Read by QxMD icon Read


Zhenze Zhao, Xiuye Ma, Spencer D Shelton, Derek C Sung, Monica Li, Daniel Hernandez, Maggie Zhang, Michael D Losiewiz, Yidong Chen, Alexander Pertsemlidis, Xiaojie Yu, Yuanhang Liu, Liqin Du
MYCN amplification is the most common genetic alteration in neuroblastoma and plays a critical role in neuroblastoma tumorigenesis. MYCN regulates neuroblastoma cell differentiation, which is one of the mechanisms underlying its oncogenic function. We recently identified a group of differentiation-inducing microRNAs. Given the demonstrated inter-regulation between MYCN and microRNAs, we speculated that MYCN and the differentiation-inducing microRNAs might form an interaction network to control the differentiation of neuroblastoma cells...
October 15, 2016: Oncotarget
Fuyumi Kato, Francesco Paolo Fiorentino, Andreu Alibés, Manuel Perucho, Montse Sánchez-Céspedes, Takashi Kohno, Jun Yokota
We aimed to elucidate the effect of JQ1, a BET inhibitor, on small cell lung cancers (SCLCs) with MYCL amplification and/or expression. Fourteen SCLC cell lines, including four with MYCL amplification, were examined for the effects of JQ1 on protein and gene expression by Western blot and mRNA microarray analyses. The sensitivity of SCLC cells to JQ1 was assessed by cell growth and apoptosis assays. MYCL was expressed in all the 14 cell lines, whereas MYC/MYCN expression was restricted mostly to cell lines with gene amplification...
October 14, 2016: Oncotarget
Federica Parodi, Roberta Carosio, Marco Ragusa, Cinzia Di Pietro, Marco Maugeri, Davide Barbagallo, Fabio Sallustio, Giorgio Allemanni, Maria Pia Pistillo, Ida Casciano, Alessandra Forlani, Francesco P Schena, Michele Purrello, Massimo Romani, Barbara Banelli
In neuroblastoma, the epigenetic landscape is more profoundly altered in aggressive compared to lower grade tumors and the concomitant hypermethylation of many genes, defined as "methylator phenotype", has been associated with poor outcome. DNA methylation can interfere with gene expression acting at distance through the methylation or demethylation of the regulatory regions of miRNAs. The multiplicity of miRNA targets may result in the simultaneous alteration of many biological pathways like cell proliferation, apoptosis, migration and differentiation...
October 14, 2016: Biochimica et Biophysica Acta
Pei Y Liu, Bernard Atmadibrata, Sujanna Mondal, Andrew E Tee, Tao Liu
Neuroblastoma is the most common solid tumor in early childhood. Patients with neuroblastoma due to the amplification of a 130-kb genomic DNA region containing the MYCN, MYCN antisense NCYM and lncUSMycN genes show poor prognosis. BET bromodomain inhibitors show anticancer efficacy against neuroblastoma partly by reducing MYCN gene transcription and N-Myc mRNA and protein expression. We have previously shown that the long nocoding RNA lncUSMycN upregulates N-Myc mRNA expression by binding to the RNA-binding protein NonO...
October 12, 2016: International Journal of Oncology
D-L Qi, D Cobrinik
Retinoblastomas can arise from cone photoreceptor precursors in response to the loss of pRB function. Cone precursor-specific circuitry cooperates with pRB loss to initiate this process and subsequently contributes to the malignancy. Intrinsic high-level MDM2 expression is a key component of the cone precursor circuitry and is thought to inactivate p53-mediated tumor surveillance, which could otherwise be induced in response to pRB loss. However, the MDM2-related MDM4 has also been proposed to abrogate p53-mediated tumor surveillance in the absence of detectable MDM2 in retinoblastoma cells, bringing into question the importance of high-level MDM2 versus MDM4 expression...
