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https://www.readbyqxmd.com/read/28933360/detection-of-alphacoronavirus-vrna-in-the-feces-of-brazilian-free-tailed-bats-tadarida-brasiliensis-from-a-colony-in-florida-usa
#1
Tania S Bonny, John P Driver, Taylor Paisie, Marco Salemi, John Glenn Morris, Lisa A Shender, Lisa Smith, Carolyn Enloe, Kevin Oxenrider, Jeffery A Gore, Julia C Loeb, Chang-Yu Wu, John A Lednicky
Bats are natural reservoirs of coronaviruses and other viruses with zoonotic potential. Florida has indigenous non-migratory populations of Brazilian free-tailed bats (Tadarida brasiliensis) that mostly roost in colonies in artificial structures. Unlike their counterparts in Brazil and Mexico, the viruses harbored by the Florida bats have been underexplored. We report the detection of an alphacoronavirus RNA-dependent RNA polymerase (RdRp) gene sequence in the feces of two of 19 different T. brasiliensis that were capture/release bats that had been evaluated for overall health...
February 27, 2017: Diseases (Basel)
https://www.readbyqxmd.com/read/28932816/a-quorum-sensing-system-that-regulates-streptococcus-pneumoniae-biofilm-formation-and-surface-polysaccharide-production
#2
Roger Junges, Gabriela Salvadori, Sudhanshu Shekhar, Heidi A Åmdal, Jimstan N Periselneris, Tsute Chen, Jeremy S Brown, Fernanda C Petersen
Despite vaccines, Streptococcus pneumoniae kills more than a million people yearly. Thus, understanding how pneumococci transition from commensals to pathogens is particularly relevant. Quorum sensing regulates collective behaviors and thus represents a potential driver of commensal-to-pathogen transitions. Rgg/small hydrophobic peptide (SHP) quorum-sensing systems are widespread in streptococci, yet they remain largely uncharacterized in S. pneumoniae. Using directional transcriptome sequencing, we show that the S...
September 2017: MSphere
https://www.readbyqxmd.com/read/28932764/antisense-oligonucleotide-mediated-knockdown-in-mammary-tumor-organoids
#3
Sarah D Diermeier, David L Spector
Primary mammary tumor organoids grown in 3D are an excellent system to study tumor biology. They resemble the organization and physiology of native epithelia more closely than cancer cell lines grown in 2D, and additionally model interactions with the ECM (Boj et al., 2015; Clevers, 2016; Shamir and Ewald, 2014). Mammary tumor organoids are therefore a promising model system to identify and characterize novel drivers of breast cancer that would be unlikely to be identified using 2D cell lines. Antisense oligonucleotides can be used to efficiently and specifically knockdown target genes in the cell (Bennett et al...
August 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28932563/a-systematic-and-genome-wide-correlation-meta-analysis-of-pd-l1-expression-and-targetable-nsclc-driver-genes
#4
Jin Li, Yaoqi Chen, Xiaoshun Shi, Xiaobing Le, Fenglan Feng, Jingyi Chen, Chengzhi Zhou, Yusong Chen, Shuai Wen, Haikang Zeng, Allen M Chen, Yu Zhang
BACKGROUND: Studies have shown that the ligand of programmed cell death protein 1 (B7-H1, CD274 or PD-L1) is related to lung cancer driver genes. Although studies have examined the association between lung cancer driver gene mutations or expression and PD-L1 expression, the present studies have not been mined the correlation systematically and genome-widely. METHODS: All relevant published PD-L1 articles with driver genes data and the RNA-seq dataset from The Cancer Genome Atlas (TCGA) were analyzed...
August 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28931451/bank-vole-immunoheterogeneity-may-limit-nephropatia-epidemica-emergence-in-a-french-non-endemic-region
#5
A Dubois, G Castel, S Murri, C Pulido, J-B Pons, L Benoit, A Loiseau, L Lakhdar, M Galan, P Marianneau, N Charbonnel
Ecoevolutionary processes affecting hosts, vectors and pathogens are important drivers of zoonotic disease emergence. In this study, we focused on nephropathia epidemica (NE), which is caused by Puumala hantavirus (PUUV) whose natural reservoir is the bank vole, Myodes glareolus. We questioned the possibility of NE emergence in a French region that is considered to be NE-free but that is adjacent to a NE-endemic region. We first confirmed the epidemiology of these two regions and we demonstrated the absence of spatial barriers that could have limited dispersal, and consequently, the spread of PUUV into the NE-free region...
