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https://www.readbyqxmd.com/read/28215225/transcription-factors-in-breast-cancer-lessons-from-recent-genomic-analyses-and-therapeutic-implications
#1
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
#2
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 3, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28007462/celecoxib-inhibits-osteoblast-maturation-by-suppressing-the-expression-of-wnt-target-genes
#3
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
#4
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
#5
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
#6
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. Herein, 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 (RNAi) strategy...
December 14, 2016: Endocrinology
https://www.readbyqxmd.com/read/27782124/wnt-and-neuregulin1-erbb-signalling-extends-3d-culture-of-hormone-responsive-mammary-organoids
#7
Thierry Jardé, Bethan Lloyd-Lewis, Mairian Thomas, Howard Kendrick, Lorenzo Melchor, Lauriane Bougaret, Peter D Watson, Kenneth Ewan, Matthew J Smalley, Trevor C Dale
The development of in vitro culture systems quantitatively and qualitatively recapitulating normal breast biology is key to the understanding of mammary gland biology. Current three-dimensional mammary culture systems have not demonstrated concurrent proliferation and functional differentiation ex vivo in any system for longer than 2 weeks. Here, we identify conditions including Neuregulin1 and R-spondin 1, allowing maintenance and expansion of mammary organoids for 2.5 months in culture. The organoids comprise distinct basal and luminal compartments complete with functional steroid receptors and stem/progenitor cells able to reconstitute a complete mammary gland in vivo...
October 26, 2016: Nature Communications
https://www.readbyqxmd.com/read/27777363/transcriptome-pathway-analysis-of-pathological-and-physiological-aldosterone-producing-human-tissues
#8
Junhua Zhou, Brian Lam, Sudeshna G Neogi, Giles S H Yeo, Elena A B Azizan, Morris J Brown
Primary aldosteronism is present in ≈10% of hypertensives. We previously performed a microarray assay on aldosterone-producing adenomas and their paired zona glomerulosa and fasciculata. Confirmation of top genes validated the study design and functional experiments of zona glomerulosa selective genes established the role of the encoded proteins in aldosterone regulation. In this study, we further analyzed our microarray data using AmiGO 2 for gene ontology enrichment and Ingenuity Pathway Analysis to identify potential biological processes and canonical pathways involved in pathological and physiological aldosterone regulation...
December 2016: Hypertension
https://www.readbyqxmd.com/read/27753830/sy-03-3-overview-of-somatic-mutations-and-epigenetic-regulation-of-aldosterone-producing-adenoma-apa
#9
Satoshi Umemura
Primary aldosteronism (PA) is a heterogeneous group of disorders including both sporadic and familial forms (familial hyperaldosteronism type I, II and III). PA is the most frequent endocrine cause of secondary hypertension and associated with a higher rate of cardiovascular complications, compared with essential hypertension.Here I review the recent progress in understanding of the genetic and molecular mechanisms leading to autonomous aldosterone production in PA.Systematic screening detects primary aldosteronism in 5 to 10% of all patients with hypertension and in approximately 20% of patients with resistant hypertension...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27694319/metamizole-dipyrone-effects-on-sevoflurane-requirements-and-postoperative-hyperalgesia-in-rats
#10
Daniel Ruiz-Pérez, Javier Benito, Carlota Largo, Gonzalo Polo, Susana Canfrán, Ignacio Alvarez Gómez de Segura
Unlike non-steroidal anti-inflammatory drugs (NSAIDs), metamizole has poor anti-inflammatory effects; and is suitable for models where analgesia, but not anti-inflammatory effects, is desirable. Like opioids, these drugs produce perioperative analgesia while reducing anaesthetic requirements, but it remains unclear whether they may develop tolerance or hyperalgesia, and thus decrease in analgesic efficacy. The aim was to determine whether tolerance or hyperalgesia to metamizole occurred in rats, and whether the sevoflurane minimum alveolar concentration (MAC) was affected...
September 30, 2016: Laboratory Animals
https://www.readbyqxmd.com/read/27646003/microrna-205-maintains-t-cell-development-following-stress-by-regulating-forkhead-box-n1-and-selected-chemokines
#11
Ashley R Hoover, Igor Dozmorov, Jessica MacLeod, Qiumei Du, M Teresa de la Morena, Joseph Forbess, Kristine Guleserian, Ondine B Cleaver, Nicolai S C van Oers
The thymus, an organ responsible for T cell development, is one of the more stress-sensitive tissues in the body. Stress, in the form of infections, radiation exposure, and steroids, impairs thymic epithelial cell (TEC) functions and induces the programmed cell death of immature thymocytes. MicroRNAs are small noncoding RNAs involved in tissue repair and homeostasis, with several supporting T cell development. We report that miR-205, an epithelial-specific miR, maintains thymopoiesis following inflammatory perturbations...
