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Peng Zhang, Dongxu He, Zhen Chen, Qiongxi Pan, Fangfang Du, Xian Zang, Yan Wang, Chunlei Tang, Hong Li, He Lu, Xiaoqiang Yao, Jian Jin, Xin Ma
It is believed that tumor cells can give rise to endothelial cells and tumor endothelium has a neoplastic origin. Yet, the stimuli and underlying mechanism remain unclear. Here, we demonstrate that adriamycin or paclitaxel, first-line chemotherapy agent, induced breast cancer cells to generate morphological, phenotypical and functional features of endothelial cells in vitro. In xenografts models, challenges from adriamycin or paclitaxel induced cancer cells to generate the majority of microvessels. Importantly, in breast cancer specimens from patients with neoadjuvant anthracycline-based or taxane-based chemotherapy, tumor-derived endothelial microvessels, lined by EGFR-amplified or/and TP53(+)-CD31(+) endothelial cells, was significantly higher in patients with progressive or stable disease (PD/SD) than in those with a partial or complete response (PR/CR)...
October 15, 2016: Biochemical Pharmacology
Yong Yang, Bing-Qiang Wang, Zhi-Hong Wu, Hai-Yan Zhang, Gui-Xing Qiu, Jian-Xiong Shen, Jian-Guo Zhang, Yu Zhao, Yi-Peng Wang, Qi Fei
Genetic etiology hypothesis is widely accepted in the development of congenital scoliosis (CS). The delta-like 3 (DLL3) gene, a member of the Notch signaling pathway, was implicated to contribute to human CS. In this study, a case-control association study was conducted to determine the association of single nucleotide polymorphism (SNP) in the DLL3 gene with CS in a Chinese Han Population. Five known tagging SNPs of the DLL3 gene were genotyped among 270 Chinese Han subjects (128 nonsyndromic CS patients and 142 matched controls)...
July 2016: Medicine (Baltimore)
Mark D Borromeo, Trisha K Savage, Rahul K Kollipara, Min He, Alexander Augustyn, Jihan K Osborne, Luc Girard, John D Minna, Adi F Gazdar, Melanie H Cobb, Jane E Johnson
Small cell lung carcinoma (SCLC) is a high-grade pulmonary neuroendocrine tumor. The transcription factors ASCL1 and NEUROD1 play crucial roles in promoting malignant behavior and survival of human SCLC cell lines. Here, we find that ASCL1 and NEUROD1 identify heterogeneity in SCLC, bind distinct genomic loci, and regulate mostly distinct genes. ASCL1, but not NEUROD1, is present in mouse pulmonary neuroendocrine cells, and only ASCL1 is required in vivo for tumor formation in mouse models of SCLC. ASCL1 targets oncogenic genes including MYCL1, RET, SOX2, and NFIB while NEUROD1 targets MYC...
August 2, 2016: Cell Reports
Scott J Dylla
Delta-like protein 3 (DLL3) is a novel and tractable tumor-initiating cell-associated target for the antibody-drug conjugate SC16LD6.5 in high-grade pulmonary neuroendocrine tumors. Elevated expression of DLL3, an inhibitor of Notch pathway activation, marks the second recent observation that impairment of Notch receptor signaling may play a critical role in neuroendocrine tumorigenesis.
March 2016: Molecular & Cellular Oncology
Zhi-Yan Liu, Tao Wu, Qing Li, Min-Cong Wang, Li Jing, Zhi-Ping Ruan, Yu Yao, Ke-Jun Nan, Hui Guo
Non-small-cell lung cancer (NSCLC) is a lethal and aggressive malignancy. Currently, the identities of prognostic and predictive makers of NSCLC have not been fully established. Dysregulated Notch signaling has been implicated in many human malignancies, including NSCLC. However, the prognostic value of measuring Notch signaling and the utility of developing Notch-targeted therapies in NSCLC remain inconclusive. The present study investigated the association of individual Notch receptor and ligand levels with lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) prognosis using the Kaplan-Meier plotte database...
