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https://www.readbyqxmd.com/read/28667493/mir-16-1-targeted-silences-far-upstream-element-binding-protein-1-to-advance-the-chemosensitivity-to-adriamycin-in-gastric-cancer
#1
Danyi Zhao, Yang Zhang, Lei Song
Chemotherapy can prevent metastasis and recurrence of gastric cancer (GC), and is a well supplement for operation. But, chemotherapy resistance has severely restricted the application of chemotherapy. This study aimed to investigate the regulatory roles and molecular mechanism of miR-16-1 to the chemosensitivity to adriamycin in GC. In this study, the expression of miR-16-1 and FUBP1 was down-regulated and up-regulated respectively in adriamycin-resistant GC tissues and cell lines, and represented a negative relationship between them...
June 30, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28588622/delayed-mesoderm-and-erythroid-differentiation-of-murine-embryonic-stem-cells-in-the-absence-of-the-transcriptional-regulator-fubp1
#2
Josephine Wesely, Marlene Steiner, Frank Schnütgen, Manuel Kaulich, Michael A Rieger, Martin Zörnig
The transcriptional regulator far upstream binding protein 1 (FUBP1) is essential for fetal and adult hematopoietic stem cell (HSC) self-renewal, and the constitutive absence of FUBP1 activity during early development leads to embryonic lethality in homozygous mutant mice. To investigate the role of FUBP1 in murine embryonic stem cells (ESCs) and in particular during differentiation into hematopoietic lineages, we generated Fubp1 knockout (KO) ESC clones using CRISPR/Cas9 technology. Although FUBP1 is expressed in undifferentiated ESCs and during spontaneous differentiation following aggregation into embryoid bodies (EBs), absence of FUBP1 did not affect ESC maintenance...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28535583/molecular-testing-of-brain-tumor
#3
REVIEW
Sung-Hye Park, Jaekyung Won, Seong-Ik Kim, Yujin Lee, Chul-Kee Park, Seung-Ki Kim, Seung-Hong Choi
The World Health Organization (WHO) classification of central nervous system (CNS) tumors was revised in 2016 with a basis on the integrated diagnosis of molecular genetics. We herein provide the guidelines for using molecular genetic tests in routine pathological practice for an accurate diagnosis and appropriate management. While astrocytomas and IDH-mutant (secondary) glioblastomas are characterized by the mutational status of IDH, TP53 , and ATRX , oligodendrogliomas have a 1p/19q codeletion and mutations in IDH, CIC , FUBP1 , and the promoter region of telomerase reverse transcriptase ( TERTp )...
May 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28472509/multicenter-phase-ii-study-of-temozolomide-and-myeloablative-chemotherapy-with-autologous-stem-cell-transplant-for-newly-diagnosed-anaplastic-oligodendroglioma
#4
Alissa A Thomas, Lauren E Abrey, Robert Terziev, Jeffrey Raizer, Nina L Martinez, Peter Forsyth, Nina Paleologos, Matthew Matasar, Craig S Sauter, Craig Moskowitz, Stephen D Nimer, Lisa M DeAngelis, Thomas Kaley, Sean Grimm, David N Louis, J Gregory Cairncross, Katherine S Panageas, Samuel Briggs, Geraldine Faivre, Nimish A Mohile, Jayesh Mehta, Philip Jonsson, Debyani Chakravarty, Jianjiong Gao, Nikolaus Schultz, Cameron W Brennan, Jason T Huse, Antonio Omuro
Background: Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytomas (AOA) are chemotherapy-sensitive tumors with prolonged survival after radiochemotherapy. We report a prospective trial using induction temozolomide (TMZ) followed by myeloablative high-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT), as a potential strategy to defer radiotherapy. Methods: Patients with AO/AOA received 6 cycles of TMZ (200mg/m2 X5/28-day). Responding patients were eligible for HDC (thiotepa 250mg/m2/day X3 days then busulfan 3...
