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HES1 Inhibitor

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https://www.readbyqxmd.com/read/29123981/coculture-of-endothelial-progenitor-cells-and-mesenchymal-stem-cells-enhanced-their-proliferation-and-angiogenesis-through-pdgf-and-notch-signaling
#1
Tangzhao Liang, Lei Zhu, Wenling Gao, Ming Gong, Jianhua Ren, Hui Yao, Kun Wang, Dehai Shi
The beneficial effects of combined use of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) on tissue repair and regeneration after injury have been demonstrated, but the underlying mechanism remains incompletely understood. This study aimed to investigate the effects of direct contact coculture of human bone marrow-derived EPCs (hEPCs)/human bone marrow-derived MSCs (hMSCs) on their proliferation and angiogenic capacities and the underlying mechanism. hEPCs and hMSCs were cocultured in a 2D mixed monolayer or a 3D transwell membrane cell-to-cell coculture system...
November 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/29100034/down-regulation-of-notch-signaling-pathway-reverses-the-th1-th2-imbalance-in-tuberculosis-patients
#2
Qifeng Li, Hui Zhang, Liang Yu, Chao Wu, Xinhui Luo, He Sun, Jianbing Ding
Th1/Th2 imbalance to Th2 is of significance in the peripheral immune responses in Tuberculosis (TB) development. However, the mechanisms for Th1/Th2 imbalance are still not well determined. Notch signaling pathway is involved in the peripheral T cell activation and effector cell differentiation. However, whether it affects Th1/Th2 imbalance in TB patients is still not known. Here, we used γ-secretase inhibitor (DAPT) to treat the peripheral blood mononuclear cells (PBMCs) from healthy people or individuals with latent or active TB infection in vitro, respectively...
October 28, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29096354/notch-signaling-pathway-dampens-tumor-infiltrating-cd8-t-cells-activity-in-patients-with-colorectal-carcinoma
#3
Weifeng Yu, Yanjun Wang, Peng Guo
CD8(+) T cells play critical role in controlling the metastasis and prognosis of cancer. Controversy remains as to the contribution of Notch signaling pathway in modulation of CD8(+) T cells activity and development of tumorigenesis. Thus, the aim of the current study was to investigate the immunoregulatory role of Notch signaling pathway to peripheral and tumor-infiltrating CD8(+) T cells in patients with colorectal carcinoma. A total of 46 patients with colorectal carcinoma and 20 health individuals were enrolled, and CD8(+) T cells were purified from both peripheral bloods and carcinoma specimens...
October 30, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29061784/bmi1-inhibitors-down-regulate-notch-signaling-and-suppress-proliferation-of-acute-leukemia-cells
#4
Mika Ohtaka, Mai Itoh, Shuji Tohda
BACKGROUND/AIM: B cell-specific Moloney murine leukemia virus integration site 1 (BMI1) is up-regulated in several cancers; therefore, we investigated the effects of BMI1 inhibitors on leukemia cells. MATERIALS AND METHODS: Four acute myeloid leukemia and two T-lymphoblastic leukemia cell lines were treated with BMI1 inhibitors artemisinin, PRT4165, and PTC-209 and analyzed for cell proliferation and gene expression by microarray and immunoblotting. RESULTS: PTC-209 and PRT4165 suppressed the growth of all cell lines through apoptosis...
November 2017: Anticancer Research
https://www.readbyqxmd.com/read/29048643/novel-transduction-of-nutrient-stress-to-notch-pathway-by-rasgrp3-promotes-malignant-aggressiveness-in-human-esophageal-squamous-cell-carcinoma
#5
Ge Hu, Yuepeng Zhou, Yu Zhu, Ling Zhou, Rui Ling, Dan Wu, Lei Mi, Xuefeng Wang, Dongfang Dai, Chaoming Mao, Deyu Chen
In the process of enlarging of tumors, the dissolving tissue structures and remodeling endothelial cells for restoring gas exchange and nutritional support, further facilitate tumor cell invasion and metastasis. Activation of Ras plays a critical role in the development of esophageal squamous cell carcinoma (ESCC), but the underlying mechanisms remain poorly understood. We therefore investigated whether Ras guanyl-releasing protein 3 (RasGRP3), a Ras activator, could promote metastasis by inducing vascular regeneration and further epithelial-mesenchymal transition under nutrient stress (NS)...
