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HES1 Inhibitor

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https://www.readbyqxmd.com/read/28086833/delta-like-4-notch-signaling-promotes-apc-min-tumor-initiation-through-angiogenic-and-non-angiogenic-related-mechanisms
#1
Marina Badenes, Alexandre Trindade, Hugo Pissarra, Luís Lopes-da-Costa, António Duarte
BACKGROUND: Delta like 4 (Dll4)/Notch signaling is a key regulator of tumor angiogenesis. Additionally, the role of Dll4 has been studied on tumor stem cells. However, as these cells are implicated in tumor angiogenesis, it is conceivable that the effect of Dll4 on these cells may be a consequence of its angiogenic function. Our aim was to evaluate the expression and dissect the functions of Dll4 in the Apc (Min/+) model of colorectal cancer. METHODS: We evaluated the protein expression pattern of Dll4 and other Notch members in the Apc (Min/+) tumors relatively to the normal gut and compared endothelial-specific with ubiquitous Dll4 knockout mice on an Apc (Min/+) background...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28079885/mirna182-regulates-percentage-of-myeloid-and-erythroid-cells-in-chronic-myeloid-leukemia
#2
Deepak Arya, Sasikala P Sachithanandan, Cecil Ross, Dasaradhi Palakodeti, Shang Li, Sudhir Krishna
The deregulation of lineage control programs is often associated with the progression of haematological malignancies. The molecular regulators of lineage choices in the context of tyrosine kinase inhibitor (TKI) resistance remain poorly understood in chronic myeloid leukemia (CML). To find a potential molecular regulator contributing to lineage distribution and TKI resistance, we undertook an RNA-sequencing approach for identifying microRNAs (miRNAs). Following an unbiased screen, elevated miRNA182-5p levels were detected in Bcr-Abl-inhibited K562 cells (CML blast crisis cell line) and in a panel of CML patients...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28058624/zebrafish-phenotypic-screen-identifies-novel-notch-antagonists
#3
Vithya Velaithan, Kazuhide Shaun Okuda, Mei Fong Ng, Norazwana Samat, Sze Wei Leong, Siti Munirah Mohd Faudzi, Faridah Abas, Khozirah Shaari, Sok Ching Cheong, Pei Jean Tan, Vyomesh Patel
Zebrafish represents a powerful in vivo model for phenotype-based drug discovery to identify clinically relevant small molecules. By utilizing this model, we evaluated natural product derived compounds that could potentially modulate Notch signaling that is important in both zebrafish embryogenesis and pathogenic in human cancers. A total of 234 compounds were screened using zebrafish embryos and 3 were identified to be conferring phenotypic alterations similar to embryos treated with known Notch inhibitors...
January 5, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28028172/histone-deacetylase-1-is-essential-for-rod-photoreceptor-differentiation-by-regulating-acetylation-at-histone-h3-lysine-9-and-histone-h4-lysine-12-in-the-mouse-retina
#4
Renata C Ferreira, Evgenya Y Popova, Jessica James, Marcelo Rs Briones, Samuel S Zhang, Colin J Barnstable
Histone acetylation has a regulatory role in gene expression and is necessary for proper tissue development. To investigate the specific roles of histone deacetylases (HDACs) in rod differentiation in neonatal mouse retinas we used a pharmacological approach which showed that inhibition of class I but not class IIa HDACs caused the same phenotypic changes seen with broad spectrum HDAC inhibitors, most notably a block in the differentiation of rod photoreceptors. Inhibition of HDAC1 resulted in increase of acetylation of lysine 9 of histone 3 (H3K9) and lysine 12 of histone 4 (H4K12), but not lysine 27 of histone 3 (H3K27), and led to maintained expression of progenitor-specific genes such as Vsx2 and Hes1 with concomitant block of expression of rod-specific genes...
December 27, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27981247/aspartate-%C3%AE-hydroxylase-asph-a-potential-therapeutic-target-in-human-malignant-gliomas
#5
Lisa-Marie Sturla, Ming Tong, Nick Hebda, Jinsong Gao, John-Michael Thomas, Mark Olsen, Suzanne M de la Monte
BACKGROUND: Despite therapeutic advances, survival with glioblastoma multiforme (GBM) remains below 15 months from diagnosis due to GBM's highly infiltrative nature which precludes complete surgical resection. Patient outcomes could potentially be improved by targeting genes and pathways that drive neoplastic cell motility and invasiveness, including hypoxia-inducible factor-1 (HIF-1α), NOTCH, and aspartate-β-hydroxylase (ASPH). METHODS: Human astrocytoma biopsy specimens (n = 37), WHO Grades II-IV, were analyzed for levels and distributions of ASPH and HIF-1α immunoreactivity by immunohistochemical staining, and ASPH, Notch, JAG, HES1, HEY1 and HIF1α mRNA expression by quantigene multiplex analysis...
