Institution
Dorset County Hospital NHS Foundation Trust
Healthcare•Dorchester, United Kingdom•
About: Dorset County Hospital NHS Foundation Trust is a healthcare organization based out in Dorchester, United Kingdom. It is known for research contribution in the topics: Population & Medicine. The organization has 160 authors who have published 113 publications receiving 2920 citations. The organization is also known as: West Dorset General Hospitals NHS Trust & West Dorset General Hospitals National Health Service Trust.
Topics: Population, Medicine, Cancer, Druggability, Hazard ratio
Papers
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French Institute of Health and Medical Research1, Pierre-and-Marie-Curie University2, Paris Descartes University3, University of Bern4, University of Erlangen-Nuremberg5, Providence Portland Medical Center6, Radboud University Nijmegen7, Umeå University8, Karolinska Institutet9, Humanitas University10, Medical University of Graz11, Dorset County Hospital NHS Foundation Trust12, Charles University in Prague13, Cornell University14, University Health Network15, University of Toronto16, Keio University17, Yamaguchi University18, Kindai University19, Harvard University20, Royal Melbourne Hospital21, University of Melbourne22, Sapporo Medical University23, Kurume University24, Xi'an Jiaotong University25, University of Texas MD Anderson Cancer Center26, Mayo Clinic27, Grigore T. Popa University of Medicine and Pharmacy28, Oregon Health & Science University29
TL;DR: In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC or UICCTNM classification.
Abstract: The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumour staging summarizes data on tumour burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can vary significantly among patients within the same stage. The current classification provides limited prognostic information and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status and gene expression-based stratification. These parameters rely on tumour-cell characteristics. Extensive literature has investigated the host immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumours. A methodology named 'Immunoscore' has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC/UICC TNM classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).
1,128 citations
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Society for Immunotherapy of Cancer1, National Institutes of Health2, French Institute of Health and Medical Research3, University of Paris4, University of Bern5, Providence Portland Medical Center6, University of Mainz7, Cornell University8, University of Erlangen-Nuremberg9, Medical University of Graz10, Karolinska Institutet11, Harvard University12, CEU San Pablo University13, Memorial Sloan Kettering Cancer Center14, Lund University15, University of Southampton16, Innsbruck Medical University17, University Health Network18, Princess Margaret Cancer Centre19, Keio University20, Yamaguchi University21, Kindai University22, Cancer Research Institute23, University of Tübingen24, Loyola University Chicago25, University of Manchester26, Université de Montréal27, Georgia Regents University28, Royal Melbourne Hospital29, University of Melbourne30, Sapporo Medical University31, Kurume University32, Umeå University33, Radboud University Nijmegen34, Xi'an Jiaotong University35, Dorset County Hospital NHS Foundation Trust36, University of Texas MD Anderson Cancer Center37, Mayo Clinic38, University of Chicago39, Oregon Health & Science University40
TL;DR: Evidence supports the notion to include immunological biomarkers, implemented as a tool for the prediction of prognosis and response to therapy, into traditional classification of cancer, designated TNM-I (TNM-Immune), and introduction of this parameter as a biomarker to classify cancers will facilitate clinical decision-making.
Abstract: Prediction of clinical outcome in cancer is usually achieved by histopathological evaluation of tissue samples obtained during surgical resection of the primary tumor. Traditional tumor staging (AJCC/UICC-TNM classification) summarizes data on tumor burden (T), presence of cancer cells in draining and regional lymph nodes (N) and evidence for metastases (M). However, it is now recognized that clinical outcome can significantly vary among patients within the same stage. The current classification provides limited prognostic information, and does not predict response to therapy. Recent literature has alluded to the importance of the host immune system in controlling tumor progression. Thus, evidence supports the notion to include immunological biomarkers, implemented as a tool for the prediction of prognosis and response to therapy. Accumulating data, collected from large cohorts of human cancers, has demonstrated the impact of immune-classification, which has a prognostic value that may add to the significance of the AJCC/UICC TNM-classification. It is therefore imperative to begin to incorporate the 'Immunoscore' into traditional classification, thus providing an essential prognostic and potentially predictive tool. Introduction of this parameter as a biomarker to classify cancers, as part of routine diagnostic and prognostic assessment of tumors, will facilitate clinical decision-making including rational stratification of patient treatment. Equally, the inherent complexity of quantitative immunohistochemistry, in conjunction with protocol variation across laboratories, analysis of different immune cell types, inconsistent region selection criteria, and variable ways to quantify immune infiltration, all underline the urgent requirement to reach assay harmonization. In an effort to promote the Immunoscore in routine clinical settings, an international task force was initiated. This review represents a follow-up of the announcement of this initiative, and of the J Transl Med. editorial from January 2012. Immunophenotyping of tumors may provide crucial novel prognostic information. The results of this international validation may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).
705 citations
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TL;DR: This work discovers and validate six previously unknown risk loci for PBC and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist.
Abstract: Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.
245 citations
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TL;DR: In ADHD there is gray matter reduction in the right putamen/globus pallidus region, which may be an anatomical marker for dysfunction in frontostriatal circuits mediating cognitive control.
