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https://www.readbyqxmd.com/read/28192800/molecular-profiling-of-the-developing-lacrimal-gland-reveals-putative-role-of-notch-signaling-in-branching-morphogenesis
#1
Galina Dvoriantchikova, Wensi Tao, Steve Pappas, Gabriel Gaidosh, David T Tse, Dmitry Ivanov, Daniel Pelaez
Purpose: Although normal function of the lacrimal gland is essential for vision (and thus for human well-being), the lacrimal gland remains rather poorly understood at a molecular level. The purpose of this study was to identify new genes and signaling cascades involved in lacrimal gland development. Methods: To identify these genes, we used microarray analysis to compare the gene expression profiles of developing (embryonic) and adult lacrimal glands. Differential data were validated by quantitative RT-PCR, and several corresponding proteins were confirmed by immunohistochemistry and Western blot analysis...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28186678/gamma-secretase-inhibitor-ix-gsi-impairs-concomitant-activation-of-notch-and-wnt-beta-catenin-pathways-in-cd44-gastric-cancer-stem-cells
#2
Samarpita Barat, Xi Chen, Khac Cuong Bui, Przemyslaw Bozko, Julian Götze, Matthias Christgen, Till Krech, Nisar P Malek, Ruben R Plentz
Cancer stem cells (CSC) are associated with tumor resistance and are characterized in gastric cancer (GC). Studies have indicated that Notch and wnt-beta-catenin pathways are crucial for CSC development. Using CD44(+) CSCs, we investigated the role of these pathways in GC carcinogenesis. We performed cell proliferation, wound healing, invasion, tumorsphere, and apoptosis assays. Immunoblot analysis of downstream signaling targets of Notch and wnt-beta-catenin were tested after gamma-secretase inhibitor IX (GSI) treatment...
February 3, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28179307/selumetinib-inhibits-melanoma-metastasis-to-mouse-liver-via-suppression-of-emt-targeted-genes
#3
Seung-Hee Ryu, Seung-Ho Heo, Eun Young Park, Kyung-Chul Choi, Je-Won Ryu, Seok Ho Lee, Sang-Wook Lee
AIM: We investigated the therapeutic effects of a mitogen-activated protein (MEK) inhibitor, selumetinib, in a hepatic melanoma metastasis model and studied its possible mechanism of action. MATERIALS AND METHODS: Melanoma cell lines were exposed to selumetinib under different experimental conditions. We established a mouse model of liver metastasis and treated mice orally with vehicle or selumetinib and then evaluated metastasis progress. RESULTS: Growth inhibition was observed in melanoma cells as a consequence of G1-phase cell-cycle arrest and the subsequent induction of apoptosis in a dose- and time-dependent manner...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28174276/synergistic-antileukemic-therapies-in-notch1-induced-t-all
#4
Marta Sanchez-Martin, Alberto Ambesi-Impiombato, Yue Qin, Daniel Herranz, Mukesh Bansal, Tiziana Girardi, Elisabeth Paietta, Martin S Tallman, Jacob M Rowe, Kim De Keersmaecker, Andrea Califano, Adolfo A Ferrando
The Notch1 gene is a major oncogenic driver and therapeutic target in T-cell acute lymphoblastic leukemia (T-ALL). However, inhibition of NOTCH signaling with γ-secretase inhibitors (GSIs) has shown limited antileukemic activity in clinical trials. Here we performed an expression-based virtual screening to identify highly active antileukemic drugs that synergize with NOTCH1 inhibition in T-ALL. Among these, withaferin A demonstrated the strongest cytotoxic and GSI-synergistic antileukemic effects in vitro and in vivo...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28157396/notch-signaling-modulates-the-balance-of-regulatory-t-cells-and-t-helper-17-cells-in-patients-with-chronic-hepatitis-c
#5
Lei Qin, Yan-Cai Zhou, Hong-Jie Wu, Ya Zhuo, Yan-Ping Wang, Chang-Yun Si, Yong-Mei Qin
The imbalance of regulatory T cells (Tregs) and T helper 17 (Th17) cells contributes to the persistent hepatitis C virus (HCV) infection. However, modulatory factors associated with Tregs-Th17 balance were not fully elucidated. A recent study demonstrated an immunoregulatory strategy by inactivation of Notch signaling to reverse the disequilibrium of Tregs-Th17 cells in immune thrombocytopenia. Thus, the aim of this study was to assess the effect of Notch signaling in regulating the functions of Tregs and Th17 cells in chronic hepatitis C...
