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https://www.readbyqxmd.com/read/28216878/nardostachys-jatamansi-root-extract-modulates-the-growth-of-imr-32-and-sk-n-mc-neuroblastoma-cell-lines-through-mycn-mediated-regulation-of-mdm2-and-p53
#1
Snehal Suryavanshi, Prerna Raina, Rashmi Deshpande, Ruchika Kaul-Ghanekar
AIM: The present study evaluated the effect of ethanolic extract of Nardostachys jatamansi roots (NJet) on MYCN mediated regulation of expression of MDM2 and p53 proteins in neuroblastoma cell lines, IMR-32 and SK-N-MC. MATERIALS AND METHODS: The effect of NJet on cell viability was determined by MTT; and on growth kinetics was evaluated by trypan blue dye exclusion method and soft agar assay. The expression of p53, MDM2 and MYCN proteins in response to NJet treatment was evaluated by immunoblotting...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28214660/enhancer-of-zeste-homologue-2-plays-an-important-role-in-neuroblastoma-cell-survival-independent-of-its-histone-methyltransferase-activity
#2
Laurel T Bate-Eya, Hinco J Gierman, Marli E Ebus, Jan Koster, Huib N Caron, Rogier Versteeg, M Emmy M Dolman, Jan J Molenaar
Neuroblastoma is predominantly characterised by chromosomal rearrangements. Next to V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma Derived Homolog (MYCN) amplification, chromosome 7 and 17q gains are frequently observed. We identified a neuroblastoma patient with a regional 7q36 gain, encompassing the enhancer of zeste homologue 2 (EZH2) gene. EZH2 is the histone methyltransferase of lysine 27 of histone H3 (H3K27me3) that forms the catalytic subunit of the polycomb repressive complex 2. H3K27me3 is commonly associated with the silencing of genes involved in cellular processes such as cell cycle regulation, cellular differentiation and cancer...
February 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28213351/mycn-drives-rb-null-retinoblastoma-initiation
#3
(no author information available yet)
Overexpression of MYCN overcomes a proliferative block to drive RB-deficient retinoblastoma.
February 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28211617/phosphorylation-of-prb-mechanism-for-rb-pathway-inactivation-in-mycn-amplified-retinoblastoma
#4
Kathryn G Ewens, Tricia R Bhatti, Kimberly A Moran, Jennifer Richards-Yutz, Carol L Shields, Ralph C Eagle, Arupa Ganguly
A small, but unique subgroup of retinoblastoma has been identified with no detectable mutation in the retinoblastoma gene (RB1) and with high levels of MYCN gene amplification. This manuscript investigated alternate pathways of inactivating pRb, the encoded protein in these tumors. We analyzed the mutation status of the RB1 gene and MYCN copy number in a series of 245 unilateral retinoblastomas, and the phosphorylation status of pRb in a subset of five tumors using immunohistochemistry. There were 203 tumors with two mutations in RB1 (RB1(-/-) , 83%), 29 with one (RB1(+/-) , 12%) and 13 with no detectable mutations (RB1(+/+) , 5%)...
