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https://www.readbyqxmd.com/read/27696085/transcriptomic-effects-of-adenosine-2a-receptor-deletion-in-healthy-and-endotoxemic-murine-myocardium
#1
Kevin J Ashton, Melissa E Reichelt, S Jamal Mustafa, Bunyen Teng, Catherine Ledent, Lea M D Delbridge, Polly A Hofmann, R Ray Morrison, John P Headrick
Influences of adenosine 2A receptor (A2AR) activity on the cardiac transcriptome and genesis of endotoxemic myocarditis are unclear. We applied transcriptomic profiling (39 K Affymetrix arrays) to identify A2AR-sensitive molecules, revealed by receptor knockout (KO), in healthy and endotoxemic hearts. Baseline cardiac function was unaltered and only 37 A2AR-sensitive genes modified by A2AR KO (≥1.2-fold change, <5 % FDR); the five most induced are Mtr, Ppbp, Chac1, Ctsk and Cnpy2 and the five most repressed are Hp, Yipf4, Acta1, Cidec and Map3k2...
September 30, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/27391150/cns-germinomas-are-characterized-by-global-demethylation-chromosomal-instability-and-mutational-activation-of-the-kit-ras-raf-erk-and-akt-pathways
#2
Simone Laura Schulte, Andreas Waha, Barbara Steiger, Dorota Denkhaus, Evelyn Dörner, Gabriele Calaminus, Ivo Leuschner, Torsten Pietsch
CNS germinomas represent a unique germ cell tumor entity characterized by undifferentiated tumor cells and a high response rate to current treatment protocols. Limited information is available on their underlying genomic, epigenetic and biological alterations. We performed a genome-wide analysis of genomic copy number alterations in 49 CNS germinomas by molecular inversion profiling. In addition, CpG dinucleotide methylation was studied by immunohistochemistry for methylated cytosine residues. Mutational analysis was performed by resequencing of candidate genes including KIT and RAS family members...
July 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27055474/germline-rras2-mutations-are-not-associated-with-noonan-syndrome
#3
John J Ceremsak, Ariel Yu, Emilio Esquivel, Christina Lissewski, Martin Zenker, Mignon L Loh, Elliot Stieglitz
No abstract text is available yet for this article.
April 7, 2016: Journal of Medical Genetics
https://www.readbyqxmd.com/read/26619011/identifying-recurrent-mutations-in-cancer-reveals-widespread-lineage-diversity-and-mutational-specificity
#4
Matthew T Chang, Saurabh Asthana, Sizhi Paul Gao, Byron H Lee, Jocelyn S Chapman, Cyriac Kandoth, JianJiong Gao, Nicholas D Socci, David B Solit, Adam B Olshen, Nikolaus Schultz, Barry S Taylor
Mutational hotspots indicate selective pressure across a population of tumor samples, but their prevalence within and across cancer types is incompletely characterized. An approach to detect significantly mutated residues, rather than methods that identify recurrently mutated genes, may uncover new biologically and therapeutically relevant driver mutations. Here, we developed a statistical algorithm to identify recurrently mutated residues in tumor samples. We applied the algorithm to 11,119 human tumors, spanning 41 cancer types, and identified 470 somatic substitution hotspots in 275 genes...
February 2016: Nature Biotechnology
https://www.readbyqxmd.com/read/26168291/genomic-landscape-of-carcinogen-induced-and-genetically-induced-mouse-skin-squamous-cell-carcinoma
#5
Dany Nassar, Mathilde Latil, Bram Boeckx, Diether Lambrechts, Cédric Blanpain
Mouse models of cancers are routinely used to study cancer biology. However, it remains unclear whether carcinogenesis in mice is driven by the same spectrum of genomic alterations found in humans. Here we conducted a comprehensive genomic analysis of 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced skin cancer, the most commonly used skin cancer model, which appears as benign papillomas that progress into squamous cell carcinomas (SCCs). We also studied genetically induced SCCs that expressed G12D mutant Kras (Kras G12D) but were deficient for p53...
