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https://www.readbyqxmd.com/read/29115373/yap-and-taz-mediate-steroid-induced-alterations-in-the-trabecular-meshwork-cytoskeleton-in-human-trabecular-meshwork-cells
#1
Jie Peng, Hailian Wang, Xin Wang, Minghan Sun, Shaoping Deng, Yi Wang
Primary open angle glaucoma is an important type of glaucoma as it is one of the most common causes of blindness. Previous studies have demonstrated that in glaucomatous patients, the human trabecular meshwork (HTM) is markedly stiffened. The purpose of the present study was to determine the regulatory role of Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in HTM cells. Primary HTM cells were cultured with different concentrations of dexamethasone (DEX), and the expression levels of YAP and TAZ were evaluated using reverse transcription-quantitative polymerase chain reaction and western blotting...
October 23, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29104411/synthesis-and-preliminary-assessment-of-the-anticancer-and-wnt-%C3%AE-catenin-inhibitory-activity-of-small-amide-libraries-of-fenamates-and-profens
#2
Bini Mathew, Judith V Hobrath, Wenyan Lu, Yonghe Li, Robert C Reynolds
As part of an ongoing program to study the anticancer activity of non-steroidal anti-inflammatory drugs (NSAIDs) through generating diversity libraries of multiple NSAID scaffolds, we synthesized a series of NSAID amide derivatives and screened these sets against three cancer cell lines (prostate, colon and breast) and Wnt/β-catenin signaling. The evaluated amide analog libraries show significant anticancer activity/cell proliferation inhibition, and specific members of the sets show inhibition of Wnt/β-catenin signaling...
2017: Medicinal Chemistry Research
https://www.readbyqxmd.com/read/29050252/opposing-roles-of-icat-and-wnt-%C3%AE-catenin-signaling-in-nsc67657-induced-monocytic-differentiation
#3
Weijia Wang, Yan Zhang, Yong Yuan, Runqiang Yuan, Youye Yang, Xiuming Zhang, Dongmei Wen, Fuda Huang, Jinshu Wang
NSC67657 is a new steroid drug that induces monocytic differentiation of acute myeloid leukemia cells. Here, we demonstrate that NSC67657 has opposing effects on expression of downstream targets of inhibitor of β-catenin and TCF (ICAT) and Wnt signaling in HL60 cells. ICAT binds to β-catenin, and this interaction is further increased in NSC67657-differentiated cells. ICAT overexpression decreases expression of Wnt downstream targets and increases sensitivity of HL60 cells to NSC67657, while ICAT silencing increases Wnt signaling and delays the NSC67657-induced cell differentiation...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977889/human-steroid-sulfatase-induces-wnt-%C3%AE-catenin-signaling-and-epithelial-mesenchymal-transition-by-upregulating-twist1-and-hif-1%C3%AE-in-human-prostate-and-cervical-cancer-cells
#4
Sangyun Shin, Hee-Jung Im, Yeo-Jung Kwon, Dong-Jin Ye, Hyoung-Seok Baek, Donghak Kim, Hyung-Kyoon Choi, Young-Jin Chun
Steroid sulfatase (STS) catalyzes the hydrolysis of estrone sulfate and dehydroepiandrosterone sulfate (DHEAS) to their unconjugated biologically active forms. Although STS is considered a therapeutic target for estrogen-dependent diseases, the cellular functions of STS remain unclear. We found that STS induces Wnt/β-catenin s Delete ignaling in PC-3 and HeLa cells. STS increases levels of β-catenin, phospho-β-catenin, and phospho-GSK3β. Enhanced translocation of β-catenin to the nucleus by STS might activate transcription of target genes such as cyclin D1, c-myc, and MMP-7...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28975994/mir-145-silencing-promotes-steroid-induced-avascular-necrosis-of-the-femoral-head-repair-via-upregulating-vegf
#5
Z-J Tian, B-Y Liu, Y-T Zhang, X-Z Chen, G-Y Qiao, S Wang, Z-L Ma
OBJECTIVE: To investigate the role of miR-145 silencing in the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), B-cell lymphoma-2 (Bcl-2), BCL2-Associated X(bax) and caspase-3 in avascular necrosis of femoral head (ANFH). MATERIALS AND METHODS: A total of 12 healthy wild-types (the control group) and 12 miR-145 knock-out (miR-145-/-) (the experimental group) adult New Zealand white rabbits were selected to construct ANFH model with a steroid...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28931847/excessive-activation-of-tlr4-nf-%C3%AE%C2%BAb-interactively-suppresses-the-canonical-wnt-%C3%AE-catenin-pathway-and-induces-sanfh-in-sd-rats
