Pag. 8

Arch Gynecol Obstet.2012 May 31. [Epub ahead of print]

Effect of mifepristone on COX-2 both in eutopic and ectopic endometrium in mouse endometriotic model.

Li X, Bao Y, Fang P, Chen Y, Qiao Z.

Source

Department of Gynecology and Obstetrics, Shanghai Fifth Hospital, Shanghai, 200240, People’s Republic of China.

Abstract

OBJECTIVE:

To study the influence of mifepristone on the expression of cyclooxygenase 2 (COX-2) protein and COX-2 mRNA and then to evaluate the mechanism.

METHODS:

After the establishment of 30 mice endometriosis models, the mice were randomly divided into six groups with 5 mice each group and assigned to experimental and control groups of 1-, 4- and 6-week circle according to whether mifepristone (0.13 mg d(-1)) was taken or not. Small animal optical imaging system was used to detect the fluorescent intensity of the ectopic tissue. Reverse transcript-polymerase chain reaction and western blot was used to examine COX-2 protein and COX-2 mRNA expression. ELISA was used to examine concentration of PGE(2) in serum.

RESULT(S):

Mifepristone could not affect the fluorescent intensity of the ectopic endometrium after it was taken 1, 4, and 6 (P > 0.05). However, it could decrease the transcription of COX-2 mRNA in the 1 and 4 week groups (P < 0.05), while the difference in the 6 week group was not significant (P > 0.05). It could decrease the expression of COX-2 protein after it was taken 4 and 6 weeks (P < 0.05). The serous PGE(2) in the trial groups was lower than that in the control groups, but the difference was not significant (P > 0.05).

CONCLUSION(S):

This study showed that mifepristone could not affect the size of the ectopic endometrium, but it could decrease the transcription of COX-2 gene and then reduce the expression of COX-2 protein and its product PGE(2) which is an important factor which mediate pain. This maybe another mechanism that mifepristone takes effect through anti-inflammatory path.

Arch Toxicol.2012 May 31. [Epub ahead of print]

Estrogen receptors and human disease: an update.

Burns KA, Korach KS.

Source

Receptor Biology Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), B3-02, PO Box 12233, Research Triangle Park, NC, 27709, USA.

Abstract

A myriad of physiological processes in mammals are influenced by estrogens and the estrogen receptors (ERs), ERα and ERβ. As we reviewed previously, given the widespread role for estrogen in normal human physiology, it is not surprising that estrogen is implicated in the development or progression of a number of diseases. In this review, we are giving a 5-year update of the literature regarding the influence of estrogens on a number of human cancers (breast, ovarian, colorectal, prostate, and endometrial), endometriosis, fibroids, and cardiovascular disease. A large number of sophisticated experimental studies have provided insights into human disease, but for this review, the literature citations were limited to articles published after our previous review (Deroo and Korach in J Clin Invest 116(3):561-570, 2006) and will focus in most cases on human data and clinical trials. We will describe the influence in which estrogen’s action, through one of or both of the ERs, mediates the aforementioned human disease states.

Fertil Steril.2012 May 31. [Epub ahead of print]

Inflammation: a link between endometriosis and preterm birth.

Petraglia F, Arcuri F, de Ziegler D, Chapron C.

Source

Obstetrics and Gynecology, Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy.

Abstract

Endometriosis is a chronic inflammatory disease affecting women’s health. Pain and infertility are the major symptoms caused by a hormonal/immunological dysfunction, which causes an endometrial impairment. The same pathogenetic mechanisms are also associated with preterm birth: hormones, cytokines, neurohormones, and growth factors interact in modulating extracellular matrix and prostaglandin secretion, thus activating the inflammatory process in placental membranes and myometrium. An overlap of molecules and mechanisms may explain the evidence that preterm birth is a common outcome in pregnant patients with endometriosis.

Transl Res.2012 May 31. [Epub ahead of print]

Antioxidant supplementation reduces endometriosis-related pelvic pain in humans.

Santanam N, Kavtaradze N, Murphy A, Dominguez C, Parthasarathy S.

