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Total 18 results found since Jan 2013.

Title: Genistein Disrupts Glucocorticoid Receptor Signaling in Human Uterine Endometrial Ishikawa Cells
Conclusions: Using Ishikawa cells, we observed that exposure to genistein resulted in distinct changes in gene expression and unique differences in the GR transcriptome. Citation: Whirledge S, Senbanjo LT, Cidlowski JA. 2015. Genistein disrupts glucocorticoid receptor signaling in human uterine endometrial Ishikawa cells. Environ Health Perspect 123:80–87; http://dx.doi.org/10.1289/ehp.1408437 Address correspondence to J.A. Cidlowski, NIH/NIEHS, MD F3-07, P.O. Box 12233, Research Triangle Park, NC 27709 USA. Telephone: (919) 541-1564. E-mail: cidlows1@niehs.nih.gov We thank X. Xu (Integrative Bioinformatic...
Source: EHP Research - December 31, 2014 Category: Environmental Health Authors: Web Admin Tags: Research Article January 2015 Source Type: research

Oligonucleotides —A Novel Promising Therapeutic Option for IBD
Conclusions In this review, we focused on recent and past approaches to test the therapeutic efficacy of oligonucleotide based therapies in IBD. The combining mechanistic mode of oligonucleotide based therapeutics is a targeted action on specific pro-inflammatory molecules, which are over activated in IBD patients and contribute significantly to disease pathogenesis. The proposed high selectivity of the agents is derived from its mode of action, that aims to specifically block certain inflammatory molecular patterns, without a general systemic effect on other molecular targets. It would be important for each oligonucleot...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Abstract 3964: NVP-BEZ235 enhances dexamethasone-induced BIM expression and apoptosis in models of T-ALL with PTEN dysfunction and increased PI3K/AKT activity
Introduction: Glucocorticoid (GC) resistance presents a major challenge in pediatric acute lymphoblastic leukemia (ALL) treatment. Increased activation of the PI3K/AKT pathway, which may occur following loss of PTEN function, may be a possible mechanism of GC resistance. We therefore investigated the effects of inhibiting the PI3K/AKT pathway with the dual PI3K/mTOR inhibitor NVP-BEZ235 on the enhancement of dexamethasone activity in in vitro and in vivo models of ALL and the role the PI3K/AKT pathway plays in resistance to GCs. Methods: Cytotoxicity of NVP-BEZ235, dexamethasone, and the combination were evaluated using DI...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Hall, C., Kang, M. Tags: Tumor Biology Source Type: research

Targeting syndecan-1 in breast cancer inhibits osteoclast functions through up-regulation of osteoprotegerin
Conclusion Thus, we identified tumor-derived syndecan-1 as a novel positive regulator of osteoclastogenesis and new player in the tumor-bone dialog.
Source: Journal of Bone Oncology - November 12, 2014 Category: Cancer & Oncology Source Type: research

Molecules, Vol. 25, Pages 6028: The Antiasthma Medication Ciclesonide Suppresses Breast Cancer Stem Cells through Inhibition of the Glucocorticoid Receptor Signaling-Dependent YAP Pathway
This study focused on investigating the effect of ciclesonide on breast cancer and CSCs and determining its underlying mechanism. Here, we showed that ciclesonide inhibits breast cancer and CSC formation. Similar glucocorticoids—dexamethasone and prednisone—did not inhibit CSC formation. Ciclesonide-induced glucocorticoid receptor (GR) degradation was dependent on ubiquitination. We showed via GR small interfering RNA (siRNA) that GR plays an important role in CSC formation. We showed via western blot and immunofluorescence assays that ciclesonide reduces the nuclear level of GR. The GR antagoni...
Source: Molecules - December 19, 2020 Category: Chemistry Authors: Su-Lim Kim Hack Sun Choi Ji-Hyang Kim Dong-Sun Lee Tags: Article Source Type: research

