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https://www.readbyqxmd.com/read/29666782/new-perspectives-on-diagnosis-and-therapy-of-malignant-pleural-mesothelioma
#1
REVIEW
Marika Rossini, Paola Rizzo, Ilaria Bononi, Anthony Clementz, Roberto Ferrari, Fernanda Martini, Mauro G Tognon
Malignant pleural mesothelioma (MPM) is a rare, but severe form of cancer, with an incidence that varies significantly within and among different countries around the world. It develops in about one to two persons per million of the general population, leading to thousands of deaths every year worldwide. To date, the MPM is mostly associated with occupational asbestos exposure. Asbestos represents the predominant etiological factor, with approximately 70% of cases of MPM with well-documented occupational exposure to asbestos, with the exposure time, on average greater than 40 years...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29665979/crosstalk-between-yap-taz-and-notch-signaling
#2
REVIEW
Antonio Totaro, Martina Castellan, Daniele Di Biagio, Stefano Piccolo
How the behavior of cells in living tissues is orchestrated according to tissue needs, size, and developmental stage is still poorly understood. Advances in these directions are essential to understand morphogenesis, 'self-organization' phenomena, to build new tissues for regenerative medicine or to reverse the changes in deranged organs, such as in cancer or in genetic disorders. This review outlines a new scenario by which the crosstalk between the Yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) transcription factors and Notch signaling influences cell self-renewal, stem cell differentiation, cell fate decisions, epithelial-stromal interactions, inflammation, morphogenesis, and large-scale gene oscillations...
April 14, 2018: Trends in Cell Biology
https://www.readbyqxmd.com/read/29665790/the-oncogenic-effects-of-hes1-on-salivary-adenoid-cystic-carcinoma-cell-growth-and-metastasis
#3
Xiao-Yu Huang, Rui-Huan Gan, Jian Xie, Lin She, Yong Zhao, Lin-Can Ding, Bo-Hua Su, Da-Li Zheng, You-Guang Lu
BACKGROUND: Our previous study demonstrated a close relationship between NOTCH signaling pathway and salivary adenoid cystic carcinoma (SACC). HES1 is a well-known target gene of NOTCH signaling pathway. The purpose of the present study was to further explore the molecular mechanism of HES1 in SACC. METHODS: Comparative transcriptome analyses by RNA-Sequencing (RNA-Seq) were employed to reveal NOTCH1 downstream gene in SACC cells. Immunohistochemical staining was used to detect the expression of HES1 in clinical samples...
April 17, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29661224/notch-signals-modulate-lgl-mediated-tumorigenesis-by-the-activation-of-jnk-signaling
#4
Maimuna Sali Paul, Ankita Singh, Debdeep Dutta, Mousumi Mutsuddi, Ashim Mukherjee
OBJECTIVES: Oncogenic potential of Notch signaling and its cooperation with other factors to affect proliferation are widely established. Notch exhibits a cooperative effect with loss of a cell polarity gene, scribble to induce neoplastic overgrowth. Oncogenic Ras also show cooperative effect with loss of cell polarity genes such as scribble (scrib), lethal giant larvae (lgl) and discs large to induce neoplastic overgrowth and invasion. Our study aims at assessing the cooperation of activated Notch with loss of function of lgl in tumor overgrowth, and the mode of JNK signaling activation in this context...
April 16, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29658611/effects-of-nicotine-on-the-metabolism-and-gene-expression-profile-of-sprague%C3%A2-dawley-rat-primary-osteoblasts
#5
Dan Liang, Ke-Jing Wang, Zhi-Qun Tang, Run-He Liu, Fulei Zeng, Miao-Ying Cheng, Qi-Si Lian, Hong-Kun Wu
Smoking is a risk factor associated with bone and oral diseases, particularly periodontitis. Nicotine, the major toxic component of tobacco, is able to affect the quality and quantity of bone. Osteoblasts serve an important role in bone formation. Thus far, the effects of nicotine on metabolism‑associated gene and protein expression in osteoblasts have been controversial and the mechanisms remain unclear. The present study assessed alterations in osteogenic activity by performing a Cell Counting kit‑8 assay to investigate proliferation, Annexin V‑fluorescein isothiocyanate/propidium iodide staining to investigate apoptosis, alizarin red staining to investigate the formation of mineralized nodules, reverse transcription‑quantitative polymerase chain reaction and western blotting to investigate the mRNA and protein levels of collagen I, alkaline phosphatase, bone osteocalcin, bone sialoprotein and osteopontin; and mRNA microarray expression analysis, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis to investigate the whole genome expression profile of Sprague‑Dawley (SD) rat primary osteoblasts following treatment with different concentrations of nicotine...