Abstract: The authors sought to map gray matter changes in Attention Deficit Hyperactivity Disorder (ADHD) using a novel technique incorporating neuro-imaging and genetic meta-analysis methods. A systematic search was conducted for voxel-based structural magnetic resonance imaging studies of patients with ADHD (or with related disorders) in relation to comparison groups. The authors carried out meta-analyses of the co-ordinates of gray matter differences. For the meta-analyses they hybridised the standard method of Activation Likelihood Estimation (ALE) with the rank approach used in Genome Scan Meta-Analysis (GSMA). This system detects three-dimensional conjunctions of co-ordinates from multiple studies and permits the weighting of studies in relation to sample size. For gray matter decreases, there were 7 studies including a total of 114 patients with ADHD (or related disorders) and 143 comparison subjects. Meta-analysis of these studies identified a significant regional gray matter reduction in ADHD in the right putamen/globus pallidus region. Four studies reported gray matter increases in ADHD but no regional increase was identified by meta-analysis. In ADHD there is gray matter reduction in the right putamen/globus pallidus region. This may be an anatomical marker for dysfunction in frontostriatal circuits mediating cognitive control. Right putamen lesions have been specifically associated with ADHD symptoms after closed head injuries in children.
231 citations
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University of Queensland1, QIMR Berghofer Medical Research Institute2, University of the Highlands and Islands3, Ohio State University4, Université Paris-Saclay5, Curie Institute6, PSL Research University7, Paris Descartes University8, Northwestern University9, Harvard University10, Fox Chase Cancer Center11, University of Helsinki12, Loyola University Medical Center13, University of Barcelona14, Carlos III Health Institute15, Karolinska University Hospital16, University of Genoa17, University of Copenhagen18, Medical University of Graz19, Erasmus University Medical Center20, Helsinki University Central Hospital21, University of Eastern Piedmont22, University of Freiburg23, Brigham and Women's Hospital24, Washington University in St. Louis25, Dorset County Hospital NHS Foundation Trust26, Royal Hobart Hospital27, Royal Adelaide Hospital28, University of Adelaide29, Leeds Teaching Hospitals NHS Trust30, Wellcome Trust Sanger Institute31, Massachusetts Eye and Ear Infirmary32, Flinders Medical Centre33, University of Miami34, Memorial Sloan Kettering Cancer Center35, National Autonomous University of Mexico36
TL;DR: The collated data confirmed the core tumor spectrum associated with the BAP1-TPDS and showed that some families carrying missense variants can exhibit this phenotype, and highlights the need for a curated registry of germline variant carriers for proper assessment of the clinical phenotype.
Abstract: Background: The BRCA1-associated protein-1 (BAP1) tumor predisposition syndrome (BAP1-TPDS) is a hereditary tumor syndrome caused by germline pathogenic variants in BAP1 encoding a tumor suppressor associated with uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, and cutaneous BAP1-inactivated melanocytic tumors. However, the full spectrum of tumors associated with the syndrome is yet to be determined. Improved understanding of the BAP1-TPDS is crucial for appropriate clinical management of BAP1 germline variant carriers and their families, including genetic counseling and surveillance for new tumors.Methods: We collated germline variant status, tumor diagnoses, and information on BAP1 immunohistochemistry or loss of somatic heterozygosity on 106 published and 75 unpublished BAP1 germline variant-positive families worldwide to better characterize the genotypes and phenotypes associated with the BAP1-TPDS. Tumor spectrum and ages of onset were compared between missense and null variants. All statistical tests were two-sided.Results: The 181 families carried 140 unique BAP1 germline variants. The collated data confirmed the core tumor spectrum associated with the BAP1-TPDS and showed that some families carrying missense variants can exhibit this phenotype. A variety of noncore BAP1-TPDS-associated tumors were found in families of variant carriers. Median ages of onset of core tumor types were lower in null than missense variant carriers for all tumors combined (P<.001), mesothelioma (P<.001), cutaneous melanoma (P<.001), and nonmelanoma skin cancer (P<.001).Conclusions: This analysis substantially increases the number of pathogenic BAP1 germline variants and refines the phenotype. It highlights the need for a curated registry of germline variant carriers for proper assessment of the clinical phenotype of the BAP1-TPDS and pathogenicity of new variants, thus guiding management of patients and informing areas requiring further research.
126 citations
Authors
Showing all 161 results
Name | H-index | Papers | Citations |
---|---|---|---|
Raymond J. MacAllister | 49 | 110 | 11139 |
Ying Cheong | 31 | 112 | 3595 |
Derek G. Waller | 14 | 77 | 977 |
Michael Tsatsos | 11 | 46 | 500 |
M. Bayne | 7 | 11 | 318 |
Edmund C.P. Chedgy | 7 | 17 | 197 |
N. Siddiqi | 5 | 5 | 160 |
Anthony Thaventhiran | 5 | 10 | 88 |
Linden Stocker | 4 | 12 | 180 |
Zechan Khawaja | 3 | 3 | 128 |
L Devoto | 3 | 5 | 132 |
Debbie Chandler | 2 | 4 | 7 |
Karolina Miller | 2 | 6 | 30 |
Sudhindra Tv Rao | 2 | 2 | 70 |
Pamela E Ellis | 2 | 8 | 8 |