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Katja Ott

Bio: Katja Ott is an academic researcher from Heidelberg University. The author has contributed to research in topics: Neoadjuvant therapy & Cancer. The author has an hindex of 22, co-authored 49 publications receiving 1623 citations. Previous affiliations of Katja Ott include Technische Universität München.

Papers
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Journal ArticleDOI
TL;DR: In a multicenter study, the expression profiles of 863 microRNAs were determined by array analysis of 454 blood samples from human individuals with different cancers or noncancer diseases, and this 'miRNome' was validated by quantitative real-time PCR.
Abstract: In a multicenter study, we determined the expression profiles of 863 microRNAs by array analysis of 454 blood samples from human individuals with different cancers or noncancer diseases, and validated this 'miRNome' by quantitative real-time PCR. We detected consistently deregulated profiles for all tested diseases; pathway analysis confirmed disease association of the respective microRNAs. We observed significant correlations (P = 0.004) between the genomic location of disease-associated genetic variants and deregulated microRNAs.

347 citations

Journal ArticleDOI
TL;DR: The meta-analysis of genome-wide association studies doubled the number of known risk loci for Barrett's oesophagus and oesphageal adenocarcinoma and revealed new insights into causes of these diseases.
Abstract: Summary Background Oesophageal adenocarcinoma represents one of the fastest rising cancers in high-income countries. Barrett's oesophagus is the premalignant precursor of oesophageal adenocarcinoma. However, only a few patients with Barrett's oesophagus develop adenocarcinoma, which complicates clinical management in the absence of valid predictors. Within an international consortium investigating the genetics of Barrett's oesophagus and oesophageal adenocarcinoma, we aimed to identify novel genetic risk variants for the development of Barrett's oesophagus and oesophageal adenocarcinoma. Methods We did a meta-analysis of all genome-wide association studies of Barrett's oesophagus and oesophageal adenocarcinoma available in PubMed up to Feb 29, 2016; all patients were of European ancestry and disease was confirmed histopathologically. All participants were from four separate studies within Europe, North America, and Australia and were genotyped on high-density single nucleotide polymorphism (SNP) arrays. Meta-analysis was done with a fixed-effects inverse variance-weighting approach and with a standard genome-wide significance threshold (p −8 ). We also did an association analysis after reweighting of loci with an approach that investigates annotation enrichment among genome-wide significant loci. Furthermore, the entire dataset was analysed with bioinformatics approaches—including functional annotation databases and gene-based and pathway-based methods—to identify pathophysiologically relevant cellular mechanisms. Findings Our sample comprised 6167 patients with Barrett's oesophagus and 4112 individuals with oesophageal adenocarcinoma, in addition to 17 159 representative controls from four genome-wide association studies in Europe, North America, and Australia. We identified eight new risk loci associated with either Barrett's oesophagus or oesophageal adenocarcinoma, within or near the genes CFTR (rs17451754; p=4·8 × 10 −10 ), MSRA (rs17749155; p=5·2 × 10 −10 ), LINC00208 and BLK (rs10108511; p=2·1 × 10 −9 ), KHDRBS2 (rs62423175; p=3·0 × 10 −9 ), TPPP and CEP72 (rs9918259; p=3·2 × 10 −9 ), TMOD1 (rs7852462; p=1·5 × 10 −8 ), SATB2 (rs139606545; p=2·0 × 10 −8 ), and HTR3C and ABCC5 (rs9823696; p=1·6 × 10 −8 ). The locus identified near HTR3C and ABCC5 (rs9823696) was associated specifically with oesophageal adenocarcinoma (p=1·6 × 10 −8 ) and was independent of Barrett's oesophagus development (p=0·45). A ninth novel risk locus was identified within the gene LPA (rs12207195; posterior probability 0·925) after reweighting with significantly enriched annotations. The strongest disease pathways identified (p −6 ) belonged to muscle cell differentiation and to mesenchyme development and differentiation. Interpretation Our meta-analysis of genome-wide association studies doubled the number of known risk loci for Barrett's oesophagus and oesophageal adenocarcinoma and revealed new insights into causes of these diseases. Furthermore, the specific association between oesophageal adenocarcinoma and the locus near HTR3C and ABCC5 might constitute a novel genetic marker for prediction of the transition from Barrett's oesophagus to oesophageal adenocarcinoma. Fine-mapping and functional studies of new risk loci could lead to identification of key molecules in the development of Barrett's oesophagus and oesophageal adenocarcinoma, which might encourage development of advanced prevention and intervention strategies. Funding US National Cancer Institute, US National Institutes of Health, National Health and Medical Research Council of Australia, Swedish Cancer Society, Medical Research Council UK, Cambridge NIHR Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre, Else Kroner Fresenius Stiftung, Wellcome Trust, Cancer Research UK, AstraZeneca UK, University Hospitals of Leicester, University of Oxford, Australian Research Council.

120 citations

Journal ArticleDOI
TL;DR: In vitro data support a functional relationship between DNMT1 and cisplatin sensitivity andDNMT1 may represent a promising target for alternative therapeutic strategies for a subset of GC patients with better outcomes following neoadjuvant chemotherapy.