Source

Department of Pharmacology, Physiology, and Toxicology, Joan C. Edwards School of Medicine, Huntington, West Virginia.

Abstract

We previously suggested that women with endometriosis have increased oxidative stress in the peritoneal cavity. To assess whether antioxidant supplementation would ameliorate endometriosis-associated symptoms, we performed a randomized, placebo-controlled trial of antioxidant vitamins (vitamins E and C) in women with pelvic pain and endometriosis. Fifty-nine women, ages 19 to 41 years, with pelvic pain and history of endometriosis or infertility were recruited for this study. Patients were randomly assigned to 2 groups: vitamin E (1200 IU) and vitamin C (1000 mg) combination or placebo daily for 8 weeks before surgery. Pain scales were administered at baseline and biweekly. Inflammatory markers were measured in the peritoneal fluid obtained from both groups of patients at the end of therapy. Our results indicated that after treatment with antioxidants, chronic pain (“everyday pain”) improved in 43% of patients in the antioxidant treatment group (P = 0.0055) compared with the placebo group. In the same group, dysmenorrhea (“pain associated with menstruation”) and dyspareunia (“pain with sex”) decreased in 37% and 24% patients, respectively. In the placebo group, dysmenorrhea-associated pain decreased in 4 patients and no change was seen in chronic pain or dyspareunia. There was a significant decrease in peritoneal fluid inflammatory markers, regulated upon activation, normal T-cell expressed and secreted (P ≤ 0.002), interleukin-6 (P ≤ 0.056), and monocyte chemotactic protein-1 (P ≤ 0.016) after antioxidant therapy compared with patients not taking antioxidants. The results of this clinical trial show that administration of antioxidants reduces chronic pelvic pain in women with endometriosis and inflammatory markers in the peritoneal fluid.

Fertil Steril.2012 May 30. [Epub ahead of print]

Developing symptom-based predictive models of endometriosis as a clinical screening tool: results from a multicenter study.

Nnoaham KE, Hummelshoj L, Kennedy SH, Jenkinson C, Zondervan KT; World Endometriosis Research Foundation Women’s Health Symptom Survey Consortium.

Source

Department of Public Health, University of Oxford, Oxford, United Kingdom.

Abstract

OBJECTIVE:

To generate and validate symptom-based models to predict endometriosis among symptomatic women prior to undergoing their first laparoscopy.

DESIGN:

Prospective, observational, two-phase study, in which women completed a 25-item questionnaire prior to surgery.

SETTING:

Nineteen hospitals in 13 countries.

PATIENT(S):

Symptomatic women (n = 1,396) scheduled for laparoscopy without a previous surgical diagnosis of endometriosis.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Sensitivity and specificity of endometriosis diagnosis predicted by symptoms and patient characteristics from optimal models developed using multiple logistic regression analyses in one data set (phase I), and independently validated in a second data set (phase II) by receiver operating characteristic (ROC) curve analysis.

RESULT(S):

Three hundred sixty (46.7%) women in phase I and 364 (58.2%) in phase II were diagnosed with endometriosis at laparoscopy. Menstrual dyschezia (pain on opening bowels) and a history of benign ovarian cysts most strongly predicted both any and stage III and IV endometriosis in both phases. Prediction of any-stage endometriosis, although improved by ultrasound scan evidence of cyst/nodules, was relatively poor (area under the curve [AUC] = 68.3). Stage III and IV disease was predicted with good accuracy (AUC = 84.9, sensitivity of 82.3% and specificity 75.8% at an optimal cut-off of 0.24).

CONCLUSION(S):

Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy. Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis. We invite other researchers to validate the key models in additional populations.

Int J Gynaecol Obstet.2012 May 30. [Epub ahead of print]

Safety of transient abdominal ovariopexy in patients with severe endometriosis.

Poncelet C, Ducarme G, Yazbeck C, Madelenat P, Carbonnel M.

Source

Department of Obstetrics and Gynecology, University Hospital Jean Verdier, AP-HP, Bondy, France.

Abstract

OBJECTIVE:

To evaluate complications of transient ovariopexy performed to reduce adhesions in patients with severe endometriosis.

