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https://www.readbyqxmd.com/read/28816361/msel-1l-deficiency-affects-vasculogenesis-and-neural-stem-cell-lineage-commitment
#1
Cardano M, Diaferia G R, Conti L, Baronchelli S, Sessa A, Broccoli V, Barbieri A, De Blasio P, Biunno I
mSEL-1L is a highly conserved ER-resident type I protein, involved in the degradation of misfolded peptides through the ubiquitin-proteasome system (UPS), a pathway known to control the plasticity of the vascular smooth muscle cells (VSMC) phenotype and survival. In this article we demonstrate that mSEL-1L deficiency interferes with the murine embryonic vascular network, showing particular irregularities in the intracranic and intersomitic neurovascular units and in the cerebral capillary microcirculation. During murine embryogenesis, mSEL-1L is expressed in cerebral areas known to harbor progenitor neural cells, while in the adult brain the protein is specifically restricted to the stem cell niches, co-localizing with Sox2 and Nestin...
August 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28814946/protein-signatures-of-molecular-pathways-in-non-small-cell-lung-carcinoma-nsclc-comparison-of-glycoproteomics-and-global-proteomics
#2
Shuang Yang, Lijun Chen, Daniel W Chan, Qing Kay Li, Hui Zhang
BACKGROUND: Non-small cell lung carcinoma (NSCLC) remains the leading cause of cancer deaths in the United States. More than half of NSCLC patients have clinical presentations with locally advanced or metastatic disease at the time of diagnosis. The large-scale genomic analysis of NSCLC has demonstrated that molecular alterations are substantially different between adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). However, a comprehensive analysis of proteins and glycoproteins in different subtypes of NSCLC using advanced proteomic approaches has not yet been conducted...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/28805807/notch-signaling-pathway-and-gene-expression-profiles-during-early-in-vitro-differentiation-of-liver-derived-mesenchymal-stromal-cells-to-osteoblasts
#3
Ksymena Urbanek, Marta Lesiak, Daniel Krakowian, Halina Koryciak-Komarska, Wirginia Likus, Piotr Czekaj, Damian Kusz, Aleksander L Sieroń
Notch signaling is a key signaling pathway for cell proliferation and differentiation. Therefore, we formulated a working hypothesis that Notch signaling can be used to detect early osteoblastic differentiation of mesenchymal stromal cells. Changes in expression and distribution of Notch 1, 2, 3, and Delta1 in the cytoplasm and nuclei of rat liver-derived mesenchymal stromal cells differentiating into osteoblasts were investigated, together with the displacement of intracellular domains (ICDs) of the receptors...
August 14, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28798480/magnesium-chloride-promotes-osteogenesis-through-notch-signaling-activation-and-expansion-of-mesenchymal-stem-cells
#4
Juan M Díaz-Tocados, Carmen Herencia, Julio M Martínez-Moreno, Addy Montes de Oca, Maria E Rodríguez-Ortiz, Noemi Vergara, Alfonso Blanco, Sonja Steppan, Yolanda Almadén, Mariano Rodríguez, Juan R Muñoz-Castañeda
Mesenchymal stem cells (MSC) are osteoblasts progenitors and a variety of studies suggest that they may play an important role for the health in the field of bone regeneration. Magnesium supplementation is gaining importance as adjuvant treatment to improve osteogenesis, although the mechanisms involving this process are not well understood. The objective of this study was to investigate the effects of magnesium on MSC differentiation. Here we show that in rat bone marrow MSC, magnesium chloride increases MSC proliferation in a dose-dependent manner promoting osteogenic differentiation and mineralization...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28796347/clinicopathological-analysis-of-atrx-daxx-and-notch-receptor-expression-in-angiosarcomas
#5
Gauri Panse, John S A Chrisinger, Cheuk H Leung, Davis R Ingram, Samia Khan, Khalida Wani, Heather Lin, Alexander J Lazar, Wei-Lien Wang
AIMS: Multiple genetic alterations including alternative lengthening of telomeres (ALT) and NOTCH mutations have been described in angiosarcoma. Loss of ATRX (α-thalessemia/mental retardation syndrome X-linked) and DAXX (death domain-associated 6) expression is frequently associated with the ALT phenotype. Additionally, inhibition of NOTCH signaling induces malignant vascular tumors in mice, indicating a tumor suppressive role of the NOTCH pathway in the pathogenesis of angiosarcoma...
