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https://www.readbyqxmd.com/read/28829835/exogenous-growth-factors-bfgf-egf-and-hgf-do-not-influence-viability-and-phenotype-of-v600ebraf-melanoma-cells-and-their-response-to-vemurafenib-and-trametinib-in-vitro
#1
Izabela Zalesna, Marta Osrodek, Mariusz L Hartman, Michal Rozanski, Malgorzata Sztiller-Sikorska, Karolina Niewinna, Dariusz Nejc, Malgorzata Czyz
It has been shown that the response of V600EBRAF melanoma cells to targeted therapeutics is affected by growth factors. We have investigated the influence of three different growth factors, bFGF, EGF and HGF used either alone or in combination, on the response of V600EBRAF melanoma cell populations established from surgical specimens to vemurafenib and trametinib, targeting V600EBRAF and MEK1/2, respectively. We report that proliferation and phenotype of V600EBRAF melanoma cell populations were not detectably influenced by exogenous growth factors...
2017: PloS One
https://www.readbyqxmd.com/read/28829282/parthenolide-promotes-differentiation-of-osteoblasts-through-the-wnt-%C3%AE-catenin-signaling-pathway-in-inflammatory-environments
#2
Xufang Zhang, Qingpiao Chen, Jianwei Liu, Chen Fan, Qi Wei, Zetao Chen, Xueli Mao
Periodontitis is a progressive inflammatory disease initiated by bacterial biofilm adhering to the tooth surface. If left untreated, periodontitis may lead to tooth loss and destruction of the alveolar bone. Regaining the lost alveolar bone is a clinical challenge because of the limited differentiation ability of osteoblasts in inflammatory environments. We have previously shown the anti-inflammatory and antiosteoclastogenic activities of parthenolide (PTL) in human periodontal ligament-derived cells by inhibiting nuclear factor kappa B (NF-κB) signaling, indicating its potential for periodontitis treatment...
August 22, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28829118/bioactive-natural-products-prioritization-using-massive-multi-informational-molecular-networks
#3
Florent Olivon, Pierre-Marie Allard, Alexey Koval, Davide Righi, Gregory Genta-Jouve, Johan Neyts, Cécile Apel, Christophe Pannecouque, Louis-Félix Nothias, Xavier Cachet, Laurence Marcourt, Fanny Roussi, Vladimir L Katanaev, David Touboul, Jean-Luc Wolfender, Marc Litaudon
Natural products represent an inexhaustible source of novel therapeutic agents. Their complex and constrained three-dimensional structures endow these molecules with exceptional biological properties, thereby giving them a major role in drug discovery programs. However, the search for new bioactive metabolites is hampered by the chemical complexity of the biological matrices in which they are found. The purification of single constituents from such matrices requires such a significant amount of work that should ideally be performed only on molecules of high potential value (i...
August 22, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28829046/twa1-gid8-is-a-%C3%AE-catenin-nuclear-retention-factor-in-wnt-signaling-and-colorectal-tumorigenesis
#4
Yi Lu, Shanshan Xie, Wen Zhang, Cheng Zhang, Cheng Gao, Qiang Sun, Yuqi Cai, Zhangqi Xu, Min Xiao, Yanjun Xu, Xiao Huang, Ximei Wu, Wei Liu, Fudi Wang, Yibin Kang, Tianhua Zhou
Hyperactivation of Wnt/β-catenin signaling is one of the major causes of human colorectal cancer (CRC). A hallmark of Wnt signaling is the nuclear accumulation of β-catenin. Although β-catenin nuclear import and export have been widely investigated, the underlying mechanism of β-catenin's nuclear retention remains largely unknown. Here, we report that Twa1/Gid8 is a key nuclear retention factor for β-catenin during Wnt signaling and colorectal carcinogenesis. In the absence of Wnt, Twa1 exists together with β-catenin in the Axin complex and undergoes ubiquitination and degradation...
August 22, 2017: Cell Research
https://www.readbyqxmd.com/read/28828438/niclosamide-conjugated-polypeptide-nanoparticles-inhibit-wnt-signaling-and-colon-cancer-growth
#5
Jayanta Bhattacharyya, Xiu-Rong Ren, Robert A Mook, Jiangbo Wang, Ivan Spasojevic, Richard T Premont, Xinghai Li, Ashutosh Chilkoti, Wei Chen
Abnormal Wnt activity is a major mechanism responsible for many diseases, including cancer. Previously, we reported that the anthelmintic drug Niclosamide (NIC) inhibits Wnt/β-catenin signaling and suppresses colon cancer cell growth. Although the pharmacokinetic properties of NIC are appropriate for use as an anthelmintic agent, its low solubility, low bioavailability and low systemic exposure limit its usefulness in treating systemic diseases. To overcome these limitations, we conjugated NIC to recombinant chimeric polypeptides (CPs), and the CP-NIC conjugate spontaneously self-assembled into sub-100 nm near-monodisperse nanoparticles...
