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https://www.readbyqxmd.com/read/28334506/molecular-features-of-the-yap-inhibitor-verteporfin-synthesis-of-hexasubstituted-dipyrrins-as-potential-inhibitors-of-yap-taz-the-downstream-effectors-of-the-hippo-pathway
#1
Floriane Gibault, Fabrice Bailly, Matthieu Corvaisier, Mathilde Coevoet, Guillemette Huet, Patricia Melnyk, Philippe Cotelle
Porphyrin derivatives, and in particular Verteporfin (VP), a photosensitizer initially designed for cancer therapy, have been identified as inhibitors of YAP-TEAD interaction and transcriptional activity. We herein report the efficient convergent synthesis of the dipyrrin western half-part of protoporphyrin IX dimethyl ester (PPIX-DME) where the sensitive vinyl group was created at the final stage by a dehydroiodation reaction. Two other dipyrrin derivatives were synthesized including dipyrrin 19 containing two vinyl groups...
March 23, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28315325/-epigallocatechin-3-gallate-stimulates-myogenic-differentiation-through-taz-activation
#2
A Rum Kim, Kyung Min Kim, Mi Ran Byun, Jun-Ha Hwang, Jung Il Park, Ho Taek Oh, Mi Gyeong Jeong, Eun Sook Hwang, Jeong-Ho Hong
Muscle loss is a typical process of aging. Green tea consumption is known to slow down the progress of aging. Their underlying mechanisms, however, remain largely unknown. In this study, we investigated the effect of (-)-epigallocatechin-3-gallate (EGCG), a polyphenolic compound of green tea, on myogenic differentiation and found that EGCG significantly increases myogenic differentiation. After EGCG treatment, the expression of myogenic marker genes, such as myosin heavy chain, are increased through activation of TAZ, a transcriptional coactivator with a PDZ-binding motif...
March 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28301614/a-phase-2-multicenter-double-blind-randomized-vehicle-controlled-clinical-study-to-assess-the-safety-and-efficacy-of-a-halobetasol-tazarotene-fixed-combination-in-the-treatment-of-plaque-psoriasis
#3
Jeffrey L Sugarman, Linda Stein Gold, Mark G Lebwohl, David M Pariser, Binu J Alexander, Radhakrishnan Pillai
<p>BACKGROUND: Psoriasis is a chronic, immune-mediated disease that varies widely in its clinical expression. Treatment options focus on relieving symptoms, reducing inflammation, induration, and scaling, and controlling the extent of the disease. Topical corticosteroids are the mainstay of treatment, however long-term safety remains a concern, particularly with the more potent formulations. Combination therapy with a corticosteroid and tazarotene may improve psoriasis signs at a lower corticosteroid concentration providing a superior safety profile...
March 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28299672/roles-of-runx-in-hippo-pathway-signaling
#4
Antonino Passaniti, Jessica L Brusgard, Yiting Qiao, Marius Sudol, Megan Finch-Edmondson
The Runt-domain (RD) transcription factors (RUNX genes) are an important family of transcriptional mediators that interact with a variety of proteins including the Hippo pathway effector proteins, YAP and TAZ. In this chapter we focus on two examples of RUNX-TAZ/YAP interactions that have particular significance in human cancer. Specifically, recent evidence has found that RUNX2 cooperates with TAZ to promote epithelial to mesenchymal transition mediated by the soluble N-terminal ectodomain of E-Cadherin, sE-Cad...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28289596/a-novel-intronic-splice-site-tafazzin-gene-mutation-detected-prenatally-in-a-family-with-barth-syndrome
#5
M Bakšienė, E Benušienė, A Morkūnienė, L Ambrozaitytė, A Utkus, V Kučinskas
Barth syndrome (BTHS) is a rare X-linked disease characterized by dilated cardiomyopathy, proximal skeletal myopathy and cyclic neutropenia. It is caused by various mutations in the tafazzin (TAZ) gene located on Xq28 that results in remodeling of cardiolipin and abnormalities in mitochondria stability and energy production. Here we report on a novel c.285-1G>C splice site mutation in intron 3 of the TAZ gene that was detected prenatally.