September 25, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29048612/regulation-of-erk-and-akt-pathways-by-hepatitis%C3%A2-b-virus%C3%A2-x-protein-via-the-notch1-pathway-in-hepatocellular-carcinoma
#6
Bo Liao, Honghao Zhou, Huifang Liang, Changhai Li
Hepatitis B virus (HBV) is the dominant risk factor for hepatocellular carcinoma (HCC). HBV X protein (HBx) plays crucial roles in HCC carcinogenesis. HBx interferes with several signaling pathways including the Notch1 pathway in HCC. In this study, we found that Notch1 was highly expressed in HCC, especially in large HCCs. Notch1 and HBx co-localized in HCC and their levels were positively correlated with each other. Notch1 expression was more elevated in HepG2.2.15 cells than that in HepG2 cells. HBx activated the Notch1 pathway in HepG2...
September 15, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29047105/%C3%AE-secretase-inhibitor-reduces-immunosuppressive-cells-and-enhances-tumour-immunity-in-head-and-neck-squamous-cell-carcinoma
#7
Liang Mao, Zhi-Li Zhao, Guang-Tao Yu, Lei Wu, Wei-Wei Deng, Yi-Cun Li, Jian-Feng Liu, Lin-Lin Bu, Bing Liu, Ashok B Kulkarni, Wen-Feng Zhang, Lu Zhang, Zhi-Jun Sun
Immune evasion is a hallmark feature of cancer, and it plays an important role in tumour initiation and progression. In addition, tumour immune evasion severely hampers the desired antitumour effect in multiple cancers. In this study, we aimed to investigate the role of the Notch pathway in immune evasion in the head and neck squamous cell carcinoma (HNSCC) microenvironment. We first demonstrated that Notch1 signalling was activated in a Tgfbr1/Pten-knockout HNSCC mouse model. Notch signalling inhibition using a γ-secretase inhibitor (GSI-IX, DAPT) decreased tumour burden in the mouse model after prophylactic treatment...
October 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29037123/ultrafine-particle-exposure-reveals-the-importance-of-foxo1-notch-activation-complex-for-vascular-regeneration
#8
Kyung In Baek, René R Sevag Packard, Jeffrey J Hsu, Arian Saffari, Zhao Ma, Anh Phuong Luu, Andrew Pietersen, Hilary Yen, Bin Ren, Yichen Ding, Constantinos Sioutas, Rongsong Li, Tzung K Hsiai
AIMS: Redox active ultrafine particles (UFP, d < 0.2 μm) promote vascular oxidative stress and atherosclerosis. Notch signaling is intimately involved in vascular homeostasis, in which forkhead box O1 (FOXO1) acts as a co-activator of the Notch activation complex. We elucidated the importance of FOXO1/Notch transcriptional activation complex to restore vascular regeneration after UFP exposure. RESULTS: In a zebrafish model of tail injury and repair, transgenic Tg(fli1:GFP) embryos developed vascular regeneration at 3 days post amputation (dpa), whereas UFP exposure impaired regeneration (p < 0...
November 17, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29035086/notch-signaling-is-essential-for-maturation-self-renewal-and-tri-differentiation-of-in-vitro-derived-human-neural-stem-cells
#9
Katari Venkatesh, L Vinod Kumar Reddy, Salar Abbas, Madhubanti Mullick, Erfath Thanjeem Begum Moghal, Janardhana Papayya Balakrishna, Dwaipayan Sen
Although neural stem cells (NSCs) have potential applications in treating neurological disorders, much still needs to be understood about the differentiation biology for their successful clinical translation. In this study, we aimed at deriving NSCs from human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) and explored the role of Notch signaling in the differentiation process. The hUCB-MSCs were characterized as per guidelines of the International Society of Cellular Therapy. NSCs were successfully generated from hUCB-MSCs by using epidermal and fibroblast growth factors under serum-free conditions...
October 16, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28959362/inhibition-of-hes1-enhances-lapatinib-sensitivity-in-gastric-cancer-sphere-forming-cells
#10
Luchun Li, Yan Li, Lulu Wang, Zhijuan Wu, Huiwen Ma, Jianghe Shao, Dairong Li, Huiqing Yu, Weiqi Nian, Donglin Wang
It has been considered that the neurogenic locus notch homolog protein (Notch) signaling pathway serves an essential role in cellular differentiation, proliferation and apoptosis. However, the function of the Notch signaling pathway in gastric cancer stem cells (GCSCs) and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) sensitivity remains unclear. The present study aimed to delineate the role of the Notch1 signaling pathway in GCSCs and lapatinib sensitivity. Sphere-forming cells were separated from human gastric cancer MKN45 parental cells...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28941308/in-vivo-and-in-vitro-effects-of-microrna-124-on-human-gastric-cancer-by-targeting-jag1-through-the-notch-signaling-pathway
#11
Hai-Juan Xiao, Qing Ji, Lin Yang, Ren-Ting Li, Cheng Zhang, Jun-Ming Hou
In this study, we aim to determine the function of miR-124 on gastric cancer (GC) cells and the underlying mechanism that involves jaddeg1 (JAG1) and the Notch signaling pathway. GC tissues and adjacent tissues from 100 patients suffering from GC were selected. GC SGC-7901 and AGS cells were selected and grouped into control, mimic-NC, miR-124 mimic, inhibitor-NC, miR-124 inhibitor, and miR-124 inhibitor + si-JAG1 groups. RT-qPCR and a western blotting assay were conducted to detect the expression of miR-124, JAG1 and Notch signaling pathway-related proteins (NICD, HES1 and HES5)...
