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Notch signaling

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https://www.readbyqxmd.com/read/28212801/notch-signaling-in-vascular-smooth-muscle-cells
#1
J T Baeten, B Lilly
The Notch signaling pathway is a highly conserved pathway involved in cell fate determination in embryonic development and also functions in the regulation of physiological processes in several systems. It plays an especially important role in vascular development and physiology by influencing angiogenesis, vessel patterning, arterial/venous specification, and vascular smooth muscle biology. Aberrant or dysregulated Notch signaling is the cause of or a contributing factor to many vascular disorders, including inherited vascular diseases, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, associated with degeneration of the smooth muscle layer in cerebral arteries...
2017: Advances in Pharmacology
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/28210556/are-breast-cancer-stem-cells-the-key-to-resolving-clinical-issues-in-breast-cancer-therapy
#3
REVIEW
Hidetaka Shima, Akimitsu Yamada, Takashi Ishikawa, Itaru Endo
Despite the dramatic advances in breast cancer treatment over the past two decades, it is still the most common malignancies in women. One of the reasons patients succumb to breast cancer is treatment resistance leading to metastasis and recurrence. Recently, cancer stem cells (CSCs) have been suggested as a cause of metastasis and recurrence in several cancers because of their unique characteristics, including self-renewal, pluripotency, and high proliferative ability. Increasing evidence has implicated breast cancer stem cells (BCSCs) as essential for tumor development, progression, recurrence, and treatment resistance...
February 2017: Gland Surgery
https://www.readbyqxmd.com/read/28207739/overexpression-of-notch-regulated-ankyrin-repeat-protein-is-associated-with-papillary-thyroid-carcinoma-progression
#4
Mingdi Zhang, Yiyu Qin, Bin Zuo, Wei Gong, Shenglai Zhang, Yurong Gong, Zhiwei Quan, Bingfeng Chu
Papillary thyroid cancer (PTC) is one of the endocrine cancers with high clinical and genetic heterogeneity. NOTCH signaling and its downstream NOTCH-Regulated Ankyrin Repeat Protein (NRARP) have been implicated in oncogenesis of many cancers, but the roles in PTCs are less studied. In this study, we show that NRARP is frequently over-expressed in thyroid carcinoma. The over-activation of NRARP is highly and positively correlated with NOTCH genes. Moreover, we find that the expression of NRARP is highly associated with several epithelial mesenchymal transition (EMT) markers and contributes to poor survival outcomes...
2017: PloS One
https://www.readbyqxmd.com/read/28205312/essential-roles-of-tbx3-in-embryonic-skin-development-during-epidermal-stratification
#5
Ryo Ichijo, Yui Iizuka, Hirokazu Kubo, Fumiko Toyoshima
Stepwise differentiation of epidermal cells is essential for development of stratified epithelium, but the underlying mechanisms remain unclear. Here, we show that Tbx3, a member of the T-box family of transcription factors, plays a pivotal role in this mechanism. Tbx3 is expressed in both basal and suprabasal cells in the interfollicular epidermis of mouse embryos. Epidermis-specific Tbx3 conditional knockout (cKO) embryos are small in size and display a thinner epidermis with an impaired barrier function...
February 16, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28202832/-prognostic-impact-of-radiation-therapy-and-molecular-classification-of-infant-atypical-teratoid-rhabdoid-tumors
#6
Yoshihiro Otani, Tomotsugu Ichikawa, Kazuhiko Kurozumi, Takao Yasuhara, Kana Washio, Akira Shimada, Norihisa Katayama, Kuniaki Katsui, Hiroyuki Yanai, Isao Date
Atypical teratoid/rhabdoid tumor(AT/RT)is a rare and lethal childhood cancer. Although radiation therapy in children less than three years of age is generally deferred because of its neural toxicity, recent studies have shown that multimodal therapies, including radiation therapy, are effective in pediatric patients with AT/RT less than three years of age. We treated four infant AT/RT patients and investigated the impact of radiation therapy and genetic classification on the prognosis. The mean age at the time of the operation was 9...
February 2017: No Shinkei Geka. Neurological Surgery
https://www.readbyqxmd.com/read/28195086/altered-expressions-of-notch-1-signaling-proteins-and-beta-catenin-in-progression-of-carcinoma-in-situ-into-squamous-carcinoma-of-uterine-cervix
#7
Na-Hye Myong
BACKGROUND: Activation of Notch-1 signaling pathway and loss of membranous beta-catenin have been known to play key roles in the progression of uterine cervix cancer and thus this study focused any alteration in the expression patterns for Notch-1, p53, and cyclin D1 as well as beta-catenin in squamous carcinoma in situ (CIS) and invasive squamous carcinomas to investigate their roles in the progression of CIS to squamous carcinomas. MATERIALS AND METHODS: Three Notch-1 signaling proteins, such as Notch-1, TP53, and cyclin D1, and a component of cell adhesion complex, beta-catenin, were immunohistochemically stained in 112 uterine cervical tumors including 74 CIS and 38 invasive squamous carcinomas (11 microinvasive and 27 invasive carcinomas)...