September 21, 2017: Parasitology
https://www.readbyqxmd.com/read/28930682/chemically-induced-degradation-of-the-oncogenic-transcription-factor-bcl6
#6
Nina Kerres, Steffen Steurer, Stefanie Schlager, Gerd Bader, Helmut Berger, Maureen Caligiuri, Christian Dank, John R Engen, Peter Ettmayer, Bernhard Fischerauer, Gerlinde Flotzinger, Daniel Gerlach, Thomas Gerstberger, Teresa Gmaschitz, Peter Greb, Bingsong Han, Elizabeth Heyes, Roxana E Iacob, Dirk Kessler, Heike Kölle, Lyne Lamarre, David R Lancia, Simon Lucas, Moriz Mayer, Katharina Mayr, Nikolai Mischerikow, Katja Mück, Christoph Peinsipp, Oliver Petermann, Ulrich Reiser, Dorothea Rudolph, Klaus Rumpel, Carina Salomon, Dirk Scharn, Renate Schnitzer, Andreas Schrenk, Norbert Schweifer, Diane Thompson, Elisabeth Traxler, Roland Varecka, Tilman Voss, Alexander Weiss-Puxbaum, Sandra Winkler, Xiaozhang Zheng, Andreas Zoephel, Norbert Kraut, Darryl McConnell, Mark Pearson, Manfred Koegl
The transcription factor BCL6 is a known driver of oncogenesis in lymphoid malignancies, including diffuse large B cell lymphoma (DLBCL). Disruption of its interaction with transcriptional repressors interferes with the oncogenic effects of BCL6. We used a structure-based drug design to develop highly potent compounds that block this interaction. A subset of these inhibitors also causes rapid ubiquitylation and degradation of BCL6 in cells. These compounds display significantly stronger induction of expression of BCL6-repressed genes and anti-proliferative effects than compounds that merely inhibit co-repressor interactions...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28929581/gain-of-function-mutation-in-ptpn11-in-histiocytic-sarcomas-of-bernese-mountain-dogs
#7
T Thaiwong, S Sirivisoot, M Takada, V Yuzbasiyan-Gurkan, M Kiupel
Histiocytic sarcoma (HS) is an aggressive malignant neoplasm of dendritic cell origin that is common in certain breeds of dogs. High prevalence of fatal, disseminated HS has been described in Bernese Mountain Dogs (BMDs). Support for genetic predisposition to develop HS has been presented in several studies, but to date, causative genetic events have not been reported. In addition, no driver mutations have been identified in tumours. Recently, E76K gain-of-function mutation in SHP2 encoded by the PTPN11 gene has been described in human histiocytic malignancies...
September 20, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/28928761/hormonal-regulation-in-shade-avoidance
#8
REVIEW
Chuanwei Yang, Lin Li
At high vegetation density, shade-intolerant plants sense a reduction in the red (660 nm) to far-red (730 nm) light ratio (R/FR) in addition to a general reduction in light intensity. These light signals trigger a spectrum of morphological changes manifested by growth of stem-like tissue (hypocotyl, petiole, etc.) instead of harvestable organs (leaves, fruits, seeds, etc.)-namely, shade avoidance syndrome (SAS). Common phenotypical changes related to SAS are changes in leaf hyponasty, an increase in hypocotyl and internode elongation and extended petioles...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28928286/hpv-integration-in-hnscc-correlates-with-survival-outcomes-immune-response-signatures-and-candidate-drivers
#9
Lada A Koneva, Yanxiao Zhang, Shama Virani, Pelle B Hall, Jonathan B McHugh, Douglas B Chepeha, Gregory Wolf, Thomas E Carey, Laura S Rozek, Maureen A Sartor
The incidence of human papillomavirus (HPV)-related oropharynx cancer has steadily increased over the past two decades, and now represents a majority of oropharyngeal cancer cases. Integration of the HPV genome into the host genome is a common event during carcinogenesis that has clinically-relevant effects if the viral early genes are transcribed. Understanding the impact of HPV integration on clinical outcomes of head and neck squamous cell carcinoma (HNSCC) is critical for implementing de-escalated treatment approaches for HPV-positive HNSCC patients...
