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Clinical Study of NK Cells in the Treatment of Severe Endometriosis

https://clinicaltrials.gov/ct2/show/NCT03948828?type=Intr&cond=Endometriosis&lupd_s=04%2F30%2F2019&lupd_d=14

Conditions :   NK Cell Mediated Immunity;   Endometriosis

Interventions :   Biological: Autologous NK cell therapy;   Drug: GnRHa combained with reverse addition therapy

Sponsor :   Shenzhen People’s Hospital

Not yet recruiting

Clinical Study of NK Cells in the Treatment of Severe Endometriosis

NCT03948828

Tue, 14 May 2019 12:00:00 EDT

Last Update Posted: 05/14/19 06:51AM

LncRNA-H19 regulates cell proliferation and invasion of ectopic endometrium by targeting ITGB3 via modulating miR-124-3p

https://www.sciencedirect.com/science/article/abs/pii/S0014482719302411?via%3Dihub

https://www.ncbi.nlm.nih.gov/pubmed/31085188?dopt=Abstract

Related Articles

LncRNA-H19 regulates cell proliferation and invasion of ectopic endometrium by targeting ITGB3 via modulating miR-124-3p.

Exp Cell Res. 2019 May 11;:

Authors: Liu S, Qiu J, Tang X, Cui H, Zhang Q, Yang Q

Abstract

Endometriosis, a common gynecological disease, is associated with pelvic pain and infertility. Endometriosis affects approximately 10% of women, but that number increases to 30-50% in symptomatic premenopausal women. Despite the prevalence of endometriosis, the cause has yet to be fully elucidated. Recent study of the molecular pathways of endometrial cancer has brought the long non-coding RNA (lncRNA) H19 to our attention. In this paper, we explored the role of lncRNA-H19 in endometrial tissue proliferation. We found that ectopic endometrial cells taken from women with endometriosis showed elevated levels of lncRNA-H19, with expression levels correlating to disease progression. Knockdown of H19 in ectopic endometrial cells inhibited cell proliferation and invasion. Coinciding with this change was an increase in microRNA-124-3p (miR-124-3p) and a decrease in integrin beta-3 (ITGB3) levels. The addition of a miR-124-3p inhibitor mitigated this decrease in ITGB3. Up-regulation of miR-124-3p markedly suppressed ITGB3 expression by binding to the 3′ untranslated region (3′ UTR), while inhibition of miR-124-3p had the opposite effect. ITGB3 overexpression potently counteracted the effects of miR-124-3p mimics on ectopic endometrial cells. From these results, we can infer that in endometriosis both miR-124-3p and ITGB3 operate as downstream effector proteins in the H19-signaling pathway. Down-regulation of lncRNA-H19 could inhibit ectopic endometrial cell proliferation and invasion by modulating miR-124-3p and ITGB3, offering a novel target for treatment.

PMID: 31085188 [PubMed – as supplied by publisher]

Experts: Research Gap Stalls Improvements in Endometriosis Care

https://labblog.uofmhealth.org/industry-dx/experts-research-gap-stalls-improvements-endometriosis-care

Experts: Research Gap Stalls Improvements in Endometriosis Care – Researchers call for advancements in treatment for a chronic disease that affects millions of women and causes chronic pain, inflammation and infertility.

Dienogest or Norethindrone acetate for the treatment of ovarian endometriomas: Can we avoid surgery?

https://www.ejog.org/article/S0301-2115(19)30165-4/fulltext

https://www.ncbi.nlm.nih.gov/pubmed/31132690?dopt=Abstract

Related Articles

Dienogest or Norethindrone acetate for the treatment of ovarian endometriomas: Can we avoid surgery?

Eur J Obstet Gynecol Reprod Biol. 2019 May 02;238:120-124

Authors: Del Forno S, Mabrouk M, Arena A, Mattioli G, Giaquinto I, Paradisi R, Seracchioli R

Abstract

OBJECTIVE: To compare the effects of Dienogest (D) and Norethindrone acetate (N) in symptomatic women with ovarian endometriomas, analyzing the efficacy in reducing endometrioma size and symptom relief and drug tolerability.

STUDY DESIGN: Retrospective study including 135 symptomatic women with ultrasonographic diagnosis of ovarian endometrioma. Women were divided into two groups: 1) women who received D 2 mg/day (group D); 2) women who received N 2.5 mg/day (group N). Women were evaluated at therapy prescription and after 6 and 12 months of treatment: transvaginal ultrasound was performed to assess the mean diameter of endometriomas, a Visual Analogue Scale was used to rank endometriosis related symptoms (dysmenorrhea, dyspareunia, chronic pelvic pain). The main outcome measure was the comparison between the 2 groups in terms of variations in endometrioma size and endometriosis related symptoms during the follow-up. Drug tolerability was also analyzed in terms of side effects.

RESULTS: A reduction in ovarian endometrioma size was observed during treatment in both groups, with no significant differences between groups D and N. Endometriosis related symptoms decreased in both groups, but the decrease was significantly higher in group D than in group N for all symptoms, both at 6 and 12 months of treatment. Regarding drug tolerability, uterine bleeding/spotting and weight gain were reported more frequently by women in the group N than women in the group D, both at 6 and 12 months of treatment.

CONCLUSION: Progestin therapy with D or N appears to be effective in reducing the size of endometriomas and related symptoms, with a greater effect on symptoms relief and higher tolerability in women treated with D.

PMID: 31132690 [PubMed – as supplied by publisher]

Silencing of Forkhead Box M1 Reverses Transforming Growth Factor-β1-Induced Invasion and Epithelial-Mesenchymal Transition of Endometriotic Epithelial Cells

https://www.karger.com/Article/Abstract/499625

https://www.ncbi.nlm.nih.gov/pubmed/31039568?dopt=Abstract

Silencing of Forkhead Box M1 Reverses Transforming Growth Factor-β1-Induced Invasion and Epithelial-Mesenchymal Transition of Endometriotic Epithelial Cells.

Gynecol Obstet Invest. 2019 Apr 30;:1-10

Authors: Zhang J, Xu Z, Dai H, Zhao J, Liu T, Zhang G

Abstract

AIM: The aim of this study was to investigate the expression of Forkhead box M1 (FoxM1) in endometriosis and determine FoxM1’s possible effects on endometriotic epithelial cells (EECs) invasion and epithelial-mesenchymal transition (EMT).

METHODS: The expression of FoxM1 and E-cadherin in endometrium and ectopic tissues was analyzed by immunohistochemistry. The transforming growth factor-β1 (TGF-β1) was added to induce EMT of EECs, which were purified from ectopic tissues. The Short hairpin RNA (ShRNA) intervention technique was used to silence FoxM1. The morphological changes of EECs were observed by microscope. The invasion ability of EECs was determined by transwell invasion assay. The expression of FoxM1 and EMT-related gene (E-cadherin, N-cadherin, vimentin, and Snail) in EECs was detected by quantitative reverse transcription-polymerase chain reaction and western blot.