October 17, 2016: Oncogene
Susana Galli, Arlene Naranjo, Collin Van Ryn, Jason U Tilan, Emily Trinh, Chao Yang, Jessica Tsuei, Sung-Hyeok Hong, Hongkun Wang, Ewa Izycka-Swieszewska, Yi-Chien Lee, Olga C Rodriguez, Chris Albanese, Joanna Kitlinska
Neuroblastoma (NB) is a pediatric malignant neoplasm of sympathoadrenal origin. Challenges in its management include stratification of this heterogeneous disease and a lack of both adequate treatments for high-risk patients and noninvasive biomarkers of disease progression. Our previous studies have identified neuropeptide Y (NPY), a sympathetic neurotransmitter expressed in NB, as a potential therapeutic target for these tumors by virtue of its Y5 receptor (Y5R)-mediated chemoresistance and Y2 receptor (Y2R)-mediated proliferative and angiogenic activities...
October 11, 2016: American Journal of Pathology
Giovanni Perini, Giorgio Milazzo, Nisha Narayan, Paul G Ekert
No abstract text is available yet for this article.
October 14, 2016: Cell Death and Differentiation
Lori S Hart, JulieAnn Rader, Pichai Raman, Vandana Batra, Michael R Russell, Matthew Tsang, Maria Gagliardi, Lucy Chen, Daniel Martinez, Yimei Li, Andrew Wood, Sunkyu Kim, Sudha Parasuraman, Scott Delach, Kristina A Cole, Shiva Krupa, Markus Boehm, Malte Peters, Giordano Caponigro, John M Maris
PURPOSE: Neuroblastoma is treated with aggressive multi-modal therapy, yet more than 50% of patients experience relapse. We recently showed that relapsed neuroblastomas frequently harbor mutations leading to hyperactivated ERK signaling and sensitivity to MEK inhibition therapy. Here we sought to define a synergistic therapeutic partner to potentiate MEK inhibition. EXPERIMENTAL DESIGN: We first surveyed 22 genetically annotated human neuroblastoma-derived cell lines (from 20 unique patients) for sensitivity to the MEK inhibitor binimetinib...
October 11, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Etienne Dardenne, Himisha Beltran, Matteo Benelli, Kaitlyn Gayvert, Adeline Berger, Loredana Puca, Joanna Cyrta, Andrea Sboner, Zohal Noorzad, Theresa MacDonald, Cynthia Cheung, Ka Shing Yuen, Dong Gao, Yu Chen, Martin Eilers, Juan-Miguel Mosquera, Brian D Robinson, Olivier Elemento, Mark A Rubin, Francesca Demichelis, David S Rickman
The transition from castration-resistant prostate adenocarcinoma (CRPC) to neuroendocrine prostate cancer (NEPC) has emerged as an important mechanism of treatment resistance. NEPC is associated with overexpression and gene amplification of MYCN (encoding N-Myc). N-Myc is an established oncogene in several rare pediatric tumors, but its role in prostate cancer progression is not well established. Integrating a genetically engineered mouse model and human prostate cancer transcriptome data, we show that N-Myc overexpression leads to the development of poorly differentiated, invasive prostate cancer that is molecularly similar to human NEPC...
October 10, 2016: Cancer Cell
Marco Kramer, Diogo Ribeiro, Marie Arsenian-Henriksson, Thomas Deller, Hermann Rohrer
: Neuroblastoma (NB) is a childhood tumor that arises from the sympathoadrenal lineage. MYCN amplification is the most reliable marker for poor prognosis and MYCN overexpression in embryonic mouse sympathetic ganglia results in NB-like tumors. MYCN cooperates with mutational activation of anaplastic lymphoma kinase (ALK), which promotes progression to NB, but the role of MYCN and ALK in tumorigenesis is still poorly understood. Here, we use chick sympathetic neuroblasts to examine the normal function of MYCN and MYC in the control of neuroblast proliferation, as well as effects of overexpression of MYCN, MYC, and activated ALK, alone and in combination...