METHODS:

A bicentric retrospective study involved 193 consecutive patients who underwent laparoscopic surgery for severe endometriosis at 2 French university hospitals from 1997 to 2009. At the end of surgery, unilateral or bilateral transient ovariopexy was performed on 297 ovaries. Immediate (e.g. reproducibility, tolerance, and hospital stay) and long-term (evaluated via vaginal access to the ovaries, ovarian function, and ovarian vascularization) complications were assessed.

RESULTS:

The technique, which was easy and reproducible, did not increase hospital stay and was well tolerated. There were 2 (0.7%) immediate complications. There was no difference in ovarian accessibility before and after surgery (177/183 [96.7%] vs 176/183 [96.1%]). Potential vaginal oocyte retrieval for in vitro fertilization was possible for all patients. The antral follicle count and the pulsatility index of suspended ovaries were not different from those of contralateral unsuspended ovaries. Endometrioma excision did not modify these results.

CONCLUSION:

The short- and long-term safety results of transient ovariopexy for adnexal adhesions in patients with severe endometriosis were encouraging.

J Clin Endocrinol Metab.2012 May 30. [Epub ahead of print]

Hypoxia-Induced MicroRNA-20a Expression Increases ERK Phosphorylation and Angiogenic Gene Expression in Endometriotic Stromal Cells.

Lin SC, Wang CC, Wu MH, Yang SH, Li YH, Tsai SJ.

Source

Departments of Physiology (S.-C.L., C.-C.W., S.-H.Y., S.-J.T.) and Obstetrics and Gynecology (M.-H.W.) and Institute of Basic Medical Sciences (Y.-H.L., S.-J.T.), College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.

Abstract

Context:Aberrant activation of MAPK has been implicated to play important roles in pathological processes of endometriosis. However, how MAPK are constitutively activated in endometriotic tissues remains largely unknown. microRNA are small noncoding RNA that regulate the stability or translational efficiency of target mRNA by interacting with the 3′ untranslated region. Thus, miRNA are thought to be modulators of the transcriptional response, fine-tuning gene expression.Objective:The aim of this study was to evaluate the functional roles of microRNA-20a (miR20a) in MAPK activation and the pathogenesis of endometriosis.Design:miR20a expression was analyzed in nonpaired (endometrium = 17; endometriosis = 37) and paired (n = 12) endometriotic tissues by quantitative RT-PCR. Overexpression of miR20a in eutopic endometrial stromal cells or inhibition of miR20a in ectopic endometriotic stromal cells was used to evaluate its impact on ERK phosphorylation and subsequently angiogenesis- and proliferation-related gene expression.Results:Levels of miR20a were up-regulated in endometriotic stromal cells. Elevation of miR20a was up-regulated by hypoxia inducible factor-1α. The up-regulation of miR20a causes the down-regulation of dual-specificity phosphatase-2, which leads to prolonged ERK phosphorylation and an increase in the expression of several angiogenic genes. Furthermore, the up-regulation of miR20a enhances the prostaglandin E(2)-induced expression of fibroblast growth factor-9, a potent mitogen that stimulates both endothelial and endometrial cell proliferation.Conclusion:Our findings provide the novel mechanism that not only functionally links together hypoxic stress, miR20a expression, aberrant ERK phosphorylation, and angiogenesis but also demonstrates that miR20a is an important modulator in the development of endometriosis.

Ultrasound Obstet Gynecol.2012 May 30. doi: 10.1002/uog.11198. [Epub ahead of print]

Transvaginal ultrasonography in the diagnosis of vesico-peritoneal fistula due to deep infiltrating endometriosis as a cause of uroperitoneum.

Guerriero S, Piras B, Peddes C, Paladino E.

Source

Department of Obstetrics and Gynecology, University of Cagliari, Cagliari, Italy. gineca.sguerriero@tiscali.it.

Colorectal Dis.2012 May 29. doi: 10.1111/j.1463-1318.2012.03111.x. [Epub ahead of print]

Quality of life and sexual function 1 year after laparoscopic rectosigmoid resection for endometriosis.

Kössi J, Setälä M, Mäkinen J, Härkki P, Luostarinen M.

