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https://www.readbyqxmd.com/read/29165358/understanding-the-molecular-genetics-of-basal-cell-carcinoma
#1
REVIEW
Cristina Pellegrini, Maria Giovanna Maturo, Lucia Di Nardo, Valeria Ciciarelli, Carlota Gutiérrez García-Rodrigo, Maria Concetta Fargnoli
Basal cell carcinoma (BCC) is the most common human cancer and represents a growing public health care problem. Several tumor suppressor genes and proto-oncogenes have been implicated in BCC pathogenesis, including the key components of the Hedgehog pathway, PTCH1 and SMO, the TP53 tumor suppressor, and members of the RAS proto-oncogene family. Aberrant activation of the Hedgehog pathway represents the molecular driver in basal cell carcinoma pathogenesis, with the majority of BCCs carrying somatic point mutations, mainly ultraviolet (UV)-induced, and/or copy-loss of heterozygosis in the PTCH1 gene...
November 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29163537/mycn-amplification-is-associated-with-repressed-cellular-immunity-in-neuroblastoma-an-in-silico-immunological-analysis-of-target-database
#2
Peng Zhang, Xiaofang Wu, Moushumi Basu, Chen Dong, Pan Zheng, Yang Liu, Anthony David Sandler
Purpose: RNA and DNA sequencing data are traditionally used to discern intrinsic cellular pathways in cancer pathogenesis, their utility for investigating the tumor microenvironment (TME) has not been fully explored. This study explores the use of sequencing data to investigate immunity within the TME. Experimental design: Here, we use immune cell fraction estimation analysis to determine the immune profiles in the microenvironment of neuroblastoma (NB) based on RNA-seq data in the TARGET database...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29156797/jq1-synergizes-with-the-bcl-2-inhibitor-abt-263-against-mycn-amplified-small-cell-lung-cancer
#3
Huogang Wang, Bo Hong, Xuemin Li, Ke Deng, Hong Li, Vivian Wai Yan Lui, Wenchu Lin
Small cell lung cancer (SCLC) is a clinically aggressive cancer with very poor prognosis. Amplification of MYC family genes and overexpression of Bcl-2 protein are common in SCLC, and they are likely therapeutic targets for SCLC. Previous clinical study showed that single agent targeting Bcl-2 with ABT-263 was of limited efficacy in SCLC. In this study, we demonstrated for the first time that co-targeting of N-Myc and Bcl-2 resulted in marked synergistic antitumor effects in MYCN-amplified SCLC. We found that MYCN-amplified SCLC cells were highly sensitive to a Bromodomain and Extra-Terminal domain (BET) inhibitor JQ1, which was able to inhibit N-Myc protein expression...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156716/using-droplet-digital-pcr-to-analyze-mycn-and-alk-copy-number-in-plasma-from-patients-with-neuroblastoma
#4
Marco Lodrini, Annika Sprüssel, Kathy Astrahantseff, Daniela Tiburtius, Robert Konschak, Holger N Lode, Matthias Fischer, Ulrich Keilholz, Angelika Eggert, Hedwig E Deubzer
The invasive nature of surgical biopsies deters sequential application, and single biopsies often fail to reflect tumor dynamics, intratumor heterogeneity and drug sensitivities likely to change during tumor evolution and treatment. Implementing molecular characterization of cell-free neuroblastoma-derived DNA isolated from blood plasma could improve disease assessment for treatment selection and monitoring of patients with high-risk neuroblastoma. We established droplet digital PCR (ddPCR) protocols for MYCN and ALK copy number status in plasma from neuroblastoma patients...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29148865/metronomic-therapy-has-low-toxicity-and-is-as-effective-as-current-standard-treatment-for-recurrent-high-risk-neuroblastoma
#5
Frank Berthold, Marc Hömberg, Inna Proleskovskaya, Pavel Mazanek, Margarita Belogurova, Angela Ernst, Jaroslav Sterba
The metronomic therapy concept uses low doses of continuously applied chemotherapeutic, anti-angiogenetic, and immunomodulating drugs. Twenty patients with recurrent and 3 with refractory high-risk neuroblastoma were treated by the metronomic concept using celecoxib, cyclophosphamide, vinblastine, and etoposide for up to 24 months. The outcome was compared to 274 matched patients with a first recurrence from stage 4 neuroblastoma using the variables time from diagnosis to first recurrence, number of organs involved, and MYCN amplification...