August 2015: Nature Medicine
https://www.readbyqxmd.com/read/26035737/microrna-regulatory-mechanism-by-which-plla-aligned-nanofibers-influence-pc12-cell-differentiation
#6
Yadong Yu, Xiaoying Lü, Fei Ding
OBJECTIVE: Aligned nanofibers (AFs) are regarded as promising biomaterials in nerve tissue engineering. However, a full understanding of the biocompatibility of AFs at the molecular level is still challenging. Therefore, the present study focused on identifying the microRNA (miRNA)-mediated regulatory mechanism by which poly-L-lactic acid (PLLA) AFs influence PC12 cell differentiation. APPROACH: Firstly, the effects of PLLA random nanofibers (RFs)/AFs and PLLA films (control) on the biological responses of PC12 cells that are associated with neuronal differentiation were examined...
August 2015: Journal of Neural Engineering
https://www.readbyqxmd.com/read/24391759/uva-and-uvb-irradiation-differentially-regulate-microrna-expression-in-human-primary-keratinocytes
#7
Anne Kraemer, I-Peng Chen, Stefan Henning, Alexandra Faust, Beate Volkmer, Michael J Atkinson, Simone Moertl, Ruediger Greinert
MicroRNA (miRNA)-mediated regulation of the cellular transcriptome is an important epigenetic mechanism for fine-tuning regulatory pathways. These include processes related to skin cancer development, progression and metastasis. However, little is known about the role of microRNA as an intermediary in the carcinogenic processes following exposure to UV-radiation. We now show that UV irradiation of human primary keratinocytes modulates the expression of several cellular miRNAs. A common set of miRNAs was influenced by exposure to both UVA and UVB...
2013: PloS One
https://www.readbyqxmd.com/read/24148564/r-ras2-overexpression-in-tumors-of-the-human-central-nervous-system
#8
Sylvia Gutierrez-Erlandsson, Pedro Herrero-Vidal, Marcos Fernandez-Alfara, Susana Hernandez-Garcia, Sandra Gonzalo-Flores, Alberto Mudarra-Rubio, Manuel Fresno, Beatriz Cubelos
Malignant tumors of the central nervous system (CNS) are the 10th most frequent cause of cancer mortality. Despite the strong malignancy of some such tumors, oncogenic mutations are rarely found in classic members of the RAS family of small GTPases. This raises the question as to whether other RAS family members may be affected in CNS tumors, excessively activating RAS pathways. The RAS-related subfamily of GTPases is that which is most closely related to classical Ras and it currently contains 3 members: RRAS, RRAS2 and RRAS3...
2013: Molecular Cancer
https://www.readbyqxmd.com/read/22790196/rras2-rhog-and-t-cell-phagocytosis
#9
Balbino Alarcón, Nuria Martínez-Martín
Activating mutations and overexpression of classical Ras subfamily members (K-Ras, N-Ras and H-Ras) have been widely investigated as key events in the development of human cancers. The role in cancer of its closest relatives, the Ras-related (RRas) subfamily members, has been less studied despite the fact that one of its members (TC21 or RRas2) is strongly transforming in vitro. Nevertheless, and in spite the paucity of publications, several studies have shown that wild type TC21 is overexpressed in different types of carcinomas and lymphomas...
April 2012: Small GTPases
https://www.readbyqxmd.com/read/22535521/the-ras-like-protein-r-ras2-tc21-is-important-for-proper-mammary-gland-development
#10
Romain M Larive, Antonio Abad, Clara M Cardaba, Teresa Hernández, Marta Cañamero, Enrique de Álava, Eugenio Santos, Balbino Alarcón, Xosé R Bustelo
R-Ras2/TC21 is a GTPase with high sequence and signaling similarity with Ras subfamily members. Although it has been extensively studied using overexpression studies in cell lines, its physiological role remains poorly characterized. Here we used RRas2-knockout mice expressing β-galactosidase under the regulation of the endogenous RRas2 promoter to investigate the function of this GTPase in vivo. Despite its expression in tissues critical for organismal viability, RRas2(-/-) mice show no major alterations in viability, growth rates, cardiovascular parameters, or fertility...
