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https://www.readbyqxmd.com/read/28072621/risk-stratification-of-pediatric-patients-with-neuroblastoma-using-volumetric-parameters-of-18f-fdg-and-18f-dopa-pet-ct
#1
Chia-Ju Liu, Meng-Yao Lu, Yen-Lin Liu, Chi-Lun Ko, Kuan-Yin Ko, Kai-Yuan Tzen, Hsiu-Hao Chang, Yung-Li Yang, Shiann-Tarng Jou, Wen-Ming Hsu, Ruoh-Fang Yen
PURPOSE: This study determined the prognostic value of volumetric parameters derived from pretreatment F-FDG and F-DOPA PET/CT of neuroblastoma and their correlation with clinical and histopathologic features. PATIENTS AND METHODS: A total of 25 children with neuroblastoma underwent pretreatment F-FDG and F-DOPA PET/CT within 4 weeks. The SUVmax of primary tumors on F-FDG and F-DOPA PET were recorded as SUVFDG and SUVDOPA, respectively. For volumetric parameters of primary tumors, 40% of SUVmax was used to generate volume of interest...
January 9, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28061374/catecholamines-profiles-at-diagnosis-increased-diagnostic-sensitivity-and-correlation-with-biological-and-clinical-features-in-neuroblastoma-patients
#2
Iedan R N Verly, André B P van Kuilenburg, Nico G G M Abeling, Susan M I Goorden, Marta Fiocco, Frédéric M Vaz, Max M van Noesel, C Michel Zwaan, GertJan L Kaspers, Johannes H M Merks, Huib N Caron, Godelieve A M Tytgat
INTRODUCTION: Neuroblastoma (NBL) accounts for 10% of the paediatric malignancies and is responsible for 15% of the paediatric cancer-related deaths. Vanillylmandelic acid (VMA) and homovanillic acid (HVA) are most commonly analysed in urine of NBL patients. However, their diagnostic sensitivity is suboptimal (82%). Therefore, we performed in-depth analysis of the diagnostic sensitivity of a panel of urinary catecholamine metabolites. PATIENTS AND METHODS: Retrospective study of a panel of 8 urinary catecholamine metabolites (VMA, HVA, 3-methoxytyramine [3MT], dopamine, epinephrine, metanephrine, norepinephrine and normetanephrine [NMN]) from 301 NBL patients at diagnosis...
January 3, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28054532/polymorphisms-of-glucose-regulated-protein-78-and-clinical-relevance-of-neuroblastoma-risk-and-prognosis
#3
Jiao Zhang, Jiaxiang Wang, Qiuliang Liu, Jingyao Gao, Qi Wang
BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Glucose/regulated protein 78 (GRP78) is a stress-associated protein. It has been reported that overexpression of GRP78 occurs in various human cancers, and GRP78 polymorphisms have effect on the expression of GRP78 with possible function of predicting clinical outcome. Upregulation of GRP78 has been detected in NB. However, little is known about the relationship of GRP78 polymorphisms and the susceptibility of NB...
July 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28036269/the-gsk461364-plk1-inhibitor-exhibits-strong-antitumoral-activity-in-preclinical-neuroblastoma-models
#4
Kristian W Pajtler, Natalie Sadowski, Sandra Ackermann, Kristina Althoff, Kerstin Schönbeck, Katharina Batzke, Simon Schäfers, Andrea Odersky, Lukas Heukamp, Kathy Astrahantseff, Annette Künkele, Hedwig E Deubzer, Alexander Schramm, Annika Sprüssel, Theresa Thor, Sven Lindner, Angelika Eggert, Matthias Fischer, Johannes H Schulte
Polo-like kinase 1 (PLK1) is a serine/threonine kinase that promotes G2/M-phase transition, is expressed in elevated levels in high-risk neuroblastomas and correlates with unfavorable patient outcome. Recently, we and others have presented PLK1 as a potential drug target for neuroblastoma, and reported that the BI2536 PLK1 inhibitor showed antitumoral actvity in preclinical neuroblastoma models. Here we analyzed the effects of GSK461364, a competitive inhibitor for ATP binding to PLK1, on typical tumorigenic properties of preclinical in vitro and in vivo neuroblastoma models...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28035057/the-long-non-coding-rna-gas5-differentially-regulates-cell-cycle-arrest-and-apoptosis-through-activation-of-brca1-and-p53-in-human-neuroblastoma
#5
Joseph Mazar, Amy Rosado, John Shelley, John Marchica, Tamarah J Westmoreland
The long non-coding RNA GAS5 has been shown to modulate cancer proliferation in numerous human cancer systems and has been correlated with successful patient outcome. Our examination of GAS5 in neuroblastoma has revealed robust expression in both MYCN-amplified and non-amplified cell lines. Knockdown of GAS5 In vitro resulted in defects in cell proliferation, apoptosis, and induced cell cycle arrest. Further analysis of GAS5 clones revealed multiple novel splice variants, two of which inversely modulated with MYCN status...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28032389/bithalamic-gliomas-may-be-molecularly-distinct-from-their-unilateral-high-grade-counterparts
#6
Alberto Broniscer, Scott N Hwang, Omar Chamdine, Tong Lin, Stanley Pounds, Arzu Onar-Thomas, Lei Chi, Sheila Shurtleff, Sariah Allen, Amar Gajjar, Paul Northcott, Brent A Orr
Bithalamic gliomas are rare cancers diagnosed based on poorly defined radiologic criteria. Infiltrative astrocytomas account for most cases. While some previous studies reported dismal outcomes for patients with bithalamic gliomas irrespective of therapy and histologic grade, others described better prognoses even without anticancer therapy. Little is known about their molecular characteristics. We reviewed clinical, radiologic, and histologic features of patients with bithalamic gliomas treated at our institution over 15 years...