May 2016: Medicine (Baltimore)
Jimmy de Melo, Cristina Zibetti, Brian S Clark, Woochang Hwang, Ana L Miranda-Angulo, Jiang Qian, Seth Blackshaw
Müller glia (MG) are the only glial cell type produced by the neuroepithelial progenitor cells that generate the vertebrate retina. MG are required to maintain retinal homeostasis and support the survival of retinal neurons. Furthermore, in certain vertebrate classes, MG function as adult stem cells, mediating retinal regeneration in response to injury. However, the mechanisms that regulate MG development are poorly understood because there is considerable overlap in gene expression between retinal progenitor cells and differentiated MG...
February 24, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Sivapriya Ponnurangam, Prasad R Dandawate, Animesh Dhar, Ossama W Tawfik, Rajashri R Parab, Prabhu Dutt Mishra, Prafull Ranadive, Rajiv Sharma, Girish Mahajan, Shahid Umar, Scott J Weir, Aravind Sugumar, Roy A Jensen, Subhash B Padhye, Arun Balakrishnan, Shrikant Anant, Dharmalingam Subramaniam
Cancer stem cells (CSCs) appear to explain many aspects of the neoplastic evolution of tumors and likely account for enhanced therapeutic resistance following treatment. Dysregulated Notch signaling, which affects CSCs plays an important role in pancreatic cancer progression. We have determined the ability of Quinomycin to inhibit CSCs and the Notch signaling pathway. Quinomycin treatment resulted in significant inhibition of proliferation and colony formation in pancreatic cancer cell lines, but not in normal pancreatic epithelial cells...
January 19, 2016: Oncotarget
Rajeswari Narayanappa, Pritilata Rout, Madhuri G S Aithal, Ashis Kumar Chand
Glioblastoma is the most common malignant brain tumor accounting for more than 54 % of all gliomas. Despite aggressive treatments, median survival remains less than 1 year. This might be due to the unavailability of effective molecular diagnostic markers and targeted therapy. Thus, it is essential to discover molecular mechanisms underlying disease by identifying dysregulated pathways involved in tumorigenesis. Notch signaling is one such pathway which plays an important role in determining cell fates. Since it is found to play a critical role in many cancers, we investigated the role of Notch genes in glioblastoma with an aim to identify biomarkers that can improve diagnosis...
May 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Emilie Denicolaï, Emeline Tabouret, Carole Colin, Philippe Metellus, Isabelle Nanni, Celine Boucard, Aurélie Tchoghandjian, David Meyronet, Nathalie Baeza-Kallee, Olivier Chinot, Dominique Figarella-Branger
Glioblastomas in adults are highly heterogeneous tumors that can develop throughout the brain. To date no predictive-location marker has been identified. We previously derived two glioblastoma cell lines from cortical and periventricular locations and demonstrated distinct transcriptomic profiles. Based on these preliminary results, the aim of this study was to correlate glioblastoma locations with the expression of ten selected genes (VEGFC, FLT4, MET, HGF, CHI3L1, PROM1, NOTCH1, DLL3, PDGFRA, BCAN). Fifty nine patients with newly diagnosed glioblastomas were retrospectively included...
January 5, 2016: Oncotarget
Chunhui Liu, Hua Gao, Lei Cao, Songbai Gui, Qian Liu, Chuzhong Li, Dan Li, Lei Gong, Yazhuo Zhang
The prediction of invasion or malignant behavior in PAs remains challenging. FSCN1, an actin-bundling protein, is associated with increased risk of mortality and metastasis in various cancer types. The objective of the study was to evaluate the expression of FSCN1 in 312 PAs cases, and to analyze its association with clinicopathologic features and invasion of PAs, thus serving as a promoter of cancer invasion. In non-function PAs (NFPA), FSCN1 nuclear-positive cases were 53/97 in the invasive group (IPA), and 21/115 in the noninvasive group (nIPA) (ⅹ(2) = 30...