January 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/28192800/molecular-profiling-of-the-developing-lacrimal-gland-reveals-putative-role-of-notch-signaling-in-branching-morphogenesis
#8
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/28191691/bace1-regulates-the-proliferation-and-cellular-functions-of-schwann-cells
#9
Xiangyou Hu, Hailong Hou, Chinthasagar Bastian, Wanxia He, Shupeng Qiu, Yingying Ge, Xinhua Yin, Grahame J Kidd, Sylvain Brunet, Bruce D Trapp, Selva Baltan, Riqiang Yan
BACE1 is an indispensable enzyme for generating β-amyloid peptides, which are excessively accumulated in brains of Alzheimer's patients. However, BACE1 is also required for proper myelination of peripheral nerves, as BACE1-null mice display hypomyelination. To determine the precise effects of BACE1 on myelination, here we have uncovered a role of BACE1 in the control of Schwann cell proliferation during development. We demonstrate that BACE1 regulates the cleavage of Jagged-1 and Delta-1, two membrane-bound ligands of Notch...
February 13, 2017: Glia
https://www.readbyqxmd.com/read/28186974/a-notch-sensitive-upar-regulated-oncolytic-adenovirus-effectively-suppresses-pancreatic-tumor-growth-and-triggers-synergistic-anticancer-effects-with-gemcitabine-and-nab-paclitaxel
#10
Ana Mato-Berciano, Giulia Raimondi, Maria Victoria Maliandi, Ramon Alemany, Lluis Montoliu, Cristina Fillat
Notch signaling pathway is an embryonic program that becomes reactivated in pancreatic cancer and contributes to cancer stem cell (CSC) maintenance. We explored the concept of oncolytic adenoviral activity in response to Notch activation signaling, in the context of a chimeric promoter with uPAR regulatory sequences, as a strategy to drive its activity in neoplastic and CSC. We explored the advantages of a chemo-virotherapy approach based on synergistic combinations. Regulatory sequences recognized by the transcriptional factor CSL upstream a minimal uPAR promoter were engineered in adenoviral vectors and in the oncolytic adenovirus AdNuPARmE1A...
February 7, 2017: Oncotarget
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
#11
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/28185609/olfactory-ensheathing-cells-inhibit-gliosis-in-retinal-degeneration-by-down-regulation-of-the-m%C3%A3-ller-cell-notch-signaling-pathway
#12
Jing Xie, Shujia Huo, Yijian Li, Jiaman Dai, Haiwei Xu, Zheng Qin Yin
Retinal regeneration and self-repair, whether in response to injury or degenerative disease, are severely impeded by glial scar formation by Müller cells (specialized retinal macroglia). We have previously demonstrated that the activation of Müller cells and gliosis in the degenerative retina are significantly suppressed by the subretinal transplantation of a mixture of olfactory ensheathing cells (OECs) and olfactory nerve fibroblasts. However, the underlying molecular mechanism has remained elusive. Here, we transplanted purified rat OECs into the subretinal space of pigmented Royal College of Surgeons (RCS) rats, a classic rodent model of retinal degeneration...
February 9, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28184337/atoh1-as-a-coordinator-of-sensory-hair-cell-development-and-regeneration-in-the-cochlea
#13
Sungsu Lee, Han-Seong Jeong, Hyong-Ho Cho
Cochlear sensory hair cells (HCs) are crucial for hearing as mechanoreceptors of the auditory systems. Clarification of transcriptional regulation for the cochlear sensory HC development is crucial for the improvement of cell replacement therapies for hearing loss. Transcription factor Atoh1 is the key player during HC development and regeneration. In this review, we will focus on Atoh1 and its related signaling pathways (Notch, fibroblast growth factor, and Wnt/β-catenin signaling) involved in the development of cochlear sensory HCs...
