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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
#1
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
#2
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
#3
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...
June 12, 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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/28586032/a-sketch-of-known-and-novel-mycn-associated-mirna-networks-in-neuroblastoma
#7
Francesca Megiorni, Moreno Colaiacovo, Samantha Cialfi, Heather P McDowell, Alessandro Guffanti, Simona Camero, Armando Felsani, Paul D Losty, Barry Pizer, Rajeev Shukla, Carlo Cappelli, Eva Ferrara, Antonio Pizzuti, Anna Moles, Carlo Dominici
Neuroblastoma (NB) originates from neural crest-derived precursors and represents the most common childhood extracranial solid tumour. MicroRNAs (miRNAs), a class of small non-coding RNAs that participate in a wide variety of biological processes by regulating gene expression, appear to play an essential role within the NB context. High-throughput next generation sequencing (NGS) was applied to study the miRNA transcriptome in a cohort of NB tumours with and without MYCN-amplification (MNA and MNnA, respectively) and in dorsal root ganglia (DRG), as a control...
June 6, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28574509/mycn-amplified-neuroblastoma-requires-the-mrna-translation-regulator-eef2-kinase-to-adapt-to-nutrient-deprivation
#8
Alberto Delaidelli, Gian Luca Negri, Asad Jan, Brandon Jansonius, Amal El-Naggar, Jonathan K M Lim, Debjit Khan, Htoo Zarni Oo, Christopher J Carnie, Marc Remke, John M Maris, Gabriel Leprivier, Poul H Sorensen
MYC family proteins are implicated in many human cancers, but their therapeutic targeting has proven challenging. MYCN amplification in childhood neuroblastoma (NB) is associated with aggressive disease and high mortality. Novel and effective therapeutic strategies are therefore urgently needed for these tumors. MYC-driven oncogenic transformation impairs cell survival under nutrient deprivation (ND), a characteristic stress condition within the tumor microenvironment. We recently identified eukaryotic Elongation Factor 2 Kinase (eEF2K) as a pivotal mediator of the adaptive response of tumor cells to ND...
June 2, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28559940/clinical-significance-of-pretreatment-fdg-pet-ct-in-mibg-avid-pediatric-neuroblastoma
#9
Seo Young Kang, Muhammad Kashif Rahim, Yong-Il Kim, Gi Jeong Cheon, Hyoung Jin Kang, Hee Young Shin, Keon Wook Kang, June-Key Chung, E Edmund Kim, Dong Soo Lee
PURPOSE: (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging is well known to have clinical significance in the initial staging and response evaluation of the many kinds of neoplasms. However, its role in the pediatric neuroblastoma is not clearly defined. In the present study, the clinical significance of FDG-PET/computed tomography (CT) in (123)I- or (131)I-metaiodobenzylguanidine (MIBG)-avid pediatric neuroblastoma was investigated. METHODS: Twenty patients with neuroblastoma who undertook pretreatment FDG PET/CT at our institute between 2008 and 2015 and showed MIBG avidity were retrospectively enrolled in the present study...
June 2017: Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28559462/expression-of-five-neuroblastoma-genes-in-bone-marrow-or-blood-of-patients-with-relapsed-refractory-neuroblastoma-provides-a-new-biomarker-for-disease-and-prognosis
#10
Araz Marachelian, Judith G Villablanca, Cathy W Liu, Betty Liu, Fariba Goodarzian, Hollie A Lai, Hiroyuki Shimada, Hung C Tran, Jaime A Parra, Richard Gallego, Nora Bedrossian, Sabrina Young, Scarlett Czarnecki, Rebekah Kennedy, Brian Weiss, Kelly C Goldsmith, Meaghan Granger, Katherine K Matthay, Susan Groshen, Shahab Asgharzadeh, Richard Sposto, Robert C Seeger
We determined if quantifying neuroblastoma (NB)-associated mRNAs (NB-mRNA) in bone marrow (BM) and blood improves assessment of disease and prediction of disease progression in patients with relapsed/refractory NB. <br /><br />Patients and Methods: mRNA for CHGA, DCX, DDC, PHOX2B, and TH was quantified in BM and blood from 101 patients concurrently with clinical disease evaluations. Correlation between NB-mRNA (delta cycle threshold [ΔCt] for the geometric mean of genes from the TaqMan® Low Density Array NB5 assay) and morphologically-defined tumor cell percentage in BM, (123)I-meta-iodobenzylguanidine (MIBG) Curie score, and CT/MRI-defined tumor longest diameter was determined...