Phytoestrogen-Induced Apoptosis
Phytoestrogens have been investigated as natural alternatives to hormone replacement therapy and their potential as chemopreventive agents. We investigated the effects of equol, genistein, and coumestrol on cell growth in fully estrogenized MCF7 cells, simulating the perimenopausal state, and long-term estrogen-deprived MCF7:5C cells, which simulate the postmenopausal state of a woman after years of estrogen deprivation, and compared the effects with that of steroidal estrogens: 17β estradiol (E2) and equilin present in conjugated equine estrogen. Steroidal and phytoestrogens induce proliferation of MCF7 cells at phys...
Source: Cancer Prevention Research - September 1, 2014 Category: Cancer & Oncology Authors: Obiorah, I. E., Fan, P., Jordan, V. C. Tags: Preclinical Intervention, Preclinical Intervention: In Vivo (Animals): Drugs, Nutritional Interventions, Mechanisms Research Articles Source Type: research

STAT3 Activates GM-CSFR{alpha} in CLL
Here, it was determined that chronic lymphocytic leukemia (CLL) cells express the α subunit, but not the β subunit, of the granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR/CSF2R). GM-CSFRα was detected on the surface, in the cytosol, and in the nucleus of CLL cells via confocal microscopy, cell fractionation, and GM-CSFRα antibody epitope mapping. Because STAT3 is frequently activated in CLL and the GM-CSFRα promoter harbors putative STAT3 consensus binding sites, MM1 cells were transfected with truncated forms of the GM-CSFRα promoter, then stimulated with IL6 to activa...
Source: Molecular Cancer Research - September 11, 2014 Category: Cancer & Oncology Authors: Li, P., Harris, D., Liu, Z., Rozovski, U., Ferrajoli, A., Wang, Y., Bueso-Ramos, C., Hazan-Halevy, I., Grgurevic, S., Wierda, W., Burger, J., O'Brien, S., Faderl, S., Keating, M., Estrov, Z. Tags: Genomics Source Type: research

Dexamethasone downregulates caveolin-1 causing muscle atrophy via inhibited insulin signaling
In this study, we report a new pathway in which glucocorticoids reduce the levels of upstream insulin signaling components by downregulating the transcription of the gene encoding caveolin-1 (CAV1), a scaffolding protein present in the caveolar membrane. Treatment with the glucocorticoid dexamethasone (DEX) decreased CAV1 protein and Cav1 mRNA expression, with a concomitant reduction in insulin receptor alpha (IRα) and IR substrate 1 (IRS1) levels in C2C12 myotubes. On the basis of the results of promoter analysis using deletion mutants and site-directed mutagenesis a negative glucocorticoid-response element in the r...
Source: Journal of Endocrinology - March 19, 2015 Category: Endocrinology Authors: Son, Y. H., Lee, S.-J., Lee, K.-B., Lee, J.-H., Jeong, E. M., Chung, S. G., Park, S.-C., Kim, I.-G. Tags: Research Source Type: research

PRIMA-1Met induces apoptosis in Waldenström's Macroglobulinemia cells independent of p53.
In this study, we evaluated the anti- tumor activity of PRIMA-1Met alone and in combination with dexamethasone or bortezomib in WM cell lines and primary samples. Treatment of WM cells with PRIMA-1Met resulted in induction of apoptosis, inhibition of migration and suppression of colony formation. Upon PRIMA-1Met treatment, p73 was upregulated and Bcl-xL was down-regulated while no significant change in expression of p53 was observed. Furthermore, siRNA knockdown of p53 in WM cell line did not influence the PRIMA-1Met-induced apoptotic response whereas silencing of p73 inhibited latter response in WM cells. Importantly, com...
Source: Cancer Biology and Therapy - March 24, 2015 Category: Cancer & Oncology Authors: Sobhani M, Abdi J, Chen C, Chang H Tags: Cancer Biol Ther Source Type: research

Modulation of glucocorticoid resistance in pediatric T-cell Acute Lymphoblastic Leukemia by increasing BIM expression with the PI3K/mTOR inhibitor BEZ235.
CONCLUSIONS: Our data support the further investigation of agents targeting the PI3K/mTOR pathway to modulate glucocorticoid resistance in T-ALL. PMID: 26080839 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - June 16, 2015 Category: Cancer & Oncology Authors: Hall CP, Reynolds CP, Kang MH Tags: Clin Cancer Res Source Type: research