RESULTS: FoxM1 expression was significantly increased, while E-cadherin expression was significantly decreased in ectopic tissues than that in endometrium tissues. After TGF-β1 treatment, EECs showed a transformation from an epithelial sheet-like structure to a mesenchymal fibroblastic spindle shape; EECs invasion ability was enhanced; the level changes of EMT-related molecule also indicated an EMT phenotype of EECs. After FoxM1-shRNA intervention, TGF-β1-induced changes of EECs in morphology, invasion ability and EMT-related molecule expressions were partially reversed.

CONCLUSIONS: Silencing of FoxM1 could reverse TGF-β1-induced invasion and EMT of EECs.

PMID: 31039568 [PubMed – as supplied by publisher]

Clinical Study to Evaluate Efficacy and Safety of TAK-385 40 mg Compared With Leuprorelin in Patients With Endometriosis

https://clinicaltrials.gov/ct2/show/NCT03931915?type=Intr&cond=Endometriosis&lupd_s=04%2F16%2F2019&lupd_d=14

Condition :   Endometriosis

Interventions :   Drug: TAK-385;   Drug: Leuprorelin acetate

Sponsor :   ASKA Pharmaceutical Co., Ltd.

Not yet recruiting

Clinical Study to Evaluate Efficacy and Safety of TAK-385 40 mg Compared With Leuprorelin in Patients With Endometriosis

NCT03931915

Tue, 30 Apr 2019 12:00:00 EDT

Last Update Posted: 04/30/19 11:33AM

Calligonum comosum (Escanbil) extract exerts anti-angiogenic, anti-proliferative and anti-inflammatory effects on endometriotic lesions

https://www.sciencedirect.com/science/article/pii/S0378874118340820?via%3Dihub

https://www.ncbi.nlm.nih.gov/pubmed/31034955?dopt=Abstract

Calligonum comosum (Escanbil) extract exerts anti-angiogenic, anti-proliferative and anti-inflammatory effects on endometriotic lesions.

J Ethnopharmacol. 2019 Apr 26;:111918

Authors: Kiani K, Rudzitis-Auth J, Scheuer C, Movahedin M, Sadati Lamardi SN, Ardakani HM, Becker V, Moini A, Aflatoonian R, Ostad SN, Menger MD, Laschke MW

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Calligonum comosum is a desert plant that is applied in traditional folkloric medicine for the treatment of abnormally heavy or prolonged menstruation and menstrual cramps. Moreover, it has been suggested for the treatment of infertility-causing conditions. Its bioactive chemical constituents inhibit multiple processes, such as angiogenesis, inflammation and invasive tissue growth, which may be beneficial in the therapy of endometriosis.

AIM OF THE STUDY: We investigated the effects of Calligonum comosum on the development of endometriotic lesions.

MATERIALS AND METHODS: We evaluated the anti-angiogenic activity of Calligonum comosum ethyl acetate fraction (CCEAF) in different in vitro angiogenesis assays. Moreover, we surgically induced endometriotic lesions in BALB/c mice, which received 50 mg/kg Calligonum comosum total extract (CCTE) or vehicle (control) over 4 weeks. The growth, cyst formation, vascularization and immune cell infiltration of the lesions were assessed with high-resolution ultrasound imaging, caliper measurements, histology and immunohistochemistry.

RESULTS: CCEAF doses of up to 10 μg/mL did not impair the viability of human dermal microvascular endothelial cells (HDMEC), but dose-dependently suppressed their migration, tube formation and sprouting, indicating a substantial anti-angiogenic effect of CCEAF. Furthermore, CCTE significantly inhibited the growth and cyst formation of developing murine endometriotic lesions when compared to vehicle-treated controls. This was associated with a reduced vascularization, cell proliferation and immune cell infiltration.

CONCLUSIONS: Our findings show that Calligonum comosum targets multiple, fundamental processes in the pathogenesis of endometriosis, which may be beneficial for the treatment of this common gynecological disorder.

PMID: 31034955 [PubMed – as supplied by publisher]

Hypomethylation of the GSTM1 promoter is associated with ovarian endometriosis: new evidence to support the notion that endometriosis may be an epigenetic disease

https://www.ncbi.nlm.nih.gov/pubmed/30989213?dopt=Abstract

Related Articles

Hypomethylation of the GSTM1 promoter is associated with ovarian endometriosis.

Hum Reprod. 2019 Apr 16;:

Authors: Zhao J, Wang L, Li Y, Zhao W, Kang S

Abstract

STUDY QUESTION: Is the methylation status of the glutathione S-transferase M1 (GSTM1) promoter region altered in patients with ovarian endometriosis, and does this affect the expression of GSTM1 in their endometrial tissues?

SUMMARY ANSWER: The promoter region of GSTM1 was significantly hypomethylated in the ectopic and eutopic endometrium of patients with ovarian endometriosis and this was associated with higher expression of GSTM1 mRNA.

WHAT IS KNOWN ALREADY: GSTM1, a member of the glutathione S-transferase family, is primarily known as a detoxification enzyme, but it has also been shown to negatively regulate apoptosis-related signalling cascades through protein-protein interactions with apoptosis signal-regulating kinase-1.

STUDY DESIGN, SIZE, DURATION: This is a case-control study between September 2013 and December 2016, involving 65 patients with ovarian endometriosis and 53 women without endometriosis. We analysed the methylation status and expression levels of GSTM1 in the ectopic and eutopic endometrium of patients with ovarian endometriosis and the endometrium of women without endometriosis. In addition, we collected endometrial samples from 12 women without endometriosis for endometrial epithelial cell cultures.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Methylation levels of the GSTM1 promoter region in the ectopic and eutopic endometrial tissues of patients with ovarian endometriosis and the endometrial tissues of women without endometriosis were analysed by pyrosequencing. The expression of GSTM1 mRNA and protein in endometrial tissues was investigated by RT-qPCR and immunohistochemistry, respectively. Primary cell culture, gene transfection, Cell Counting Kit-8 assay and flow cytometry were used to analyse the effect of GSTM1 on viability and apoptosis in endometrial epithelial cells.

MAIN RESULTS AND THE ROLE OF CHANCE: Compared with that in the endometrium of women without endometriosis, the GSTM1 promoter region was significantly hypomethylated in the ectopic and eutopic endometrium of patients with ovarian endometriosis. Additionally, GSTM1 mRNA and protein levels were significantly higher in the ectopic and eutopic endometrium than in the control endometrium. Moreover, the methylation levels of the GSTM1 promoter region were significantly negatively correlated with the mRNA expression of GSTM1. Furthermore, in vitro results suggested that the over-expression of GSTM1 could significantly increase viability and inhibit apoptosis in endometrial epithelial cells following hormone treatment and withdrawal.

LIMITATIONS, REASONS FOR CAUTION: Due to restrictions in the isolation and culture of pure populations of endometrial epithelial cells, as well as limitations in the number of passages possible in primary cells, we could not explore the underlying molecular mechanism by which GSTM1 modulates apoptosis in endometrial cells.

WIDER IMPLICATIONS OF THE FINDINGS: This study provides new evidence to support the notion that endometriosis may be an epigenetic disease.

STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the Natural Science Foundation of Hebei Province (Grant number: H2018206200) and the Department of Education of Hebei Province (Grant number: CXZZBS2017114). The authors have no conflicts of interest to declare.

