Fertil Steril. 2011 Mar 15;95(4):1284-90. Epub 2011 Jan 26.

Distinct expression of the soluble and the membrane-bound forms of interleukin-1 receptor accessory protein in the endometrium of women with endometriosis.

Guay S, Michaud N, Bourcier N, Leboeuf M, Lemyre M, Mailloux J, Akoum A.

Source

Faculty of Medicine, Reproductive Endocrinology, Research Centre, Saint-Francis of Assisi Hospital, CHUQ, Laval University, Quebec, Canada.

Abstract

OBJECTIVE:

To investigate interleukin (IL) 1 receptor accessory protein (IL1RAcP) expression in the eutopic endometrium of women with endometriosis.

DESIGN:

Retrospective study.

SETTING:

Human reproduction research laboratory.

PATIENT(S):

Sixty-six women with endometriosis and 60 healthy women with no laparoscopic evidence of endometriosis.

INTERVENTION(S):

Endometrial tissue samples were obtained during laparoscopic surgery.

MAIN OUTCOME MEASURE(S):

IL1RAcP protein expression was analyzed by immunohistochemistry, Western blot, and ELISA, and IL1RAcP mRNA expression was analyzed by quantitative real-time polymerase chain reaction.

RESULT(S):

This study showed a significant downregulation of soluble (s)IL1RAcP expression in the eutopic endometrium of women with endometriosis compared to normal women, occurring at the protein or mRNA level. This finding appeared to vary according to endometriosis stage, being more obvious in the earliest (I and II) than the latest (III and IV) stages of the disease. However, the membrane-bound IL1RAcP did not show any noticeable endometriosis-related change, neither at the protein or mRNA level.

CONCLUSION(S):

In view of the wide spectrum of IL-1 inflammatory and growth-promoting effects, downregulation of sIL1RAcP, which is known for inhibiting IL1, indicates a profound defect in the capability of endometrial cells of women with endometriosis to counterregulate IL-1 effects and may represent an important mechanism underlying the ability of these cells to implant and develop into host tissues.

Fertil Steril. 2011 Mar 15;95(4):1261-6.e1-6. Epub 2011 Jan 21.

Urinary peptide profiling identifies a panel of putative biomarkers for diagnosing and staging endometriosis.

El-Kasti MM, Wright C, Fye HK, Roseman F, Kessler BM, Becker CM.

Source

Nuffield Department of Obstetrics and Gynaecology, University of Oxford,Women’s Centre, John Radcliffe Hospital, Oxford, United Kingdom.

Abstract

OBJECTIVE:

To identify a potential diagnostic endometriosis marker using matrix-enhanced laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS)-based urinary proteomics.

DESIGN:

Prospective randomized pilot study.

SETTING:

University hospital, tertiary referral center for endometriosis.

PATIENT(S):

53 women undergoing laparoscopic surgery for pain and/or infertility comprising 30 women without endometriosis and 23 with endometriosis.

INTERVENTION(S):

Laparoscopy and urine specimens.

MAIN OUTCOME MEASURE(S):

Urinary peptide profiles.

RESULT(S):

We observed distinct patterns of peptide profiles in the urine samples of women presenting with typical clinical symptoms of endometriosis. Six statistically significant putative peptide markers were identified (four during the periovulatory phase and two during the luteal phase) by comparing controls with moderate/severe endometriosis patients. The periovulatory peptide mass of 1,767.1 Da and the luteal peptide mass of 1,824.3 Da both showed a sensitivity of 75% and a specificity of 85% and 71%, respectively. Also detected were seven peptide markers (two during the periovulatory phase and five during the luteal phase) by comparing the urinary peptide profiles of patients with minimal/mild to moderate/severe endometriosis. The periovulatory peptide mass of 3,280.9 Da and the luteal peptide mass of 1,933.8 Da showed a sensitivity of 82% and 75% and a specificity of 88% and 75%, respectively.

CONCLUSION(S):

Urinary proteomic analysis may provide a novel method of diagnosing and staging endometriosis.

Fertil Steril. 2011 Mar 15;95(4):1308-15.e1. Epub 2010 Nov 3.

Comparative study of human eutopic and ectopic endometrial mesenchymal stem cells and the development of an in vivo endometriotic invasion model.

Kao AP, Wang KH, Chang CC, Lee JN, Long CY, Chen HS, Tsai CF, Hsieh TH, Tsai EM.

Source

Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Abstract

OBJECTIVE:

To elucidate the role of endometrial stem-progenitor cells in the etiology of endometriosis and to develop an animal model to study the invasion ability of endometrial cells.

DESIGN:

Gene expression and cell function studies were designed.

SETTING:

Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

PATIENT(S):

Human endometrial mesenchymal stem cells (MSCs) were isolated from 22 different endometrium biopsies after surgery for treatment of endometriosis.

