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https://www.readbyqxmd.com/read/29350464/predictors-of-response-progression-free-survival-and-overall-survival-using-nant-response-criteria-v1-0-in-relapsed-and-refractory-high-risk-neuroblastoma
#1
Judith G Villablanca, Lingyun Ji, Adi Shapira-Lewinson, Araz Marachelian, Hiroyuki Shimada, Randall A Hawkins, Miguel Pampaloni, Hollie Lai, Fariba Goodarzian, Richard Sposto, Julie R Park, Katherine K Matthay
PURPOSE: The New Approaches to Neuroblastoma Therapy Response Criteria (NANTRC) were developed to optimize response assessment in patients with recurrent/refractory neuroblastoma. Response predictors and associations of the NANTRC version 1.0 (NANTRCv1.0) and prognostic factors with outcome were analyzed. METHODS: A retrospective analysis was performed of patients with recurrent/refractory neuroblastoma enrolled from 2000 to 2009 on 13 NANT Phase 1/2 trials. NANTRC overall response integrated CT/MRI (Response Evaluation Criteria in Solid Tumors [RECIST]), metaiodobenzylguanidine (MIBG; Curie scoring), and percent bone marrow (BM) tumor (morphology)...
January 19, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29343221/a-case-of-molecularly-profiled-extraneural-medulloblastoma-metastases-in-a-child
#2
Nahla Ali Mobark, Musa Al-Harbi, Othman Mosleh, Sandro Santagata, Matija Snuderl, Malak Abedalthagafi
BACKGROUND: Extraneural metastases are relatively rare manifestations of medulloblastoma. CASE PRESENTATION: We present the case of a young boy with group three MYCN-amplified medulloblastoma. He received multimodal chemotherapy consisting of gross total resection followed by postoperative craniospinal radiation and adjuvant chemotherapy. The patient developed extraneural metastases 4 months after the end of therapy. Literature review identifies the poor prognosis of MYCN-amplified medulloblastomas as well as extraneural metastases; we review the current limitations and future directions of medulloblastoma treatment options...
January 17, 2018: BMC Medical Genetics
https://www.readbyqxmd.com/read/29328367/tumorigenic-proteins-upregulated-in-the-mycn-amplified-imr-32-human-neuroblastoma-cells-promote-proliferation-and-migration
#3
Hayat Zaatiti, Jad Abdallah, Zeina Nasr, George Khazen, Anthony Sandler, Tamara J Abou-Antoun
Childhood neuroblastoma is one of the most common types of extra-cranial cancer affecting children with a clinical spectrum ranging from spontaneous regression to malignant and fatal progression. In order to improve the clinical outcomes of children with high-risk neuroblastoma, it is crucial to understand the tumorigenic mechanisms that govern its malignant behaviors. MYCN proto-oncogene, bHLH transcription factor (MYCN) amplification has been implicated in the malignant, treatment-evasive nature of aggressive, high-risk neuroblastoma...
January 4, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29322842/cd133-expression-and-mycn-amplification-induce-chemoresistance-and-reduce-average-survival-time-in-pediatric-neuroblastoma
#4
Zhi-Yong Zhong, Bao-Jun Shi, Hui Zhou, Wen-Bo Wang
Objectives Neuroblastoma (NB) is the most common pediatric solid tumor derived from the sympathetic nervous system. MYCN is amplified in nearly half of patients with NB, and its association with rapid disease progression and poor outcome is controversial. Characterization of cancer stem cells (CSCs) in NBs has been rarely studied. This study was performed to determine whether MYCN and CD133+ CSCs are associated with chemotherapy resistance and the survival time of patients with NB. Methods Fifty patients with an unequivocal pathological diagnosis of NB were recruited...
January 1, 2018: Journal of International Medical Research
https://www.readbyqxmd.com/read/29321660/activated-alk-signals-through-the-erk-etv5-ret-pathway-to-drive-neuroblastoma-oncogenesis
#5
Lucille Lopez-Delisle, Cécile Pierre-Eugène, Caroline Louis-Brennetot, Didier Surdez, Virginie Raynal, Sylvain Baulande, Valentina Boeva, Sandrine Grossetête-Lalami, Valérie Combaret, Michel Peuchmaur, Olivier Delattre, Isabelle Janoueix-Lerosey
Activating mutations of the ALK receptor occur in a subset of neuroblastoma tumors. We previously demonstrated that Alk mutations cooperate with MYCN overexpression to induce neuroblastoma in mice and identified Ret as being strongly upregulated in MYCN/Alkmut tumors. By a genetic approach in vivo, we now document an oncogenic cooperation between activated Ret and MYCN overexpression in neuroblastoma formation. We show that MYCN/RetM919T tumors exhibit histological features and expression profiles close to MYCN/Alkmut tumors...