April 13, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29657712/recent-advances-in-understanding-the-biology-of-marginal-zone-lymphoma
#6
REVIEW
Francesco Bertoni, Davide Rossi, Emanuele Zucca
There are three different marginal zone lymphomas (MZLs): the extranodal MZL of mucosa-associated lymphoid tissue (MALT) type (MALT lymphoma), the splenic MZL, and the nodal MZL. The three MZLs share common lesions and deregulated pathways but also present specific alterations that can be used for their differential diagnosis. Although trisomies of chromosomes 3 and 18, deletions at 6q23, deregulation of nuclear factor kappa B, and chromatin remodeling genes are frequent events in all of them, the three MZLs differ in the presence of recurrent translocations, mutations affecting the NOTCH pathway, and the transcription factor Kruppel like factor 2 ( KLF2) or the receptor-type protein tyrosine phosphatase delta ( PTPRD )...
2018: F1000Research
https://www.readbyqxmd.com/read/29643474/histone-deacetylase-6-controls-notch3-trafficking-and-degradation-in-t-cell-acute-lymphoblastic-leukemia-cells
#7
Marica Pinazza, Margherita Ghisi, Sonia Minuzzo, Valentina Agnusdei, Gianluca Fossati, Vincenzo Ciminale, Laura Pezzè, Yari Ciribilli, Giorgia Pilotto, Carolina Venturoli, Alberto Amadori, Stefano Indraccolo
Several studies have revealed that endosomal sorting controls the steady-state levels of Notch at the cell surface in normal cells and prevents its inappropriate activation in the absence of ligands. However, whether this highly dynamic physiologic process can be exploited to counteract dysregulated Notch signaling in cancer cells remains unknown. T-ALL is a malignancy characterized by aberrant Notch signaling, sustained by activating mutations in Notch1 as well as overexpression of Notch3, a Notch paralog physiologically subjected to lysosome-dependent degradation in human cancer cells...
April 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29642462/new-challenges-in-targeting-signaling-pathways-in-acute-lymphoblastic-leukemia-by-ngs-approaches-an-update
#8
REVIEW
Adrián Montaño, Maribel Forero-Castro, Darnel Marchena-Mendoza, Rocío Benito, Jesús María Hernández-Rivas
The identification and study of genetic alterations involved in various signaling pathways associated with the pathogenesis of acute lymphoblastic leukemia (ALL) and the application of recent next-generation sequencing (NGS) in the identification of these lesions not only broaden our understanding of the involvement of various genetic alterations in the pathogenesis of the disease but also identify new therapeutic targets for future clinical trials. The present review describes the main deletions, amplifications, sequence mutations, epigenetic lesions, and new structural DNA rearrangements detected by NGS in B-ALL and T-ALL and their clinical importance for therapeutic procedures...
April 7, 2018: Cancers
https://www.readbyqxmd.com/read/29630035/an-optogenetic-method-to-control-and-analyze-gene-expression-patterns-in-cell-to-cell-interactions
#9
Akihiro Isomura, Ryoichiro Kageyama
Cells should respond properly to temporally changing environments, which are influenced by various factors from surrounding cells. The Notch signaling pathway is one of such essential molecular machinery for cell-to-cell communications, which plays key roles in normal development of embryos. This pathway involves a cell-to-cell transfer of oscillatory information with ultradian rhythms, but despite the progress in molecular biology techniques, it has been challenging to elucidate the impact of multicellular interactions on oscillatory gene dynamics...
March 22, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29627423/a-jagged1-notch4-molecular-switch-mediates-airway-inflammation-by-ultrafine-particles
#10
Mingcan Xia, Hani Harb, Arian Saffari, Constantinos Sioutas, Talal A Chatila
BACKGROUND: Exposure to traffic-related particulate matter (PM) promotes asthma and allergic diseases. However, the precise cellular and molecular mechanisms by which PM exposure acts to mediate these effects remain unclear. OBJECTIVE: We sought to elucidate the cellular targets and signaling pathways critical for the augmentation of allergic airway inflammation induced by ambient ultra fine particles (UFP). METHODS: We employed in vitro cell culture assays using lung-derived antigen presenting cells and allergen-specific T cells, and in vivo mouse models of allergic airway inflammation that employed myeloid lineage-specific gene deletions, cellular reconstitution approaches and antibody inhibition studies...
