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https://www.readbyqxmd.com/read/28211523/pedf-mediates-pathological-neovascularization-by-regulating-macrophage-recruitment-and-polarization-in-the-mouse-model-of-oxygen-induced-retinopathy
#1
Sha Gao, Changwei Li, Yanji Zhu, Yanuo Wang, Ailing Sui, Yisheng Zhong, Bing Xie, Xi Shen
Macrophages have been demonstrated to play a proangiogenic role in retinal pathological vascular growth. Pigment epithelium-derived factor (PEDF) works as a powerful endogenous angiogenesis inhibitor, but its role in macrophage recruitment and polarization is largely unknown. To explore the underlying mechanisms, we first evaluated macrophage polarization in the retinas of the oxygen-induced retinopathy (OIR) mouse model. Compared to that in normal controls, M1- and M2-like macrophages were all abundantly increased in the retinas of OIR mice...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28210849/developmental-changes-in-notch1-and-nle1-expression-in-a-genetic-model-of-absence-epilepsy
#2
Fariba Karimzadeh, Sayed Mostafa Modarres Mousavi, Fatemeh Alipour, Hassan Hosseini Ravandi, Stjepana Kovac, Ali Gorji
Childhood absence epilepsy (CAE) is an epilepsy syndrome with seizures occurring in the early childhood, highlighting that seizures susceptibility in CAE is dependent on brain development. The Notch 1 signalling pathway is important in brain development, yet the role of the Notch1 signalling pathway in CAE remains elusive. We here explored Notch1 and its modulator notchless homologue 1 (NLE1) expression in WAG/Rij and control rats using immunohistochemistry. Functional Notch 1 effects were assessed in WAG/Rij rats in vivo...
February 16, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28208520/re-activation-of-notch1-synergizes-with-multiple-pathways-in-promoting-castration-resistant-prostate-cancer
#3
Anthony Atala
No abstract text is available yet for this article.
March 2017: Journal of Urology
https://www.readbyqxmd.com/read/28205268/the-effect-of-delta-like-1-homologue-on-the-proliferation-and-odontoblastic-differentiation-in-human-dental-pulp-stem-cells
#4
Shengcai Qi, Yanhong Yan, Yue Wen, Jialiang Li, Jing Wang, Fubo Chen, Xiaoshan Tang, Guangwei Shang, Yuanzhi Xu, Raorao Wang
INTRODUCTION: This study aimed to investigate the functions of delta-like homologue 1 (DLK1) in the proliferation and differentiation of human dental pulp stem cells (hDPSCs). METHODS: Immunohistochemical analysis was used to determine the expression of alkaline phosphatase (ALP), dentin sialophosphoprotein (DSPP), DLK1, NOTCH1 and p-ERK1/2 in the mouse first maxillary molar. Recombinant lentivirus was constructed to overexpress DLK1 stably in hDPSCs. The cell viability and proliferation of hDPSCs were examined by CCK8 and EdU incorporation assay respectively...
February 15, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28199989/presence-of-cancer-associated-mutations-in-exhaled-breath-condensates-of-healthy-individuals-by-next-generation-sequencing
#5
Omar Youssef, Aija Knuuttila, Päivi Piirilä, Tom Böhling, Virinder Sarhadi, Sakari Knuutila
Exhaled breath condensate (EBC) is a non-invasive source that can be used for studying different genetic alterations occurring in lung tissue. However, the low yield of DNA available from EBC has hampered the more detailed mutation analysis by conventional methods. We applied the more sensitive amplicon-based next generation sequencing (NGS) to identify cancer related mutations in DNA isolated from EBC. In order to apply any method for the purpose of mutation screening in cancer patients, it is important to clarify the incidence of these mutations in healthy individuals...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28195818/notch1-overexpression-correlates-to-improved-survival-in-cancer-of-the-oropharynx
#6
Azeem S Kaka, Nicholas B Nowacki, Bhavna Kumar, Songzhu Zhao, Matthew O Old, Amit Agrawal, Enver Ozer, Ricardo L Carrau, David E Schuller, Pawan Kumar, Theodoros N Teknos
Objectives The Notch1 signaling pathway has recently been shown to be highly dysregulated in head and neck squamous cell carcinoma, but the value of Notch1 as a predictive biomarker is yet to be elucidated in oropharyngeal squamous cell carcinoma (OPSCC). The objective of this study is to evaluate Notch1 expression in surgical OPSCC specimens and determine clinicopathologic correlates. Study Design Case series with planned data collection. Setting Tertiary academic medical center. Subjects and Methods Surgical specimens from 181 patients with OPSCC were collected to create a tissue microarray (TMA)...