January 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29320761/expandable-arterial-endothelial-precursors-from-human-cd34-cells-differ-in-their-proclivity-to-undergo-an-endothelial-to-mesenchymal-transition
#6
Auston Z Miller, Alexander Satchie, Alex P Tannenbaum, Aman Nihal, James A Thomson, David T Vereide
Arterial diseases continue to pose a major health concern but in vitro studies are limited because explanted cells can exhibit poor proliferative capacity and a loss of specificity. Here, we find that two transcription factors, MYCN and SOX17, induce and indefinitely expand in culture precursors of human arterial endothelial cells (expandable arterial endothelial precursors [eAEPs]). The eAEPs are derived from CD34+ cells found in umbilical cord blood or adult bone marrow. Independent eAEP lines differ in their proclivity to undergo an endothelial-to-mesenchymal transition (EndoMT), a hallmark event in a broad array of vascular diseases and disorders...
January 9, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29314142/retinoblastoma-the-visible-cns-tumor-a-review
#7
Helen Dimaras, Timothy W Corson
The pediatric ocular cancer retinoblastoma is the only central nervous system (CNS) tumor readily observed without specialized equipment: it can be seen by, and in, the naked eye. This accessibility enables unique imaging modalities. Here, we review this cancer for a neuroscience audience, highlighting these clinical and research imaging options, including fundus imaging, optical coherence tomography, ultrasound, and magnetic resonance imaging. We also discuss the subtype of retinoblastoma driven by the MYCN oncogene more commonly associated with neuroblastoma, and consider trilateral retinoblastoma, in which an intracranial tumor arises along with ocular tumors in patients with germline RB1 gene mutations...
January 3, 2018: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29301505/optimising-the-chick-chorioallantoic-membrane-xenograft-model-of-neuroblastoma-for-drug-delivery
#8
Rasha Swadi, Grace Mather, Barry L Pizer, Paul D Losty, Violaine See, Diana Moss
BACKGROUND: Neuroblastoma is a paediatric cancer that despite multimodal therapy still has a poor outcome for many patients with high risk tumours. Retinoic acid (RA) promotes differentiation of some neuroblastoma tumours and cell lines, and is successfully used clinically, supporting the view that differentiation therapy is a promising strategy for treatment of neuroblastoma. To improve treatment of a wider range of tumour types, development and testing of novel differentiation agents is essential...
January 4, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29298329/molecular-and-functional-analysis-of-anchorage-independent-treatment-evasive-neuroblastoma-tumorspheres-with-enhanced-malignant-properties-a-possible-explanation-for-radio-therapy-resistance
#9
Tamara J Abou-Antoun, Javad Nazarian, Anthony Ghanem, Stanislav Vukmanovic, Anthony D Sandler
Despite significant advances in cancer treatment and management, more than 60% of patients with neuroblastoma present with very poor prognosis in the form of metastatic and aggressive disease. Solid tumors including neuroblastoma are thought to be heterogeneous with a sub-population of stem-like cells that are treatment-evasive with highly malignant characteristics. We previously identified a phenomenon of reversible adaptive plasticity (RAP) between anchorage dependent (AD) cells and anchorage independent (AI) tumorspheres in neuroblastoma cell cultures...
2018: PloS One
https://www.readbyqxmd.com/read/29296183/identification-of-the-genetic-and-clinical-characteristics-of-neuroblastomas-using-genome-wide-analysis
#10
Kumiko Uryu, Riki Nishimura, Keisuke Kataoka, Yusuke Sato, Atsuko Nakazawa, Hiromichi Suzuki, Kenichi Yoshida, Masafumi Seki, Mitsuteru Hiwatari, Tomoya Isobe, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Katsuyoshi Koh, Ryoji Hanada, Akira Oka, Yasuhide Hayashi, Miki Ohira, Takehiko Kamijo, Hiroki Nagase, Tetsuya Takimoto, Tatsuro Tajiri, Akira Nakagawara, Seishi Ogawa, Junko Takita
To provide better insight into the genetic signatures of neuroblastomas, we analyzed 500 neuroblastomas (included specimens from JNBSG) using targeted-deep sequencing for 10 neuroblastoma-related genes and SNP arrays analysis. ALK expression was evaluated using immunohistochemical analysis in 259 samples. Based on genetic alterations, the following 6 subgroups were identified: groups A (ALK abnormalities), B (other gene mutations), C (MYCN amplification), D (11q loss of heterozygosity [LOH]), E (at least 1 copy number variants), and F (no genetic changes)...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29295562/oncomirs-expression-profiling-in-uterine-leiomyosarcoma-cells
#11
Bruna Cristine de Almeida, Natalia Garcia, Giovana Maffazioli, Laura Gonzalez Dos Anjos, Edmund Chada Baracat, Katia Candido Carvalho
MicroRNAs (miRNAs) are small non-coding RNAs that act as regulators of gene expression at the post-transcriptional level. They play a key role in several biological processes. Their abnormal expression may lead to malignant cell transformation. This study aimed to evaluate the expression profile of 84 miRNAs involved in tumorigenesis in immortalized cells of myometrium (MM), uterine leiomyoma (ULM), and uterine leiomyosarcoma (ULMS). Specific cell lines were cultured and qRT-PCR was performed. Thirteen miRNAs presented different expression profiles in ULM and the same thirteen in ULMS compared to MM...
