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https://www.readbyqxmd.com/read/28735070/suppression-of-the-atp-binding-cassette-transporter-abcc4-impairs-neuroblastoma-tumour-growth-and-sensitises-to-irinotecan-in%C3%A2-vivo
#1
Jayne Murray, Emanuele Valli, Denise M T Yu, Alan M Truong, Andrew J Gifford, Georgina L Eden, Laura D Gamble, Kimberley M Hanssen, Claudia L Flemming, Alvin Tan, Amanda Tivnan, Sophie Allan, Federica Saletta, Leanna Cheung, Michelle Ruhle, John D Schuetz, Michelle J Henderson, Jennifer A Byrne, Murray D Norris, Michelle Haber, Jamie I Fletcher
The ATP-binding cassette transporter ABCC4 (multidrug resistance protein 4, MRP4) mRNA level is a strong predictor of poor clinical outcome in neuroblastoma which may relate to its export of endogenous signalling molecules and chemotherapeutic agents. We sought to determine whether ABCC4 contributes to development, growth and drug response in neuroblastoma in vivo. In neuroblastoma patients, high ABCC4 protein levels were associated with reduced overall survival. Inducible knockdown of ABCC4 strongly inhibited the growth of human neuroblastoma cells in vitro and impaired the growth of neuroblastoma xenografts...
July 20, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28731047/targeted-next-generation-sequencing-supports-epidermoid-metaplasia-of-the-esophagus-as-a-precursor-to-esophageal-squamous-neoplasia
#2
Aatur D Singhi, Christina A Arnold, Dora M Lam-Himlin, Marina N Nikiforova, Lysandra Voltaggio, Marcia I Canto, Kevin M McGrath, Elizabeth A Montgomery
Esophageal epidermoid metaplasia is a rare condition that involves the proximal-to-middle third of the esophagus. It is sharply demarcated and defined histologically by epithelial hyperplasia, a prominent granular cell layer, and superficial hyperorthokeratosis. In addition, preliminary studies have suggested an association between esophageal epidermoid metaplasia and esophageal squamous neoplasia (squamous dysplasia and esophageal squamous cell carcinoma). To further characterize esophageal epidermoid metaplasia and better define its relationship to squamous neoplasia of the esophagus, we performed targeted next-generation sequencing on uninvolved esophageal squamous mucosa and matching esophageal epidermoid metaplasia specimens from 18 patients...
July 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28722675/using-droplet-digital-pcr-to-analyze-mycn-and-alk-copy-number-in-plasma-from-patients-with-neuroblastoma
#3
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...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28717423/contribution-of-neuroblastoma-derived-exosomes-to-the-production-of-pro-tumorigenic-signals-by-bone-marrow-mesenchymal-stromal-cells
#4
Rie Nakata, Hiroyuki Shimada, G Esteban Fernandez, Rob Fanter, Muller Fabbri, Jemily Malvar, Pascale Zimmermann, Yves A DeClerck
The bone marrow (BM) niche is a microenvironment promoting survival, dormancy and therapeutic resistance in tumor cells. Central to this function are mesenchymal stromal cells (MSCs). Here, using neuroblastoma (NB) as a model, we demonstrate that NB cells release an extracellular vesicle (EVs) whose protein cargo is enriched in exosomal proteins but lacks cytokines and chemokines. Using three different purification methods, we then demonstrate that NB-derived exosomes were captured by MSCs and induced the production of pro-tumorigenic cytokines and chemokines, including interleukin-6 (IL-6), IL-8/CXCL8, vascular endothelial cell growth factor and monocyte-chemotactic protein-1, with exosomes prepared by size exclusion chromatography having the highest activity...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28711493/anti-cancer-effect-of-oncolytic-adenovirus-armed-shrna-targeting-mycn-gene-on-doxorubicin-resistant-neuroblastoma-cells
#5
Yuan Li, Baobiao Zhuo, Yiyu Yin, Tao Han, Shixian Li, Zhengwei Li, Jian Wang
Chemotherapy is one of the few effective choices for patients with neuroblastoma. However, the development of muti-drug resistance (MDR) to chemotherapy is a major obstacle to the effective treatment of advanced or recurrent neuroblastoma. The muti-drug resistance-associated protein (MRP), which encodes a transmembrane glycoprotein, is a key regulator of MDR. The expression of MRP is a close correlation with MYCN oncogene in neuroblastoma. We have recently shown ZD55-shMYCN (oncolytic virus armed with shRNA against MYCN) can down-regulate MYCN to inhibit tumor cells proliferation and induce apoptosis in neuroblastoma...