February 17, 2017: Cancer Medicine
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/28192521/acquired-resistance-to-oxaliplatin-is-not-directly-associated-with-increased-resistance-to-dna-damage-in-sk-n-asroxali4000-a-newly-established-oxaliplatin-resistant-sub-line-of-the-neuroblastoma-cell-line-sk-n-as
#6
Emily Saintas, Liam Abrahams, Gulshan T Ahmad, Anu-Oluwa M Ajakaiye, Abdulaziz S H A M AlHumaidi, Candice Ashmore-Harris, Iain Clark, Usha K Dura, Carine N Fixmer, Chinedu Ike-Morris, Mireia Mato Prado, Danielle Mccullough, Shishir Mishra, Katia M U Schöler, Husne Timur, Maxwell D C Williamson, Markella Alatsatianos, Basma Bahsoun, Edith Blackburn, Catherine E Hogwood, Pamela E Lithgow, Michelle Rowe, Lyto Yiangou, Florian Rothweiler, Jindrich Cinatl, Richard Zehner, Anthony J Baines, Michelle D Garrett, Campbell W Gourlay, Darren K Griffin, William J Gullick, Emma Hargreaves, Mark J Howard, Daniel R Lloyd, Jeremy S Rossman, C Mark Smales, Anastasios D Tsaousis, Tobias von der Haar, Mark N Wass, Martin Michaelis
The formation of acquired drug resistance is a major reason for the failure of anti-cancer therapies after initial response. Here, we introduce a novel model of acquired oxaliplatin resistance, a sub-line of the non-MYCN-amplified neuroblastoma cell line SK-N-AS that was adapted to growth in the presence of 4000 ng/mL oxaliplatin (SK-N-ASrOXALI4000). SK-N-ASrOXALI4000 cells displayed enhanced chromosomal aberrations compared to SK-N-AS, as indicated by 24-chromosome fluorescence in situ hybridisation. Moreover, SK-N-ASrOXALI4000 cells were resistant not only to oxaliplatin but also to the two other commonly used anti-cancer platinum agents cisplatin and carboplatin...
2017: PloS One
https://www.readbyqxmd.com/read/28187790/retinoic-acid-and-tgf-%C3%AE-signalling-cooperate-to-overcome-mycn-induced-retinoid-resistance
#7
David J Duffy, Aleksandar Krstic, Melinda Halasz, Thomas Schwarzl, Anja Konietzny, Kristiina Iljin, Desmond G Higgins, Walter Kolch
BACKGROUND: Retinoid therapy is widely employed in clinical oncology to differentiate malignant cells into their more benign counterparts. However, certain high-risk cohorts, such as patients with MYCN-amplified neuroblastoma, are innately resistant to retinoid therapy. Therefore, we employed a precision medicine approach to globally profile the retinoid signalling response and to determine how an excess of cellular MYCN antagonises these signalling events to prevent differentiation and confer resistance...
February 10, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28187004/didymin-an-orally-active-citrus-flavonoid-for-targeting-neuroblastoma
#8
REVIEW
Sharad S Singhal, Sulabh Singhal, Preeti Singhal, Jyotsana Singhal, David Horne, Sanjay Awasthi
Neuroblastoma, a rapidly growing yet treatment responsive cancer, is the third most common cancer of children and the most common solid tumor in infants. Unfortunately, neuroblastoma that has lost p53 function often has a highly treatment-resistant phenotype leading to tragic outcomes. In the context of neuroblastoma, the functions of p53 and MYCN (which is amplified in ~25% of neuroblastomas) are integrally linked because they are mutually transcriptionally regulated, and because they together regulate the catalytic activity of RNA polymerases...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178969/neuroblastoma-treatment-in-the-post-genomic-era
#9
REVIEW
Maria Rosaria Esposito, Sanja Aveic, Anke Seydel, Gian Paolo Tonini
Neuroblastoma is an embryonic malignancy of early childhood originating from neural crest cells and showing heterogeneous biological, morphological, genetic and clinical characteristics. The correct stratification of neuroblastoma patients within risk groups (low, intermediate, high and ultra-high) is critical for the adequate treatment of the patients.High-throughput technologies in the Omics disciplines are leading to significant insights into the molecular pathogenesis of neuroblastoma. Nonetheless, further study of Omics data is necessary to better characterise neuroblastoma tumour biology...
February 8, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28165337/a-mouse-model-of-mycn-driven-retinoblastoma-reveals-mycn-independent-tumor-reemergence
#10
Nan Wu, Deshui Jia, Breanna Bates, Ryan Basom, Charles G Eberhart, David MacPherson
The most frequent focal alterations in human retinoblastoma are mutations in the tumor-suppressor gene retinoblastoma (RB) and amplification of the oncogene MYCN. Whether MYCN overexpression drives retinoblastoma has not been assessed in model systems. Here, we have shown that Rb inactivation collaborates strongly with MYCN overexpression and leads to retinoblastoma in mice. Overexpression of human MYCN in the context of Rb inactivation increased the expression of MYC-, E2F-, and ribosome-related gene sets, promoted excessive proliferation, and led to retinoblastoma with anaplastic changes...