May 2, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28388591/genetic-landscape-of-extreme-responders-with-anaplastic-oligodendroglioma
#5
Matthias Holdhoff, Gregory J Cairncross, Thomas M Kollmeyer, Ming Zhang, Peixin Zhang, Minesh P Mehta, Maria Werner-Wasik, Luis Souhami, Jean-Paul Bahary, Young Kwok, Alan C Hartford, Arnab Chakravarti, Srinivasan Yegnasubramanian, Bert Vogelstein, Nickolas Papadopoulos, Kenneth Kinzler, Robert B Jenkins, Chetan Bettegowda
BACKGROUND: The NRG Oncology RTOG 9402 trial showed significant survival benefit in patients with 1p/19q co-deleted anaplastic oligodendrogliomas (AO) who received both radiation (RT) and chemotherapy (PCV regimen) versus RT alone. Substantial separation of the survival curves was only seen after 7.3 years. We aimed to determine whether there are specific genetic alterations that distinguish co-deleted AO patients who benefit from the addition of PCV from those who do not. METHODS: We performed whole exome sequencing on matched tumor and normal DNA from all available short-term (STS) and long-term survivors (LTS) who received RT+PCV...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28381186/the-expression-pattern-of-long-non-coding-rna-pvt1-in-tumor-tissues-and-in-extracellular-vesicles-of-colorectal-cancer-correlates-with-cancer-progression
#6
Kai Guo, Jie Yao, Qiang Yu, Zijian Li, Hu Huang, Jianguo Cheng, Zhigang Wang, Yunfeng Zhu
The plasmacytoma variant translocation 1 gene (PVT1) is a large non-coding locus at adjacent of c-Myc, and long non-coding RNA PVT1 is now recognized as a cancerous gene co-amplified with c-Myc in various cancers. But the expression and functional role of PVT1 in colorectal cancer are still unelucidated. In addition, all the reported long non-coding RNAs so far are discovered in either cells or tissues, but no research about long non-coding RNAs detection in extracellular vesicles has been reported yet. In the present study, we firstly investigated the expression of PVT1 in colorectal cancer specimens and its correlation with the expression of c-Myc and other related genes by real-time polymerase chain reaction...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28270234/genetic-and-epigenetic-stability-of-oligodendrogliomas-at-recurrence
#7
Koki Aihara, Akitake Mukasa, Genta Nagae, Masashi Nomura, Shogo Yamamoto, Hiroki Ueda, Kenji Tatsuno, Junji Shibahara, Miwako Takahashi, Toshimitsu Momose, Shota Tanaka, Shunsaku Takayanagi, Shunsuke Yanagisawa, Takahide Nejo, Satoshi Takahashi, Mayu Omata, Ryohei Otani, Kuniaki Saito, Yoshitaka Narita, Motoo Nagane, Ryo Nishikawa, Keisuke Ueki, Hiroyuki Aburatani, Nobuhito Saito
Among diffuse gliomas, oligodendrogliomas show relatively better prognosis, respond well to radiotherapy and chemotherapy, and seldom progress to very aggressive tumors. To elucidate the genetic and epigenetic background for such behavior and tumor evolution during tumor relapse, we comparatively analyzed 12 pairs of primary and recurrent oligodendrogliomas with 1p/19q-codeletion. Initial treatment for these patients was mostly chemotherapy alone. Temozolomide was used for 3, and procarbazine, nimustine and vincristine (PAV chemotherapy) were used for 7 patients...
March 7, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28170390/multiscale-mutation-clustering-algorithm-identifies-pan-cancer-mutational-clusters-associated-with-pathway-level-changes-in-gene-expression
#8
William Poole, Kalle Leinonen, Ilya Shmulevich, Theo A Knijnenburg, Brady Bernard
Cancer researchers have long recognized that somatic mutations are not uniformly distributed within genes. However, most approaches for identifying cancer mutations focus on either the entire-gene or single amino-acid level. We have bridged these two methodologies with a multiscale mutation clustering algorithm that identifies variable length mutation clusters in cancer genes. We ran our algorithm on 539 genes using the combined mutation data in 23 cancer types from The Cancer Genome Atlas (TCGA) and identified 1295 mutation clusters...