August 22, 2017: Nanoscale
https://www.readbyqxmd.com/read/28827822/comparative-gene-expression-study-and-pathway-analysis-of-the-human-iris-and-the-retinal-pigment-epithelium
#6
Anna Bennis, Jacoline B Ten Brink, Perry D Moerland, Vivi M Heine, Arthur A Bergen
BACKGROUND: The retinal pigment epithelium (RPE) is a neural monolayer lining the back of the eye. Degeneration of the RPE leads to severe vision loss in, so far incurable, diseases such as age-related macular degeneration and some forms of retinitis pigmentosa. A promising future replacement therapy may be autologous iris epithelial cell transdifferentiation into RPE in vitro and, subsequently, transplantation. In this study we compared the gene expression profiles of the iris epithelium (IE) and the RPE...
2017: PloS One
https://www.readbyqxmd.com/read/28827763/peroxiredoxin1-a-novel-regulator-of-pronephros-development-influences-retinoic-acid-and-wnt-signaling-by-controlling-ros-levels
#7
Soomin Chae, Hyun-Kyung Lee, Yoo-Kyung Kim, Hyo Jung Sim, Yoorim Ji, Chowon Kim, Tayaba Ismail, Jeen-Woo Park, Oh-Shin Kwon, Beom-Sik Kang, Dong-Seok Lee, Jong-Sup Bae, Sang-Hyun Kim, Kyoung-Jin Min, Taeg Kyu Kwon, Mae-Ja Park, Jin-Kwan Han, Taejoon Kwon, Tae-Joo Park, Hyun-Shik Lee
Peroxiredoxin1 (Prdx1) is an antioxidant enzyme belonging to the peroxiredoxin family of proteins. Prdx1 catalyzes the reduction of H2O2 and alkyl hydroperoxide and plays an important role in different biological processes. Prdx1 also participates in various age-related diseases and cancers. In this study, we investigated the role of Prdx1 in pronephros development during embryogenesis. Prdx1 knockdown markedly inhibited proximal tubule formation in the pronephros and significantly increased the cellular levels of reactive oxygen species (ROS), which impaired primary cilia formation...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28827348/reversal-of-hyperactive-wnt-signaling-dependent-adipocyte-defects-by-peptide-boronic-acids
#8
Tianyi Zhang, Fu-Ning Hsu, Xiao-Jun Xie, Xiao Li, Mengmeng Liu, Xinsheng Gao, Xun Pei, Yang Liao, Wei Du, Jun-Yuan Ji
Deregulated Wnt signaling and altered lipid metabolism have been linked to obesity, diabetes, and various cancers, highlighting the importance of identifying inhibitors that can modulate Wnt signaling and aberrant lipid metabolism. We have established a Drosophila model with hyperactivated Wnt signaling caused by partial loss of axin, a key component of the Wnt cascade. The Axin mutant larvae are transparent and have severe adipocyte defects caused by up-regulation of β-catenin transcriptional activities. We demonstrate pharmacologic mitigation of these phenotypes in Axin mutants by identifying bortezomib and additional peptide boronic acids...
August 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28827139/reduced-glutathione-level-promotes-epithelial-mesenchymal-transition-in-lens-epithelial-cells-via-a-wnt-%C3%AE-catenin-mediated-pathway-relevance-for-cataract-therapy
#9
Zongbo Wei, Jane Caty, Jeremy Whitson, Amy D Zhang, Ramkumar Srinivasagan, Terrance J Kavanagh, Hong Yan, Xingjun Fan
The epithelial-mesenchymal transition (EMT) process plays a pivotal role in the pathogenesis of posterior capsular opacification (PCO) owing to remnant lens epithelial cell proliferation, migration and transformation after cataract surgery. The latter, we hypothesize, may result in posterior capsule wrinkling and opacification due to a profound change in the lens growth environment via a 1000-fold reduction of extracellular glutathione (GSH) levels. To test this hypothesis, we investigated the EMT process in cell culture and GSH biosynthesis deficiency mouse models...