Source

Department of Surgery and Department of Obstetrics and Gynaecology, Päijät-Häme Central Hospital, Lahti, Finland Department of Obstetrics and Gynaecology, Turku University Hospital, Turku, Finland Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Helsinki, Finland.

Abstract

Aim:Endometriosis is relatively common condition in fertile women and may affect the alimentary tract. Laparoscopic rectosigmoid resection for endometriosis has been found to be both feasible and safe. The aim of the present study was to prospectively evaluate the quality of life and sexual function of patients who have undergone rectosigmoid resection for endometriosis. Method: All patients undergoing rectal or sigmoid resection for endometriosis in two specialist hospitals were prospectively recruited in the study. Details regarding demography, endometriosis-related symptoms, procedure and postoperative recovery were collected. One year after the operation patients were sent a postal questionnaire asking about endometriosis-related symptoms, quality of life and sexual functioning. The 15D Questionnaire and McCoy Female Sexuality Questionnaire were used for this purpose. Results: A total of 26 patients responded to the 15D questionnaire. Endometriosis-related bowel symptoms decreased significantly after the operation. The responses showed improvements in the overall score and scores for five different dimensions (usual activities, p=0.04, discomfort and symptoms, p<0.001, distress, p<0.001, vitality, p<0.001, and sexual activity, p<0.001). Sexual satisfaction was greater one year after the operation (p=0.01). Sexual problems and partner satisfaction scores had not changed significantly. Conclusion: Laparoscopic rectal and sigmoid resection for endometriosis significantly reduce endometriosis-related symptoms and improve quality of life and sexual well-being. © 2012 The Authors Colorectal Disease © 2012 The Association of Coloproctology of Great Britain and Ireland.

J Obstet Gynaecol Res.2012 May 28. doi: 10.1111/j.1447-0756.2012.01891.x. [Epub ahead of print]

Robotic surgery and standard laparoscopy: A surgical hybrid technique for use in colorectal endometriosis.

Vitobello D, Fattizzi N, Santoro G, Rosati R, Baldazzi G, Bulletti C, Palmara V.

Source

Department of Gynaecology General Mini-Invasive Surgery, Clinical Institute Humanitas, Rozzano, MilanoDepartments of Biomorphology and Biotechnologies Gynaecologic and Obstetric Sciences, University of Messina, Messina General Surgery, Policlinic, Abano Terme, Padova, Italy.

Abstract

Aim: The aim of our work was to assess the feasibility and possible benefits of a novel hybrid surgical technique in rectosigmoidal resection in patients with bowel endometriosis. Material and Methods: A total of seven symptomatic and infertile women with severe bowel endometriosis underwent segmental bowel resection using the da Vinci surgical system and conventional laparoscopy. Statistical analysis was performed by Friedman test for non-parametric multiple comparisons. Results: The surgical procedure has a determined short mean operative time (210min) and short postoperative hospitalization (five days). In 100% of patients, the resected area showed disease-free margins. Follow-up, carried out at three, six and 12months after operation, showed a regression of painful symptoms in all operated patients (100%). Two patients (28.6%) aged35years eventually had natural pregnancies. Conclusion: To the best of our knowledge, this report is the first concerning the use of a hybrid technique for intestinal resection in severe endometriosis, and comparing our data with that in the literature, its methodological and clinical advantages are evident. Moreover, the complete removal of endometriotic implants seems to offer good results in terms of postoperative fertility, although the study data do not allow us to draw definitive conclusions on the management of fertility.

Arch Physiol Biochem.2012 May 26. [Epub ahead of print]

Analysis of cytokines in the peritoneal fluid of endometriosis patients as a function of the menstrual cycle stage using the Bio-Plex® platform.

Bersinger NA, Dechaud H, McKinnon B, Mueller MD.

Source

Department of Clinical Research, University of Berne , Switzerland.