July 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28710315/shallow-whole-genome-sequencing-on-circulating-cell-free-dna-allows-reliable-non-invasive-copy-number-profiling-in-neuroblastoma-patients
#6
Nadine Van Roy, Malaika Van der Linden, Björn Menten, Annelies Dheedene, Charlotte Vandeputte, Jo Van Dorpe, Geneviève Laureys, Marleen Renard, Tom Sante, Tim Lammens, Bram De Wilde, Frank Speleman, Katleen De Preter
<p>Neuroblastoma (NB) is a heterogeneous disease characterized by distinct clinical features and by the presence of typical copy number alterations (CNAs). Given the strong association of these CNA profiles with prognosis, analysis of the CNA profile at diagnosis is mandatory. Therefore, we tested whether the analysis of circulating cell-free DNA (cfDNA) present in plasma samples of NB patients could offer a valuable alternative to primary tumor DNA for CNA profiling.</p> <br /><br />Experimental Design: <p>In 37 NB patients cfDNA analysis using shallow whole genome sequencing (sWGS) was compared to arrayCGH analysis of primary tumor tissue...
July 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28709933/identification-of-novel-biomarker-and-therapeutic-target-candidates-for-diagnosis-and-treatment-of-follicular-carcinoma
#7
Xianyin Lai, Christopher B Umbricht, Kurt Fisher, Justin Bishop, Qiuying Shi, Shaoxiong Chen
Distinguishing follicular carcinoma from follicular adenoma, based on cytomorphological features, has always been challenging to cytopathologists. Identification of biomarkers for improving diagnostic accuracy is important for clinical management. Meanwhile, it is critical to identify therapeutic target candidates for treatment of follicular carcinoma. Currently, no reliable diagnostic protein biomarkers and therapeutic targets are available. To explore novel protein biomarker and therapeutic target candidates, a liquid chromatography-tandem mass spectrometry approach was applied to analyze control, follicular adenoma, and follicular carcinoma using formalin-fixed, paraffin-embedded tissue samples...
July 11, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28702620/nanoparticle-delivery-of-curcumin-induces-cellular-hypoxia-and-ros-mediated-apoptosis-via-modulation-of-bcl-2-bax-in-human-neuroblastoma
#8
Irina Kalashnikova, Joseph Mazar, Craig J Neal, Amy L Rosado, Soumen Das, Tamarah J Westmoreland, Sudipta Seal
In this study, several formulations of nanoceria and dextran-nanoceria with curcumin, each demonstrated to have anti-cancer properties, were synthesized and applied as treatment for human childhood neuroblastoma. The anti-cancer activities of these formulations were explored in neuroblastoma models of both MYCN-amplified and non-amplified cell lines. Ceria nanoparticles, coated with dextran and loaded with curcumin, were found to induce substantial cell death in neuroblastoma cells (up to a 2-fold and a 1.6-fold decrease in cell viability for MYCN-upregulated and normal expressing cell lines, respectively; *p < 0...
July 12, 2017: Nanoscale
https://www.readbyqxmd.com/read/28696504/association-of-mycn-copy-number-with-clinical-features-tumor-biology-and-outcomes-in-neuroblastoma-a-report-from-the-children-s-oncology-group
#9
Kevin Campbell, Julie M Gastier-Foster, Meegan Mann, Arlene H Naranjo, Collin Van Ryn, Rochelle Bagatell, Katherine K Matthay, Wendy B London, Meredith S Irwin, Hiroyuki Shimada, M Meaghan Granger, Michael D Hogarty, Julie R Park, Steven G DuBois
BACKGROUND: High-level MYCN amplification (MNA) is associated with poor outcome and unfavorable clinical and biological features in patients with neuroblastoma. To the authors' knowledge, less is known regarding these associations in patients with low-level MYCN copy number increases. METHODS: In this retrospective study, the authors classified patients has having tumors with MYCN wild-type tumors, MYCN gain (2-4-fold increase in MYCN signal compared with the reference probe), or MNA (>4-fold increase)...
