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https://www.readbyqxmd.com/read/29150595/notch1-signaling-activation-contributes-to-adult-hippocampal-neurogenesis-following-traumatic-brain-injury
#1
Ming Tu, Penglei Zhu, Shaobo Hu, Wei Wang, Zhipeng Su, Jiaqing Guan, Chongran Sun, Weiming Zheng
BACKGROUND Neural stem cells are reported to exist in the hippocampus of adult mammals and are important sources of neurons for repair. The Notch1 signaling pathway is considered as one of the important regulators of neural stem cells, but its role in adult brains is unclear. We aimed to describe the role of Notch1 signaling in the adult rat hippocampus after traumatic brain injury. MATERIAL AND METHODS The model rats were randomly divided into 4 groups as follows: sham, sham-TBI, sham-Ad-TBI, and NICD-Ad-TBI...
November 18, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29146722/the-notch4-hey1-pathway-induces-epithelial-mesenchymal-transition-in-head-and-neck-squamous-cell-carcinoma
#2
Takahito Fukusumi, Theresa Guo, Akihiro Sakai, Mizuo Ando, Shuling Ren, Sunny Haft, Chao Liu, Panomwat Amornphimoltham, J Silvio Gutkind, Joseph Califano
BACKGROUND: Recently, several comprehensive genomic analyses demonstrated NOTCH1 and NOTCH3 mutations in head and neck squamous cell carcinoma (HNSCC) in approximately 20% of cases. Similar to other types of cancers, these studies also indicate that the NOTCH pathway is closely related to HNSCC progression. However, the role of NOTCH4 in HNSCC is less well understood. METHODS: We analyzed NOTCH4 pathway and downstream gene expression in the TCGA data set. To explore the functional role of NOTCH4, we performed in vitro proliferation, cisplatin viability, apoptosis, and cell cycle assays...
November 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29141398/the-prognostic-significance-of-notch1-and-fatty-acid-binding-protein-7-fabp7-expression-in-resected-tracheobronchial-adenoid-cystic-carcinoma-a-multicenter-retrospective-study
#3
Mian Xie, Xiaojun Wu, Jinjun Zhang, Chaosheng He, Shenhai Wei, Junyao Huang, Xinge Fu, Yingying Gu
Purpose: Adenoid cystic carcinoma (ACC) of the trachea and bronchus is a rare tumor. Although MYB-NFIB oncogene fusion and Notch1 mutation have been identified in adenoid cystic carcinoma (ACC), little is known about the expression and clinical significance of Notch1 and its target gene fatty acid binding protein 7 (FABP7) in tracheobronchial ACC. Materials and Methods: Primary tracheobronchial ACC that were resected between 1998 and 2014 were identified through the pathology and oncology database from five thoracic oncology centers in China...
November 15, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29140246/an-eya1-notch-axis-specifies-bipotential-epibranchial-differentiation-in-mammalian-craniofacial-morphogenesis
#4
Haoran Zhang, Li Wang, Elaine Yee Man Wong, Sze Lan Tsang, Pin-Xian Xu, Urban Lendahl, Mai Har Sham
Craniofacial morphogenesis requires proper development of pharyngeal arches and epibranchial placodes. We show that the epibranchial placodes, in addition to giving rise to cranial sensory neurons, generate a novel lineage-related non-neuronal cell population for mouse pharyngeal arch development. Eya1 is essential for the development of epibranchial placodes and proximal pharyngeal arches. We identify an Eya1-Notch regulatory axis that specifies both the neuronal and non-neuronal commitment of the epibranchial placode, where Notch acts downstream of Eya1 and promotes the non-neuronal cell fate...
November 15, 2017: ELife
https://www.readbyqxmd.com/read/29139178/notch1-and-notch2-coordinately-regulate-stem-cell-function-in-the-quiescent-and-activated-states-of-muscle-satellite-cells
#5
Shin Fujimaki, Daiki Seko, Yasuo Kitajima, Kiyoshi Yoshioka, Yoshifumi Tsuchiya, Shinya Masuda, Yusuke Ono
Satellite cells, the muscle tissue stem cells, express three Notch receptors (Notch1-3). The function of Notch1 and Notch2 in satellite cells has to date not been fully evaluated. We investigated the role of Notch1 and Notch2 in myogenic progression in adult skeletal muscle using tamoxifen-inducible satellite cell-specific conditional knockout mice for Notch1 (N1-scKO), Notch2 (N2-scKO), and Notch1/Notch2 (scDKO). In the quiescent state, the number of satellite cells was slightly reduced in N2-scKO, but not significantly in N1-scKO, and almost completely depleted in scDKO mice...
