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https://www.readbyqxmd.com/read/28078112/molecular-spectrum-of-kras-nras-braf-pik3ca-tp53-and-apc-somatic-gene-mutations-in-arab-patients-with-colorectal-cancer-determination-of-frequency-and-distribution-pattern
#1
Humaid O Al-Shamsi, Jeremy Jones, Yazan Fahmawi, Ibrahim Dahbour, Aziz Tabash, Reham Abdel-Wahab, Ahmed O S Abousamra, Kenna R Shaw, Lianchun Xiao, Manal M Hassan, Benjamin R Kipp, Scott Kopetz, Amr S Soliman, Robert R McWilliams, Robert A Wolff
BACKGROUND: The frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA in colorectal cancer (CRC) differ among populations. The aim of this study was to assess mutation frequencies in the Arab population and determine their correlations with certain clinicopathological features. METHODS: Arab patients from the Arab Gulf region and a population of age- and sex-matched Western patients with CRC whose tumors were evaluated with next-generation sequencing (NGS) were identified and retrospectively reviewed...
December 2016: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28069547/overexpression-of-mir-92a-promotes-the-tumor-growth-of-osteosarcoma-by-suppressing-f-box-and-wd-repeat-containing-protein-7
#2
Xuesheng Jiang, Xiongfeng Li, Fengfeng Wu, Hongliang Gao, Guorong Wang, Hua Zheng, Huajun Wang, Jianyou Li, Chao Chen
MicroRNAs (miRNAs) have been reported to be critical players in osteosarcoma (OS). Among numerous cancer-related miRNAs, the expression level of miR-92a and its potential role in OS has not been investigated. Here, We showed that overexpression of miR-92a was identified in OS specimens and cells compared to normal bone tissues. The high level of miR-92a was correlated with high T classification and advanced clinical stages of OS patients. Notably, miR-92a highly expressing OS patients showed a notably reduced survival rate...
January 6, 2017: Gene
https://www.readbyqxmd.com/read/28053206/gsk3b-mediated-phosphorylation-of-mcl1-regulates-axonal-autophagy-to-promote-wallerian-degeneration
#3
Shuji Wakatsuki, Shinji Tokunaga, Megumi Shibata, Toshiyuki Araki
Macroautophagy is a catabolic process, in which portions of cytoplasm or organelles are delivered to lysosomes for degradation. Emerging evidence has indicated a pathological connection between axonal degeneration and autophagy. However, the physiological function and induction mechanism of autophagy in axons remain elusive. We herein show that, through activation of BECLIN1, glycogen synthase kinase 3B (GSK3B)-mediated phosphorylation of BCL2 family member MCL1 induces axonal autophagy and axonal degeneration...
January 4, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28029553/somatic-mutation-detection-using-various-targeted-detection-assays-in-paired-samples-of-circulating-tumor-dna-primary-tumor-and-metastases-from-patients-undergoing-resection-of-colorectal-liver-metastases
#4
Nick Beije, Jean C Helmijr, Marjolein J A Weerts, Corine M Beaufort, Matthew Wiggin, Andre Marziali, Cornelis Verhoef, Stefan Sleijfer, Maurice P H M Jansen, John W M Martens
Assessing circulating tumor DNA (ctDNA) is a promising method to evaluate somatic mutations from solid tumors in a minimally-invasive way. In a group of twelve metastatic colorectal cancer (mCRC) patients undergoing liver metastasectomy, from each patient DNA from cell-free DNA (cfDNA), the primary tumor, metastatic liver tissue, normal tumor-adjacent colon or liver tissue, and whole blood were obtained. Investigated was the feasibility of a targeted NGS approach to identify somatic mutations in ctDNA. This targeted NGS approach was also compared with NGS preceded by mutant allele enrichment using synchronous coefficient of drag alteration technology embodied in the OnTarget assay, and for selected mutations with digital PCR (dPCR)...