Abstract

Objective: Endometriosis is a painful disease affecting 10-15% of reproductive-age women. Concentrations of several cytokines and angiogenic factors in peritoneal fluid (PF) have been found to correlate with the severity of the disease. However, levels of some analytes vary across the menstrual cycle, and an ideal biomarker of endometriosis has not yet been identified. We have compared the PF concentrations of different cytokines in proliferative and secretory phases in women with and without the disease using the Bio-Plex platform. Methods: PF was aspirated during laparoscopy (N = 133) and the PF concentrations of 18 cytokines from Bio-Plex panels I and II determined with the serum protocol. Results: Increased PF concentrations of IL-6, IL-18, eotaxin, and MCP-1 were found in endometriosis with no changes with menstrual cycle. Levels of IL-12(p70), ICAM-1, and GRO-α were higher in the secretory phase, while eotaxin concentrations were lower. Conclusion: Of the 18 cytokines tested, IL-6, IL-18 and MCP-1 were the best PF markers of endometriosis.

Fertil Steril.2012 May 24. [Epub ahead of print]

The ferroimmunomodulatory role of ectopic endometriotic stromal cells in ovarian endometriosis.

Kobayashi H, Yamashita Y, Iwase A, Yoshikawa Y, Yasui H, Kawai Y, Uchida K, Uno N, Akatsuka S, Takahashi T, Kikkawa F, Toyokuni S.

Source

Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan; Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.

Abstract

OBJECTIVE:

To understand the role of ectopic endometriotic stromal cells in ovarian endometriosis (OEM) and the associated risks for infertility and carcinogenesis.

DESIGN:

Analyses of secreted proteins and gene expression using immortalized eutopic/ectopic endometrial(-otic) stromal cells from OEM.

SETTING:

University.

PATIENT(S):

Women with and without OEM.

INTERVENTION(S):

Samples of endometrial(-otic) tissue from women with or without OEM.

MAIN OUTCOME MEASURE(S):

Immunohistochemical analysis of oxidative stress in OEM, gene expression profiles, and the identification of secreted proteins by mass spectrometry in immortalized endometrial(-otic) stromal cells.

RESULT(S):

4-Hydroxy-2-nonenal-modified proteins and carboxymethyllysine were abundant in the stroma, rather than epithelia, of OEM patients, indicating the presence of oxidative stress. Immortalized ectopic endometriotic stromal cells exhibited high IRP1/IRP2/HIF-1β expression and contained lower amounts of iron and copper than their eutopic counterparts. Expression profiles, in combination with protein identification, revealed that complement component 3 (C3) and pentraxin-3 (PTX3) are the major proteins secreted from immortalized ectopic endometriotic stromal cells. Complement-3/PTX3 promoted the secretion of various cytokines by THP1 macrophage cells and thus supported M1 differentiation.

CONCLUSION(S):

Immortalized ectopic endometriotic stromal cells in OEM predominantly secrete C3 and PTX3 and exhibit a differential regulation of iron metabolism.

Gynecol Endocrinol.2012 May 24. [Epub ahead of print]

Costs of in-patient treatment for endometriosis in Germany 2006: an analysis based on the G-DRG-Coding.

Oppelt P, Chavtal R, Haas D, Reichert B, Wagner S, Müller A, Lermann JH, Renner SP.

Source

Department of Gynecolocy & Obsterics , General Hospital Linz , Linz.

Abstract

Objective: The aim of this study was to estimate the financial burden of in-patients costs for endometriosis treatment in Germany in 2006. Methods: Data from a national in-patient database for women of reproductive age who were admitted for surgical treatment for endometriosis were analysed retrospectively. The number and type of hospital admissions involving surgical interventions for endometriosis were identified, and the costs of these hospitalizations to funding bodies in Germany were estimated using the diagnosis-related group reimbursement rates. Results: A total of 20,835 patients were admitted to hospital for endometriosis treatment in Germany in 2006 (1.27 per 1,000 women in reproductive age). The average cost per patient was estimated at 3,056.21 €. The total in-patient costs for endometriosis treatment in 2006 were estimated at 40,708,716.26 €. The surgical procedure most often performed in treating endometriosis was hysterectomy (in 24.70% of cases). Conclusion: The burden of admissions and the economic impact associated with the inpatients treatment of endometriosis in Germany is substantial. The results presented here may enable those responsible in the field of medicine and health-care policy to improve the allocation of resources and manage expenses on a more sustained basis.