December 1, 2016: Balkan Journal of Medical Genetics: BJMG
https://www.readbyqxmd.com/read/28286324/effects-of-dihydroorotate-dehydrogenase-dhodh-inhibitors-on-the-growth-of-theileria-equi-and-babesia-caballi-in%C3%A2-vitro
#6
Ketsarin Kamyingkird, Shinuo Cao, Bumduuren Tuvshintulga, Akram Salama, Ahmed Abdelmoniem Mousa, Artemis Efstratiou, Yoshifumi Nishikawa, Naoaki Yokoyama, Ikuo Igarashi, Xuenan Xuan
Theileria equi and Babesia caballi are the causative agents of equine piroplasmosis (EP), which affects equine production in various parts of the world. However, a safe and effective drug is not currently available for treatment of EP. Dihydroorotate dehydrogenase (DHODH) is the fourth enzyme in the de novo pyrimidine synthesis pathway and has been known as a novel drug target for several apicomplexan protozoan parasites. In this study, we evaluated four DHODH inhibitors; atovaquone (ATV), leflunomide (LFN), brequinar (Breq), and 7-hydroxy-5-[1,2,4] triazolo [1,5,a] pyrimidine (TAZ) on the growth of T...
March 9, 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28280397/pharmacokinetics-and-outcome-of-tazobactam-piperacillin-in-japanese-patients-undergoing-low-flow-continuous-renal-replacement-therapy-dosage-considerations
#7
Hanako Kohama, Takeshi Ide, Kazuro Ikawa, Norifumi Morikawa, Shinichi Nishi
BACKGROUND: Tazobactam/piperacillin (TAZ/PIPC), which is often combined with continuous renal replacement therapy (CRRT), induces renal excretion and is thought to have a high component removal rate for blood purification. CRRT procedures vary depending on the country, region, and institution. It is not clear whether the dose of TAZ/PIPC for use in Japan can be determined based on studies conducted in other countries. Therefore, in this study, we examined the suitability of recommended dose in Japan...
2017: Clinical Pharmacology: Advances and Applications
https://www.readbyqxmd.com/read/28279717/yap-and-wwtr1-new-targets-for-skin-cancer-treatment
#8
Thomas Andl, Linli Zhou, Kun Yang, Ana Luisa Kadekaro, Yuhang Zhang
The core components of the Hippo signaling pathway are a cascade of kinases that govern the phosphorylation of downstream transcriptional co-activators, namely, YES-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1, also known as TAZ). The Hippo signaling pathway is considered an important tumor-suppressor pathway, and its dysregulation has been noted in a variety of human cancers, in which YAP/WWTR1 enable cancerous cells to overcome contact inhibition, and to grow and spread uncontrollably...
March 6, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28277669/control-of-primary-particle-spacing-in-gold-nanoparticle-clusters-for-both-high-nir-extinction-and-full-reversibility
#9
Ehsan Moaseri, Robert J Stover, Behzad Changalvaie, Alexis J Cepeda, Thomas M Truskett, Konstantin Sokolov, Keith P Johnston
Reversible NIR-active nanoparticle clusters with controlled size from 20 to 100 nm were assembled from 5nm gold nanoparticles (Au NP), with either citrate (CIT) or various binary ligands on the surface, by tuning the electrostatic repulsion and the hydrogen bonding via pH. The nanoclusters were bound together by vdW forces between the cores and the hydrogen bonds between the surface ligands and dissociated to primary nanoparticles over a period of 20 days at pH 5 and at pH 7. When high levels of citrate ligands were used on the primary particle surfaces, the large particle spacings in the nanoclusters led to only modest NIR extinction...
March 9, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28276640/prospective-review-of-mesenchymal-stem-cells-differentiation-into-osteoblasts
#10
REVIEW
Priyanka Garg, Matthew M Mazur, Amy C Buck, Meghan E Wandtke, Jiayong Liu, Nabil A Ebraheim
Stem cell research has been a popular topic in the past few decades. This review aims to discuss factors that help regulate, induce, and enhance mesenchymal stem cell (MSC) differentiation into osteoblasts for bone regeneration. The factors analyzed include bone morphogenic protein (BMP), transforming growth factor β (TGF-β), stromal cell-derived factor 1 (SDF-1), insulin-like growth factor type 1 (IGF-1), histone demethylase JMJD3, cyclin dependent kinase 1 (CDK1), fucoidan, Runx2 transcription factor, and TAZ transcriptional coactivator...