PMID: 30989213 [PubMed – as supplied by publisher]

Once-daily Tablet of V-Endo as Immunotherapy of Endometriosis

https://clinicaltrials.gov/ct2/show/NCT03340324?type=Intr&cond=Endometriosis&lupd_s=04%2F02%2F2019&lupd_d=14

Condition :   Endometriosis

Intervention :   Biological: V-Endo

Sponsors :   Immunitor LLC;   Ekomed LLC

Recruiting

Open Label Immunotherapy of Endometriosis

NCT03340324

Mon, 13 Nov 2017 12:00:00 EST

Last Update Posted: 04/16/19 09:05AM

Doxycycline, in combination with progestins such as dienogest, may be an additional therapeutic approach in patients with infiltrative endometriosis with insufficient response to current treatment options

https://rbej.biomedcentral.com/articles/10.1186/s12958-019-0481-z

https://www.ncbi.nlm.nih.gov/pubmed/30981279?dopt=Abstract

Doxycycline reduces MMP-2 activity and inhibits invasion of 12Z epithelial endometriotic cells as well as MMP-2 and -9 activity in primary endometriotic stromal cells in vitro.

Reprod Biol Endocrinol. 2019 Apr 13;17(1):38

Authors: Samartzis EP, Fink D, Stucki M, Imesch P

Abstract

BACKGROUND: Matrix metalloproteinases (MMPs), especially the gelatinases MMP-2 and MMP-9, play a crucial role in the pathogenesis of endometriosis by enabling invasion. Doxycycline is a well-tolerated antibiotic and a potent MMP-inhibitor in subantimicrobial doses.

METHODS: Gelatin zymography and activity assays were used to detect latent and active MMP-2 and -9 in cell culture supernatants of immortalized epithelial (12Z) and two isolates of primary endometriotic stromal cells treated with doxycycline. The invasiveness of 12Z endometriotic cells treated with doxycycline was assessed in matrigel-coated invasion chambers. The effect on latent and active MMP-2 expression of the combination of progesterone and doxycycline was tested in 12Z.

RESULTS: Doxycycline significantly reduced the MMP-2 activity and pro-MMP-2 expression in 12Z and the MMP-2 and -9 activity as well as expression of pro-MMP-2 and -9 in primary endometriotic stromal cells. The percentage of 12Z cells invading through a matrigel-coated membrane was reduced to 65 and 22% of the control after treatment with doxycycline at doses of 1 μg/ml and 10 μg/ml, respectively. Furthermore, a combination of progesterone and doxycycline showed an additive effect in low doses on the reduction of MMP-2 activity and pro-MMP2 expression in 12Z endometriotic cells.

CONCLUSIONS: In conclusion, the MMP-inhibiting features of subantimicrobial-dose doxycycline may be further evaluated as a well-tolerable additional therapeutic approach, e.g. in combination with progestins such as dienogest, in patients with infiltrative endometriosis with insufficient response to current medical treatment options.

PMID: 30981279 [PubMed – in process]

Downregulation of lncRNA UCA1 is involved in the pathogenesis of ovarian endometriosis and may serve as a promising diagnostic and prognostic biomarker for the disease

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0104-42302019000300336&lng=en&tlng=en

https://www.ncbi.nlm.nih.gov/pubmed/30994830?dopt=Abstract

Downregulation of lncrna uca1 as a diagnostic and prognostic biomarker for ovarian endometriosis.

Rev Assoc Med Bras (1992). 2019 Mar;65(3):336-341

Authors: Huang H, Zhu Z, Song Y

Abstract

OBJECTIVE: Ovarian endometriosis seriously affects the quality of life of females, and long non-coding RNA lncRNA urothelial carcinoma-associated 1 (UCA1) plays pivotal roles in the pathogenesis of various ovarian diseases. However, the involvement of lncRNA UCA1 in ovarian endometriosis remains unknown to date. Therefore, the present study aims to study the role of UCA1 in ovarian endometriosis.

METHODS: A total of 98 patients with ovarian endometriosis and 28 healthy females were included. The expression of lncRNA UCA1 in ectopic and eutopic endometrium tissues of ovarian endometriosis patients and controls was detected using qRT-PCR. A ROC curve analysis was performed to evaluate the diagnostic values of serum lncRNA UCA1 for ovarian endometriosis. Patients were followed up for 2 years after discharge, and the recurrence of ovarian endometriosis was recorded.

RESULTS: The expression level of lncRNA UCA1 was significantly higher in ectopic endometrium tissues than in paired eutopic endometrium tissues for most of the patients. The serum lncRNA UCA1 level showed no significant correlations with either patients’ age or living habits. After the treatment, the serum lncRNA UCA1 level increased, and serum levels of lncRNA UCA1 on the day of discharge were significantly lower in patients with recurrence than those in patients without recurrence. Conclusion: The downregulation of lncRNA UCA1 is involved in the pathogenesis of ovarian endometriosis and may serve as a promising diagnostic and prognostic biomarker for the disease.

PMID: 30994830 [PubMed – in process]

Evaluation of Oxidative Stress and Severity of Endometriosis – “oxidative stress status represents a mechanism which is amenable to treatment or prevention of endometriosis”

https://www.ncbi.nlm.nih.gov/pubmed/31007466?dopt=Abstract

http://www.jhrsonline.org/article.asp?issn=0974-1208;year=2019;volume=12;issue=1;spage=40;epage=46;aulast=Amreen

Evaluation of Oxidative Stress and Severity of Endometriosis.

J Hum Reprod Sci. 2019 Jan-Mar;12(1):40-46

Authors: Amreen S, Kumar P, Gupta P, Rao P

Abstract

Aims: The aim was to evaluate the association between oxidative stress with the severity of endometriosis in blood and peritoneal fluid.

Settings and Design: This study was a prospective observational study conducted in the department of obstetrics and gynecology in a tertiary center over 2 years in patients with endometriosis requiring laparoscopy.

Methodology: Patients diagnosed with endometriosis and undergoing laparoscopy for infertility and/or chronic pelvic pain were included in the study. Out of the 64 patients recruited, only 55 patients formed the part of our study. Blood and peritoneal fluid was evaluated for oxidative stress parameters such as glutathione peroxidase, superoxide dismutase (SOD), and lipid peroxides.

Results: The severity of endometriosis was assessed intraoperatively by the revised American Society for Reproductive Medicine scoring in all 55 patients who underwent laparoscopy into minimal (n = 3), mild (n = 7), moderate (n = 32), and severe (n = 17). Median activity of SOD and glutathione peroxidase was lowest in the severe stage of endometriosis, whereas the median activity of lipid peroxide was highest in the severe stage of endometriosis in both blood and peritoneal fluid samples. There was a statistically significant increase in oxidative stress with the severity of endometriosis.

Conclusions: Oxidative stress might play a role in the disease process of endometriosis. Control of oxidative stress can be used as the latest treatment option for the management of endometriosis.

