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c-Myc, neuroblastoma

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https://www.readbyqxmd.com/read/28521631/immunohistochemical-profile-of-myc-protein-in-pediatric-small-round-blue-cell-tumors
#1
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/28394338/parp-inhibitors-enhance-replication-stress-and-cause-mitotic-catastrophe-in-mycn-dependent-neuroblastoma
#2
V Colicchia, M Petroni, G Guarguaglini, F Sardina, M Sahún-Roncero, M Carbonari, B Ricci, C Heil, C Capalbo, F Belardinilli, A Coppa, G Peruzzi, I Screpanti, P Lavia, A Gulino, G Giannini
High-risk and MYCN-amplified neuroblastomas are among the most aggressive pediatric tumors. Despite intense multimodality therapies, about 50% of these patients succumb to their disease, making the search for effective therapies an absolute priority. Due to the important functions of poly (ADP-ribose) polymerases, PARP inhibitors have entered the clinical settings for cancer treatment and are being exploited in a variety of preclinical studies and clinical trials. PARP inhibitors based combination schemes have also been tested in neuroblastoma preclinical models with encouraging results...
April 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28246384/a-c-myc-regulated-stem-cell-like-signature-in-high-risk-neuroblastoma-a-systematic-discovery-target-neuroblastoma-esc-like-signature
#3
Xinan Holly Yang, Fangming Tang, Jisu Shin, John M Cunningham
c-Myc dysregulation is hypothesized to account for the 'stemness' - self-renewal and pluripotency - shared between embryonic stem cells (ESCs) and adult aggressive tumours. High-risk neuroblastoma (HR-NB) is the most frequent, aggressive, extracranial solid tumour in childhood. Using HR-NB as a platform, we performed a network analysis of transcriptome data and presented a c-Myc subnetwork enriched for genes previously reported as ESC-like cancer signatures. A subsequent drug-gene interaction analysis identified a pharmacogenomic agent that preferentially interacted with this HR-NB-specific, ESC-like signature...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28245597/myc-in-regulating-immunity-metabolism-and-beyond
#4
REVIEW
J N Rashida Gnanaprakasam, Ruoning Wang
Myelocytomatosis oncogene (MYC) family members, including cellular MYC (c-Myc), neuroblastoma derived MYC (MYCN), and lung carcinoma derived MYC (MYCL), have all been implicated as key oncogenic drivers in a broad range of human cancers. Beyond cancer, MYC plays an important role in other physiological and pathological processes, namely immunity and immunological diseases. MYC largely functions as a transcription factor that promotes the expression of numerous target genes to coordinate death, proliferation, and metabolism at the cellular, tissue, and organismal levels...
February 25, 2017: Genes
https://www.readbyqxmd.com/read/28209620/the-histone-methyltransferase-dot1l-promotes-neuroblastoma-by-regulating-gene-transcription
#5
Matthew Wong, Andrew El Tee, Giorgio Milazzo, Jessica L Bell, Rebecca C Poulos, Bernard Atmadibrata, Yuting Sun, Duohui Jing, Nicholas Ho, Dora Ling, Pei Yan Liu, Xu Dong Zhang, Stefan Hüttelmaier, Jason W H Wong, Jenny Wang, Patsie Polly, Giovanni Perini, Christopher J Scarlett, Tao Liu
Myc oncoproteins exert tumorigenic effects by regulating expression of target oncogenes. Histone H3 lysine 79 (H3K79) methylation at Myc-responsive elements of target gene promoters is a strict prerequisite for Myc-induced transcriptional activation, and DOT1L is the only known histone methyltransferase that catalyses H3K79 methylation. Here we show that N-Myc upregulatsd DOT1L mRNA and protein expression by binding to the DOT1L gene promoter. shRNA-mediated depletion of DOT1L reduced mRNA and protein expression of N-Myc target genes ODC1 and E2F2...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28179207/down-regulation-of-c-terminal-binding-protein-2-ctbp2-inhibits-proliferation-migration-and-invasion-of-human-shsy5y-cells-in-vitro
#6
Jiang Nan, Sun Guan, Xu Jin, Zhu Jian, Fu Linshan, Guo Jun
Neuroblastoma is the most common extracranial solid tumor in children and is responsible for ∼15% of pediatric cancer deaths. CtBP2 is a member of the CtBP family of proteins that functions as a transcription regulator and has been demonstrated to interact with the C-terminus of the adenoviral E1A oncoprotein. In this study, the expression of CtBP2 in the human neuroblastoma cell line SHSY5Y was down-regulated using lentiviral-mediated RNA interference. Down-regulation of CtBP2 inhibited the expression of c-myc, MMP2, and MMP9 proteins...
