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- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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- Seufferlein, T, et al.
(författare)
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[S3-guideline exocrine pancreatic cancer]
- 2013
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Ingår i: Zeitschrift fur Gastroenterologie. - : Georg Thieme Verlag KG. - 1439-7803 .- 0044-2771. ; 51:12, s. 1395-1440
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Tidskriftsartikel (refereegranskat)
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- Del Chiaro, M, et al.
(författare)
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European evidence-based guidelines on pancreatic cystic neoplasms
- 2018
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 67:5, s. 789-804
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Tidskriftsartikel (refereegranskat)abstract
- Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring <40 mm without an enhancing nodule. Relative indications for surgery in IPMN include a main pancreatic duct (MPD) diameter between 5 and 9.9 mm or a cyst diameter ≥40 mm. Absolute indications for surgery in IPMN, due to the high-risk of malignant transformation, include jaundice, an enhancing mural nodule >5 mm, and MPD diameter >10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN.
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- Allum, W., et al.
(författare)
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ECCO essential requirements for quality cancer care: Oesophageal and gastric cancer
- 2018
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Ingår i: Critical reviews in oncology/hematology. - : Elsevier BV. - 1040-8428. ; 122, s. 179-193
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Tidskriftsartikel (refereegranskat)abstract
- Background: ECCO essential requirements for quality cancer care (ERQCC) are checklists and explanations of organisation and actions that are necessary to give high-quality care to patients who have a specific type of cancer. They are written by European experts representing all disciplines involved in cancer care. ERQCC papers give oncology teams, patients, policymakers and managers an overview of the elements needed in any healthcare system to provide high quality of care throughout the patient journey. References are made to clinical guidelines and other resources where appropriate, and the focus is on care in Europe. Oesophageal and gastric: essential requirements for quality care: • Oesophageal and gastric (OG) cancers are a challenging tumour group with a poor prognosis and wide variation in outcomes among European countries. Increasing numbers of older people are contracting the diseases, and treatments and care pathways are becoming more complex in both curative and palliative settings.• High-quality care can only be a carried out in specialised OG cancer units or centres which have both a core multidisciplinary team and an extended team of allied professionals, and which are subject to quality and audit procedures. Such units or centres are far from universal in all European countries.• It is essential that, to meet European aspirations for comprehensive cancer control, healthcare organisations implement the essential requirements in this paper, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship. Conclusion: Taken together, the information presented in this paper provides a comprehensive description of the essential requirements for establishing a high-quality OG cancer service. The ERQCC expert group is aware that it is not possible to propose a ‘one size fits all’ system for all countries, but urges that access to multidisciplinary units or centres must be guaranteed for all those with OG cancer.
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- Beets, G., et al.
(författare)
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ECCO Essential Requirements for Quality Cancer Care: Colorectal Cancer. A critical review
- 2017
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Ingår i: Critical Reviews in Oncology Hematology. - : Elsevier BV. - 1040-8428. ; 110, s. 81-93
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Tidskriftsartikel (refereegranskat)abstract
- Background: ECCO essential requirements for quality cancer care (ERQCC) are checklists and explanations of organisation and actions that are necessary to give high-quality care to patients who have a specific tumour type. They are written by European experts representing all disciplines involved in cancer care. ERQCC papers give oncology teams, patients, policymakers and managers an overview of the elements needed in any healthcare system to provide high quality of care throughout the patient journey. References are made to clinical guidelines and other resources where appropriate, and the focus is on care in Europe. Colorectal cancer (CRC) is the second most common cause of cancer death in Europe and has wide variation in outcomes among countries. Increasing numbers of older people are contracting the disease, and treatments for advanced stages are becoming more complex. A growing number of survivors also require specialist support. High-quality care can only be a carried out in specialised CRC units or centres which have both a core multidisciplinary team and an extended team of allied professionals, and which are subject to quality and audit procedures. Such units or centres are far from universal in all European countries. It is essential that, to meet European aspirations for comprehensive cancer control, healthcare organisations implement the essential requirements in this paper, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship. Conclusion: Taken together, the information presented in this paper provides a comprehensive description of the essential requirements for establishing a high-quality CRC service. The ECCO expert group is aware that it is not possible to propose a 'one size fits all' system for all countries, but urges that access to multidisciplinary units or centres must be guaranteed for all those with CRC. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.
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- Baust, H., et al.
(författare)
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Evidence for radiosensitizing by gliotoxin in HL-60 cells : implications for a role of NF-kappa B independent mechanisms
- 2003
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 22:54, s. 8786-8796
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Tidskriftsartikel (refereegranskat)abstract
- Radioresistance markedly impairs the efficacy of tumor radiotherapy and may involve antiapoptotic signal transduction pathways that prevent radiation-induced cell death. A common cellular response to genotoxic stress induced by radiation is the activation of the nuclear factor kappa B (NF-kappaB). NF-kappaB activation in turn can lead to an inhibition of radiation-induced apoptotic cell death. Thus, inhibition of NF-kappaB activation is commonly regarded as an important strategy to abolish radioresistance. Among other compounds, the fungal metabolite gliotoxin (GT) has been reported to be a highly selective inhibitor of NF-kappaB activation. Indeed, low doses of GT were sufficient to significantly enhance radiation-induced apoptosis in HL-60 cells. However, this effect turned out to be largely independent of NF-kappaB activation since radiation of HL-60 cells with clinically relevant doses of radiation induced only a marginal increase in NF-kappaB activity, and selective inhibition of NF-kappaB by SN50 did not result in a marked enhancement of GT-induced apoptosis. GT induced activation of JNKs, cytochrome c release from the mitochondria and potently stimulated the caspase cascade inducing cleavage of caspases -9, -8, -7 and -3. Furthermore, cleavage of the antiapoptotic protein X-linked IAP and downregulation of the G2/M-specific IAP-family member survivin were observed during GT-induced apoptosis. Finally, the radiation-induced G2/M arrest was markedly reduced in GT-treated cells most likely due to the rapid induction of apoptosis. Our data demonstrate that various other pathways apart from the NF-kappaB signaling complex can sensitize tumor cells to radiation and propose a novel mechanism for radio-sensitization by GT, the interference with the G2/M checkpoint that is important for repair of radiation-induced DNA damage in p53-deficient tumor cells.
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- Burra, P, et al.
(författare)
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UEG position paper: Obesity and digestive health
- 2022
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Ingår i: United European gastroenterology journal. - : Wiley. - 2050-6414 .- 2050-6406. ; 10:10, s. 1199-1201
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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