Recent submissions
Now showing items 501-520 of 4698
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Codon-specific KRAS mutations predict survival benefit of trifluridine/tipiracil in metastatic colorectal cancer.
(NATURE PORTFOLIO, 2023-03-01)Genomics has greatly improved how patients with cancer are being treated; however, clinical-grade genomic biomarkers for chemotherapies are currently lacking. Using whole-genome analysis of 37 patients with metastatic ... -
Expression of Mitochondrial Cytochrome C Oxidase Chaperone Gene (COX20) Improves Tolerance to Weak Acid and Oxidative Stress during Yeast Fermentation.
(PUBLIC LIBRARY SCIENCE, 2015-10-01)INTRODUCTION: Saccharomyces cerevisiae is the micro-organism of choice for the conversion of fermentable sugars released by the pre-treatment of lignocellulosic material into bioethanol. Pre-treatment of lignocellulosic ... -
Phase I Study of the Novel Enhancer of Zeste Homolog 2 (EZH2) Inhibitor GSK2816126 in Patients with Advanced Hematologic and Solid Tumors.
(AMER ASSOC CANCER RESEARCH, 2019-12-15)PURPOSE: Enhancer of zeste homolog 2 (EZH2) activity is dysregulated in many cancers. PATIENTS AND METHODS: This phase I study determined the safety, maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of ... -
Phase 1/2a trial of intravenous BAL101553, a novel controller of the spindle assembly checkpoint, in advanced solid tumours.
(SPRINGERNATURE, 2020-08-03)BACKGROUND: BAL101553 (lisavanbulin), the lysine prodrug of BAL27862 (avanbulin), exhibits broad anti-proliferative activity in human cancer models refractory to clinically relevant microtubule-targeting agents. METHODS: ... -
First-in-human study of the safety, pharmacokinetics, and pharmacodynamics of first-in-class fatty acid synthase inhibitor TVB-2640 alone and with a taxane in advanced tumors.
(ELSEVIER, 2021-04-01)BACKGROUND: We conducted a first-in-human dose-escalation study with the oral FASN inhibitor TVB-2640 to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), as monotherapy and with a taxane. ... -
Ceralasertib (AZD6738), an Oral ATR Kinase Inhibitor, in Combination with Carboplatin in Patients with Advanced Solid Tumors: A Phase I Study.
(AMER ASSOC CANCER RESEARCH, 2021-10-01)PURPOSE: This study reports the safety, tolerability, MTD, recommended phase II dose (RP2D), pharmacokinetic/pharmacodynamic profile, and preliminary antitumor activity of ceralasertib combined with carboplatin in patients ... -
Utility of polygenic risk scores in UK cancer screening: a modelling analysis.
(ELSEVIER SCIENCE INC, 2023-05-10)BACKGROUND: It is proposed that, through restriction to individuals delineated as high risk, polygenic risk scores (PRSs) might enable more efficient targeting of existing cancer screening programmes and enable extension ... -
A Phase 1/2 trial of SRA737 (a Chk1 inhibitor) administered orally in patients with advanced cancer.
(SPRINGERNATURE, 2023-07-27)BACKGROUND: This was a first-in-human Phase 1/2 open-label dose-escalation study of the novel checkpoint kinase 1 (Chk1) inhibitor SRA737. METHODS: Patients with advanced solid tumours enrolled in dose-escalation cohorts ... -
The EN-TEx resource of multi-tissue personal epigenomes & variant-impact models.
(CELL PRESS, 2023-03-30)Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on a single haploid reference genome. Here, we present the EN-TEx resource of 1,635 ... -
Structural basis of catalytic activation in human splicing.
(NATURE PORTFOLIO, 2023-05-25)Pre-mRNA splicing follows a pathway driven by ATP-dependent RNA helicases. A crucial event of the splicing pathway is the catalytic activation, which takes place at the transition between the activated Bact and the ... -
Structural basis of intron selection by U2 snRNP in the presence of covalent inhibitors
(Springer Science and Business Media LLC, 2021-07-23)<jats:title>Abstract</jats:title><jats:p>Intron selection during the formation of prespliceosomes is a critical event in pre-mRNA splicing. Chemical modulation of intron selection has emerged as a route for cancer therapy. ... -
Roles of Elongator Dependent tRNA Modification Pathways in Neurodegeneration and Cancer.
(MDPI, 2018-12-28)Transfer RNA (tRNA) is subject to a multitude of posttranscriptional modifications which can profoundly impact its functionality as the essential adaptor molecule in messenger RNA (mRNA) translation. Therefore, dynamic ... -
A Role for COX20 in Tolerance to Oxidative Stress and Programmed Cell Death in Saccharomyces cerevisiae.
(MDPI, 2019-11-18)Industrial production of bioethanol from lignocellulosic materials (LCM's) is reliant on a microorganism being tolerant to the stresses inherent to fermentation. Previous work has highlighted the importance of a cytochrome ... -
Redox requirements for ubiquitin-like urmylation of Ahp1, a 2-Cys peroxiredoxin from yeast.
(ELSEVIER, 2020-02-01)The yeast peroxiredoxin Ahp1, like related anti-oxidant enzymes in other species, undergoes urmylation, a lysine-directed conjugation to ubiquitin-like modifier Urm1. Ahp1 assembles into a homodimer that detoxifies peroxides ... -
Molecular basis for the bifunctional Uba4-Urm1 sulfur-relay system in tRNA thiolation and ubiquitin-like conjugation.
(WILEY, 2020-10-01)The chemical modification of tRNA bases by sulfur is crucial to tune translation and to optimize protein synthesis. In eukaryotes, the ubiquitin-related modifier 1 (Urm1) pathway is responsible for the synthesis of 2-thiolated ... -
Urm1, not quite a ubiquitin-like modifier?
(SHARED SCIENCE PUBLISHERS OG, 2021-11-01)Ubiquitin related modifier 1 (Urm1) is a unique eukaryotic member of the ubiquitin-fold (UbF) protein family and conserved from yeast to humans. Urm1 is dual-functional, acting both as a sulfur carrier for thiolation of ... -
E2/E3-independent ubiquitin-like protein conjugation by Urm1 is directly coupled to cysteine persulfidation.
(WILEY, 2022-10-17)Post-translational modifications by ubiquitin-like proteins (UBLs) are essential for nearly all cellular processes. Ubiquitin-related modifier 1 (Urm1) is a unique UBL, which plays a key role in tRNA anticodon thiolation ... -
Identifying and characterising Thrap3, Bclaf1 and Erh interactions using cross-linking mass spectrometry
(F1000 Research Ltd, 2023-01-06)<ns3:p><ns3:bold>Background: </ns3:bold>Cross-linking mass spectrometry (XL-MS) is a powerful technology capable of yielding structural insights across the complex cellular protein interaction network. However, up to date ... -
Regulators of male and female sexual development are critical for the transmission of a malaria parasite.
(CELL PRESS, 2023-02-08)Malaria transmission to mosquitoes requires a developmental switch in asexually dividing blood-stage parasites to sexual reproduction. In Plasmodium berghei, the transcription factor AP2-G is required and sufficient for ...