December 28, 2016: Brain Pathology
https://www.readbyqxmd.com/read/28007786/myc-mycn-mediated-glycolysis-enhances-mouse-spermatogonial-stem-cell-self-renewal
#7
Mito Kanatsu-Shinohara, Takashi Tanaka, Narumi Ogonuki, Atsuo Ogura, Hiroko Morimoto, Pei Feng Cheng, Robert N Eisenman, Andreas Trumpp, Takashi Shinohara
Myc plays critical roles in the self-renewal division of various stem cell types. In spermatogonial stem cells (SSCs), Myc controls SSC fate decisions because Myc overexpression induces enhanced self-renewal division, while depletion of Max, a Myc-binding partner, leads to meiotic induction. However, the mechanism by which Myc acts on SSC fate is unclear. Here we demonstrate a critical link between Myc/Mycn gene activity and glycolysis in SSC self-renewal. In SSCs, Myc/Mycn are regulated by Foxo1, whose deficiency impairs SSC self-renewal...
December 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/28003306/microrna-221-enhances-mycn-via-targeting-nemo-like-kinase-and-functions-as-an-oncogene-related-to-poor-prognosis-in-neuroblastoma
#8
Xiao-Yan He, Zheng-Lan Tan, Qin Mou, Fang-Jie Liu, Shan Liu, Chao-Wen Yu, Jin Zhu, Lin-Ya Lv, Jun Zhang, Shan Wang, Liming Bao, Bin Peng, Hui Zhao, Lin Zou
PURPOSE: MYCN is one of the most well-characterized genetic markers of neuroblastoma (NB). However, the mechanisms as to how MYCN mediate NB tumorigenesis is not fully clear. Increasing evidence has confirmed that the dysregulation of miRNAs is involved in MYCN-mediated NB tumorigenesis, supporting their potential as therapeutic targets for NB. Though miR-221 has been reported as one of the upregulated miRNAs, the interplay between miR-221 and MYCN-mediated NB progression remains largely elusive...
December 21, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27966455/a-multidisciplinary-team-care-approach-improves-outcomes-in-high-risk-pediatric-neuroblastoma-patients
#9
Hsiu-Hao Chang, Yen-Lin Liu, Meng-Yao Lu, Shiann-Tarng Jou, Yung-Li Yang, Dong-Tsamn Lin, Kai-Hsin Lin, Kai-Yuan Tzen, Ruoh-Fang Yen, Ching-Chu Lu, Chia-Ju Liu, Steven Shinn-Forng Peng, Yung-Ming Jeng, Shiu-Feng Huang, Hsinyu Lee, Hsueh-Fen Juan, Min-Chuan Huang, Yung-Feng Liao, Ya-Ling Lee, Wen-Ming Hsu
We assessed the impact of a multidisciplinary team care program on treatment outcomes in neuroblastoma patients. Newly diagnosed neuroblastoma patients received treatment under the Taiwan Pediatric Oncology Group (TPOG) N2002 protocol at the National Taiwan University Hospital beginning in 2002. A multidisciplinary team care approach that included nurse-led case management for patients treated under this protocol began in January 2010. Fifty-eight neuroblastoma patients, including 29 treated between 2002 and 2009 (Group 1) and 29 treated between 2010 and 2014 (Group 2), were enrolled in the study...
December 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27935099/mcpip1-exogenous-overexpression-inhibits-pathways-regulating-mycn-oncoprotein-stability-in-neuroblastoma
#10
Elżbieta Boratyn, Iwona Nowak, Małgorzata Durbas, Irena Horwacik, Anna Sawicka, Hanna Rokita
The main physiological function of MCPIP1 (regnase-1) is negative regulation of inflammation. Moreover, roles of regnase-1 in apoptosis and differentiation have also been described, but its involvement in cancer is yet to be fully recognized. Earlier, we showed a lack of expression of MCPIP1 in both primary tumors and several neuroblastoma cell lines. Additionally, we reported that levels of MCPIP1 and the key neuroblastoma oncoprotein - MYCN were inversely correlated in BE(2)-C clones overexpressing the MCPIP1 gene...