February 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28076379/upregulation-of-far-upstream-element-binding-protein-1-fubp1-promotes-tumor-proliferation-and-tumorigenesis-of-clear-cell-renal-cell-carcinoma
#9
Junyao Duan, Xu Bao, Xin Ma, Yu Zhang, Dong Ni, Hanfeng Wang, Fan Zhang, Qingshan Du, Yang Fan, Jianwen Chen, Shengpan Wu, Xintao Li, Yu Gao, Xu Zhang
OBJECTIVE: The far upstream element (FUSE)-binding protein 1 (FUBP1) is a transactivator of human c-myc proto-oncogene transcription, with important roles in carcinogenesis. However, the expression pattern and potential biological function of FUBP1 in clear cell renal cell carcinoma (ccRCC) is yet to be established. METHODS: FUBP1 expression was detected in ccRCC tissues and cell lines by real-time RT-PCR, Western blot analysis, and immunohistochemistry. The correlations of FUBP1 mRNA expression levels with clinicopathological factors were evaluated...
2017: PloS One
https://www.readbyqxmd.com/read/27729195/pyrazolo-1-5a-pyrimidines-as-a-new-class-of-fuse-binding-protein-1-fubp1-inhibitors
#10
Stefanie Hauck, Kerstin Hiesinger, Sabrina Khageh Hosseini, Janosch Achenbach, Ricardo M Biondi, Ewgenij Proschak, Martin Zörnig, Dalibor Odadzic
The transcriptional regulator FUSE binding protein 1 (FUBP1) is aberrantly upregulated in various malignancies, fulfilling its oncogenic role by the deregulation of critical genes involved in cell cycle control and apoptosis regulation. Thus, the pharmaceutical inhibition of this protein would represent an encouraging novel targeted chemotherapy. Here, we demonstrate the identification and initial optimization of a pyrazolo[1,5a]pyrimidine-based FUBP1 inhibitor derived from medium throughput screening, which interferes with the binding of FUBP1 to its single stranded target DNA FUSE...
September 14, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27566151/alternative-splicing-of-u2af1-reveals-a-shared-repression-mechanism-for-duplicated-exons
#11
Jana Kralovicova, Igor Vorechovsky
The auxiliary factor of U2 small nuclear ribonucleoprotein (U2AF) facilitates branch point (BP) recognition and formation of lariat introns. The gene for the 35-kD subunit of U2AF gives rise to two protein isoforms (termed U2AF35a and U2AF35b) that are encoded by alternatively spliced exons 3 and Ab, respectively. The splicing recognition sequences of exon 3 are less favorable than exon Ab, yet U2AF35a expression is higher than U2AF35b across tissues. We show that U2AF35b repression is facilitated by weak, closely spaced BPs next to a long polypyrimidine tract of exon Ab...
January 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27496889/a-novel-long-intergenic-noncoding-rna-indispensable-for-the-cleavage-of-mouse-two-cell-embryos
#12
Jiaqiang Wang, Xin Li, Leyun Wang, Jingyu Li, Yanhua Zhao, Gerelchimeg Bou, Yufei Li, Guanyi Jiao, Xinghui Shen, Renyue Wei, Shichao Liu, Bingteng Xie, Lei Lei, Wei Li, Qi Zhou, Zhonghua Liu
Endogenous retroviruses (ERVs) are transcriptionally active in cleavage stage embryos, yet their functions are unknown. ERV sequences are present in the majority of long intergenic noncoding RNAs (lincRNAs) in mouse and humans, playing key roles in many cellular processes and diseases. Here, we identify LincGET as a nuclear lincRNA that is GLN-, MERVL-, and ERVK-associated and essential for mouse embryonic development beyond the two-cell stage. LincGET is expressed in late two- to four-cell mouse embryos. Its depletion leads to developmental arrest at the late G2 phase of the two-cell stage and to MAPK signaling pathway inhibition...