October 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Mengling Liu, Yingfeng Xia, Jane Ding, Bingwei Ye, Erhu Zhao, Jeong-Hyeon Choi, Ahmet Alptekin, Chunhong Yan, Zheng Dong, Shuang Huang, Liqun Yang, Hongjuan Cui, Yunhong Zha, Han-Fei Ding
High-risk neuroblastoma remains one of the deadliest childhood cancers. Identification of metabolic pathways that drive or maintain high-risk neuroblastoma may open new avenues of therapeutic interventions. Here, we report the isolation and propagation of neuroblastoma sphere-forming cells with self-renewal and differentiation potential from tumors of the TH-MYCN mouse, an animal model of high-risk neuroblastoma with MYCN amplification. Transcriptional profiling reveals that mouse neuroblastoma sphere-forming cells acquire a metabolic program characterized by transcriptional activation of the cholesterol and serine-glycine synthesis pathways, primarily as a result of increased expression of sterol regulatory element binding factors and Atf4, respectively...
October 4, 2016: Cell Reports
Nermine O Basta, Gail C Halliday, Guy Makin, Jillian Birch, Richard Feltbower, Nick Bown, Martin Elliott, Lucas Moreno, Giuseppe Barone, Andrew Dj Pearson, Peter W James, Deborah A Tweddle, Richard Jq McNally
BACKGROUND: Despite therapeutic advances, survival following relapse for neuroblastoma patients remains poor. We investigated clinical and biological factors associated with length of progression-free and overall survival following relapse in UK neuroblastoma patients. METHODS: All cases of relapsed neuroblastoma, diagnosed during 1990-2010, were identified from four Paediatric Oncology principal treatment centres. Kaplan-Meier and Cox regression analyses were used to calculate post-relapse overall survival (PROS), post-relapse progression-free survival (PRPFS) between relapse and further progression, and to investigate influencing factors...
October 4, 2016: British Journal of Cancer
Tomoko Tanaka, Mayumi Higashi, Koseki Kimura, Junko Wakao, Shigehisa Fumino, Tomoko Iehara, Hajime Hosoi, Toshiyuki Sakai, Tatsuro Tajiri
BACKGROUND: A recent study reported that relapsed neuroblastomas had frequent RAS-ERK pathway mutations. We herein investigated the effects and pathways of MEK inhibitors, which inhibit the RAS-ERK pathway, as a new molecular-targeted therapy for refractory neuroblastomas. METHOD: Five neuroblastoma cell lines were treated with trametinib (MEK inhibitor) or CH5126766 (RAF/MEK inhibitor). Growth inhibition was analyzed using a cell viability assay. ERK phosphorylation and the MYCN expression were analyzed by immunoblotting or immunohistochemistry...
September 16, 2016: Journal of Pediatric Surgery
Koseki Kimura, Tsunao Kishida, Junko Wakao, Tomoko Tanaka, Mayumi Higashi, Shigehisa Fumino, Shigeyoshi Aoi, Taizo Furukawa, Osam Mazda, Tatsuro Tajiri
BACKGROUND: Human mesenchymal stem cells (hMSCs) are multipotent stem-like cells that are reported to have tumor-suppression effects and migration ability toward damaged tissues or tumors. The aim of this study was to analyze the tumor-homing ability of hMSCs and antitumor potency in a transgenic TH-MYCN mouse model of neuroblastoma (NB). METHODS: hMSCs (3×10(6)) labeled with DiR, a lipophilic near-infrared dye, were intraperitoneally (i.p.) or intravenously (i...