PMID: 31007466 [PubMed]

SPIRIT 1: Efficacy and Safety Study of Relugolix in Women With Endometriosis-Associated Pain

https://clinicaltrials.gov/ct2/show/NCT03204318?type=Intr&cond=Endometriosis&lupd_s=03%2F22%2F2019&lupd_d=14

Condition :   Endometriosis Related Pain

Interventions :   Drug: Relugolix;   Drug: Estradiol/norethindrone acetate;   Drug: Placebo for E2/NETA;   Drug: Placebo for relugolix

Sponsor :   Myovant Sciences GmbH

Recruiting

SPIRIT 1: Efficacy and Safety Study of Relugolix in Women With Endometriosis-Associated Pain

NCT03204318

Sun, 02 Jul 2017 12:00:00 EDT

Last Update Posted: 04/05/19 08:45AM

Surgical Eradication of Deep Infiltrating Endometriosis of the Vagina

https://clinicaltrials.gov/ct2/show/NCT03744143?type=Intr&cond=Endometriosis&lupd_s=03%2F19%2F2019&lupd_d=14

Condition :   Endometriosis

Interventions :   Procedure: longitudinal suture;   Procedure: transverse suture;   Procedure: Removal of vaginal endometriotic nodule

Sponsor :   Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi

Completed

Surgical Eradication of Deep Infiltrating Endometriosis of the Vagina

NCT03744143

Fri, 16 Nov 2018 12:00:00 EST

Last Update Posted: 04/02/19 08:14AM

A research on the protein expression of p53, p16, and MDM2 in endometriosis

https://www.ncbi.nlm.nih.gov/pubmed/30946310?dopt=Abstract

https://journals.lww.com/md-journal/fulltext/2019/04050/A_research_on_the_protein_expression_of_p53,_p16,.2.aspx

A research on the protein expression of p53, p16, and MDM2 in endometriosis.

Medicine (Baltimore). 2019 Apr;98(14):e14776

Authors: Sang L, Fang QJ, Zhao XB

Abstract

This study aims to examine the expression of p53, p16, and murine double minute 2 (MDM2) protein in normal endometrium and endometriosis, in order to discuss the role of p53, p16, and MDM2 protein and apoptosis in the pathogenesis and development of endometriosis, and provide a theoretical basis for clinical diagnosis and treatment.The immunohistochemical streptavidin-biotin peroxidase method was used to detect the expression of p53, p16, and MDM2 in tissue samples obtained from 30 women with pathologically confirmed ovarian endometriosis and 29 women with pathologically confirmed normal endometrium. The relationship between p53, p16, and MDM2 expression and apoptosis was analyzed.In normal endometrium, the positive rate of p53 in the secretory phase was higher than that in the proliferative phase (P < .05). Furthermore, the positive rate of p53 in normal endometrium was higher than that in ovarian endometriosis (P < .05). There was a significant difference between normal endometrium and ovarian endometriosis.The positive rate of p16 in normal endometrium was higher than that in ovarian endometriosis (P < .05). Furthermore, there was a significant difference between normal endometrium and ovarian endometriosis. The positive rate of MDM2 in normal endometrium was lower than that in ovarian endometriosis (P < .05).In ovarian endometriosis, the expression of p53 and p16 was positively correlated with each other (r = 0.611, P < .01). However, the expression of p53 and MDM2 was negatively correlated with each other (r = -0.541, P < .01). Furthermore, the expression of p16 and MDM2 might not be relevant in the endometriosis (r = 0.404, P > .05).As important apoptosis regulatory genes, p53, p16, and MDM2 might be involved in the pathogenesis and development of endometriosis.

PMID: 30946310 [PubMed – in process]

A Study to Assess the Effectiveness and Safety of Different Doses of ASP1707 Compared to Placebo for Endometriosis Associated Pelvic Pain

https://clinicaltrials.gov/ct2/show/NCT01767090?type=Intr&cond=Endometriosis&lupd_s=03%2F15%2F2019&lupd_d=14

Condition :   Endometriosis

Interventions :   Drug: ASP1707;   Drug: Placebo;   Drug: Leuprorelin acetate

Sponsor :   Astellas Pharma Europe B.V.

Completed

A Study to Assess the Effectiveness and Safety of Different Doses of ASP1707 Compared to Placebo for Endometriosis Associated Pelvic Pain

NCT01767090

Mon, 14 Jan 2013 12:00:00 EST

Last Update Posted: 03/29/19 09:45AM

Study to Compare the Oestradiol Suppression, Clinical Efficacy and Safety of Two Formulations of Triptorelin (Triptorelin Pamoate PR 3-month and Triptorelin Acetate PR 1-month) in Subjects With Endometriosis

https://clinicaltrials.gov/ct2/show/NCT03232281?type=Intr&cond=Endometriosis&lupd_s=03%2F14%2F2019&lupd_d=14

Condition :   Endometriosis

Interventions :   Drug: Triptorelin Pamoate PR 3-month;   Drug: Triptorelin Acetate PR 1-month

Sponsor :   Ipsen

Active, not recruiting

Study to Compare the Oestradiol Suppression, Clinical Efficacy and Safety of Two Formulations of Triptorelin (Triptorelin Pamoate PR 3-month and Triptorelin Acetate PR 1-month) in Chinese Subjects With Endometriosis

NCT03232281

Thu, 27 Jul 2017 12:00:00 EDT

Last Update Posted: 03/28/19 09:30AM

Effect of danefukang (DEFK) on symptoms and biomarkers in women with endometriosis

https://www.sciencedirect.com/science/article/pii/S1028455919300099?via%3Dihub

https://www.ncbi.nlm.nih.gov/pubmed/30910142?dopt=Abstract

Related Articles

Effect of danefukang on symptoms and biomarkers in women with endometriosis.

Taiwan J Obstet Gynecol. 2019 Mar;58(2):218-222

Authors: Zhong YC, Zhou XF, Hou CM, Li WP

Abstract

OBJECTIVE: The purpose of this study was to observe the efficacy of Danefukang (DEFK) soft extract for the treatment of symptoms associated with endometriosis, and its effect on quality of life, the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) scores, and on levels of carbohydrate antigen (CA)-125, tumor necrosis factor (TNF)-α, and interleukin (IL)-6.

MATERIALS AND METHODS: A total of 174 patients with endometriosis treated from January 2010 to December 2013 were randomly divided into a control group treated with mifepristone (n = 87) or DEFK (n = 87). Both groups were treated for 3 months. Symptoms, quality of life, SAS, SD scores, and levels of CA-125, TNF-α, and IL-6 were evaluated before and after treatment.

RESULTS: The effectiveness rate was 93.10% in the DEFK group and 81.61% in the mifepristone control group (χ2 = 4.215, P < 0.05). Treatment with DEFK resulted in a greater improvement in quality of life, SDS, and SAS scores compared with mifepristone (all, P < 0.05). DEFK treatment also resulted in a greater decrease of CA-125, TNF-α, and IL-6 levels compared with mifepristone (all, P < 0.05). CONCLUSION: Based on the current results - improved symptoms, attenuated depression and anxiety, and reduced the levels of pro-inflammatory cytokines and CA-125 -treatment with DEFK is a meaningful option for patients with endometriosis. DEFK fills an unmet need in the pharmacologic treatment of endometriosis. PMID: 30910142 [PubMed - in process]

Synergistic and protective effect of atorvastatin and amygdalin against histopathological and biochemical alterations in Sprague-Dawley rats with experimental endometriosis

https://amb-express.springeropen.com/articles/10.1186/s13568-019-0760-2

https://www.ncbi.nlm.nih.gov/pubmed/30888523?dopt=Abstract

Synergistic and protective effect of atorvastatin and amygdalin against histopathological and biochemical alterations in Sprague-Dawley rats with experimental endometriosis.