July 11, 2017: Cancer
https://www.readbyqxmd.com/read/28696319/combined-epigenetic-and-differentiation-based-treatment-inhibits-neuroblastoma-tumor-growth-and-links-hif2%C3%AE-to-tumor-suppression
#10
Isabelle Westerlund, Yao Shi, Konstantinos Toskas, Stuart M Fell, Shuijie Li, Olga Surova, Erik Södersten, Per Kogner, Ulrika Nyman, Susanne Schlisio, Johan Holmberg
Neuroblastoma is a pediatric cancer characterized by variable outcomes ranging from spontaneous regression to life-threatening progression. High-risk neuroblastoma patients receive myeloablative chemotherapy with hematopoietic stem-cell transplant followed by adjuvant retinoid differentiation treatment. However, the overall survival remains low; hence, there is an urgent need for alternative therapeutic approaches. One feature of high-risk neuroblastoma is the high level of DNA methylation of putative tumor suppressors...
July 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28680756/amplification-of-n-myc-is-associated-with-a-t-cell-poor-microenvironment-in-metastatic-neuroblastoma-restraining-interferon-pathway-activity-and-chemokine-expression
#11
Julian P Layer, Marie T Kronmüller, Thomas Quast, Debby van den Boorn-Konijnenberg, Maike Effern, Daniel Hinze, Kristina Althoff, Alexander Schramm, Frank Westermann, Martin Peifer, Gunther Hartmann, Thomas Tüting, Waldemar Kolanus, Matthias Fischer, Johannes Schulte, Michael Hölzel
Immune checkpoint inhibitors have significantly improved the treatment of several cancers. T-cell infiltration and the number of neoantigens caused by tumor-specific mutations are correlated to favorable responses in cancers with a high mutation load. Accordingly, checkpoint immunotherapy is thought to be less effective in tumors with low mutation frequencies such as neuroblastoma, a neuroendocrine tumor of early childhood with poor outcome of the high-risk disease group. However, spontaneous regressions and paraneoplastic syndromes seen in neuroblastoma patients suggest substantial immunogenicity...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28680748/mycn-is-an-immunosuppressive-oncogene-dampening-the-expression-of-ligands-for-nk-cell-activating-receptors-in-human-high-risk-neuroblastoma
#12
Elisa Brandetti, Irene Veneziani, Ombretta Melaiu, Annalisa Pezzolo, Aurora Castellano, Renata Boldrini, Elisa Ferretti, Doriana Fruci, Lorenzo Moretta, Vito Pistoia, Franco Locatelli, Loredana Cifaldi
Neuroblastoma (NB) is the most common extracranial solid tumor occurring in childhood. Amplification of the MYCN oncogene is associated with poor prognosis. Downregulation on NB cells of ligands recognized by Natural Killer (NK) cell-activating receptors, involved in tumor cell recognition and lysis, may contribute to tumor progression and relapse. Here, we demonstrate that in human NB cell lines MYCN expression inversely correlates with that of ligands recognized by NKG2D and DNAM1 activating receptors in human NB cell lines...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28671688/the-genomic-landscape-of-pediatric-and-young-adult-t-lineage-acute-lymphoblastic-leukemia
#13
Yu Liu, John Easton, Ying Shao, Jamie Maciaszek, Zhaoming Wang, Mark R Wilkinson, Kelly McCastlain, Michael Edmonson, Stanley B Pounds, Lei Shi, Xin Zhou, Xiaotu Ma, Edgar Sioson, Yongjin Li, Michael Rusch, Pankaj Gupta, Deqing Pei, Cheng Cheng, Malcolm A Smith, Jaime Guidry Auvil, Daniela S Gerhard, Mary V Relling, Naomi J Winick, Andrew J Carroll, Nyla A Heerema, Elizabeth Raetz, Meenakshi Devidas, Cheryl L Willman, Richard C Harvey, William L Carroll, Kimberly P Dunsmore, Stuart S Winter, Brent L Wood, Brian P Sorrentino, James R Downing, Mignon L Loh, Stephen P Hunger, Jinghui Zhang, Charles G Mullighan
Genetic alterations that activate NOTCH1 signaling and T cell transcription factors, coupled with inactivation of the INK4/ARF tumor suppressors, are hallmarks of T-lineage acute lymphoblastic leukemia (T-ALL), but detailed genome-wide sequencing of large T-ALL cohorts has not been carried out. Using integrated genomic analysis of 264 T-ALL cases, we identified 106 putative driver genes, half of which had not previously been described in childhood T-ALL (for example, CCND3, CTCF, MYB, SMARCA4, ZFP36L2 and MYCN)...
