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https://www.readbyqxmd.com/read/28329682/the-swi-snf-protein-pbrm1-restrains-vhl-loss-driven-clear-cell-renal-cell-carcinoma
#1
Amrita M Nargund, Can G Pham, Yiyu Dong, Patricia I Wang, Hatice U Osmangeyoglu, Yuchen Xie, Omer Aras, Song Han, Toshinao Oyama, Shugaku Takeda, Chelsea E Ray, Zhenghong Dong, Mathieu Berge, A Ari Hakimi, Sebastien Monette, Carl L Lekaye, Jason A Koutcher, Christina S Leslie, Chad J Creighton, Nils Weinhold, William Lee, Satish K Tickoo, Zhong Wang, Emily H Cheng, James J Hsieh
PBRM1 is the second most commonly mutated gene after VHL in clear cell renal cell carcinoma (ccRCC). However, the biological consequences of PBRM1 mutations for kidney tumorigenesis are unknown. Here, we find that kidney-specific deletion of Vhl and Pbrm1, but not either gene alone, results in bilateral, multifocal, transplantable clear cell kidney cancers. PBRM1 loss amplified the transcriptional outputs of HIF1 and STAT3 incurred by Vhl deficiency. Analysis of mouse and human ccRCC revealed convergence on mTOR activation, representing the third driver event after genetic inactivation of VHL and PBRM1...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28322723/nucleosomes-influence-multiple-steps-during-replication-initiation
#2
Ishara F Azmi, Shinya Watanabe, Michael F Maloney, Sukhyun Kang, Jason A Belsky, David M MacAlpine, Craig L Peterson, Stephen P Bell
Eukaryotic replication origin licensing, activation and timing are influenced by chromatin but a mechanistic understanding is lacking. Using reconstituted nucleosomal DNA replication assays, we assessed the impact of nucleosomes on replication initiation. To generate distinct nucleosomal landscapes, different chromatin-remodeling enzymes (CREs) were used to remodel nucleosomes on origin-DNA templates. Nucleosomal organization influenced two steps of replication initiation: origin licensing and helicase activation...
March 21, 2017: ELife
https://www.readbyqxmd.com/read/28318691/evaluation-of-simulated-dredging-to-control-internal-phosphorus-release-from-sediments-focused-on-phosphorus-transfer-and-resupply-across-the-sediment-water-interface
#3
Juhua Yu, Shiming Ding, Jicheng Zhong, Chengxin Fan, Qiuwen Chen, Hongbin Yin, Lei Zhang, Yinlong Zhang
Sediment dredging is an effective restoration method to control the internal phosphorus (P) loading of eutrophic lakes. However, the core question is that the real mechanism of dredging responsible for sediment internal P release still remains unclear. In this study, we investigated the P exchange across the sediment-water interface (SWI) and the internal P resupply ability from the sediments after dredging. The study is based on a one-year field simulation study in Lake Taihu, China, using a Rhizon soil moisture sampler, high-resolution dialysis (HR-Peeper), ZrO-Chelex diffusive gradients in thin film (ZrO-Chelex DGT), and P fractionation and adsorption isotherm techniques...
March 16, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28303890/baf60b-mediated-atm-p53-activation-blocks-cell-identity-conversion-by-sensing-chromatin-opening
#4
Shuyi Ji, Linying Zhu, Yimeng Gao, Xiaoran Zhang, Yupeng Yan, Jin Cen, Rongxia Li, Rong Zeng, Lujian Liao, Chunhui Hou, Yawei Gao, Shaorong Gao, Gang Wei, Lijian Hui
Lineage conversion by expression of lineage-specific transcription factors is a process of epigenetic remodeling that has low efficiency. The mechanism by which a cell resists lineage conversion is largely unknown. Using hepatic-specific transcription factors Foxa3, Hnf1α and Gata4 (3TF) to induce hepatic conversion in mouse fibroblasts, we showed that 3TF induced strong activation of the ATM-p53 pathway, which led to proliferation arrest and cell death, and it further prevented hepatic conversion. Notably, ATM activation, independent of DNA damage, responded to chromatin opening during hepatic conversion...
March 17, 2017: Cell Research
https://www.readbyqxmd.com/read/28303374/potentially-reversible-acute-cerebellar-toxicity-associated-with-minnelide
#5
Sara Khanipour Roshan, Anthony D Spano, Alexander M McKinney, David R Nascene
PURPOSE: Minnelide is an experimental antineoplastic agent that is currently the subject of a phase 1 clinical trial for the treatment of pancreatic and gastrointestinal malignancies. In this study, we documented two cases of reversible acute cerebellar toxicity (REACT) associated with Minnelide and compared its radiological manifestations with other cerebellotoxic agents. METHODS: Both patients had histories of progressive metastatic cancer and participated in a phase 1 clinical trial with Minnelide...
