keyword
MENU ▼
Read by QxMD icon Read
search

Gsk3 Inhibitor

keyword
https://www.readbyqxmd.com/read/29146887/targeted-therapy-of-gastroenteropancreatic-neuroendocrine-tumours-preclinical-strategies-and-future-targets
#1
Elke Tatjana Aristizabal Prada, Christoph J Auernhammer
Molecular targeted therapy of advanced neuroendocrine tumours (NETs) of the gastroenteropancreatic (GEP) system currently encompasses approved therapy with the mTOR-inhibitor everolimus and the multi-tyrosinkinase inhibitor sunitinib. However clinical efficacy of these treatment strategies is limited by low objective response rates and limited progression free survival due to tumor resistance. Further novel strategies for molecular targeted therapy of NETs of the GEP-system are needed. This paper reviews preclinical research models and signaling pathways in NETs of the GEP-system...
November 16, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29092089/notch-wnt-cross-signalling-regulates-stemness-of-dental-pulp-stem-cells-through-expression-of-neural-crest-and-core-pluripotency-factors
#2
V Uribe-Etxebarria, J Luzuriaga, P García-Gallastegui, A Agliano, F Unda, G Ibarretxe
Dental pulp stem cells (DPSCs) from adult teeth express neural crest (NC) markers together with core transcriptional factors associated with stem cell pluripotency, such as Oct4a, Sox2, c-Myc, Rex1, Stella/Dppa3, Ssea1/Fut4, Lin28 and Nanog. The possibility to boost the natural stemness features of DPSCs by mild methods, that do not involve gene and/or chromatin modification or gene transfection, is highly desirable for cell therapy. Canonical Wnt and Notch are two highly conserved developmental signalling pathways that are involved in NC emergence and stem cell self-renewal...
November 1, 2017: European Cells & Materials
https://www.readbyqxmd.com/read/29024409/the-natural-agent-rhein-induces-%C3%AE-catenin-degradation-and-tumour-growth-arrest
#3
Shu Liu, Jiao Wang, Ting Shao, Peiying Song, Qingbin Kong, Hui Hua, Ting Luo, Yangfu Jiang
The natural agent rhein is an ananthraquinone derivative of rhubarb, which has anticancer effects. To determine the mechanisms underlying the anticancer effects of rhein, we detected the effect of rhein on several oncoproteins. Here, we show that rhein induces β-catenin degradation in both hepatoma cell HepG2 and cervical cancer cell Hela. Treatment of HepG2 and Hela cells with rhein shortens the half-life of β-catenin. The proteasome inhibitor MG132 blunts the downregulation of β-catenin by rhein. The induction of β-catenin degradation by rhein is dependent on GSK3 but independent of Akt...
October 11, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29021340/downregulation-of-the-wnt-%C3%AE-catenin-signaling-pathway-by-cacnb4
#4
Mohamad Rima, Marwa Daghsni, Anaïs Lopez, Ziad Fajloun, Lydie Lefrancois, Mireia Dunach, Yasuo Mori, Philippe Merle, Juan L Brusés, Michel de Waard, Michel Ronjat
The β4 isoform of the β-subunits of Voltage-Gated Calcium Channel regulates cell proliferation and cell cycle progression. Herein we show that co-expression of the β4-subunit with actors of the canonical Wnt/β-catenin signaling pathway in a hepatoma cell line inhibits Wnt responsive gene transcription and decreases cell division, in agreement with the role of the Wnt pathway in cell proliferation. β4-subunit-mediated inhibition of Wnt signaling is observed in the presence of LiCl, an inhibitor of GSK3 that promotes β-catenin translocation to the nucleus...
October 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29016121/synthesis-binding-mode-and-antihyperglycemic-activity-of-potent-and-selective-5-imidazol-2-yl-4-phenylpyrimidin-2-yl-2-2-pyridylamino-ethyl-amine-inhibitors-of-glycogen-synthase-kinase-3
#5
Allan S Wagman, Rustum S Boyce, Sean P Brown, Eric Fang, Dane Goff, Johanna M Jansen, Vincent P Le, Barry H Levine, Simon C Ng, Zhi-Jie Ni, John M Nuss, Keith B Pfister, Savithri Ramurthy, Paul A Renhowe, David B Ring, Wei Shu, Sharadha Subramanian, Xiaohui A Zhou, Cynthia M Shafer, Stephen D Harrison, Kirk W Johnson, Dirksen E Bussiere
In an effort to identify new antidiabetic agents, we have discovered a novel family of (5-imidazol-2-yl-4-phenylpyrimidin-2-yl)[2-(2-pyridylamino)ethyl]amine analogues which are inhibitors of human glycogen synthase kinase 3 (GSK3). We developed efficient synthetic routes to explore a wide variety of substitution patterns and convergently access a diverse array of analogues. Compound 1 (CHIR-911, CT-99021, or CHIR-73911) emerged from an exploration of heterocycles at the C-5 position, phenyl groups at C-4, and a variety of differently substituted linker and aminopyridine moieties attached at the C-2 position...