October 2016: EMBO Reports
https://www.readbyqxmd.com/read/27407063/mantle-cell-lymphoma-variant-richter-syndrome-detailed-molecular-cytogenetic-and-backtracking-analysis-reveals-slow-evolution-of-a-pre-mcl-clone-in-parallel-with-cll-over-several-years
#13
Pavel Klener, Eva Fronkova, Adela Berkova, Radek Jaksa, Halka Lhotska, Kristina Forsterova, Jan Soukup, Vojtech Kulvait, Jarmila Vargova, Karel Fiser, Dana Prukova, Mahmudul Alam, Bokang Calvin Lenyeletse Maswabi, Kyra Michalova, Zuzana Zemanova, Tereza Jancuskova, Sona Pekova, Marek Trneny
Richter syndrome represents the transformation of the chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, most frequently the diffuse large B-cell lymphoma (DLBCL). In this report we describe a patient with CLL, who developed a clonally-related pleomorphic highly-aggressive mantle cell lymphoma (MCL) after five cycles of a fludarabine-based second-line therapy for the first relapse of CLL. Molecular cytogenetic methods together with whole-exome sequencing revealed numerous gene alterations restricted to the MCL clone (apart from the canonical t(11;14)(q13;q32) translocation) including gain of one copy of ATM gene or emergence of TP53, CREBBP, NUP214, FUBP1 and SF3B1 gene mutations...
November 15, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27197155/oncogenic-mutation-of-aimp2-p38-inhibits-its-tumor-suppressive-interaction-with-smurf2
#14
Dae Gyu Kim, Jin Young Lee, Ji-Hyun Lee, Ha Yeon Cho, Beom Sik Kang, Song-Yee Jang, Myung Hee Kim, Min Guo, Jung Min Han, Seong-Jin Kim, Sunghoon Kim
AIMP2/p38 is a multifunctional tumor suppressor that normally resides in the cytosol as a scaffold protein of the multi-tRNA synthetase complex (MSC). One of the tumor-suppressive functions of AIMP2 is to facilitate ubiquitin-mediated degradation of FUSE-binding protein (FBP, FUBP1), a transcriptional activator of c-Myc. However, the mechanism by which AIMP2 functions within this pathway and its significance in tumorigenesis are uncertain. Here, we report that Smurf2 is responsible for AIMP2-mediated ubiquitination of FBP, and a mutation in AIMP2 that inhibited its nuclear interaction with Smurf2 enhanced cellular transformation and tumorigenesis in vivo Treatment of HeLa cells with TGFβ resulted in the phosphorylation of AIMP2 on S156, a residue that is exposed on the embedded GST domain of AIMP2...
June 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27157613/mir-16-mediates-trastuzumab-and-lapatinib-response-in-erbb-2-positive-breast-and-gastric-cancer-via-its-novel-targets-ccnj-and-fubp1
#15
L Venturutti, R I Cordo Russo, M A Rivas, M F Mercogliano, F Izzo, R H Oakley, M G Pereyra, M De Martino, C J Proietti, P Yankilevich, J C Roa, P Guzmán, E Cortese, D H Allemand, T H Huang, E H Charreau, J A Cidlowski, R Schillaci, P V Elizalde
ErbB-2 amplification/overexpression accounts for an aggressive breast cancer (BC) subtype (ErbB-2-positive). Enhanced ErbB-2 expression was also found in gastric cancer (GC) and has been correlated with poor clinical outcome. The ErbB-2-targeted therapies trastuzumab (TZ), a monoclonal antibody, and lapatinib, a tyrosine kinase inhibitor, have proved highly beneficial. However, resistance to such therapies remains a major clinical challenge. We here revealed a novel mechanism underlying the antiproliferative effects of both agents in ErbB-2-positive BC and GC...
December 1, 2016: Oncogene
https://www.readbyqxmd.com/read/26925132/influence-of-far-upstream-element-binding-protein-1-gene-on-chemotherapy-sensitivity-in-human-u251-glioblastoma-cells
#16
Yang Hong, Yu Shi, Chao Shang, Yixue Xue, Yunhui Liu
INTRODUCTION: The aim of this study was to determine the influence of the far upstream element binding protein 1 gene (FUBP1) on chemotherapy sensitivity in human U251 glioblastoma cells. MATERIAL AND METHODS: Real-time polymerase chain reaction (PCR) was used to determine the expression of the FUBP1 gene in 43 cases of human brain gliomas. Western blot analysis was used to determine the inhibitory effect of RNA interference on FUBP1 gene expression. Methyl thiazolyl tetrazolium assay (MTT) and flow cytometry methods were used to determine the growth inhibitory rate and apoptosis rate of the U251 cells with FUBP1 silencing...