December 9, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27923830/a-myc-activity-signature-predicts-poor-clinical-outcomes-in-myc-associated-cancers
#11
MoonSun Jung, Amanda J Russell, Bing Liu, Joshy George, Pei Yan Liu, Tao Liu, Anna DeFazio, David D L Bowtell, Andre Oberthuer, Wendy B London, Jamie I Fletcher, Michelle Haber, Murray D Norris, Michelle J Henderson
Myc transcriptional activity is frequently deregulated in human cancers, but a Myc-driven gene signature with prognostic ability across multiple tumor types remains lacking. Here we selected 18 Myc-regulated genes from published studies of Myc family targets in epithelial ovarian cancer (EOC) and neuroblastoma. A Myc family activity score derived from the 18 genes was correlated to MYC/MYCN/MYCL1 expression in a panel of 35 cancer cell lines. The prognostic ability of this signature was evaluated in neuroblastoma, medulloblastoma, diffuse large B-cell lymphoma (DLBCL), and EOC microarray gene expression datasets using Kaplan-Meier and multivariate Cox-regression analyses, and was further validated in 42 primary neuroblastomas using qPCR...
December 6, 2016: Cancer Research
https://www.readbyqxmd.com/read/27919448/fx11-inhibits-aerobic-glycolysis-and-growth-of-neuroblastoma-cells
#12
Eric J Rellinger, Brian T Craig, Alexandra L Alvarez, Haley L Dusek, Kwang W Kim, Jingbo Qiao, Dai H Chung
BACKGROUND: The MYC family of proteins promotes neuroblastoma tumorigenesis at least in part through the induction of aerobic glycolysis by promoting the transcription of key glycolytic enzymes, such as LDHA. FX11 is a selective inhibitor of LDHA that has demonstrated preclinical efficacy in adult cancers. Herein, we hypothesized that FX11 would inhibit aerobic glycolysis and block growth of neuroblastoma cells. METHODS: We surveyed 3 MYCN-single copy and 5 MYCN-amplified neuroblastoma cell lines to correlate C-MYC/N-MYC protein levels with LDHA expression...
December 2, 2016: Surgery
https://www.readbyqxmd.com/read/27907905/association-of-high-microvessel-%C3%AE-v%C3%AE-3-and-low-pten-with-poor-outcome-in-stage-3-neuroblastoma-rationale-for-using-first-in-class-dual-pi3k-brd4-inhibitor-sf1126
#13
Anat Erdreich-Epstein, Alok R Singh, Shweta Joshi, Francisco M Vega, Pinzheng Guo, Jingying Xu, Susan Groshen, Wei Ye, Melissa Millard, Mihaela Campan, Guillermo Morales, Joseph R Garlich, Peter W Laird, Robert C Seeger, Hiroyuki Shimada, Donald L Durden
Neuroblastoma (NB) is the most common extracranial solid tumor in children. Our previous studies showed that the angiogenic integrin αvβ3 was increased in high-risk metastatic (stage 4) NB compared with localized neuroblastomas. Herein, we show that integrin αvβ3 was expressed on 68% of microvessels in MYCN-amplified stage 3 neuroblastomas, but only on 34% (means) in MYCN-non-amplified tumors (p < 0.001; n = 54). PTEN, a tumor suppressor involved in αvβ3 signaling, was expressed in neuroblastomas either diffusely, focally or not at all (immunohistochemistry)...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27906629/purification-activity-and-expression-levels-of-two-uridine-cytidine-kinase-isoforms-in-neuroblastoma-cell-lines
#14
R Meinsma, A B P van Kuilenburg
Uridine-cytidine kinase (UCK) catalyzes the phosphorylation of uridine, cytidine, and several pyrimidine ribonucleoside analogs. We overexpressed and purified the two known isoforms of human UCK in Escherichia coli, produced a specific antibody against UCK1 and characterized the kinetic properties of UCK1 and 2. The Vmax of purified recombinant UCK2 was 22- and 8-fold higher with uridine and cytidine, respectively, compared to those observed for the purified recombinant UCK1 enzyme. The Km of UCK1 was 39- and 40-fold higher with uridine and cytidine, respectively, compared to those observed for the purified recombinant UCK2 enzyme...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27895778/regulatory-network-analysis-of-genes-and-micrornas-in-human-hepatoblastoma
#15
Jimin He, Xiaoxin Guo, Linlin Sun, Ning Wang, Jiwei Bao
Hepatoblastoma (HB) is a common type of primary tumor in children. Previous studies have examined the expression of genes, including transcription factors (TFs), target genes, host genes and microRNAs (miRNAs or miRs) associated with HB. However, the regulatory pathways of miRNAs and genes remain unclear. In the present study, a novel perspective is proposed, which focuses on HB and the associated regulatory pathways, to construct three networks at various levels, including a differentially expressed network, an associated network and a global network...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27894074/lsd1-mediates-mycn-control-of-epithelial-mesenchymal-transition-through-silencing-of-metastatic-suppressor-ndrg1-gene
