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ICG-001

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https://www.readbyqxmd.com/read/29596326/differentiation-therapy-targeting-the-%C3%AE-catenin-cbp-interaction-in-pancreatic-cancer
#1
Philipp Manegold, Keane K Y Lai, Yongfeng Wu, Jia-Ling Teo, Heinz-Josef Lenz, Yuri S Genyk, Stephen J Pandol, Kaijin Wu, David P Lin, Yibu Chen, Cu Nguyen, Yi Zhao, Michael Kahn
BACKGROUND: Although canonical Wnt signaling is known to promote tumorigenesis in pancreatic ductal adenocarcinoma (PDAC), a cancer driven principally by mutant K-Ras , the detailed molecular mechanisms by which the Wnt effector β-catenin regulates such tumorigenesis are largely unknown. We have previously demonstrated that β-catenin's differential usage of the Kat3 transcriptional coactivator cyclic AMP-response element binding protein-binding protein (CBP) over its highly homologous coactivator p300 increases self-renewal and suppresses differentiation in other types of cancer...
March 29, 2018: Cancers
https://www.readbyqxmd.com/read/29514683/a-loss-of-function-genetic-screening-reveals-synergistic-targeting-of-akt-mtor-and-wtn-%C3%AE-catenin-pathways-for-treatment-of-aml-with-high-prl-3-phosphatase
#2
Jianbiao Zhou, Sabrina Hui-Min Toh, Zit-Liang Chan, Jessie Yiying Quah, Jing-Yuan Chooi, Tuan Zea Tan, Phyllis S Y Chong, Qi Zeng, Wee-Joo Chng
BACKGROUND: Protein tyrosine phosphatase of regenerating liver 3 (PRL-3) is overexpressed in a subset of AML patients with inferior prognosis, representing an attractive therapeutic target. However, due to relatively shallow pocket of the catalytic site of PRL-3, it is difficult to develop selective small molecule inhibitor. METHODS: In this study, we performed whole-genome lentiviral shRNA library screening to discover synthetic lethal target to PRL-3 in AML. We used specific small molecule inhibitors to validate the synthetic lethality in human PRL-3 high vs PRL-3 low human AML cell lines and primary bone marrow cells from AML patients...
March 7, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29499919/ultrasound-irradiation-combined-with-hepatocyte-growth-factor-accelerate-the-hepatic-differentiation-of-human-bone-marrow-mesenchymal-stem-cells
#3
Fan Li, Yang Liu, Yingyu Cai, Xin Li, Min Bai, Ting Sun, Lianfang Du
This study investigated the impact of ultrasound (US) irradiation on the hepatic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) induced by hepatocyte growth factor (HGF) and the possible mechanisms. We treated hBMSCs, using HGF with and without US irradiation. Cell viability and stem cell surface markers were analyzed. Hepatocyte-like cell markers and functional markers including α-fetoprotein (αFP/AFP), cytokeratin 18 (CK18), albumin (ALB) and glycogen content were analyzed at the time point of day 1, 3 and 5 after treatment...
February 28, 2018: Ultrasound in Medicine & Biology
https://www.readbyqxmd.com/read/29481294/mmp20-overexpression-disrupts-molar-ameloblast-polarity-and-migration
#4
M Shin, M B Chavez, A Ikeda, B L Foster, J D Bartlett
Ameloblasts responsible for enamel formation express matrix metalloproteinase 20 (MMP20), an enzyme that cleaves enamel matrix proteins, including amelogenin (AMELX) and ameloblastin (AMBN). Previously, we showed that continuously erupting incisors from transgenic mice overexpressing active MMP20 had a massive cell infiltrate present within their enamel space, leading to enamel mineralization defects. However, effects of MMP20 overexpression on mouse molars were not analyzed, although these teeth more accurately represent human odontogenesis...
