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https://www.readbyqxmd.com/read/28075457/high-resolution-melting-analysis-for-rapid-and-sensitive-notch1-screening-in-chronic-lymphocytic-leukemia
#1
Jing-Jing Xu, Fei-Rong Yao, Min Jiang, You-Tao Zhang, Feng Guo
Chronic lymphocytic leukemia (CLL) is a biological and clinical heterogeneous disease. Activating mutations of NOTCH1 have been implicated to be associated with adverse prognosis in CLL. The objective of the present study was to develop an effective high-resolution melting (HRM) assay for detecting NOTCH1 mutations. Genomic DNA (gDNA) extracted from 133 CLL patients was screened by HRM assay, and the results were compared with the data obtained using direct sequencing. The relative sensitivity of the HRM assay and direct sequencing was evaluated using diluted gDNA with different NOTCH1 mutational frequencies...
January 5, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28062544/somatic-mutation-profiling-of-hobnail-variant-of-papillary-thyroid-carcinoma
#2
Luca Morandi, Alberto Righi, Francesca Maletta, Paola Rucci, Fabio Pagni, Marco Gallo, Sabrina Rossi, Leonardo Caporali, Anna Sapino, Ricardo Lloyd, Sofia Asioli
Hobnail variant of papillary thyroid carcinoma (HPTC) represents a recently described, aggressive and rare group of thyroid tumors with poorly understood pathogenesis. Molecular data about this group of cancers are few and a more detailed molecular characterization of these tumors is needed. The main objective of the study is to define a comprehensive molecular typing of HPTC. Eighteen patients affected by HPTC, including eighteen primary tumors and four lymph node metastases, were screened for NRAS, KRAS, HRAS, BRAF, TP53, PIK3CA, hTERT, PTEN, CDKN2A, EGFR, AKT1, CTNNB1, and NOTCH1 gene mutations...
January 6, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28061457/prognostic-roles-of-mrna-expression-of-notch-receptors-in-non-small-cell-lung-cancer
#3
Jianwen Xiong, Xiaoqiang Zhang, Xianglai Chen, Yiping Wei, De-Guo Lu, Yun-Wei Han, Jianjun Xu, Dongliang Yu
Notch signalling is aberrantly activated in human non-small cell lung cancer (NSCLC). Nevertheless, the prognostic roles of mRNA expression of four Notch receptors in NSCLC patients remain elusive. In this report, we reported the prognostic roles of Notch receptors in a total of 1,926 NSCLC patients through "The Kaplan-Meier plotter" (KM plotter) database which is capable to assess the effect of 22,277 genes on survival of NSCLC patients. We found that mRNA high expression level of Notch1 was associated with better overall survival (OS) for all NSCLC patients, hazard ratio (HR) 0...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28060745/expression-of-notch1-and-numb-in-small-cell-lung-cancer
#4
Hajime Kikuchi, Jun Sakakibara-Konishi, Megumi Furuta, Hiroshi Yokouchi, Hiroshi Nishihara, Shigeo Yamazaki, Hidetaka Uramoto, Fumihiro Tanaka, Masao Harada, Kenji Akie, Fumiko Sugaya, Yuka Fujita, Kei Takamura, Tetsuya Kojima, Toshiyuki Harada, Mitsunori Higuchi, Osamu Honjo, Yoshinori Minami, Naomi Watanabe, Satoshi Oizumi, Hiroyuki Suzuki, Takashi Ishida, Hirotoshi Dosaka-Akita, Hiroshi Isobe, Mitsuru Munakata, Masaharu Nishimura
Notch signaling in tumorigenesis functions as an oncogene or tumor suppressor according to the type of malignancy. Numb represses intracellular Notch signaling. Previous studies have demonstrated that Notch signaling suppresses the proliferation of small cell lung cancer (SCLC) cell lines. However, in SCLC, the association between Notch1 and Numb expression and clinicopathological factors or prognosis has remained unclear. In this study, we evaluated the expression of Notch1 and Numb in SCLC. We immunohistochemically assessed 125 SCLCs that were surgically resected at 16 institutions participating in either the Hokkaido Lung Cancer Clinical Study Group Trial (HOT) or the Fukushima Investigative Group for Healing Thoracic Malignancy (FIGHT) between 2003 and 2013...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28058624/zebrafish-phenotypic-screen-identifies-novel-notch-antagonists
#5
Vithya Velaithan, Kazuhide Shaun Okuda, Mei Fong Ng, Norazwana Samat, Sze Wei Leong, Siti Munirah Mohd Faudzi, Faridah Abas, Khozirah Shaari, Sok Ching Cheong, Pei Jean Tan, Vyomesh Patel
Zebrafish represents a powerful in vivo model for phenotype-based drug discovery to identify clinically relevant small molecules. By utilizing this model, we evaluated natural product derived compounds that could potentially modulate Notch signaling that is important in both zebrafish embryogenesis and pathogenic in human cancers. A total of 234 compounds were screened using zebrafish embryos and 3 were identified to be conferring phenotypic alterations similar to embryos treated with known Notch inhibitors...