August 10, 2017: Histopathology
https://www.readbyqxmd.com/read/28794048/hepatitis-c-virus-core-protein-modulates-endoglin-cd105-signaling-pathway-for-liver-pathogenesis
#6
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 our previous study, we have shown that hepatitis C virus (HCV) infection induces epithelial-mesenchymal transition state (EMT) 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 HCV core expressing hepatocellular carcinoma (HepG2) cell line or immortalized human hepatocytes (IHH) and activation of its downstream signaling molecules...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28793339/modeling-mirna-mrna-interactions-that-cause-phenotypic-abnormality-in-breast-cancer-patients
#7
Sanghoon Lee, Xia Jiang
BACKGROUND: The dysregulation of microRNAs (miRNAs) alters expression level of pro-oncogenic or tumor suppressive mRNAs in breast cancer, and in the long run, causes multiple biological abnormalities. Identification of such interactions of miRNA-mRNA requires integrative analysis of miRNA-mRNA expression profile data. However, current approaches have limitations to consider the regulatory relationship between miRNAs and mRNAs and to implicate the relationship with phenotypic abnormality and cancer pathogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28791758/agent-based-computational-model-of-retinal-angiogenesis-simulates-microvascular-network-morphology-as-a-function-of-pericyte-coverage
#8
Joseph Walpole, Feilim Mac Gabhann, Shayn M Peirce, John C Chappell
OBJECTIVE: Define a role for perivascular cells during developmental retinal angiogenesis in the context of endothelial cell Notch1-DLL4 signaling at the multicellular network level. METHODS: The retinal vasculature is highly sensitive to growth factor mediated intercellular signaling. Although endothelial cell signaling has been explored in detail, it remains unclear how pericytes function to modulate these signals that lead to a diverse set of vascular network patterns in health and disease...
August 8, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28791751/the-gene-network-underlying-the-glial-regenerative-response-to-central-nervous-system-injury
#9
REVIEW
Kentaro Kato, Maria Losada-Perez, Alicia Hidalgo
Although the central nervous system does not regenerate, injury induces repair and regenerative responses in glial cells. In mammals, activated microglia clear up apoptotic cells and debris resulting from the injury, astrocytes form a scar that contains the lesion, and NG2-glia elicit a prominent regenerative response. NG2-glia regenerate themselves and differentiate into oligodendrocytes, which remyelinate axons leading to some recovery of locomotion. The regenerative response of glial cells is evolutionarily conserved across the animals and Drosophila genetics revealed an underlying gene network...
August 9, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28791383/a-mutation-in-notch1-ligand-binding-region-detected-in-patients-with-oral-squamous-cell-carcinoma-reduces-notch1-oncogenic-effect
#10
Masahiro Uchibori, Ken-Ichi Aoyama, Yoshihide Ota, Kagemasa Kajiwara, Masafumi Tanaka, Minoru Kimura
NOTCH1 is known as an oncogenic or tumor suppressive gene in solid cancer. NOTCH1 mutations in oral squamous cell carcinoma (OSCC) frequently occur near the ligand-binding region. These mutations change the domain structure of this protein and affect the ligand binding activity. When NOTCH1 is activated by ligand binding, NOTCH1 intracellular domain (NICD) is cleaved from the cell membrane. This study investigated the functional change induced by a NOTCH1 mutation detected in OSCC clinical samples using stable transformant analysis...