March 9, 2017: Orthopaedic Surgery
https://www.readbyqxmd.com/read/28275646/producing-tissue-specific-stem-cells-for-regeneration-how-yap-taz-may-prove-useful
#11
EDITORIAL
Steven J Henle, Brian A Link
No abstract text is available yet for this article.
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28273460/agrin-as-a-mechanotransduction-signal-regulating-yap-through-the-hippo-pathway
#12
Sayan Chakraborty, Kizito Njah, Ajaybabu V Pobbati, Ying Bena Lim, Anandhkumar Raju, Manikandan Lakshmanan, Vinay Tergaonkar, Chwee Teck Lim, Wanjin Hong
The Hippo pathway effectors YAP and TAZ act as nuclear sensors of mechanical signals in response to extracellular matrix (ECM) cues. However, the identity and nature of regulators in the ECM and the precise pathways relaying mechanoresponsive signals into intracellular sensors remain unclear. Here, we uncover a functional link between the ECM proteoglycan Agrin and the transcriptional co-activator YAP. Importantly, Agrin transduces matrix and cellular rigidity signals that enhance stability and mechanoactivity of YAP through the integrin-focal adhesion- and Lrp4/MuSK receptor-mediated signaling pathways...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28249901/endothelin-promotes-colorectal-tumorigenesis-by-activating-yap-taz
#13
Zhen Wang, Peng Liu, Xin Zhou, Tianxiang Wang, Xu Feng, Yi-Ping Sun, Yue Xiong, Hai-Xin Yuan, Kun-Liang Guan
Endothelin receptor A (ETAR) promotes tumorigenesis by stimulating cell proliferation, migration and survival. However, the mechanism of ETAR in promoting tumor growth is largely unknown. In this study, we demonstrate that ETAR stimulates colon cell proliferation, migration, and tumorigenesis through the activation of YAP/TAZ, two transcription co-activators of the Hippo tumor suppressor pathway. Endothelin-1 (ET-1) treatment induced YAP/TAZ dephosphorylation, nuclear accumulation, and transcriptional activation in multiple colon cancer cells...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28248929/rnai-screens-for-rho-gtpase-regulators-of-cell-shape-and-yap-taz-localisation-in-triple-negative-breast-cancer
#14
Patricia Pascual-Vargas, Samuel Cooper, Julia Sero, Vicky Bousgouni, Mar Arias-Garcia, Chris Bakal
In order to metastasise, triple negative breast cancer (TNBC) must make dynamic changes in cell shape. The shape of all eukaryotic cells is regulated by Rho Guanine Nucleotide Exchange Factors (RhoGEFs), which activate Rho-family GTPases in response to mechanical and informational cues. In contrast, Rho GTPase-activating proteins (RhoGAPs) inhibit Rho GTPases. However, which RhoGEFs and RhoGAPS couple TNBC cell shape to changes in their environment is very poorly understood. Moreover, whether the activity of particular RhoGEFs and RhoGAPs become dysregulated as cells evolve the ability to metastasise is not clear...
March 1, 2017: Scientific Data
https://www.readbyqxmd.com/read/28229253/the-biology-of-uveal-melanoma
#15
Adriana Amaro, Rosaria Gangemi, Francesca Piaggio, Giovanna Angelini, Gaia Barisione, Silvano Ferrini, Ulrich Pfeffer
Uveal melanoma (UM), a rare cancer of the eye, is distinct from cutaneous melanoma by its etiology, the mutation frequency and profile, and its clinical behavior including resistance to targeted therapy and immune checkpoint blockers. Primary disease is efficiently controlled by surgery or radiation therapy, but about half of UMs develop distant metastasis mostly to the liver. Survival of patients with metastasis is below 1 year and has not improved in decades. Recent years have brought a deep understanding of UM biology characterized by initiating mutations in the G proteins GNAQ and GNA11...