May 30, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28549783/irinotecan-temozolomide-with-temsirolimus-or-dinutuximab-in-children-with-refractory-or-relapsed-neuroblastoma-cog-anbl1221-an-open-label-randomised-phase-2-trial
#11
Rajen Mody, Arlene Naranjo, Collin Van Ryn, Alice L Yu, Wendy B London, Barry L Shulkin, Marguerite T Parisi, Sabah-E-Noor Servaes, Mitchell B Diccianni, Paul M Sondel, Julia G Bender, John M Maris, Julie R Park, Rochelle Bagatell
BACKGROUND: Outcomes for children with relapsed and refractory neuroblastoma are dismal. The combination of irinotecan and temozolomide has activity in these patients, and its acceptable toxicity profile makes it an excellent backbone for study of new agents. We aimed to test the addition of temsirolimus or dinutuximab to irinotecan-temozolomide in patients with relapsed or refractory neuroblastoma. METHODS: For this open-label, randomised, phase 2 selection design trial of the Children's Oncology Group (COG; ANBL1221), patients had to have histological verification of neuroblastoma or ganglioneuroblastoma at diagnosis or have tumour cells in bone marrow with increased urinary catecholamine concentrations at diagnosis...
May 23, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28546523/alk-protein-expression-is-related-to-neuroblastoma-aggressiveness-but-is-not-independent-prognostic-factor
#12
Ji Won Lee, Sung Hye Park, Hyoung Jin Kang, Kyung Duk Park, Hee Young Shin, Hyo Seop Ahn
Purpose: In this study, anaplastic lymphoma kinase (ALK) mutation and amplification, ALK protein expression, loss of the nuclear alpha thalassemia/mental retardation syndrome X-linked (ATRX) protein, and telomerase reverse transcriptase (TERT) protein expression were studied to investigate potential correlations between these molecular characteristics and clinical features or outcomes in neuroblastoma. Materials and Methods: Seventy-two patients were enrolled in this study...
May 22, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28525978/notch-ligand-delta-like-1-as-a-novel-molecular-target-in-childhood-neuroblastoma
#13
P Bettinsoli, G Ferrari-Toninelli, S A Bonini, C Prandelli, M Memo
BACKGROUND: Neuroblastoma is the most common extracranial solid malignancy in childhood, responsible for 15% of all pediatric cancer deaths. It is an heterogeneous disease that does not always respond to classical therapy; so the identification of new and specific molecular targets to improve existing therapy is needed. We have previously demonstrated the involvement of the Notch pathway in the onset and progression of neuroblastoma. In this study we further investigated the role of Notch signaling and identified Delta-like 1 (DLL1) as a novel molecular target in neuroblastoma cells with a high degree of MYCN amplification, which is a major oncogenic driver in neuroblastoma...
May 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28521631/immunohistochemical-profile-of-myc-protein-in-pediatric-small-round-blue-cell-tumors
#14
Karen M Chisholm, Chandra Krishnan, Amy Heerema-McKenney, Yasodha Natkunam
Deregulation of MYC oncoprotein in cancers can result from multiple oncogenic mechanisms. Although MYC translocations define Burkitt lymphoma and MYC protein expression is a poor prognostic factor in undifferentiated neuroblastomas, the distribution of MYC protein (c-MYC) across other pediatric small round blue cell tumors (SRBCT) has not been well characterized. We undertook this study to assess MYC protein expression in a large cohort of pediatric lymphomas, sarcomas, and other SRBCT. Tissue microarrays containing 302 SRBCT were successfully evaluated by immunohistochemistry using anti-MYC clone Y69, with nuclear positivity scored as 0%, 1%-25%, 26%-50%, 51%-75%, or 76%-100%...
June 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28521285/arid1b-alterations-identify-aggressive-tumors-in-neuroblastoma
#15
Soo Hyun Lee, Jung-Sun Kim, Siyuan Zheng, Jason T Huse, Joon Seol Bae, Ji Won Lee, Keon Hee Yoo, Hong Hoe Koo, Sungkyu Kyung, Woong-Yang Park, Ki Woong Sung
Targeted panel sequencing was performed to determine molecular targets and biomarkers in 72 children with neuroblastoma. Frequent genetic alterations were detected in ALK (16.7%), BRCA1 (13.9%), ATM (12.5%), and PTCH1 (11.1%) in an 83-gene panel. Molecular targets for targeted therapy were identified in 16 of 72 patients (22.2%). Two-thirds of ALK mutations were known to increase sensitivity to ALK inhibitors. Sequence alterations in ARID1B were identified in 5 of 72 patients (6.9%). Four of five ARID1B alterations were detected in tumors of high-risk patients...