February 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/27919448/fx11-inhibits-aerobic-glycolysis-and-growth-of-neuroblastoma-cells
#7
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...
March 2017: Surgery
https://www.readbyqxmd.com/read/27832522/combined-treatments-with-a-retinoid-receptor-agonist-and-epigenetic-modulators-in-human-neuroblastoma-cells
#8
Viviane Rösner Almeida, Igor Araujo Vieira, Marienela Buendia, André Tesainer Brunetto, Lauro J Gregianin, Algemir Lunardi Brunetto, Fábio Klamt, Caroline Brunetto de Farias, Ana Lucia Abujamra, Patrícia Luciana da Costa Lopez, Rafael Roesler
Neuroblastoma (NB) is the most common extracranial solid childhood tumor accounting for around 15% of pediatric cancer deaths and most probably originates from a failure in the development of embryonic neural crest cells. Retinoids can inhibit the proliferation and stimulate differentiation of NB cells. In addition, epigenetic events involving changes in chromatin structure and DNA methylation can mediate the effects of retinoids; hence, the scope of this study is to investigate the use of retinoids and epigenetic drugs in NB cell lines...
November 10, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27764804/a-combined-gene-expression-and-functional-study-reveals-the-crosstalk-between-n-myc-and-differentiation-inducing-micrornas-in-neuroblastoma-cells
#9
Zhenze Zhao, Xiuye Ma, Spencer D Shelton, Derek C Sung, Monica Li, Daniel Hernandez, Maggie Zhang, Michael D Losiewicz, 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...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27626059/n-myc-expression-enhances-the-oncolytic-effects-of-vesicular-stomatitis-virus-in-human-neuroblastoma-cells
#10
Juan C Corredor, Nicole Redding, Karen Bloté, Stephen M Robbins, Donna L Senger, John C Bell, Paul Beaudry
N-myc oncogene amplification is associated but not present in all cases of high-risk neuroblastoma (NB). Since oncogene expression could often modulate sensitivity to oncolytic viruses, we wanted to examine if N-myc expression status would determine virotherapy efficacy to high-risk NB. We showed that induction of exogenous N-myc in a non-N-myc-amplified cell line background (TET-21N) increased susceptibility to oncolytic vesicular stomatitis virus (mutant VSVΔM51) and alleviated the type I IFN-induced antiviral state...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27622013/the-proto-oncogene-myc-drives-expression-of-the-nk-cell-activating-nkp30-ligand-b7-h6-in-tumor-cells
#11
Sonja Textor, Felicitas Bossler, Kai-Oliver Henrich, Moritz Gartlgruber, Julia Pollmann, Nathalie Fiegler, Annette Arnold, Frank Westermann, Nina Waldburger, Kai Breuhahn, Sven Golfier, Mathias Witzens-Harig, Adelheid Cerwenka
Natural Killer (NK) cells are innate effector cells that are able to recognize and eliminate tumor cells through engagement of their surface receptors. NKp30 is a potent activating NK cell receptor that elicits efficient NK cell-mediated target cell killing. Recently, B7-H6 was identified as tumor cell surface expressed ligand for NKp30. Enhanced B7-H6 mRNA levels are frequently detected in tumor compared to healthy tissues. To gain insight in the regulation of expression of B7-H6 in tumors, we investigated transcriptional mechanisms driving B7-H6 expression by promoter analyses...
