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Objective: To analyze the expression of estrogen receptors α and β as well as their target genes implicated in proliferation, c-myc, cyclin D1, and GREB1, in the endometrium of women with or without endometriosis.Design: Expression analysis in human tissue.Setting: University hospitals and a clinic.Patient(s): Ninety-one premenopausal women (59 patients with endometriosis and 32 controls) undergoing laparoscopic surgery.Intervention(s): Biopsies were obtained at time of surgery, performed during the proliferative phase of the cycle.Main Outcome Measure(s): Estrogen receptors α and β as well as c-myc, cyclin D1, and GREB1 mRNA expression levels were determined by quantitative reverse transcriptase-polymerase chain reaction. Tissue localization of these estrogen-regulated genes was analyzed by immunohistochemistry.Result(s): Estrogen receptors α and β as well as c-myc, cyclin D1, and GREB1 mRNA expression levels were increased in ectopic tissue in comparison with both normal and eutopic endometrium. Estrogen receptor mRNA levels also were upregulated in the eutopic peritoneal tissue of patients with endometriosis. Cyclin D1 and GREB1 expression was augmented in eutopic endometrium. c-myc, cyclin D1, and GREB1 proteins exhibited a nuclear localization in ectopic endometrial tissue.Conclusion(s): This constitutes the first report of increased expression of GREB1, as well as cyclin D1 and c-myc, in peritoneal endometriotic lesions, implicating these proteins in estrogen-dependent growth in this context. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) represents the deadliest form of gynecological tumors currently lacking targeted therapies. The ethanol extract of the North Pacific brittle star Ophiura sarsii presented promising anti-TNBC activities. After elimination of the inert material, the active extract was submitted to a bioguided isolation approach using high-resolution semipreparative HPLC-UV, resulting in one-step isolation of an unusual porphyrin derivative possessing strong cytotoxic activity. HRMS and 2D NMR resulted in the structure elucidation of the compound as (3 S ,4 S )-14-Ethyl-9-(hydroxymethyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid. Never identified before in Ophiuroidea, porphyrins have found broad applications as photosensitizers in the anticancer photodynamic therapy. The simple isolation of a cytotoxic porphyrin from an abundant brittle star species we describe here may pave the way for novel natural-based developments of targeted anti-cancer therapies.

Objective: To compare the expression of the prostaglandin (PG) E(2) transporter multidrug resistance-associated protein 4 (MRP4) in eutopic and ectopic endometrial tissue from endometriosis patients with that of control subjects and to examine whether MRP4 is regulated by the antiinflammatory lipid lipoxin A(4) (LXA(4)) in endometriotic epithelial cells., Design: Molecular analysis in human samples and a cell line., Setting: Two university hospitals and a private clinic., Patient(s): A total of 59 endometriosis patients and 32 age- and body mass index-matched control subjects undergoing laparoscopy or hysterectomy., Intervention(s): Normal, eutopic, and ectopic endometrial biopsies as well as peritoneal fluid were obtained during surgery performed during the proliferative phase of the menstrual cycle. 12Z endometriotic epithelial cells were used for in vitro mechanistic studies., Main Outcome Measure(s): Tissue MRP4 mRNA levels were quantified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and localization was analyzed with the use of immunohistochemistry. Cellular MRP4 mRNA and protein were quantified by qRT-PCR and Western blot, respectively. PGE(2) was measured in peritoneal fluid and cell supernatants using an enzyme immunoassay (EIA)., Result(s): MRP4 was expressed in eutopic and ectopic endometrium, where it was overexpressed in peritoneal lesions and localized in the cytoplasm of glandular epithelial cells. LXA(4) attenuated MRP4 mRNA and protein levels in endometriotic epithelial cells in a dose-dependent manner, while not affecting the expression of enzymes involved in PGE(2) metabolism. Investigations employing receptor antagonists and small interfering RNA revealed that this occurred through estrogen receptor α. Accordingly, LXA(4) treatment inhibited extracellular PGE(2) release., Conclusion(s): We report for the first time that MRP4 is expressed in human endometrium, elevated in peritoneal endometriosis, and modulated by LXA(4) in endometriotic epithelial cells., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of the study was to assess the feasibility of intraoperative sentinel node (SN) detection using injection of patent blue dye and radioactive tracer beneath the tumor of patients with endometrial carcinoma., Methods: Hysteroscopy was used for injection of 2 ml of patent-V blue, followed by 20-50 MBq technetium-99 m-labelled nanocolloids into the subendometrial layer underlying the tumor of 60 patients with endometrial cancer. Then SN biopsy, pelvic and paraaortic lymphadenectomy, hysterectomy and bilateral salpingo-oophorectomy were carried out through laparotomy or laparoscopy., Results: Sixty patients aged 43 years to 87 years (median age 65 years) were enrolled in this study. Sentinel nodes were identified in 49 of 60 patients (82%). The mean number of SN retrieved was 3.7 per patient (range, 1 to 8). Sixteen patients (33%) had SN in both pelvic and paraaortic areas. No patient had SN only at the paraaortic level. Metastatic disease was found in 9 patients (15%). In 8 of them at least one SN was positive., Conclusion: Intraoperative sentinel node detection is feasible in patients with endometrial carcinoma using hysteroscopy for injection of blue dye and technetium-99 m beneath the tumor. This technique may actually enhance the chances of detecting metastatic disease, while reducing the extent of the surgery.