July 3, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28662353/neuroblastoma-in-children-update-on-clinicopathologic-and-genetic-prognostic-factors
#14
Atif A Ahmed, Lei Zhang, Naresh Reddivalla, Maxine Hetherington
Neuroblastoma is the most common extracranial solid tumor in childhood accounting for 8-10% of all childhood malignancies. The tumor is characterized by a spectrum of histopathologic features and a heterogeneous clinical phenotype. Modern multimodality therapy results in variable clinical response ranging from cure in localized tumors to limited response in aggressive metastatic disease. Accurate clinical staging and risk assessment based on clinical, surgical, biologic and pathologic criteria are of pivotal importance in assigning prognosis and planning effective treatment approaches...
June 29, 2017: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/28647884/fluoxetine-induces-apoptosis-through-endoplasmic-reticulum-stress-via-mitogen-activated-protein-kinase-activation-and-histone-hyperacetylation-in-sk-n-be-2-m17-human-neuroblastoma-cells
#15
Ji Hyun Choi, Yeon Ju Jeong, Ah-Ran Yu, Kyung-Sik Yoon, Wonchae Choe, Joohun Ha, Sung Soo Kim, Eui-Ju Yeo, Insug Kang
Fluoxetine (FLX) is an antidepressant drug that belongs to the class of selective serotonin reuptake inhibitors. FLX is known to induce apoptosis in multiple types of cancer cells. In this study, the molecular mechanisms underlying the anti-cancer effects of FLX were investigated in SK-N-BE(2)-M17 human neuroblastoma cells. FLX induced apoptotic cell death, activation of caspase-4, -9, and -3, and expression of endoplasmic reticulum (ER) stress-associated proteins, including C/EBP homologous protein (CHOP)...
June 24, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28637693/neuroblast-differentiation-during-development-and-in-neuroblastoma-requires-kif1b%C3%AE-mediated-transport-of-trka
#16
Stuart M Fell, Shuijie Li, Karin Wallis, Anna Kock, Olga Surova, Vilma Rraklli, Carolin S Höfig, Wenyu Li, Jens Mittag, Marie Arsenian Henriksson, Rajappa S Kenchappa, Johan Holmberg, Per Kogner, Susanne Schlisio
We recently identified pathogenic KIF1Bβ mutations in sympathetic nervous system malignancies that are defective in developmental apoptosis. Here we deleted KIF1Bβ in the mouse sympathetic nervous system and observed impaired sympathetic nervous function and misexpression of genes required for sympathoadrenal lineage differentiation. We discovered that KIF1Bβ is required for nerve growth factor (NGF)-dependent neuronal differentiation through anterograde transport of the NGF receptor TRKA. Moreover, pathogenic KIF1Bβ mutations identified in neuroblastoma impair TRKA transport...