October 10, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28008299/kras-mutation-as-a-potential-prognostic-biomarker-of-biliary-tract-cancers
#5
Masaaki Yokoyama, Hiroaki Ohnishi, Kouki Ohtsuka, Satsuki Matsushima, Yasuo Ohkura, Junji Furuse, Takashi Watanabe, Toshiyuki Mori, Masanori Sugiyama
BACKGROUND: The aim of this study was to identify the unique molecular characteristics of biliary tract cancer (BTC) for the development of novel molecular-targeted therapies. MATERIALS AND METHODS: We performed mutational analysis of KRAS, BRAF, PIK3CA, and FBXW7 and immunohistochemical analysis of EGFR and TP53 in 63 Japanese patients with BTC and retrospectively evaluated the association between the molecular characteristics and clinicopathological features of BTC...
2016: Japanese Clinical Medicine
https://www.readbyqxmd.com/read/28007894/the-pseudophosphatase-styx-targets-the-f-box-of-fbxw7-and-inhibits-scffbxw7-function
#6
Veronika Reiterer, Cristina Figueras-Puig, Francois Le Guerroue, Stefano Confalonieri, Manuela Vecchi, Dasaradha Jalapothu, Sandip M Kanse, Raymond J Deshaies, Pier Paolo Di Fiore, Christian Behrends, Hesso Farhan
The F-box protein FBXW7 is the substrate-recruiting subunit of an SCF ubiquitin ligase and a major tumor-suppressor protein that is altered in several human malignancies. Loss of function of FBXW7 results in the stabilization of numerous proteins that orchestrate cell proliferation and survival. Little is known about proteins that directly regulate the function of this protein. In the current work, we have mapped the interactome of the enigmatic pseudophosphatase STYX We reasoned that a catalytically inactive phosphatase might have adopted novel mechanisms of action...
December 22, 2016: EMBO Journal
https://www.readbyqxmd.com/read/28000899/mir-367-promotes-the-proliferation-and-invasion-of-non-small-cell-lung-cancer-via-targeting-fbxw7
#7
Jing Xu, Weibing Wu, Jun Wang, Chenjun Huang, Wei Wen, Fei Zhao, Xinfeng Xu, Xianglong Pan, Wei Wang, Quan Zhu, Liang Chen
The involvement of miR-367 in lung cancer development remains unclear. In the present study, we analyzed the expression of miR-367 in tumor and adjacent tissue samples from 113 patients with non-small cell lung cancer (NSCLC) utilizing real-time PCR. miR-367 expression was significantly upregulated in the cancer tissues compared with non-cancer controls. Based on the median value of the miR-367 expression level, we divided the NSCLC patients into miR-367 high-expression and miR-367 low-expression groups. Overexpression of miR-367 was correlated with a poorer prognosis of NSCLC patients Chi-square (χ2) test showed a significant statistical correlation between tumor size, tumor stage, metastasis and miR-367 expression...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/28000896/mir%C3%A2-223%C3%A2-3p-regulates-cell-growth-and-apoptosis-via-fbxw7-suggesting-an-oncogenic-role-in-human-testicular-germ-cell-tumors
#8
Jikai Liu, Hao Shi, Xidan Li, Gang Chen, Catharina Larsson, Weng-Onn Lui
miR‑223‑3p is deregulated in several tumor types and plays an important role in tumorigenesis and progression. However, its role in the pathogenesis of testicular germ cell tumor (TGCT) remains uncharacterized. We previously demonstrated that miR‑223‑3p expression was increased in TGCTs compared with normal testes (NT), suggesting that miR‑223‑3p may have an oncogenic role in TGCT. Using published dataset and The Cancer Genome Atlas database, we validated higher miR‑223‑3p expression in TGCTs than NT, and found a negative correlation between miR-223-3p and FBXW7 mRNA expression levels...