January 5, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28053547/anticancer-activities-of-epigallocatechin-3-gallate-against-cholangiocarcinoma-cells
#6
Tae Won Kwak, Su Bum Park, Hyun-Jung Kim, Young-Il Jeong, Dae Hwan Kang
PURPOSE: Epigallocatechin-3-gallate (EGCG) is an antioxidant agent derived from green tea. Because it has chemopreventive and anti-invasive effect against various cancer cells, EGCG can be used to inhibit proliferation and invasion of cholangiocarcinoma (CCA) cells. METHODS: The anticancer effects of EGCG were studied using human CCA cells (HuCC-T1). Apoptosis was analyzed by Western blotting. Invasion and migration of cancer cells were assessed with Matrigel(®) and wound healing assays...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28045068/elucidating-the-genetic-basis-of-an-oligogenic-birth-defect-using-whole-genome-sequence-data-in-a-non-model-organism-bubalus-bubalis
#7
Lynsey K Whitacre, Jesse L Hoff, Robert D Schnabel, Sara Albarella, Francesca Ciotola, Vincenzo Peretti, Francesco Strozzi, Chiara Ferrandi, Luigi Ramunno, Tad S Sonstegard, John L Williams, Jeremy F Taylor, Jared E Decker
Recent strong selection for dairy traits in water buffalo has been associated with higher levels of inbreeding, leading to an increase in the prevalence of genetic diseases such as transverse hemimelia (TH), a congenital developmental abnormality characterized by absence of a variable distal portion of the hindlimbs. Limited genomic resources available for water buffalo required an original approach to identify genetic variants associated with the disease. The genomes of 4 bilateral and 7 unilateral affected cases and 14 controls were sequenced...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28042945/minicircle-orip-mir-31-as-a-novel-ebna1-specific-mirna-therapy-approach-for-nasopharyngeal-carcinoma
#8
Jiang-Xue Wu, Xin Tan, Jiaxin Lin, Luping Yuan, Jiemin Chen, Lin Qiu, Wen-Lin Huang
MicroRNAs (miRNAs) are important post-transcriptional regulators that control cancer development and progression. However, the application of miRNA therapy in cancer has been hampered by a lack of an efficient and targeted delivery system. In our previous studies, an oriP promoter-based minicircle system successfully mediated targeted foreign gene expression in EBNA1-positive nasopharyngeal carcinoma (NPC). However, it remains to be evaluated whether this system can be applied for tumor miRNA therapy. miR-31-5p, a tumor suppressive miRNA involved in the tumorigenesis of EBV-positive NPC, was selected as the therapeutic miRNA to be transferred...
January 2, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28042545/comparative-in-vitro-evaluation-of-human-dental-pulp-and-follicle-stem-cell-commitment
#9
Razieh Karamzadeh, Mohamadreza Baghaban Eslaminejad, Ali Sharifi-Zarchi
OBJECTIVE: Pulp and periodontal tissues are well-known sources of mesenchymal stem cells (MSCs) that provide a promising place in tissue engineering and regenerative medicine. The molecular mechanisms underlying commitment and differentiation of dental stem cells that originate from different dental tissues are not fully understood. In this study, we have compared the expression levels of pluripotency factors along with immunological and developmentally-related markers in the culture of human dental pulp stem cells (hDPSCs), human dental follicle stem cells (hDFSCs), and human embryonic stem cells (hESCs)...
2017: Cell Journal
https://www.readbyqxmd.com/read/28042317/cd54-notch1-axis-controls-tumor-initiation-and-cancer-stem-cell-functions-in-human-prostate-cancer
#10
Chong Li, Shengwu Liu, Ruping Yan, Ning Han, Kwok-Kin Wong, Lei Li
Cancer stem cells (CSCs) are considered one of the key contributors to chemoresistance and tumor recurrence. Therefore, the precise identification of reliable CSC markers and clarification of the intracellular signaling involved in CSCs remains a great challenge in fields relating to cancer biology. Here, we implemented a novel chemoresistant prostate cancer patient-derived xenograft (PDX) model in NOD/SCID mice and identified CD54 as a candidate gene among the most highly enriched gene expression profiles in prostate tumors exposed to chronic cisplatin administration...