We developed a new instrument specifically designed to facilitate the removal of large tissue masses through a vaginal incision during laparoscopic surgery without any loss of gas. It consists of a cannula fitted with a ball-shaped head at one end. After laparoscopic culpotomy, tissue is seized with a grasping forceps introduced vaginally through the cannula. To prevent dissemination and to facilitate passage through the incision, tissue masses may be placed in a tied plastic pouch prior to extraction. The entire procedure is safe because of continual endoscopic control. It was performed in 57 women to extract cysts, tubal pregnancies, adnexa, myomas, and ovaries. It took an average of 10 minutes, and no intraoperative or postoperative complications were observed. Preliminary experience suggests that this technique is safe, fast, inexpensive, and easy to perform under continuous endoscopic control.

1. The sucrose-gap technique was employed to examine the different types of after potentials that follow, in desheathed rabbit vagus nerves, a single action potential (AP) elicited by a short (0.4 ms) supramaximal depolarizing pulse. 2. A fast and a slow hyperpolarizing after potential (fHAP and sHAP) as well as a depolarizing after potential (DAP) followed a single spike. Both the fHAP and the sHAP showed a dependence on the K+ electrochemical gradient, indicating that they are due to an outwardly oriented current of K+ ions. 3. The fHAP was sensitive to low concentrations of tetraethylammonium (TEA; 1 mM) and 4-aminopyridine (4-AP; 10 microM) and to millimolar concentrations of Ba2+. We conclude that the fHAP reflects the tail of the delayed rectifier K+ current. 4. The sHAP contained a Ca(2+)-sensitive component that showed a requirement for voltage-dependent Ca2+ entry during the AP. This component was completely blocked by low concentration of TEA (1 mM) and by Cd2+ (1 mM), but unaffected by 4-AP. These observations suggest that it reflects a current flowing through Ca(2+)-activated K+ channels. The remaining, apparently Ca(2+)-insensitive, component was insensitive to 4-AP and could be blocked by TEA only at concentrations greater than 50 mM. 5. The DAP usually appeared when the external concentration of K+ was increased to above approximately 8 mM, but sometimes it was clearly visible even at lower [K+]o. The DAP was TEA insensitive and entirely Ca2+ dependent. This latter property is inconsistent with the widely accepted hypothesis according to which the DAP reflect the accumulation of K+ in the extracellular space during the AP. 6. The origins of both the Ca(2+)-insensitive component of the sHAP and the DAP are not clear. However, in view of the fact that the sucrose-gap technique records not only the membrane potential of the nerve fibers but also of the surrounding glia, there is the possibility that these after potentials reflect changes in the electrical properties of the satellite Schwann cells.