August 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28826820/antagonistic-activities-of-sox2-and-brachyury-control-the-fate-choice-of-neuro-mesodermal-progenitors
#10
Frederic Koch, Manuela Scholze, Lars Wittler, Dennis Schifferl, Smita Sudheer, Phillip Grote, Bernd Timmermann, Karol Macura, Bernhard G Herrmann
The spinal cord and mesodermal tissues of the trunk such as the vertebral column and skeletal musculature derive from neuro-mesodermal progenitors (NMPs). Sox2, Brachyury (T), and Tbx6 have been correlated with NMP potency and lineage choice; however, their exact role and interaction in these processes have not yet been revealed. Here we present a global analysis of NMPs and their descending lineages performed on purified cells from embryonic day 8.5 wild-type and mutant embryos. We show that T, cooperatively with WNT signaling, controls the progenitor state and the switch toward the mesodermal fate...
August 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28822229/vasculogenesis-and-angiogenesis-initiation-under-normoxic-conditions-through-wnt-%C3%AE-catenin-pathway-in-gliomas
#11
Alexandre Vallée, Rémy Guillevin, Jean-Noël Vallée
The canonical Wnt/β-catenin pathway is up-regulated in gliomas and involved in proliferation, invasion, apoptosis, vasculogenesis and angiogenesis. Nuclear β-catenin accumulation correlates with malignancy. Hypoxia activates hypoxia-inducible factor (HIF)-1α by inhibiting HIF-1α prolyl hydroxylation, which promotes glycolytic energy metabolism, vasculogenesis and angiogenesis, whereas HIF-1α is degraded by the HIF prolyl hydroxylase under normoxic conditions. We focus this review on the links between the activated Wnt/β-catenin pathway and the mechanisms underlying vasculogenesis and angiogenesis through HIF-1α under normoxic conditions in gliomas...
August 19, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28821761/enhanced-therapeutic-effects-of-human-ips-cell-derived-cardiomyocyte-by-combined-cell-sheets-with-omental-flap-technique-in-porcine-ischemic-cardiomyopathy-model
#12
Masashi Kawamura, Shigeru Miyagawa, Satsuki Fukushima, Atsuhiro Saito, Kenji Miki, Shunsuke Funakoshi, Yoshinori Yoshida, Shinya Yamanaka, Tatsuya Shimizu, Teruo Okano, Takashi Daimon, Koichi Toda, Yoshiki Sawa
Transplant of human induced pluripotent stem cell derived cardiomyocytes (hiPS-CMs) cell-sheet is a promising approach for treating ischemic cardiomyopathy (ICM). However, poor blood supply to the transplanted cell-sheet is a concern related to the effectiveness and durability of the treatment. Herein, we hypothesized that the combined the omentum flap might enhance survival and the therapeutic effects of hiPS-CM cell-sheet transplant for ICM treatment. Treatment by Wnt signaling molecules in hiPS cells produced hiPS-CMs, which were magnetically labeled by superparamagnetic iron oxide (SPIO), followed by culture in the thermoresponsive dishes to generate hiPS-CMs cell-sheets...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821654/wnt9a-can-influence-cell-fates-and-neural-connectivity-across-the-radial-axis-of-the-developing-cochlea
#13
Vidhya Munnamalai, Ulrike J Sienknecht, R Keith Duncan, M Katie Scott, Ankita Thawani, Kristen N Fantetti, Nadia M Atallah, Deborah J Biesemeier, Kuhn H Song, Kirsten Luethy, Eric Traub, Donna M Fekete
Vertebrate hearing organs manifest cellular asymmetries across the radial axis that underlie afferent versus efferent circuits between the inner ear and the brain. Thus, understanding the molecular control of patterning across this axis has important functional implications. Radial axis patterning begins before the cells become postmitotic, and is likely linked to the onset of asymmetric expression of secreted factors adjacent to the sensory primordium. This study explores one such asymmetrically-expressed gene, Wnt9a, that becomes restricted to the neural edge of the avian auditory organ, the basilar papilla, by embryonic day (E) 5...
August 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821575/ldl-switches-the-lrp6-internalization-route-from-flotillin-dependent-to-clathrin-dependent-in-hepatic-cells
#14
Hideki Yamamoto, Daisuke Umeda, Shinji Matsumoto, Akira Kikuchi
Low-density lipoprotein (LDL) receptor-related protein 6 (LRP6) was originally identified as a coreceptor of the Wnt signaling pathway and has been shown to be involved in LDL transport. In polarized hepatocytes, many apical proteins are sorted to the basolateral membrane and then internalized and transported to the apical bile canalicular membrane-a process known as transcytosis. Herein, we show that LRP6 is transcytosed to the apical membrane of polarized hepatic HepG2 cells via a flotillin-dependent manner in the absence of LDL...