AMB Express. 2019 Mar 19;9(1):37

Authors: Hu F, Hu Y, Peng F

Abstract

The aim of the present study was to evaluate the protective effects of combined atorvastatin and amygdalin in a rat model of endometriosis. Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-2 (MMP-2) and MMP-9 levels in the peritoneal fluid were determined. The expression of TNF-α, IL-6, MMP-2, and MMP-9 mRNA, and the levels of lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD), catalase, and glutathione peroxidase (Gpx) were measured. Histopathological analysis was also conducted. The results showed that peritoneal TNF-α, IL-6, MMP-2, and MMP-9 levels were reduced by > 50%, and mRNA expression was decreased. Lipid peroxidation was considerably reduced, while GSH, SOD, Gpx, and catalase levels increased by > 40%. Reductions in leukocyte infiltration and fibrosis following treatment were also observed. Thus, our study suggested that combined treatment consisting of atorvastatin and amygdalin attenuates endometriosis. A detailed investigation of molecular mechanism of atorvastatin and amygdalin in endometriosis is needed.

PMID: 30888523 [PubMed]

Effects of clarithromycin on inflammatory markers and clinical manifestations in postsurgical follow-up of patients with endometriosis: a double-blinded randomized placebo-controlled clinical trial

https://link.springer.com/article/10.1007%2Fs00404-019-05057-4

https://www.ncbi.nlm.nih.gov/pubmed/30888478?dopt=Abstract

Effects of clarithromycin on inflammatory markers and clinical manifestations in postsurgical follow-up of patients with endometriosis: a double-blinded randomized placebo-controlled clinical trial.

Arch Gynecol Obstet. 2019 Mar 19;:

Authors: Alborzi S, Poordast T, Askary E, Dorniani G

Abstract

PURPOSE: Studies showed anti-inflammatory and immunomodulatory effects of macrolide antibiotics such as clarithromycin in endometriosis. Therefore, the present study aims to investigate the therapeutic efficacy of clarithromycin in patients with endometriosis.

METHODS: This was a double-blinded randomized placebo-controlled trial conducted on endometriotic women during March 2016-2017 in Dena Hospital, Shiraz, Iran. Immediately after surgery, the patients were randomly divided into clarithromycin (real) (n = 120) and placebo group (n = 169). The real group received 500 mg of clarithromycin everyday for 6 months and the placebo group received the placebo. The serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), Erythrocyte sedimentation rate (ESR) and C-reactive protein as well as clinical symptoms at baseline and 3 and 6 months of post-surgery were compared within and between groups.

RESULTS: The scores of dysmenorrhea, dyschezia, dyspareunia, and non-menstrual pain significantly decreased in both real and placebo groups compared with the baseline values. However, the real group showed greater reductions compared with the placebo group (p < 0.001). Similarly, the serum levels of CRP, TNF-α, and IL-10 decreased in both groups compared with the baseline values, but the real group showed greater reductions. Interestingly, the reductions in the clinical symptoms and serum levels did not significantly differ between the real and placebo groups. Moreover, the reductions in the studied variables showed no dependence on the time. CONCLUSION: Clarithromycin may be an appropriate treatment in endometriotic patients. However, the non-significant differences between the real and placebo groups necessitate further studies on the therapeutic efficacy of clarithromycin.

PMID: 30888478 [PubMed – as supplied by publisher]

Assess Safety and Efficacy of Vilaprisan in Subjects With Endometriosis

https://clinicaltrials.gov/ct2/show/NCT03573336?type=Intr&cond=Endometriosis&lupd_s=03%2F05%2F2019&lupd_d=14

Condition :   Endometriosis

Interventions :   Drug: Vilaprisan (BAY1002670);   Drug: Matching Placebo

Sponsor :   Bayer

Active, not recruiting

Assess Safety and Efficacy of Vilaprisan in Subjects With Endometriosis

NCT03573336

Fri, 29 Jun 2018 12:00:00 EDT

Last Update Posted: 03/19/19 09:28AM

TGR5 agonist INT-777 mitigates inflammatory response in human endometriotic stromal cells: A therapeutic implication for endometriosis

https://www.sciencedirect.com/science/article/pii/S1567576918314437?via%3Dihub

https://www.ncbi.nlm.nih.gov/pubmed/30878820?dopt=Abstract

TGR5 agonist INT-777 mitigates inflammatory response in human endometriotic stromal cells: A therapeutic implication for endometriosis.

Int Immunopharmacol. 2019 Mar 14;71:93-99

Authors: Lyu D, Tang N, Wang J, Zhang Y, Chang J, Liu Z, Liu H

Abstract

Endometriosis is a condition characterized by the presence of endometrial tissues outside the uterus. Endometriotic stromal cells (ESCs) are known to undergo regeneration and are linked to the causation of endometriosis. Activation of stromal cells by local inflammatory cytokines is proposed to be one of the mechanisms of endometriosis development. Takeda-G-protein-receptor-5 (TGR5) is a G protein-coupled bile acid receptor that plays multiple roles in various cells and tissues. In this study, we show that activation of TGR5 by its specific agonist, INT-777, protects ESCs from inflammation and oxidative stress induced by tumor necrosis factor-α (TNF-α). TGR5 is fairly expressed in cultured ESCs, and TNF-α treatment suppresses TGR5 expression. Activation of TGR5 by its synthetic agonist, INT-777, dramatically reduces the production of pro-inflammatory cytokines and adhesion molecules by TNF-α, including interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Moreover, INT-777 suppresses TNF-α-induced NADPH oxidase 4 (NOX4) expression and ameliorates cellular oxidative stress. Mechanistically, our findings demonstrate that INT-777 suppresses TNF-α-induced c-Jun N-terminal kinase (JNK) activation via suppression of p-JNK. INT-777 inhibits TNF-α-induced activation of the activator protein-1 (AP-1) pathway owing to its suppression of c-Jun and c-fos as well as transfected AP-1 promoter. INT-777 also inhibits nuclear factor-κB (NF-κB) activation as revealed by its suppression of TNF-α-induced nuclear p65 accumulation and NF-κB promoter. Collectively, our data indicate that activation of TGR5 by its agonist has protective effects against inflammation and reactive oxygen species (ROS) in cytokine-induced activation of ESCs. Therefore, INT-777 may have an implication in the clinical treatment of endometriosis.

PMID: 30878820 [PubMed – as supplied by publisher]

Published: March 14, 2019
Posted: March 18, 2019

ATM expression is attenuated by promoter hypermethylation in human ovarian endometriotic stromal cells

https://academic.oup.com/molehr/advance-article-abstract/doi/10.1093/molehr/gaz016/5380590?redirectedFrom=fulltext

https://www.ncbi.nlm.nih.gov/pubmed/30869775?dopt=Abstract

ATM expression is attenuated by promoter hypermethylation in human ovarian endometriotic stromal cells.

