Mechanism of progestin resistance in endometrial precancer/cancer through Nrf2-AKR1C1 pathway

Wang, Yiying; Wang, Yue; Zhang, Zhenbo; Park, Ji Young; Guo, Dongwei; Liao, Hong; Yi, Xiaofang; Zheng, Yu; Zhang, Donna; Chambers, Setsuko K.; Zheng, Wenxin

doi:10.18632/oncotarget.7004

Cited by 50 publications

(42 citation statements)

References 41 publications

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“…Collagen II is generally used to measure the viability of chondrocytes. 26 Moreover, results of our study indicated that the VEGF level was increased in the BMSCs transfected with Pc-DNA PDGF-B. VEGF is widely thought to play a crucial role in creating new blood vessels after injury.…”

Section: Discussionmentioning

confidence: 58%

Retracted: Platelet‐derived growth factor subunit B is required for tendon‐bone healing using bone marrow–derived mesenchymal stem cells after rotator cuff repair in rats

Wang

Yin

Chu

et al. 2017

J of Cellular Biochemistry

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As a common cause of shoulder pain and disability, rotator cuff injury (RCI) represents a debilitating condition affecting an individual's quality of life. Although surgical repair has been shown to be somewhat effective, many patients may still suffer from reduced shoulder function. The aim of the current study was to identify a more effective mode of RCI treatment by investigating the effect of platelet-derived growth factor subunit B (PDGF-B) on tendon-bone healing after RCI repair by modifying bone marrow-derived mesenchymal stem cells (BMSCs). Surface markers of BMSCs were initially detected by means of flow cytometry, followed by establishment of the rat models and construction of the lentiviral vector. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide (MTT) assay, alizarin red staining, and oil red O staining were used to provide verification that PDGF-B was indeed capable of promoting BMSC viability, osteogenic and adipogenic differentiation capability. Furthermore, biomechanical assessment results indicated that PDGF-B could increase the ultimate load and stiffness of the tendon tissue. Real-time reverse-transcription quantitative polymerase chain reaction and Western blot analysis methods provided evidence suggesting that PDGF-B facilitated the expression of tendon-bone healing-related genes and proteins, while contrasting results were obtained after PDGF-B silencing. Taken together, the key findings of the current study provided evidence suggesting that overexpressed PDGF-B could act to enhance tendon-bone healing after RCI repair, thus highlighting the potential of the functional promotion of PDGF-B as a future RCI therapeutic approach.

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Section: Discussionmentioning

confidence: 58%

Retracted: Platelet‐derived growth factor subunit B is required for tendon‐bone healing using bone marrow–derived mesenchymal stem cells after rotator cuff repair in rats

Wang

Yin

Chu

et al. 2017

J of Cellular Biochemistry

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“…Also, inhibition of overall protein synthesis was observed in some cell lines derived from leukemia, lung adenocarcinoma, Ehrlich carcinoma, and hepatoma when the concentration of BRU is higher than 500 nM2122. Recently, BRU has been identified as an unique inhibitor of the Nrf2 pathway at nanomolar concentrations without affecting protein synthesis1423, enhancing the anti-tumor efficacy of cisplatin1424. In this study, we identified for the first time that BRU has the capability to inhibit HIF-1 signaling pathway.…”

Section: Discussionmentioning

confidence: 82%

Brusatol inhibits HIF-1 signaling pathway and suppresses glucose uptake under hypoxic conditions in HCT116 cells

Shi

et al. 2016

Sci Rep

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Hypoxia-inducible factor-1 (HIF-1) is an important transcription factor that induces adaptive responses upon low oxygen conditions in human cancers and triggers off a poor prognostic outcome of conventional treatments. In this study, we discovered for the first time that brusatol (BRU), a quassinoid extracted from Brucea Esters, has the capability to inhibit HIF-1 signaling pathway. We found that BRU concentration-dependently down-regulated HIF-1α protein levels under hypoxia or CoCl2-induced mimic hypoxia in HCT116 cells without causing significant cytotoxicity. Besides, the transactivation activity of HIF-1 was suppressed by BRU under hypoxic conditions, as well as the expression of HIF-1 target genes, including VEGF, GLUT1, HK2 and LDHA. In addition, BRU can also decrease glucose consumption under hypoxia through inhibition of HIF-1 signaling pathway. Further studies revealed that the inhibitory effect of BRU on HIF-1 signaling pathway might be attributed to promoting degradation of HIF-1α. Interestingly, intracellular reactive oxygen species (ROS) levels and mitochondrial ROS level were both decreased by BRU treatment, indicating the involvment of mitochondrial ROS regulation in the action of BRU. Taken together, these results provided clear evidence for BRU-mediated HIF-1α regulation and suggested its therapeutic potential in colon tumors.

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“…This could be due to the absence of those receptors or to progestin resistance. New biomarkers and molecules are being explored to predict progestin resistance, such as Nrf2/AKR1C1 pathways and in situ metabolism and synthesis of estrogen . The absence of association in our meta‐analysis between hormonal receptors and remission rate could also be due to unknown complex mechanisms of progestin resistance.…”

Section: Discussionmentioning

confidence: 89%

A systematic review and meta‐analysis of prognostic factors for remission in fertility‐sparing management of endometrial atypical hyperplasia and adenocarcinoma

Guillon

Popescu

Phelippeau

et al. 2019

Intl J Gynecology & Obste

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Background: Endometrial cancer and atypical hyperplasia are rare in young women but create a dilemma between desire for pregnancy and oncologic outcomes.Objective: To identify remission rates and associated prognostic factors in patients undergoing fertility-sparing management for endometrial cancer and atypical hyperplasia. Search strategy: MEDLINE was searched for studies published between January 1, 1950 and July 31, 2017 using various search terms. Selection criteria: Studies evaluating fertility-sparing management in patients aged between 19 and 44 years with atypical hyperplasia or stage I endometrial cancer. Data collection and analysis: Use of PRISMA guidelines to conduct a meta-analysis of the proportion of patients in remission and meta-regression analysis to test the effect of possible prognostic factors for remission.Main results: A total of 3673 studies were screened; 65 studies including 1604 patients met the inclusion criteria. The remission rate was 0.75 (95% CI, 0.73-0.77).Operative hysteroscopy for endometrial sampling was associated with higher remission rates (OR 2.31; 95% CI, 1.10-4.84; P=0.03). Studies with higher ratios of infertile women were associated with higher remission rates (OR 4.21; 95% CI, 1.44-12.33; P<0.01). Conclusion:Operative hysteroscopy is the preferred endometrial sampling method for patients with atypical hyperplasia or endometrial cancer undergoing fertilitysparing management.

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Mechanism of progestin resistance in endometrial precancer/cancer through Nrf2-AKR1C1 pathway

Cited by 50 publications

References 41 publications

Retracted: Platelet‐derived growth factor subunit B is required for tendon‐bone healing using bone marrow–derived mesenchymal stem cells after rotator cuff repair in rats

Retracted: Platelet‐derived growth factor subunit B is required for tendon‐bone healing using bone marrow–derived mesenchymal stem cells after rotator cuff repair in rats

Brusatol inhibits HIF-1 signaling pathway and suppresses glucose uptake under hypoxic conditions in HCT116 cells

A systematic review and meta‐analysis of prognostic factors for remission in fertility‐sparing management of endometrial atypical hyperplasia and adenocarcinoma

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