December 15, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27998038/whole-exome-sequencing-predicted-cancer-epitope-trees-of-23-early-cervical-cancers-in-chinese-women
#9
Xia Li, Hailiang Huang, Yanfang Guan, Yuhua Gong, Cheng-Yi He, Xin Yi, Ming Qi, Zhi-Ying Chen
Emerging evidence suggest that the heterogeneity of cancer limits the efficacy of immunotherapy. To search for optimal therapeutic targets for enhancing the efficacy, we used whole-exome sequencing data of 23 early cervical tumors from Chinese women to investigate the hierarchical structure of the somatic mutations and the neo-epitopes. The putative neo-epitopes were predicted based on the mutant peptides' strong binding with major histocompatibility complex class I molecules. We found that each tumor carried an average of 117 mutations and 61 putative neo-epitopes...
December 20, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27925341/skeletal-muscle-atrophy-is-induced-by-fbxw7%C3%AE-via-atrogene-upregulation
#10
Kyungshin Shin, Young-Gyu Ko, Jaemin Jeong, Heechung Kwon
Muscle atrophy decreases skeletal muscle mass and is induced by inherited cachectic symptoms, genetic disorders, and sarcopenia. However, the molecular pathways associated with the onset of muscle atrophy are still unclear. In this study, we evaluated Fbxw7β, a gene associated with the development of muscle atrophy in vitro and in vivo. Among the three Fbxw7 isoforms, ectopically overexpressed Fbxw7β induced the expression of myogenin and major atrogene markers (atrogin-1 and MuRF-1) and reduced myoblast differentiation...
December 7, 2016: Cell Biology International
https://www.readbyqxmd.com/read/27904771/tumor-suppressive-function-of-long-noncoding-rna-malat1-in-glioma-cells-by-suppressing-mir-155-expression-and-activating-fbxw7-function
#11
Shuanzhu Cao, Yanzhou Wang, Jinquan Li, Mingliang Lv, Haitao Niu, Yong Tian
The human metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA associated with metastasis, and is a favorable prognostic factor for lung cancer. Recent studies have shown that MALAT1 plays an important role in many malignancies. However, little is known about the role of MALAT1 in glioma. In this study, we determined the expression of MALAT1 and explored its prognostic value in glioma. Further, we investigated the regulatory mechanism of MALAT1 in glioma progression. Our results showed that the expression of MALAT1 was significantly decreased in glioma specimens than in noncancerous brain tissues...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27900032/mir-223-decreases-cell-proliferation-and-enhances-cell-apoptosis-in-acute-myeloid-leukemia-via-targeting-fbxw7
#12
Yi Xiao, Changliang Su, Taoran Deng
The expression of microRNA-223 (miR-233) has been investigated in various types of cancer. However, to the best of our knowledge, the expression and function of miR-223 in acute myeloid leukemia (AML) remains to be elucidated. The expression of miR-223 was measured by reverse transcription-quantitative polymerase chain reaction. Following transfection with miR-223, cell viability assays, cell apoptosis assays, western blot analysis and luciferase assays were conducted in AML cell lines. In the present study, it was initially observed that miR-223 was downregulated in AML patients compared with healthy subjects...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27890934/egr2-mutations-define-a-new-clinically-aggressive-subgroup-of-chronic-lymphocytic-leukemia
#13
E Young, D Noerenberg, L Mansouri, V Ljungström, M Frick, L-A Sutton, S J Blakemore, J Galan-Sousa, K Plevova, P Baliakas, D Rossi, R Clifford, D Roos-Weil, V Navrkalova, B Dörken, C A Schmitt, K E Smedby, G Juliusson, B Giacopelli, J S Blachly, C Belessi, P Panagiotidis, N Chiorazzi, F Davi, A W Langerak, D Oscier, A Schuh, G Gaidano, P Ghia, W Xu, L Fan, O A Bernard, F Nguyen-Khac, L Rassenti, J Li, T J Kipps, K Stamatopoulos, S Pospisilova, T Zenz, C C Oakes, J C Strefford, R Rosenquist, F Damm
Recurrent mutations within EGR2 were recently reported in advanced-stage chronic lymphocytic leukemia (CLL) patients and associated with a worse outcome. To study their prognostic impact, 2403 CLL patients were examined for mutations in the EGR2 hotspot region including a screening (n=1283) and two validation cohorts (UK CLL4 trial patients, n=366; CLL Research Consortium (CRC) patients, n=490). Targeted deep-sequencing of 27 known/postulated CLL driver genes was also performed in 38 EGR2-mutated patients to assess concurrent mutations...