February 6, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28139105/-establishment-of-a-preclinical-neuroblastoma-model-in-immunocompetent-mice
#11
A L Luis, M Espinoza, L Franco, A González-Murillo, G J Melen, J C Ollero Fresno, L Madero, M Ramírez
AIM: To develop a NB animal model which makes possible studies related to tumor immunity. MATERIALS AND METHODS: Two types of NB cells were used. Cell line 36769 was derived from TH-MYCN+ mouse in which overexpression of the MYCN gene is governed by rat tyrosine hydroxylase promotor. Cell line 4040 was derived from TH-MYCN/ALK mice, which in addition express an activating mutation of ALK gene. For each cell type, 1x10(6) neurospheres were implanted in 129/SVJ mice (with the same genetic background as donors, n=8), via orthotopic injection in the left suprarenal gland by intraperitoneal approach, through a transverse supraumbilical laparotomy...
April 10, 2016: Cirugía Pediátrica: Organo Oficial de la Sociedad Española de Cirugía Pediátrica
https://www.readbyqxmd.com/read/28138962/pax3-foxo1-is-essential-for-tumour-initiation-and-maintenance-but-not-recurrence-in-a-human-myoblast-model-of-rhabdomyosarcoma
#12
Puspa R Pandey, Bishwanath Chatterjee, Mary E Olanich, Javed Khan, Markku M Miettinen, Stephen M Hewitt, Frederic G Barr
The PAX3-FOXO1 fusion gene is generated by a 2;13 chromosomal translocation and is a characteristic feature of an aggressive subset of rhabdomyosarcoma (RMS). To dissect the mechanism of oncogene action during RMS tumourigenesis and progression, doxycycline-inducible PAX3-FOXO1 and constitutive MYCN expression constructs were introduced into immortalised human myoblasts. Though myoblasts expressing PAX3-FOXO1 or MYCN alone were not transformed in focus formation assays, combined PAX3-FOXO1 and MYCN expression resulted in transformation...
January 31, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28118667/restoration-of-mesenchymal-rpe-by-transcription-factor-mediated-reprogramming
#13
Ying-Hsuan Shih, Monte J Radeke, Carolyn M Radeke, Pete J Coffey
Purpose: Transforming growth factor β-mediated epithelial-to-mesenchymal transition (EMT) is a major component of the wound healing response and a negative determinant of retinal pigment epithelium (RPE) differentiation. We have shown previously that inhibition of TGFβ signaling restored the capacity of mesenchymal RPE to differentiate; however, the potential lessens with extensive passaging. We investigated TGFβ-independent mechanisms that regulate RPE differentiation following repetitive passaging...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28104398/down-regulation-of-boris-ctcfl-efficiently-regulates-cancer-stemness-and-metastasis-in-mycn-amplified-neuroblastoma-cell-line-by-modulating-wnt-%C3%AE-catenin-signaling-pathway
#14
Koteswara Rao Garikapati, Nibedita Patel, Venkata Krishna Kanth Makani, Priyanka Cilamkoti, Utpal Bhadra, Manika Pal Bhadra
BORIS/CTCFL is a vital nucleotide binding protein expressed during embryogenesis and gametogenesis. BORIS/CTCFL is the paralogue of transcriptional repressor protein CTCF, which is aberrantly expressed in various malignancies and primarily re-expressed in cancer stem cells (CSCs). The mechanism behind regulation of BORIS in various cancer conditions and tumor metastases is so far not explored in detail. The aim of the study was to understand the influence of BORIS/CTCFL on stemness and metastasis by regulating well-known oncogenes and related signaling pathways...
January 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28072621/risk-stratification-of-pediatric-patients-with-neuroblastoma-using-volumetric-parameters-of-18f-fdg-and-18f-dopa-pet-ct
#15
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...
March 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
#16
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...
February 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
#17
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
#18
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...
January 24, 2017: 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
#19
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...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28032389/bithalamic-gliomas-may-be-molecularly-distinct-from-their-unilateral-high-grade-counterparts
#20
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
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