March 16, 2017: Neuroradiology
https://www.readbyqxmd.com/read/28302608/ipsilateral-prominent-thalamostriate-vein-on-susceptibility-weighted-imaging-predicts-poor-outcome-after-intravenous-thrombolysis-in-acute-ischemic-stroke
#6
X Zhang, S Zhang, Q Chen, W Ding, B C V Campbell, M Lou
BACKGROUND AND PURPOSE: The impact of deep cerebral veins on neurologic outcome after intravenous thrombolysis in patients with acute ischemic stroke is unclear. We investigated the relationship between the appearance of deep cerebral veins on susceptibility-weighted imaging and neurologic outcome in patients who underwent thrombolysis. MATERIALS AND METHODS: We retrospectively analyzed 109 consecutive patients with acute ischemic stroke who had pretreatment SWI and received intravenous thrombolysis within 6 hours...
March 16, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28300755/vitamin-d-impacts-the-expression-of-runx2-target-genes-and-modulates-inflammation-oxidative-stress-and-membrane-vesicle-biogenesis-gene-networks-in-143b-osteosarcoma-cells
#7
Rama Garimella, Priyanka Tadikonda, Ossama Tawfik, Sumedha Gunewardena, Peter Rowe, Peter Van Veldhuizen
Osteosarcoma (OS) is an aggressive malignancy of bone affecting children, adolescents and young adults. Understanding vitamin D metabolism and vitamin D regulated genes in OS is an important aspect of vitamin D/cancer paradigm, and in evaluating vitamin D as adjuvant therapy for human OS. Vitamin D treatment of 143B OS cells induced significant and novel changes in the expression of genes that regulate: (a) inflammation and immunity; (b) formation of reactive oxygen species, metabolism of cyclic nucleotides, sterols, vitamins and mineral (calcium), quantity of gap junctions and skeletogenesis; (c) bone mineral density; and (d) cell viability of skeletal cells, aggregation of bone cancer cells and exocytosis of secretory vesicles...
March 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28297605/identifying-cell-cycle-modulators-that-selectively-target-arid1a-deficiency-using-high-throughput-image-based-screening
#8
Lihong Zhang, Jianfeng Shen, Yuping Yin, Yang Peng, Lulu Wang, Hui-Ju Hsieh, Qian Shen, Powel H Brown, Kaixiong Tao, Ivan P Uray, Guang Peng
ARID1A, a component of the chromatin remodeling complex SWI/SNF, is an evolutionarily conserved complex that uses the energy of adenosine triphosphate hydrolysis to remodel chromatin structure and functions as a master regulator of gene transcription. Recent genomic studies have revealed that ARID1A is one of the most frequently mutated genes in human cancers. However, therapeutic approaches that selectively target ARID1A-mutant tumors are not yet clinically available. Our previous study showed that ARID1A facilitates chromatin response and cell cycle checkpoint activation after DNA damage...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28294063/cerebral-microbleeds-do-not-predict-hemorrhagic-transformation-in-acute-ischemic-stroke-patients-with-atrial-fibrillation-and-or-rheumatic-heart-disease
#9
Junfeng Liu, Deren Wang, Jie Li, Jing Lin, Yao Xiong, Bian Liu, Chenchen Wei, Bo Wu, Zhenxing Ma, Shihong Zhang, Ming Liu
Background and Purpose Cerebral microbleeds (CMBs) are known to be potential risk factors for intracerebral hemorrhage (ICH), but there is controversy on the relationship between CMBs and hemorrhagic transformation (HT) after ischemic stroke. Besides, the question regarding whether the relationship between CMBs and HT can be affected by antithrombotic drugs in acute stage of ischemic stroke has not yet reached a consensus. Methods 174 acute ischemic stroke patients with atrial fibrillation (AF) and/or rheumatic heart disease (RHD) were prospectively and consecutively enrolled in the study, of which 160 patients (mean 68...