August 3, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28790933/mechanisms-of-smooth-muscle-cell-differentiation-are-distinctly-altered-in-thoracic-aortic-aneurysms-associated-with-bicuspid-or-tricuspid-aortic-valves
#11
Elena Ignatieva, Daria Kostina, Olga Irtyuga, Vladimir Uspensky, Alexey Golovkin, Natalia Gavriliuk, Olga Moiseeva, Anna Kostareva, Anna Malashicheva
Cellular and molecular mechanisms of thoracic aortic aneurysm are not clear and therapeutic approaches are mostly absent. Thoracic aortic aneurysm is associated with defective differentiation of smooth muscle cells (SMC) of aortic wall. Bicuspid aortic valve (BAV) comparing to tricuspid aortic valve (TAV) significantly predisposes to a risk of thoracic aortic aneurysms. It has been suggested recently that BAV-associated aortopathies represent a separate pathology comparing to TAV-associated dilations. The only proven candidate gene that has been associated with BAV remains NOTCH1...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28790107/runx1-is-required-for-oncogenic-myb-and-myc-enhancer-activity-in-t-cell-acute-lymphoblastic-leukemia
#12
AHyun Choi, Anuradha Illendula, John A Pulikkan, Justine E Roderick, Jessica Tesell, Jun Yu, Nicole Hermance, Lihua Julie Zhu, Lucio H Castilla, John H Bushweller, Michelle A Kelliher
The gene encoding the RUNX1 transcription factor is mutated in a subset of T cell acute lymphoblastic leukemia (T-ALL) patients and RUNX1 mutations are associated with a poor prognosis. These mutations cluster in the DNA binding Runt domain, are thought to represent loss-of-function mutations, indicating that RUNX1 suppresses T cell transformation. RUNX1 has been proposed to have tumor suppressor roles in TLX1/3 transformed human T-ALL cell lines and NOTCH1 T-ALL mouse models. Yet retroviral insertional mutagenesis screens identify RUNX genes as collaborating oncogenes in MYC-driven leukemia mouse models...
August 8, 2017: Blood
https://www.readbyqxmd.com/read/28781077/embryonic-stem-cell-differentiation-to-functional-arterial-endothelial-cells-through-sequential-activation-of-etv2-and-notch1-signaling-by-hif1%C3%AE
#13
Kit Man Tsang, James S Hyun, Kwong Tai Cheng, Micaela Vargas, Dolly Mehta, Masuko Ushio-Fukai, Li Zou, Kostandin V Pajcini, Jalees Rehman, Asrar B Malik
The generation of functional arterial endothelial cells (aECs) from embryonic stem cells (ESCs) holds great promise for vascular tissue engineering. However, the mechanisms underlying their generation and the potential of aECs in revascularizing ischemic tissue are not fully understood. Here, we observed that hypoxia exposure of mouse ESCs induced an initial phase of HIF1α-mediated upregulation of the transcription factor Etv2, which in turn induced the commitment to the EC fate. However, sustained activation of HIF1α in these EC progenitors thereafter induced NOTCH1 signaling that promoted the transition to aEC fate...
July 24, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28776955/antineoplastic-effects-of-histone-deacetylase-inhibitors-in-neuroendocrine-cancer-cells-are-mediated-through-transcriptional-regulation-of-notch1-by-activator-protein-1
#14
Samuel Jang, Haining Jin, Madhuchhanda Roy, Alice L Ma, Shaoqin Gong, Renata Jaskula-Sztul, Herbert Chen
Notch signaling is minimally active in neuroendocrine (NE) cancer cells. While histone deacetylase inhibitors (HDACi) suppress NE cancer growth by inducing Notch, the molecular mechanism underlying this interplay has not yet been defined. NE cancer cell lines BON, H727, and MZ-CRC-1 were treated with known HDACi Thailadepsin-A (TDP-A) and valproic acid (VPA), and Notch1 mRNA expression was measured with RT-PCR. Truncated genomic fragments of the Notch1 promotor region fused with luciferase reporter were used to identify the potential transcription factor (TF) binding site...
August 4, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28776666/potential-role-of-the-jagged1-notch1-signaling-pathway-in-the-endothelial-myofibroblast-transition-during-blm-induced-pulmonary-fibrosis
#15
Qian Yin, Weihua Wang, Guangbin Cui, Linfeng Yan, Song Zhang
Endothelial cell myofibroblast transition (EndoMT) is found during the process of bleomycin (BLM)-induced pulmonary fibrosis in rats, and plays a very important role in sustaining inflammation and collagen secretion. Moreover, some studies have suggested that the Notch1 signaling pathway may be involved in the expression of Î ± -smooth muscle actin (Î ± -SMA) in pulmonary microvascular endothelial cells (PMVECs), a protein marker of EndoMT. Therefore, we aimed to investigate the expression level of Î ± -SMA and Notch1-related signaling molecules in PMVECs from BLM-induced rats and determine the relationship between the Notch1 signaling pathway and the expression of Î ± -SMA in PMVECs...
