Investigation of New Therapeutic Targets in Undifferentiated Endometrial Sarcoma

Baek, Min-Hyun; Rhim, Chae Chun; Kim, Jong-Hyeok; Park, Yangsoon; Kim, Kyu-Rae; Nam, Joo‐Hyun

doi:10.1159/000454769

Cited by 11 publications

(12 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…She then continued the GnRH‐a therapy and remained no new metastasis or enlargement of the existing lesions for 2 years. For RMS, FSH, and LH receptors were reported to be expressed in its established cell lines and primary tumor tissues isolated from patients . And the stimulation of pituitary and gonadal sex hormone triggered the enhancement of proliferation, chemotaxis, cell adhesion as well as the phosphorylation of MAPK and AKT signaling in human RMS cell lines.…”

Section: Hormonal Therapy In Other Types Of Uterine Sarcomasmentioning

confidence: 99%

Hormonal therapy in uterine sarcomas

et al. 2019

View full text Add to dashboard Cite

Uterine sarcomas (USs) are a group of rare but aggressive uterine malignancies, accounting for only 1% of the malignant tumors of female reproductive organs. Due to the high rate of recurrence and metastasis, the prognosis of USs is poor. Given the high mortality rate and limited clinical benefit of surgery and adjuvant chemoradiotherapy, hormonal therapy has shown good prospects in recent years. Hormonal agents include progestins, aromatase inhibitors (AIs), and gonadotropin‐releasing hormone analogue (GnRH‐a). According to the literature, hormonal therapy has been confirmed effective for recurrent, metastatic or unresectable low‐grade endometrial stromal sarcoma (LGESS) and hormone receptor positive (ER+/PR+) uterine leiomyosarcoma (uLMS) with favorable tolerance and compliance. Besides, hormonal therapy can also be used in patients with early‐staged disease who desire to preserve fertility. However, due to the rarity of USs, the rationale of hormonal therapy is generally extrapolated from data of hormone‐sensitive breast cancer, and present studies of hormonal therapy in USs were almost limited to case reports and small‐sized retrospective studies. Therefore, further systematic researches and standardized clinical trials are needed to establish the optimal hormonal therapy regimen of USs. Herein, we reviewed the existing studies related to the hormonal therapy in USs in order to provide reference for clinical management in specific settings.

show abstract

Section: Hormonal Therapy In Other Types Of Uterine Sarcomasmentioning

confidence: 99%

Hormonal therapy in uterine sarcomas

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In EGFR- and HER2-overexpression transgenic models larger tumors appear that respond to tyrosine kinase inhibitors [ 68 ]. Although the relation among aromatase, estrogens, and EGFR have been studied in different tumors such as breast [ 69 ], endometrial [ 70 ], lung [ 71 ], and liver [ 72 ] tumors, among others, the relationship between EGFR and aromatase in pituitary gland or prolactinomas has not been well analyzed to date, but its participation should not be ruled out.…”

Section: Estrogens Prolactin and Aromatasementioning

confidence: 99%

Relation among Aromatase P450 and Tumoral Growth in Human Prolactinomas

Garcı́a-Barrado

Blanco

Iglesias-Osma

et al. 2017

IJMS

View full text Add to dashboard Cite

The pituitary gland is part of hypothalamic-pituitary–gonadal axis, which controls development, reproduction, and aging in humans and animals. In addition, the pituitary gland is regulated mainly by hormones and neurotransmitters released from the hypothalamus and by systemic hormones secreted by target glands. Aromatase P450, the enzyme responsible for the catabolization of aromatizable androgens to estrogens, is expressed in different parts of body, including the pituitary gland. Moreover, aromatase P450 is involved in sexual dimorphism where alteration in the level of aromatase can initiate a number of diseases in both genders. On the other hand, the direct actions of estrogens, mainly estradiol, are well known for stimulating prolactin release. Numerous studies have shown that changes in the levels of estrogens, among other factors, have been implicated in the genesis and development of prolactinoma. The pituitary gland can produce estradiol locally in several types of endocrine cells, and it is possible that aromatase could be responsible for the maintenance of the population of lactotroph cells and the modulation of the action of central or peripheral regulators. Aromatase overexpression due to inappropriate gene regulation has clinical effects such as the pathogenesis of prolactinomas. The present study reports on the synthesis of pituitary aromatase, its regulation by gonadal steroids, and the physiological roles of aromatase on pituitary endocrine cells. The involvement of aromatase in the pathogenesis of pituitary tumors, mainly prolactinomas, through the auto-paracrine production of estradiol is reviewed.

show abstract

“…Therefore, new target therapies or therapeutic options are needed to decrease the morbidity and mortality rates observed for advanced stage endometrial cancer [ 5 , 6 ]. Recently, endometrial cancer was extensively studied at the molecular level to develop effective therapies using histone deacetylase (HDAC) inhibitors, which have shown their potential as therapeutic agents for endometrial cancer [ 7 , 8 ]. HDACs play an important role in regulating the epigenetic processes that lead to the expression of target genes in the development of multiple cancers [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

A New Synthetic Histone Deacetylase Inhibitor, MHY2256, Induces Apoptosis and Autophagy Cell Death in Endometrial Cancer Cells via p53 Acetylation

Son

Sachan

et al. 2018

IJMS

View full text Add to dashboard Cite

We previously discovered a novel sirtuin (SIRT) inhibitor, MHY2256, that exerts anticancer activity through p53 acetylation in MCF-7 human breast cancer cells. We investigated the anticancer activity of MHY2256 against hormone-related cancer, an endometrial cancer with a poor prognosis. The IC50 values of MHY2256 were shown to be much lower than those of salermide, a well-known SIRT inhibitor. Furthermore, MHY2256 significantly reduced the protein expression and activities of SIRT1, 2, and 3, with similar effects to salermide. Particularly, MHY2256 markedly inhibited tumor growth in a tumor xenograft mouse model of Ishikawa cancer cells. During the experimental period, there was no significant change in the body weight of mice treated with MHY2256. A detailed analysis of the sensitization mechanisms of Ishikawa cells revealed that late apoptosis was largely increased by MHY2256. Additionally, MHY2256 increased G1 arrest and reduced the number of cell cyclic-related proteins, suggesting that apoptosis by MHY2256 was achieved by cellular arrest. Particularly, p21 was greatly increased by MHY225656, suggesting that cell cycle arrest by p21 is a major factor in MHY2256 sensitization in Ishikawa cells. We also detected a significant increase in acetylated p53, a target protein of SIRT1, in Ishikawa cells after MHY2256 treatment. In a mouse xenograft model, MHY2256 significantly reduced tumor growth and weight without apparent side effects. These results suggest that MHY2256 exerts its anticancer activity through p53 acetylation in endometrial cancer and can be used for targeting hormone-related cancers.

show abstract

Investigation of New Therapeutic Targets in Undifferentiated Endometrial Sarcoma

Cited by 11 publications

References 26 publications

Hormonal therapy in uterine sarcomas

Hormonal therapy in uterine sarcomas

Relation among Aromatase P450 and Tumoral Growth in Human Prolactinomas

A New Synthetic Histone Deacetylase Inhibitor, MHY2256, Induces Apoptosis and Autophagy Cell Death in Endometrial Cancer Cells via p53 Acetylation

Contact Info

Product

Resources

About