March 13, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28292935/selective-killing-of-smarca2-and-smarca4-deficient-small-cell-carcinoma-of-the-ovary-hypercalcemic-type-cells-by-inhibition-of-ezh2-in-vitro-and-in-vivo-preclinical-models
#10
Elayne Chan-Penebre, Kelli Armstrong, Allison Drew, Alexandra R Grassian, Igor Feldman, Sarah K Knutson, Kristy Kuplast-Barr, Maria Roche, John Campbell, Peter Ho, Robert A Copeland, Richard Chesworth, Jesse J Smith, Heike Keilhack, Scott A Ribich
The SWI/SNF complex is a major regulator of gene expression and is increasingly thought to play an important role in human cancer, as evidenced by the high frequency of subunit mutations across virtually all cancer types. We previously reported that in preclinical models, malignant rhabdoid tumors, which are deficient in the SWI/SNF core component INI1 (SMARCB1), are selectively killed by inhibitors of the H3K27 histone methyltransferase EZH2. Given the demonstrated antagonistic activities of the SWI/SNF complex and the EZH2-containing PRC2 complex, we investigated whether additional cancers with SWI/SNF mutations are sensitive to selective EZH2 inhibition...
March 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28291122/smarcb1-ini-1-deficient-sinonasal-carcinoma-a-series-of-39-cases-expanding-the-morphologic-and-clinicopathologic-spectrum-of-a-recently-described-entity
#11
Abbas Agaimy, Arndt Hartmann, Cristina R Antonescu, Simion I Chiosea, Samir K El-Mofty, Helene Geddert, Heinrich Iro, James S Lewis, Bruno Märkl, Stacey E Mills, Marc-Oliver Riener, Thomas Robertson, Ann Sandison, Sabine Semrau, Roderick H W Simpson, Edward Stelow, William H Westra, Justin A Bishop
To more fully characterize the clinical and pathologic spectrum of a recently described tumor entity of the sinonasal tract characterized by loss of nuclear expression of SMARCB1 (INI1), we analyzed 39 SMARCB1-deficient sinonasal carcinomas collected from multiple medical centers. The tumors affected 23 males and 16 females with an age range of 19 to 89 years (median, 52). All patients presented with locally advanced disease (T3, n=5; T4, n=27) involving the sinuses (mainly ethmoid) with variable involvement of the nasal cavity...
April 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28290939/susceptibility-weighted-imaging-and-white-matter-abnormality-findings-in-service-members-with-persistent-cognitive-symptoms-following-mild-traumatic-brain-injury
#12
David F Tate, Maria Gusman, Jonathan Kini, Matthew Reid, Carmen S Velez, Ann Marie Drennon, Douglas B Cooper, Jan E Kennedy, Amy O Bowles, Erin D Bigler, Jeffrey D Lewis, John Ritter, Gerald E York
Mild traumatic brain injury (mTBI) is a major health concern among active duty service members and Veterans returning from combat operations, and it can result in variable clinical and cognitive outcomes. Identifying biomarkers that can improve diagnosis and prognostication has been at the forefront of recent research efforts. The purpose of this study was to compare the sensitivity and specificity of abnormalities identified using more traditional magnetic resonance imaging (MRI) sequences such as fluid attenuation inversion recovery (FLAIR) to more advanced MRI sequences such as susceptibility weighted imaging (SWI) among a cohort of active duty service members experiencing persistent cognitive symptoms after mTBI...
March 2017: Military Medicine
https://www.readbyqxmd.com/read/28289221/gentamicin-b1-is-a-minor-gentamicin-component-with-major-nonsense-mutation-suppression-activity
#13
Alireza Baradaran-Heravi, Jürgen Niesser, Aruna D Balgi, Kunho Choi, Carla Zimmerman, Andrew P South, Hilary J Anderson, Natalie C Strynadka, Marcel B Bally, Michel Roberge
Nonsense mutations underlie about 10% of rare genetic disease cases. They introduce a premature termination codon (PTC) and prevent the formation of full-length protein. Pharmaceutical gentamicin, a mixture of several related aminoglycosides, is a frequently used antibiotic in humans that can induce PTC readthrough and suppress nonsense mutations at high concentrations. However, testing of gentamicin in clinical trials has shown that safe doses of this drug produce weak and variable readthrough activity that is insufficient for use as therapy...
March 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28278577/translational-feasibility-of-soluble-nanobiotherapeutics-with-enhanced-red-blood-cell-functions
#14
Thomas Ming Swi Chang
No abstract text is available yet for this article.