Mol Hum Reprod. 2019 Mar 14;:

Authors: Hirakawa T, Nasu K, Aoyagi Y, Takebayashi K, Zhu R, Narahara H

Abstract

A number of genes involved in the pathogenesis of endometriosis are silenced by the hypermethylation of their promoter regions. We assessed the effect and mechanism of the DNA demethylating agent 5-aza-2′-deoxycytidine (5-aza-dC) (10 μM) on the cell cycle in human endometriotic cyst stromal cells (ECSCs) and normal endometrial stromal cells (NESCs) by flow cytometry. The DNA methylation status of G2/M checkpoint regulators were investigated by methylation-specific polymerase chain reaction (PCR). The expression of ATM and the effect of 5-aza-dC on its expression were also evaluated by quantitative reverse transcription-PCR and western blotting analysis. 5-aza-dC treatment resulted in the cell cycle arrest of ECSCs at the G2/M phase. In contrast, 5-aza-dC did not affect the cell cycle of NESCs. The promoter region of the ataxia telangiectasia mutated (ATM) gene was hypermethylated in ECSCs, but not in NESCs. ATM mRNA expression was attenuated in ECSCs compared to that in NESCs. Further, 5-aza-dC was found to restore ATM expression of in ECSCs by its promoter demethylation. Our findings indicate that ATM promoter hypermethylation occurs in endometriosis, and that ATM silencing is involved in tumorigenesis during this disease; moreover, selective DNA demethylating agents and molecular target drugs against ATM silencing are promising for the treatment of endometriosis.

PMID: 30869775 [PubMed – as supplied by publisher]

Efficacy of Cryoablation of Abdominal Wall Endometriosis

https://clinicaltrials.gov/ct2/show/NCT03627676?type=Intr&cond=Endometriosis&lupd_s=02%2F28%2F2019&lupd_d=14

Conditions :   Nodule;   Endometriosis

Intervention :   Procedure: Cryoablation

Sponsor :   Assistance Publique – Hôpitaux de Paris

Recruiting

Efficacy of Cryoablation of Abdominal Wall Endometriosis

NCT03627676

Mon, 13 Aug 2018 12:00:00 EDT

Last Update Posted: 03/14/19 09:43AM

Effect of Cannabinoid (THC / CBD 50%) on Hyperalgesia in Patients With Deep Endometriosis

https://clinicaltrials.gov/ct2/show/NCT03875261?type=Intr&cond=Endometriosis&lupd_s=02%2F28%2F2019&lupd_d=14

Condition :   Endometriosis

Intervention :   Drug: Cannabinoid treatment

Sponsors :   David Garcia Cinca;   Fundació Clínic per la Recerca Biomedica;   Dr. Christian Dursteler

Not yet recruiting

Effect of Cannabinoid (THC / CBD 50%) on Hyperalgesia in Patients With Deep Endometriosis

NCT03875261

Thu, 14 Mar 2019 12:00:00 EDT

Last Update Posted: 03/14/19 09:43AM

Comparison of long-term use of combined oral contraceptive after gonadotropin-releasing hormone agonist plus add-back therapy versus dienogest to prevent recurrence of ovarian endometrioma after surgery

https://www.ejog.org/article/S0301-2115(19)30104-6/fulltext

https://www.ncbi.nlm.nih.gov/pubmed/30884336?dopt=Abstract

Comparison of long-term use of combined oral contraceptive after gonadotropin-releasing hormone agonist plus add-back therapy versus dienogest to prevent recurrence of ovarian endometrioma after surgery.

Eur J Obstet Gynecol Reprod Biol. 2019 Mar 11;236:53-57

Authors: Seo JW, Lee DY, Kim SE, Yoon BK, Choi D

Abstract

OBJECTIVE: The aim of this study was to compare long-term use of combined oral contraceptive (COC) after gonadotropin-releasing hormone (GnRH) agonist plus add-back therapy with dienogest (DNG) treatment as medical treatments after surgery for ovarian endometrioma.

METHODS: This prospective cohort study analyzed 52 reproductive-aged women who underwent surgery for ovarian endometrioma and received postoperative medical treatment with either COC after GnRH agonist (n = 20) or DNG (n = 32) for 24 months. Changes in quality-of-life (QOL) and bone mineral density (BMD) were compared according to treatment. In addition, recurrence of pain and lesions were compared.

RESULTS: Baseline characteristics did not differ in demographic profiles and factors associated with endometriosis or QOL. During 24 months of treatment, no differences in any component of QOL were found between the two groups. BMD at the lumbar spine significantly decreased after the first 6 months of treatment in both COC after GnRH agonist (-3.5%) and DNG (-2.3%) groups, but the groups did not differ statistically. After 6 months, further decrease in BMD was not observed until 24 months in both groups. In addition, no cases of pain or endometrioma recurrence were found.

CONCLUSION: Our results suggest that long-term use of COC after GnRH agonist plus add-back therapy is comparable to dienogest as a long-term postoperative medical treatment for endometriosis.

PMID: 30884336 [PubMed – as supplied by publisher]

A Study to Evaluate the Efficacy and Safety of Gefapixant (MK-7264) in Women With Endometriosis-Related Pain (MK-7264-034)

https://clinicaltrials.gov/ct2/show/NCT03654326?type=Intr&cond=Endometriosis&lupd_s=02%2F25%2F2019&lupd_d=14

Condition :   Endometriosis-related Pain

Interventions :   Drug: Gefapixant;   Drug: Placebo;   Drug: Naproxen

Sponsor :   Merck Sharp & Dohme Corp.

Recruiting

A Study to Evaluate the Efficacy and Safety of Gefapixant (MK-7264) in Women With Endometriosis-Related Pain (MK-7264-034)

NCT03654326

Fri, 31 Aug 2018 12:00:00 EDT

Last Update Posted: 03/11/19 10:08AM

Eutopic endometrium from patients with endometriosis modulates the expression of CD36 and SIRP-α in peritoneal macrophages

https://obgyn.onlinelibrary.wiley.com/doi/full/10.1111/jog.13938

https://www.ncbi.nlm.nih.gov/pubmed/30843336?dopt=Abstract

Related Articles

Eutopic endometrium from patients with endometriosis modulates the expression of CD36 and SIRP-α in peritoneal macrophages.

J Obstet Gynaecol Res. 2019 Mar 06;:

Authors: Xie Q, He H, Wu YH, Zou LJ, She XL, Xia XM, Wu XQ

Abstract

AIM: This study aimed to investigate the in vitro alterations of the expression of signal regulatory protein-α (SIRP-α) and CD36 in macrophages in the endometriosis condition.

METHODS: The expression of SIRP-α and CD36 was measured in peritoneal macrophages and peripheral blood mononuclear cells of endometriosis patients and control participants. The expressions of SIRP-α and CD36 were measured in human acute monocytic leukemia (THP-1) cell-derived macrophages that were treated with interleukin-6 (IL-6)-induced conditioned medium, eutopic versus normal endometrial homogenate, or lipopolysaccharide in the presence or absence of nuclear factor kappa-B (NF-κB) or transforming growth factor (TGF-β) inhibitors, respectively.