May 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28604107/accelerating-drug-development-for-neuroblastoma-new-drug-development-strategy-an-innovative-therapies-for-children-with-cancer-european-network-for-cancer-research-in-children-and-adolescents-and-international-society-of-paediatric-oncology-europe-neuroblastoma
#17
REVIEW
Lucas Moreno, Hubert Caron, Birgit Geoerger, Angelika Eggert, Gudrun Schleiermacher, Penelope Brock, Dominique Valteau-Couanet, Louis Chesler, Johannes H Schulte, Katleen De Preter, Jan Molenaar, Alexander Schramm, Martin Eilers, Tom Van Maerken, John Inge Johnsen, Michelle Garrett, Sally L George, Deborah A Tweddle, Per Kogner, Frank Berthold, Jan Koster, Giuseppe Barone, Elizabeth R Tucker, Lynley Marshall, Ralf Herold, Jaroslav Sterba, Koen Norga, Gilles Vassal, Andrew Dj Pearson
Neuroblastoma, the commonest paediatric extra-cranial tumour, remains a leading cause of death from cancer in children. There is an urgent need to develop new drugs to improve cure rates and reduce long-term toxicity and to incorporate molecularly targeted therapies into treatment. Many potential drugs are becoming available, but have to be prioritised for clinical trials due to the relatively small numbers of patients. Areas covered: The current drug development model has been slow, associated with significant attrition, and few new drugs have been developed for neuroblastoma...
August 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28602975/the-small-molecule-inhibitor-yk-4-279-disrupts-mitotic-progression-of-neuroblastoma-cells-overcomes-drug-resistance-and-synergizes-with-inhibitors-of-mitosis
#18
Madhu Kollareddy, Alice Sherrard, Ji Hyun Park, Marianna Szemes, Kelli Gallacher, Zsombor Melegh, Sebastian Oltean, Martin Michaelis, Jindrich Cinatl, Abderrahmane Kaidi, Karim Malik
Neuroblastoma is a biologically and clinically heterogeneous pediatric malignancy that includes a high-risk subset for which new therapeutic agents are urgently required. As well as MYCN amplification, activating point mutations of ALK and NRAS are associated with high-risk and relapsing neuroblastoma. As both ALK and RAS signal through the MEK/ERK pathway, we sought to evaluate two previously reported inhibitors of ETS-related transcription factors, which are transcriptional mediators of the Ras-MEK/ERK pathway in other cancers...
June 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28592245/in-silico-identification-of-potential-key-regulatory-factors-in-smoking-induced-lung-cancer
#19
Salem A El-Aarag, Amal Mahmoud, Medhat H Hashem, Hatem Abd Elkader, Alaa E Hemeida, Mahmoud ElHefnawi
BACKGROUND: Lung cancer is a leading cause of cancer-related death worldwide and is the most commonly diagnosed cancer. Like other cancers, it is a complex and highly heterogeneous disease involving multiple signaling pathways. Identifying potential therapeutic targets is critical for the development of effective treatment strategies. METHODS: We used a systems biology approach to identify potential key regulatory factors in smoking-induced lung cancer. We first identified genes that were differentially expressed between smokers with normal lungs and those with cancerous lungs, then integrated these differentially expressed genes (DEGs) with data from a protein-protein interaction database to build a network model with functional modules for pathway analysis...
June 7, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28591696/clinical-evaluation-of-integrated-panel-testing-by-nextgeneration-sequencing-for-somatic-mutations-in-neuroblastomas-with-mycn-unamplification
#20
Yanna Cao, Yan Jin, Jinpu Yu, Jingfu Wang, Yanli Qiu, Xiaofeng Duan, Yingnan Ye, Yanan Cheng, Li Dong, Xiaolong Feng, Daowei Wang, Zhongyuan Li, Xiangdong Tian, Huijuan Wang, Jie Yan, Qiang Zhao
Neuroblastomas (NBs) exhibit heterogeneity and show clinically significant prognosis classified by genetic alterations. Among prognostic genes or genome factors, MYCN amplification (MNA) is the most established genomic marker of poor prognosis in patients with NB. However, the prognostic classification of more than 60% of patients without MNA has yet to be clarified. In this study, the application of target next-generation sequencing (NGS) was extended on the basis of a comprehensive panel of regions where copy number variations (CNVs) or point mutations occurred to improve the prognostic evaluation of these patients and obtain the sequence of 33 patients without MNA...
May 17, 2017: Oncotarget
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