February 1, 2016: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/26839368/far-upstream-element-binding-protein-1-binds-the-3-untranslated-region-of-pkd2-and-suppresses-its-translation
#17
Wang Zheng, Fan Shen, Ruikun Hu, Birbickram Roy, JungWoo Yang, Qian Wang, Fan Zhang, Jennifer C King, Consolato Sergi, Song-Mei Liu, Emmanuelle Cordat, Jingfeng Tang, Ying Cao, Declan Ali, Xing-Zhen Chen
Autosomal dominant polycystic kidney disease pathogenesis can be recapitulated in animal models by gene mutations in or dosage alterations of polycystic kidney disease 1 (PKD1) or PKD2, demonstrating that too much and too little PKD1/PKD2 are both pathogenic. Gene dosage manipulation has become an appealing approach by which to compensate for loss or gain of gene function, but the mechanisms controlling PKD2 expression remain incompletely characterized. In this study, using cultured mammalian cells and dual-luciferase assays, we found that the 3' untranslated region (3'UTR) of PKD2 mRNA inhibits luciferase protein expression...
September 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/26774856/far-upstream-element-binding-protein-plays-a-crucial-role-in-embryonic-development-hematopoiesis-and-stabilizing-myc-expression-levels
#18
Weixin Zhou, Yang Jo Chung, Edgardo R Parrilla Castellar, Ying Zheng, Hye-Jung Chung, Russell Bandle, Juhong Liu, Lino Tessarollo, Eric Batchelor, Peter D Aplan, David Levens
The transcription factor far upstream element binding protein (FBP) binds and activates the MYC promoter when far upstream element is via TFIIH helicase activity early in the transcription cycle. The fundamental biology and pathology of FBP are complex. In some tumors FBP seems pro-oncogenic, whereas in others it is a tumor suppressor. We generated an FBP knockout (Fubp1(-/-)) mouse to study FBP deficiency. FBP is embryo lethal from embryonic day 10.5 to birth. A spectrum of pathology is associated with FBP loss; besides cerebral hyperplasia and pulmonary hypoplasia, pale livers, hypoplastic spleen, thymus, and bone marrow, cardiac hypertrophy, placental distress, and small size were all indicative of anemia...
March 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/26671986/the-diagnostic-use-of-immunohistochemical-surrogates-for-signature-molecular-genetic-alterations-in-gliomas
#19
REVIEW
Jantima Tanboon, Erik A Williams, David N Louis
A number of key mutations that affect treatment and prognosis have been identified in human gliomas. Two major ways to identify these mutations in a tumor sample are direct interrogation of the mutated DNA itself and immunohistochemistry to assess the effects of the mutated genes on proteins. Immunohistochemistry is an affordable, robust, and widely available technology that has been in place for decades. For this reason, the use of immunohistochemical approaches to assess molecular genetic changes has become an essential component of state-of-the-art practice...
January 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/26545048/molecular-background-of-oligodendroglioma-1p-19q-idh-tert-cic-and-fubp1
#20
REVIEW
Daniel P Cahill, David N Louis, John Gregory Cairncross
Oligodendroglioma is the quintessential molecularly-defined brain tumor. The characteristic whole-arm loss of the long arm of chromosome 1 and the short arm of chromosome 19 (1p/19q-codeletion) within the genome of these tumors facilitated the reproducible molecular identification of this subcategory of gliomas. More recently, recurrent molecular genetic alterations have been identified to occur concurrently with 1p/19q-codeletion, and definitively identify these tumors, including mutations in IDH1/2, CIC, FUBP1, and the TERT promoter, as well as the absence of ATRX and TP53 alterations...
2015: CNS Oncology
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