Application of the histone deacetylase inhibitors for the treatment of endometriosis: histone modifications as pathogenesis and novel therapeutic target

Kawano, Yukie; Nasu, Kaei; Li, Haili; Tsuno, Akitoshi; Abe, Wakana; Takai, Noriyuki; Narahara, Hisashi

doi:10.1093/humrep/der203

Cited by 70 publications

(72 citation statements)

References 36 publications

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“…14 Our findings are of clinical interest, because there is increasing evidence for the therapeutic action of HDACi in endometriosis according to several preclinical studies [10][11][12]28,29 and a clinical pilot study of 3 patients with symptomatic adenomyosis. 19 Furthermore, HDACis, which have increased specificity for certain HDAC enzymes or classes, are currently being investigated in several diseases.…”

Section: Discussionmentioning

confidence: 84%

“…2 The correlation between HDAC and hormonal receptor expression is of course purely descriptive and does not substantiate any functional links, but it is nevertheless an important observation in regard to an epigenetic approach in the therapy of endometriosis using HDACi. [10][11][12] To date, it is unclear whether epigenetic aberrations in endometriosis are the cause or a consequence of the disease. 5 In addition, our data cannot explain why HDAC-1 is increased in endometriosis in contrast to other class I HDACs.…”

Section: Discussionmentioning

confidence: 99%

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The Expression of Histone Deacetylase 1, But Not Other Class I Histone Deacetylases, Is Significantly Increased in Endometriosis

et al. 2013

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Class I histone deacetylases (HDACs-1-3) play an important role in steroid hormone-dependent gene expression and in modulating cell survival and proliferation. We analyzed their expression in a tissue microarray including 74 endometriosis samples and 30 normal endometrium controls. The mean HDAC-1 immunoreactivity score (IRS + standard deviation) was 7.6 + 2.5 in endometriosis and 5.3 + 2.3 in normal endometrium (P < .001). In contrast, the IRSs of HDAC-2 and -3 were 11.7 + 0.7 and 11.8 + 1.1 in endometriosis and 11.6 + 1.0 and 11.9 + 0.4 in normal endometrium (P ¼ .7 and P ¼ .2), respectively. Significant correlations were found between HDAC-1 and estrogen (-alpha/-beta) and progesterone receptor expression. In conclusion, HDAC-1, but not HDAC-2/-3, was significantly increased in endometriosis and associated with steroid hormone receptor expression that may reflect interdependence. In context with the literature, specific inhibitors of HDAC-1 may have inhibitory activities similar to those of broad-spectrum HDAC inhibitors and may be clinically tolerated, which would increase their chance as an option in the treatment of endometriosis.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

The Expression of Histone Deacetylase 1, But Not Other Class I Histone Deacetylases, Is Significantly Increased in Endometriosis

et al. 2013

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“…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

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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

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“…Die aktuellen Ergebnisse konnten in Endometriosegewebe Histonaberrationen nachweisen. Sie zeigten zudem, dass HDACIs in diesem Gewebe epigentisch ausgeschaltete Gene reaktivierten, was zu einer Suppression der Zellproliferation, Induktion des Zellzyklusarrestes und zu Apoptose führte [16].…”

Section: Histon-deacetylase-inhibitorunclassified

Systemische Therapie der Endometriose: Alternativen zur Hormontherapie

2014

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Endometriose ist eine der häufigs-ten benignen, allerdings meist chronischen gynäkologischen Erkrankungen. Häufig leiden die Betroffenen unter Dysmenorrhö, Dyspareunie, Defäkationsbeschwerden, Dysurie und Infertilität. Oft sind die Patientinnen durch schmerzbedingte Arbeitsunfähigkeit und Einschränkung der körperlichen Integrität stark in ihrer Lebensqualität eingeschränkt und stehen unter hohem Leidensdruck. Die Inanspruchnahme kostenintensiver medizinischer Versorgung und die Einschränkung der Arbeitskraft begründen die hohe ökonomische Relevanz der Erkrankung. Kurative Therapieverfahren gibt es derzeit nicht.Daher ist neben einer akuten Behandlungsoption i. S. einer Operation insbesondere auch die Notwendigkeit einer möglichst nebenwirkungsarmen konservativen Langzeittherapie gegeben. Begleitende komplementäre Therapieverfahren und eine suffiziente Schmerztherapie können den Krankheitsverlauf und den Umgang der Patientinnen mit der Krankheit zudem positiv beeinflussen und die Lebensqualität verbessern. Der individuelle Therapieansatz sollte insbesondere bei endometrioseassoziierter Infertilität das Alter der Frau, die Dauer der Infertilität, die Familienanamnese, die Schmerzsymptomatik sowie das Endometriosestadium berücksichtigen.

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Application of the histone deacetylase inhibitors for the treatment of endometriosis: histone modifications as pathogenesis and novel therapeutic target

Cited by 70 publications

References 36 publications

The Expression of Histone Deacetylase 1, But Not Other Class I Histone Deacetylases, Is Significantly Increased in Endometriosis

The Expression of Histone Deacetylase 1, But Not Other Class I Histone Deacetylases, Is Significantly Increased in Endometriosis

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

Systemische Therapie der Endometriose: Alternativen zur Hormontherapie

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