February 3, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28157201/longitudinal-in-vivo-bioimaging-of-hepatocyte-transcription-factor-activity-following-cholestatic-liver-injury-in-mice
#6
Juliette M K M Delhove, Suzanne M K Buckley, Dany P Perocheau, Rajvinder Karda, Patrick Arbuthnot, Neil C Henderson, Simon N Waddington, Tristan R McKay
Molecular mechanisms regulating liver repair following cholestatic injury remain largely unknown. We have combined a mouse model of acute cholestatic liver injury, partial bile duct ligation (pBDL), with a novel longitudinal bioimaging methodology to quantify transcription factor activity during hepatic injury and repair. We administered lentiviral transcription factor activated luciferase/eGFP reporter (TFAR) cassettes to neonatal mice enabling longitudinal TFAR profiling by continued bioimaging throughout the lives of the animals and following pBDL in adulthood...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28148821/the-notch-pathway-in-the-annelid-platynereis-insights-into-chaetogenesis-and-neurogenesis-processes
#7
Eve Gazave, Quentin I B Lemaître, Guillaume Balavoine
Notch is a key signalling pathway playing multiple and varied functions during development. Notch regulates the selection of cells with a neurogenic fate and maintains a pool of yet uncommitted precursors through lateral inhibition, both in insects and in vertebrates. Here, we explore the functions of Notch in the annelid Platynereis dumerilii (Lophotrochozoa). Conserved components of the pathway are identified and a scenario for their evolution in metazoans is proposed. Unexpectedly, neither Notch nor its ligands are expressed in the neurogenic epithelia of the larva at the time when massive neurogenesis begins...
February 2017: Open Biology
https://www.readbyqxmd.com/read/28145431/mir-34a-inhibits-pancreatic-cancer-progression-through-snail1-mediated-epithelial-mesenchymal-transition-and-the-notch-signaling-pathway
#8
Yan Tang, Yong Tang, Ying-Sheng Cheng
Epithelial-mesenchymal transition (EMT) and Notch signaling are important for the growth and invasion of pancreatic cancer, which is a leading cause of cancer-related deaths worldwide. miR-34a has been shown to play pivotal roles in the progression of several types of cancer. However, little is known about the regulatory mechanisms of miR-34a in pancreatic cancer processes. The aim of this study was to determine whether miR-34a has negative effects on pancreatic cancer and whether these effects are related to EMT and Notch signaling...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28143872/musashi-rna-binding-proteins-as-cancer-drivers-and-novel-therapeutic-targets
#9
Alexander E Kudinov, John Karanicolas, Erica A Golemis, Yanis Boumber
Aberrant gene expression that drives human cancer can arise from epigenetic dysregulation. While much attention has focused on altered activity of transcription factors and chromatin-modulating proteins, proteins that act post-transcriptionally can potently affect expression of oncogenic signaling proteins. The RNA-binding proteins (RBPs) Musashi-1 (MSI1) and Musashi-2 (MSI2) are emerging as regulators of multiple critical biological processes relevant to cancer initiation, progression, and drug resistance...
January 31, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28140690/effects-of-cell-penetrating-notch-inhibitory-peptide-conjugated-to-elastin-like-polypeptide-on-glioblastoma-cells
#10
Teuta Opačak-Bernardi, Jung Su Ryu, Drazen Raucher
Notch pathway was found to be activated in most glioblastomas (GBM), underlining the importance of Notch in formation and recurrence of GBM. In this study, a Notch inhibitory peptide, dominant negative MAML (dnMAML), was conjugated to Elastin-like polypeptide (ELP) for tumor targeted delivery. ELP is a thermally responsive polypeptide that can be actively and passively targeted to the tumor site by localized application of hyperthermia. This complex was further modified with the addition of a cell penetrating peptide, SynB1, for improved cellular uptake and blood-brain barrier penetration...
