PGF2alpha levels might be detrimental to reproductive outcome in women with SMM or IMM.

Topics: Adolescent; Adult; Animals; Antibodies, Monoclonal; Antibodies, Neoplasm; Biopsy; Cell Line, Tumor; Chemokine CCL2; Dinoprost; Female; Humans; Immunohistochemistry; Leiomyoma; Macrophages; Mice; Middle Aged; Prostaglandins; Ultrasonography; Uterine Neoplasms

To identify oxidative stress in peritoneum during laparoscopic and open surgery by measuring products of lipid peroxidation, and to determine whether surgical approach influences the type of oxidative metabolite synthesized.. Retrospective analysis (Canadian Task Force classification II-2).. University-affiliated hospital.. Twenty-eight consecutive women with uterine myomas or ovarian cysts.. Laparoscopic or open surgery (14 patients each).. We obtained 1 x 1-cm squares of peritoneum at the beginning and end of surgical procedures away from sites of surgery. 8-Isoprostaglandin F(2alpha), hydroxyeicosatetranoic acids (HETEs), and malondyaldehyde (MDA) were measured by enzyme-immunoassay, high-performance liquid chromatography, and thiobarbituric acid adduction method, respectively. Comparisons showed significant increases in 5-HETE and 8-prostane in the laparoscopy group, which were correlated with duration of pneumoperitoneum and volume of carbon dioxide (CO(2)) insufflated, respectively. In the laparotomy group only MDA rose significantly related to duration of surgery.. Lipid peroxidation was observed in peripheral peritoneum during laparoscopic surgery, mediated through noncyclooxygenase and lipoxygenase pathways, and appears to be due to effects of CO(2) pneumoperitoneum. Biochemical reactions were also observed in the laparotomy group, but are thought to be related to mechanisms other than lipid peroxidation.

Topics: Adult; Chromatography, High Pressure Liquid; Cohort Studies; Dinoprost; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hydroxyeicosatetraenoic Acids; Laparoscopy; Laparotomy; Leiomyoma; Lipid Peroxidation; Malondialdehyde; Middle Aged; Ovarian Cysts; Oxidative Stress; Peritoneum; Pneumoperitoneum, Artificial; Probability; Retrospective Studies; Sensitivity and Specificity; Statistics, Nonparametric; Uterine Neoplasms

To present a case of one-step total hysteroscopic myomectomy using prostaglandin F(2alpha).. Case report.. University hospital.. A 38-year-old woman with a sessile submucous leiomyoma.. Hysteroresectoscopy using an intraoperative injection of prostaglandin F(2alpha) under laparoscopic monitoring.. Endoscopic appearance, clinical symptoms, and imaging diagnosis.. After resection of the protruding portion of the myoma, injection of prostaglandin F(2alpha) was used to cause the remnant to project into the uterine cavity, allowing complete removal.. Intraoperative use of prostaglandin F(2alpha) may allow one-step hysteroresectoscopy of a sessile submucous leiomyoma.

Topics: Adult; Dinoprost; Female; Gynecologic Surgical Procedures; Humans; Hysteroscopy; Injections; Leiomyoma; Uterine Neoplasms

Apoptosis has been described in placental (trophoblast) tissues during both normal and abnormal pregnancies. We have studied the effects of the cyclopentenone prostaglandins (PGs) on trophoblast cell death using JEG3 choriocarcinoma cells. PGJ(2), Delta(12)PGJ(2), and 15-deoxy-Delta(12,14)-PGJ(2) (15dPGJ(2)) (10 microM) significantly reduced mitochondrial activity (MTT assay) over 16 h by 17.4 +/- 4.7%, 28 +/- 9.3%, and 62.5 +/- 2.8%, respectively (mean +/- sem), while PGA(2) and PGD(2) had no effect. The synthetic PPAR-gamma ligand ciglitizone (12.5 microM) had a potency similar to 15dPGJ(2) (69 +/- 3% reduction). Morphological examination of cultures treated with PGJ(2) and its derivatives revealed the presence of numerous cells with dense, pyknotic nuclei, a hallmark of apoptosis. FACS analysis revealed an abundance (approximately 40%) of apoptotic cells after 16-h treatment with 15dPGJ(2) (10 microM). The caspase inhibitor ZVAD-fmk (5 microM) significantly diminished the apoptotic effects of Delta(12)PGJ(2) and 15dPGJ(2). JEG3 cells expressed PPAR-gamma mRNA by Northern analysis. These novel findings imply a role for PPAR-gamma ligands in various processes associated with pregnancy and parturition.

Topics: Amino Acid Chloromethyl Ketones; Apoptosis; Choriocarcinoma; Dinoprost; Female; Humans; Labor, Obstetric; Mitochondria; Nuclear Proteins; Pregnancy; Prostaglandin D2; Prostaglandins A; Receptors, Cytoplasmic and Nuclear; RNA, Messenger; Transcription Factors; Transcription, Genetic; Tumor Cells, Cultured; Uterine Neoplasms

The mechanism of labor initiation in humans has not been completely elucidated. Prostaglandins, estrogens, and corticotropin-releasing factor (CRF) have all been shown to affect uterine myocytes and enhance uterine contractility. There are also indications that these uterine regulators have additional effects on other sites involved in labor and that they may act in concert or, perhaps, by regulating each other. Therefore, we evaluated the CRF promoter for transcriptional regulation by prostaglandins and estrogens. Human placental choriocarcinoma cell lines were transfected with CRF-luciferase reporter genes and treated with prostaglandins. Prostaglandin E2 (PGE2), but not prostaglandin F2alpha (PGF2alpha), stimulated CRF-luciferase expression in choriocarcinoma cell lines via a cAMP-dependent pathway. A combination of transfections and in vitro binding studies tested for potential regulation of CRF by estrogen receptor (ER). ER neither regulated the CRF promoter nor interacted with steroid response half-sites from the CRF promoter. Our results provide a molecular regulatory link between PGE2 and CRF, two compounds that enhance uterine contractile function. Combined with the stimulation of prostaglandin release by CRF, these data support a potentially important "feed-forward" regulatory loop involving CRF and PGE2 in parturition. In contrast, we found no evidence for direct effects of estrogens or PGF2alpha on CRF transcription.