#6
Junpeng Pei, Lihong Fan, Kai Nan, Jia Li, Zhibin Shi, Xiaoqian Dang, Kunzheng Wang
Nuclear factor-kappa B (NF-κB) interactively affects the Wnt/β-catenin pathway and is closely related to different diseases. However, such crosstalk effect in steroid-associated necrosis of femoral head (SANFH) has not been fully explored and evaluated. In this study, early-stage SANFH was induced by two doses of lipopolysaccharide (LPS, 2 mg/kg/day) and three doses of methylprednisolone (MPS, 40 mg/kg/day). LPS and pyrrolidine dithiocarbamate (PDTC) were administered to activate the TLR4/NF-κB pathway and selectively block the activation of NF-κB, respectively...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28919264/prolactin-alters-the-mammary-epithelial-hierarchy-increasing-progenitors-and-facilitating-ovarian-steroid-action
#7
Kathleen A O'Leary, Michael P Shea, Stephanie Salituro, Courtney E Blohm, Linda A Schuler
Hormones drive mammary development and function and play critical roles in breast cancer. Epidemiologic studies link prolactin (PRL) to increased risk for aggressive cancers that express estrogen receptor α (ERα). However, in contrast to ovarian steroids, PRL actions on the mammary gland outside of pregnancy are poorly understood. We employed the transgenic NRL-PRL model to examine the effects of PRL alone and with defined estrogen/progesterone exposure on stem/progenitor activity and regulatory networks that drive epithelial differentiation...
October 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28817727/pilot-study-of-lithium-to-restore-intestinal-barrier-function-in-severe-graft-versus-host-disease
#8
Gideon Steinbach, David M Hockenbery, Gerwin Huls, Terry Furlong, David Myerson, Keith R Loeb, Jesse R Fann, Christina Castilla-Llorente, George B McDonald, Paul J Martin
Severe intestinal graft-vs-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) causes mucosal ulceration and induces innate and adaptive immune responses that amplify and perpetuate GVHD and the associated barrier dysfunction. Pharmacological agents to target mucosal barrier dysfunction in GVHD are needed. We hypothesized that induction of Wnt signaling by lithium, an inhibitor of glycogen synthase kinase (GSK3), would potentiate intestinal crypt proliferation and mucosal repair and that inhibition of GSK3 in inflammatory cells would attenuate the deregulated inflammatory response to mucosal injury...
2017: PloS One
https://www.readbyqxmd.com/read/28808213/the-interaction-between-the-wnt-%C3%AE-catenin-signaling-cascade-and-pkg-activation-in-cancer
#9
Kevin Lee, Gary A Piazza
The activation of the Wnt/β-catenin signaling cascade has been well studied and documented in colorectal cancer (CRC). The long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to reduce the incidence and risk of death from CRC in numerous epidemiological studies. The NSAID sulindac has also been reported to cause regression of precancerous adenomas in individuals with familial adenomatous polyposis who are at high risk of developing CRC. The mechanism responsible for cancer chemopreventive activity of NSAIDs is not well understood but may be unrelated to their cyclooxygenase inhibitory activity...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28767451/opposing-roles-of-icat-and-wnt-%C3%AE-catenin-signaling-in-nsc67657-induced-monocytic-differentiation
#10
Weijia Wang, Yan Zhang, Yong Yuan, Runqiang Yuan, Youye Yang, Xiuming Zhang, Dongmei Wen, Fuda Huang, Jinshu Wang
NSC67657 is a new steroid drug that induces monocytic differentiation of acute myeloid leukemia cells. Here, we demonstrate that NSC67657 has opposing effects on expression of downstream targets of inhibitor of β-catenin and TCF (ICAT) and Wnt signaling in HL60 cells. ICAT binds to β-catenin, and this interaction is further increased in NSC67657-differentiated cells. ICAT overexpression decreases expression of Wnt downstream targets and increases sensitivity of HL60 cells to NSC67657, while ICAT silencing increases Wnt signaling and delays the NSC67657-induced cell differentiation...