November 15, 2017: Stem Cells
https://www.readbyqxmd.com/read/29138545/activation-of-notch1-signaling-alleviates-dysfunction-of-bone-marrow-derived-mesenchymal-stem-cells-induced-by-cigarette-smoke-extract
#6
Yi Cheng, Wen Gu, Guorui Zhang, Xiaoming Li, Xuejun Guo
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are considered attractive therapeutic agents for the treatment of COPD. However, little is known about the impact of Notch on the proliferation, migration, and survival of MSCs in a cigarette smoke (CS) microenvironment. Here, we used CS extract to mimic the CS microenvironment in vitro, with the intention to investigate the effect of Notch in regulating proliferation, migration, and survival of BM-MSCs. Rat bone marrow mesenchymal stem cells were infected with lentivirus vector containing the intracellular domain of Notch1 (N1ICD) and challenged with CS extract...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29138297/mafb-enhances-oncogenic-notch-signaling-in-t-cell-acute-lymphoblastic-leukemia
#7
Kostandin V Pajcini, Lanwei Xu, Lijian Shao, Jelena Petrovic, Karol Palasiewicz, Yumi Ohtani, Will Bailis, Curtis Lee, Gerald B Wertheim, Rajeswaran Mani, Natarajan Musuthamy, Yunlei Li, Jules P P Meijerink, Stephen C Blacklow, Robert B Faryabi, Sara Cherry, Warren S Pear
Activating mutations in the gene encoding the cell-cell contact signaling protein Notch1 are common in human T cell acute lymphoblastic leukemias (T-ALLs). However, expressing Notch1 mutant alleles in mice fails to efficiently induce the development of leukemia. We performed a gain-of-function screen to identify proteins that enhanced signaling by leukemia-associated Notch1 mutants. The transcription factors MAFB and ETS2 emerged as candidates that individually enhanced Notch1 signaling, and when coexpressed, they synergistically increased signaling to an extent similar to that induced by core components of the Notch transcriptional complex...
November 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/29136506/a-paradoxical-tumor-suppressor-role-for-the-rac1-exchange-factor-vav1-in-t-cell-acute-lymphoblastic-leukemia
#8
Javier Robles-Valero, L Francisco Lorenzo-Martín, Mauricio Menacho-Márquez, Isabel Fernández-Pisonero, Antonio Abad, Mireia Camós, María L Toribio, Lluis Espinosa, Anna Bigas, Xosé R Bustelo
Rho guanine exchange factors (GEFs), the enzymes that stimulate Rho GTPases, are deemed as potential therapeutic targets owing to their protumorigenic functions. However, the understanding of the spectrum of their pathobiological roles in tumors is still very limited. We report here that the GEF Vav1 unexpectedly possesses tumor-suppressor functions in immature T cells. This function entails the noncatalytic nucleation of complexes between the ubiquitin ligase Cbl-b and the intracellular domain of Notch1 (ICN1) that favors ICN1 ubiquitinylation and degradation...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29126793/inhibition-of-notch1-hes1-signaling-pathway-improves-radiosensitivity-of-colorectal-cancer-cells
#9
Hongzhi Zhang, Huijuan Jiang, Lei Chen, Juncai Liu, Xigang Hu, Huixiang Zhang
Notch signaling pathway has been demonstrated to mediate radioresistance of several tumors. Our study aims to explore the function of Notch1/HES1 pathway in the radioresistance of colorectal cancer (CRC). The results demonstrated that expressions of Notch1 and Hes1 were up-regulated with the increasing irradiation dose. DAPT (N-[(3,5-difluorophenacetyl)acety1]-L-alanyl-2-phenyl]glycine-1,1-dimethylethyl ester) or si-Notch1 reduced expressions of Notch1 and Hes1, exacerbated irradiation-induced cell proliferation inhibition, and improved radiosensitivity of CRC cells...
November 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29126187/med12-regulates-ovarian-steroidogenesis-uterine-development-and-maternal-effects-in-the-mammalian-egg
#10
Xinye Wang, Priya Mittal, Carlos A Castro, Gabriel Rajkovic, Aleksandar Rajkovic
The transcriptional factor MED12 is part of the essential mediator transcriptional complex that acts as a transcriptional coactivator in all eukaryotes. Missense gain of function mutations in human MED12 are associated with uterine leiomyomas, yet the role of MED12 deficiency in tumorigenesis and reproductive biology has not been fully explored. We generated a Med12 reproductive conditional knockout mouse model to evaluate its role in uterine mesenchyme, granulosa cells, and oocytes. Mice heterozygous for Med12 deficiency in granulosa cells and uterus (Med12fl/+ Amhr2-Cre) were subfertile, while mice homozygous for Med12 deficiency in granulosa cells and uterus (Med12fl/fl Amhr2-Cre) were infertile...