June 2012: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/21820331/t-cell-receptor-internalization-from-the-immunological-synapse-is-mediated-by-tc21-and-rhog-gtpase-dependent-phagocytosis
#11
Nuria Martínez-Martín, Elena Fernández-Arenas, Saso Cemerski, Pilar Delgado, Martin Turner, John Heuser, Darrell J Irvine, Bonnie Huang, Xosé R Bustelo, Andrey Shaw, Balbino Alarcón
The immunological synapse (IS) serves a dual role for sustained T cell receptor (TCR) signaling and for TCR downregulation. TC21 (Rras2) is a RRas subfamily GTPase that constitutively associates with the TCR and is implicated in tonic TCR signaling by activating phosphatidylinositol 3-kinase. In this study, we demonstrate that TC21 both cotranslocates with the TCR to the IS and is necessary for TCR internalization from the IS through a mechanism dependent on RhoG, a small GTPase previously associated with phagocytosis...
August 26, 2011: Immunity
https://www.readbyqxmd.com/read/21793795/%C3%AE-thalassemia-trait-association-with-autoimmune-diseases-%C3%AE-globin-locus-proximity-to-the-immunity-genes-or-role-of-hemorphins
#12
REVIEW
Meric A Altinoz, Gunduz Gedikoglu, Gunnur Deniz
Thalassemia major continues to be a significant health problem for Mediterranean, Afro-Arabic countries, India and South Easth Asia. It was generally assumed that the β-thalassemia heterozygotes do not bear significant medical risks except a mild microcytic anemia. Nonetheless, increasing number of reports associate β-thalassemia trait with autoimmune conditions, nephritis, diabetes, arthritis, fibromyalgia and asthma. Available sparse data indicate reduced incidence of systemic lupus erythematosus (SLE) in β-thalassemia heterozygotes; yet, if two conditions coexist, the SLE manifestations occur much severer...
April 2012: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/21482774/genome-wide-functional-screen-identifies-a-compendium-of-genes-affecting-sensitivity-to-tamoxifen
#13
Ana M Mendes-Pereira, David Sims, Tim Dexter, Kerry Fenwick, Ioannis Assiotis, Iwanka Kozarewa, Costas Mitsopoulos, Jarle Hakas, Marketa Zvelebil, Christopher J Lord, Alan Ashworth
Therapies that target estrogen signaling have made a very considerable contribution to reducing mortality from breast cancer. However, resistance to tamoxifen remains a major clinical problem. Here we have used a genome-wide functional profiling approach to identify multiple genes that confer resistance or sensitivity to tamoxifen. Combining whole-genome shRNA screening with massively parallel sequencing, we have profiled the impact of more than 56,670 RNA interference reagents targeting 16,487 genes on the cellular response to tamoxifen...
February 21, 2012: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/21085126/snps-in-axon-guidance-pathway-genes-and-susceptibility-for-parkinson-s-disease-in-the-korean-population
#14
Jong-Min Kim, Sue K Park, Jae Jeong Yang, Eun-Soon Shin, Jee-Young Lee, Ji Young Yun, Ji Seon Kim, Sung Sup Park, Beom S Jeon
Single-nucleotide polymorphisms (SNPs) in genes of the axon guidance pathway have been reported to be a possible susceptibility factor for Parkinson's disease (PD). This study investigated whether the genetic variability in the axon guidance pathway is a susceptibility factor in PD patients in the Korean population. A total of 373 patients and 384 healthy subjects were included. A set of 22 SNPs was analyzed, and the risk of PD was evaluated using odds ratios in an unconditional and conditional logistic regression models of age- and gender-matched subsets...