August 18, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28820056/involvement-of-cd24-in-multiple-cancer-related-pathways-makes-it-an-interesting-new-target-for-cancer-therapy
#15
Shirin Eyvazi, Bahram Kazemi, Siavoush Dastmalchi, Mojgan Bandehpour
CD24 (cluster of differentiation 24) is a small heavy glycosylated protein, which is overexpressed in many cancer and some cancer stem cells and is associated with the development, invasion, and metastasis of cancer cells. The exact role of CD24 in these processes is not fully understood, however, in this article, it has been tried to present collection of cancer-related mechanisms attributed to CD24. Based on the literature, CD24 dis-regulates different signaling pathways in various cancer cells, including; Src kinases, STAT3, EGFR, Wnt/β-catenin and MAPK...
August 18, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28819426/central-role-of-cemip-in-tumorigenesis-and-its-potential-as-therapeutic-target
#16
REVIEW
Li Li, Lin-Hai Yan, Shwetha Manoj, Ying Li, Lu Lu
CEMIP (KIAA1199) was identified as migratory indicator protein which had been crudely studied in the last decade. Firstly its mutation site was reported to cause hearing loss due to the folding change of protein structure, meanwhile the over-expression of CEMIP referred to dreadful invasion and uncontrolled proliferation of tumor with distant metastasis, dedifferentiation, and limited survival opportunity of patients. Especially, over-expressed CEMIP also protected malignant tumor from strict microenvironment in hypoxia, low glucose and cracked barrier, leading to enhanced adaptability of tumor by stimulating the Wnt, EGFR, FGFR pathway...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819413/the-role-of-%C3%AE-catenin-in-the-initiation-and-metastasis-of-ta2-mice-spontaneous-breast-cancer
#17
Dan Zhang, Fei Fei, Shuyuan Li, Yongjie Zhao, Zhengduo Yang, Jie Qu, Xipeng Zhang, Yu Yin, Shiwu Zhang
Purpose: Tientsin Albino 2 (TA2) mice have a high incidence of spontaneous breast cancer. Tumor initiation is related to mouse mammary tumor virus (MMTV) infection. MMTV is hormonally regulated and may promote tumor formation via Wnt/β-catenin signaling pathway. This study attempts to clarify the relationship between β-catenin expression and the initiation and metastasis of spontaneous breast cancer in TA2 mice. Materials and Methods: Pathological samples illustrating the development of spontaneous breast cancer in TA2 mice were collected and the presence of virus particles was verified in the cancer tissue by electron microscope...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819407/ccr7-promote-lymph-node-metastasis-via-regulating-vegf-c-d-r3-pathway-in-lung-adenocarcinoma
#18
Jie Yu, Shaolin Tao, Pingping Hu, Ruwen Wang, Chunshu Fang, Yi Xu, Di Qi, Zhuanqin Wei, Jingge Zhang, Qunyou Tan
Lymph node metastasis is still an important issue in metastatic process of lung adenocarcinoma. C-C chemokine receptor 7 (CCR7) has been proved to be closely associated with the metastasis of lung adenocarcinoma, and the mechanism is poorly understood. In order to investigate the relationship between CCR7 and lymph node metastasis in lung adenocarcinoma, and to explore the role of CCR7 in treating lung adenocarcinoma, 40 clinical specimens were collected to define the relationship between CCR7 and lymph node metastasis in lung adenocarcinoma by immunohistochemistry...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28818668/a-bipolar-role-of-the-transcription-factor-erg-for-cnidarian-germ-layer-formation-and-apical-domain-patterning
#19
Aldine R Amiel, Hereroa Johnston, Taylor Chock, Paul Dahlin, Marta Iglesias, Michael Layden, Eric Röttinger, Mark Q Martindale
Germ layer formation and axial patterning are biological processes that are tightly linked during embryonic development of most metazoans. In addition to canonical WNT, it has been proposed that ERK-MAPK signaling is involved in specifying oral as well as aboral territories in cnidarians. However, the effector and the molecular mechanism underlying latter phenomenon is unknown. By screening for potential effectors of ERK-MAPK signaling in both domains, we identified a member of the ETS family of transcription factors, Nverg that is bi-polarily expressed prior to gastrulation...
August 14, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28817727/pilot-study-of-lithium-to-restore-intestinal-barrier-function-in-severe-graft-versus-host-disease
#20
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
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