Topics: Animals; Cell Line; Choriocarcinoma; Corticotropin-Releasing Hormone; Dinoprost; Dinoprostone; Estradiol; Female; Gene Expression Regulation; Haplorhini; Humans; Luciferases; Placenta; Pregnancy; Prostaglandins; Recombinant Fusion Proteins; Transcription, Genetic; Transfection; Tumor Cells, Cultured; Uterine Neoplasms

In order to investigate the production of eicosanoids in human endometrium, myometrium, leiomyoma, adenomyosis, normal ovary, non-endometrial cyst and endometrial cyst, slices of each tissue were incubated. 6-Keto-prostaglandin (PG) F1 alpha, thromboxane (TX) B2, PGF2 alpha and PGE2 concentrations in the incubation medium were measured by direct RIA. 6-Keto-PGF1 alpha production of adenomyosis was significantly higher than that of endometrium, myometrium and leiomyoma, especially in the menstrual phase. The production of eicosanoids in endometrial cyst was significantly higher than that of non-endometrial cyst and normal ovary. These results suggest that endometriosis is associated with increased eicosanoid production in vivo.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Cysts; Dinoprost; Dinoprostone; Eicosanoids; Endometriosis; Female; Humans; Leiomyoma; Middle Aged; Myometrium; Ovary; Thromboxane B2; Uterine Neoplasms

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

Topics: Adult; Complement C3; Dinoprost; Endometriosis; Female; Humans; Immunoglobulins; Infertility, Female; Prostaglandins F; Uterine Neoplasms

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

Effects of prostaglandin F2 alpha, E2, D2 and J2 on the DNA and RNA contents of a human endometrial cancer cell lines (SNG and Ishikawa) were studied using flow cytometry. Cytotoxic effects of various prostaglandins on SNG and Ishikawa cell lines were examined and PG J2 and PG D2 were found most active. Among other prostaglandins PG E2 showed a comparable inhibitory activity to cellular growth but PG F2 alpha didn't. In SNG and Ishikawa cell lines after RNase treatment, PG J2, PG D2 and PG E2 caused a decrease of the S-phase and G2 + M-phase cell population in cell cycle. On the other hand, PG F2 alpha caused a increase of the S-phase cell population in cell cycle PG J2, PG D2 and PG E2 after DNase treatment caused a decrease of the relative RNA content in both of cell lines. On the other hand, PG F2 alpha caused a increase of the relative RNA content. It is a noteworthy that PG J2 and PG D2 were remarkably recognized delay of doubling time and decrease of survival fraction under the time and dose dependence. These effects occur not only by direct lethal influence of the prostaglandins, but also by substantially inhibit RNA and DNA synthesis with a delay of the cell cycle. These results might be suggested a role for prostaglandin J2 and D2 in the regulation of growth of endometrial adenocarcinoma cells.

Topics: Adenocarcinoma; Cell Cycle; Cell Division; Cells, Cultured; Colony-Forming Units Assay; Dinoprost; Dinoprostone; Female; Flow Cytometry; Humans; Prostaglandin D2; Prostaglandins D; Prostaglandins E; Prostaglandins F; Tumor Stem Cell Assay; Uterine Neoplasms

The effects of prostaglandin (PG) F2 alpha in 16 patients with vascular malignant intestinal tumors were analyzed by angiography. It was found that PGF2 alpha reduced tumor vascular flow selectively in all but one patient, a rectal carcinoma case. Among the remaining group, a case of intestinal choriocarcinoma complicated by massive gastrointestinal hemorrhage was successfully controlled with intraarterial infusion of PGF2 alpha into the superior mesenteric artery. Owing to the reduced blood flow in tumors, PGF2 alpha is expected to be used extensively as a vasoconstrictor to control bleeding from tumors of the alimentary tract.

Topics: Adult; Aged; Choriocarcinoma; Colonic Neoplasms; Dinoprost; Female; Humans; Intestinal Neoplasms; Intestine, Small; Male; Mesenteric Arteries; Middle Aged; Pregnancy; Prostaglandins F; Radiography; Renal Artery; Uterine Neoplasms

Three hundred fifty-four evaluable cases of hydatidiform mole diagnosed from 1970 to 1979 in 10 regional hospitals in Lombardy are analyzed in the present report. Twenty-six (7.3%) of the patients developed persistent trophoblastic disease. Younger (less than 20 years) and older (40 years or more) age at diagnosis, a large-for-dates uterus, and ovarian enlargement were associated with an increased risk of developing persistent trophoblastic disease. Twenty-three (9%) cases of persistent trophoblastic disease were observed among 250 women not prophylactically treated, but only in 3 (3%) among 104 who received prophylactic chemotherapy. High-risk groups are defined and the role of prophylactic chemotherapy is discussed.

Topics: Adolescent; Adult; Chorionic Gonadotropin; Dilatation and Curettage; Dinoprost; Female; Humans; Interinstitutional Relations; Italy; Methotrexate; Middle Aged; Obstetrics and Gynecology Department, Hospital; Ovary; Pregnancy; Prostaglandins F; Trophoblastic Neoplasms; Uterine Neoplasms