February 1, 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29416335/human-%C3%AE-defensin-3-combined-gold-nanoparticles-for-enhancement-of-osteogenic-differentiation-of-human-periodontal-ligament-cells-in-inflammatory-microenvironments
#5
Jing Zhou, Yangheng Zhang, Lingjun Li, Huangmei Fu, Wenrong Yang, Fuhua Yan
Objective: It is a great challenge to absorb and conduct biophysicochemical interactions at the nano-bio interface. Peptides are emerging as versatile materials whose function can be programmed to perform specific tasks. Peptides combined nanoparticles might be utilized as a new approach of treatment. Human β-defensin 3 (hBD3), possesses both antimicrobial and proregeneration properties. Gold nanoparticles (AuNPs) have shown promising applications in the field of tissue engineering. However, the coordinating effects of AuNPs and hBD3 on human periodontal ligament cells (hPDLCs) remain unknown...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29363326/wnt-signaling-is-required-for-peritoneal-membrane-angiogenesis
#6
Manreet Kaur Padwal, Genyang Cheng, Limin Liu, Felix J Boivin, Azim Gangji, Kenneth Scott Brimble, Darren Bridgewater, Peter J Margetts
The WNT signaling pathway is involved in wound healing and fibrosis. We evaluated the WNT signaling pathway in peritoneal membrane injury. We assessed WNT1 protein expression in the peritoneal effluents of 54 stable peritoneal dialysis (PD) patients and WNT-related gene expression in ex vivo mesothelial cell cultures from 21 PD patients. In a transforming growth factor beta (TGFB) mediated animal model of peritoneal fibrosis, we evaluated regulation of the WNT pathway and the effect of WNT inhibition on peritoneal fibrosis and angiogenesis...
January 24, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29332125/icg-001-exerts-potent-anticancer-activity-against-uveal-melanoma-cells
#7
Salma Kaochar, Jianrong Dong, Marie Torres, Kimal Rajapakshe, Fotis Nikolos, Christel M Davis, Erik A Ehli, Cristian Coarfa, Nicholas Mitsiades, Vasiliki Poulaki
Purpose: Uveal melanoma (UM) is uniformly refractory to all available systemic chemotherapies, thus creating an urgent need for novel therapeutics. In this study, we investigated the sensitivity of UM cells to ICG-001, a small molecule reported to suppress the Wnt/β-catenin-mediated transcriptional program. Methods: We used a panel of UM cell lines to examine the effects of ICG-001 on cellular proliferation, migration, and gene expression. In vivo efficacy of ICG-001 was evaluated in a UM xenograft model...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29316250/dual-inhibition-of-wnt-and-yes-associated-protein-signaling-retards-the-growth-of-triple-negative-breast-cancer-in-both-mesenchymal-and-epithelial-states
#8
Andrew Sulaiman, Sarah McGarry, Li Li, Deyong Jia, Sarah Ooi, Christina Addison, Jim Dimitroulakos, Angel Arnaout, Carolyn Nessim, Zemin Yao, Guang Ji, Haiyan Song, Suresh Gadde, Xuguang Li, Lisheng Wang
Triple-negative breast cancer (TNBC), the most refractory subtype of breast cancer to current treatments, accounts disproportionately for the majority of breast cancer-related deaths. This is largely due to cancer plasticity and the development of cancer stem cells (CSCs). Recently, distinct yet interconvertible mesenchymal-like and epithelial-like states have been revealed in breast CSCs. Thus, strategies capable of simultaneously inhibiting bulk and CSC populations in both mesenchymal and epithelial states have yet to be developed...