RESULTS: Peritoneal macrophages that were isolated from women with endometriosis exhibited an enhanced expression of SIRP-α and a decreased expression of CD36 compared to control participants. Women with endometriosis had significantly higher levels of SIRP-α and CD36 in peripheral circulating mononuclear cells than in control participants. SIRP-α expression was significantly increased, whereas the CD36 expression was decreased in THP-1 cell-derived macrophages after treatment with eutopic endometrial homogenate. Intervention with IL-6-induced conditioned medium resulted in the downregulation of SIRP-α but the upregulation of CD36 in THP-1 cells. Incubation with the NF-κBp50 inhibitor decreased the expression of CD36 and SIRP-α in macrophages that were treated with normal endometrial homogenate, whereas the TGF-β inhibitor enhanced the CD36 expression of THP-1 cell-derived macrophages treated with eutopic endometrial homogenate.

CONCLUSION: The eutopic endometrium could reduce the phagocytic ability of peritoneal macrophages in women with endometriosis through the modulation of SIRP-α and CD36 expression. Inhibition of the TGF-β signal pathway may be a potential therapeutic target for the treatment of endometriosis.

PMID: 30843336 [PubMed – as supplied by publisher]

Resveratrol reduces the expression of insulin-like growth factor-1 and hepatocyte growth factor in stromal cells of women with endometriosis compared with nonendometriotic women

https://onlinelibrary.wiley.com/doi/abs/10.1002/ptr.6298

https://www.ncbi.nlm.nih.gov/pubmed/30838714?dopt=Abstract

Related Articles

Resveratrol reduces the expression of insulin-like growth factor-1 and hepatocyte growth factor in stromal cells of women with endometriosis compared with nonendometriotic women.

Phytother Res. 2019 Mar 06;:

Authors: Arablou T, Delbandi AA, Khodaverdi S, Arefi S, Kolahdouz-Mohammadi R, Heydari S, Mohammadi T, Aryaeian N

Abstract

Resveratrol, a phytoalexin polyphenol, has antiproliferative, antiangiogenic, anti-inflammatory, and antioxidant properties. The present study has assessed the effect of resveratrol treatment on the expression of insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) in endometrial stromal cells (ESCs) from women with and without endometriosis. Endometrial tissues were obtained from 40 endometriotic patients and 15 nonendometriotic control women. After the enzymatic digestion, 13 eutopic ESCs (EuESCs), 8 ectopic ESCs (EESCs), and 11 control ESCs (CESCs) were treated with resveratrol (100 μM) for 6, 24, and 48 hr. The gene and protein expressions of IGF-1 and HGF were measured using real-time polymerase chain reaction and enzyme-linked immunosorbent assay methods, respectively. Results showed that resveratrol treatment decreased significantly the gene expression of IGF-1 and HGF in EuESCs, EESCs, and CESCs (p < 0.05). The effect of resveratrol treatment on the reduction of IGF-1 gene expression was statistically more noticeable in EESCs compared with CESCs (p < 0.05). Also, in the case of HGF gene expression, the reducing effect of resveratrol treatment was statistically more considerable in EESCs compared with EuESCs and CESCs (p < 0.05 and p < 0.01, respectively). The IGF-1 and HGF protein production decreased significantly in EuESCs and EESCs (p < 0.05) but not in CESCs. These findings suggest that resveratrol treatment could reduce the expression of IGF-1 and HGF in ESCs especially in EESCs, which play a pivotal role in disease progression. PMID: 30838714 [PubMed - as supplied by publisher]

Ameliorative effects of luteolin, a therapeutic phytochemical, against endometriosis progression in vitro and in vivo

https://www.sciencedirect.com/science/article/pii/S0955286318312191?via%3Dihub

https://www.ncbi.nlm.nih.gov/pubmed/30925413?dopt=Abstract

Ameliorative effects of luteolin against endometriosis progression in vitro and in vivo.

J Nutr Biochem. 2019 Mar 03;67:161-172

Authors: Park S, Lim W, You S, Song G

Abstract

Endometriosis is a common gynecological disease in reproductive-aged women. Generally, accumulation of backflow and debris of endometrial tissue develops into a lesion outside of the endometrium, inducing severe pelvic pain and infertility in some patients. Hormone therapy and surgery are the main treatments available, but various therapeutic phytochemicals are being reviewed in animal studies or clinical trials for endometriosis patients nowadays. However, the therapeutic effects of luteolin in human endometriosis have not been studied well. Here, we demonstrate that luteolin exerts antiproliferative and apoptotic effects in human VK2/E6E7 and End1/E6E7 and in an animal endometriosis model. Luteolin inhibits cell proliferation through cell cycle arrest and induces apoptosis through DNA fragmentation in VK2/E6E7 and End1/E6E7 cells. Cytosolic calcium levels, ROS production and lipid peroxidation also increased dose-dependently (0, 5, 10 and 20 μM) in the treatment with luteolin. In VK2/E6E7 and End1/E6E7 cells, luteolin decreased ERK1/2, JNK and PI3K/AKT signal proteins while activating P38. In addition, intraperitoneal injection of luteolin in the endometriosis mouse model reduced lesion size compared to vehicle-injected mice. Ccne1, Cdk2 and Cdk4 were significantly down-regulated in the autoimplanted endometriosis lesions of mice intraperitoneally injected with luteolin. Knockdown of CCNE1 mRNA in VK2/E6E7 and End1/E6E7 cells decreased cell viability through inhibition of G0/G1 phase progression and increased apoptosis. Together, our results imply that luteolin suppresses endometriosis development by regulation of the PI3K/AKT and MAPK signal proteins as well as the expression of CCNE1 in vitro and in vivo.

PMID: 30925413 [PubMed – as supplied by publisher]

Endometriosis and nuclear receptors

https://academic.oup.com/humupd/advance-article-abstract/doi/10.1093/humupd/dmz005/5365598?redirectedFrom=fulltext

https://www.ncbi.nlm.nih.gov/pubmed/30809650

New synthetic ligands, targeting PGR, retinoic acid receptors and ESR2, may offer novel treatment options.

Telocytes enhanced the proliferation, adhesion and motility of endometrial stromal cells as mediated by the ERK pathway in vitro

https://www.ncbi.nlm.nih.gov/pubmed/30899363?dopt=Abstract

Related Articles

Telocytes enhanced the proliferation, adhesion and motility of endometrial stromal cells as mediated by the ERK pathway in vitro.

Am J Transl Res. 2019;11(2):572-585

Authors: Tang XL, Zhang FL, Jiang XJ, Yang XJ

Abstract

Telocytes (TCs) is special interstitial cell that have recently been identified in the female reproductive system. Endometriosis (EMs) is a benign gynecological disease whose etiology is still not fully clear. Implantation and proliferation of endometrial stromal cells (ESCs) out of the uterus are essential processes in the development of EMs. Herein, we investigate the in vitro changes of ESCs when cocultured with TCs, and the potential mechanisms involved. The current results demonstrated that, vimentin-positive/pan cytokeratin-negative ESCs, and TCs with a characteristic structure and immunophenotype (CD34/vimentin double-positive) were successfully isolated and harvested. Morphologically, direct cell-to-cell contacts were observed between TCs and ESCs. Quantitatively, TCs treatment clearly promotes the viability of ESCs, enhances cell cycle progression at G2/M phase and upregulates p-ERK1/2 and cyclin-D3 (all P < 0.05). Functionally, ESCs educated by TCs displayed significantly enhanced adhesion ability and accelerated invasion and migration capacity (all P < 0.05). However, no significant changes were found in the rate of apoptosis and in the expression of AKT signaling pathway proteins in TCs-educated ESCs (both P > 0.05). Therefore, TCs treatment obviously enhanced the in vitro motile and invasive capacity of ESCs, which were mediated by the ERK-cyclin-D3 signaling pathway, likely through direct intercellular contacts and/or juxta-paracrine effects; signaling through this axis therefore increased the likelihood of EMs. The enhanced functions of TCs-educated ESCs not only contribute to a deeper understanding of TCs, but also highlight a new concept regarding the physiopathology and therapy of EMs and associated impaired reproductive function.