February 22, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28202507/yap-taz-mediated-upregulation-of-gab2-leads-to-increased-sensitivity-to-growth-factor-induced-activation-of-the-pi3k-pathway
#16
Chao Wang, Chao Gu, Kang Jin Jeong, Dong Zhang, Wei Guo, Yiling Lu, Zhenlin Ju, Nattapon Panupinthu, Ji Yeon Yang, Mihai Mike Gagea, Patrick Kwok Shing Ng, Fan Zhang, Gordon B Mills
The transcription regulators YAP and TAZ function as effectors of the HIPPO signaling cascade, critical for organismal development, cell growth, and cellular reprogramming, and YAP/TAZ is commonly misregulated in human cancers. The precise mechanism by which aberrant YAP/TAZ promotes tumor growth remains unclear. The HIPPO tumor suppressor pathway phosphorylates YAP and TAZ, resulting in cytosolic sequestration with subsequent degradation. Here, we report that the PI3K/AKT pathway, which is critically involved in the pathophysiology of endometrial cancer, interacts with the HIPPO pathway at multiple levels...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28195168/taz-contributes-to-pulmonary-fibrosis-by-activating-profibrotic-functions-of-lung-fibroblasts
#17
Satoshi Noguchi, Akira Saito, Yu Mikami, Hirokazu Urushiyama, Masafumi Horie, Hirotaka Matsuzaki, Hideyuki Takeshima, Kosuke Makita, Naoya Miyashita, Akihisa Mitani, Taisuke Jo, Yasuhiro Yamauchi, Yasuhiro Terasaki, Takahide Nagase
Transcriptional coactivator with PDZ-binding motif (TAZ) regulates a variety of biological processes. Nuclear translocation and activation of TAZ are regulated by multiple mechanisms, including actin cytoskeleton and mechanical forces. TAZ is involved in lung alveolarization during lung development and Taz-heterozygous mice are resistant to bleomycin-induced lung fibrosis. In this study, we explored the roles of TAZ in the pathogenesis of idiopathic pulmonary fibrosis (IPF) through histological analyses of human lung tissues and cell culture experiments...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28183853/mark4-inhibits-hippo-signaling-to-promote-proliferation-and-migration-of-breast-cancer-cells
#18
Emad Heidary Arash, Ahmed Shiban, Siyuan Song, Liliana Attisano
The Hippo pathway is a critical regulator of tissue size, and aberrations in pathway regulation lead to cancer. MST1/2 and LATS1/2 kinases comprise the core of the pathway that, in association with adaptor proteins SAV and MOB, functions in a sequential manner to phosphorylate and inhibit the transcription factors YAP and TAZ. Here we identify mammalian MARK family members as activators of YAP/TAZ. We show that depletion of MARK4 in MDA-MB-231 breast cancer cells results in the loss of nuclear YAP/TAZ and decreases the expression of YAP/TAZ targets...
March 2017: EMBO Reports
https://www.readbyqxmd.com/read/28183324/identification-of-taz-mutations-in-pediatric-patients-with-cardiomyopathy-by-targeted-next-generation-sequencing-in-a-chinese-cohort
#19
Jian Wang, Ying Guo, Meirong Huang, Zhen Zhang, Junxue Zhu, Tingliang Liu, Lin Shi, Fen Li, Huimin Huang, Lijun Fu
BACKGROUND: Barth syndrome (BTHS) is a rare X-linked recessive disease characterized by cardiomyopathy, neutropenia, skeletal myopathy and growth delay. Early diagnosis and appropriate treatment may improve the prognosis of this disease. The purpose of this study is to determine the role of targeted next-generation sequencing (NGS) in the early diagnosis of BTHS in children with cardiomyopathy. METHODS: During the period between 2012 and 2015, a gene panel-based NGS approach was used to search for potentially disease-causing genetic variants in all patients referred to our institution with a clinical diagnosis of primary cardiomyopathy...
February 10, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28166194/mutant-p53-oncogenic-functions-in-cancer-stem-cells-are-regulated-by-wip-through-yap-taz
#20
M Escoll, R Gargini, A Cuadrado, I M Anton, F Wandosell
Wild-type p53 (wtp53) is described as a tumour suppressor gene; mutations in this gene occur in many human cancers and promote oncogenic capacity. Here, we establish that the oncogenic activity of mutant p53 (mtp53) is driven by the WASP-interacting protein (WIP). WIP knockdown from mtp53-expressing glioblastoma and breast cancer cells (BCC) greatly reduced proliferation and growth capacity of cancer stem cell (CSC)-like cells and decreased CSC-like markers (CD133, CD44 or YAP/TAZ). mtp53 overexpression in human astrocytes enhanced their proliferative capacity in suspension culture and increased expression of CSC markers and WIP...
February 6, 2017: Oncogene
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