October 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28993455/ehrlichia-activation-of-wnt-pi3k-mtor-signaling-inhibits-autolysosome-generation-and-autophagic-destruction-by-the-mononuclear-phagocyte
#6
Taslima T Lina, Tian Luo, Thangam-Sudha Velayutham, Seema Das, Jere W McBride
In multicellular organisms, autophagy is induced as an innate defense mechanism. Notably, the obligate intracellular bacterium, Ehrlichia chaffeensis, resides in early endosome-like vacuoles and circumvents lysosomal fusion through an unknown mechanism, thereby avoiding destruction in the autophagolysosome. In this study, we reveal that Wnt signaling plays a crucial role in inhibition of lysosomal fusion and autolysosomal destruction of ehrlichiae. During early infection, autophagosomes fuse with ehrlichial vacuoles to form an amphisome indicated by presence of autophagy markers such as LC3, Beclin-1 and p62...
October 9, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28939105/protein-kinase-c-eta-regulates-mcl-1-level-via-erk1
#7
Deepanwita Pal, Alakananda Basu
Protein kinase C (PKC)-eta (PKCη) is a member of the novel category of PKC family. It is overexpressed in breast cancer and was shown to inhibit apoptosis and contribute to chemoresistance. Since the anti-apoptotic Bcl-2 family protein myeloid cell leukemia-1 (Mcl-1) plays an important role in breast cancer cell survival and chemoresistance, we investigated if PKCη regulates Mcl-1 level. Silencing of PKCη decreased Mcl-1 in several breast cancer cells, including MCF-7 and T47D cells. PKCη depletion had no effect on MCL1 mRNA but the decrease in Mcl-1 by PKCη knockdown was blocked by proteasomal inhibitors, such as MG132 and lactacystin...
December 2017: Cellular Signalling
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/28817124/directed-differentiation-and-long-term-maintenance-of-epicardial-cells-derived-from-human-pluripotent-stem-cells-under-fully-defined-conditions
#9
Xiaoping Bao, Xiaojun Lian, Tongcheng Qian, Vijesh J Bhute, Tianxiao Han, Sean P Palecek
Here, we describe how to efficiently direct human pluripotent stem cells (hPSCs) differentiation into self-renewing epicardial cells in a completely defined, xeno-free system by temporal modulation of regulators of canonical Wnt signaling. Appropriate differentiation-stage-specific application of Gsk3 inhibitor, Wnt inhibitor, and Gsk3 inhibitor (GiWiGi) is sufficient to produce cells expressing epicardial markers and exhibiting epicardial phenotypes with a high yield and purity from multiple hPSC lines in 16 d...
September 2017: Nature Protocols
https://www.readbyqxmd.com/read/28800359/the-selective-pi3k%C3%AE-inhibitor-byl719-as-a-novel-therapeutic-option-for-neuroendocrine-tumors-results-from-multiple-cell-line-models
#10
Svenja Nölting, Jakob Rentsch, Helma Freitag, Katharina Detjen, Franziska Briest, Markus Möbs, Victoria Weissmann, Britta Siegmund, Christoph J Auernhammer, Elke Tatjana Aristizabal Prada, Michael Lauseker, Ashley Grossman, Samantha Exner, Christian Fischer, Carsten Grötzinger, Jörg Schrader, Patricia Grabowski
BACKGROUND/AIMS: The therapeutic options for metastatic neuroendocrine tumors (NETs) are limited. As PI3K signaling is often activated in NETs, we have assessed the effects of selective PI3Kp110α inhibition by the novel agent BYL719 on cell viability, colony formation, apoptosis, cell cycle, signaling pathways, differentiation and secretion in pancreatic (BON-1, QGP-1) and pulmonary (H727) NET cell lines. METHODS: Cell viability was investigated by WST-1 assay, colony formation by clonogenic assay, apoptosis by caspase3/7 assay, the cell cycle by FACS, cell signaling by Western blot analysis, expression of chromogranin A and somatostatin receptors 1/2/5 by RT-qPCR, and chromogranin A secretion by ELISA...
