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M Larrayoz, M J J Rose-Zerilli, L Kadalayil, H Parker, S Blakemore, J Forster, Z Davis, A J Steele, A Collins, M Else, D Catovsky, D G Oscier, J C Strefford
Leukemia accepted article preview online, 24 October 2016. doi:10.1038/leu.2016.298.
October 24, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Christian Ostalecki, Sebastian Wittki, Jung-Hyun Lee, Miriam M Geist, Nadine Tibroni, Thomas Harrer, Gerold Schuler, Oliver T Fackler, Andreas S Baur
Tumor necrosis factor (TNF) is a key cytokine in HIV replication and pathogenesis. For reasons that are not entirely clear, the cytokine remains upregulated despite anti-retroviral therapy (ART). Here we demonstrate that HIV Nef induces an alternative TNF secretion mechanism that remains active in chronic infection. Ingestion of Nef-containing plasma extracellular vesicles (pEV) from ART patients by primary immune cells, but also Nef expression, induced intracellular proTNF cleavage and secretion of vesicular TNF endosomes...
October 19, 2016: EBioMedicine
Soraya Sajadimajd, Razieh Yazdanparast
Trastuzumab (Herceptin) monoclonal antibody directed against HER2 receptor has been administered as a treatment for metastatic HER2 positive breast cancer. The problematic issue in treatment of HER2 positive breast cancer cells is commonly the induction of resistance to trastuzumab which might be due to modulation of some vital signaling elements such as Notch1 and Pin1. In this study, we were aimed to investigate whether the cross talk between pin1 and Notch1 has a role in this event. Our results indicated that the expression level of Pin1 in resistant SKBR3 cells increased by about twofold relative to sensitive SKBR3 cells...
October 21, 2016: Apoptosis: An International Journal on Programmed Cell Death
Rodrigo Lopes de Lima, Rosenilde Carvalho de Holanda Afonso, Vivaldo Moura Neto, Ana Maria Bolognese, Marcos Fabio Henriques Dos Santos, Margareth Maria Gomes de Souza
OBJECTIVE: This study was conducted to identify and characterize dental follicle stem cells (DFSCs) by analyzing expression of embryonic, mesenchymal and neural stem cells surface markers. Design Dental follicle cells (DFCs) were evaluated by immunocytochemistry using embryonic stem cells markers (OCT4 and SOX2), mesenchmal stem cells (MSCs) markers (Notch1, active Notch1, STRO, CD44, HLA-ABC, CD90), neural stem cells markers (Nestin and β-III-tubulin), neural crest stem cells (NCSCs) markers (p75 and HNK1) and a glial cells marker (GFAP)...
October 8, 2016: Archives of Oral Biology
Shasha Li, Hao Hu, Zhiheng He, Deguang Liang, Rui Sun, Ke Lan
Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is an oncogenic pathogen that displays latent and lytic life cycles. In KS lesions, infiltrated immune cells, secreted viral and/or cellular cytokines, and hypoxia orchestrate a chronic pro-lytic microenvironment that can promote KSHV reactivation. However, only a small subset of viruses spontaneously undergoes lytic replication in this pro-lytic microenvironment while the majority remains in latency. Here, we show that the expression of the Notch ligand JAG1 is induced by KSHV-encoded replication and transcription activator (RTA) during reactivation...
October 2016: PLoS Pathogens
Christoph Preuss, Melanie Capredon, Florian Wünnemann, Philippe Chetaille, Andrea Prince, Beatrice Godard, Severine Leclerc, Nara Sobreira, Hua Ling, Philip Awadalla, Maryse Thibeault, Paul Khairy, Mark E Samuels, Gregor Andelfinger
Left-ventricular outflow tract obstructions (LVOTO) encompass a wide spectrum of phenotypically heterogeneous heart malformations which frequently cluster in families. We performed family based whole-exome and targeted re-sequencing on 182 individuals from 51 families with multiple affected members. Central to our approach is the family unit which serves as a reference to identify causal genotype-phenotype correlations. Screening a multitude of 10 overlapping phenotypes revealed disease associated and co-segregating variants in 12 families...
October 2016: PLoS Genetics
Jolanta Skalska-Sadowska, Małgorzata Dawidowska, Bronisława Szarzyńska-Zawadzka, Małgorzata Jarmuż-Szymczak, Joanna Czerwińska-Rybak, Ludomiła Machowska, Katarzyna Derwich
We report a pediatric case of acute T-lymphoblastic leukemia (T-ALL) with NOTCH1(wt) , FBXW7(wt) , STIL/TAL1, and PTEN (exons 2, 3, 4, 5) monoallelic deletions, biallelic CDKN2A/B deletion, and a minor t(8;14)(q24;q11)-positive subclone. Undetectable by a flow cytometric minimal residual disease assay, the t(8;14)(q24;q11) subclone expanded as detected by fluorescence in situ hybridization from 5% at diagnosis to 26% before consolidation and 100% at relapse bearing a monoallelic deletion (exons 2, 3) with a new frameshift mutation of PTEN and the same set of remaining molecular alterations...
