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1.
Neurooncol Pract ; 6(3): 226-236, 2019 May.
Article in English | MEDLINE | ID: mdl-31385996

ABSTRACT

BACKGROUND: Brain cancer has a strong impact on health-related quality of life (HRQoL), and its evaluation in clinical practice can improve the quality of care provided. The aim of this project was to integrate routine collection of HRQoL information from patients with brain tumor or metastasis in 2 specialized United Kingdom tertiary centers, and to evaluate the implementation process. METHODS: Since October 2016, routine collection of electronic self-reported HRQoL information has been progressively embedded in the participating centers using standard questionnaires. During the first year, the project was implemented, and the process evaluated, through regular cycles of process evaluation followed by an action plan, monitoring of questionnaire completion rates, and assessment of patient views. RESULTS: Main challenges encountered included reluctance to change usual practice and limited resources. Key measures for success included strong leadership of senior staff, involvement of stakeholders in project design and evaluation, and continuous strategic support to professionals. Final project workflow included 6 process steps, 1 decision step, and 4 outputs. Questionnaires were mostly self-completed (75.1%), and completion took 6-9 minutes. Most patients agreed that the questionnaire items were easy to understand (97.0%), important for them (93.0%), and helped them think what they wanted to discuss in their clinical consultation (75.4%). CONCLUSIONS: Integrating HRQoL information as a routine part of clinical assessments has the potential to enhance individually tailored patient care in our institutions. Challenges involved in innovations of this nature can be overcome through a systematic approach involving strong leadership, wide stakeholder engagement, and strategic planning.

2.
Chem Commun (Camb) ; 55(39): 5627-5630, 2019 May 09.
Article in English | MEDLINE | ID: mdl-31025680

ABSTRACT

The reversible photocontrol of an enzyme governing blood coagulation is demonstrated. The thrombin binding aptamer (TBA), was rendered photochromic by modification with two anthracene groups. Light-triggered anthracene photodimerisation distorts its structure, inhibiting binding of the enzyme thrombin, which in turn triggers catalysis and the resulting clotting process.


Subject(s)
Aptamers, Nucleotide/metabolism , G-Quadruplexes , Thrombin/metabolism , Ultraviolet Rays , Anthracenes/chemistry , Aptamers, Nucleotide/chemistry , Biocatalysis , Blood Coagulation , Circular Dichroism , Dimerization , Humans , Protein Binding , Temperature , Thrombin/chemistry
3.
ACS Chem Biol ; 11(3): 717-21, 2016 Mar 18.
Article in English | MEDLINE | ID: mdl-26580817

ABSTRACT

The ability to discriminate between epigenetic variants in DNA is a necessary tool if we are to increase our understanding of the roles that they play in various biological processes and medical conditions. Herein, it is demonstrated how a simple two-step fluorescent probe assay can be used to differentiate all three major epigenetic variants of cytosine at a single locus site in a target strand of DNA.


Subject(s)
5-Methylcytosine/chemistry , Anthracenes/chemistry , Cytosine/analogs & derivatives , Cytosine/chemistry , DNA/chemistry , Fluorescent Dyes/chemistry , Nucleic Acid Conformation
4.
Chem Commun (Camb) ; 51(38): 8130-3, 2015 May 11.
Article in English | MEDLINE | ID: mdl-25872872

ABSTRACT

The unprecedented use of anthracene photodimerization within a protein or peptide system is explored through its incorporation into a DNA-binding peptide, derived from the GCN4 transcription factor. This study demonstrates an effective and dynamic interplay between a photoreaction and a peptide-DNA assembly, with each process able to exert control over the other.


Subject(s)
Anthracenes/chemistry , Basic-Leucine Zipper Transcription Factors/chemistry , DNA/chemistry , Peptides/chemistry , Saccharomyces cerevisiae Proteins/chemistry , Ultraviolet Rays , Binding Sites , Dimerization , Photochemical Processes
5.
J Inorg Biochem ; 117: 298-305, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22902235

ABSTRACT

The coordination of the therapeutically interesting [AuCl(PEt(3))] to the de novo designed peptide, TRIL23C, under aqueous conditions, is reported here. TRIL23C represents an ideal model to investigate the binding of [AuCl(PEt(3))] to small proteins in an effort to develop novel gold(I) phosphine peptide adducts capable of mimicking biological recognition and targeting. This is due to the small size of TRIL23C (30 amino acids), yet stable secondary and tertiary fold, symmetric nature and the availability of only one thiol binding site. [AuCl(PEt(3))] was found to react readily with the Cys side chain in a 1:1 ratio as confirmed by UV-visible, (31)P NMR and mass spectrometry. Circular dichroism confirmed that the coiled coil structure was retained on coordination of the {Au(PEt(3))}(+) unit. Redesign of the exterior of TRIL23C based on a biologically relevant recognition sequence found in GCN4, did not alter the coordination chemistry of [AuCl(PEt(3))]. To the best of our knowledge, this represents the first report on the coordination of gold(I) phosphine compounds to de novo designed peptides, and could lead to the generation of novel gold(I) phosphine peptide therapeutics in the future.


Subject(s)
Coordination Complexes/chemistry , Gold/chemistry , Organogold Compounds/chemistry , Peptides/chemistry , Phosphines/chemistry , Amino Acid Sequence , Circular Dichroism , Models, Molecular , Molecular Sequence Data , Protein Conformation , Protein Folding , Protein Structure, Secondary , Spectrometry, Mass, Electrospray Ionization
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