April 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29290987/icg-001-affects-drp1-activity-and-er-stress-correlative-with-its-anti-proliferative-effect
#9
Heidi Zinecker, Djamila Ouaret, Daniel Ebner, Moritz M Gaidt, Steve Taylor, Anna Aulicino, Marta Jagielowicz, Veit Hornung, Alison Simmons
Mitochondria form a highly dynamic network driven by opposing scission and fusion events. DRP1 is an essential modulator of mitochondrial fission and dynamics within mammalian cells. Its fission activity is regulated by posttranslational modifications such as activating phosphorylation at serine 616. DRP1 activity has recently been implicated as being dysregulated in numerous human disorders such as cancer and neurodegenerative diseases. Here we describe the development of a cell-based screening assay to detect DRP1 activation...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29237155/paracrine-activation-of-the-wnt-%C3%AE-catenin-pathway-by-bone-marrow-stem-cell-attenuates-cisplatin-induced-kidney-injury
#10
Xiaoyan Jiao, Jieru Cai, Xiaofang Yu, Xiaoqiang Ding
BACKGROUND/AIMS: Cisplatin-induced acute kidney injury (AKI) involves damage to tubular cells via excess reactive oxygen species (ROS) generation. Stem cell-based therapies have shown great promise in AKI treatment. In this study, we aimed to assess the protective effect and mechanism of bone marrow mesenchymal stem cell (BMSC)-derived conditioned medium (CM) against cisplatin-induced AKI. METHODS: In vitro, NRK-52E cells were incubated with cisplatin in the presence or absence of CM, followed by the assessment of cell viability, apoptosis and cell cycle distribution...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29224185/tension-force-induced-bone-formation-in-orthodontic-tooth-movement-via-modulation-of-the-gsk-3%C3%AE-%C3%AE-catenin-signaling-pathway
#11
Yelin Mao, Liangliang Wang, Ye Zhu, Yu Liu, Hongwei Dai, Jianping Zhou, Dechun Geng, Lin Wang, Yong Ji
Orthodontic force-induced osteogenic differentiation and bone formation at tension sites play a critical role in orthodontic tooth movement. However, the molecular mechanism underlying this phenomenon is poorly understood. In the current study, we investigated the involvement of the GSK-3β/β-catenin signaling pathway, which is critical for bone formation during tooth movement. We established a rat tooth movement model to test the hypothesis that orthodontic force may stimulate bone formation at the tension site of the moved tooth and promote the rate of tooth movement via regulation of the GSK-3β/β-catenin signaling pathway...
February 2018: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29217140/inhibition-of-canonical-wnt-signaling-pathway-by-%C3%AE-catenin-cbp-inhibitor-icg-001-ameliorates-liver-fibrosis-in-vivo-through-suppression-of-stromal-cxcl12
#12
Büsra Öztürk Akcora, Gert Storm, Ruchi Bansal
Quiescent hepatic stellate cells (HSCs), in response to liver injury, undergo characteristic morphological transformation into proliferative, contractile and ECM-producing myofibroblasts. In this study, we investigated the implication of canonical Wnt signaling pathway in HSCs and liver fibrogenesis. Canonical Wnt signaling pathway activation and inhibition using β-catenin/CBP inhibitor ICG001 was examined in-vitro in TGFβ-activated 3T3, LX2, primary human HSCs, and in-vivo in CCl4 -induced acute liver injury mouse model...
March 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29180394/redirecting-tgf-%C3%AE-signaling-through-the-%C3%AE-catenin-foxo-complex-prevents-kidney-fibrosis
#13
Xi Qiao, Padmashree Rao, Yun Zhang, Lixin Liu, Min Pang, Hailong Wang, Min Hu, Xinrui Tian, Jianlin Zhang, Ye Zhao, Xin Maggie Wang, Chengshi Wang, Hong Yu, Fei Guo, Qi Cao, Yiping Wang, Yuan Min Wang, Geoff Yu Zhang, Vincent W Lee, Stephen I Alexander, Guoping Zheng, David C H Harris
TGF- β is a key profibrotic factor, but targeting TGF- β to prevent fibrosis also abolishes its protective anti-inflammatory effects. Here, we investigated the hypothesis that we can redirect TGF- β signaling by preventing downstream profibrotic interaction of β -catenin with T cell factor (TCF), thereby enhancing the interaction of β -catenin with Foxo, a transcription factor that controls differentiation of TGF- β induced regulatory T cells (iTregs), and thus, enhance anti-inflammatory effects of TGF- β In iTregs derived from EL4 T cells treated with recombinant human TGF- β 1 (rhTGF- β 1) in vitro , inhibition of β -catenin/TCF transcription with ICG-001 increased Foxp3 expression, interaction of β -catenin and Foxo1, binding of Foxo1 to the Foxp3 promoter, and Foxo transcriptional activity...
