Read by QxMD icon Read

actionable mutation

J H Francis, T Milman, H Grossniklaus, D M Albert, R Folberg, G M Levitin, S E Coupland, F Catalanotti, D Rabady, C Kandoth, K J Busam, D H Abramson
PURPOSE: GNAQ mutations have been identified in port wine stains (both syndromic and non-syndromic) and melanocytic ocular neoplasms. This study investigates the presence of GNAQ mutations in diffuse- (those associated with Sturge-Weber syndrome (SWS)) and solitary choroidal hemangiomas. PARTICIPANTS: Tissue from 11 patients with the following diagnoses: port wine stain (n = 3), diffuse choroidal hemangioma (n = 1), solitary choroidal hemangioma (n = 6), choroidal nevus (n =1) METHODS: Ten specimens were interrogated with Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT), a hybridization capture-based next-generation sequencing assay for targeted deep sequencing of all exons and selected introns of 468 key cancer genes in formalin-fixed, paraffin-embedded tumors...
December 8, 2018: Ophthalmology
Xuandi Zhang, Guo-Ning Zhang, Yujia Wang, Mei Zhu, Juxian Wang, Ziqiang Li, Donghui Li, Shan Cen, Yucheng Wang
Influenza A virus (IAV), a highly pathogenic virus to human beings, is most susceptible to mutation and thus causes rapid, severe global pandemics resulting in millions of fatalities worldwide. Since resistance to the existing anti-influenza drugs is developing, innovative inhibitors with a different mode of action are urgently needed. The lead compound 6092B-E5 has proven to be an effective antiviral reagent in our previous work. Using the principles of substitution and bioisosterism of the indole ring, six series of novel anti-IAV target products were designed, synthesized and evaluated for their antiviral effect in this work...
December 9, 2018: Chemistry & Biodiversity
L H Pottenger, G Boysen, K Brown, J Cadet, R P Fuchs, G E Johnson, J A Swenberg
The interpretation and significance of DNA adduct data, their causal relationship to mutations, and their role in risk assessment have been debated for many years. An extended effort to identify key questions and collect relevant data to address them was focused on the ubiquitous low MW N7-alkyl/hydroxyalkylguanine adducts. Several academic, governmental, and industrial laboratories collaborated to gather new data aimed at better understanding the role and potential impact of these adducts in quantifiable genotoxic events (gene mutations/micronucleus)...
December 10, 2018: Environmental and Molecular Mutagenesis
Suk-Chul Bae, Arun Mouli Kolinjivadi, Yoshiaki Ito
RUNX genes belong to a three-membered family of transcription factors, which are well established as master regulators of development. Of them, aberrations in RUNX3 expression are frequently observed in human malignancies primarily due to epigenetic silencing which is often overlooked. At the G1 phase of the cell cycle, RUNX3 regulates the restriction (R)-point, a mechanism that decides cell cycle entry. Deregulation at the R-point or loss of RUNX3 results in premature entry into S phase, leading to a proliferative advantage...
December 11, 2018: Journal of Molecular Cell Biology
Dirk Jan Stenvers, Frank A J L Scheer, Patrick Schrauwen, Susanne E la Fleur, Andries Kalsbeek
Insulin resistance is a main determinant in the development of type 2 diabetes mellitus and a major cause of morbidity and mortality. The circadian timing system consists of a central brain clock in the hypothalamic suprachiasmatic nucleus and various peripheral tissue clocks. The circadian timing system is responsible for the coordination of many daily processes, including the daily rhythm in human glucose metabolism. The central clock regulates food intake, energy expenditure and whole-body insulin sensitivity, and these actions are further fine-tuned by local peripheral clocks...
December 7, 2018: Nature Reviews. Endocrinology
Ohoud Al Mohareb, Mussa H Al Malki, O Thomas Mueller, Imad Brema
Resistance to thyroid hormone-beta (RTHbeta) is a rare inherited syndrome characterized by variable reduced tissue responsiveness to the intracellular action of triiodothyronine (T3), the active form of the thyroid hormone. The presentation of RTHbeta is quite variable and mutations in the thyroid hormone receptor beta (THR-B) gene have been detected in up to 90% of patients. The proband was a 34-year-old Jordanian male who presented with intermittent palpitations. His thyroid function tests (TFTs) showed a discordant profile with high free T4 (FT4) at 45...
December 5, 2018: Endocrinology, Diabetes & Metabolism Case Reports
Yannan Fan, Sehrish K Bazai, Fabrice Daian, Maria Arechederra, Sylvie Richelme, Nuri A Temiz, Annie Yim, Bianca H Habermann, Rosanna Dono, David A Largaespada, Flavio Maina
BACKGROUND & AIMS: The variety of alterations found in hepatocellular carcinoma (HCC) challenges the identification of functionally relevant genes and their combinatorial actions in tumorigenesis. Deregulation of Receptor Tyrosine Kinases (RTKs) is frequent in HCC, yet little is known about the molecular events that cooperate with RTKs and whether these cooperative events play an active role at the root of liver tumorigenesis. METHODS: A forward genetic screen was performed using Sleeping Beauty transposon insertional mutagenesis to accelerate liver tumour formation in a genetic context in which subtly increased MET RTK levels predispose towards tumorigenesis...