INTERVENTION(S):

Endometrial MSCs developed from eutopic and ectopic endometrial tissues.

MAIN OUTCOME MEASURE(S):

Characterization of MSC phenotypes (i.e., differentiation induction and gene expression by flow cytometric analysis); comparative study of cell functions (i.e., cell growth, migration, and invasion assays). The invasion of implants in an animal model was examined by histologic staining.

RESULT(S):

We compared the characteristics of eutopic and ectopic endometrial MSCs from the same endometrial donor. Although both showed similar mesenchymal cell phenotypes, ectopic endometrial MSCs showed distinctly greater ability of cell migration and invasion. Furthermore, in an in vivo cell invasion model using cells grown in scaffold and transplantation in immune-deficient mice, the ectopic endometrial MSCs were found to form many new blood vessels and to invade surrounding tissue.

CONCLUSION(S):

These results indicate unique invasion and angiogenesis characteristics of ectopic endometrial MSCs that may underlie the pathogenesis of ectopic endometriosis. The animal invasion model will be useful for future characterization of endometrial MSCs.

Fertil Steril. 2011 Mar 15;95(4):1295-301.e1. Epub 2010 Oct 8.

Development and prevention of postsurgical adhesions in a chimeric mouse model of experimental endometriosis.

Herington JL, Crispens MA, Carvalho-Macedo AC, Camargos AF, Lebovic DI, Bruner-Tran KL, Osteen KG.

Source

Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, Women’s Reproductive Health Research Center, Nashville, Tennessee, USA.

Abstract

OBJECTIVE:

To examine the impact of a recent surgery on development of endometriosis-related adhesions in a chimeric model and to determine the therapeutic efficacy of pioglitazone (PIO).

DESIGN:

Human endometrial biopsies were maintained in E(2) with or without PIO for 24 h before intraperitoneal injection into immunocompromised mice also treated with or without PIO at multiple time points after peritoneal surgery. The presence and extent of adhesions were examined in animals relative to the initial establishment of experimental endometriosis.

SETTING:

Medical school research center.

PATIENT(S):

Endometrial biopsies for experimental studies were provided by normally cycling women without a medical history indicative of endometriosis or adhesions.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Examination of the development of endometriosis-related adhesions in an experimental model.

RESULT(S):

Without therapeutic intervention, injection of E(2)-treated human endometrial tissue into mice near the time of peritoneal surgery resulted in multiple adhesions and extensive endometriotic-like disease. In contrast, PIO treatment reduced adhesive disease and experimental endometriosis related to surgical injury.

CONCLUSION(S):

The presence of human endometrial tissue fragments in the peritoneal cavity of mice with a recent surgical injury promoted development of both adhesive disease and experimental endometriosis. Targeting inflammation and angiogenesis with PIO therapy limited the development of postsurgical adhesions associated with ectopic endometrial growth.

Fertil Steril. 2011 Mar 15;95(4):1338-43.e1-3. Epub 2010 Aug 30.

Evaluation of endometrial biomarkers for semi-invasive diagnosis of endometriosis.

Kyama CM, Mihalyi A, Gevaert O, Waelkens E, Simsa P, Van de Plas R, Meuleman C, De Moor B, D’Hooghe TM.

Source

Leuven University Fertility Center, and Experimental Gynecology Laboratory, Department of Obstetrics and Gynecology, University Hospital Gasthuisberg, Leuven, Belgium.

Abstract

OBJECTIVE:

To test the hypothesis that specific proteins and peptides are expressed differentially in eutopic endometrium of women with and without endometriosis and at specific stages of the disease (minimal, mild, moderate, or severe) during the secretory phase.

DESIGN:

Patients with endometriosis were compared with controls.

SETTING:

University hospital.

PATIENT(S):

A total of 29 patients during the secretory phase were selected for this study on the basis of cycle phase and presence or absence of endometriosis.

INTERVENTION(S):

Endometriosis was confirmed laparoscopically and histologically in 19 patients with endometriosis of revised American Society for Reproductive Medicine stages (9 minimal-mild and 10 moderate-severe), and the presence of a normal pelvis was documented by laparoscopy in 10 controls.

MAIN OUTCOME MEASURE(S):

Protein expression of endometrium was evaluated with use of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. The differential expression of protein mass peaks was analyzed with use of support vector machine algorithms and logistic regression models.