PMID: 30899363 [PubMed]

Cai’s Neiyi Prescription (CNYP) promotes apoptosis and inhibits inflammation in endometrial stromal cells with endometriosis through inhibiting USP10

https://www.ncbi.nlm.nih.gov/pubmed/30468519?dopt=Abstract

Related Articles

Cai’s Neiyi Prescription promotes apoptosis and inhibits inflammation in endometrial stromal cells with endometriosis through inhibiting USP10.

Biotechnol Appl Biochem. 2019 Mar;66(2):231-239

Authors: Li S, Zhu Y, Zhang T, Hang Y, Chen Q, Jin Y

Abstract

To observe the effect of Cai’s Neiyi Prescription (CNYP) on the apoptosis and inflammation in endometrial stromal cells with endometriosis (EM) both in vivo and in vitro, EM model rats and endometrial stromal cells were treated with CNYP and the level of USP10, p-ERK1/2, ERK1/2, and apoptosis-related protein as well as the levels of proinflammatory factors were measured by Western blotting and ELISA, respectively. Rats with surgically induced EM showed increased USP10 expression and ERK/2 activation. Intragastric administration of CNYP granule significantly inhibited EM-induced ERK1/2 activation and expression of USP10 and Bcl-2, but increased the expression of Bax and Caspase-7 in EM-induced rats. CNYP granule administration also inhibited EM-induced inflammation in rats. Moreover, the ectopic endometrial stromal cells isolated from EM patients demonstrated decreased ERK1/2 activation and expression of USP10 and Bcl-2 and increased expression of Bax and Caspase-7 after cultured in DMEM containing CNYP-medicated rat serum, which were reversed by USP10 overexpression and were enhanced by USP10 siRNA. USP10 overexpression also inhibited while USP10 siRNA enhanced the CNYP-induced inhibition of inflammation in ectopic endometrial stromal cells. Taken together, our results suggest that CNYP granule promotes apoptosis and inhibits inflammation in endometrial stromal cells with EM through inhibiting USP10.

PMID: 30468519 [PubMed – indexed for MEDLINE]

Nobiletin alleviates endometriosis via down-regulating NF-κB activity in endometriosis mouse model

http://www.bioscirep.org/content/38/3/BSR20180470

https://www.ncbi.nlm.nih.gov/pubmed/29871974?dopt=Abstract

Related Articles

Nobiletin alleviates endometriosis via down-regulating NF-κB activity in endometriosis mouse model.

Biosci Rep. 2018 06 29;38(3):

Authors: Wei X, Shao X

Abstract

Nobiletin exhibits protective potential on inflammation and inhibits the activation of transcription factors nuclear factor-κB (NF-κB). However, its effects on the progression of endometriosis remain unsettled. The present study aimed to explore the in vivo alleviation of nobiletin on endometriosis and its mechanism of action. The mouse model of endometriosis was established and administered with nobiletin. The ectopic lesion size was measured and the hotplate test was performed to assess the amelioration of nobiletin on endometriosis. The expression of proliferation and angiogenesis relevant genes including proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), and E-cadherin was measured by immunostaining and the mRNA expression of proinflammatory mediators including interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, matrix metalloproteinases (MMP)-1, and MMP-3 was measured by RT-PCR. The change of NF-κB activity in endometriotic cells was evaluated by Western blotting and confirmed by luciferase assay. Administration of nobiletin significantly reduced lesions size and pain in endometriosis mice. Nobiletin significantly altered the expression of PCNA, VEGF, and E-cadherin in ectopic endometrium, as well as the levels of IL-6, IL-1β, TNF-α, MMP-1, and MMP-3. Nobiletin also showed remarkably impairment on the activation of NF-κB in promoting endometriotic cells, likely targeting on the activity of IκB kinases (IKKs). The present study provides the first evidence that nobiletin exerts protection on endometriosis via inhibition the activation of NF-κB, specifically on the activity of IκB kinases.

PMID: 29871974 [PubMed – indexed for MEDLINE]

Daidzein-rich isoflavone aglycones inhibit cell growth and inflammation in endometriosis – “DRIAs might be a potential therapeutic option for management of endometriosis”

https://www.sciencedirect.com/science/article/abs/pii/S0960076018301961?via%3Dihub

https://www.ncbi.nlm.nih.gov/pubmed/29679753?dopt=Abstract

Related Articles

Daidzein-rich isoflavone aglycones inhibit cell growth and inflammation in endometriosis.

J Steroid Biochem Mol Biol. 2018 07;181:125-132

Authors: Takaoka O, Mori T, Ito F, Okimura H, Kataoka H, Tanaka Y, Koshiba A, Kusuki I, Shigehiro S, Amami T, Kitawaki J

Abstract

Endometriosis is an estrogen-dependent disease, and isoflavones interact with estrogen receptors. The purposes of this study are to investigate the in vitro and in vivo effects of daidzein-rich isoflavone aglycones (DRIAs), dietary supplements, on cellular proliferation in endometriosis. Stromal cells isolated from ovarian endometrioma (OESCs) and normal endometrium (NESCs) were cultured with DRIAs, i.e., each of the DRIA components (daidzein, genistein, or glycitein), or isoflavone glycosides (IG; DRIA precursors). A mouse model of endometriosis was established by transplanting donor-mouse uterine fragments into recipient mice. Our results showed that DRIAs (0.2-20 μM) inhibited the proliferation of OESCs (P < 0.05 for 0.2 μM; P < 0.01 for 2 and 20 μM) but not of NESCs. However, daidzein, genistein, glycitein, and IG did not inhibit their proliferation. DRIA-induced suppression was reversed by inhibition of the estrogen receptor (ER)β by an antagonist, PHTPP, or by ERβ siRNA (P < 0.05), but not by MPP, an ERα antagonist. In OESCs, DRIAs led to reduced expression of IL-6, IL-8, COX-2, and aromatase, as well as reduced aromatase activity, serum glucocorticoid-regulated kinase levels, and PGE2 levels (P < 0.05). Western blot and immunofluorescence assays revealed that DRIAs inhibited TNF-α-induced IκB phosphorylation and p65 uptake into the nuclei of OESCs. In the mouse model, a DRIA-containing feed significantly decreased the number, weight, and Ki-67 proliferative activity of endometriosis-like lesions compared to in mice fed with an IG-containing feed and the control feed (P < 0.01). In conclusion, DRIAs inhibit cellular proliferation in endometriosis, thus representing a potential therapeutic option for the management of endometriosis. PMID: 29679753 [PubMed - indexed for MEDLINE]

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