July 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27260669/does-mw-radiation-affect-gene-expression-apoptotic-level-and-cell-cycle-progression-of-human-sh-sy5y-neuroblastoma-cells
#12
Handan Kayhan, Meric Arda Esmekaya, Atiye Seda Yar Saglam, Mehmed Zahid Tuysuz, Ayşe Gulnihal Canseven, Abdullah Munci Yagci, Nesrin Seyhan
Neuroblastoma (NB) is a cancer that occurs in sympathetic nervous system arising from neuroblasts and nerve tissue of the adrenal gland, neck, chest, or spinal cord. It is an embryonal malignancy and affects infants and children. In this study, we investigated the effects of microwave (MW) radiation on apoptotic activity, cell viability, and cell cycle progression in human SH-SY5Y NB cells which can give information about MW radiation effects on neural cells covering the period from the embryonic stages to infants...
June 2016: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27235712/berberine-induces-neuronal-differentiation-through-inhibition-of-cancer-stemness-and-epithelial-mesenchymal-transition-in-neuroblastoma-cells
#13
C R Naveen, Sagar Gaikwad, Reena Agrawal-Rajput
BACKGROUND: Berberine, a plant alkaloid, has been used since many years for treatment of gastrointestinal disorders. It also shows promising medicinal use against metabolic disorders, neurodegenerative disorders and cancer; however its efficacy in neuroblastoma (NB) is poorly explored. HYPOTHESIS: EMT is important in cancer stemness and metastasis resulting in failure to differentiate; thus targeting EMT and related pathways can have clinical benefits. STUDY DESIGN: Potential of berberine was investigated for (i) neuronal differentiation and cancer stemness inhibition, (ii) underlying molecular mechanisms regulating cancer-stemness and (iii) EMT reversal...
June 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27197232/p53-loss-in-myc-driven-neuroblastoma-leads-to-metabolic-adaptations-supporting-radioresistance
#14
Orli Yogev, Karen Barker, Arti Sikka, Gilberto S Almeida, Albert Hallsworth, Laura M Smith, Yann Jamin, Ruth Ruddle, Alexander Koers, Hannah T Webber, Florence I Raynaud, Sergey Popov, Chris Jones, Kevin Petrie, Simon P Robinson, Hector C Keun, Louis Chesler
Neuroblastoma is the most common childhood extracranial solid tumor. In high-risk cases, many of which are characterized by amplification of MYCN, outcome remains poor. Mutations in the p53 (TP53) tumor suppressor are rare at diagnosis, but evidence suggests that p53 function is often impaired in relapsed, treatment-resistant disease. To address the role of p53 loss of function in the development and pathogenesis of high-risk neuroblastoma, we generated a MYCN-driven genetically engineered mouse model in which the tamoxifen-inducible p53ER(TAM) fusion protein was expressed from a knock-in allele (Th-MYCN/Trp53(KI))...
May 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27197171/myc-driven-neuroblastomas-are-addicted-to-a-telomerase-independent-function-of-dyskerin
#15
Rosemary O'Brien, Sieu L Tran, Michelle F Maritz, Bing Liu, Cheng Fei Kong, Stefania Purgato, Chen Yang, Jayne Murray, Amanda J Russell, Claudia L Flemming, Georg von Jonquieres, Hilda A Pickett, Wendy B London, Michelle Haber, Preethi H Gunaratne, Murray D Norris, Giovanni Perini, Jamie I Fletcher, Karen L MacKenzie
The RNA-binding protein dyskerin, encoded by the DKC1 gene, functions as a core component of the telomerase holoenzyme as well as ribonuclear protein complexes involved in RNA processing and ribosome biogenesis. The diverse roles of dyskerin across many facets of RNA biology implicate its potential contribution to malignancy. In this study, we examined the expression and function of dyskerin in neuroblastoma. We show that DKC1 mRNA levels were elevated relative to normal cells across a panel of 15 neuroblastoma cell lines, where both N-Myc and c-Myc directly targeted the DKC1 promoter...
June 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27183205/downregulation-of-c-myc-is-involved-in-tlr3-mediated-tumor-death-of-neuroblastoma-xenografts
#16
Li-Ling Lin, Chao-Cheng Huang, Chia-Ling Wu, Min-Tsui Wu, Wen-Ming Hsu, Jiin-Haur Chuang
Neuroblastoma (NB) is the deadliest pediatric solid tumor due to its pleomorphic molecular characteristics. In the innate immune system, toll-like receptor 3 (TLR3) recognizes viral double-stranded RNAs to initiate immune signaling. Positive TLR3 expression indicates a favorable prognosis in NB patients, and is associated with MYCN-non-amplified. However, TLR3-mediated innate immune responses remain elusive in NB. In this study, we attempted to dissect the molecular mechanism underlying TLR3-agonist polyinosinic-polycytidylic acid [poly(I:C)] treatment in NB in vivo...