RESULT(S):

Data preprocessing resulted in differential expression of 73, 30, and 131 mass peaks between controls and patients with endometriosis (all stages), with minimal-mild endometriosis, and with moderate-severe endometriosis, respectively. Endometriosis was diagnosed with high sensitivity (89.5%) and specificity (90%) with use of five down-regulated mass peaks (1.949 kDa, 5.183 kDa, 8.650 kDa, 8.659 kDa, and 13.910 kDa) obtained after support vector machine ranking and logistic regression classification. With use of a similar analysis, minimal-mild endometriosis was diagnosed with four mass peaks (two up-regulated: 35.956 kDa and 90.675 kDa and two down-regulated: 1.924 kDa and 2.504 kDa) with maximal sensitivity (100%) and specificity (100%). The 90.675-kDa and 35.956-kDa mass peaks were identified as T-plastin and annexin V, respectively.

CONCLUSION(S):

Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry analysis of secretory phase endometrium combined with bioinformatics puts forward a prospective panel of potential biomarkers with sensitivity of 100% and specificity of 100% for the diagnosis of minimal to mild endometriosis.

Mol Cell Endocrinol. 2011 Mar 15;335(1):42-51. Epub 2010 Aug 17.

Inflammatory pathways in endometrial disorders.

Maybin JA, Critchley HO, Jabbour HN.

Source

University of Edinburgh Centre for Reproductive Biology, The Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.

Abstract

Complex interactions between the endocrine and immune systems govern the key endometrial events of implantation and menstruation. In contrast to other tissue sites, cyclical endometrial inflammation is physiological. However, dysregulation of this inflammatory response can lead to endometrial disorders. This review examines the inflammatory processes occurring in the normal endometrium during menstruation and implantation, highlighting recent advances in our understanding and gaps in current knowledge. Subsequently, the role of inflammatory pathways in the pathology of various common endometrial conditions is discussed, including heavy menstrual bleeding, dysmenorrhoea (painful periods), uterine fibroids, endometriosis and recurrent miscarriage.

Fertil Steril. 2011 Mar 9. [Epub ahead of print]

T helper (Th)1, Th2, and Th17 interleukin pathways in infertile patients with minimal/mild endometriosis.

Andreoli CG, Genro VK, Souza CA, Michelon T, Bilibio JP, Scheffel C, Cunha-Filho JS.

Source

Programa de Pós-Graduação em Ciências Médicas, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

Abstract

In the present study, interleukin (IL)-10, IL-12, IL-17, and IL-23 levels were measured in serum and peritoneal fluid of women with minimal or mild endometriosis and compared with levels in controls without endometriosis. Higher IL-23 levels were encountered in the peritoneal fluid of women with endometriosis, suggesting a possible role of this cytokine in these women’s infertility.

ChemMedChem. 2011 Mar 7;6(3):476-87. doi: 10.1002/cmdc.201000457. Epub 2011 Feb 17.

Bicyclic substituted hydroxyphenylmethanone type inhibitors of 17 β-hydroxysteroid dehydrogenase Type 1 (17 β-HSD1): the role of the bicyclic moiety.

Oster A, Klein T, Henn C, Werth R, Marchais-Oberwinkler S, Frotscher M, Hartmann RW.

Source

Pharmaceutical and Medicinal Chemistry, Saarland University, & the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus C2 3, P.O. Box 151150, 66123 Saarbrücken, Germany.

Abstract

An attractive target that has still to be explored for the treatment of estrogen-dependent diseases, such as breast cancer and endometriosis, is the enzyme responsible for the last step in the biosynthesis of estradiol (E2): 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1). It catalyzes the reduction of the weakly active estrone (E1) into E2, which is the most potent estrogen in humans. Inhibition of 17β-HSD1 lowers intracellular E2 concentrations and thus presents a therapeutic target for estrogen-dependent pathologies. Recently, we reported a new class of highly active and selective 17β-HSD1 inhibitors: bicyclic substituted hydroxyphenylmethanones. Here, further structural variations on the bicyclic moiety are described, especially focusing on the exchange of its hydroxy function. Twenty-nine novel inhibitors were synthesized and evaluated for 17β-HSD1 inhibition in a cell-free and cellular assay, for selectivity toward 17βHSD2 and estrogen receptors (ER) alpha and beta, as well as for metabolic stability. The best compound exhibited IC50 values of 12 nM (cell-free assay) and 78 nM (cellular assay), high selectivity for 17β-HSD1, and reasonable metabolic stability. A molecular docking study provided insight into the protein-ligand interactions of this compound with 17β-HSD1.

J Endocrinol. 2011 Mar 7. [Epub ahead of print]

The role of microRNAs and FOXO transcription factors in cycling endometrium and cancer.

Lam EW, Shah K, Brosens J.

Source

E Lam, Surgery and Cancer, Imperial College London, London W12 0NN, United Kingdom.