November 17, 2017: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29138344/targeting-the-mycn-parp-dna-damage-response-pathway-inneuroendocrine-prostate-cancer
#6
Wei Zhang, Bo Liu, Wenhui Wu, Likun Li, Bradley M Broom, Spyridon M Basourakos, Dimitrios Korentzelos, Yang Luan, Jianxiang Wang, Guang Yang, Sanghee Park, Abul K Azad, Xuhong Cao, Jeri Kim, Paul Corn, Christopher Logothetis, Ana M Aparicio, Arul M Chinnayan, Nora M Navone, Patricia Troncoso, Timothy C Thompson
PURPOSE: We investigated MYCN-regulated molecular pathways in castration-resistant prostate cancer (CRPC) classified by morphological criteria as adenocarcinoma or neuroendocrine to extend the molecular phenotype, establish driver pathways, and identify novel approaches to combination therapy for NEPC. RESULTS: Using comparative bioinformatics analyses of CRPC-Adeno and CRPC-Neuro RNA sequence data from public datasets and a panel of 28 PDX models we identified a MYCN-PARP-DNA damage response (DDR) pathway that is enriched in CRPC with neuroendocrine differentiation (NED) and CRPC-Neuro...
November 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29137381/gene-expression-and-molecular-pathway-activation-signatures-of-mycn-amplified-neuroblastomas
#7
Ivan Petrov, Maria Suntsova, Elena Ilnitskaya, Sergey Roumiantsev, Maxim Sorokin, Andrew Garazha, Pavel Spirin, Timofey Lebedev, Nurshat Gaifullin, Sergey Larin, Olga Kovalchuk, Dmitry Konovalov, Vladimir Prassolov, Alexander Roumiantsev, Anton Buzdin
Neuroblastoma is a pediatric cancer arising from sympathetic nervous system. Remarkable heterogeneity in outcomes is one of its widely known features. One of the traits strongly associated with the unfavorable subtype is the amplification of oncogene MYCN. Here, we performed cross-platform biomarker detection by comparing gene expression and pathway activation patterns from the two literature reports and from our experimental dataset, combining profiles for the 761 neuroblastoma patients with known MYCN amplification status...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137288/elevated-timp-1-expression-is-associated-with-a-prometastatic-phenotype-disease-relapse-and-poor-survival-in-neuroblastoma
#8
Pritha Paul, Eric J Rellinger, Jingbo Qiao, Sora Lee, Natasha Volny, Chandrasekhar Padmanabhan, Carmelle V Romain, Bret Mobley, Hernan Correa, Dai H Chung
Approximately two-thirds of patients with neuroblastoma are found to have metastatic disease at time of diagnosis with frequent skeletal, lymph node, central nervous system, and liver involvement. Using a serial in vivo splenic injection model, we have isolated an aggressive subclone (BE(2)-C/LM2) from MYCN-amplified neuroblastomas that demonstrate an enhanced propensity to develop metastatic liver lesions. BE(2)-C/LM2 subclone cells demonstrate increased adherent, soft agar colony and tumorsphere growth in vitro...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29124525/heterogeneity-in-retinoblastoma-a-tale-of-molecules-and-models
#9
REVIEW
Sonya Stenfelt, Maria K E Blixt, Charlotta All-Ericsson, Finn Hallböök, Henrik Boije
Retinoblastoma, an intraocular pediatric cancer, develops in the embryonic retina following biallelic loss of RB1. However, there is a wide range of genetic and epigenetic changes that can affect RB1 resulting in different clinical outcomes. In addition, other transformations, such as MYCN amplification, generate particularly aggressive tumors, which may or may not be RB1 independent. Recognizing the cellular characteristics required for tumor development, by identifying the elusive cell-of-origin for retinoblastoma, would help us understand the development of these tumors...
November 9, 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/29117357/evaluation-of-genetic-predisposition-for-mycn-amplified-neuroblastoma
#10
Eric A Hungate, Mark A Applebaum, Andrew D Skol, Zalman Vaksman, Maura Diamond, Lee McDaniel, Samuel L Volchenboum, Barbara E Stranger, John M Maris, Sharon J Diskin, Kenan Onel, Susan L Cohn
To investigate genetic predispositions for MYCN-amplified neuroblastoma, we performed a meta-analysis of three genome-wide association studies totaling 615 MYCN-amplified high-risk neuroblastoma cases and 1869 MYCN-nonamplified non-high-risk neuroblastoma cases as controls using a fixed-effects model with inverse variance weighting. All statistical tests were two-sided. We identified a novel locus at 3p21.31 indexed by the single nucleotide polymorphism (SNP) rs80059929 (odds ratio [OR] = 2.95, 95% confidence interval [CI] = 2...