January 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27852700/genomic-evolution-after-chemoradiotherapy-in-anal-squamous-cell-carcinoma
#14
Kent W Mouw, James M Cleary, Brendan Reardon, Jonathan Pike, Lior Z Braunstein, Jaegil Kim, Ali Amin-Mansour, Diana Miao, Alexis Damish, Joanna Chin, Patrick A Ott, Charles S Fuchs, Neil E Martin, Gad Getz, Scott Carter, Harvey Mamon, Jason L Hornick, Eliezer Van Allen, Alan D D'Andrea
PURPOSE: Squamous cell carcinoma of the anal canal (ASCC) accounts for 2-4% of gastrointestinal (GI) malignancies in the US and is increasing in incidence; however, genomic features of ASCC are incompletely characterized. Primary treatment of ASCC involves concurrent chemotherapy and radiation (CRT), but the mutational landscape of resistance to CRT is unknown. Here, we aim to compare mutational features of ASCC in the pre- and post-CRT setting. EXPERIMENTAL DESIGN: We perform whole exome sequencing of primary (n=31) and recurrent (n=31) ASCCs and correlate findings with clinical data...
November 16, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27837025/structural-basis-of-n-myc-binding-by-aurora-a-and-its-destabilization-by-kinase-inhibitors
#15
Mark W Richards, Selena G Burgess, Evon Poon, Anne Carstensen, Martin Eilers, Louis Chesler, Richard Bayliss
Myc family proteins promote cancer by inducing widespread changes in gene expression. Their rapid turnover by the ubiquitin-proteasome pathway is regulated through phosphorylation of Myc Box I and ubiquitination by the E3 ubiquitin ligase SCF(FbxW7) However, N-Myc protein (the product of the MYCN oncogene) is stabilized in neuroblastoma by the protein kinase Aurora-A in a manner that is sensitive to certain Aurora-A-selective inhibitors. Here we identify a direct interaction between the catalytic domain of Aurora-A and a site flanking Myc Box I that also binds SCF(FbxW7) We determined the crystal structure of the complex between Aurora-A and this region of N-Myc to 1...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27822062/dysfunction-of-microrna-32-regulates-ubiquitin-ligase-fbxw7-in-multiple-myeloma-disease
#16
Jingsheng Hua, Tianling Ding, Linjun Yang
Dysfunction of microRNA (miRNA) expression has been associated with tumor occurrence, progression, and development. The aim of this work was to study the dysfunction of miR-32 - an miRNA that was abnormally regulated in different tumors - in clinical tissues from patients with multiple myeloma (MM). The tumor tissues in which we assessed miR-32 expression levels were collected during our 5 years of clinical practice. Our study found an increase in miR-32 expression in MM tissues. Assessment of F-box and WD repeat domain-containing 7 (FBXW7) in MM tissues showed an inverse relation between the expression of FBXW7 and miR-32...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27812198/visceral-adipose-microrna-223-is-upregulated-in-human-and-murine-obesity-and-modulates-the-inflammatory-phenotype-of-macrophages
#17
Jeffrey A Deiuliis, Rafay Syed, Dheeraj Duggineni, Jessica Rutsky, Palanivel Rengasamy, Jie Zhang, Kun Huang, Bradley Needleman, Dean Mikami, Kyle Perry, Jeffrey Hazey, Sanjay Rajagopalan
Obesity in humans and mice is typified by an activated macrophage phenotype in the visceral adipose tissue (VAT) leading to increased macrophage-mediated inflammation. microRNAs (miRNAs) play an important role in regulating inflammatory pathways in macrophages, and in this study we compared miRNA expression in the VAT of insulin resistant morbidly obese humans to a non-obese cohort with normal glucose tolerance. miR-223-3p was found to be significantly upregulated in the whole omental tissue RNA of 12 human subjects, as were 8 additional miRNAs...