December 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29290991/early-and-late-effects-of-pharmacological-alk-inhibition-on-the-neuroblastoma-transcriptome
#12
Shana Claeys, Geertrui Denecker, Robrecht Cannoodt, Candy Kumps, Kaat Durinck, Frank Speleman, Katleen De Preter
Background: Neuroblastoma is an aggressive childhood malignancy of the sympathetic nervous system. Despite multi-modal therapy, survival of high-risk patients remains disappointingly low, underscoring the need for novel treatment strategies. The discovery of ALK activating mutations opened the way to precision treatment in a subset of these patients. Previously, we investigated the transcriptional effects of pharmacological ALK inhibition on neuroblastoma cell lines, six hours after TAE684 administration, resulting in the 77-gene ALK signature, which was shown to gradually decrease from 120 minutes after TAE684 treatment, to gain deeper insight into the molecular effects of oncogenic ALK signaling...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290949/neurocan-an-extracellular-chondroitin-sulfate-proteoglycan-stimulates-neuroblastoma-cells-to-promote-malignant-phenotypes
#13
Zhendong Su, Satoshi Kishida, Shoma Tsubota, Kazuma Sakamoto, Dongliang Cao, Shinichi Kiyonari, Miki Ohira, Takehiko Kamijo, Atsushi Narita, Yinyan Xu, Yoshiyuki Takahashi, Kenji Kadomatsu
Neurocan (NCAN), a secreted chondroitin sulfate proteoglycan, is one of the major inhibitory molecules for axon regeneration in nervous injury. However, its role in cancer is not clear. Here we observed that high NCAN expression was closely associated with the unfavorable outcome of neuroblastoma (NB). NCAN was also highly and ubiquitously expressed in the early lesions and terminal tumor of TH-MYCN mice, a NB model. Interestingly, exogenous NCAN (i.e., overexpression, recombinant protein and conditioned medium) transformed adherent NB cells into spheres whose malignancies in vitro (anchorage-independent growth and chemoresistance) and in vivo (xenograft tumor growth) were potentiated...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29287594/comprehensive-molecular-biomarker-identification-in-breast-cancer-brain-metastases
#14
Hans-Juergen Schulten, Mohammed Bangash, Sajjad Karim, Ashraf Dallol, Deema Hussein, Adnan Merdad, Fatma K Al-Thoubaity, Jaudah Al-Maghrabi, Awatif Jamal, Fahad Al-Ghamdi, Hani Choudhry, Saleh S Baeesa, Adeel G Chaudhary, Mohammed H Al-Qahtani
BACKGROUND: Breast cancer brain metastases (BCBM) develop in about 20-30% of breast cancer (BC) patients. BCBM are associated with dismal prognosis not at least due to lack of valuable molecular therapeutic targets. The aim of the study was to identify new molecular biomarkers and targets in BCBM by using complementary state-of-the-art techniques. METHODS: We compared array expression profiles of three BCBM with 16 non-brain metastatic BC and 16 primary brain tumors (prBT) using a false discovery rate (FDR) p < 0...
December 29, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29284669/c-myc-drives-a-subset-of-high-risk-pediatric-neuroblastomas-and-is-activated-through-mechanisms-including-enhancer-hijacking-and-focal-enhancer-amplification
#15
Mark W Zimmerman, Yu Liu, Shuning He, Adam D Durbin, Brian J Abraham, John Easton, Ying Shao, Beisi Xu, Shizhen Zhu, Xiaoling Zhang, Zhaodong Li, Nina Weichert-Leahey, Richard A Young, Jinghui Zhang, A Thomas Look
The amplified MYCN gene serves as an oncogenic driver in approximately 20% of high-risk pediatric neuroblastomas. Here we show that the family member c-MYC is a potent transforming gene in a separate subset of high-risk neuroblastoma cases (~10%), based on (i) its upregulation by focal enhancer amplification or genomic rearrangements leading to enhancer hijacking, and (ii) its ability to transform neuroblastoma precursor cells in a transgenic animal model. The aberrant regulatory elements associated with oncogenic c-MYC activation include focally amplified distal enhancers and translocation of highly active enhancers from other genes to within topologically associating domains containing the c-MYC gene locus...