July 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/26914605/long-term-continuous-exposure-to-panobinostat-induces-terminal-differentiation-and-long-term-survival-in-the-th-mycn-neuroblastoma-mouse-model
#17
Kelly Waldeck, Carleen Cullinane, Kerry Ardley, Jake Shortt, Ben Martin, Richard W Tothill, Jason Li, Ricky W Johnstone, Grant A McArthur, Rodney J Hicks, Paul J Wood
Neuroblastoma is the most common extra-cranial malignancy in childhood and accounts for ∼15% of childhood cancer deaths. Amplification of MYCN in neuroblastoma is associated with aggressive disease and predicts for poor prognosis. Novel therapeutic approaches are therefore essential to improving patient outcomes in this setting. The histone deacetylases are known to interact with N-Myc and regulate numerous cellular processes via epigenetic modulation, including differentiation. In this study, we used the TH-MYCN mouse model of neuroblastoma to investigate the antitumor activity of the pan-HDAC inhibitor, panobinostat...
July 1, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/26870275/expression-of-hepatocyte-growth-factor-and-c-met-is-characteristic-of-%C3%AE-fetoprotein-producing-colorectal-adenocarcinoma-a-report-of-three-cases
#18
Jun Li, Yue Liu, Jing-Hong Xu, Zheng-Ping Xu, Shu Zheng, Ke-Feng Ding
α-fetoprotein (AFP)-producing colorectal adenocarcinoma is rare and typically not well recognized. In the present study, 3 cases of AFP-producing colorectal cancer are described. All 3 of these cases demonstrated increased levels of blood AFP associated with disease progression. Only case 2 exhibited classical histological hepatoid features. Following immunohistochemical tissue staining, all 3 cases were observed to be positive for AFP expression. In addition, the expression of hepatocyte growth factor (HGF), c-Met receptor and the transcription factor c-Myc were identified to be associated with the expression of AFP...
January 2016: Oncology Letters
https://www.readbyqxmd.com/read/26474287/direct-inhibition-of-c-myc-max-heterodimers-by-celastrol-and-celastrol-inspired-triterpenoids
#19
Huabo Wang, Peter Teriete, Angela Hu, Dhanya Raveendra-Panickar, Kelsey Pendelton, John S Lazo, Julie Eiseman, Toril Holien, Kristine Misund, Ganna Oliynyk, Marie Arsenian-Henriksson, Nicholas D P Cosford, Anders Sundan, Edward V Prochownik
Many oncogenic signals originate from abnormal protein-protein interactions that are potential targets for small molecule inhibitors. However, the therapeutic disruption of these interactions has proved elusive. We report here that the naturally-occurring triterpenoid celastrol is an inhibitor of the c-Myc (Myc) oncoprotein, which is over-expressed in many human cancers. Most Myc inhibitors prevent the association between Myc and its obligate heterodimerization partner Max via their respective bHLH-ZIP domains...
October 20, 2015: Oncotarget
https://www.readbyqxmd.com/read/26469830/interactions-between-myc-and-mondoa-transcription-factors-in-metabolism-and-tumourigenesis
#20
REVIEW
Blake R Wilde, Donald E Ayer
Metabolic reprogramming towards aerobic glycolysis is a common feature of transformed cells and can be driven by a network of transcription factors. It is well established that c-Myc and hypoxia-inducible factor-1α (HIF-1α) contribute to metabolic reprogramming by driving the expression of glycolytic target genes. More recently, the c-Myc-related transcription factor MondoA has been shown to restrict glucose uptake and aerobic glycolysis via its induction of thioredoxin-interacting protein (TXNIP). Three recent studies demonstrate that complex and cancer type-specific interactions between c-Myc, MondoA and HIF-1α underlie metabolism, tumourigenesis and drug response...
December 1, 2015: British Journal of Cancer
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