Introduction
Colorectal cancer (CRC) is a highly heterogeneous disease, with pathologically similar cancers having completely different responses to treatment and patient survival. Intra-tumour ...heterogeneity (defined as distinct morphological and phenotypic differences) has recently been demonstrated to be an important factor in the development and behaviour of cancer cells and can be used to determine response to anticancer therapy.
Method
Patients with resected CRC had DNA extracted from eight defined tumour areas which were analysed for two genetic mutations (BRAF and KRAS) and one epigenetic trait (CpG island methylator phenotype/CIMP). Normal adjacent tissue was studied as control.
Results
Twelve patients with CRC were included. Intra-tumoural heterogeneity for KRAS mutation was seen in 2 patients (17%). There was no statistical evidence of CIMP status heterogeneity (
p
= 0.85), but 6 of the 12 patients (50%) demonstrated at least one heterogeneous area within the tumour.
Discussion
Intra-tumoural heterogeneity for both genetic and epigenetic factors in CRC is more prevalent than previously thought in Stage II and Stage III CRC. This study provides new insight into epigenetic heterogeneity of CRC and supports the development of a more targeted biopsy strategy to support expansion of personalised treatment.
Molecular characterisation of tumours is increasing personalisation of cancer therapy, tailored to an individual and their cancer. FOCUS4 is a molecularly stratified clinical trial for patients with ...advanced colorectal cancer. During an initial 16-week period of standard first-line chemotherapy, tumour tissue will undergo several molecular assays, with the results used for cohort allocation, then randomisation. Laboratories in Leeds and Cardiff will perform the molecular testing. The results of a rigorous pre-trial inter-laboratory analytical validation are presented and discussed.
Wales Cancer Bank supplied FFPE tumour blocks from 97 mCRC patients with consent for use in further research. Both laboratories processed each sample according to an agreed definitive FOCUS4 laboratory protocol, reporting results directly to the MRC Trial Management Group for independent cross-referencing.
Pyrosequencing analysis of mutation status at KRAS codons12/13/61/146, NRAS codons12/13/61, BRAF codon600 and PIK3CA codons542/545/546/1047, generated highly concordant results. Two samples gave discrepant results; in one a PIK3CA mutation was detected only in Leeds, and in the other, a PIK3CA mutation was only detected in Cardiff. pTEN and mismatch repair (MMR) protein expression was assessed by immunohistochemistry (IHC) resulting in 6/97 discordant results for pTEN and 5/388 for MMR, resolved upon joint review. Tumour heterogeneity was likely responsible for pyrosequencing discrepancies. The presence of signet-ring cells, necrosis, mucin, edge-effects and over-counterstaining influenced IHC discrepancies.
Pre-trial assay analytical validation is essential to ensure appropriate selection of patients for targeted therapies. This is feasible for both mutation testing and immunohistochemical assays and must be built into the workup of such trials.
ISRCTN90061564.
The Jeryl Lynn (JL) vaccine against mumps virus (MuV) contains two components, MuV(JL5) and MuV(JL2), which differ by over 400 nt. Due to the occurrence of bias in the direction of mutation, these ...differences and those found in nucleotide sequences of different isolates of the minor component in the vaccine (MuV(JL2)) might be due to the effect of ADAR-like deaminases on MuV grown in tissue-cultured cells. A molecular clone of MuV(JL2) (pMuV(JL2)) and MuV(JL2)-specific helper plasmids were constructed in order to investigate molecular interactions between MuV(JL5) and MuV(JL2), to augment the existing molecular clone of MuV(JL5) (pMuV(JL5)) and MuV(JL5)-specific helper plasmids. Genome and mRNA termini of MuV(JL2) were characterized, and an unusual oligo-G insertion transcriptional editing event was detected near the F mRNA polyadenylation site of MuV(JL2), but not of MuV(JL5). Genes encoding glycoproteins of rMuV(JL2) and rMuV(JL5) have been exchanged to characterize the oligo-G insertion, which associated with the specific sequence of the F gene of MuV(JL2) and not with any other genes or the RNA-dependent RNA polymerase of strain MuV(JL2). The results indicate that a single G-to-A sequence change obliterates the co-transcriptional editing of the F mRNA and that this oligo-G insertion does not affect the growth of the virus.
Accelerate your learning Chambers, Phil
Industrial and commercial training,
10/2005, Letnik:
37, Številka:
6
Journal Article
Recenzirano
Purpose - To introduce the framework of accelerated learning and some of the pioneers who have helped to shape it. It also aims to give the reader tips on improving the speed and effectiveness of ...their learning.Design methodology approach - A description of the MESSAGE model and review of research behind it. Practical approach to applying accelerated learning in personal learning and training situations.Findings - Insight into the multiple facets of a very wide subject area.Practical implications - Improvement of learning effectiveness or at least curiosity to find out more.Originality value - An overview of accelerated learning. Useful for anyone studying or developing training.