November 8, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29123981/coculture-of-endothelial-progenitor-cells-and-mesenchymal-stem-cells-enhanced-their-proliferation-and-angiogenesis-through-pdgf-and-notch-signaling
#11
Tangzhao Liang, Lei Zhu, Wenling Gao, Ming Gong, Jianhua Ren, Hui Yao, Kun Wang, Dehai Shi
The beneficial effects of combined use of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) on tissue repair and regeneration after injury have been demonstrated, but the underlying mechanism remains incompletely understood. This study aimed to investigate the effects of direct contact coculture of human bone marrow-derived EPCs (hEPCs)/human bone marrow-derived MSCs (hMSCs) on their proliferation and angiogenic capacities and the underlying mechanism. hEPCs and hMSCs were cocultured in a 2D mixed monolayer or a 3D transwell membrane cell-to-cell coculture system...
November 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/29120527/castle-tumor-of-the-parotid-first-documented-case-literature-review-and-genetic-analysis-of-the-cancer
#12
Eugene Hung Chih Wong, Nora Tetter, Alexandar Tzankov, Laurent Muller
BACKGROUND: Carcinoma showing thymus-like elements (CASTLE) is a rare tumor that normally affects the thyroid gland and was thought to arise from either the remnants of the branchial pouch or the ectopic cervical thymic tissue. These tumors show strong immunopositivity for CD5, P63, and CD117. Most CASTLE of the thyroid gland is treated with surgery with or without adjuvant radiotherapy or chemotherapy. METHOD: A 55-year-old woman presented with a slow-growing right parotid mass...
November 9, 2017: Head & Neck
https://www.readbyqxmd.com/read/29117785/notch1-regulates-tongue-cancer-cells-proliferation-apoptosis-and-invasion
#13
Rui-Huan Gan, Hua Wei, Jing Xie, Dan-Ping Zheng, Er-Ling Luo, Xiao-Yu Huang, Jian Xie, Yong Zhao, Lin-Can Ding, Bo-Hua Su, Li-Song Lin, Da-Li Zheng, You-Guang Lu
OBJECTIVES: Notch1 regulates tumor biology in a complex, context-dependent manner. The roles of Notch1 in tongue cancer are still controversial. The aim of this study is to investigate the roles of Notch1 in tongue cancer. MATERIALS AND METHODS: The expression of Notch1 was tested between tongue cancer and normal samples by using immunohistochemistry. Tongue cancer cells were transfected with siRNA or plasmid, respectively. Cell proliferation, apoptosis, migration and invasion ability were tested in appropriate ways...
November 8, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29117356/spatio-temporal-genomic-heterogeneity-phylogeny-and-metastatic-evolution-in-salivary-adenoid-cystic-carcinoma
#14
Bin Liu, Yoshitsugu Mitani, Xiayu Rao, Mark Zafereo, Jianjun Zhang, Jianhua Zhang, P Andrew Futreal, Guillermina Lozano, Adel K El-Naggar
Background: Adenoid cystic carcinoma (ACC), an uncommon and indolent salivary gland malignancy, is characterized by varied morphologic and clinical manifestations. Molecular genetic studies of ACC identified certain structural and mutational alterations that may play a driver role in tumor development. The evolution and regional consistency of these events in ACC development progression are uncertain. Methods: To investigate the spatial and temporal clonal landscape of ACC, whole-genome sequencing and variant analyses were performed on 34 regionally sampled primary tumors and their concurrent and metachronous metastatic deposits from eight patients...
October 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29115891/the-mutational-landscape-of-small-lymphocytic-lymphoma-compared-to-non-early-stage-chronic-lymphocytic-leukemia
#15
Alejandra Martínez-Trillos, Magda Pinyol, Julio Delgado, Marta Aymerich, Maria Rozman, Tycho Baumann, Marcos González-Díaz, Jesus M Hernández, Miguel Alcoceba, Anna Muntañola, Maria José Terol, Blanca Navarro, Eva Giné, Pedro Jares, Sílvia Beà, Alba Navarro, Dolors Colomer, Ferran Nadeu, Enrique Colado, Angel R Payer, Tomás García-Cerecedo, Xosé S Puente, Carlos López-Otin, Elias Campo, Armando López-Guillermo, Neus Villamor
Small lymphocytic lymphoma (SLL) is considered as the non-leukemic form of presentation of chronic lymphocytic leukemia (CLL). We have compared the features, genomic alterations, and outcome of 890 patients with CLL and SLL. One hundred and thirteen patients presented as SLL and more frequently had unmutated-IGHV, CD38(high), ZAP-70(high), CD49d(high), +12, alterations in genes of NOTCH1, cell cycle, RNA metabolism, and NFkB pathways than CLL. During the follow-up, 46% of SLL patients developed CLL. Time to first treatment (TTFT) was shorter in SLL (10-year: 75% vs 62%; p = ...