#16
Susanna Ambrosio, Stefano Amente, Carmen D Saccà, Mario Capasso, Raffaele A Calogero, Luigi Lania, Barbara Majello
Neuroblastoma (NB) with MYCN amplification is a highly aggressive and metastatic tumor in children. The high recurrence rate and resistance of NB cells to drugs urgently demands a better therapy for this disease. We have recently found that MYCN interacts with the lysine-specific demethylase 1 (LSD1), a histone modifier that participates in key aspects of gene transcription. In cancer cells, LSD1 contributes to the genetic reprogramming that underlies to Epithelial-Mesenchymal Transition (EMT) and tumor metastasis...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888620/identification-of-different-alk-mutations-in-a-pair-of-neuroblastoma-cell-lines-established-at-diagnosis-and-relapse
#17
Lindi Chen, Angharad Humphreys, Lisa Turnbull, Angela Bellini, Gudrun Schleiermacher, Helen Salwen, Susan L Cohn, Nick Bown, Deborah A Tweddle
Anaplastic Lymphoma Kinase (ALK) is a transmembrane receptor kinase that belongs to the insulin receptor superfamily and has previously been shown to play a role in cell proliferation, migration and invasion in neuroblastoma. Activating ALK mutations are reported in both hereditary and sporadic neuroblastoma tumours, and several ALK inhibitors are currently under clinical evaluation as novel treatments for neuroblastoma. Overall, mutations at codons F1174, R1275 and F1245 together account for ~85% of reported ALK mutations in neuroblastoma...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27880818/merkel-cell-polyomavirus-small-t-antigen-promotes-pro-glycolytic-metabolic-perturbations-required-for-transformation
#18
Christian Berrios, Megha Padi, Mark A Keibler, Donglim Esther Park, Vadim Molla, Jingwei Cheng, Soo Mi Lee, Gregory Stephanopoulos, John Quackenbush, James A DeCaprio
Merkel cell polyomavirus (MCPyV) is an etiological agent of Merkel cell carcinoma (MCC), a highly aggressive skin cancer. The MCPyV small tumor antigen (ST) is required for maintenance of MCC and can transform normal cells. To gain insight into cellular perturbations induced by MCPyV ST, we performed transcriptome analysis of normal human fibroblasts with inducible expression of ST. MCPyV ST dynamically alters the cellular transcriptome with increased levels of glycolytic genes, including the monocarboxylate lactate transporter SLC16A1 (MCT1)...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27876123/blm-germline-and-somatic-pkmyt1-and-ahcy-mutations-genetic-variations-beyond-mycn-and-prognosis-in-neuroblastoma
#19
E M Novak, N S Halley, T M Gimenez, A Rangel-Santos, A M P Azambuja, M Brumatti, P L Pereira, C S C Vince, R R Giorgi, I Bendit, L M Cristofani, V Odone-Filho
Neuroblastoma (NB) is the most common extra cranial solid tumor of childhood and often lethal in childhood. Clinical and biologic characteristics that are independently prognostic of outcome in NB are currently used for risk stratification to optimally the therapy. It includes age at diagnosis, International Neuroblastoma Staging System tumor histopathology and MYCN amplification. However, even in patients with theoretically good prognosis, such as localized tumor and non-amplified MYCN, either disease progress or recurrence may occur...
December 2016: Medical Hypotheses
https://www.readbyqxmd.com/read/27873103/differential-regulation-of-angiogenic-cellular-processes-and-claudin-5-by-histamine-and-vegf-via-pi3k-signaling-transcription-factor-snai2-and-interleukin-8
#20
Johanna P Laakkonen, Jari P Lappalainen, Thomas L Theelen, Pyry I Toivanen, Tiina Nieminen, Suvi Jauhiainen, Minna U Kaikkonen, Judith C Sluimer, Seppo Ylä-Herttuala
AIMS: Histamine and vascular endothelial growth factor A (VEGF) are central regulators in vascular pathologies. Their gene regulation leading to vascular remodeling has remained obscure. In this study, EC regulation mechanisms of histamine and VEGF were compared by RNA sequencing of primary endothelial cells (ECs), functional in vitro assays and in vivo permeability mice model. METHODS AND RESULTS: By RNA sequencing, similar transcriptional alterations of genes involved in activation of primary ECs, cell proliferation and adhesion were observed between histamine and VEGF...
November 21, 2016: Angiogenesis
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