Academic enquiry in higher education is an aspect of lifelong learning, which both defines and creates the learning culture through highly specialised and innovative means. This article examines and ...evaluates the impact of the contribution made by the professional dissertation in the context of Continuing Professional Development. Employing illustrations from dissertations in an international context and written as the culmination of a workplace based Master's programme, the article characterises the practitioner-researcher as typically engaged in fostering creativity, personal professional development, and aptitudes and skills both specific and transferable. In its conclusion, the article considers the ways in which the professional dissertation may be seen to meet the Dearing Committee recommendation that postgraduate research training should include the development of professional skills such as communication, self-management and planning. The professional dissertation is then offered as a model through which to encourage, promote and develop lifelong learning in postcompulsory education
Book Reviews Stammers, Peter; Kirkham, Glynn; Kirkham, Glynn ...
Journal of In-Service Education,
20/3/1/, Letnik:
26, Številka:
1
Book Review
The following books are reviewed.
Reschooling and the Global Future: politics, economics and the English experience JAMES PORTER, 1999 Oxford: Symposium Books. 128 pp., ISBN 1 873927 53 3, paperback, ...£18.00
Reshaping Education in the 1990s: perspectives on secondary schooling C.J. POLE & R. CHAWLA-DUGGAN (Eds), 1996 London: Falmer Press 186 pp., ISBN 0 7507 0529 9, £13.95
Gender and Management Issues in Education: an international perspective P. DRAKE & P. OWEN (Eds), 1998 Stoke-on-Trent: Trentham Books. 164 pp., ISBN 1 85856 087 X, £13.95
Awakening the Sleeping Giant: leadership development for teachers M. KATZENMEYER & G. MOLLER, 1996 Thousand Oaks: Corwin Press. 146 pp., ISBN 0 8039 6475 7, £16.50
The Adjunct Faculty Handbook V. BIANCO-MATHIS & N. CHALOFSKY (Eds), 1996 Thousand Oaks: Sage. 266 pp., ISBN 0 7619 9278 3, £18.95
Effective Teaching of Science: a review of research W. HARLEN, 1999 Edinburgh: Scottish Council for Research in Education. 105 pp., ISBN 1 86003 048 3, £10.50
Teaching Reading, Writing and Spelling V. TALBOT, 1997 Orland: Corwin Press. 296 pp., ISBN 0 8039 6592 3, £22.00
Postmodernism in Educational Theory: education and the politics of human resistance D. HILL, P. MCLAREN, M. COLE & G. RIKOWSKI (Eds), 1999 London: Tufnell Press. 232 pp., ISBN 1 872767 81 8, £15.00
Increasing Competence through Collaborative Problem Solving G. HANKO, 1999 London: David Fulton. 176 pp., ISBN 1 85346 600 X, £15.00
Tales for Trainers MARGARET PARKIN, 1998 London: Kogan Page. 178 pp., ISBN 0 7494 25210 5, paperback, £16.99
Professional Ethics and the Teacher: towards a General Teaching Council MERYL THOMPSON, 1997 Stoke-on-Trent: Trentham Books. 84 pp., ISBN 1 85856 079 9, £6.95
What's Worth Fighting for in Education? A. HARGREAVES & M. FULLAN, 1998 Buckingham: Open University Press. 146 pp., ISBN 0 335 20272 1, £10.99
The Art of Constructivist Teaching in the Primary School NICK SELLEY, 1999 London: David Fulton. 112 pp., ISBN 1 85346 572 0, £12.00
Finding One's Way: how mentoring can lead to dynamic leadership G. M. CROW & L. J. MATTHEWS, 1998 Thousand Oaks: Corwin Press. 168 pp., ISBN 0 8039 6546 X, paperback, £18.99, ISBN 0 8039 6545 1, hardback, £43.00
School-based Teacher Education: telling tales from a fictional primary school A. CAMPBELL & I. KANE, 1998 London: David Fulton. 160 pp., ISBN 1 85346 509 7, £14.00
Unmanned aerial vehicles (UAVs) can provide observations of high spatio-temporal resolution to enable operational landslide monitoring. In this research, the construction of digital elevation models ...(DEMs) and orthomosaics from UAV imagery is achieved using structure-from-motion (SfM) photogrammetric procedures. The study examines the additional value that the morphological attribute of openness, amongst others, can provide to surface deformation analysis. Image-cross-correlation functions and DEM subtraction techniques are applied to the SfM outputs. Through the proposed integrated analysis, the automated quantification of a landslide's motion over time is demonstrated, with implications for the wider interpretation of landslide kinematics via UAV surveys.
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