2017: Theranostics
https://www.readbyqxmd.com/read/28035539/brucine-inhibits-bone-metastasis-of-breast-cancer-cells-by-suppressing-jagged1-notch1-signaling-pathways
#11
Ke-Fei Hu, Xiang-Ying Kong, Mi-Cun Zhong, Hong-Ye Wan, Na Lin, Xiao-Hua Pei
OBJECTIVE: To examine the effects of brucine on the invasion, migration and bone resorption of receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis. METHODS: The osteoclastogenesis model was builded by co-culturing human breast tumor MDA-MB-231 and mouse RAW264.7 macrophages cells. RANKL (50 ng/mL) and macrophage-colony stimulating factor (50 ng/mL) were added to this system, followed by treatment with brucine (0.02, 0.04 and 0...
December 29, 2016: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28035069/pdgf-d-promotes-cell-growth-aggressiveness-angiogenesis-and-emt-transformation-of-colorectal-cancer-by-activation-of-notch1-twist1-pathway
#12
Jinhuang Chen, Wenzheng Yuan, Liang Wu, Qiang Tang, Qinghua Xia, Jintong Ji, Zhengyi Liu, Zhijun Ma, Zili Zhou, Yifeng Cheng, Xiaogang Shu
Platelet-derived growth factor-D (PDGF-D) plays a crucial role in the progression of several cancers. However, its role in colorectal cancer (CRC) remains unclear. Our study showed that PDGF-D was highly expressed in CRC tissues and was positively associated with the clinicopathological features. Down-regulation of PDGF-D inhibited the tumor growth, migration and angiogenesis of SW480 cells in vitro and in vivo. Whereas up-regulation of PDGF-D promoted the malignant behaviors of HCT116 cells. Moreover, PDGF-D up-regulated the expression of Notch1 and Twist1 in CRC cells...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28030818/asic1-promotes-differentiation-of-neuroblastoma-by-negatively-regulating-notch-signaling-pathway
#13
Mingli Liu, Koichi Inoue, Tiandong Leng, An Zhou, Shanchun Guo, Zhi-Gang Xiong
In neurons, up-regulation of Notch activity either inhibits neurite extension or causes retraction of neurites. Conversely, inhibition of Notch1 facilitates neurite extension. Acid-sensing ion channels (ASICs) are a family of proton-gated cation channels, which play critical roles in synaptic plasticity, learning and memory and spine morphogenesis. Our pilot proteomics data from ASIC1a knock out mice implicated that ASIC1a may play a role in regulating Notch signaling, therefore, we explored whether or not ASIC1a regulates neurite growth during neuronal development through Notch signaling...
24, 2016: Oncotarget
https://www.readbyqxmd.com/read/28030808/inhibition-of-gamma-secretase-in-notch1-signaling-pathway-as-a-novel-treatment-for-ovarian-cancer
#14
Zhaoyi Feng, Wandong Xu, Chenguang Zhang, Mengran Liu, Hongwu Wen
Epithelial ovarian cancer (EOC) is the leading cause of death for gynecological cancer. Most patients are not diagnosed until the cancer is at an advanced stage with poor prognosis. Notch1 signaling pathway plays an oncogenic role in EOC. There have been few studies on enzymatic activity of γ-secretase and the mechanism of how γ-secretase inhibitor works on cancer cell. Here, we show that Jagged1 and NICD were highly expressed in ovarian carcinoma. The expressions of Notch1, Jagged1 and NICD in Notch1 pathway did not correlate with outcome in ovarian cancer...
December 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/28027303/olfactory-sensory-neurons-control-dendritic-complexity-of-mitral-cells-via-notch-signaling
#15
Yuko Muroyama, Atsushi Baba, Motoo Kitagawa, Tetsuichiro Saito
Mitral cells (MCs) of the mammalian olfactory bulb have a single primary dendrite extending into a single glomerulus, where they receive odor information from olfactory sensory neurons (OSNs). Molecular mechanisms for controlling dendritic arbors of MCs, which dynamically change during development, are largely unknown. Here we found that MCs displayed more complex dendritic morphologies in mouse mutants of Maml1, a crucial gene in Notch signaling. Similar phenotypes were observed by conditionally misexpressing a dominant negative form of MAML1 (dnMAML1) in MCs after their migration...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/28026975/the-notch1-autophagy-interaction-regulating-self-eating-for-survival
#16
Apurva Sarin, Nimi Marcel
T-cell subsets in the mammalian immune system use varied mechanisms for survival, a demand imposed by the diverse and dynamic niches that they function in. In a recent study, we showed that survival of natural T-regulatory cells (Tregs) was determined by spatially regulated NOTCH1 activity signaling leading to the activation of macroautophagy/autophagy. While this interaction was revealed in experimental conditions of limited nutrient availability in vitro, the consequences of this interaction were confirmed in the context of immune physiology...