February 2011: Journal of Human Genetics
https://www.readbyqxmd.com/read/19561613/essential-function-for-the-gtpase-tc21-in-homeostatic-antigen-receptor-signaling
#15
Pilar Delgado, Beatriz Cubelos, Enrique Calleja, Nuria Martínez-Martín, Angel Ciprés, Isabel Mérida, Carmen Bellas, Xosé R Bustelo, Balbino Alarcón
T cell antigen receptors (TCRs) and B cell antigen receptors (BCRs) transmit low-grade signals necessary for the survival and maintenance of mature cell pools. We show here that TC21, a small GTPase encoded by Rras2, interacted constitutively with both kinds of receptors. Expression of a dominant negative TC21 mutant in T cells produced a rapid decrease in cell viability, and Rras2(-/-) mice were lymphopenic, possibly as a result of diminished homeostatic proliferation and impaired T cell and B cell survival...
August 2009: Nature Immunology
https://www.readbyqxmd.com/read/19032775/egr1-regulates-the-coordinated-expression-of-numerous-egf-receptor-target-genes-as-identified-by-chip-on-chip
#16
Shilpi Arora, Yipeng Wang, Zhenyu Jia, Saynur Vardar-Sengul, Ayla Munawar, Kutbuddin S Doctor, Michael Birrer, Michael McClelland, Eileen Adamson, Dan Mercola
BACKGROUND: UV irradiation activates the epidermal growth factor receptor, induces Egr1 expression and promotes apoptosis in a variety of cell types. We examined the hypothesis that Egr1 regulates genes that mediate this process by use of a chip-on-chip protocol in human tumorigenic prostate M12 cells. RESULTS: UV irradiation led to significant binding of 288 gene promoters by Egr1. A major functional subgroup consisted of apoptosis related genes. The largest subgroup of 24 genes belongs to the epidermal growth factor receptor-signal transduction pathway...
2008: Genome Biology
https://www.readbyqxmd.com/read/17312387/basic-transcription-factor-3-btf3-regulates-transcription-of-tumor-associated-genes-in-pancreatic-cancer-cells
#17
Grace Kusumawidjaja, Hany Kayed, Nathalia Giese, Andrea Bauer, Mert Erkan, Thomas Giese, Jörg D Hoheise, Helmut Friess, Jörg Kleeff
Basic transcription factor 3 (BTF3) acts as a transcription factor and modulator of apoptosis, and is differentially expressed in colorectal cancer and glioblastomas. In the present study, the expression of BTF3, as well as its role in apoptosis and gene transcription, was analyzed in pancreatic ductal adenocarcinoma (PDAC). QRT-PCR, immunohistochemistry, immunoblotting, and immunofluorescence analyses were carried out to investigate BTF3 mRNA/protein expression and localization. BTF3 silencing in pancreatic cancer cells was performed using specific siRNA molecules...
March 2007: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/12525640/genome-based-identification-of-cancer-genes-by-proviral-tagging-in-mouse-retrovirus-induced-t-cell-lymphomas
#18
Rachel Kim, Alla Trubetskoy, Takeshi Suzuki, Nancy A Jenkins, Neal G Copeland, Jack Lenz
The identification of tumor-inducing genes is a driving force for elucidating the molecular mechanisms underlying cancer. Many retroviruses induce tumors by insertion of viral DNA adjacent to cellular oncogenes, resulting in altered expression and/or structure of the encoded proteins. The availability of the mouse genome sequence now allows analysis of retroviral common integration sites in murine tumors to be used as a genetic screen for identification of large numbers of candidate cancer genes. By positioning the sequences of inverse PCR-amplified, virus-host junction fragments within the mouse genome, 19 target genes were identified in T-cell lymphomas induced by the retrovirus SL3-3...
February 2003: Journal of Virology
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