The mechanisms and significance of up‐regulation of RhoB expression by hypoxia and glucocorticoid in rat lung and A549 cells
In this study, we investigated the effects of hypoxia or/and GC on the expression and activition of RhoB in the lung of rats and human A549 lung carcinoma cells, and further studied its mechanism and significance. We found that hypoxia and dexamethasone (Dex), a synethic GC, not only significantly increased the expression and activation of RhoB independently but also coregulated the expresion of RhoB in vitro and in vivo. Up‐regulation of RhoB by hypoxia was in part through stabilizing the RhoB mRNA and protein. Inhibiting hypoxia‐activated hypoxia‐inducible transcription factor‐1α (HIF‐1α), c‐Jun N‐termina...
Source: Journal of Cellular and Molecular Medicine - February 24, 2016 Category: Molecular Biology Authors: Gao‐Xiang Huang, Xiao‐Yu Pan, Yi‐Duo Jin, Yan Wang, Xiao‐Lian Song, Chang‐Hui Wang, Yi‐Dong Li, Jian Lu Tags: Original Article Source Type: research

The mechanisms and significance of up ‐regulation of RhoB expression by hypoxia and glucocorticoid in rat lung and A549 cells
In this study, we investigated the effects of hypoxia or/and GC on the expression and activition of RhoB in the lung of rats and human A549 lung carcinoma cells, and further studied its mechanism and significance. We found that hypoxia and dexamethasone (Dex), a synethic GC, not only significantly increased the expression and activation of RhoB independently but also coregulated the expresion of RhoB in vitro and in vivo. Up‐regulation of RhoB by hypoxia was in part through stabilizing the RhoB mRNA and protein. Inhibiting hypoxia‐activated hypoxia‐inducible transcription factor‐1α (HIF‐1α), c‐Jun N‐termina...
Source: Journal of Cellular and Molecular Medicine - February 23, 2016 Category: Molecular Biology Authors: Gao ‐Xiang Huang, Xiao‐Yu Pan, Yi‐Duo Jin, Yan Wang, Xiao‐Lian Song, Chang‐Hui Wang, Yi‐Dong Li, Jian Lu Tags: Original Article Source Type: research

Akt2 Mediates Glucocorticoid Resistance in Acute Lymphoblastic Leukemia through FoxO3a/Bim Axis and Serves As a Direct Target for Resistance Reversal
Conclusions: Akt2 might serve as a more direct and specific kinase mediating GC resistance through FoxO3a/Bim-signaling pathway in ALL, and targeting Akt2 with CCT128930 may be explored as a promising therapeutic strategy for resistance reversal.Figure.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Xie, M., Xie, Y., Yang, A., Ma, J., Wu, M., Jin, Y. Tags: 605. Molecular Pharmacology, Drug Resistance-Lymphoid and Other Diseases: Poster III Source Type: research

MiR-221/222 Promote Dexamethasone Resistance of Multiple Myeloma through Inhibition of Autophagy By Targeting ATG12
In conclusion, our data reveal that upregulation of miR-221/222 promotes Dex resistance of MM cells through inhibition of autophagy by targeting ATG12. Therefore, miR-221/222-ATG12 autophagy-regulatory axis may potentially be applied in glucocorticoid resistance prediction and treatment.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Xu, J., Su, Y., Xu, A., Fan, F., Huang, H., Hu, Y., Sun, C. Tags: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research

Ability to Suppress TGF- β-Activated Myofibroblast Differentiation Distinguishes the Anti-pulmonary Fibrosis Efficacy of Two Danshen-Containing Chinese Herbal Medicine Prescriptions
Conclusion: This study suggests that a clinically efficacious cardiovascular Chinese herbal medicine (DLP) can be successfully repurposed to treat a lung disease in pulmonary fibrosis guided by TCM theory. Our comparative study between DLP and DHP demonstrated a critical requirement of suppressing both pro-inflammatory and pro-fibrotic pathways for the treatment of pulmonary fibrosis, supporting that a multi-component prescription capable of “removing both phlegm and blood stasis” will better achieve co-protection of heart and lung in PHD. Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic ...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research