December 27, 2016: Autophagy
https://www.readbyqxmd.com/read/28025657/mir-200a-controls-hepatic-stellate-cell-activation-and-fibrosis-via-sirt1-notch1-signal-pathway
#17
Jing-Jing Yang, Hui Tao, Li-Ping Liu, Wei Hu, Zi-Yu Deng, Jun Li
OBJECTIVES: miR-200a has been established as a key regulator of HSC activation processes in liver fibrosis. Epigenetic silencing of miR-200a contributing to SIRT1 over-expression has been discussed in breast cancer; however, whether miR-200a controls SIRT1 gene expression in hepatic fibrosis is still unknown. METHODS AND MATERIALS: We analyzed miR-200a regulation of SIRT1 expression in CCl4-induced liver fibrosis and TGF-β1-mediated activation of HSC. miR-200a, SIRT1, α-SMA, Col1A1, Notch1 and NICD expression were estimated by Western blotting, qRT-PCR and Immunohistochemistry...
December 26, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28019674/hairy-and-enhancer-of-split-related-with-yrpw-motif-like-heyl-is-dispensable-for-bone-remodeling-in-mice
#18
Ernesto Canalis, Stefano Zanotti
Notch induces Hairy Enhancer of Split (Hes)1 and Hes-related with YRPW motif (Hey) Hey1, Hey2 and Hey-like (HeyL) expression in osteoblasts, but it is not known whether any of these target genes mediates the effect of Notch in the skeleton. We demonstrated that Notch1 activation in osteoblasts/osteocytes induces Hes1, Hey1, Hey2 and HeyL, but HeyL was induced to a greater extent than other target genes. To characterize HeyL null mice for their skeletal phenotype, microcomputed tomography (µCT) and histomorphometric analysis of HeyL null and sex-matched littermate controls was performed...
December 26, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28017968/mutations-in-notch1-pest-domain-orchestrate-ccl19-driven-homing-of-chronic-lymphocytic-leukemia-cells-by-modulating-the-tumor-suppressor-gene-dusp22
#19
F Arruga, B Gizdic, C Bologna, S Cignetto, R Buonincontri, S Serra, T Vaisitti, K Gizzi, N Vitale, G Garaffo, E Mereu, F Diop, F Neri, D Incarnato, M Coscia, J Allan, R Piva, S Oliviero, R R Furman, D Rossi, G Gaidano, S Deaglio
Even if NOTCH1 is commonly mutated in Chronic Lymphocytic Leukemia (CLL), its functional impact in the disease remains unclear. Using CRISPR/Cas9-generated Mec-1 cell line models, we show that NOTCH1 regulates growth and homing of CLL cells by dictating expression levels of the tumor suppressor gene DUSP22. Specifically, NOTCH1 affects the methylation of DUSP22 promoter by modulating a nuclear complex, which tunes the activity of DNA methyltransferase 3A (DNMT3A). These effects are enhanced by PEST-domain mutations, which stabilize the molecule and prolong signaling...
December 26, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28012856/increased-fndc5-irisin-expression-in-human-hepatocellular-carcinoma
#20
Melania Gaggini, Manuela Cabiati, Serena Del Turco, Teresa Navarra, Paolo De Simone, Franco Filipponi, Silvia Del Ry, Amalia Gastaldelli, Giuseppina Basta
The fibronectin type III domain containing 5 (FNDC5)/Irisin, a novel energy-regulating hormone, is associated with lipid and carbohydrate metabolism. It is produced in low amounts by normal hepatic tissue, while in human hepatocellular carcinoma (HCC), in which aberrant de novo lipogenesis (DNL) occurs, the hepatic expression of FNDC5/Irisin is still unknown. The gene expression of FNDC5/Irisin, associated to key regulators of DNL, inflammation and cancer progression was evaluated in liver tissue of 18 patients with HCC undergoing liver transplantation and of 18 deceased donors...
December 21, 2016: Peptides
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