September 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28881812/a-combination-of-valproic-acid-sodium-salt-chir99021-e-616452-tranylcypromine-and-3-deazaneplanocin-a-causes-stem-cell-like-characteristics-in-cancer-cells
#12
Shuang Sha, Yuanfen Zhai, Chengzhao Lin, Heyong Wang, Qing Chang, Shuang Song, Mingqiang Ren, Gentao Liu
Many studies are based on the hypothesis that recurrence and drug resistance in lung carcinoma are due to a subpopulation of cancer stem-like cells (CSLCs) in solid tumors. Therefore it is crucial to screen for and recognize lung CSLCs. In this study, we stimulated non-small cell lung cancer (NSCLC) A549 cells to display stem cell-like characteristics using a combination of five small molecule compounds. The putative A549 stem cells activated an important CSLC marker, CD133 protein, as well multiple CSLC-related genes including ATP-binding cassette transporter G2 (ABCG2), C-X-C chemokine receptor type 4 (CXCR4), NESTIN, and BMI1...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28860516/indirect-immobilized-jagged1-suppresses-cell-cycle-progression-and-induces-odonto-osteogenic-differentiation-in-human-dental-pulp-cells
#13
Jeeranan Manokawinchoke, Praphawi Nattasit, Tanutchaporn Thongngam, Prasit Pavasant, Kevin A Tompkins, Hiroshi Egusa, Thanaphum Osathanon
Notch signaling regulates diverse biological processes in dental pulp tissue. The present study investigated the response of human dental pulp cells (hDPs) to the indirect immobilized Notch ligand Jagged1 in vitro. The indirect immobilized Jagged1 effectively activated Notch signaling in hDPs as confirmed by the upregulation of HES1 and HEY1 expression. Differential gene expression profiling using an RNA sequencing technique revealed that the indirect immobilized Jagged1 upregulated genes were mainly involved in extracellular matrix organization, disease, and signal transduction...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28817274/notch-inhibitors-from-calotropis-gigantea-that-induce-neuronal-differentiation-of-neural-stem-cells
#14
Tatsuro Yoneyama, Midori A Arai, Ryuta Akamine, Kazune Koryudzu, Anna Tsuchiya, Samir K Sadhu, Firoj Ahmed, Motoyuki Itoh, Ryuichi Okamoto, Masami Ishibashi
Neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease occur due to loss of the structure and function of neurons. For the potential treatment of neurodegenerative diseases, accelerators of neuronal differentiation of neural stem cells (NSCs) have been focused on and a cell-based assay system for measuring Notch signaling pathway activity was constructed. Using this assay system, eight compounds isolated from Calotropis gigantea were identified as inhibitors of the Notch signaling pathway...