December 5, 2018: Journal of Hepatology
Arnaud Depeyre, Matthias Schlund, Romain Nicot, Joel Ferri
One of the most common causes of short stature is a defect of the short stature homeobox-containing (SHOX) gene, which is located in pseudoautosomal region 1 on the distal end of the short arm of chromosomes Xp22.33 and Yp11.32. More than 300 different mutations in the SHOX gene responsible for short stature syndrome have been described. The phenotypic expression of SHOX haploinsufficiency is remarkably varied. The 3 typical clinical presentations, from least to most severe, are idiopathic short stature without skeletal malformations, Leri-Weill dyschondrosteosis (LWD), and Langer mesomelic dysplasia, which is believed to represent the homozygous form of LWD...
November 12, 2018: Journal of Oral and Maxillofacial Surgery
Di Wu, Rui Guo, Huiling Guo, Yushu Li, Haixia Guan, Zhongyan Shan
BACKGROUND: Resistance to thyroid hormone beta (RTHβ) results in symptoms of both increased and decreased thyroid hormone action. The effect of thyroid hormone changes in different types of autoimmune thyroid disease (AITD) in RTHβ is dynamic. CASE PRESENTATION: A 25-year-old Asian female had a RTHβ Y321C mutation with Hashimoto's thyroiditis and type 2 diabetes mellitus. She was followed-up through gestation and two years postpartum, revealing development of postpartum thyroiditis (PPT) with characteristic wide fluctuations in serum thyrotropin levels, and of spontaneous recovery from an episode of transient hypothyroidism...
December 3, 2018: BMC Pregnancy and Childbirth
Meghan Robinson, Ian Fraser, Emily McKee, Kali Scheck, Lillian Chang, Stephanie M Willerth
Cellular transdifferentiation changes mature cells from one phenotype into another by altering their gene expression patterns. Manipulating expression of transcription factors, proteins that bind to DNA promoter regions, regulates the levels of key developmental genes. Viral delivery of transcription factors can efficiently reprogram somatic cells, but this method possesses undesirable side effects, including mutations leading to oncogenesis. Using protein transduction domains (PTDs) fused to transcription factors to deliver exogenous transcription factors serves as an alternative strategy that avoids the issues associated with DNA integration into the host genome...
2018: Frontiers in Bioengineering and Biotechnology
Sònia Martínez-Servat, Daniel Yero, Pol Huedo, Roser Marquez, Gara Molina, Xavier Daura, Isidre Gibert
The polymyxin antibiotic colistin shows in vitro activity against Stenotrophomonas maltophilia . However, an increased incidence of colistin-resistant isolates has been recently observed. In addition, in vitro evaluation of colistin susceptibility for this organism has been problematic. The aims of this study were to investigate the colistin-resistance phenotypes displayed by S. maltophilia and their potential association with the challenging determination of colistin susceptibilities for this organism by even the recommended method...
2018: Frontiers in Microbiology
Antoine Italiano
Soft-tissue sarcomas represent a heterogeneous group of diseases accounting for up to 1% of cancer in adults and 15% of cancer in children. Introduction of next-generation sequencing (NGS) technologies has allowed to gain additional insight into the genetic diversity and complexity of sarcomas, including the potential therapeutic implications of some genetic alterations.Two large studies have investigated the role of targeted NGS to identify actionable mutations in patients with soft-tissue sarcomas. In these two studies, actionable alterations were identified in up to 50% of patients...
December 7, 2018: Current Treatment Options in Oncology
Xin Chen, Zhixiong Chen, Bin Zheng, Wei Tang
Castration-resistant prostate cancer (CRPC) lacks effective treatment, and studies have shown that PARPi inhibitors, such as Olaparib, are somewhat effective; however, the efficacy of Olaparib in CRPC still needs to be further improved. Nitrogen permease regulator-like 2 (NPRL2) is reported to be a tumor suppressor candidate gene and is closely related to the DNA repair pathway, which can affect the sensitivity of many chemotherapeutic drugs. However, there is no research on whether NPRL2 is associated with sensitivity to Olaparib...
December 3, 2018: Biochemical and Biophysical Research Communications
Kyung Hwa Choi, Jeong Yong Jeon, Young-Eun Lee, Seung Won Kim, Sang Yong Kim, Yeo Jin Yun, Ki Cheong Park
Advanced cancer has been shown to be associated with a higher percentage of epigenetic changes than with genetic mutations. Preclinical models have shown that the combination of paclitaxel, sorafenib, and radiation therapy (RT) plays a crucial role in renal cell carcinoma (RCC) and breast cancer. This study aimed to investigate the involvement of mitochondrial cytochrome c-dependent apoptosis in the mechanism of action of a combination of paclitaxel, sorafenib, and RT in RCC and breast cancer. RCC and breast cancer cell lines were exposed to paclitaxel and sorafenib alone or combined in the presence of radiation, and cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay...