October 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29092957/molecular-characterisation-of-metastatic-pancreatic-neuroendocrine-tumours-pnets-using-whole-genome-and-transcriptome-sequencing
#11
Hui-Li Wong, Kevin C Yang, Yaoqing Shen, Eric Y Zhao, Jonathan M Loree, Hagen F Kennecke, Steve E Kalloger, Joanna M Karasinska, Howard J Lim, Andrew J Mungall, Xiaolan Feng, Janine M Davies, Kasmintan Schrader, Chen Zhou, Aly Karsan, Steven Jm Jones, Janessa Laskin, Marco A Marra, David F Schaeffer, Sharon M Gorski, Daniel J Renouf
Pancreatic neuroendocrine tumours (PNETs) are a genomically and clinically heterogeneous group of pancreatic neoplasms often diagnosed with distant metastases. Recurrent somatic mutations, chromosomal aberrations and gene expression signatures in PNETs have been described, but the clinical significance of these molecular changes is still poorly understood, and the clinical outcomes of PNET patients remain highly variable. To help identify the molecular factors that contribute to PNET progression and metastasis, and as part of an ongoing clinical trial at the BC Cancer Agency (clinicaltrials...
November 1, 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/29091799/molecular-classification-substitutes-for-the-prognostic-variables-stage-age-and-mycn-status-in-neuroblastoma-risk-assessment
#12
Carolina Rosswog, Rene Schmidt, André Oberthuer, Dilafruz Juraeva, Benedikt Brors, Anne Engesser, Yvonne Kahlert, Ruth Volland, Christoph Bartenhagen, Thorsten Simon, Frank Berthold, Barbara Hero, Andreas Faldum, Matthias Fischer
BACKGROUND: Current risk stratification systems for neuroblastoma patients consider clinical, histopathological, and genetic variables, and additional prognostic markers have been proposed in recent years. We here sought to select highly informative covariates in a multistep strategy based on consecutive Cox regression models, resulting in a risk score that integrates hazard ratios of prognostic variables. METHODS: A cohort of 695 neuroblastoma patients was divided into a discovery set (n=75) for multigene predictor generation, a training set (n=411) for risk score development, and a validation set (n=209)...
October 26, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29061788/expression-of-truncated-neurokinin-1-receptor-in-childhood-neuroblastoma-is-independent-of-tumor-biology-and-stage
#13
Alexandra Pohl, Roland Kappler, Jakob Mühling, Dietrich VON Schweinitz, Michael Berger
BACKGROUND: Neuroblastoma is an embryonal malignancy arising from the aberrant growth of neural crest progenitor cells of the sympathetic nervous system. The tachykinin receptor 1 (TACR1) - substance P complex is associated with tumoral angiogenesis and cell proliferation in a variety of cancer types. Inhibition of TACR1 was recently described to impede growth of NB cell lines. However, the relevance of TACR1 in clinical settings is unknown. PATIENTS AND METHODS: We investigated gene expression levels of full-length and truncated TACR1 in 59 neuroblastomas and correlated these data with the patients' clinical parameters such as outcome, metastasis, International Neuroblastoma Staging System (INSS) status, MYCN proto-oncogene, bHLH transcription factor (MYCN) status, gender and age...
November 2017: Anticancer Research
https://www.readbyqxmd.com/read/29050113/-long-term-follow-up-of-neuroblastoma-in-children-less-than-18-months-of-age
#14
J Zhao, C Pan, M Xu, M Zhou, Y J Gao, W T Hu, J Y Tang
Objective: To assess the clinical features and long-term outcomes of neuroblastoma (NB) in children less than 18 months of age, so as to provide evidence for further improvement of treatment. Method: Clinical data(sex, age, stage, risk group, treatment response, follow-up, etc.) of 155 NB patients under age of 18 months from June 2000 to December 2015 in Shanghai Children's Medical Center were analyzed retrospectively. The clinical features were summarized and the long-term follow-up results were evaluated...
October 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/29043399/immunohistochemical-evaluation-of-molecular-radiotherapy-target-expression-in-neuroblastoma-tissue
#15
Jennifer E Gains, Neil J Sebire, Veronica Moroz, Keith Wheatley, Mark N Gaze
PURPOSE: Neuroblastoma may be treated with molecular radiotherapy, (131)I meta-Iodobenzylguanidine and (177)Lu Lutetium DOTATATE, directed at distinct molecular targets: Noradrenaline Transporter Molecule (NAT) and Somatostatin Receptor (SSTR2), respectively. This study used immunohistochemistry to evaluate target expression in archival neuroblastoma tissue, to determine whether it might facilitate clinical use of molecular radiotherapy. METHODS: Tissue bank samples of formalin fixed paraffin embedded neuroblastoma tissue from patients for whom clinical outcome data were available were sectioned and stained with haematoxylin and eosin, and monoclonal antibodies directed against NAT and SSTR2...