2017: PloS One
https://www.readbyqxmd.com/read/28790065/gsk3-inhibition-drives-maturation-of-nk-cells-and-enhances-their-antitumor-activity
#11
Frank Cichocki, Bahram Valamehr, Ryan Bjordahl, Bin Zhang, Betsy Rezner, Paul Rogers, Svetlana Gaidarova, Stacey Moreno, Katie Tuininga, Phillip Dougherty, Valarie McCullar, Peter Howard, Dhifaf Sarhan, Emily Taras, Heinrich Schlums, Stewart Abbot, Daniel Shoemaker, Yenan T Bryceson, Bruce R Blazar, Scott Wolchko, Sarah Cooley, Jeffrey S Miller
Maturation of human natural killer (NK) cells as defined by accumulation of cell-surface expression of CD57 is associated with increased cytotoxic character and TNF and IFNγ production upon target-cell recognition. Notably, multiple studies point to a unique role for CD57(+) NK cells in cancer immunosurveillance, yet there is scant information about how they mature. In this study, we show that pharmacologic inhibition of GSK3 kinase in peripheral blood NK cells expanded ex vivo with IL15 greatly enhances CD57 upregulation and late-stage maturation...
October 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28772167/glycogen-synthase-kinase-3-inhibition-sensitizes-human-induced-pluripotent-stem-cells-to-thiol-containing-antioxidants-induced-apoptosis
#12
Chengyi Tu, Robert Xu, Meghana Koleti, Janet Zoldan
Inhibition of glycogen synthase kinase 3 (GSK3) is an extensively used strategy to activate Wnt pathway for pluripotent stem cell (PSC) differentiation. However, the effects of such inhibition on PSCs, besides upregulating the Wnt pathway, have rarely been investigated despite that GSK3 is broadly involved in other cellular activities such as insulin signaling and cell growth/survival regulation. Here we describe a previously unknown synergistic effect between GSK3 inhibition (e.g., Chir99021 and LY2090314) and various normally non-toxic thiol-containing antioxidants (e...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28714403/gsk3-inhibitors-in-the-therapeutic-development-of-diabetes-cancer-and-neurodegeneration-past-present-and-future
#13
Mudasir Maqbool, Nasimul Hoda
GSK3 has gained a considerable attention of researchers in the late 1970s as an inevitable drug target to treat diabetes. Furthermore, it was found to have a key role in the development of diseases like cancer and neurodegeneration (ND). A broad spectrum of GSK3 inhibitors have been discovered from time to time in order to curb these diseases. Inhibition of GSK3 by insulin boosts the dephosphorylation of glycogen synthase, hence its activation to convert UDP glucose into glycogen. Lack of insulin and insulin-resistance is supposed to be the cause of type 2 diabetes (Diabetes mellitus)...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28713919/ganetespib-induces-g2-m-cell-cycle-arrest-and-apoptosis-in-gastric-cancer-cells-through-targeting-of-receptor-tyrosine-kinase-signaling
#14
Harry Lee, Nipun Saini, Amanda B Parris, Ming Zhao, Xiaohe Yang
Heat shock protein 90 (HSP90) regulates several important cellular processes via its repertoire of 'client proteins'. These client proteins have been found to play fundamental roles in signal transduction, cell proliferation, cell cycle progression and survival, as well as other features of malignant cells, such as invasion, tumor angiogenesis and metastasis. Thus, HSP90 is an emerging target for cancer therapy. To this end, we evaluated ganetespib (STA-9090), a novel and potent HSP90 inhibitor, for its activity in gastric cancer cell lines...
September 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28710230/the-tissue-reconstructing-ability-of-colon-cscs-is-enhanced-by-fk506-and-suppressed-by-gsk3-inhibition
#15
Ryo Ishida, Michiyo Koyanagi-Aoi, Nobu Oshima, Yoshihiro Kakeji, Takashi Aoi
Cancer stem cells (CSC) are capable of reconstructing cancer tissues, are involved in both recurrence and metastasis, and contribute to therapeutic resistance. Therefore, elucidating the molecular mechanism in CSCs is important to successfully treat unresectable cancers. Previously, we observed that colon cancer stem-like cells can be induced from human colon cancer cell lines by retrovirally introducing OCT3/4, SOX2, and KLF4, and we have designated such cells as induced cancer stem cells (iCSC). In the current study, we used iCSCs to evaluate the molecular mechanism of colon CSCs and developed new methods to control them...