July 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28718684/role-of-gsk-3%C3%AE-in-regulation-of-canonical-wnt-%C3%AE-catenin-signaling-and-pi3-k-akt-oncogenic-pathway-in-colon-cancer
#11
Shelly Jain, Preety Ghanghas, Chandan Rana, S N Sanyal
Non-steroidal anti-inflammatory drugs (NSAIDs) are emerging as novel chemopreventive agents because of their ability in blocking cellular proliferation, and thereby tumor development, and also by promoting apoptosis. GSK-3β, a serine threonine kinase and a negative regulator of the oncogenic Wnt/β-catenin signaling pathway, plays a critical role in the regulation of oncogenesis. Celecoxib and etoricoxib, the two cyclooxygenase-2 (COX-2) selective NSAIDs, and Diclofenac, a preferential COX-2 inhibitory NSAID, had shown uniformly the chemopreventive and anti-neoplastic effects in the early stage of colon cancer by promoting apoptosis as well as an over-expression of GSK-3β while down-regulating the PI3-K/Akt oncogenic pathway...
August 9, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28711911/human-steroid-sulfatase-induces-wnt-%C3%AE-catenin-signaling-and-epithelial-mesenchymal-transition-by-upregulating-twist1-and-hif-1%C3%AE-in-human-prostate-and-cervical-cancer-cells
#12
Sangyun Shin, Hee-Jung Im, Yeo-Jung Kwon, Dong-Jin Ye, Hyoung-Seok Baek, Donghak Kim, Hyung-Kyoon Choi, Young-Jin Chun
Steroid sulfatase (STS) catalyzes the hydrolysis of estrone sulfate and dehydroepiandrosterone sulfate (DHEAS) to their unconjugated biologically active forms. Although STS is considered a therapeutic target for estrogen-dependent diseases, the cellular functions of STS remain unclear. We found that STS induces Wnt/β-catenin s Delete ignaling in PC-3 and HeLa cells. STS increases levels of β-catenin, phospho-β-catenin, and phospho-GSK3β. Enhanced translocation of β-catenin to the nucleus by STS might activate transcription of target genes such as cyclin D1, c-myc, and MMP-7...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28678390/small-molecules-inspired-by-the-natural-product-withanolides-as-potent-inhibitors-of-wnt-signaling
#13
Michael Sheremet, Shobhna Kapoor, Peter Schröder, Kamal Kumar, Slava Ziegler, Herbert Waldmann
Wnt signaling is a fundamental pathway that drives embryonic development and is essential for stem cell maintenance and tissue homeostasis. Dysregulation of Wnt signaling is linked to various diseases, and a constitutively active Wnt pathway drives tumorigenesis. Thus, disruption of the Wnt response is deemed a promising strategy for cancer drug discovery. However, only few clinical drug candidates that target Wnt signaling are available so far, and new small-molecule modulators of Wnt-related processes are in high demand...
September 19, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28627630/gene-expression-profiling-of-human-blastocysts-from-in%C3%A2-vivo-and-rescue-ivm-with-or-without-melatonin-treatment
#14
Yan Hao, Zhiguo Zhang, Dan Han, Yunxia Cao, Ping Zhou, Zhaolian Wei, Mingrong Lv, Dawei Chen
To evaluate the effect of melatonin supplementation in maturation medium for human 'rescue IVM' and investigate differences in transcriptomic profile of blastocysts developed from oocytes matured in vitro with/without melatonin treatment and in vivo, a total of 314 GV oocytes and 320 MI oocytes were collected from 200 patients younger than 35 years old undergoing ICSI cycle. The oocytes were randomly distributed in the control group (no melatonin) and four other groups of varying melatonin concentrations (10‑11, 10‑9, 10‑7, 10‑5 mol/l)...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28546515/the-interaction-between-the-wnt-%C3%AE-catenin-signaling-cascade-and-pkg-activation-in-cancer
#15
Kevin Lee, Gary A Piazza
The activation of the Wnt/β-catenin signaling cascade has been well studied and documented in colorectal cancer (CRC). The long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to reduce the incidence and risk of death from CRC in numerous epidemiological studies. The NSAID sulindac has also been reported to cause regression of precancerous adenomas in individuals with familial adenomatous polyposis who are at high risk of developing CRC. The mechanism responsible for cancer chemopreventive activity of NSAIDs is not well understood but may be unrelated to their cyclooxygenase inhibitory activity...