February 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29141249/%C3%AE-catenin-cooperates-with-creb-binding-protein-to-promote-the-growth-of-tumor-cells
#14
Wendan Yu, Liren Li, Fufu Zheng, Wenjing Yang, Shilei Zhao, Chunfang Tian, Wenwen Yin, Yiming Chen, Wei Guo, Lijuan Zou, Wuguo Deng
BACKGROUND/AIMS: β-catenin is an integral component of the canonical Wnt signaling pathway, and its mutations are an autosomal recessive cause of colorectal cancer (CRC), medulloblastoma (MDB), and ovarian cancer. Nevertheless, little is known about its function in lung cancers. METHODS: We first knocked down β-catenin by siRNA to investigate its effects on lung cancer cell proliferation, migration and apoptosis. Then we verified the interaction between β-catenin and CREB binding protein (CBP) by immunofluoresence and co-immunoprecipition assays...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#15
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
November 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28933312/characterization-of-imatinib-resistant-cml-leukemic-stem-initiating-cells-and-their-sensitivity-to-cbp-catenin-antagonists
#16
Yi Zhao, Kaijin Wu, Yongfeng Wu, Elizabeth Melendez, Goar Smbatyan, David Massiello, Michael Kahn
The development of the tyrosine kinase inhibitor Imatinib (IM) represents a milestone breakthrough in CML (Chronic Myeloid Leukemia) treatment. However, it is not curative and patients develop IM resistance. IM resistance has been previously correlated with the emergence of drug-resistant LIC/LSC (Leukemia Initiating Cell/Leukemia Stem Cell) and increased nuclear catenin levels and enhanced Wnt signaling. It has been demonstrated previously that drug resistant CML LIC/LSC can be safely eliminated both in vitro and in vivo via disruption of the CBP/catenin interaction, utilizing the highly biochemically selective small molecule CBP/catenin antagonist ICG-001...
September 19, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28893318/icg-001-suppresses-growth-of-gastric-cancer-cells-and-reduces-chemoresistance-of-cancer-stem-cell-like-population
#17
Yi Liu, Hui Chen, Peiming Zheng, Yingxia Zheng, Qin Luo, Guohua Xie, Yanhui Ma, Lisong Shen
BACKGROUND: ICG-001, a small molecule, binds CREB-binding protein (CBP) to disrupt its interaction with β-catenin and inhibits CBP function as a co-activator of Wnt/β-catenin-mediated transcription. Given its ability to inhibit Wnt/β-catenin signaling pathway, ICG-001 has been used in some tumor types to exert its anticarcinogenic effect. Here, we examined ICG-001 and its potential role as a therapeutic in gastric cancer (GC). METHODS: The gastric cancer cell lines SGC-7901, MGC-803, BGC-823 and MKN-45 were used in vitro and in vivo...
September 11, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28837560/wnt-%C3%AE-catenin-signaling-pathway-inhibits-the-proliferation-and-apoptosis-of-u87-glioma-cells-via-different-mechanisms
#18
Liyang Gao, Bing Chen, Jinhong Li, Fan Yang, Xuecheng Cen, Zhuangbing Liao, Xiao'ao Long
The Wnt signaling pathway is necessary for the development of the central nervous system and is associated with tumorigenesis in various cancers. However, the mechanism of the Wnt signaling pathway in glioma cells has yet to be elucidated. Small-molecule Wnt modulators such as ICG-001 and AZD2858 were used to inhibit and stimulate the Wnt/β-catenin signaling pathway. Techniques including cell proliferation assay, colony formation assay, Matrigel cell invasion assay, cell cycle assay and Genechip microarray were used...
2017: PloS One
https://www.readbyqxmd.com/read/28810055/impact-of-mir-26b-on-cardiomyocyte-differentiation-in-p19-cells-through-regulating-canonical-non-canonical-wnt-signalling
#19
Duo Wang, Chang Liu, Yumei Wang, Wenjing Wang, Kang Wang, Xiujuan Wu, Zhigang Li, Cuimei Zhao, Li Li, Luying Peng
BACKGROUND AND OBJECTIVES: The control of cardiomyocyte differentiation is tightly linked to microRNAs (miRNAs), which have been emerging as important players in heart development. However, the regulation mechanisms mediated by miRNAs in early heart development remains speculative. Here, we evaluated the impact of miR-26b during the progression of cardiomyocyte differentiation from the P19 cell line. MATERIALS AND METHODS: The overexpression of miR-26b in P19 cells was performed by transduction with lentivirus vector...
December 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28732196/sam68-offers-selectively-aimed-modulation-of-transcription-in-cancer-stem-cells
#20
COMMENT
Kai Fu, Fengyi Wan
In this issue of Cell Chemical Biology,Benoit et al. (2017) report the selective targeting of cancer stem cells (CSCs) by the ICG-001/CWP family of molecules. Their findings reveal that Sam68 is a transcriptional modulator uniquely required for the dysregulated Wnt/β-catenin signaling in CSCs over healthy stem cells.
July 20, 2017: Cell Chemical Biology
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