December 2016: Heliyon
https://www.readbyqxmd.com/read/27966788/notch-signaling-participates-in-tgf-%C3%AE-induced-sost-expression-under-intermittent-compressive-stress
#6
Jeeranan Manokawinchoke, Piyamas Sumrejkanchanakij, Prasit Pavasant, Thanaphum Osathanon
Notch signaling is regulated by mechanical stimuli in various cell types. It has previously been reported that intermittent compressive stimuli enhanced sclerostin (SOST) expression in human periodontal ligament cells (hPDLs) by regulating transforming growth factor-β (TGF-β) expression. The aim of the present study was to determine the involvement of Notch signaling in the TGF-β induced SOST expression in hPDLs. Cells were treated with intermittent compressive stress in a computer-controlled apparatus for 24 h...
December 14, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27939630/endosulfan-inhibits-proliferation-through-the-notch-signaling-pathway-in-human-umbilical-vein-endothelial-cells
#7
Jialiu Wei, Lianshuang Zhang, Lihua Ren, Jin Zhang, Yang Yu, Ji Wang, Junchao Duan, Cheng Peng, Zhiwei Sun, Xianqing Zhou
Our previous research showed that endosulfan triggers the extrinsic coagulation pathway by damaging endothelial cells and causes hypercoagulation of blood. To identify the mechanism of endosulfan-impaired endothelial cells, we treated human umbilical vein endothelial cells (HUVECs) with different concentrations of endosulfan, with and without an inhibitor for Notch, N-[N-(3, 5-difluorophenacetyl)-1-alanyl]S-Phenylglycinet-butylester (DAPT, 20 μM), or a reactive oxygen species (ROS) scavenger, N-Acetyl-l-cysteine (NAC, 3 mM), for 24 h...
February 2017: Environmental Pollution
https://www.readbyqxmd.com/read/27908834/gamma-secretase-inhibitor-impairs-epithelial-to-mesenchymal-transition-induced-by-tgf-%C3%AE-in-ovarian-tumor-cell-lines
#8
M C Pazos, D Abramovich, A Bechis, P Accialini, F Parborell, M Tesone, G Irusta
Ovarian cancer is characterized by being highly metastatic, a feature that represents the main cause of failure of the treatment. This study investigated the effects of γ-secretase inhibition on the TGF-β-induced epithelial-mesenchymal transition (EMT) process in ovarian cancer cell lines. SKOV3 cells incubated in the presence of TGF-β showed morphological and biochemical changes related to EMT, which were blocked by co-stimulation with TGF-β and the γ-secretase inhibitor DAPT. In SKOV3 and IGROV1 cells, the co-stimulation blocked the cadherin switch and the increase in the transcription factors Snail, Slug, Twist and Zeb1 induced by TGF-β...
January 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27880939/inhibition-of-the-transcriptional-repressor-complex-bcl-6-bcor-induces-endothelial-sprouting-but-does-not-promote-tumor-growth
#9
Elisabeth Buchberger, Dietmar Payrhuber, Miriam El Harchi, Branislav Zagrapan, Katharina Scheuba, Anna Zommer, Edina Bugyik, Balazs Dome, Julia Barbara Kral, Waltraud Cornelia Schrottmaier, Gernot Schabbauer, Peter Petzelbauer, Marion Gröger, Martin Bilban, Christine Brostjan
The oncogenic potential of the transcriptional repressor Bcl-6 (B-cell lymphoma 6) was originally discovered in non-Hodgkin patients and the soluble Bcl-6 inhibitor 79-6 was developed to treat diffuse large B-cell lymphomas with aberrant Bcl-6 expression. Since we found Bcl-6 and its co-repressor BCoR (Bcl-6 interacting co-repressor) to be regulated in human microvascular endothelium by colorectal cancer cells, we investigated their function in sprouting angiogenesis which is central to tumor growth. Based on Bcl-6/BCoR gene silencing we found that the transcriptional repressor complex in fact constitutes an endogenous inhibitor of vascular sprouting by supporting the stalk cell phenotype: control of Notch target genes (HES1, HEY1, DLL4) and cell cycle regulators (cyclin A and B1)...