October 19, 2016: Pediatric Blood & Cancer
Haiwei Lian, Dun Li, Yun Zhou, Esther Landesman-Bollag, Guanglan Zhang, Nicole M Anderson, Kevin Charles Tang, Justine E Roderick, Michelle A Kelliher, David C Seldin, Hui Fu, Hui Feng
No abstract text is available yet for this article.
October 6, 2016: Haematologica
A Drouillard, F Puleo, J B Bachet, S Ouazzani, A Calomme, P Demetter, G Verset, J L Van Laethem, R Maréchal
BACKGROUND: There is an increasing interest for Notch signalling pathway and particularly Delta-like ligand 4 (DLL4) as potential therapeutic target to improve outcome for patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Using immunohistochemistry (IHC) and tissue microarray (TMA), we assessed the expression patterns of DLL4, Notch1 and Notch3 in 151 patients from two independent cohorts of resected PDAC. We investigated the prognostic and the predictive significance of these proteins...
October 18, 2016: British Journal of Cancer
Katya Zelentsova, Ziv Talmi, Ghada Abboud-Jarrous, Tamar Sapir, Tal Capucha, Maria Nassar, Tal Burstyn-Cohen
Neurons are continuously produced in brains of adult mammalian organisms throughout life - a process tightly regulated to ensure a balanced homeostasis. In the adult brain, quiescent Neural Stem Cells (NSCs) residing in distinct niches engage in proliferation, to self-renew and to give rise to differentiated neurons and astrocytes. The mechanisms governing the intricate regulation of NSC quiescence and neuronal differentiation are not completely understood. Here, we report the expression of Protein S (PROS1) in adult NSCs, and show that genetic ablation of Pros1 in neural progenitors increased hippocampal NSC proliferation by 47%...
October 18, 2016: Stem Cells
Liming Yu, Chongxi Fan, Zhi Li, Jian Zhang, Xiaodong Xue, Yinli Xu, Guolong Zhao, Yang Yang, Huishan Wang
Stress hyperglycemia is commonly observed in patients suffering from ischemic heart disease. It not only worsens cardiovascular prognosis but also attenuates the efficacies of various cardioprotective agents. This study aimed to investigate the protective effect of melatonin against myocardial ischemia-reperfusion (MI/R) injury in acute hyperglycemic state with a focus on Notch1/Hes1/Akt signaling and intracellular thioredoxin (Trx) system. Sprague-Dawley rats were subjected to MI/R surgery and high glucose (HG, 500 g/L) infusion (4 ml/kg/h) to induce temporary hyperglycemia...
October 18, 2016: Journal of Pineal Research
Michael Rehman, Sreeharsha Gurrapu, Gabriella Cagnoni, Lorena Capparuccia, Luca Tamagnone
The secreted semaphorin Sema3E controls cell migration and invasiveness in cancer cells. Sema3E-receptor, PlexinD1, is frequently upregulated in melanoma, breast, colon, ovarian and prostate cancers; however, the mechanisms underlying PlexinD1 upregulation and the downstream events elicited in tumor cells are still unclear. Here we show that the canonical RBPjk-dependent Notch signaling cascade controls PlexinD1 expression in primary endothelial and cancer cells. Transcriptional activation was studied by quantitative PCR and promoter activity reporter assays...
2016: PloS One
Carlos I Amaya-Chanaga, Laura Z Rassenti
Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a variable clinical course. The Rai and Binet staging systems are often used to predict survival. However, they do not take into account other biological characteristics of CLL cells that may influence the disease course and response to treatment. Prognostic factors such as chromosome abnormalities (trisomy 12, 11q deletions and 17p deletions), β2 microglobulin, thymidine kinase, CD38 and ZAP-70 expression, IGHV mutation status, and mutations in genes such as NOTCH1, MYD88, SF3B1, and ATM are also predictors of prognosis...
March 2016: Best Practice & Research. Clinical Haematology
Davide Rossi
Richter's syndrome (RS) is the development of an aggressive lymphoma in patients with a previous or concomitant diagnosis of chronic lymphocytic leukemia (CLL). The incidence rate for RS is ∼0.5% per year of observation. In the presence of clinical suspicious of RS, diagnosis of transformation and choice of the site of biopsy may take advantage of (18)FDG PET/CT. Molecular lesions of tumor suppression regulators (TP53), cell cycle (CDKN2A) and cell proliferation (NOTCH1, MYC) overall account for ∼90% of RS and may be responsible for its aggressive clinical phenotype...
March 2016: Best Practice & Research. Clinical Haematology
Ke Xu, Ke Shen, Xin Liang, Yueqi Li, Norio Nagao, Jiyu Li, Jianwen Liu, Peihao Yin
MiRNAs may promote or inhibit tumor recurrence and drug resistance. MiR-139-5p is reportedly downregulated in colorectal cancer patient samples, but it is unknown whether and how miR-139-5p regulates drug resistance. Cancer stem cells (CSCs) are postulated to be important promoters of multiple drug resistance (MDR). In this study, we established a MDR cell model which strongly expressed the CSC-associated biomarkers CD44 and CD133. MiR-139-5p expression was reduced in MDR cell lines, while overexpression of miR-139-5p reversed CD44+/CD133+-associated MDR...