July 14, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28698144/inhibiting-glycogen-synthase-kinase-3-and-transforming-growth-factor-%C3%AE-signaling-to-promote-epithelial-transition-of-human-adipose-mesenchymal-stem-cells
#16
Melina Setiawan, Xiao-Wei Tan, Tze-Wei Goh, Gary Hin-Fai Yam, Jodhbir S Mehta
BACKGROUND: This study was aimed to investigate the epithelial differentiation of human adipose-derived mesenchymal stem cells (ADSCs) by inhibiting glycogen synthase kinase-3 (GSK3) and transforming growth factor β (TGFβ) signaling. METHODS AND RESULTS: STEMPRO human ADSCs at passage 2 were treated with CHIR99021 (GSK3 inhibitor), E-616452 (TGFβ1 receptor kinase inhibitor), A-83-01 (TGFβ type 1 receptor inhibitor), valproic acid (histone deacetylase inhibitor), tranylcypromine (monoamine oxidase inhibitor) and all-trans retinoic acid for 72 h...
September 2, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28662520/regulation-of-ap-1-by-mapk-signaling-in-metal-stressed-sea-anemone
#17
Maayan Agron, Vera Brekhman, David Morgenstern, Tamar Lotan
BACKGROUND/AIMS: AP-1 transcription factor plays a conserved role in the immediate response to stress. Activation of AP-1 members jun and fos is mediated by complex signaling cascades to control cell proliferation and survival. To understand the evolution of this broadly-shared pathway, we studied AP-1 regulation by MAPK signaling in a basal metazoan. METHODS: Metal- stressed cnidarian Nematostella vectensis anemones were tested with kinase inhibitors and analyzed for gene expression levels and protein phosphorylation...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28638078/the-stress-response-factor-daf-16-foxo-is-required-for-multiple-compound-families-to-prolong-the-function-of-neurons-with-huntington-s-disease
#18
Francesca Farina, Emmanuel Lambert, Lucie Commeau, François-Xavier Lejeune, Nathalie Roudier, Cosima Fonte, J Alex Parker, Jacques Boddaert, Marc Verny, Etienne-Emile Baulieu, Christian Neri
Helping neurons to compensate for proteotoxic stress and maintain function over time (neuronal compensation) has therapeutic potential in aging and neurodegenerative disease. The stress response factor FOXO3 is neuroprotective in models of Huntington's disease (HD), Parkinson's disease and motor-neuron diseases. Neuroprotective compounds acting in a FOXO-dependent manner could thus constitute bona fide drugs for promoting neuronal compensation. However, whether FOXO-dependent neuroprotection is a common feature of several compound families remains unknown...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28625976/a-genome-wide-crispr-screen-identifies-genes-critical-for-resistance-to-flt3-inhibitor-ac220
#19
Panpan Hou, Chao Wu, Yuchen Wang, Rui Qi, Dheeraj Bhavanasi, Zhixiang Zuo, Cedric Dos Santos, Shuliang Chen, Yu Chen, Hong Zheng, Hong Wang, Alexander Perl, Deyin Guo, Jian Huang
Acute myeloid leukemia (AML) is a malignant hematopoietic disease and the most common type of acute leukemia in adults. The mechanisms underlying drug resistance in AML are poorly understood. Activating mutations in FMS-like tyrosine kinase 3 (FLT3) are the most common molecular abnormality in AML. Quizartinib (AC220) is a potent and selective second-generation inhibitor of FLT3. It is in clinical trials for the treatment of relapsed or refractory FLT3-ITD-positive and -negative AML patients and as maintenance therapy...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28606794/antifibrotic-actions-of-peroxisome-proliferator-activated-receptor-%C3%AE-ligands-in-corneal-fibroblasts-are-mediated-by-%C3%AE-catenin-regulated-pathways
#20
Kye-Im Jeon, Richard P Phipps, Patricia J Sime, Krystel R Huxlin
Wound healing after corneal injury typically involves fibrosis, with transforming growth factor β1 (TGF-β1) as one of its strongest mediators. A class of small molecules-peroxisome proliferator-activated receptor γ (PPARγ) ligands-exert potent antifibrotic effects in the cornea by blocking phosphorylation of p38 mitogen-activated protein kinase (MAPK). However, why this blocks fibrosis remains unknown. Herein, we show that PPARγ ligands (rosiglitazone, troglitazone, and 15-deoxy-Δ12,14-prostaglandin J2) decrease levels of β-catenin...
August 2017: American Journal of Pathology
keyword
keyword
115967
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"