January 31, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28139517/role-of-jagged1-hey1-signal-in-angiotensin-ii-induced-impairment-of-myocardial-angiogenesis
#11
Ai-Li Guan, Tao He, Yi-Bing Shao, Yi-Fan Chi, Hong-Yan Dai, Yan Wang, Li Xu, Xuan Yang, Hua-Min Ding, Shang-Lang Cai
BACKGROUND: Angiotensin II (Ang II) is a major contributor to the development of heart failure. However, the molecular and cellular mechanisms that underlie this process remain elusive. Inadequate angiogenesis in the myocardium leads to a transition from cardiac hypertrophy to dysfunction, and our previous study showed that Ang II significantly impaired the angiogenesis response. The current study was designed to examine the role of Jagged1-Notch signaling in the effect of Ang II during impaired angiogenesis and cardiac hypertrophy...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28137842/enteroviruses-infect-human-enteroids-and-induce-antiviral-signaling-in-a-cell-lineage-specific-manner
#12
Coyne G Drummond, Alexa M Bolock, Congrong Ma, Cliff J Luke, Misty Good, Carolyn B Coyne
Enteroviruses are among the most common viral infectious agents of humans and are primarily transmitted by the fecal-oral route. However, the events associated with enterovirus infections of the human gastrointestinal tract remain largely unknown. Here, we used stem cell-derived enteroids from human small intestines to study enterovirus infections of the intestinal epithelium. We found that enteroids were susceptible to infection by diverse enteroviruses, including echovirus 11 (E11), coxsackievirus B (CVB), and enterovirus 71 (EV71), and that contrary to an immortalized intestinal cell line, enteroids induced antiviral and inflammatory signaling pathways in response to infection in a virus-specific manner...
January 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28129650/microrna-34a-regulates-liver-regeneration-and-the-development-of-liver-cancer-in-rats-by-targeting-notch-signaling-pathway
#13
Xiao-Ping Wang, Jian Zhou, Ming Han, Chuan-Bao Chen, Yi-Tao Zheng, Xiao-Shun He, Xiao-Peng Yuan
OBJECTIVE: This study aimed to investigate the role of microRNA-34a (miR-34a) in regulating liver regeneration (LR) and the development of liver cancer in rats by targeting Notch signaling pathway. METHODS: Thirty male Sprague-Dawley (SD) rats were randomly assigned into partial hepatectomy (PH) group and sham hepatectomy (SH) group. Hematoxylin and eosin (HE) staining was used to observe the histological change in liver tissues. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels...
January 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28124402/knock-in-strategy-at-3-end-of-crx-gene-by-crispr-cas9-system-shows-the-gene-expression-profiles-during-human-photoreceptor-differentiation
#14
Kohei Homma, Sumiko Usui, Makoto Kaneda
Fluorescent reporter gene knock-in induced pluripotent stem cell (iPSC) lines have been used to evaluate the efficiency of differentiation into specific cell lineages. Here, we report a knock-in strategy for the generation of human iPSC reporter lines in which a 2A peptide sequence and a red fluorescent protein (E2-Crimson) gene were inserted at the termination codon of the cone-rod homeobox (Crx) gene, a photoreceptor-specific transcriptional factor gene. The knock-in iPSC lines were differentiated into fluorescence-expressing cells in 3D retinal differentiation culture, and the fluorescent cells also expressed Crx specifically in the nucleus...
January 26, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28122586/mir-182-promotes-cancer-invasion-by-linking-ret-oncogene-activated-nf-%C3%AE%C2%BAb-to-loss-of-the-hes1-notch1-regulatory-circuit
#15
Alf Spitschak, Claudia Meier, Bhavani Kowtharapu, David Engelmann, Brigitte M Pützer
BACKGROUND: Dominant-activating mutations in the RET proto-oncogene, a receptor tyrosine kinase, are responsible for the development of medullary thyroid carcinoma (MTC) and causative for multiple endocrine neoplasia (MEN) type 2A and 2B. These tumors are highly aggressive with a high propensity for early metastasis and chemoresistance. This attribute makes this neoplasia an excellent model for probing mechanisms underlying cancer progression. METHODS: The expression level of miR-182 was measured in MTC tumor specimens and in TT cells by real-time RT-PCR...
