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https://www.readbyqxmd.com/read/28919264/prolactin-alters-the-mammary-epithelial-hierarchy-increasing-progenitors-and-facilitating-ovarian-steroid-action
#1
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...
September 7, 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
#2
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
#3
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
#4
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
#5
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...
July 18, 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
#6
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
#7
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...
July 5, 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
#8
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
#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...
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28215225/transcription-factors-in-breast-cancer-lessons-from-recent-genomic-analyses-and-therapeutic-implications
#15
E Zacksenhaus, J C Liu, Z Jiang, Y Yao, L Xia, M Shrestha, Y Ben-David
Multiplatform genomic analyses have identified 93 frequently altered genes in breast cancer. Of these, as many as 49 genes are directly or indirectly involved in transcription. These include constitutive and inducible DNA-binding transcription factors (DB-TFs, 13 genes), corepressors/coactivators (14 genes), epigenetic (10), and mediator/splicing/rRNA (3) factors. At least nine additional genes are immediate upstream regulators of transcriptional cofactors. G:profiler analysis reveals that these alterations affect cell cycle, development/differentiation, steroid hormone, and chromatin modification pathways...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28045158/metabolomics-and-proteomics-technologies-to-explore-the-herbal-preparation-affecting-metabolic-disorders-using-high-resolution-mass-spectrometry
#16
Aihua Zhang, Xiaohang Zhou, Hongwei Zhao, Shiyu Zou, Chung Wah Ma, Qi Liu, Hui Sun, Liang Liu, Xijun Wang
An integrative metabolomics and proteomics approach can provide novel insights in the understanding of biological systems. We have integrated proteome and metabolome data sets for a holistic view of the molecular mechanisms in disease. Using quantitative iTRAQ-LC-MS/MS proteomics coupled with UPLC-Q-TOF-HDMS based metabolomics, we determined the protein and metabolite expression changes in the kidney-yang deficiency syndrome (KYDS) rat model and further investigated the intervention effects of the Jinkui Shenqi Pill (JSP)...
January 31, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28007462/celecoxib-inhibits-osteoblast-maturation-by-suppressing-the-expression-of-wnt-target-genes
#17
Akihiro Nagano, Masaki Arioka, Fumi Takahashi-Yanaga, Etsuko Matsuzaki, Toshiyuki Sasaguri
Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to impair bone healing. We previously reported that in colon cancer cells, celecoxib, a COX-2-selective NSAID, inhibited the canonical Wnt/β-catenin signaling pathway. Since this pathway also plays an important role in osteoblast growth and differentiation, we examined the effect of celecoxib on maturation of osteoblast-like cell line MC3T3-E1. Celecoxib induced degradation of transcription factor 7-like 2, a key transcription factor of the canonical Wnt pathway...
January 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27997581/identification-of-polycystic-ovary-syndrome-pcos-specific-genes-in-cumulus-and-mural-granulosa-cells
#18
Alp Aydos, Aykut Gurel, Yasemin Oztemur Islakoglu, Senem Noyan, Bagdagul Gokce, Tolga Ecemis, Cemil Kaya, Arif Tarik Aksu, Bala Gur Dedeoglu
Polycystic ovary syndrome (PCOS) is a metabolic and endocrine disorder which affects women of reproductive age with prevalence of 8-18%. The oocyte within the follicle is surrounded by cumulus cells (CCs), which connect with mural granulosa cells (MGCs) that are responsible for secreting steroid hormones. The main aim of this study is comparing gene expression profiles of MGCs and CCs in PCOS and control samples to identify PCOS-specific differentially expressed genes (DEGs). In this study, two microarray databases were searched for mRNA expression microarray studies performed with CCs and MGCs obtained from PCOS patients and control samples...
2016: PloS One
https://www.readbyqxmd.com/read/27973612/long-lasting-wnt-tcf-response-blocking-and-epigenetic-modifying-activities-of-withanolide-f-in-human-cancer-cells
#19
Chandan Seth, Christophe Mas, Arwen Conod, Jens Mueller, Karsten Siems, Monika Kuciak, Isabel Borges, Ariel Ruiz I Altaba
The WNT-TCF signaling pathway participates in adult tissue homeostasis and repair, and is hyperactive in a number of human diseases including cancers of the colon. Whereas to date there are no antagonists approved for patient use, a potential problem for their sustained use is the blockade of WNT signaling in healthy tissues, thus provoking potentially serious co-lateral damage. Here we have screened a library of plant and microorganism small molecules for novel WNT signaling antagonists and describe withanolide F as a potent WNT-TCF response blocker...
2016: PloS One
https://www.readbyqxmd.com/read/27967206/silencing-med12-gene-reduces-proliferation-of-human-leiomyoma-cells-mediated-via-wnt-%C3%AE-catenin-signaling-pathway
#20
Ayman Al-Hendy, Archana Laknaur, Michael P Diamond, Nahed Ismail, Thomas G Boyer, Sunil K Halder
Uterine fibroids, or leiomyoma, are the most common benign tumors in women of reproductive age. In this work, the effect of silencing the mediator complex subunit 12 (Med12) gene in human uterine fibroid cells was evaluated. The role of Med12 in the modulation of Wnt/β-catenin and cell proliferation-associated signaling was evaluated in human uterine fibroid cells. Med12 was silenced in the immortalized human uterine fibroid cell line (HuLM) using a lentivirus-based Med12 gene-specific RNA interference strategy...
March 1, 2017: Endocrinology
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