Inhibition of Proliferation of Endometrial Stromal Cells by Trichostatin A, RU486, CDB-2914, N-Acetylcysteine, and ICI 182780

Wu, Yan; Guo, Sun‐Wei

doi:10.1159/000093975

Cited by 60 publications

(54 citation statements)

References 235 publications

(142 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In conclusion, based on the data obtained to date, endometriosis may have an important epigenetic component involving nucleoside and histone modifications; as such, this disease is a good candidate for epigenetic reprogramming through HDACi and HMTi that should be explored further. 62,63 6. Recommendation (new): Studies should be undertaken on all aspects of epigenetic regulation of endometriosis.…”

Section: Recommendation (New)mentioning

confidence: 99%

Research Priorities for Endometriosis: Recommendations From a Global Consortium of Investigators in Endometriosis

et al. 2017

View full text Add to dashboard Cite

The 3rd International Consensus Workshop on Research Priorities in Endometriosis was held in São Paulo on May 4, 2014, following the 12th World Congress on Endometriosis. The workshop was attended by 60 participants from 19 countries and was divided into 5 main sessions covering pathogenesis/pathophysiology, symptoms, diagnosis/classification/prognosis, disease/ symptom management, and research policy. This research priorities consensus statement builds on earlier efforts to develop research directions for endometriosis. Of the 56 research recommendations from the 2011 meeting in Montpellier, a total of 41 remained unchanged, 13 were updated, and 2 were deemed to be completed. Fifty-three new research recommendations were made at the 2014 meeting in Sao Paulo, which in addition to the 13 updated recommendations resulted in a total of 66 new recommendations for research. The research recommendations published herein, as well as those from the 2 previous papers from international consensus workshops, are an attempt to promote high-quality research in endometriosis by identifying and

show abstract

Section: Recommendation (New)mentioning

confidence: 99%

Research Priorities for Endometriosis: Recommendations From a Global Consortium of Investigators in Endometriosis

et al. 2017

View full text Add to dashboard Cite

show abstract

“…RU486, an anti-progestin, has been shown to suppress proliferation of endometrial cells [346][347][348] and to relieve symptoms in endometriosis [349,350] . Other anti-progestins, such as ZK230211, also exhibit anti-proliferative effects in the same tissue [351] .…”

Section: Existing and Investigational Therapeutics For Endometriosis:mentioning

confidence: 99%

“…Trichostatin A and valproic acid, two histone deacetylase inhibitors (HDACIs), that have been recently found to inhibit proliferation of endometriotic and endometrial cells [348] , also suppress TNF ␣ -induced NF-B activation (Wu and Guo, unpublished data). Selective progesterone receptor modulators or SPRMs that hold promise in treating endometriosis [379] are also likey to exhibit their anti-proliferative effect through similar effects.…”

Section: Existing and Investigational Therapeutics For Endometriosis:mentioning

confidence: 99%

Nuclear Factor-κB (NF-κB): An Unsuspected Major Culprit in the Pathogenesis of Endometriosis That Is Still at Large?