November 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27861873/notch-signaling-pathway-regulates-angiogenesis-via-endothelial-cell-in-3d-co-culture-model
#10
Dan Zhao, Changyue Xue, Shiyu Lin, Sirong Shi, Qianshun Li, Mengting Liu, Xiaoxiao Cai, Yunfeng Lin
This study aimed to investigate the role of Notch signaling pathway for angiogenesis in a three-dimensional (3D) collagen gel model with co-culture of adipose-derived stromal cells (ASCs) and endothelial cells (ECs). A 3D collagen gel model was established in vitro by implanting both ASCs from green fluorescent protein-labeled mouse and ECs from red fluorescent protein-labeled mouse, and the phenomena of angiogenesis with Notch signaling inducer Jagged1, inhibitor DAPT and PBS, respectively were observed by confocal laser scanning microscopy...
November 10, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27852366/-effects-and-mechanisms-of-notch-signaling-pathway-on-immune-imbalance-in-chronic-obstructive-pulmonary-disease
#11
X N Yang, X J Liu, L T Zhao, X L Zeng, H R Bao
Objective: To explore the role of Notch signaling pathway on immune imbalance in chronic obstructive pulmonary disease (COPD). Methods: Thirty BALB/c mice were randomly assigned into the healthy control group, COPD group, and COPD Gamma secretase inhibitors (GSI) group. Cigarette smoke exposure was used to establish the COPD model. T cells were enriched by filtering through nylon wool columns. The proportion of spleen-derived T-lymphocyte subsets was detected by flow cytometry. Real-time quantitative polymerase chain reaction (RT-PCR) and Western blot (WB) were used to detect the expression of splenic T cells' Notch1 and its downstream Hes1 mRNA and protein respectively...
November 12, 2016: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/27821050/stringent-comparative-sequence-analysis-reveals-sox10-as-a-putative-inhibitor-of-glial-cell-differentiation
#12
Chetna Gopinath, William D Law, José F Rodríguez-Molina, Arjun B Prasad, Lingyun Song, Gregory E Crawford, James C Mullikin, John Svaren, Anthony Antonellis
BACKGROUND: The transcription factor SOX10 is essential for all stages of Schwann cell development including myelination. SOX10 cooperates with other transcription factors to activate the expression of key myelin genes in Schwann cells and is therefore a context-dependent, pro-myelination transcription factor. As such, the identification of genes regulated by SOX10 will provide insight into Schwann cell biology and related diseases. While genome-wide studies have successfully revealed SOX10 target genes, these efforts mainly focused on myelinating stages of Schwann cell development...
November 7, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27807176/hiv-tat-impairs-neurogenesis-through-functioning-as-a-notch-ligand-and-activation-of-notch-signaling-pathway
#13
Yan Fan, Xiang Gao, Jinhui Chen, Ying Liu, Johnny J He
: Alterations in adult neurogenesis have been noted in the brain of HIV-infected individuals and are likely linked to HIV-associated neurocognitive deficits, including those in learning and memory. But the underlying molecular mechanisms are not fully understood. In the study, we took advantage of doxycycline-inducible and astrocyte-specific HIV-1 Tat transgenic mice (iTat) and determined the relationship between Tat expression and neurogenesis. Tat expression in astrocytes was associated with fewer neuron progenitor cells (NPCs), fewer immature neurons, and fewer mature neurons in the dentate gyrus of the hippocampus of the mouse brain...
November 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27760204/fine-tuning-of-the-kaposi-s-sarcoma-associated-herpesvirus-life-cycle-in-neighboring-cells-through-the-rta-jag1-notch-pathway
#14
Shasha Li, Hao Hu, Zhiheng He, Deguang Liang, Rui Sun, Ke Lan
Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is an oncogenic pathogen that displays latent and lytic life cycles. In KS lesions, infiltrated immune cells, secreted viral and/or cellular cytokines, and hypoxia orchestrate a chronic pro-lytic microenvironment that can promote KSHV reactivation. However, only a small subset of viruses spontaneously undergoes lytic replication in this pro-lytic microenvironment while the majority remains in latency. Here, we show that the expression of the Notch ligand JAG1 is induced by KSHV-encoded replication and transcription activator (RTA) during reactivation...
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27753144/melatonin-rescues-cardiac-thioredoxin-system-during-ischemia-reperfusion-injury-in-acute-hyperglycemic-state-by-restoring-notch1-hes1-akt-signaling-in-a-membrane-receptor-dependent-manner
#15
Liming Yu, Chongxi Fan, Zhi Li, Jian Zhang, Xiaodong Xue, Yinli Xu, Guolong Zhao, Yang Yang, Huishan Wang
Stress hyperglycemia is commonly observed in patients suffering from ischemic heart disease. It not only worsens cardiovascular prognosis but also attenuates the efficacies of various cardioprotective agents. This study aimed to investigate the protective effect of melatonin against myocardial ischemia-reperfusion (MI/R) injury in acute hyperglycemic state with a focus on Notch1/Hes1/Akt signaling and intracellular thioredoxin (Trx) system. Sprague Dawley rats were subjected to MI/R surgery and high-glucose (HG, 500 g/L) infusion (4 mL/kg/h) to induce temporary hyperglycemia...