February 1, 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/28192800/molecular-profiling-of-the-developing-lacrimal-gland-reveals-putative-role-of-notch-signaling-in-branching-morphogenesis
#7
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
#8
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/28183698/constitutively-active-notch1-converts-cranial-neural-crest-derived-frontonasal-mesenchyme-to-perivascular-cells-in-vivo
#9
Sophie R Miller, Surangi N Perera, Clare V H Baker
Perivascular/mural cells originate from either the mesoderm or the cranial neural crest. Regardless of their origin, Notch signalling is necessary for their formation. Furthermore, in both chicken and mouse, constitutive Notch1 activation (via expression of the Notch1 intracellular domain) is sufficient in vivo to convert trunk mesoderm-derived somite cells to perivascular cells, at the expense of skeletal muscle. In experiments originally designed to investigate the effect of premature Notch1 activation on the development of neural crest-derived olfactory ensheathing glial cells (OECs), we used in ovo electroporation to insert a tetracycline-inducible NotchΔE construct (encoding a constitutively active mutant of mouse Notch1) into the genome of chicken cranial neural crest cell precursors, and activated NotchΔE expression by doxycycline injection at embryonic day 4...
February 9, 2017: Biology Open
https://www.readbyqxmd.com/read/28181739/absence-of-the-frequently-reported-pik3ca-casp8-and-notch1-mutations-in-south-indian-oral-cancers
#10
Ganesan Arunkumar, Avaniyapuram Kannan Murugan, Maharajan Nagarajan, Chandrasekar Ajay, Ramamurthy Rajaraman, Arasambattu Kannan Munirajan
OBJECTIVES: Somatic mutations of the PIK3CA, CASP8 and NOTCH1 have been frequently detected in various human cancers. Our study aims to analyze the mutational status of these genes in South Indian oral cancers. SUBJECTS AND METHODS: We performed mutational analysis of the PIK3CA (exons 9 & 20), CASP8 (exon 9) and NOTCH1 (exons 5, 6, 7, 8 & 9) genes in 96, 48 and 44 oral cancer samples, respectively. All the specified exons were PCR (polymerase chain reaction) amplified and directly sequenced by Sanger sequencing...
February 9, 2017: Oral Diseases
https://www.readbyqxmd.com/read/28177944/metformin-depresses-overactivated-notch1-hes1-signaling-in-colorectal-cancer-patients-with-type-2-diabetes-mellitus
#11
Bin Yang, Can-Ze Huang, Tao Yu, Sheng-Ning Zhou, Qi Liu, Gao-Jie Liu, Shuang Chen, Fang-Hai Han
The function of metformin in colorectal cancer (CRC) patients with diabetes mellitus (DM) remains a controversial topic because studies are increasingly focusing on epidemiologic features. We examined Notch1/Hes1 signaling in CRC with DM (DM-CRC) and investigated alterations in signaling caused by metformin treatment. For this purpose, information on pathological characteristics was collected from each patient. The proliferation of epithelium labeled with proliferating cell nuclear antigen and the differentiation of goblet cells were investigated using immunohistochemistry and periodic acid-Schiff staining, respectively...
February 7, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28174276/synergistic-antileukemic-therapies-in-notch1-induced-t-all
#12
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/28169962/parkin-mediates-neuroprotection-through-activation-of-notch1-signaling
#13
Ji-Hye Yoon, Eun-Jung Ann, Mi-Yeon Kim, Ji-Seon Ahn, Eun-Hye Jo, Hye-Jin Lee, Hye-Won Lee, Young Chul Lee, Jeong-Sun Kim, Hee-Sae Park
Parkin, an E3 ubiquitin ligase, is the most frequently mutated gene in hereditary Parkinson's disease. Inactivation of Parkin leads to impairment of the ubiquitin-proteasome system, resulting in the accumulation of misfolded or aggregated proteins and ensuing neurodegeneration. In this study, we show that Parkin positively regulates the Notch1 signaling pathway. Overexpression of Parkin stabilized Notch1-IC protein levels, whereas knockdown of Parkin decreased Notch1-IC protein stability. Notably, overexpression of Parkin disrupted oxidative stress-induced apoptosis in neuronal cells...
February 4, 2017: Neuroreport
https://www.readbyqxmd.com/read/28160419/adams-oliver-syndrome-review-of-the-literature-refining-the-diagnostic-phenotype
#14
Susan Hassed, Shibo Li, John Mulvihill, Christopher Aston, Susan Palmer
The Adams-Oliver syndrome (AOS) is defined as aplasia cutis congenita (ACC) with transverse terminal limb defects (TTLD). Frequencies of associated anomalies are not well characterized. Six causative genes have been identified: ARHGAP31, DOCK6, EOGT, RBPJ, NOTCH1, and DLL4. We review 385 previously described individuals (139 non-familial and 246 familial probands and family members) and add clinical data on 13 previously unreported individuals with AOS. In addition to ACC and TTLD, the most commonly associated anomalies included a wide variety of central nervous system (CNS) anomalies and congenital heart defects each seen in 23%...