Abstract

The rise and fall in ovarian estrogen and progesterone production orchestrates a series of events that are indispensable for reproduction, including ovulation, implantation, decidualisation and menstruation. In the uterus, these events involve extensive tissue remodelling, characterised by waves of endometrial cell proliferation, differentiation, recruitment of inflammatory cells, apoptosis, tissue breakdown, menstruation and regeneration. The ability of ovarian hormones to trigger such diverse physiological responses is foremost dependent upon interaction of activated steroid receptors with specific transcription factors, such FOXO proteins, involved in cell fate decisions. Furthermore, microRNAs, small non-coding RNAs that function as posttranscriptional regulators of gene expression, have emerged as a major regulator system of steroid hormone responses in the female reproductive tract. Consequently, increasing evidence shows that deregulated uterine microRNA expression underpins a spectrum of common reproductive disorders, ranging from implantation failure to endometriosis. Furthermore, by targeting FOXO transcription factors and other key regulators of tissue homeostasis, oncogenic endometrial microRNAs promote tumorigenesis and cancer progression.

Br J Pharmacol. 2011 Mar 3. doi: 10.1111/j.1476-5381.2011.01292.x. [Epub ahead of print]

In vitro and in vivo evaluation of the anti-angiogenic actions of 4-hydroxybenzyl alcohol.

Laschke M, Vorsterman van Oijen A, Scheuer C, Menger M.

Source

Institute for Clinical & Experimental Surgery, University of Saarland, 66421 Homburg/Saar, Germany.

Abstract

Background and purpose: 4-Hydroxybenzyl alcohol (HBA) is a phenolic plant compound, which has been shown to influence many cellular mechanisms. In the present study, we analyzed in vitro and in vivo the anti-angiogenic actions of this pleiotropic agent. Experimental approach: Migration and protein expression of HBA- and vehicle-treated endothelial-like eEND2 cells was assessed by cell migration assay and Western blot analyses. HBA action on vascular sprouting was analyzed in an aortic ring assay. In vivo anti-angiogenic actions of HBA was studied in the dorsal skinfold chamber model of endometriosis in mice. Key results: Western blot analyses demonstrated that HBA inhibited proliferation of eEND2 cells, as indicated by down-regulation of proliferating cell nuclear antigen expression, and reduced expression of vascular endothelial growth factor and matrix metalloproteinase 9. HBA suppressed the migration of eEND2 cells, accompanied by inhibition of actin filament reorganization, revealed by fluorescence staining of the cytoskeleton. In addition, HBA reduced vascular sprouting in the aortic ring assay. Finally, we found, in the dorsal skinfold chamber model in vivo using intravital fluorescence microscopy, that HBA inhibited the vascularization of developing endometriotic lesions, as indicated by a decreased functional capillary density of lesions in HBA-treated mice and a reduced lesion size, compared with control animals. Conclusions and implications: HBA targets several angiogenic mechanisms and, therefore, represents a promising anti-angiogenic agent for the treatment of angiogenic diseases, such as endometriosis.

© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Ultrasound Obstet Gynecol. 2011 Mar 3. doi: 10.1002/uog.8985. [Epub ahead of print]

A case of polypoïd endometriosis of the bladder during pregnancy mimicking urachal carcinoma.

Lambrechts S, Van Calsteren K, Capoen A, Op de Beeck K, Joniau S, Timmerman D, Amant F.

Source

Department of Obstetrics and Gynecology, UZ Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.

Abstract

We report a case of polypoid bladder endometriosis in pregnancy. Diagnostic workup showed a vesico-uterine well-vascularised polypoid mass, suspicious for malignancy. During pregnancy, the mass was surgically resected with safe oncological margins. Pathological examination of the resected specimen revealed pseudotumoral polypoid endometriosis of the bladder. We illustrate diagnostic pitfalls in the differentiation between bladder endometriosis during pregnancy and malignancy. Due to pregnancy related decidualization of vesical endometriosis differentiation between this rare occurrence and malignant transformation is challenging. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

Am J Med Sci. 2011 Mar;341(3):240-2.

Anaphylactic reaction to different gonadotropin-releasing hormone agonists for the treatment of endometriosis.

Lüchinger AB, Mijatovic V, Rustemeyer T, Hompes PG.

Source

Department of Reproductive Medicine, Endometriosis Center, VU University Medical Center, Amsterdam, The Netherlands.

Abstract

Anaphylactic reactions to gonadotropin-releasing hormone (GnRH) agonists are exceedingly rare, but if they occur, they can be life threatening. This case describes a 33-year-old patient with endometriosis who developed an acute allergic reaction on leuprolide (Lucrin) administration. Although skin tests with the replacement goserelin (Zoladex) were negative, usage of this medication resulted in a similar allergic reaction. This is the first case report that shows that, in case of a proven allergy to one GnRH agonist, a switch to another GnRH agonist should not be made even if allergy tests are negative for this medication.