April 5, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29625050/oncogenic-signaling-pathways-in-the-cancer-genome-atlas
#11
Francisco Sanchez-Vega, Marco Mina, Joshua Armenia, Walid K Chatila, Augustin Luna, Konnor C La, Sofia Dimitriadoy, David L Liu, Havish S Kantheti, Sadegh Saghafinia, Debyani Chakravarty, Foysal Daian, Qingsong Gao, Matthew H Bailey, Wen-Wei Liang, Steven M Foltz, Ilya Shmulevich, Li Ding, Zachary Heins, Angelica Ochoa, Benjamin Gross, Jianjiong Gao, Hongxin Zhang, Ritika Kundra, Cyriac Kandoth, Istemi Bahceci, Leonard Dervishi, Ugur Dogrusoz, Wanding Zhou, Hui Shen, Peter W Laird, Gregory P Way, Casey S Greene, Han Liang, Yonghong Xiao, Chen Wang, Antonio Iavarone, Alice H Berger, Trever G Bivona, Alexander J Lazar, Gary D Hammer, Thomas Giordano, Lawrence N Kwong, Grant McArthur, Chenfei Huang, Aaron D Tward, Mitchell J Frederick, Frank McCormick, Matthew Meyerson, Eliezer M Van Allen, Andrew D Cherniack, Giovanni Ciriello, Chris Sander, Nikolaus Schultz
Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFβ signaling, p53 and β-catenin/Wnt...
April 5, 2018: Cell
https://www.readbyqxmd.com/read/29622724/single-cell-transcriptomics-of-the-mouse-kidney-reveals-potential-cellular-targets-of-kidney-disease
#12
Jihwan Park, Rojesh Shrestha, Chengxiang Qiu, Ayano Kondo, Shizheng Huang, Max Werth, Mingyao Li, Jonathan Barasch, Katalin Suszták
Our understanding of kidney disease pathogenesis is limited by an incomplete molecular characterization of the cell types responsible for the organ's multiple homeostatic functions. To help fill this knowledge gap, we characterized 57,979 cells from healthy mouse kidneys using unbiased single-cell RNA sequencing. Based on gene expression patterns, we infer that inherited kidney diseases that arise from distinct genetic mutations but share the same phenotypic manifestation originate from the same cell differentiated type...
April 5, 2018: Science
https://www.readbyqxmd.com/read/29622701/the-role-of-notch3-in-cancer
#13
REVIEW
Zviadi Aburjania, Samuel Jang, Jason Whitt, Renata Jaskula-Stzul, Herbert Chen, J Bart Rose
The Notch family is a highly conserved gene group that regulates cell-cell interaction, embryogenesis, and tissue commitment. This review article focuses on the third Notch family subtype, Notch3. Regulation via Notch3 signaling was first implicated in vasculogenesis. However, more recent findings suggest that Notch3 signaling may play an important role in oncogenesis, tumor maintenance, and resistance to chemotherapy. Its role is mainly oncogenic, although in some cancers it appears to be tumor suppressive...
April 5, 2018: Oncologist
https://www.readbyqxmd.com/read/29620522/mpdz-promotes-dll4-induced-notch-signaling-during-angiogenesis
#14
Fabian Tetzlaff, M Gordian Adam, Anja Feldner, Iris Moll, Amitai Menuchin, Juan Rodriguez-Vita, David Sprinzak, Andreas Fischer
Angiogenesis is coordinated by VEGF and Notch signaling. DLL4-induced Notch signaling inhibits tip cell formation and vessel branching. To ensure proper Notch signaling, receptors and ligands are clustered at adherens junctions. However, little is known about factors that control Notch activity by influencing the cellular localization of Notch ligands. Here we show that the multiple PDZ domain protein (MPDZ) enhances Notch signaling activity. MPDZ physically interacts with the intracellular carboxyterminus of DLL1 and DLL4 and enables their interaction with the adherens junction protein Nectin-2...
April 5, 2018: ELife
https://www.readbyqxmd.com/read/29620159/foxp3-expression-is-modulated-by-tgf%C3%A2-%C3%AE-1-notch1-pathway-in-human-melanoma
#15
Eva Skarmoutsou, Valentina Bevelacqua, Fabio D' Amico, Angela Russo, Demetrios A Spandidos, Aurora Scalisi, Grazia Malaponte, Claudio Guarneri
Forkhead box protein 3 (FOXP3) transcription factor is expressed by immune cells and several human cancers and is associated with tumor aggressiveness and unfavorable clinical outcomes. NOTCH and transforming growth factor‑β (TGF‑β) protumorigenic effects are mediated by FOXP3 expression in several cancer models; however, their interaction and role in melanoma is unknown. We investigated TGF‑β‑induced FOXP3 gene expression during NOTCH1 signaling inactivation. Primary (WM35) and metastatic melanoma (A375 and A2058) cell lines and normal melanocytes (NHEM) were used...