November 8, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29109859/candidate-synthetic-lethality-partners-to-parp-inhibitors-in-the-treatment-of-ovarian-clear-cell-cancer
#16
Naoki Kawahara, Kenji Ogawa, Mika Nagayasu, Mai Kimura, Yoshikazu Sasaki, Hiroshi Kobayashi
Inhibitors of poly(ADP-ribose) polymerase (PARP) are new types of personalized treatment of relapsed platinum-sensitive ovarian cancer harboring BRCA1/2 mutations. Ovarian clear cell cancer (CCC), a subset of ovarian cancer, often appears as low-stage disease with a higher incidence among Japanese. Advanced CCC is highly aggressive with poor patient outcome. The aim of the present study was to determine the potential synthetic lethality gene pairs for PARP inhibitions in patients with CCC through virtual and biological screenings as well as clinical studies...
November 2017: Biomedical Reports
https://www.readbyqxmd.com/read/29101245/area-specific-regulation-of-quiescent-neural-stem-cells-by-notch3-in-the-adult-mouse-subependymal-zone
#17
Hiroki Kawai, Daichi Kawaguchi, Benjamin D Kuebrich, Takeo Kitamoto, Masahiro Yamaguchi, Yukiko Gotoh, Shohei Furutachi
In the adult mammalian brain, neural stem cells (NSCs) generate new neurons throughout lifetime. The balance between quiescence and active cell division among NSCs is crucial in producing appropriate numbers of neurons while maintaining the stem cell pool for a long period. The Notch signaling pathway plays a central role in both maintaining quiescent NSCs (qNSCs) and promoting cell division of active NSCs (aNSCs), although it remains elusive how this pathway regulates these apparently opposite functions. Notch1 has been shown to promote proliferation of aNSCs without affecting qNSCs in the adult mouse subependymal zone (SEZ)...
November 3, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29099834/identification-of-small-molecules-uncoupling-the-notch-jagged-interaction-through-an-integrated-high-throughput-screening
#18
Natalia Platonova, Chiara Parravicini, Cristina Sensi, Alessandro Paoli, Michela Colombo, Antonino Neri, Ivano Eberini, Raffaella Chiaramonte
Notch signaling plays an important role in several cellular functions including growth, differentiation, cell fate determination and stemness. Increased Notch activity has been linked to several types of cancers. Activation of Notch signaling is triggered by the interaction of Notch receptors (Notch1-4) with 5 different ligands (Jagged1-2 and Dll1-3-4) expressed on the neighbouring cells. Currently, indirect approaches to inhibit Notch signalling are based on the inhibition of the key step of Notch activation catalyzed by the γ-Secretase and thereby affect several different γ-Secretase substrates; conversely direct strategies get advantage of antibody-based drugs...
2017: PloS One
https://www.readbyqxmd.com/read/29099504/atypical-fibroxanthoma-and-pleomorphic-dermal-sarcoma-harbor-frequent-notch1-2-and-fat1-mutations-and-similar-dna-copy-number-alteration-profiles
#19
Klaus G Griewank, Thomas Wiesner, Rajmohan Murali, Carina Pischler, Hansgeorg Müller, Christian Koelsche, Inga Möller, Cindy Franklin, Ioana Cosgarea, Antje Sucker, Dirk Schadendorf, Jörg Schaller, Susanne Horn, Thomas Brenn, Thomas Mentzel
Atypical fibroxanthomas and pleomorphic dermal sarcomas are tumors arising in sun-damaged skin of elderly patients. They have differing prognoses and are currently distinguished using histological criteria, such as invasion of deeper tissue structures, necrosis and lymphovascular or perineural invasion. To investigate the as-yet poorly understood genetics of these tumors, 41 atypical fibroxanthomas and 40 pleomorphic dermal sarcomas were subjected to targeted next-generation sequencing approaches as well as DNA copy number analysis by comparative genomic hybridization...
November 3, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29098541/notch1-expression-is-regulated-at-the-post-transcriptional-level-by-the-3-untranslated-region-in-hematopoietic-stem-cell-development
#20
Shinichi Mizuno, Tadafumi Iino, Hidetoshi Ozawa, Yojiro Arinobu, Yong Chong, Koichi Akashi
In hematopoiesis, the expression of critical genes is regulated in a stage-specific manner to maintain normal hematopoiesis. Notch1 is an essential gene involved in the commitment and development of the T-cell lineage. However, the regulation of Notch1 in hematopoiesis is controversial, particularly at the level of hematopoietic stem cell (HSC). Here, we found that the expression of Notch1 is controlled at the post-transcriptional level in HSCs. HSCs express a considerable level of Notch1 mRNA, but its protein level is very low, suggesting a post-transcriptional suppression for Notch1...
November 2, 2017: International Journal of Hematology
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