September 19, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28926105/loss-of-runx1-is-associated-with-aggressive-lung-adenocarcinomas
#10
Jon Ramsey, Kelly Butnor, Zhihua Peng, Tim Leclair, Jos van der Velden, Gary Stein, Jane Lian, C Matthew Kinsey
The mammalian runt-related factor 1 (RUNX1) is a master transcription factor that regulates lineage specification of hematopoietic stem cells. RUNX1 translocations result in the development of myeloid leukemias. Recently, RUNX1 has been implicated as a tumor suppressor in other cancers. We postulated RUNX1 expression may be associated with lung adenocarcinoma etiology and/or progression. We evaluated the association of RUNX1 mRNA expression with overall survival data from The Cancer Genome Atlas (TCGA), a publically available database...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28924241/clinical-impact-of-the-subclonal-architecture-and-mutational-complexity-in-chronic-lymphocytic-leukemia
#11
F Nadeu, G Clot, J Delgado, D Martín-García, T Baumann, I Salaverria, S Beà, M Pinyol, P Jares, A Navarro, H Suárez-Cisneros, M Aymerich, M Rozman, N Villamor, D Colomer, M González, M Alcoceba, M J Terol, B Navarro, E Colado, Á R Payer, X S Puente, C López-Otín, A López-Guillermo, A Enjuanes, E Campo
Genome studies of chronic lymphocytic leukemia (CLL) have revealed the remarkable subclonal heterogeneity of the tumors, but the clinical implications of this phenomenon are not well known. We assessed the mutational status of 28 CLL driver genes by deep-targeted next-generation sequencing and copy number alterations (CNA) in 406 previously untreated patients and 48 sequential samples. We detected small subclonal mutations (0.6-25% of cells) in nearly all genes (26/28), and they were the sole alteration in 22% of the mutated cases...
September 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28923920/microrna-dysregulation-to-identify-therapeutic-target-combinations-for-chronic-lymphocytic-leukemia
#12
Laura Z Rassenti, Veronica Balatti, Emanuela M Ghia, Alexey Palamarchuk, Luisa Tomasello, Paolo Fadda, Yuri Pekarsky, George F Widhopf, Thomas J Kipps, Carlo M Croce
Loss of miR-15/16 is the most common genetic lesion in chronic lymphocytic leukemia (CLL), promoting overexpression of BCL2, which factors in leukemia pathogenesis. Indeed, an inhibitor of Bcl2, venetoclcax, is highly active in the treatment of patients with CLL. However, single-agent venetoclcax fails to eradicate minimal residual disease in most patients. Accordingly, we were interested in other genes that may be regulated by miR-15/16, which may target other drivers in CLL. We found that miR-15/16 targets ROR1, which encodes an onco-embryonic surface protein expressed on the CLL cells of over 90% of patients, but not on virtually all normal postpartum tissues...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923882/mutational-profiling-of-acute-myeloid-leukemia-with-normal-cytogenetics-in-brazilian-patients-the-value-of-next-generation-sequencing-for-genomic-classification
#13
Thiago Rodrigo de Noronha, Miguel Mitne-Neto, Maria de Lourdes Chauffaille
Karyotype (KT) aberrations are important prognostic factors for acute myeloid leukemia (AML); however, around 50% of cases present normal results. Single nucleotide polymorphism array can detect chromosomal gains, losses or uniparental disomy that are invisible to KT, thus improving patients' risk assessment. However, when both tests are normal, important driver mutations can be detected by the use of next-generation sequencing (NGS). Fourteen adult patients with AML with normal cytogenetics were investigated by NGS for 19 AML-related genes...
September 18, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28923828/attenuated-pdgf-signaling-drives-alveolar-and-microvascular-defects-in-neonatal-chronic-lung%C3%A2-disease
#14
Prajakta Oak, Tina Pritzke, Isabella Thiel, Markus Koschlig, Daphne S Mous, Anita Windhorst, Noopur Jain, Oliver Eickelberg, Kai Foerster, Andreas Schulze, Wolfgang Goepel, Tobias Reicherzer, Harald Ehrhardt, Robbert J Rottier, Peter Ahnert, Ludwig Gortner, Tushar J Desai, Anne Hilgendorff
Neonatal chronic lung disease (nCLD) affects a significant number of neonates receiving mechanical ventilation with oxygen-rich gas (MV-O2). Regardless, the primary molecular driver of the disease remains elusive. We discover significant enrichment for SNPs in the PDGF-Rα gene in preterms with nCLD and directly test the effect of PDGF-Rα haploinsufficiency on the development of nCLD using a preclinical mouse model of MV-O2 In the context of MV-O2, attenuated PDGF signaling independently contributes to defective septation and endothelial cell apoptosis stemming from a PDGF-Rα-dependent reduction in lung VEGF-A...
September 18, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28923030/the-eef1a2-gene-expression-as-risk-predictor-in-localized-prostate-cancer
#15
Thomas Stefan Worst, Frank Waldbillig, Abdallah Abdelhadi, Cleo-Aron Weis, Maria Gottschalt, Annette Steidler, Jost von Hardenberg, Maurice Stephan Michel, Philipp Erben
BACKGROUND: Besides clinical stage and Gleason score, risk-stratification of prostate cancer in the pretherapeutic setting mainly relies on the serum PSA level. Yet, this is associated with many uncertainties. With regard to therapy decision-making, additional markers are needed to allow an exact risk prediction. Eukaryotic translation elongation factor 1 alpha 2 (EEF1A2) was previously suggested as driver of tumor progression and potential biomarker. In the present study its functional and prognostic relevance in prostate cancer was investigated...