February 4, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28158917/autophagy-is-involved-in-mouse-kidney-development-and-podocyte-differentiation-regulated-by-notch-signalling
#15
Chuyue Zhang, Wen Li, Junkai Wen, Zhuo Yang
Podocyte dysfunction results in glomerular diseases accounted for 90% of end-stage kidney disease. The evolutionarily conserved Notch signalling makes a crucial contribution in podocyte development and function. However, the underlying mechanism of Notch pathway modulating podocyte differentiation remains less obvious. Autophagy, reported to be related with Notch signalling pathways in different animal models, is regarded as a possible participant during podocyte differentiation. Here, we found the dynamic changes of Notch1 were coincided with autophagy: they both increased during kidney development and podocyte differentiation...
February 3, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28157712/the-interference-of-notch1-target-hes1-affects-cell-growth-differentiation-and-invasiveness-of-glioblastoma-stem-cells-through-modulation-of-multiple-oncogenic-targets
#16
Carlo Cenciarelli, Hany E Marei, Manuela Zonfrillo, Patrizia Casalbore, Armando Felsani, Stefano Giannetti, Gianluca Trevisi, Asma Althani, Annunziato Mangiola
The invasive and lethal nature of Glioblastoma multiforme (GBM) necessitates the continuous identification of molecular targets and search of efficacious therapies to inhibit GBM growth. The GBM resistance to chemotherapy and radiation it is attributed to the existence of a rare fraction of cancer stem cells (CSC) that we have identified within the tumor core and in peritumor tissue of GBM. Since Notch1 pathway is a potential therapeutic target in brain cancer, earlier we highlighted that pharmacological inhibition of Notch1 signalling by γ-secretase inhibitor-X (GSI-X), reduced cell growth of some c-CSC than to their respective p-CSC, but produced negligible effects on cell cycle distribution, apoptosis and cell invasion...
February 2, 2017: Oncotarget
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
#17
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/28157189/identification-of-cell-type-specific-mutations-in-nodal-t-cell-lymphomas
#18
T B Nguyen, M Sakata-Yanagimoto, Y Asabe, D Matsubara, J Kano, K Yoshida, Y Shiraishi, K Chiba, H Tanaka, S Miyano, K Izutsu, N Nakamura, K Takeuchi, H Miyoshi, K Ohshima, T Minowa, S Ogawa, M Noguchi, S Chiba
Recent genetic analysis has identified frequent mutations in ten-eleven translocation 2 (TET2), DNA methyltransferase 3A (DNMT3A), isocitrate dehydrogenase 2 (IDH2) and ras homolog family member A (RHOA) in nodal T-cell lymphomas, including angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified. We examined the distribution of mutations in these subtypes of mature T-/natural killer cell neoplasms to determine their clonal architecture. Targeted sequencing was performed for 71 genes in tumor-derived DNA of 87 cases...
January 6, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28157139/genetic-basis-of-aortic-valvular-disease
#19
Sara N Koenig, Joy Lincoln, Vidu Garg
PURPOSE OF REVIEW: Aortic valve disease is relatively common and encompasses both congenital and acquired forms. Bicuspid aortic valve (BAV) is the most common type of cardiac malformation and predisposes to the development of calcific aortic valve disease (CAVD). Since the description of the link between NOTCH1, BAV and CAVD approximately a decade ago, there have been significant advances in the genetic and molecular understanding of these diseases. RECENT FINDINGS: Recent work has defined the congenital cardiac phenotypes linked to mutations in NOTCH1, and in addition, novel etiologic genes for BAV have been discovered using new genetic technologies in humans...
February 2, 2017: Current Opinion in Cardiology
https://www.readbyqxmd.com/read/28151717/synergistic-drug-combinations-with-a-cdk4-6-inhibitor-in-t-cell-acute-lymphoblastic-leukemia
#20
Yana Pikman, Gabriela Alexe, Giovanni Roti, Amy Saur Conway, Andrew Furman, Emily S Lee, Andrew E Place, Sunkyu Kim, Chitra Saran, Rebecca Modiste, David M Weinstock, Marian Harris, Andrew L Kung, Lewis B Silverman, Kimberly Stegmaier
PURPOSE: While significant progress has been made in the treatment of T-cell acute lymphoblastic leukemia (T-ALL), many patients will require additional therapy for relapsed/refractory disease. Cyclin D3 (CCND3) and CDK6 are highly expressed in T-ALL and have been effectively targeted in mutant NOTCH1-driven mouse models of this disease with a CDK4/6 small-molecule inhibitor. Combination therapy, however, will be needed for the successful treatment of human disease. EXPERIMENTAL DESIGN: We performed preclinical drug testing using a panel of T-ALL cell lines first with LEE011, a CDK4/6 inhibitor, and next with the combination of LEE011 with a panel of drugs relevant to T-ALL treatment...
November 9, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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