October 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27642883/sy-03-3-overview-of-somatic-mutations-and-epigenetic-regulation-of-aldosterone-producing-adenoma-apa
#12
Satoshi Umemura
Primary aldosteronism (PA) is a heterogeneous group of disorders including both sporadic and familial forms (familial hyperaldosteronism type I, II and III). PA is the most frequent endocrine cause of secondary hypertension and associated with a higher rate of cardiovascular complications, compared with essential hypertension.Here I review the recent progress in understanding of the genetic and molecular mechanisms leading to autonomous aldosterone production in PA.Systematic screening detects primary aldosteronism in 5 to 10% of all patients with hypertension and in approximately 20% of patients with resistant hypertension...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27626976/antisecretive-and-antitumor-activity-of-abiraterone-acetate-in-human-adrenocortical-cancer-a-preclinical-study
#13
Chiara Fiorentini, Martina Fragni, Paola Perego, Sara Vezzoli, Sara A Bonini, Monica Tortoreto, Diego Galli, Melanie Claps, Guido A Tiberio, Massimo Terzolo, Cristina Missale, Maurizio Memo, Giuseppe Procopio, Nadia Zaffaroni, Alfredo Berruti, Sandra Sigala
CONTEXT: Patients with adrenocortical carcinoma (ACC) frequently suffer from cortisol excess, which portends a negative prognosis. Rapid control of cortisol hypersecretion and tumor growth are the main goals of ACC therapy. Abiraterone acetate (AA) is a potent inhibitor of 17alpha-hydroxylase/17,20-lyase, a key enzyme of adrenal steroidogenesis. OBJECTIVE: This study sought to investigate the therapeutic use of AA in preclinical models of ACC. DESIGN: AA antisecretive and antiproliferative effects were investigated in vitro using NCI-H295R and SW13 ACC cell lines and human primary ACC cell cultures, as well as in vivo using immunodeficient mice...
December 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27566230/expression-profiling-identifies-sertoli-and-leydig-cell-genes-as-fsh-targets-in-adult-zebrafish-testis
#14
Diego Crespo, Luiz H C Assis, Tomasz Furmanek, Jan Bogerd, Rüdiger W Schulz
Spermatogonial stem cells are quiescent, undergo self-renewal or differentiating divisions, thereby forming the cellular basis of spermatogenesis. This cellular development is orchestrated by follicle-stimulating hormone (FSH), through the production of Sertoli cell-derived factors, and by Leydig cell-released androgens. Here, we investigate the transcriptional events induced by Fsh in a steroid-independent manner on the restart of zebrafish (Danio rerio) spermatogenesis ex vivo, using testis from adult males where type A spermatogonia were enriched by estrogen treatment in vivo...
December 5, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27554815/age-dictates-a-steroid-resistant-cascade-of-wnt5a-transglutaminase-2-and-leukotrienes-in-inflamed-airways
#15
Katharina Dietz, Marta de Los Reyes Jiménez, Eva S Gollwitzer, Adam M Chaker, Ulrich M Zissler, Olof P Rådmark, Hoeke A Baarsma, Melanie Königshoff, Carsten B Schmidt-Weber, Benjamin J Marsland, Julia Esser-von Bieren
BACKGROUND: Airway remodeling is a detrimental and refractory process showing age-dependent clinical manifestations that are mechanistically undefined. The leukotriene (LT) and wingless/integrase (Wnt) pathways have been implicated in remodeling, but age-specific expression profiles and common regulators remained elusive. OBJECTIVE: We sought to study the activation of the LT and Wnt pathways during early- or late-onset allergic airway inflammation and to address regulatory mechanisms and clinical relevance in normal human bronchial epithelial cells (NHBEs) and nasal polyp tissues...