August 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28776427/etv6-and-notch1-germline-variants-in-adult-acute-leukemia
#16
Vaidas Dirse, Rimvydas Norvilas, Egle Gineikiene, Rėda Matuzevičienė, Laimonas Griskevicius, Egle Preiksaitiene
No abstract text is available yet for this article.
August 4, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28771672/med12-mutations-and-notch-signalling-in-chronic-lymphocytic-leukaemia
#17
Bian Wu, Mikołaj Słabicki, Leopold Sellner, Sascha Dietrich, Xiyang Liu, Alexander Jethwa, Jennifer Hüllein, Tatjana Walther, Lena Wagner, Zhiqin Huang, Marc Zapatka, Thorsten Zenz
Mutations in the N-terminus of MED12 protein occur at high frequency in uterine leiomyomas and breast fibroepithelial tumours, and are frequently found in chronic lymphocytic leukaemia (CLL). MED12 mutations have been previously linked to aberrant Cyclin C-CDK8 kinase activity, but the exact oncogenic function in CLL is unknown. Here, we characterized MED12 mutations in CLL and identified recurrent mutations in 13 out of 188 CLL patients (6·9%), which clustered in the N-terminus. MED12 mutations were associated with unmutated IGHV (P = 0·024)...
August 2, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28771191/somatic-host-cell-alterations-in-hpv-carcinogenesis
#18
REVIEW
Tamara R Litwin, Megan A Clarke, Michael Dean, Nicolas Wentzensen
High-risk human papilloma virus (HPV) infections cause cancers in different organ sites, most commonly cervical and head and neck cancers. While carcinogenesis is initiated by two viral oncoproteins, E6 and E7, increasing evidence shows the importance of specific somatic events in host cells for malignant transformation. HPV-driven cancers share characteristic somatic changes, including apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC)-driven mutations and genomic instability leading to copy number variations and large chromosomal rearrangements...
August 3, 2017: Viruses
https://www.readbyqxmd.com/read/28765912/disorder-of-the-mevalonate-pathway-inhibits-calcium-induced-differentiation-of-keratinocytes
#19
Rui Jin, Xin Luo, Kang Luan, Li Liu, Liang-Dan Sun, Sen Yang, Sheng-Quan Zhang, Xue-Jun Zhang
Mutation of genes encoding the enzymes of the mevalonate pathway cause a variety of diseases, including skin disorders. Mutation of four genes in this pathway, including mevalonate kinase, phosphomevalonate kinase, mevalonate diphosphate decarboxylase and farnesyl diphosphate synthase, have demonstrated to be responsible for porokeratosis (PK). However, the pathogenesis of PK remains unclear. In the present study, specific enzyme inhibitors of the mevalonate pathway, including pravastatin (PRA), alendronate (ALD), farnesyl transferase inhibitor (FTI‑277) and geranylgeranyl transferase inhibitor (GGTI‑298), were used to investigate the effect on differentiation of keratinocytes (KCs)...
August 1, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28765900/mir-30a-inhibits-the-biological-function-of-breast-cancer-cells-by-targeting-notch1
#20
He-Da Zhang, Lin-Hong Jiang, Da-Wei Sun, Jian Li, Jin-Hai Tang
miR-30a is situated on chromosome 6q.13 and is produced by an intronic transcriptional unit. However, its role in regulating the apoptosis, invasion and metastasis of breast cancer cells is not yet fully understood. The aim of this study was to research the biological function of miR‑30a and its direct target gene in breast cancer. The biological function of miR‑30a was determined by examining breast cancer cell growth, apoptosis, metastasis and invasion. In addition, Notch1 expression was measured by western blot analysis, and a luciferase reporter vector was constructed to identify the miR‑30a target gene...
July 31, 2017: International Journal of Molecular Medicine
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