April 4, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29617759/regulation-of-gene-expression-by-thyroid-hormone-in-primary-astrocytes-factors-influencing-the-genomic-response
#16
Beatriz Morte, Pilar Gil-Ibáñez, Juan Bernal
Astrocytes mediate the action of thyroid hormone in the brain on other neural cells through the production of the active hormone triiodothyronine (T3) from its precursor thyroxine (T4). T3 has also many effects on the astrocytes in vivo and in culture, but whether these actions are directly mediated by transcriptional regulation is not clear. In this work we have analyzed the genomic response to T3 of cultured astrocytes isolated from the postnatal mouse cerebral cortex, using RNA sequencing. Cultured astrocytes express relevant genes of thyroid hormone metabolism and action encoding type 2 deiodinase (Dio2), Mct8 transporter (Slc16a2), T3 receptors (Thra1 and Thrb), and nuclear corepressor (Ncor1) and coactivator (Ncoa1)...
April 2, 2018: Endocrinology
https://www.readbyqxmd.com/read/29616725/cell-biological-mechanisms-regulating-chick-neurogenesis
#17
Ioannis Kasioulis, Kate G Storey
Signalling pathways that regulate neural progenitor proliferation and neuronal differentiation have been identified. However, we know much less about how transduction of such signals is regulated within neuroepithelial cells to direct cell fate choice during mitosis and subsequent neuronal differentiation. Here we review recent advances in the experimentally amenable chick embryo, which reveal that this involves association of signalling pathway components with cell biological entities, including mitotic centrosomes and ciliary structures...
2018: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/29615616/heterogeneity-in-vegfr3-levels-drives-lymphatic-vessel-hyperplasia-through-cell-autonomous-and-non-cell-autonomous-mechanisms
#18
Yan Zhang, Maria H Ulvmar, Lukas Stanczuk, Ines Martinez-Corral, Maike Frye, Kari Alitalo, Taija Mäkinen
Incomplete delivery to the target cells is an obstacle for successful gene therapy approaches. Here we show unexpected effects of incomplete targeting, by demonstrating how heterogeneous inhibition of a growth promoting signaling pathway promotes tissue hyperplasia. We studied the function of the lymphangiogenic VEGFR3 receptor during embryonic and post-natal development. Inducible genetic deletion of Vegfr3 in lymphatic endothelial cells (LECs) leads to selection of non-targeted VEGFR3+ cells at vessel tips, indicating an indispensable cell-autonomous function in migrating tip cells...
April 3, 2018: Nature Communications
https://www.readbyqxmd.com/read/29610298/mechanosensitivity-of-jagged-notch-signaling-can-induce-a-switch-type-behavior-in-vascular-homeostasis
#19
Sandra Loerakker, Oscar M J A Stassen, Fleur M Ter Huurne, Marcelo Boareto, Carlijn V C Bouten, Cecilia M Sahlgren
Hemodynamic forces and Notch signaling are both known as key regulators of arterial remodeling and homeostasis. However, how these two factors integrate in vascular morphogenesis and homeostasis is unclear. Here, we combined experiments and modeling to evaluate the impact of the integration of mechanics and Notch signaling on vascular homeostasis. Vascular smooth muscle cells (VSMCs) were cyclically stretched on flexible membranes, as quantified via video tracking, demonstrating that the expression of Jagged1, Notch3, and target genes was down-regulated with strain...
April 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29602546/decreased-expression-of-tfap2b-in-endometrial-cancer-predicts-poor-prognosis-a-study-based-on-tcga-data
#20
Hongrong Wu, Jian Zhang
BACKGROUND: Transcription factor activator protein-2β (TFAP-2β) was previously reported to constituted promoter activity in endometrial carcinoma (EC). We evaluated the role of TFAP2B in ECs using publicly available data from The Cancer Genome Atlas (TCGA). METHODS: The relationship between clinical pathologic features and TFAP2B were analyzed with the Wilcoxon signed-rank test and logistic regression. Clinicopathologic characteristics associated with overall survival in TCGA patients using Cox regression and the Kaplan-Meier method...
March 28, 2018: Gynecologic Oncology
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