Ann N Y Acad Sci. 2011 Mar;1221(1):70-4. doi: 10.1111/j.1749-6632.2010.05933.x.

Potential cures for endometriosis.

Jacobson TZ.

Source

Department of Obstetrics and Gynaecology, Mater Mother’s Hospital, Brisbane, Australia.

Abstract

Treatment of endometriosis usually requires highly individualized management and varies depending on the presenting symptoms and the life stage of the patient. Surgical treatment of endometriosis starts with clinical recognition of the condition that may be enhanced by narrow band imaging. Surgery is effective in pain control and enhancing fertility. Tubal ligation or salpingectomy can be considered. Robotic surgery is unlikely to create a cure, but may assist surgery. Medical treatment including aromatase inhibitors may also be effective. Tubal flushing with lipiodol increases fecundity; other immunomodulators and neuromodulators may also be effective. Complementary therapies, however, have not been subjected to randomized clinical trials. Environmental factors, diet, and lifestyle modification may be effective.

Ann N Y Acad Sci. 2011 Mar;1221(1):61-9. doi: 10.1111/j.1749-6632.2011.05951.x.

Ultrasonographic staging: a new staging system for deep endometriosis.

Coccia ME, Rizzello F.

Source

Department of Science for the Health of Woman and Child, University of Florence, Florence, Italy. Department of Medical Pathophysiology, Sapienza University of Rome, Rome, Italy.

Abstract

Modern imaging techniques allow for the noninvasive diagnosis of endometriosis. Preoperative staging of pelvic endometriosis helps the gynecologist plan therapy and offer a prognosis to patients. The challenge of creating a satisfactory classification of endometriosis remains. The ability of the current classification schemes to predict pregnancy outcome, or aid in the management of pelvic pain, is recognized to be inadequate. The study of deeply infiltrating endometriosis and adenomyosis is greatly hampered by a lack of clear terminology and the absence of a consensus classification of the lesions. A reviewed consensus classification of endometriosis in general, with a more detailed consideration on deep endometriosis, is urgently required. We suggest a new staging system for deep, infiltrating endometriosis based on ultrasonographic findings. Prospective data collection and review in large centers may provide a larger clinical base from which to derive empirical point scores and breakpoints in the classification scheme.

Ann N Y Acad Sci. 2011 Mar;1221(1):10-7. doi: 10.1111/j.1749-6632.2011.05969.x.

Stem cells in endometrium and their role in the pathogenesis of endometriosis.

Figueira PG, Abrão MS, Krikun G, Taylor H.

Source

Department of Obstetrics and Gynecology, Sao Paulo University, Sao Paulo, Brazil. Department of Obstetrics, Gynecology, and Reproductive Science, School of Medicine, Yale University, New Haven, Connecticut.

Abstract

The human endometrium is a dynamic tissue that undergoes cycles of growth and regression with each menstrual cycle. Adult progenitor stem cells are likely responsible for this remarkable regenerative capacity; these same progenitor stem cells may also have an enhanced capacity to generate endometriosis if shed in a retrograde fashion. The progenitor stem cells reside in the uterus; however, less-committed mesenchymal stem cells may also travel from other tissues such as bone marrow to repopulate the progenitor population. Mesenchymal stem cells are also involved in the pathogenesis of endometriosis and may be the principle source of endometriosis outside of the peritoneal cavity when they differentiate into endometriosis in ectopic locations. Finally, besides progenitor stem cells, recent publications have identified multipotent stem cells in the endometrium. These multipotent stem cells are a readily available source of cells that are useful in tissue engineering and regenerative medicine. Endometrial stem cells have been used to generate chondrocytes, myocytes, neurons, and adiposites in vitro as well as to replace dopaminergic neurons in a murine model of Parkinson’s disease.

Arch Gynecol Obstet. 2011 Mar;283(3):513-8. Epub 2010 Sep 7.

A systematic review: endometriosis presenting with ascites.

Gungor T, Kanat-Pektas M, Ozat M, Zayifoglu Karaca M.

Source

Department of Gynecology, Dr. Zekai Tahir Burak Women Health Research and Education Hospital, Ankara, Turkey.

Abstract

BACKGROUND:

The present review aims to increase the awareness of the gynecologists by analyzing all the case reports which refer to endometriosis presenting either with only ascites or with massive ascites with pleural effusion.

METHODS:

To conduct the present review, the CENTRAL (in the Cochrane Library, current issue), MEDLINE (Silver Platter, from 1950 to 2010), and EMBASE (from 1950 to 2010) electronic databases were searched. As a result, all the publications based on the keywords relating to the review topic were acquired.