January 26, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28122332/the-homeoprotein-dlx5-drives-murine-t-cell-lymphomagenesis-by-directly-transactivating-notch-and-upregulating-akt-signaling
#16
Yinfei Tan, Eleonora Sementino, Jinfei Xu, Jianming Pei, Zemin Liu, Timothy K Ito, Kathy Q Cai, Suraj Peri, Andres J P Klein-Szanto, David L Wiest, Joseph R Testa
Homeobox genes play a critical role in embryonic development, but they have also been implicated in cancer through mechanisms that are largely unknown. While not expressed during normal T-cell development, homeobox transcription factor genes can be reactivated via recurrent chromosomal rearrangements in human T-cell acute leukemia/lymphoma (T-ALL), a malignancy often associated with activated Notch and Akt signaling. To address how epigenetic reprogramming via an activated homeobox gene might contribute to T-lymphomagenesis, we investigated a transgenic mouse model with thymocyte-specific overexpression of the Dlx5 homeobox gene...
January 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28108315/essential-role-of-notch4-stat3-signaling-in-epithelial-mesenchymal-transition-of-tamoxifen-resistant-human-breast-cancer
#17
Quyen Thu Bui, Ji Hye Im, Sung Baek Jeong, Young-Mi Kim, Sung Chul Lim, Bumseok Kim, Keon Wook Kang
We previously demonstrated that tamoxifen (TAM)-resistant human breast cancer (TAMR-MCF-7) cells showed increased expression of mesenchymal marker proteins compared to the parent MCF-7 cells. Notch is functionally important in the promotion of epithelial-mesenchymal transition (EMT) during both development and tumor progression. Notch1 and Notch4 have been reported as prognostic markers in human breast cancer. Here, we indicated that Notch4, but not Notch1, plays a critical role in the regulation of EMT signaling in TAMR-MCF-7 cells...
April 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28092987/emerging-treatment-approaches-for-myeloma-related-bone-disease
#18
Maria Gavriatopoulou, Meletios A Dimopoulos, Efstathios Kastritis, Evangelos Terpos
Multiple myeloma is characterized by the presence of osteolytic lesions that leads to devastating skeletal-related events in the majority of patients. Myeloma bone disease is attributed to increased osteoclastic and suppressed osteoblastic activity. Areas covered: Bisphosphonates remain the main treatment option, however they have limitations on their own. Understanding the pathogenesis of myeloma bone disease may provide a roadmap for new therapeutic approaches. The pathway of RANKRANKLOPG pathway has revealed denosumab, a monoclonal antibody targeting RANKL as a novel emerging therapy for myeloma-related bone disease...
January 17, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28086833/delta-like-4-notch-signaling-promotes-apc-min-tumor-initiation-through-angiogenic-and-non-angiogenic-related-mechanisms
#19
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/28071720/polychlorinated-biphenyls-target-notch-dll-and-vegf-r2-in-the-mouse-placenta-and-human-trophoblast-cell-lines-for-their-anti-angiogenic-effects
#20
Satyan Kalkunte, Zheping Huang, Eliana Lippe, Sunil Kumar, Larry W Robertson, Surendra Sharma
The intrauterine environment is particularly vulnerable to environmental exposures. We previously established a mouse model that provided evidence for pregnancy complications and placental anti-angiogenesis in response to Aroclor 1254 (A-1254), a mixture of polychlorinated biphenyls (PCBs). Importantly, these effects were observed in IL-10(-/-), but not wild type, mice, suggesting that IL-10 deficiency predisposes to pregnancy disruptive effects of environmental toxicants. However, the mechanisms by which PCBs cause anti-angiogenic effects are unclear...
January 10, 2017: Scientific Reports
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