February 24, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28266523/abnormalities-in-a-to-i-rna-editing-patterns-in-cns-injuries-correlate-with-dynamic-changes-in-cell-type-composition
#15
Nurit Gal-Mark, Lea Shallev, Sahar Sweetat, Michal Barak, Jin Billy Li, Erez Y Levanon, Eli Eisenberg, Oded Behar
Adenosine to Inosine (A-to-I) RNA editing is a co- or post-transcriptional mechanism that modifies genomically encoded nucleotides at the RNA level. A-to-I RNA editing is abundant in the brain, and altered editing levels have been reported in various neurological pathologies and following spinal cord injury (SCI). The prevailing concept is that the RNA editing process itself is dysregulated by brain pathologies. Here we analyzed recent RNA-seq data, and found that, except for few mammalian conserved editing sites, editing is significantly higher in neurons than in other cell populations of the brain...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28265713/fate-of-metals-in-relation-to-water-and-sediment-properties-in-a-subtropical-lake-in-central-himalaya-india
#16
Shaikhom Inaotombi, Prem Kumar Gupta
Lakes of Himalaya are one of the most fragile ecosystems on earth. Tourism and urban development in the upland region strongly affect its water resources. The high rate of sedimentation and organic matter deposition alters the ecological state of sediment bed, which indirectly influences on dynamics of metallic elements. We investigated spatial and temporal variations of water and sediment characteristic in Lake Sattal of Central Himalaya, India. Samples were collected seasonally from four sampling locations from January 2011 to December 2012...
April 2017: Archives of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/28262751/the-swi-snf-chromatin-remodelling-complex-is-required-for-maintenance-of-lineage-specific-enhancers
#17
Burak H Alver, Kimberly H Kim, Ping Lu, Xiaofeng Wang, Haley E Manchester, Weishan Wang, Jeffrey R Haswell, Peter J Park, Charles W M Roberts
Genes encoding subunits of SWI/SNF (BAF) chromatin remodelling complexes are collectively altered in over 20% of human malignancies, but the mechanisms by which these complexes alter chromatin to modulate transcription and cell fate are poorly understood. Utilizing mouse embryonic fibroblast and cancer cell line models, here we show via ChIP-seq and biochemical assays that SWI/SNF complexes are preferentially targeted to distal lineage specific enhancers and interact with p300 to modulate histone H3 lysine 27 acetylation...
March 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28260124/prions-and-the-concept-of-polyprionic-inheritance
#18
REVIEW
Alexey P Galkin
Discovery of prions-proteins that are able to convert between structurally distinct states, of which one or more is transmissible, led to the concept of "protein-based inheritance". According to this concept, the formation of prion fibrils causes DNA-independent heritable traits in microorganisms. Recently, we described a new and unusual type of prion inheritance. We showed that the yeast prions [PIN (+)] and [SWI (+)], like classical genes, demonstrate complementary interaction that causes a phenotypic change in yeast cells...
March 4, 2017: Current Genetics
https://www.readbyqxmd.com/read/28256572/clinicopathological-and-molecular-characterization-of-smarca4-deficient-thoracic-sarcomas-with-comparison-to-potentially-related-entities
#19
Akihiko Yoshida, Eisuke Kobayashi, Takashi Kubo, Makoto Kodaira, Toru Motoi, Noriko Motoi, Kan Yonemori, Yuichiro Ohe, Shun-Ichi Watanabe, Akira Kawai, Takashi Kohno, Hiroshi Kishimoto, Hitoshi Ichikawa, Nobuyoshi Hiraoka
A growing number of studies suggest critical tumor suppressor roles of the SWI/SNF chromatin remodeling complex in a variety of human cancers. The recent discovery of SMARCA4-deficient thoracic sarcomas has added to the list of tumor groups with the SMARCA4 inactivating mutation. To better characterize these tumors and establish their nosological status, we undertook a clinicopathological and molecular analysis of 12 SMARCA4-deficient thoracic sarcomas and compared them with three potentially related disease entities...
March 3, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28253716/arid1a-gene-knockdown-promotes-neuroblastoma-migration-and-invasion
#20
C Li, Z Xu, Z Zhao, Q An, L Wang, Y Yu, D Piao
Neuroblastoma is the most common extracranial solid tumor in childhood which often acquires drug resistance and becomes aggressive phenotypes. The high-risk patients suffer from high mortality due to the limitation of the treatment strategies. ARID1A (AT-rich interactive domain-containing protein 1A), a subunit of SWI/SNF complexes, is considered as a tumor suppressor in many cancers. The aim of the present study was to investigate the effect of ARID1A on migration and invasion in neuroblastoma cells. The shRNA targeting ARID1A was designed and delivered into SK-N-SH cells to knock down ARID1A expression...
March 3, 2017: Neoplasma
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