J Neuroimmunol.2012 May 24. [Epub ahead of print]

Eutopic endometrium from women with endometriosis does not exhibit neurotrophic properties.

Barcena de Arellano ML, Arnold J, Sacher F, Blöchle M, Staube M, Bartley J, Vercellino GF, Chiantera V, Schneider A, Mechsner S.

Source

Endometriosis Research Centre Charité, Department of Gynaecology, Charité, Campus Benjamin Franklin, Berlin, Germany.

Abstract

The role of neurotrophins in eutopic endometrium from endometriosis-patients was investigated in a prospective study using immunofluorescence-staining, Western blot and a neuronal growth assay. The nerve growth factor is expressed in primary endometrial cell culture from women with and without endometriosis. Western blot analysis of endometrial biopsies or uterine fluid from patients with and without endometriosis shows no difference in the neurotrophin expression. We could not find a difference between patients with and without endometriosis with regards to the neurite outgrowth of sensory ganglia when treated with conditioned cultured medium or uterine fluid. This result refutes the assumed neurotrophic properties of eutopic endometrium of patients with endometriosis.

Eur J Obstet Gynecol Reprod Biol.2012 May 23. [Epub ahead of print]

Association between TGF-β1-509C/T polymorphism and endometriosis: a systematic review and meta-analysis.

Zhang F, Yang Y, Wang Y.

Source

School of Public Health and Health Management, Chongqing Medical University, Chongqing, China.

Abstract

OBJECTIVE:

To evaluate the association between the transforming growth factor β1 gene-509C/T (TGF-β1-509C/T) polymorphism and the risk of endometriosis.

STUDY DESIGN:

Relevant studies published before October 2011 were identified by searching PubMed and Embase. Studies were selected using prior defined criteria. The strength of the relationship between the TGF-β1-509C/T polymorphism and endometriosis risk was assessed by Odds Ratios (ORs). Fixed- or random-effects model was calculated according to study heterogeneity. Stratification analysis and sensitivity analysis were also conducted. Possible publication bias was tested by funnel plots and Egger’s test.

RESULTS:

Of 49 potentially relevant studies, six case-control studies were identified in this meta-analysis. The integrated result showed that the TGF-β1-509C/T polymorphism was not associated with the endometriosis risk for the allele contrast (T vs. C: OR=1.57, 95%CI=0.88-2.79), the additive genetic model (T/T vs. C/C: OR=2.96, 95%CI=0.97-9.10), the dominant genetic model (T/T+T/C vs. C/C: OR=1.80, 95%CI=0.80-4.07) and the recessive genetic model (T/T vs. C/C+T/C: OR=1.91, 95%CI=0.89-4.12). In the stratified analysis by ethnicity, genotyping method and source of control, no significantly association was found. Publication bias was not detected in the included studies.

CONCLUSIONS:

Meta-analyses of the available data showed that the association between TGF-β1-509C/T polymorphism and susceptibility of endometriosis was not significant. More studies are needed to elucidate its role in endometriosis.

Endocrinology.2012 May 22. [Epub ahead of print]

Raf-1, a Potential Therapeutic Target, Mediates Early Steps in Endometriosis Lesion Development by Endometrial Epithelial and Stromal Cells.

De La Garza EM, Binkley PA, Ganapathy M, Krishnegowda NK, Tekmal RR, Schenken RS, Kirma NB.

Source

Department of Obstetrics and Gynecology (E.M.D.L.G., P.A.B., M.G., N.K.K., R.R.T., R.S.S., N.B.K.), University of Texas Health Science Center at San Antonio and Cancer Therapy and Research Center (R.R.T., N.B.K.), San Antonio, Texas 78229.