September 17, 2016: Journal of Pediatric Surgery
Renata Colla, Alberto Izzotti, Chiara De Ciucis, Daniela Fenoglio, Silvia Ravera, Andrea Speciale, Roberta Ricciarelli, Anna Lisa Furfaro, Alessandra Pulliero, Mario Passalacqua, Nicola Traverso, Maria Adelaide Pronzato, Cinzia Domenicotti, Barbara Marengo
Neuroblastoma, a paediatric malignant tumor, is initially sensitive to etoposide, a drug to which many patients develop chemoresistance. In order to investigate the molecular mechanisms responsible for etoposide chemoresistance, HTLA-230, a human MYCN-amplified neuroblastoma cell line, was chronically treated with etoposide at a concentration that in vitro mimics the clinically-used dose. The selected cells (HTLA-Chr) acquire multi-drug resistance (MDR), becoming less sensitive than parental cells to high doses of etoposide or doxorubicin...
September 23, 2016: Oncotarget
Gordana Samardzija, Tamara Kravic Stevovic, Slavisa Djuricic, Dragomir Djokic, Marina Djurisic, Darko Ciric, Tamara Martinovic, Vladimir Bumbasirevic, Dragana Vujic
Autophagy is activated in cancer cells in response to multiple stresses and has been demonstrated to promote tumor cell survival and drug resistance in neuroblastoma (NB). This study was conducted to analyze the ultrastructural features of peripheral neuroblastic tumors (pNTs) and identify the relation of the types of NTs, the proliferation rate, and MYCN gene amplification with a number of autophagic vacuoles. Our results indicate that aggressive human NBs show a massive increase in the number of autophagic vacuoles associated with proliferation rate and that alteration of the mitochondria might be an important factor for the induction of autophagy in NTs...
September 2016: Ultrastructural Pathology
Karin Zins, Daniel Kovatchki, Trevor Lucas, Dietmar Abraham
Neuroblastoma (NB) is the most common extracranial solid tumor of childhood and is a rapidly growing, highly-vascularized cancer. NBs frequently express angiogenic factors and high tumor angiogenesis has been associated with poor outcomes. Placental growth factor (PlGF) is an angiogenic protein belonging to the vascular endothelial growth factor (VEGF) family and is up-regulated mainly in pathologic conditions. Recently, PlGF was identified as a member of a gene expression signature characterizing highly malignant NB stem cells drawing attention as a potential therapeutic target in NB...
2016: International Journal of Molecular Sciences
Bryan King, Francesco Boccalatte, Kelly Moran-Crusio, Elmar Wolf, Jingjing Wang, Clarisse Kayembe, Charalampos Lazaris, Xiaofeng Yu, Beatriz Aranda-Orgilles, Anna Lasorella, Iannis Aifantis
Hematopoietic stem cells (HSCs) are dormant in the bone marrow and can be activated in response to diverse stresses to replenish all blood cell types. We identified the ubiquitin ligase Huwe1 as a crucial regulator of HSC function via its post-translational control of the oncoprotein N-myc (encoded by Mycn). We found Huwe1 to be essential for HSC self-renewal, quiescence and lymphoid-fate specification in mice. Through the use of a fluorescent fusion allele (Mycn(M)), we observed that N-myc expression was restricted to the most immature, multipotent stem and progenitor populations...
September 26, 2016: Nature Immunology
(no author information available yet)
USP7 deubiquitinates MYCN to enhance its stability and transcriptional activity in neuroblastoma.
September 23, 2016: Cancer Discovery
Brian H Kushner, Nai-Kong V Cheung, Shakeel Modak, Oren J Becher, Ellen M Basu, Stephen S Roberts, Kim Kramer, Ira J Dunkel
AKT plays a pivotal role in driving the malignant phenotype of many cancers, including high-risk neuroblastoma (HR-NB). AKT signaling, however, is active in normal tissues, raising concern about excessive toxicity from its suppression. The oral AKT inhibitor perifosine showed tolerable toxicity in adults and in our phase I trial in children with solid tumors ( NCT00776867). We now report on the HR-NB experience. HR-NB patients received perifosine 50-75mg/m(2) /day after a loading dose of 100-200mg/m(2) on day 1, and continued on study until progressive disease...
September 20, 2016: International Journal of Cancer. Journal International du Cancer
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"