RESULTS:

Since the description of first case in 1954, endometriosis-related ascites was reported to occur in a total of 63 women who were aged between 19 and 51 years. Approximately 63.0% of the recruited women for whom ethnicity was specified were of African origin (29 out of 46). Of the 50 subjects with known obstetric history, 41 (82.0%) were nulliparous. Abdominal distention, anorexia/weight loss, abdominal pain, and menometrorrhagia were the most frequently encountered clinical symptoms, whereas pelvic mass was the most common physical finding. The serum concentrations of CA 125 were between 20 and 3,504 IU/ml for 19 women whose CA 125 levels were determined. Pleural effusion was also present in 38.1% of the reviewed subjects (24 out of 63). The clinical features of the women with endometriosis-related ascites and pleural effusion were similar to those of the women who had only endometriosis-related ascites.

CONCLUSION:

Endometriosis-related ascites and/or pleural effusion refers to extensive disease with a high risk for recurrence which usually affects non-Caucasian, nulliparous women of reproductive age and leads to clinical symptoms resembling those of an ovarian malignancy. Therefore, clinicians should consider endometriosis in differential diagnosis of pelvic masses and also include endometriosis in diagnostic workup of ascites or pleural effusion.

Cancer Prev Res (Phila). 2011 Mar;4(3):414-24. Epub 2010 Nov 30.

CDB-4124, a progesterone receptor modulator, inhibits mammary carcinogenesis by suppressing cell proliferation and inducing apoptosis.

Wiehle R, Lantvit D, Yamada T, Christov K.

Source

Repros Therapeutics, Inc., The Woodlands, TX 77380, USA. rwiehle@reprosrx.com

Abstract

CDB-4124 (Proellex or telapristone acetate) is a modulator of progesterone receptor (PR) signaling, which is currently employed in preclinical studies for prevention and treatment of breast cancer and has been used in clinical studies for treatment of uterine fibroids and endometriosis. Here we provide evidence for its action on steroid hormone-signaling, cell cycle-regulated genes and in vivo on mammary carcinogenesis. When CDB-4124 is given to rats at 200 mg/kg for 24 months, it prevents the development of spontaneous mammary hyperplastic and premalignant lesions. Also, CDB-4124 given as subcutaneous pellets at two different doses suppressed, dose dependently, N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis. The high dose (30 mg, over 84 days) increased tumor latency from 66 ± 24 days to 87 ± 20 days (P < 0.02), decreased incidence from 85% to 35% (P < 0.001), and reduced multiplicity from 3.0 to 1.1 tumors/animal (P < 0.001). Tumor burden decreased from 2.6 g/animal to 0.26 g/animal (P < 0.01). CDB-4124 inhibited cell proliferation and induced apoptosis in MNU-induced mammary tumors, which correlated with a decreased proportion of PR(+) tumor cells and with decreased serum progesterone. CDB-4124 did not affect serum estradiol. In a mechanistic study employing T47D cells we found that CDB-4124 suppressed G(1)/G(0)-S transition by inhibiting CDK2 and CDK4 expressions, which correlated with inhibition of estrogen receptor (ER) expression. Taken together, these data indicate that CDB-4124 can suppress the development of precancerous lesions and carcinogen-induced ER(+) mammary tumors in rats, and may have implications for prevention and treatment of human breast cancer.

Cytotechnology. 2011 Mar;63(2):205-10. Epub 2011 Mar 16.

Lactobacillus gasseri OLL2809 inhibits development of ectopic endometrial cell in peritoneal cavity via activation of NK cells in a murine endometriosis model.

Itoh H, Sashihara T, Hosono A, Kaminogawa S, Uchida M.

Source

Food Science Institute, Division of Research and Development, Meiji Dairies Corporation, 540 Naruda, Odawara, Kanagawa, 250-0862, Japan.

Abstract

We have previously reported that peritoneal administration of interleukin-12 (IL-12) suppresses development of ectopic endometriotic lesions via activation of natural killer (NK) cells in a mouse endometriosis model. Lactobacillus gasseri OLL2809 is one of a probiotic lactobacillus that has been selected on an ability to stimulate production of IL-12 from murine splenocytes. In this study, we examined whether the oral administration of heat-killed L. gasseri OLL2809 suppressed development of endometriosis. Administration of L. gasseri OLL2809 for 21 consecutive days resulted in reduction of the development of ectopic endometriotic lesions in an extent similar to IL-12. Although obvious effects of L. gasseri OLL2809 on the peritoneal cytokine levels, population of peritoneal cells as well as cytotoxicity of splenic NK cells, gene expression analysis of the peritoneal cells revealed enhancement in the transcription of IL-2 and natural killer cell triggering receptor 1 genes. Therefore, it was suggested that L. gasseri OLL2809 suppressed development of endometriosis via activation of NK cells.

Cytotechnology. 2011 Mar;63(2):133-41. Epub 2011 Mar 15.