Abstract

Endometriosis is a hormone-sensitive gynecological disorder characterized by the benign growth of endometrial-like tissue in the pelvic cavity. Endometriotic lesions composed of endometrial stromal cells (ESC) and glandular epithelial cells (EEC) are thought to arise from menstrual endometrial tissue reaching the pelvic cavity via retrograde menstruation. The cause of endometriotic lesion formation is still not clear. Recent evidence suggest that cytokines may play a role in the early development of endometriosis lesions. Because cytokines and growth factors signal via the Raf-1 kinase pathway, we have examined the role of Raf-1 in early steps of endometriosis lesion formation, specifically attachment of endometrial cells to peritoneal mesothelial cells (PMC) and invasion of endometrial cells through PMC (trans-mesothelial invasion). Raf-1 antagonist GW5074 decreased attachment to PMC and trans-mesothelial invasion by primary EEC and ESC. Raf-1 also mediated TGFβ-induced trans-mesothelial invasion by the established, low-invasive EEC line EM42. TGFβ treatment of EEC resulted in Raf-1 phosphorylation at S338 and phosphorylation of ERK, suggesting that TGFβ activates Raf-1 signaling in these cells. GW5074 had little effect on ESC proliferation but inhibited EEC growth significantly under reduced serum conditions. Antagonizing Raf-1 activity and expression via GW5074 and specific Raf-1 small interfering RNA, respectively, did not alter EEC resistance to growth inhibition by TGFβ. Raf-1 inhibition blocked induction of EEC growth by epidermal growth factor. Our data suggest that Raf-1 may mediate pathologic steps involved in early endometriosis lesion formation and may be a mediator of TGFβ and epidermal growth factor actions in endometriosis.

Hum Pathol.2012 May 22. [Epub ahead of print]

Involvement of pelvic inflammation-related mismatch repair abnormalities and microsatellite instability in the malignant transformation of ovarian endometriosis.

Fuseya C, Horiuchi A, Hayashi A, Suzuki A, Miyamoto T, Hayashi T, Shiozawa T.

Source

Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.

Abstract

Inflammation in the ovary, including ovulation and pelvic inflammatory disease, has been proposed to play a role in the pathogenesis of ovarian cancer. Endometriotic lesions trigger a local inflammatory reaction and have been reported to be associated with an increased risk of epithelial ovarian cancer. However, the precise molecular mechanisms of ovarian cancer arising from endometriosis are still to be elucidated. To clarify the involvement of mismatch repair (MMR) abnormalities in the inflammation-associated malignant transformation of endometriosis, the immunohistochemical expression of mismatch repair proteins (human mutL homolog 1 [hMLH1] and human mutS homolog 2 [hMSH2]) was examined in 27 cases of ovarian endometriosis, 25 cases of ovarian carcinoma accompanied by endometriosis, and 39 cases of solitary ovarian carcinoma. In addition, the relationship between mismatch repair abnormalities including the microsatellite instability, PTEN (phosphatase and tensin homolog) mutation, and clinicopathologic parameters was analyzed. The expression of mismatch repair proteins was stepwisely decreased in endometriosis, ovarian carcinoma accompanied by endometriosis, and ovarian carcinoma. Tumors harboring multiple microsatellite instability (high-frequency microsatellite instability [MSI-H]) were detected in 4 (14.8%) of 27 cases of endometriosis and 7 (30.4%) of 23 cases of ovarian carcinomas. The frequency of PTEN mutations was higher in MSI-H cases than in microsatellite instability-stable (MSI-S) cases. In 2 cases of ovarian carcinoma accompanied by endometriosis, the decreased expression of mismatch repair proteins and MSI-H was observed in both the endometriosis and carcinoma lesions. Clinicopathologically, the MSI-H cases were associated with elevated serum levels of C-reactive protein and higher white blood cell counts. These findings suggest that mismatch repair abnormalities might be involved in the malignant transformation of ovarian endometriosis and that inflammation induces mismatch repair abnormalities during ovarian carcinogenesis arising from endometriosis.

Mol Hum Reprod.2012 May 21. [Epub ahead of print]

RNAi-mediated blocking of ezrin reduces migration of ectopic endometrial cells in endometriosis.

Jiang QY, Xia JM, Ding HG, Fei XW, Lin J, Wu RJ.