October 12, 2016: Oncotarget
Alon Peled, Ofer Sarig, Liat Samuelov, Marta Bertolini, Limor Ziv, Daphna Weissglas-Volkov, Marina Eskin-Schwartz, Christopher A Adase, Natalia Malchin, Ron Bochner, Gilad Fainberg, Ilan Goldberg, Koji Sugawara, Avital Baniel, Daisuke Tsuruta, Chen Luxenburg, Noam Adir, Olivier Duverger, Maria Morasso, Stavit Shalev, Richard L Gallo, Noam Shomron, Ralf Paus, Eli Sprecher
Despite recent advances in our understanding of the pathogenesis of ectodermal dysplasias (EDs), the molecular basis of many of these disorders remains unknown. In the present study, we aimed at elucidating the genetic basis of a new form of ED featuring facial dysmorphism, scalp hypotrichosis and hypodontia. Using whole exome sequencing, we identified 2 frameshift and 2 missense mutations in TSPEAR segregating with the disease phenotype in 3 families. TSPEAR encodes the thrombospondin-type laminin G domain and EAR repeats (TSPEAR) protein, whose function is poorly understood...
October 2016: PLoS Genetics
Wenjin Liu, Jeff M Snell, William R Jeck, Katherine A Hoadley, Matthew D Wilkerson, Joel S Parker, Nirali Patel, Yohannie B Mlombe, Gift Mulima, N George Liomba, Lindsey L Wolf, Carol G Shores, Satish Gopal, Norman E Sharpless
Esophageal squamous cell carcinoma (ESCC) is endemic in regions of sub-Saharan Africa (SSA), where it is the third most common cancer. Here, we describe whole-exome tumor/normal sequencing and RNA transcriptomic analysis of 59 patients with ESCC in Malawi. We observed similar genetic aberrations as reported in Asian and North American cohorts, including mutations of TP53, CDKN2A, NFE2L2, CHEK2, NOTCH1, FAT1, and FBXW7. Analyses for nonhuman sequences did not reveal evidence for infection with HPV or other occult pathogens...
October 6, 2016: JCI Insight
Riikka Kivelä, Ida Salmela, Yen Hoang Nguyen, Tatiana V Petrova, Heikki A Koistinen, Zoltan Wiener, Kari Alitalo
The remarkable adaptive and regenerative capacity of skeletal muscle is regulated by several transcription factors and pathways. Here we show that the transcription factor Prox1 is an important regulator of myoblast differentiation and of slow muscle fibre type. In both rodent and human skeletal muscles Prox1 is specifically expressed in slow muscle fibres and in muscle stem cells called satellite cells. Prox1 activates the NFAT signalling pathway and is necessary and sufficient for the maintenance of the gene program of slow muscle fibre type...
October 12, 2016: Nature Communications
Agata A Filip, Anna Grenda, Sylwia Popek, Dorota Koczkodaj, Małgorzata Michalak-Wojnowska, Michał Budzyński, Ewa Wąsik-Szczepanek, Szymon Zmorzyński, Agnieszka Karczmarczyk, Krzysztof Giannopoulos
Expression of microRNAs is altered in cancer. Circulating miRNA level assessed in body fluids commonly reflects their expression in tumor cells. In leukemias, however, both leukemic and nonleukemic cells compose circulating miRNA expression profile of peripheral blood. The latter contribution to extracellular miRNA pool may result in specific microenvironmental signaling, which promotes proliferation and survival. In our study, we used qT-PCR to assay peripheral blood serum of 22 chronic lymphocytic leukemia (CLL) patients for the expression of 84 miRNAs associated with activation and differentiation of B and T lymphocytes...
October 12, 2016: Annals of Hematology
Tian-Hui An, Quan-Wei He, Yuan-Peng Xia, Sheng-Cai Chen, Suraj Baral, Ling Mao, Hui-Juan Jin, Ya-Nan Li, Meng-Die Wang, Jian-Guo Chen, Ling-Qiang Zhu, Bo Hu
Atherosclerotic plaque vulnerability is the major cause for acute stroke and could be regulated by macrophage polarization. MicroRNA-181b (miR-181b) was involved in macrophage differential. Here, we explore whether miR-181b could regulate atherosclerotic plaque vulnerability by modulating macrophage polarization and the underline mechanisms. In acute stroke patients with atherosclerotic plaque, we found that the serum level of miR-181b was decreased. Eight-week apolipoprotein E knockout (ApoE(-/-)) mice were randomly divided into three groups (N = 10): mice fed with normal saline (Ctrl), mice fed with high-fat diet, and tail vein injection with miRNA agomir negative control (AG-NC)/miR-181b agomir (181b-AG, a synthetic miR-181b agonist)...
October 8, 2016: Molecular Neurobiology
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