Interleukin-12 inhibits development of ectopic endometriotic tissues in peritoneal cavity via activation of NK cells in a murine endometriosis model.

Itoh H, Sashihara T, Hosono A, Kaminogawa S, Uchida M.

Source

Food Science Institute, Division of Research and Development, Meiji Dairies Corporation, 540 Naruda, Odawara, Kanagawa, 250-0862, Japan.

Abstract

Involvement of impaired peritoneal immunosurveillance systems has been well established in the pathology of endometriosis. On the other hand, it has been observed that peritoneal administration of IL-12 suppress development of endometriotic lesions in a mouse endometriosis model. We investigated the effect of peritoneal administration of IL-12 on the peritoneal immunosurveillance system regarding NK cells in the mouse model. Treating the endometrial-tissue challenged mice with IL-12 for 5 consecutive days, from day -2 to day 2 (implantation of the endometrial tissues was done on day 0), cytotoxicity of splenic NK cells was enhanced immediately after the administration, on day 3, and development of the endometriotic lesions was reduced on day 21. In vivo NK cell depletion by administration of anti-IL-2Rβ mAb resulted in reduction of the cytotoxicity of splenic NK cells concomitant with a significant attenuation of suppressive effect of IL-12 on development of endometriotic lesions. Therefore, it was suggested that IL-12 suppresses development of endometriotic lesions via activation of NK cells, and that NK cells are involved in the primary defense for the development of endometriotic lesions.

Cytotechnology. 2011 Mar;63(2):153-61. Epub 2010 Dec 10.

Lactobacillus gasseri OLL2809 is effective especially on the menstrual pain and dysmenorrhea in endometriosis patients: randomized, double-blind, placebo-controlled study.

Itoh H, Uchida M, Sashihara T, Ji ZS, Li J, Tang Q, Ni S, Song L, Kaminogawa S.

Source

Food Science Institute, Meiji Dairies Corporation, 540 Naruda, Odawara, Kanagawa, 250-0862, Japan.

Abstract

In this study, we evaluated the efficacy of Lactobacillus gasseri OLL2809 on endometriosis by the randomized, double-blind and placebo-controlled clinical study, especially against pain, which is one of the causative factors to decrease the quality of life. Sixty-six patients clinically diagnosed with endometriosis were enrolled in this study, 62 of which have successfully completed the trial. The tablets containing 100 mg of L. gasseri OLL2809 (active tablet, n = 29) or placebo tablets (n = 33) were ingested once a day for 12 weeks. Visual analog scale (VAS) of pain intensity at the menstrual period and verbal rating scale (VRS) of dysmenorrhea were significantly improved by the ingestion of the active tablets as compared with placebo tablets. There was no significant change of blood examination and biochemical examination of blood in the enrolled patients. Above results show that the tablet containing L. gasseri OLL2809 is effective on endometriosis, especially against menstrual pain and dysmenorrhea. Moreover, it was found that the tablet has no adverse effects. Therefore, it was suggested that the tablet containing L. gaserri OLL2809 contributes to improve the quality of life in the patients with endometriosis.

Dis Model Mech. 2011 Mar;4(2):139-40. Epub 2011 Jan 31.

Progression of endometriosis to cancer: too MUCh FoxP3+ regulatory T-cell response?

Prieto GA.

Source

Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697-4545, USA. aleph.prieto@uci.edu

Comment on

Eur J Obstet Gynecol Reprod Biol. 2011 Mar;155(1):85-8. Epub 2010 Nov 26.

Attachment to extracellular matrices is enhanced in human endometriotic stromal cells: a possible mechanism underlying the pathogenesis of endometriosis.

Adachi M, Nasu K, Tsuno A, Yuge A, Kawano Y, Narahara H.

Source

Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Yufu-shi, Oita, Japan.

Abstract

OBJECTIVE:

Endometriosis is characterized by the ectopic growth of endometrial tissue. One of the first steps to the spread of endometriosis in the peritoneal cavity is the attachment of endometriotic cells to peritoneal surfaces after they have been released into the peritoneal fluid from pre-existing endometriotic lesions. The increased adhesive and proliferative potential of endometriotic cells in response to specific extracellular matrix (ECM) components has been suggested to contribute to the pathogenesis of endometriosis.

STUDY DESIGN:

Adhesive properties of endometriotic stromal cells (ECSC) and normal eutopic endometrial cells (NESC) to various extracellular matrix proteins were investigated by in vitro cell adhesion assays. The expression levels of integrins in these cells were also examined by Western blot analysis.

RESULTS:

Both ECSC and NESC significantly adhered to collagen type I and collagen type IV. ECSC revealed higher adhesive properties to these ECM proteins than NESC did. ECSC, but not NESC, adhered to fibronectin and laminin. Higher levels integrin of α1, α2, αv, β1, and β3 protein expression were observed in ECSC than in NESC. On the other hand, the levels of integrin α3 and αL proteins were lower in ECSC than in NESC.