August 20, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27535961/niclosamide-as-a-potential-nonsteroidal-therapy-for-endometriosis-that-preserves-reproductive-function-in-an-experimental-mouse-model
#16
Genna R Prather, James A MacLean, Mingxin Shi, Daniel K Boadu, Marilène Paquet, Kanako Hayashi
Endometriosis causes severe chronic pelvic pain and infertility. Because the standard medication and surgical treatments of endometriosis show high recurrence of symptoms, it is necessary to improve current treatment options. In the initial study, we examined whether niclosamide can be a useful drug for endometriosis in a preclinical setting. Endometriotic implants were induced using an established mouse model involving transimplantation of mouse endometrial fragments to the peritoneal wall of recipient mice...
August 17, 2016: Biology of Reproduction
https://www.readbyqxmd.com/read/27471492/mouse-models-recapitulating-human-adrenocortical-tumors-what-is-lacking
#17
REVIEW
Felicia Leccia, Marie Batisse-Lignier, Isabelle Sahut-Barnola, Pierre Val, A-Marie Lefrançois-Martinez, Antoine Martinez
Adrenal cortex tumors are divided into benign forms, such as primary hyperplasias and adrenocortical adenomas (ACAs), and malignant forms or adrenocortical carcinomas (ACCs). Primary hyperplasias are rare causes of adrenocorticotropin hormone-independent hypercortisolism. ACAs are the most common type of adrenal gland tumors and they are rarely "functional," i.e., producing steroids. When functional, adenomas result in endocrine disorders, such as Cushing's syndrome (hypercortisolism) or Conn's syndrome (hyperaldosteronism)...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/27450649/impaired-osteogenic-differentiation-associated-with-connexin43-microrna-206-in-steroid-induced-avascular-necrosis-of-the-femoral-head
#18
Gang Liu, Gaobin Luo, Zhandong Bo, Xiaonan Liang, Jie Huang, Donghui Li
Connexin(Cx)43 and microRNA(miR)-206 play an important role in osteogenesis. However, their role in steroid-induced femoral head osteonecrosis (SANFH) is still ambiguous. The present study aimed to establish a rabbit model and investigate osteogenesis in steroid-induced femoral head osteonecrosis occurring via Cx43/miR-206 and the changes of Wnt/β-catenin signal pathway-related proteins. A total of 72 adult New Zealand white rabbits were divided randomly into a model group (Group A) and a control group (Group B) of 36 rabbits each...
August 2016: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/27297409/eosinophils-enhance-wnt-5a-and-tgf-%C3%AE-1-genes-expression-in-airway-smooth-muscle-cells-and-promote-their-proliferation-by-increased-extracellular-matrix-proteins-production-in-asthma
#19
RANDOMIZED CONTROLLED TRIAL
Andrius Januskevicius, Simona Vaitkiene, Reinoud Gosens, Ieva Janulaityte, Deimante Hoppenot, Raimundas Sakalauskas, Kestutis Malakauskas
BACKGROUND: Recent studies have suggested that eosinophils may have a direct effect on airway smooth muscle cells (ASMC), causing their proliferation in patients with asthma, but the precise mechanism of the interaction between these cells remains unknown. We propose that changes in Wnt signaling activity and extracellular matrix (ECM) production may help explain these findings. Therefore, the aim of this study was to investigate the effect of eosinophils from asthmatic and non-asthmatic subjects on Wnt-5a, transforming growth factor β1 (TGF-β1), and ECM protein (fibronectin and collagen) gene expression and ASMC proliferation...
June 13, 2016: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/27150989/-effect-of-inhibiting-and-activating-wnt-signalling-pathway-on-nsc67657-inducing-monocytic-differentiation-of-hl-60-cells
#20
Wei-Jia Wang, Xiu-Ming Zhang, Yan Zhang, Jin-Shu Wang
OBJECTIVE: To investigate the effect of inhibiting and activating Wnt signalling pathway on monocyte differentiation of HL-60 cells induced with a new steroidal drug NSC67657 and its possible mechamism. METHODS: The HL-60 cells were treated with 5, 10 and 20 µmol/L XAV-939 (inhibitor of Wnt signalling pathway) for 3 days, and with 10, 20 and 30 mmol/L LiCl (activator of Wnt signalling pathway) for 1 day; the expression levels of down-stream genes and proteins of Wnt signolling pathway were detected by RT-PCR and Western blot, respectively; the expression of cell surface differentiation antigen CD14 and early apoptosis of HL-60 cells was detected by flow cytometry, moreover the most suitable concentration of Wnt inhibitor and activator for HL-60 cells was determined...
April 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
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