نتایج جستجو برای: mycn

تعداد نتایج: 1228  

Journal: :Cancer research 2014
Johannes Fabian Marco Lodrini Ina Oehme Marie C Schier Theresa M Thole Thomas Hielscher Annette Kopp-Schneider Lennart Opitz David Capper Andreas von Deimling Inga Wiegand Till Milde Ulrich Mahlknecht Frank Westermann Odilia Popanda Frederik Roels Barbara Hero Frank Berthold Matthias Fischer Andreas E Kulozik Olaf Witt Hedwig E Deubzer

Neuroblastoma is an embryonic solid tumor of neural crest origin and accounts for 11% of all cancer-related deaths in children. Novel therapeutic strategies are therefore urgently required. MYCN oncogene amplification, which occurs in 20% of neuroblastomas, is a hallmark of high risk. Here, we aimed to exploit molecular mechanisms that can be pharmacologically addressed with epigenetically modi...

Journal: :Carcinogenesis 2011
Bjørn Helge Haug Jørn R Henriksen Jochen Buechner Dirk Geerts Ellen Tømte Per Kogner Tommy Martinsson Trond Flægstad Baldur Sveinbjørnsson Christer Einvik

The MYCN oncogene is frequently amplified in neuroblastoma. It is one of the most consistent markers of bad prognosis for this disease. Dickkopf-3 (DKK3) is a secreted protein of the DKK family of Wnt regulators. It functions as a tumor suppressor in a range of cancers, including neuroblastoma. MYCN was recently found to downregulate DKK3 mRNA. In this study, we show that MYCN knockdown in MYCN...

2014
Yann Jamin Laura Glass Albert Hallsworth Rani George Dow-Mu Koh Andrew D. J. Pearson Louis Chesler Simon P. Robinson

The early identification of children presenting ALK(F1174L)-mutated neuroblastoma, which are associated with resistance to the promising ALK inhibitor crizotinib and a marked poorer prognosis, has become a clinical priority. In comparing the radiology of the novel Th-ALK(F1174L)/Th-MYCN and the well-established Th-MYCN genetically-engineered murine models of neuroblastoma using MRI, we have ide...

Journal: :Cell 2014
Edmond Chipumuro Eugenio Marco Camilla L. Christensen Nicholas Kwiatkowski Tinghu Zhang Clark M. Hatheway Brian J. Abraham Bandana Sharma Caleb Yeung Abigail Altabef Antonio Perez-Atayde Kwok-Kin Wong Guo-Cheng Yuan Nathanael S. Gray Richard A. Young Rani E. George

The MYC oncoproteins are thought to stimulate tumor cell growth and proliferation through amplification of gene transcription, a mechanism that has thwarted most efforts to inhibit MYC function as potential cancer therapy. Using a covalent inhibitor of cyclin-dependent kinase 7 (CDK7) to disrupt the transcription of amplified MYCN in neuroblastoma cells, we demonstrate downregulation of the onc...

Journal: :Science translational medicine 2015
Daniel R Carter Jayne Murray Belamy B Cheung Laura Gamble Jessica Koach Joanna Tsang Selina Sutton Heyam Kalla Sarah Syed Andrew J Gifford Natalia Issaeva Asel Biktasova Bernard Atmadibrata Yuting Sun Nicolas Sokolowski Dora Ling Patrick Y Kim Hannah Webber Ashleigh Clark Michelle Ruhle Bing Liu André Oberthuer Matthias Fischer Jennifer Byrne Federica Saletta Le Myo Thwe Andrei Purmal Gary Haderski Catherine Burkhart Frank Speleman Katleen De Preter Anneleen Beckers David S Ziegler Tao Liu Katerina V Gurova Andrei V Gudkov Murray D Norris Michelle Haber Glenn M Marshall

Amplification of the MYCN oncogene predicts treatment resistance in childhood neuroblastoma. We used a MYC target gene signature that predicts poor neuroblastoma prognosis to identify the histone chaperone FACT (facilitates chromatin transcription) as a crucial mediator of the MYC signal and a therapeutic target in the disease. FACT and MYCN expression created a forward feedback loop in neurobl...

Journal: :PLoS ONE 2008
Laura Fontana Micol E. Fiori Sonia Albini Loredana Cifaldi Serena Giovinazzi Matteo Forloni Renata Boldrini Alberto Donfrancesco Valentina Federici Patrizio Giacomini Cesare Peschle Doriana Fruci

We identified a key oncogenic pathway underlying neuroblastoma progression: specifically, MYCN, expressed at elevated level, transactivates the miRNA 17-5p-92 cluster, which inhibits p21 and BIM translation by interaction with their mRNA 3' UTRs. Overexpression of miRNA 17-5p-92 cluster in MYCN-not-amplified neuroblastoma cells strongly augments their in vitro and in vivo tumorigenesis. In vitr...

Journal: :Proceedings of the National Academy of Sciences of the United States of America 2017
Cecilia Dyberg Susanne Fransson Teodora Andonova Baldur Sveinbjörnsson Jessika Lännerholm-Palm Thale K Olsen David Forsberg Eric Herlenius Tommy Martinsson Bertha Brodin Per Kogner John Inge Johnsen Malin Wickström

Neuroblastoma is a peripheral neural system tumor that originates from the neural crest and is the most common and deadly tumor of infancy. Here we show that neuroblastoma harbors frequent mutations of genes controlling the Rac/Rho signaling cascade important for proper migration and differentiation of neural crest cells during neuritogenesis. RhoA is activated in tumors from neuroblastoma pati...

2013
Md. Kamrul Hasan Asmaa Nafady Atsushi Takatori Satoshi Kishida Miki Ohira Yusuke Suenaga Shamim Hossain Jesmin Akter Atsushi Ogura Yohko Nakamura Kenji Kadomatsu Akira Nakagawara

Human anaplastic lymphoma kinase (ALK) has been identified as an oncogene that is mutated or amplified in NBLs. To obtain a better understanding of the molecular events associated with ALK in the pathogenesis of NBL, it is necessary to clarify how ALK gene contributes to NBL progression. In the present study, we found that ALK expression was significantly high in NBL clinical samples with ampli...

Journal: :The EMBO journal 1997
W A Weiss K Aldape G Mohapatra B G Feuerstein J M Bishop

The proto-oncogene MYCN is often amplified in human neuroblastomas. The assumption that the amplification contributes to tumorigenesis has never been tested directly. We have created transgenic mice that overexpress MYCN in neuroectodermal cells and develop neuroblastoma. Analysis of tumors by comparative genomic hybridization revealed gains and losses of at least seven chromosomal regions, all...

Journal: :Carcinogenesis 2014
Nora I Hipp Lisa Christner Thomas Wirth Wolfgang Mueller-Klieser Stefan Walenta Evelin Schröck Klaus-Michael Debatin Christian Beltinger

The oncogenes MYCN and survivin (BIRC5) maintain aggressiveness of diverse cancers including sarcomas. To investigate whether these oncogenes cooperate in initial malignant transformation, we transduced them into Rat-1 fibroblasts. Indeed, survivin enhanced MYCN-driven contact-uninhibited and anchorage-independent growth in vitro. Importantly, upon subcutaneous transplantation into mice, cells ...

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