January 5, 2016: Molecular and Cellular Endocrinology
Yong Yuan, Yang Hu, Yongfan Zhao, Longqi Chen
OBJECTIVE: To investigate the expressions and the role of Notch signaling-associated proteins in esophageal squamous cell carcinoma (ESCC). METHODS: Fifty patients with ESCC were included in this study. The expressions of Notch signaling-associated protein (4 receptors: Notch1, Notch2, Notch3, Notch4; 5 ligands: Dll1, Dll3, Dll4, Jagged1, Jagged2) in cancer foci and adjacent normal tissues (5 cm distance to cancer) were examined by immunohistochemitry. Correlations of these proteins with cancer cell proliferation(Ki-67 index) and clinicopathologic features were investigated...
September 2015: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
Laura R Saunders, Alexander J Bankovich, Wade C Anderson, Monette A Aujay, Sheila Bheddah, KristenAnn Black, Radhika Desai, Paul A Escarpe, Johannes Hampl, Amy Laysang, David Liu, Javier Lopez-Molina, Milly Milton, Albert Park, Marybeth A Pysz, Hui Shao, Brian Slingerland, Michael Torgov, Samuel A Williams, Orit Foord, Philip Howard, Jacek Jassem, Andrzej Badzio, Piotr Czapiewski, David H Harpole, Afshin Dowlati, Pierre P Massion, William D Travis, M Catherine Pietanza, J T Poirier, Charles M Rudin, Robert A Stull, Scott J Dylla
The high-grade pulmonary neuroendocrine tumors, small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), remain among the most deadly malignancies. Therapies that effectively target and kill tumor-initiating cells (TICs) in these cancers should translate to improved patient survival. Patient-derived xenograft (PDX) tumors serve as excellent models to study tumor biology and characterize TICs. Increased expression of delta-like 3 (DLL3) was discovered in SCLC and LCNEC PDX tumors and confirmed in primary SCLC and LCNEC tumors...
August 26, 2015: Science Translational Medicine
Galina Dvoriantchikova, Isabel Perea-Martinez, Steve Pappas, Ariel Faye Barry, Dagmara Danek, Xenia Dvoriantchikova, Daniel Pelaez, Dmitry Ivanov
The oscillatory expression of Notch signaling in neural progenitors suggests that both repressors and activators of neural fate specification are expressed in the same progenitors. Since Notch1 regulates photoreceptor differentiation and contributes (together with Notch3) to ganglion cell fate specification, we hypothesized that genes encoding photoreceptor and ganglion cell fate activators would be highly expressed in Notch1 receptor-bearing (Notch1+) progenitors, directing these cells to differentiate into photoreceptors or into ganglion cells when Notch1 activity is diminished...
2015: PloS One
Xun Yuan, Hua Wu, Hanxiao Xu, Na Han, Qian Chu, Shiying Yu, Yuan Chen, Kongming Wu
Various studies have assessed the clinicopathological and prognostic value of Notch1 and Notch3 expression in Non-small cell lung cancer (NSCLC), but their results remain controversial. This meta-analysis was conducted to address the above issues by using a total of 19 studies involving 3663 patients. The correlations between Notch1 and Notch3 expression and clinicopathological features and NSCLC prognosis were analyzed. The meta-analysis indicated that higher expression of Notch1 was associated with greater possibility of lymph node metastasis and higher TNM stages...
2015: Scientific Reports
Persefoni Fragkiadaki, Nikolaos Soulitzis, Stavros Sifakis, Demetrios Koutroulakis, Victor Gourvas, Nikolaos Vrachnis, Demetrios A Spandidos
Preeclampsia (PE) is a major cause of maternal mortality and morbidity, affecting 3-5% of all pregnancies. The Notch signaling pathway plays an important role during placental development, activating several target genes. Defects in the Notch pathway have adverse effect on placentation. The aim of this study was to investigate the expression of receptors NOTCH1,-2,-3,-4, ligands DLL1,-3,-4, JAG1,-2 and target genes HEY1,-2 in placental tissue samples from 20 late preterm or term pregnancies complicated by PE versus 20 normal pregnancies...