Guo¹

2006

Gynecol Obstet Invest

Self Cite

127

106

View full text Add to dashboard Cite

Endometriosis, defined as the ectopic presence of endometrial glandular and stromal cells outside the uterine cavity, is a common benign gynecological disorder with an enigmatic pathogenesis. Many genes and gene products have been reported to be altered in endometriosis, yet some of them may not be major culprits but merely unwitting accomplices or even innocent bystanders. Therefore, the identification and apprehension of major culprits in the pathogenesis of endometriosis are crucial to the understanding of the pathogenesis and would help to develop better therapeutics for endometriosis. Although so far NF-ĸB only has left few traces of incriminating fingerprints, several lines of investigation suggest that NF-ĸB, a pivotal pro-inflammatory transcription factor, could promote and maintain endometriosis. Various inflammatory agents, growth factors, and oxidative stress activate NF-ĸB. NF-ĸB proteins themselves and proteins regulated by them have been linked to cellular transformation, proliferation, apoptosis, angiogenesis, and invasion. Interestingly, all existing and nearly all investigational medications for endometriosis appear to act through suppression of NF-ĸB activation. In endometriotic cells, NF-ĸB appears to be constitutively activated, and suppression of NF-ĸB activity by NF-ĸB inhibitors or proteasome inhibitors suppresses proliferation in vitro. Viewing NF-ĸB as a major culprit, an autoregulatory loop model can be postulated, which is consistent with existing data and, more importantly, can explain several puzzling phenomena that are otherwise difficult to interpret based on prevailing theories. This view has immediate and important implications for novel ways to treat endometriosis. Further research is warranted to precisely delineate the roles of NF-ĸB in the pathogenesis of endometriosis and to indict and convict its aiders and abettors.

show abstract

“…Although without further detail it is difficult to know precisely whether the trial did not advance to later stages because of problems in efficacy or safety profiles or both, it is reasonable to assume that the trial stopped because of an unacceptably high risk/benefit ratio. In fact, a recent study using an immortalized human endometrial stromal cell line reports that fulvestrant has no significant inhibitory effect on the proliferation of endometrial cells [36] , suggesting that the termination of the trial was very likely due to the efficacy issue.…”

Section: Fulvestrant and Raloxifene: Potential Therapies For Endometrmentioning

confidence: 99%

“…This contrasts sharply with encouraging clinical trials on the use of aromatase inhibitors in treating endometriosis [100][101][102] : the first clinical use of aromatase inhibitors to treat endometriosis involved a severe case of postmenopausal endometriosis [89] , following rather extensive in vitro investigation [103,104] . Interestingly, recent work indicates that fulvestrant has no significant suppressive effect on the proliferation of endometrial cells [36] .…”

Section: Lesson 4: Human Endometrial and Endometriotic Cell Lines Maymentioning

confidence: 99%

Two Unsuccessful Clinical Trials on Endometriosis and a Few Lessons Learned

Guo

Olive

2007

Gynecol Obstet Invest

Self Cite

View full text Add to dashboard Cite

In 1999, a phase II clinical trial on the use of fulvestrant to treat endometriosis was launched; yet after 7 years there is still no report on its outcome. In 2005, another trial on the use of raloxifene to treat endometriosis was terminated early due to unfavorable outcome. The two apparently unsuccessful clinical trials on endometriosis have taught us a few important lessons. First, we need to understand endometriosis through more basic research. We have also been reminded that human endometriosis trials differ from animal studies; anatomy and physiology are often divergent, and outcome measures are certainly different. Ectopic endometrium can differ significantly from eutopic tissue, and this issue needs to be more thoroughly explored. We believe human cell lines will prove to be an inexpensive and valuable tool for future preliminary evaluation of medical therapies as well as discerning pathophysiologic processes of the disease. Based on our current understanding of endometriosis, some concrete benchmarks can be established for testing or screening potential compounds in vitro. Finally, estrogen receptor modulators are often tissue-, cell-, and context-specific in their actions; they should not be simplistically grouped together nor should extrapolations from one compound to another be undertaken in a cavalier manner.

show abstract

Inhibition of Proliferation of Endometrial Stromal Cells by Trichostatin A, RU486, CDB-2914, N-Acetylcysteine, and ICI 182780

Cited by 60 publications

References 235 publications

Research Priorities for Endometriosis: Recommendations From a Global Consortium of Investigators in Endometriosis

Research Priorities for Endometriosis: Recommendations From a Global Consortium of Investigators in Endometriosis

Nuclear Factor-κB (NF-κB): An Unsuspected Major Culprit in the Pathogenesis of Endometriosis That Is Still at Large?

Two Unsuccessful Clinical Trials on Endometriosis and a Few Lessons Learned

Contact Info

Product

Resources

About