Source

Department of Obstetrics and Gynecology, Women’s Hospital, School of Medicine, Zhejiang University, No. 1 Xueshi Road, Hangzhou, Zhejiang Province 310006, People’s Republic of China.

Abstract

Ezrin is a member of the ezrin-radixin-moesin (ERM) family of membrane-cytoskeletal linkage proteins. It is important for maintenance of cell shape, adhesion, migration and division. The overexpression of ezrin in some tumours is associated with increased cell migration that is mediated by the Rho/ROCK family of small GTPases. To investigate the role of ezrin in the migration of ectopic endometrial cells in endometriosis, we conducted real-time quantitative RT-PCR analysis of the eutopic and ectopic endometrium from women with endometriosis compared with those without the disease. RNAi, wound healing assays and western blot analysis of endometriotic cells were also included in this research. We found significantly higher levels of mRNA expression of ezrin (0.42 versus 0.27, P < 0.05), RhoA (0.99 versus 0.74, P < 0.05), RhoC (0.79 versus 0.43, P < 0.005) and ROCK1 (0.68 versus 0.38, P < 0.005) in the ectopic endometrial cells compared with the eutopic endometrial cells in endometriosis. Blocking ezrin with small-interfering RNA reduced the migration of ectopic endometrial cells with decreased expression of RhoA (42.68%), RhoC (58.42%) and ROCK1 (59.88%). Our results indicate that the over-expression of ezrin in endometriosis may play a significant role in the migration of endometrial cells of endometriosis, and the RhoC/Rock pathway may provide a promising treatment target.

Ugeskr Laeger.2012 May 21;174(21):1459-1460.

Atypical course of Budd-Chiari syndrome with hydrothorax.

[Article in Danish]

Bilenko A, Mahdi B.

Source

Morgenfruevænget 1, 5270 Odense N. antonbilenko@yahoo.dk.

Abstract

Budd-Chiari syndrome is a very rare condition with an incidence and a prevalence of respectively 0.8 and 1.4 per million inhabitants per year. Significant large right-sided pleural effusion without significant ascites is well-known in portal hypertension and cirrhosis, where it occurs in 5-10% of the patients. Due to the presence of endometriosis and the dominant symptom in the form of hydrothorax up to 5 l per day delayed the correct diagnosis in a case with a 33 year-old woman. Reviews of the initially performed computed tomographies could have been made shortly after admission thus avoiding long time illness and hospitalization.

Eur J Obstet Gynecol Reprod Biol.2012 May 19. [Epub ahead of print]

Association of endometriosis risk and genetic polymorphisms involving biosynthesis of sex steroids and their receptors: an updating meta-analysis.

Hu X, Zhou Y, Feng Q, Wang R, Su L, Long J, Wei B.

Source

School of Public Health, Guangxi Medical University, Nanning, People’s Republic of China.

Abstract

The objective of our study is to assess the association of endometriosis risk and genetic polymorphisms involving biosynthesis of sex steroids and their receptors. A systematic search of three databases was conducted. Twenty-seven studies on the association of the cytochrome P450 subfamily 17 (CYP17), estrogen receptor gene (ER), progesterone receptor gene (PR), 17-beta-hydroxysteroid dehydrogenase type 1 gene (HSD17B1), and cytochrome P450 subfamily 19 (CYP19) polymorphisms with endometriosis risk were identified. When all groups were pooled, we found an association between HSD17B1 (A variant allele vs. G wild allele: odds ratio (OR)=1.42, 95% confidence interval (CI)=1.10-1.84, P=0.007) and PR (P2 variant allele vs. P1 wild allele, OR=1.43, 95% CI=0.99-2.08, P=0.058) polymorphisms and endometriosis risk, while failing to detect links with CYP17, ER, and CYP19 polymorphisms examined. In the subgroup analysis, a significant association of CYP17 and ERα-PvuII polymorphisms with endometriosis was found neither in a Caucasian population nor in an Asian population. The findings of our study suggest that HSD17B1 and PR polymorphisms are associated with an increased risk of endometriosis. Further investigation into the association between CYP17, ER, PR, HSD17B1, and CYP19 polymorphisms and endometriosis risk is warranted and should include larger sample sizes.

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