October 17, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29040002/fak-src-paxillin-system-expression-and-disease-outcome-in-human-neuroblastoma
#16
Panagiotis Kratimenos, Ioannis Koutroulis, Vasiliki Syriopoulou, Christina Michailidi, Maria Delivoria-Papadopoulos, Jerzy Klijanienko, Stamatios Theocharis
BACKGROUND: Neuroblastoma (NB) often presents with metastatic disease and poor survival. The need for new prognostic markers remains invaluable. The FAK-Src-Paxillin protein system is associated with aggressive phenotype in adult malignancies but is largely unexplored in pediatric NB. OBJECTIVE: To assess FAK-Src-Paxillin protein expression in human NB cell lines and clinical cytology material and to delineate its association with survival. DESIGN/METHODS: Western blot and immunohistochemistry were applied for FAK-Src-Paxillin expression in NB cell lines and 23 human cytology specimens, respectively...
October 17, 2017: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29039999/treatment-and-survival-of-childhood-neuroblastoma-evidence-from-a-population-based-study-in-the-united-states
#17
Diarmuid Coughlan, Matthew Gianferante, Charles F Lynch, Jennifer L Stevens, Linda C Harlan
BACKGROUND: Childhood neuroblastoma describes a heterogeneous group of extracranial solid tumors, that are treated per risk profile. We sought to describe treatment patterns and survival using population-based data from throughout the United States. MATERIALS AND METHODS: Using the National Cancer Institute (NCI)'s Patterns of Care data, we analyzed treatment provided to newly diagnosed, histologically confirmed neuroblastoma patients in 2010 and 2011, registered to one of 14 Surveillance, Epidemiology, and End Results (SEER) cancer registries...
October 17, 2017: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29024729/integrating-genome-wide-association-study-and-expression-quantitative-trait-locus-study-identifies-multiple-genes-and-gene-sets-associated-with-schizophrenia
#18
Yan Zhao, Awen He, Feng Zhu, Miao Ding, Jingcan Hao, Qianrui Fan, Ping Li, Li Liu, Yanan Du, Xiao Liang, Xiong Guo, Feng Zhang, Xiancang Ma
Schizophrenia is a serious mental disease with high heritability. To better understand the genetic basis of schizophrenia, we conducted a large scale integrative analysis of genome-wide association study (GWAS) and expression quantitative trait loci (eQTLs) data. GWAS summary data was derived from a published GWAS of schizophrenia, containing 9394 schizophrenia patients and 12,462 healthy controls. The eQTLs dataset was obtained from an eQTLs meta-analysis of 5311 subjects, containing 923,021 cis-eQTLs for 14,329 genes and 4732 trans-eQTLs for 2612 genes...
October 9, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29022893/mycn-contributes-to-the-malignant-characteristics-of-erythroleukemia-through-ezh2-mediated-epigenetic-repression-of-p21
#19
Li Liu, Feng Xu, Chun-Kang Chang, Qi He, Ling-Yun Wu, Zheng Zhang, Xiao Li
MYC proto-oncogene family including c-myc and n-myc (MYCN) are critical for normal cell development and tumorigenesis. Overexpression of c-myc causes acute erythroleukemia in vivo. However, the role of MYCN in acute erythroleukemia remains poorly understood. In this study, we found that the patients with erythroleukemia showed higher expression of MYCN than normal controls. In vitro experiments, knockdown of MYCN resulted in decreased cell proliferation, elevated autonomously cell apoptosis and increased P21-mediated cell senescence...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29018329/cddo-and-atra-instigate-differentiation-of-imr32-human-neuroblastoma-cells
#20
Namrata Chaudhari, Priti Talwar, Christian Lefebvre D'hellencourt, Palaniyandi Ravanan
Neuroblastoma is the most common solid extra cranial tumor in infants. Improving the clinical outcome of children with aggressive tumors undergoing one of the multiple treatment options has been a major concern. Differentiating neuroblastoma cells holds promise in inducing tumor growth arrest and treating minimal residual disease. In this study, we investigated the effect of partial PPARγ agonist 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) on human neuroblastoma IMR32 cells. Our results demonstrate that treatment with low concentration of CDDO and particularly in combination with all trans retinoic acid (ATRA) induced neurite outgrowth, increased the percentage of more than two neurites bearing cells, and decreased viability in IMR32 cells...
2017: Frontiers in Molecular Neuroscience
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