January 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/27677287/numb-notch-signaling-pathway-modulation-enhances-human-pancreatic-cancer-cell-radiosensitivity
#16
Yi-Liang Bi, Min Min, Wei Shen, Yan Liu
The present study aims to evaluate whether repression of the Numb/Notch signaling pathway affects the radiosensitivity of human pancreatic cancer cell lines. Different doses of X-rays (0, 2, 3, 4, and 5 Gy) were applied to the PANC-1, SW1990, and MIA PaCa-2 human pancreatic cancer cell lines, and the Numb/Notch pathway inhibitor DAPT was added at different doses (0, 1, 3, and 5 μmol/l). MTT assay, colony formation assay, flow cytometry, scratch assay, and Transwell experiments were performed, and qRT-PCR and Western blot were conducted for the detection of Numb expression...
November 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27661116/targeting-notch-signaling-as-a-novel-therapy-for-retinoblastoma
#17
Laura Asnaghi, Arushi Tripathy, Qian Yang, Harpreet Kaur, Allison Hanaford, Wayne Yu, Charles G Eberhart
Retinoblastoma is the most common intraocular malignancy of childhood. Notch plays a key role in retinal cells from which retinoblastomas arise, and we therefore studied the role of Notch signaling in promoting retinoblastoma proliferation. Moderate or strong nuclear expression of Hes1 was found in 10 of 11 human retinoblastoma samples analyzed immunohistochemically, supporting a role for Notch in retinoblastoma growth. Notch pathway components were present in WERI Rb1 and Y79 retinoblastoma lines, with Jag2 and DLL4 more highly expressed than other ligands, and Notch1 and Notch2 more abundant than Notch3...
September 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27630117/protective-effect-of-melatonin-on-soluble-a%C3%AE-1-42-induced-memory-impairment-astrogliosis-and-synaptic-dysfunction-via-the-musashi1-notch1-hes1-signaling-pathway-in-the-rat-hippocampus
#18
Shuman Zhang, Pan Wang, Lili Ren, Chunli Hu, Jing Bi
BACKGROUND: Amyloid-beta (Aβ) plays a key role in Alzheimer's disease (AD) pathogenesis, and soluble Aβ oligomers are more cytotoxic than Aβ fibrils. Recent evidence suggests that Notch signaling is affected by AD and other brain diseases. Melatonin exerts beneficial effects on many aspects of AD and may protect against myocardial ischemia via Notch1 signaling regulation. Therefore, we hypothesized that the Notch1 signaling pathway is involved in the neuroprotective role of melatonin against soluble Aβ1-42...
2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27570480/gamma-secretase-inhibitor-prevents-proliferation-and-migration-of-ductus-arteriosus-smooth-muscle-cells-through-the-notch3-hes1-2-5-pathway
#19
Jiunn-Ren Wu, Jwu-Lai Yeh, Shu-Fen Liou, Zen-Kong Dai, Bin-Nan Wu, Jong-Hau Hsu
Patent ductus arteriosus (PDA) can cause morbidity and mortality in neonates. Vascular remodeling, characterized by proliferation and migration of smooth muscle cells (SMCs), is an essential process for postnatal DA closure. Notch signaling is an important mediator of vascular remodelling but its role in DA is unkonwn. We investigated the effects and underlying mechanisms of γ-secretase inhibitor DAPT, a Notch signaling inhibitor on angiotensin II (Ang II)-induced proliferation and migration of DASMCs. Proliferation and migration of DASMCs cultured from neonatal Wistar rats were induced by Ang II, with or without DAPT pre-treatment...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27476167/inhibition-on-numb-notch-signal-pathway-enhances-radiosensitivity-of-lung-cancer-cell-line-h358
#20
Shi-Gang Song, Hong-Yang Yu, Yan-Wei Ma, Feng Zhang, Xiang-Ying Xu
The objective of the study is to investigate the effects of the Numb/Notch signal pathway on the radiosensitivity of lung cancer cell line H358. MTT assay and colony forming assay were used to detect the effects of different doses of X-rays and MW167 on the in vitro proliferation of the lung cancer cell line H358. Flow cytometry was applied to evaluate the effects of X rays on the apoptosis of H358. Scratch assay and Transwell invasion assay were used to examine the effects of X-rays on the migration and invasion abilities of H358...
October 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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