April 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28506690/romidepsin-induces-caspase-dependent-cell-death-in-human-neuroblastoma-cells
#16
Shane V Hegarty, Katie L Togher, Eimear O'Leary, Franziska Solger, Aideen M Sullivan, Gerard W O'Keeffe
Neuroblastoma is the most common extracranial pediatric solid tumor, arising from the embryonic sympathoadrenal lineage of the neural crest, and is responsible for 15% of childhood cancer deaths. Although survival rates are good for some patients, those children diagnosed with high-risk neuroblastoma have survival rates as low as 35%. Thus, neuroblastoma remains a significant clinical challenge and the development of novel therapeutic strategies is essential. Given that there is widespread epigenetic dysregulation in neuroblastoma, epigenetic pharmacotherapy holds promise as a therapeutic approach...
May 12, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28467792/assessment-of-citalopram-and-escitalopram-on-neuroblastoma-cell-lines-cell-toxicity-and-gene-modulation
#17
Laurent Sakka, Nathalie Delétage, Maryse Chalus, Youssef Aissouni, Valérie Sylvain-Vidal, Stéphane Gobron, Guillaume Coll
Selective serotonin reuptake inhibitors (SSRI) are common antidepressants which cytotoxicity has been assessed in cancers notably colorectal carcinomas and glioma cell lines. We assessed and compared the cytotoxicity of 2 SSRI, citalopram and escitalopram, on neuroblastoma cell lines. The study was performed on 2 non-MYCN amplified cell lines (rat B104 and human SH-SY5Y) and 2 human MYCN amplified cell lines (IMR32 and Kelly). Citalopram and escitalopram showed concentration-dependent cytotoxicity on all cell lines...
April 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28465480/clinical-and-biological-features-of-neuroblastic-tumors-a-comparison-of-neuroblastoma-and-ganglioneuroblastoma
#18
Wen-Guang He, Yu Yan, Wen Tang, Rong Cai, Gang Ren
Neuroblastoma (NB), ganglioneuroblastoma intermixed (GNBi) and ganglioneuroblastoma nodular (GNBn) are neuroblastic tumors that present with a wide range of symptoms and variable prognoses. We retrospectively reviewed the pretreatment clinical (age, sex and tumor stage) and biological (MYCN amplification; and levels of lactate dehydrogenase, ferritin and neuron-specific enolase) characteristics of 279 patients who were diagnosed with pathologically confirmed NB and GNB from January 2005 to December 2015. The median age at diagnosis increased with grade of differentiation (NB: 28...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28465359/elevated-foxg1-and-sox2-in-glioblastoma-enforces-neural-stem-cell-identity-through-transcriptional-control-of-cell-cycle-and-epigenetic-regulators
#19
Harry Bulstrode, Ewan Johnstone, Maria Angeles Marques-Torrejon, Kirsty M Ferguson, Raul Bardini Bressan, Carla Blin, Vivien Grant, Sabine Gogolok, Ester Gangoso, Sladjana Gagrica, Christine Ender, Vassiliki Fotaki, Duncan Sproul, Paul Bertone, Steven M Pollard
Glioblastoma multiforme (GBM) is an aggressive brain tumor driven by cells with hallmarks of neural stem (NS) cells. GBM stem cells frequently express high levels of the transcription factors FOXG1 and SOX2. Here we show that increased expression of these factors restricts astrocyte differentiation and can trigger dedifferentiation to a proliferative NS cell state. Transcriptional targets include cell cycle and epigenetic regulators (e.g., Foxo3, Plk1, Mycn, Dnmt1, Dnmt3b, and Tet3). Foxo3 is a critical repressed downstream effector that is controlled via a conserved FOXG1/SOX2-bound cis-regulatory element...
April 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28459463/mycn-induces-neuroblastoma-in-primary-neural-crest-cells
#20
R R Olsen, J H Otero, J García-López, K Wallace, D Finkelstein, J E Rehg, Z Yin, Y-D Wang, K W Freeman
Neuroblastoma (NBL) is an embryonal cancer of the sympathetic nervous system (SNS), which causes 15% of pediatric cancer deaths. High-risk NBL is characterized by N-Myc amplification and segmental chromosomal gains and losses. Owing to limited disease models, the etiology of NBL is largely unknown, including both the cell of origin and the majority of oncogenic drivers. We have established a novel system for studying NBL based on the transformation of neural crest cells (NCCs), the progenitor cells of the SNS, isolated from mouse embryonic day 9...
May 1, 2017: Oncogene
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