April 6, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28529816/sclerostin-activity-plays-a-key-role-in-the-negative-effect-of-glucocorticoid-signaling-on-osteoblast-function-in-mice
#16
Eric E Beier, Tzong-Jen Sheu, Emily A Resseguie, Masahiko Takahata, Hani A Awad, Deborah A Cory-Slechta, J Edward Puzas
Stress during prenatal development is correlated with detrimental cognitive and behavioral outcomes in offspring. However, the long-term impact of prenatal stress (PS) and disrupted glucocorticoid signaling on bone mass and strength is not understood. In contrast, the detrimental effect of lead (Pb) on skeletal health is well documented. As stress and Pb act on common biological targets via glucocorticoid signaling pathways and co-occur in the environment, this study first sought to assess the combined effect of stress and Pb on bone quality in association with alterations in glucocorticoid signaling...
2017: Bone Research
https://www.readbyqxmd.com/read/28529456/ethyl-acetate-fraction-of-huogu-formula-inhibits-adipogenic-differentiation-of-bone-marrow-stromal-cells-via-the-bmp-and-wnt-signaling-pathways
#17
Xiangying Kong, Xiaomin Li, Cun Zhang, Liuluan Zhu, Chunfang Liu, Qingxia Qin, Cuiling Liu, Qianqian Wang, Jia Zhu, Xuan Wu, Hongye Wan, Weiheng Chen, Na Lin
Elevated adipogenesis of bone marrow stromal cells (BMSCs) is closely associated with non-traumatic osteonecrosis of femoral head (ONFH). Our previous studies have shown that Huogu (HG) formula was effective both in clinic experience and experimental ONFH. How HG impacts the differentiation of BMSCs and what is the underlying molecular mechanism remain largely unknown. Our results showed that ethyl acetate extract of HG (HGE) significantly decreased the adipocyte differentiation as determined by oil red staining, while slightly increased the ALP activity...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28526237/small-molecule-inhibition-of-wnt-signaling-abrogates-dexamethasone-induced-phenotype-of-primary-human-trabecular-meshwork-cells
#18
Sarah D Ahadome, Chi Zhang, Elizabeth Tannous, James Shen, Jie J Zheng
Trabecular meshwork (TM) cells are the governing regulators of the TM structure. When the functionality of these cells is impaired, the structure of the TM is perturbed which often results in increased ocular hypertension. High intraocular pressure is the most significant risk factor for steroid-induced glaucoma. Dexamethasone (Dex)-induced phenotype of TM cells is widely utilized as a model system to gain insight into mechanisms underlying damaged TM in glaucoma. In this study, to assess the possible role of abnormal Wnt signaling in steroid-induced glaucoma, we analyzed the effects of small-molecule Wnt signaling modulators on Dex-induced expression extracellular matrix proteins of primary human TM cells...
August 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28451590/molecular-signaling-of-progesterone-growth-hormone-wnt-and-her-in-mammary-glands-of-dogs-rodents-and-humans-new-treatment-target-identification
#19
REVIEW
Elpetra P M Timmermans-Sprang, Ana Gracanin, Jan A Mol
Mammary tumors are the most common form of neoplasia in the bitch. Female dogs are protected when they are spayed before the first estrus cycle, but this effect readily disappears and is already absent when dogs are spayed after the second heat. As the ovaries are removed during spaying, ovarian steroids are assumed to play an essential role in tumor development. The sensitivity toward tumor development is already present during early life, which may be caused by early mutations in stem cells during the first estrus cycles...
2017: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/28373842/breast-cancer-stem-like-cells-are-inhibited-by-diosgenin-a-steroidal-saponin-by-the-attenuation-of-the-wnt-%C3%AE-catenin-signaling-via-the-wnt-antagonist-secreted-frizzled-related-protein-4
#20
G Bhuvanalakshmi, Basappa, Kanchugarakoppal S Rangappa, Arun Dharmarajan, Gautam Sethi, Alan P Kumar, Sudha Warrier
Background: Identification of breast cancer stem cells as the chemo-resistant and tumor-initiating population represents an important milestone in approaching anticancer therapies. Targeting this minor subpopulation of chemo- and radio-resistant stem-like cells, termed as the cancer stem cells (CSCs) and their eradication could significantly enhance clinical outcomes. Most of the presently administered chemotherapeutics target the tumor bulk but are ineffective against the CSCs. We report here that diosgenin (DG), a naturally occurring steroidal saponin, could effectively inhibit CSCs from three breast cancer cell lines, MCF7, T47D and MDA-MB-231, by inducing apoptosis and inhibiting the CSC associated phenotypes...
2017: Frontiers in Pharmacology
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