September 18, 2017: BMC Urology
https://www.readbyqxmd.com/read/28921466/roles-of-hdacs-in-the-responses-of-innate-immune-cells-and-as-targets-in-inflammatory-diseases
#16
Yiqun Hu, Bandar Ali Suliman
Histone deacetylases (HDACs) are an emerging class of molecules involved in the epigenetic regulation of innate immune responses through Toll-like receptor (TLR) and interferon (IFN) signaling pathways. HDACs are also key drivers of inflammatory diseases via epigenetic regulation through chromatin DNA and histone modification by methylation and acetylation, among other mechanisms, which control innate immune cell gene expression. Importantly, these epigenetic changes are reversible, and HDACs may also be targeted by small-molecule HDAC inhibitors, which have been used in clinical settings for cancer therapy...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28918056/the-therapeutic-potential-of-crispr-cas9-systems-in-oncogene-addicted-cancer-types-virally-driven-cancers-as-a-model-system
#17
REVIEW
Luqman Jubair, Nigel A J McMillan
The field of gene editing is undergoing unprecedented growth. The first ex vivo human clinical trial in China started in 2016, more than 1000 US patents have been filed, and there is exponential growth in publications. The ability to edit genes with high fidelity is promising for the development of new treatments for a range of diseases, particularly inherited conditions, infectious diseases, and cancers. For cancer, a major issue is the identification of driver mutations and oncogenes to target for therapeutic effect, and this requires the development of robust models with which to prove their efficacy...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918044/targeted-disruption-of-v600e-mutant-braf-gene-by-crispr-cpf1
#18
Meijia Yang, Heng Wei, Yuelong Wang, Jiaojiao Deng, Yani Tang, Liangxue Zhou, Gang Guo, Aiping Tong
BRAF-V600E (1799T > A) is one of the most frequently reported driver mutations in multiple types of cancers, and patients with such mutations could benefit from selectively inactivating the mutant allele. Near this mutation site, there are two TTTN and one NGG protospacer-adjacent motifs (PAMs) for Cpf1 and Cas9 CRISPR nucleases, respectively. The 1799T > A substitution also leads to the occurrence of a novel NGNG PAM for the EQR variant of Cas9. We examined the editing efficacy and selectivity of Cpf1, Cas9, and EQR variant to this mutation site...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28916654/biallelic-dicer1%C3%A2-loss-mediated-by-ap2-cre-drives-angiosarcoma
#19
Jason A Hanna, Catherine J Drummond, Matthew R Garcia, Jonathan C Go, David Finkelstein, Jerold E Rehg, Mark E Hatley
Angiosarcoma is an aggressive vascular sarcoma with an extremely poor prognosis. Due to the relative rarity of this disease, its molecular drivers and optimal treatment strategies are obscure. DICER1 is an RNase III endoribonuclease central to microRNA biogenesis, and germline DICER1 mutations result in a cancer predisposition syndrome, associated with an increased risk of many tumor types. Here we show that biallelic Dicer1 deletion with aP2-Cre drives aggressive and metastatic angiosarcoma independent of other genetically engineered oncogenes or tumor suppressor loss...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28916652/lsd1-mediated-epigenetic-reprogramming-drives-cenpe-expression-and-prostate-cancer-progression
#20
Yi Liang, Musaddeque Ahmed, Haiyang Guo, Fraser Soares, Junjie T Hua, Shuai Gao, Catherine Lu, Christine Poon, Wanting Han, Jens Langstein, Muhammad B Ekram, Brian Li, Elai Davicioni, Mandeep Takhar, Nicholas Erho, R Jeffrey Karnes, Dianne Chadwick, Theodorus van der Kwast, Paul C Boutros, Cheryl H Arrowsmith, Felix Y Feng, Anthony Michael Joshua, Amina Zoubeidi, Changmeng Cai, Housheng H He
Androgen receptor (AR) signaling is a key driver of prostate cancer (PCa), and androgen-deprivation therapy (ADT) is a standard treatment for patients with advanced and metastatic disease. However, patients receiving ADT eventually develop incurable castration-resistant PCa (CRPC). Here we report that the chromatin modifier LSD1, an important regulator of AR transcriptional activity, undergoes epigenetic reprogramming in CRPC. LSD1 reprogramming in this setting activated a subset of cell cycle genes including CENPE, a centromere binding protein and mitotic kinesin...
September 15, 2017: Cancer Research
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