CONCLUSIONS:

The results suggest that endometriotic cells possess stronger adhesion to ECM proteins, and that increase may be mediated, in part, through integrins. These findings may elucidate one of the mechanisms underlying the formation of peritoneal endometriotic lesions.

Eur J Obstet Gynecol Reprod Biol. 2011 Mar;155(1):41-3. Epub 2010 Dec 15.

The usefulness of transvaginal hydrolaparoscopy in infertile women with abnormal hysterosalpingogram results but with no obvious pelvic pathology.

Yang R, Ma C, Qiao J, Li TC, Yang Y, Chen X, Yang S, Liu P.

Source

Department of Obstetrics and Gynecology, Reproductive Medical Centre, Peking University Third Hospital, Beijing, China.

Abstract

OBJECTIVE:

To evaluate the value of transvaginal hydrolaparoscopy (THL) in infertile women with abnormal hysterosalpingogram results but with no history of previous pelvic surgery and with normal gynecological examination and vaginal sonography.

STUDY DESIGN:

This is a retrospective study. From January 2008 to October 2009, 51 infertile women were planned to undergo standard laparoscopy because of abnormal HSG. None of the patients had any history of previous pelvic surgery and all had normal findings on gynecological examination and vaginal sonography. These women underwent THL.

RESULTS:

Among the 51 cases, successful access to the pouch of Douglas was achieved in 49. There were two failures due to obesity, and the operation was converted to standard laparoscopy. No complication was observed in this study period. In 26 patients (53.1%) the THL procedure showed normal pelvic organs. Four patients were lost to follow-up. Of the remaining 22 cases, four became pregnant (4/22, 18.2%) through intercourse or intrauterine insemination (IUI). There were some morphologic abnormalities seen in the remaining 23 patients such as adhesions, endometriosis and hydrosalpinx. Six cases with mild adhesions and endometriosis were treated with THL alone, and four (4/6, 66.7%) became pregnant with or without IUI. Among the 19 who underwent standard laparoscopy, three were lost to follow-up. In the other 16 cases, natural pregnancy occurred in six (6/16, 37.5%) patients with or without IUI.

CONCLUSIONS:

For women with abnormal HSG results but with no obvious pelvic pathology, THL should be recommended and about 50% could avoid an unnecessary laparoscopy. Adhesiolysis and coagulation of endometriotic lesions under THL in mild adhesion and endometriosis cases could lead to encouraging results.

Fertil Steril. 2011 Mar 1;95(3):889-94. Epub 2011 Jan 26.

Does advanced-stage endometriosis affect the gene expression of estrogen and progesterone receptors in granulosa cells?

Karita M, Yamashita Y, Hayashi A, Yoshida Y, Hayashi M, Yamamoto H, Tanabe A, Terai Y, Ohmichi M.

Source

Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Osaka, Japan.

Abstract

OBJECTIVE:

To evaluate how endometriosis affects the expression of estrogen and progesterone receptors mRNA in granulosa cells.

DESIGN:

Prospective study.

SETTING:

IVF-ET program at Osaka Medical College.

PATIENT(S):

Eighteen patients with revised American Fertility Society stage IV endometriosis and 23 patients with tubal infertility without endometriosis.

INTERVENTION(S):

Granulosa cells obtained from patients with endometriosis were examined for estrogen (ER-β, ER-α) and progesterone (PR-A, PR-B) receptor mRNA expression ratio against GAPDH.

MAIN OUTCOME MEASURE(S):

Hormonal environment and clinical outcome were investigated. Expression of ER and PR mRNA were evaluated by StepOne real-time polymerase chain reaction (PCR) analysis.

RESULT(S):

Total hMG/FSH levels were statistically higher in patients with endometriosis; however, high-quality embryo rates and pregnancy rates were lower in patients with endometriosis than in patients with tubal infertility. Expression of PR-A and ER-α in patients with endometriosis was statistically higher than in patients with tubal infertility. The expression of PRs and ERs in patients with tubal infertility showed a positive correlation; however, it was not identified in the endometriosis group.

CONCLUSION(S):

The higher PR-A and ER-α gene expression in granulosa cells in patients with endometriosis, compared with patients with tubal infertility, might be a leading cause of ovarian dysfunction due to endometriosis.

Lascia un commento

Cerca

Utilizzando il sito, accetti l'utilizzo dei cookie da parte nostra. maggiori informazioni

Questo sito utilizza i cookie per fornire la migliore esperienza di navigazione possibile. Continuando a utilizzare questo sito senza modificare le impostazioni dei cookie o cliccando su "Accetta" permetti il loro utilizzo.

Chiudi