September 22, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28794048/hepatitis-c-virus-core-protein-modulates-endoglin-cd105-signaling-pathway-for-liver-pathogenesis
#15
Young-Chan Kwon, Reina Sasaki, Keith Meyer, Ranjit Ray
Endoglin is part of the TGF-β receptor complex and has a crucial role in fibrogenesis and angiogenesis. It is also an important protein for tumor growth, survival, and cancer cell metastasis. In a previous study, we have shown that hepatitis C virus (HCV) infection induces epithelial-mesenchymal transition (EMT) state and cancer stem-like cell (CSC) properties in human hepatocytes. Our array data suggested that endoglin (CD105) mRNA is significantly upregulated in HCV-associated CSCs. In this study, we have observed increased endoglin expression on the cell surface of an HCV core-expressing hepatocellular carcinoma (HepG2) cell line or immortalized human hepatocytes (IHH) and activation of its downstream signaling molecules...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28740236/reduced-expression-of-the-murine-hla-g-homolog-qa-2-is-associated-with-malignancy-epithelial-mesenchymal-transition-and-stemness-in-breast-cancer-cells
#16
Istéfani L da Silva, Lucía Montero-Montero, Ester Martín-Villar, Jorge Martin-Pérez, Bruno Sainz, Jaime Renart, Renata Toscano Simões, Émerson Soares Veloso, Cláudia Salviano Teixeira, Mônica C de Oliveira, Enio Ferreira, Miguel Quintanilla
Qa-2 is believed to mediate a protective immune response against cancer; however, little is known about the role of Qa-2 in tumorigenesis. Here, we used 4T1 breast cancer cells to study the involvement of Qa-2 in tumor progression in a syngeneic host. Qa-2 expression was reduced during in vivo tumor growth and in cell lines derived from 4T1-induced tumors. Tumor-derived cells elicited an epithelial-mesenchymal transition associated with upregulation of Zeb1 and Twist1/2 and enhanced tumor initiating and invasive capacities...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28687730/fluvoxamine-stimulates-oligodendrogenesis-of-cultured-neural-stem-cells-and-attenuates-inflammation-and-demyelination-in-an-animal-model-of-multiple-sclerosis
#17
Majid Ghareghani, Kazem Zibara, Heibatollah Sadeghi, Shima Dokoohaki, Hossein Sadeghi, Roya Aryanpour, Amir Ghanbari
Multiple Sclerosis (MS) require medications controlling severity of the pathology and depression, affecting more than half of the patients. In this study, the effect of antidepressant drug fluvoxamine, a selective serotonin reuptake inhibitor, was investigated in vitro and in vivo. Nanomolar concentrations of fluvoxamine significantly increased cell viability and proliferation of neural stem cells (NSCs) through increasing mRNA expression of Notch1, Hes1 and Ki-67, and protein levels of NICD. Also, physiological concentrations of fluvoxamine were optimal for NSC differentiation toward oligodendrocytes, astrocytes and neurons...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637014/a-combination-of-valproic-acid-sodium-salt-chir99021-e-616452-tranylcypromine-and-3-deazaneplanocin-a-causes-stem-cell-like-characteristics-in-cancer-cells
#18
Shuang Sha, Yuanfen Zhai, Chengzhao Lin, Heyong Wang, Qing Chang, Shuang Song, Mingqiang Ren, Gentao Liu
Many studies are based on the hypothesis that recurrence and drug resistance in lung carcinoma are due to a subpopulation of cancer stem-like cells (CSLCs) in solid tumors. Therefore it is crucial to screen for and recognize lung CSLCs. In this study, we stimulated non-small cell lung cancer (NSCLC) A549 cells to display stem cell-like characteristics using a combination of five small molecule compounds. The putative A549 stem cells activated an important CSLC marker, CD133 protein, as well multiple CSLC-related genes including ATP-binding cassette transporter G2 (ABCG2), C-X-C chemokine receptor type 4 (CXCR4), NESTIN, and BMI1...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28627674/mir-200c-serves-an-important-role-in-h5v-endothelial-cells-in-high-glucose-by-targeting-notch1
#19
Yunfeng Zhang, Qiang Guan, Xing Jin
Diabetic vasculopathy is the leading cause of impairment and death in diabetic patients, a variety of factors are involved in its underlying pathological process, however, endothelial cell (EC) dysfunction serves a significant role in the process. MicroRNAs (miRNAs) have emerged as potential therapeutic candidates, due to their ability to regulate multiple targets involved in ECs. The aim of the present study was to investigate the role of miR‑200c in regulating ECs in high glucose condition. To investigate the role of miR‑200c in regulating hyperglycemia induced ECs by targeting Notch1, ECs H5V cells were cultured in high sugar conditions to initiate the inhibition of Notch1, the same cells in normal medium as the control...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28601732/intermittent-compressive-stress-regulates-notch-target-gene-expression-via-transforming-growth-factor-%C3%AE-signaling-in-murine-pre-osteoblast-cell-line
#20
Jeeranan Manokawinchoke, Prasit Pavasant, Thanaphum Osathanon
OBJECTIVE: Different mechanical stimuli regulate behaviors of various cell types, including osteoblasts, osteocytes, and periodontal ligament fibroblasts. Notch signaling participates in the mechanical stress-regulated cell responses. The present study investigated the regulation of Notch target gene and sclerostin (Sost) expression in murine pre-osteoblast cell line (MC3T3-E1) under intermittent compressive stress. METHODS: MC3T3-E1 were subjected to the intermittent compressive force under the computerized controlled machine...
October 2017: Archives of Oral Biology
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