January 2017: Chonnam Medical Journal
https://www.readbyqxmd.com/read/28183698/constitutively-active-notch1-converts-cranial-neural-crest-derived-frontonasal-mesenchyme-to-perivascular-cells-in-vivo
#14
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/28178391/amino-terminal-enhancer-of-split-gene-aes-encodes-a-tumor-and-metastasis-suppressor-of-prostate-cancer
#15
Yoshiyuki Okada, Masahiro Sonoshita, Fumihiko Kakizaki, Naoki Aoyama, Yoshiro Itatani, Masayuki Uegaki, Hiromasa Sakamoto, Takashi Kobayashi, Takahiro Inoue, Tomomi Kamba, Akira Suzuki, Osamu Ogawa, M Mark Taketo
Major cause of cancer death is its metastasis to the vital organs. Few effective therapies are available for metastatic castration-resistant prostate cancer (PCa), and progressive metastatic lesions such as lymph nodes and bones cause mortality. We recently identified AES as a metastasis suppressor for colon cancer. Here, we have studied the roles of AES in PCa progression. We analyzed the relationship between AES expression and PCa stages of progression by immunohistochemistry of human needle biopsy samples...
February 8, 2017: Cancer Science
https://www.readbyqxmd.com/read/28176674/a-model-for-generating-synthetic-arterial-blood-pressure
#16
A Mahdi, G D Clifford, S J Payne
A new model capable of simulating many important aspects of human arterial blood pressure (ABP) is proposed. Both data-driven approach and physiological principles have been applied to describe the time series of diastolic, systolic, dicrotic notch and dicrotic peak pressure points. Major static and dynamic features of the model can be prescribed by the user, including heart rate, mean systolic and diastolic pressure, and the corresponding physiological control quantities, such as baroreflex sensitivity coefficient and Windkessel time constant...
February 8, 2017: Physiological Measurement
https://www.readbyqxmd.com/read/28176469/epcam-liver-cancer-stem-like-cells-exhibiting-autocrine-wnt-signaling-potentially-originate-in-cirrhotic-patients
#17
Ritu Khosla, Archana Rastogi, Gayatri Ramakrishna, Viniyendra Pamecha, Ashok Mukhopadhyay, Madavan Vasudevan, Shiv Kumar Sarin, Nirupma Trehanpati
Hepatocellular carcinoma (HCC) is believed to originate from cancer stem cells (CSCs). While epithelial cell adhesion molecule (EpCAM) is a marker of normal hepatic stem cells (HSCs), EpCAM+ cells from HCC behave like CSCs. Since HCC mostly develops on a cirrhotic background, we sought to determine whether CSC-like EpCAM+ cells exist in patients with advanced cirrhosis. Both flow cytometry and immunohistochemistry showed that frequency of EpCAM+ cells in advanced cirrhosis was increased as compared to control...
February 8, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28174757/transcriptional-regulation-by-atoh1-and-its-target-spdef-in%C3%A2-the%C3%A2-intestine
#18
Yuan-Hung Lo, Eunah Chung, Zhaohui Li, Ying-Wooi Wan, Maxime M Mahe, Min-Shan Chen, Taeko K Noah, Kristin N Bell, Hari Krishna Yalamanchili, Tiemo J Klisch, Zhandong Liu, Joo-Seop Park, Noah F Shroyer
BACKGROUND & AIMS: The transcription factor atonal homolog 1 (ATOH1) controls the fate of intestinal progenitors downstream of the Notch signaling pathway. Intestinal progenitors that escape Notch activation express high levels of ATOH1 and commit to a secretory lineage fate, implicating ATOH1 as a gatekeeper for differentiation of intestinal epithelial cells. Although some transcription factors downstream of ATOH1, such as SPDEF, have been identified to specify differentiation and maturation of specific cell types, the bona fide transcriptional targets of ATOH1 still largely are unknown...
January 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28174276/synergistic-antileukemic-therapies-in-notch1-induced-t-all
#19
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/28174252/trbp-maintains-mammalian-embryonic-neural-stem-cell-properties-by-enhancing-the-notch-signaling-pathway-as-a-novel-transcriptional-coactivator
#20
Sung-Hyun Byun, Juwan Kim, Dasol Han, Mookwang Kwon, Jae Youl Cho, Hui Xuan Ng, Samuel J Pleasure, Keejung Yoon
Transactivation response element RNA-binding protein (TRBP) is known to play important roles in human immunodeficiency virus (HIV) replication and microRNA biogenesis. However, recent studies implicate TRBP in a variety of biological processes as a mediator for cross-talk between signal transduction pathways. Here, we provide the first evidence that TRBP is required for efficient neurosphere formation, and expression of neural stem cell markers and Notch target genes in primary neural progenitor cells in vitro Consistent with this, introduction of TRBP into the mouse embryonic brain in utero increased the fraction of cells expressing Sox2 in the ventricular zone (VZ)...
February 7, 2017: Development
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