December 3, 2018: Translational Oncology
Erica S Tsang, Yaoqing Shen, Negar Chooback, Cheryl Ho, Martin Jones, Daniel J Renouf, Howard Lim, Sophie Sun, Stephen Yip, Erin Pleasance, Diana N Ionescu, Karen Mungall, Katayoon Kasaian, Yussanne Ma, Yongjun Zhao, Andrew Mungall, Richard Moore, Steven J M Jones, Marco Marra, Janessa Laskin
BACKGROUND: The Personalized OncoGenomics (POG) program at the British Columbia Cancer Agency integrates whole genome (DNA) and RNA sequencing into practice for metastatic malignancies. We examined the subgroup of patients with metastatic non-small cell lung cancer (NSCLC) and report the prevalence of actionable targets, treatments, and outcomes. METHODS: We identified patients who were enrolled in the POG program between 2012-2016 who had a tumor biopsy and blood samples with comprehensive DNA (80X;40X normal) and RNA sequencing followed by in-depth bioinformatics to identify potential cancer drivers and actionable targets...
December 4, 2018: Cold Spring Harbor Molecular Case Studies
Tajudeen O Yahaya, Titilola F Salisu
INTRODUCTION: Scientists are considering the possibility of treating diabetes mellitus (DM) using a personalized approach in which various forms of the diseases will be treated based on the causal gene and its pathogenesis. To this end, scientists have identified mutations in certain genes as probable causes of Type 2 diabetes mellitus (T2DM) with diverse mechanisms. AIM: This review was aimed at articulating already identified T2DM genes with their mechanisms of action and phenotypic presentations for the awareness of all stakeholders...
December 4, 2018: Current Diabetes Reviews
Tanja Mesti, Nadia Bouchemal, Claire Banissi, Mohamed N Triba, Carole Marbeuf-Gueye, Maja Cemazar, Laurence Le Moyec, Antoine F Carpentier, Philippe Savarin, Janja Ocvirk
Background Malignant gliomas are rapidly growing tumours that extensively invade the brain and have bad prognosis. Our study was performed to assess the metabolic effects of bevacizumab on the glioma cells carrying the IDH1 mutation, a mutation, associated with better prognosis and treatment outcome. Bevacizumab is known to inhibit tumour growth by neutralizing the biological activity of vascular endothelial growth factor (VEGF). However, the direct effects of bevacizumab on tumour cells metabolism remain poorly known...
November 26, 2018: Radiology and Oncology
Michal Halpert, Varda Liveanu, Fabian Glaser, Gadi Schuster
Arabidopsis chloroplast RNase J displaces both exo- and endo-ribonucleolytic activities and contains a unique GT-1 DNA binding domain. Control of chloroplast gene expression is predominantly at the post-transcriptional level via the coordinated action of nuclear encoded ribonucleases and RNA-binding proteins. The 5' end maturation of mRNAs ascribed to the combined action of 5'→3' exoribonuclease and gene-specific RNA-binding proteins of the pentatricopeptide repeat family and others that impede the progression of this nuclease...
December 3, 2018: Plant Molecular Biology
Ryan E Schaub, Krizia M Perez-Medina, Kathleen T Hackett, Daniel L Garcia, Joseph P Dillard
Neisseria gonorrhoeae releases peptidoglycan fragments during growth, and these molecules induce an inflammatory response in the human host. The proinflammatory molecules include peptidoglycan monomers, peptidoglycan dimers, and free peptides. These molecules can be released by the actions of lytic transglycosylases or an amidase. However, over 40% of the gonococcal cell wall is crosslinked, where the peptide stem on one peptidoglycan strand is linked to the peptide stem on a neighboring strand, suggesting that endopeptidases may be required for release of many peptidoglycan fragments...
December 3, 2018: Infection and Immunity
Maria Luisa Romero Romero, Fan Yang, Yu-Ru Lin, Agnes Toth-Petroczy, Igor N Berezovsky, Alexander Goncearenco, Wen Yang, Alon Wellner, Fanindra Kumar-Deshmukh, Michal Sharon, David Baker, Gabriele Varani, Dan S Tawfik
Abundant and essential motifs, such as phosphate-binding loops (P-loops), are presumed to be the seeds of modern enzymes. The Walker-A P-loop is absolutely essential in modern NTPase enzymes, in mediating binding, and transfer of the terminal phosphate groups of NTPs. However, NTPase function depends on many additional active-site residues placed throughout the protein's scaffold. Can motifs such as P-loops confer function in a simpler context? We applied a phylogenetic analysis that yielded a sequence logo of the putative ancestral Walker-A P-loop element: a β-strand connected to an α-helix via the P-loop...
November 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"