2015: PloS One
Katrin Serth, Karin Schuster-Gossler, Elisabeth Kremmer, Birte Hansen, Britta Marohn-Köhn, Achim Gossler
Delta-like 3 (DLL3) is a member of the DSL family of Notch ligands in amniotes. In contrast to DLL1 and DLL4, the other Delta-like proteins in the mouse, DLL3 does not bind in trans to Notch and does not activate the receptor, but shows cis-interaction and cis-inhibitory properties on Notch signaling in vitro. Loss of the DSL protein DLL3 in the mouse results in severe somite patterning defects, which are virtually indistinguishable from the defects in mice that lack lunatic fringe (LFNG), a glycosyltransferase involved in modifying Notch signaling...
2015: PloS One
Kumar Natesh, Dipali Bhosale, Aarti Desai, Goparaju Chandrika, Radha Pujari, Jayashree Jagtap, Ashish Chugh, Deepak Ranade, Padma Shastry
Glioblastoma (GBM), the most malignant of the brain tumors is classified on the basis of molecular signature genes using TCGA data into four subtypes- classical, mesenchymal, proneural and neural. The mesenchymal phenotype is associated with greater aggressiveness and low survival in contrast to GBMs enriched with proneural genes. The proinflammatory cytokines secreted in the microenvironment of gliomas play a key role in tumor progression. The study focused on the role of Oncostatin-M (OSM), an IL-6 family cytokine in inducing mesenchymal properties in GBM...
February 2015: Neoplasia: An International Journal for Oncology Research
Cali E Willet, Mariano Makara, George Reppas, George Tsoukalas, Richard Malik, Bianca Haase, Claire M Wade
Spondylocostal dysostosis is a congenital disorder of the axial skeleton documented in human families from diverse racial backgrounds. The condition is characterised by truncal shortening, extensive hemivertebrae and rib anomalies including malalignment, fusion and reduction in number. Mutations in the Notch signalling pathway genes DLL3, MESP2, LFNG, HES7 and TBX6 have been associated with this defect. In this study, spondylocostal dysostosis in an outbred family of miniature schnauzer dogs is described. Computed tomography demonstrated that the condition mirrors the skeletal defects observed in human cases, but unlike most human cases, the affected dogs were stillborn or died shortly after birth...
2015: PloS One
Aideen M McInerney-Leo, Duncan B Sparrow, Jessica E Harris, Brooke B Gardiner, Mhairi S Marshall, Victoria C O'Reilly, Hongjun Shi, Matthew A Brown, Paul J Leo, Andreas Zankl, Sally L Dunwoodie, Emma L Duncan
Segmentation defects of the vertebrae (SDV) are caused by aberrant somite formation during embryogenesis and result in irregular formation of the vertebrae and ribs. The Notch signal transduction pathway plays a critical role in somite formation and patterning in model vertebrates. In humans, mutations in several genes involved in the Notch pathway are associated with SDV, with both autosomal recessive (MESP2, DLL3, LFNG, HES7) and autosomal dominant (TBX6) inheritance. However, many individuals with SDV do not carry mutations in these genes...
March 1, 2015: Human Molecular Genetics
Akihiko Murata, Miya Yoshino, Mari Hikosaka, Kazuki Okuyama, Lan Zhou, Seiji Sakano, Hideo Yagita, Shin-Ichi Hayashi
Notch family members were first identified as cell adhesion molecules by cell aggregation assays in Drosophila studies. However, they are generally recognized as signaling molecules, and it was unclear if their adhesion function was restricted to Drosophila. We previously demonstrated that a mouse Notch ligand, Delta-like 1 (Dll1) functioned as a cell adhesion molecule. We here investigated whether this adhesion function was conserved in the diversified mammalian Notch ligands consisted of two families, Delta-like (Dll1, Dll3 and Dll4) and Jagged (Jag1 and Jag2)...
2014: PloS One
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