2016: PloS One
https://www.readbyqxmd.com/read/27764699/fbxw7-deletion-accelerates-kras-g12d-driven-pancreatic-tumorigenesis-via-yap-accumulation
#18
Qiang Zhang, Yaqing Zhang, Joshua D Parsels, Ines Lohse, Theodore S Lawrence, Marina Pasca di Magliano, Yi Sun, Meredith A Morgan
Pancreatic cancers driven by KRAS mutations require additional mutations for tumor progression. The tumor suppressor FBXW7 is altered in pancreatic cancers, but its contribution to pancreatic tumorigenesis is unknown. To determine potential cooperation between Kras mutation and Fbxw7 inactivation in pancreatic tumorigenesis, we generated P48-Cre;LSL-Kras(G12D);Fbxw7(fl/fl) (KFC(fl/fl)) compound mice. We found that KFC(fl/fl) mice displayed accelerated tumorigenesis: all mice succumbed to pancreatic ductal adenocarcinoma (PDA) by 40 days of age, with PDA onset occurring by 2 weeks of age...
November 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27759908/translocation-t-8-14-q24-q11-with-concurrent-pten-alterations-and-deletions-of-stil-tal1-and-cdkn2a-b-in-a-pediatric-case-of-acute-t-lymphoblastic-leukemia-a-genetic-profile-associated-with-adverse-prognosis
#19
Jolanta Skalska-Sadowska, Małgorzata Dawidowska, Bronisława Szarzyńska-Zawadzka, Małgorzata Jarmuż-Szymczak, Joanna Czerwińska-Rybak, Ludomiła Machowska, Katarzyna Derwich
We report a pediatric case of acute T-lymphoblastic leukemia (T-ALL) with NOTCH1(wt) , FBXW7(wt) , STIL/TAL1, and PTEN (exons 2, 3, 4, 5) monoallelic deletions, biallelic CDKN2A/B deletion, and a minor t(8;14)(q24;q11)-positive subclone. Undetectable by a flow cytometric minimal residual disease assay, the t(8;14)(q24;q11) subclone expanded as detected by fluorescence in situ hybridization from 5% at diagnosis to 26% before consolidation and 100% at relapse bearing a monoallelic deletion (exons 2, 3) with a new frameshift mutation of PTEN and the same set of remaining molecular alterations...
October 19, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27756406/spatio-temporal-mutation-profiles-of-case-matched-colorectal-carcinomas-and-their-metastases-reveal-unique-de-novo-mutations-in-metachronous-lung-metastases-by-targeted-next-generation-sequencing
#20
Valentina Kovaleva, Anna-Lena Geissler, Lisa Lutz, Ralph Fritsch, Frank Makowiec, Sebastian Wiesemann, Ulrich T Hopt, Bernward Passlick, Martin Werner, Silke Lassmann
BACKGROUND: Targeted next generation sequencing (tNGS) has become part of molecular pathology diagnostics for determining RAS mutation status in colorectal cancer (CRC) patients as predictive tool for decision on EGFR-targeted therapy. Here, we investigated mutation profiles of case-matched tissue specimens throughout the disease course of CRC, to further specify RAS-status dynamics and to identify de novo mutations associated with distant metastases. METHODS: Case-matched formalin-fixed and paraffin-embedded (FFPE) resection specimens (n = 70; primary tumours, synchronous and/or metachronous liver and/or lung metastases) of 14 CRC cases were subjected to microdissection of normal colonic epithelial, primary and metastatic tumour cells, their DNA extraction and an adapted library protocol for limited DNA using the 48 gene TruSeq Amplicon Cancer Panel(TM), MiSeq sequencing and data analyses (Illumina)...
October 18, 2016: Molecular Cancer
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