December 28, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29282022/chromosomal-instability-induced-by-increased-birc5-survivin-levels-affects-tumorigenicity-of-glioma-cells
#16
Marina Conde, Susanne Michen, Ralf Wiedemuth, Barbara Klink, Evelin Schröck, Gabriele Schackert, Achim Temme
BACKGROUND: Survivin, belonging to the inhibitor of apoptosis (IAP) gene family, is abundantly expressed in tumors. It has been hypothesized that Survivin facilitates carcinogenesis by inhibition of apoptosis resulting in improved survival of tumorigenic progeny. Additionally, Survivin plays an essential role during mitosis. Together with its molecular partners Aurora B, Borealin and inner centromere protein it secures bipolar chromosome segregation. However, whether increased Survivin levels contribute to progression of tumors by inducing chromosomal instability remains unclear...
December 28, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29277758/sphingosine-induces-apoptosis-and-down-regulation-of-mycn-in-pax3-foxo1-positive-alveolar-rhabdomyosarcoma-cells-irrespective-of-tp53-mutation
#17
Eun Hyun Ahn, Michael B Lee, Dong Joo Seo, Juseong Lee, Yonghyun Kim, Kshitiz Gupta
BACKGROUND/AIM: Rhabdomyosarcoma is the most common type of pediatric soft-tissue sarcoma. Among the subsets of this disease, alveolar rhabdomyosarcoma (ARMS) expressing paired box 3 (PAX3) and forkhead box O1 (PAX3-FOXO1) fusion oncoprotein has the worst prognosis. The goal of this study was to investigate the chemotherapeutic effects of sphingosine on PAX3-FOXO1-positive ARMS cells [tumor protein p53 (TP53)-mutated RH30 and TP53 wild-type RH18 cells]. MATERIALS AND METHODS: The proliferation, cell death, apoptosis, cell cycle, and MYCN proto-oncogene (MYCN) expression of RH30 and RH18 cells were determined...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29274926/3-methoxytyramine-an-independent-prognostic-biomarker-that-associates-with-high-risk-disease-and-poor-clinical-outcome-in-neuroblastoma-patients
#18
I R N Verly, A B P van Kuilenburg, N G G M Abeling, S M I Goorden, M Fiocco, F M Vaz, M M van Noesel, C M Zwaan, G J L Kaspers, J H M Merks, H N Caron, G A M Tytgat
INTRODUCTION: Prognosis of neuroblastoma patients is very diverse, indicating the need for more accurate prognostic parameters. The excretion of catecholamine metabolites by most neuroblastomas is used for diagnostic purposes, but their correlation with prognosis has hardly been investigated. Therefore, we performed an in-depth analysis of a panel of elevated urinary catecholamine metabolites at diagnosis and their correlation with prognosis. PATIENTS AND METHODS: Retrospective study of eight urinary catecholamine metabolites in a test (n = 96) and validation (n = 205) cohort of patients with neuroblastoma (all stages) at diagnosis...
December 21, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29247836/coexpression-network-analysis-identifies-transcriptional-modules-associated-with-genomic-alterations-in-neuroblastoma
#19
Liulin Yang, Yun Li, Zhi Wei, Xiao Chang
Neuroblastoma is a highly complex and heterogeneous cancer in children. Acquired genomic alterations including MYCN amplification, 1p deletion and 11q deletion are important risk factors and biomarkers in neuroblastoma. Here, we performed a co-expression-based gene network analysis to study the intrinsic association between specific genomic changes and transcriptome organization. We identified multiple gene coexpression modules which are recurrent in two independent datasets and associated with functional pathways including nervous system development, cell cycle, immune system process and extracellular matrix/space...
December 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29238067/alternative-nhej-pathway-proteins-as-components-of-mycn-oncogenic-activity-in-human-neural-crest-stem-cell-differentiation-implications-for-neuroblastoma-initiation
#20
Erika A Newman, Sahiti Chukkapalli, Daniela Bashllari, Tina T Thomas, Raelene A Van Noord, Elizabeth R Lawlor, Mark J Hoenerhoff, Anthony W Opipari, Valerie P Opipari
Neuroblastoma is a cancer of neural crest stem cell (NCSC) lineage. Signaling pathways that regulate NCSC differentiation have been implicated in neuroblastoma tumorigenesis. This is exemplified by MYCN oncogene targets that balance proliferation, differentiation, and cell death similarly in normal NCSC and in high-risk neuroblastoma. Our previous work discovered a survival mechanism by which MYCN-amplified neuroblastoma circumvents cell death by upregulating components of the error-prone non-canonical alternative nonhomologous end-joining (alt-NHEJ) DNA repair pathway...
December 13, 2017: Cell Death & Disease
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