117 citations

Journal ArticleDOI
TL;DR: The effect of preoperative chemotherapy in esophageal adenocarcinomas can be assessed by the determination of histological tumor regression, providing highly valuable prognostic information, which may even exceed the prognostic impact of the current TNM classification of these tumors.

110 citations

Journal ArticleDOI
TL;DR: Only established prognostic Factors like ypTNM stage, R category, and complications were identified as independent prognostic factors in resected patients after neoadjuvant chemotherapy in contrast to histopathological tumour regression, which was not found as anindependent prognostic marker.
Abstract: Recently, histopathological tumour regression, prevalence of signet ring cells, and localisation were reported as prognostic factors in neoadjuvantly treated oesophagogastric (junctional and gastric) cancer. This exploratory retrospective study analyses independent prognostic factors within a large patient cohort after preoperative chemotherapy including clinical and histopathological factors. In all, 850 patients presenting with oesophagogastric cancer staged cT3/4 Nany cM0/x were treated with neoadjuvant chemotherapy followed by resection in two academic centres. Patient data were documented in a prospective database and retrospectively analysed. Of all factors prognostic on univariate analysis, only clinical response, complications, ypTNM stage, and R category were independently prognostic (P<0.01) on multivariate analysis. Tumour localisation and signet ring cells were independently prognostic only when investigator-dependent clinical response evaluation was excluded from the multivariate model. Histopathological tumour regression correlates with tumour grading, Lauren classification, clinical response, ypT, ypN, and R categories but was not identified as an independent prognostic factor. Within R0-resected patients only surgical complications and ypTNM stage were independent prognostic factors. Only established prognostic factors like ypTNM stage, R category, and complications were identified as independent prognostic factors in resected patients after neoadjuvant chemotherapy. In contrast, histopathological tumour regression was not found as an independent prognostic marker.

97 citations


Cited by
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01 Aug 2000
TL;DR: Assessment of medical technology in the context of commercialization with Bioentrepreneur course, which addresses many issues unique to biomedical products.
Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

4,833 citations

Journal ArticleDOI
TL;DR: In the EU, the highest age-standardised incidence rates for oesophageal cancer are in the Netherlands for men and the UK for women, and variation between countries is high and may reflect different prevalence of risk factors, use of screening and diagnostic methods.

810 citations

Journal ArticleDOI
TL;DR: The REMARK “elaboration and explanation” guideline, by Doug Altman and colleagues, provides a detailed reference for authors on important issues to consider when designing, conducting, and analyzing tumor marker prognostic studies.
Abstract: Background The Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) checklist consists of 20 items to report for published tumor marker prognostic studies. It was developed to address widespread deficiencies in the reporting of such studies. In this paper we expand on the REMARK checklist to enhance its use and effectiveness through better understanding of the intent of each item and why the information is important to report.

804 citations

Journal ArticleDOI
TL;DR: A trend of steady decline in gastric cancer incidence rates is the effect of the increased standards of hygiene, conscious nutrition, and Helicobacter pylori eradication, which together constitute primary prevention.
Abstract: Gastric cancer is the second most common cause of cancer-related deaths in the world, the epidemiology of which has changed within last decades. A trend of steady decline in gastric cancer incidence rates is the effect of the increased standards of hygiene, conscious nutrition, and Helicobacter pylori eradication, which together constitute primary prevention. Avoidance of gastric cancer remains a priority. However, patients with higher risk should be screened for early detection and chemoprevention. Surgical resection enhanced by standardized lymphadenectomy remains the gold standard in gastric cancer therapy. This review briefly summarizes the most important aspects of gastric cancers, which include epidemiology, risk factors, classification, diagnosis, prevention, and treatment. The paper is mostly addressed to physicians who are interested in updating the state of art concerning gastric carcinoma from easily accessible and credible source.

699 citations

Book ChapterDOI
TL;DR: A critical overview of miRNA dysregulation in cancer is provided, first discussing the methods currently available for studying the role of miRNAs in cancer and then reviewing miRNA genomic organization, biogenesis, and mechanism of target recognition.
Abstract: Mature microRNAs (miRNAs) are single-stranded RNA molecules of 20–23-nucleotide (nt) length that control gene expression in many cellular processes. These molecules typically reduce the translation and stability of mRNAs, including those of genes that mediate processes in tumorigenesis, such as inflammation, cell cycle regulation, stress response, differentiation, apoptosis, and invasion. miRNA targeting is initiated through specific base-pairing interactions between the 5′ end (“seed” region) of the miRNA and sites within coding and untranslated regions (UTRs) of mRNAs; target sites in the 3′ UTR lead to more effective mRNA destabilization. Since miRNAs frequently target hundreds of mRNAs, miRNA regulatory pathways are complex. To provide a critical overview of miRNA dysregulation in cancer, we first discuss the methods currently available for studying the role of miRNAs in cancer and then review miRNA genomic organization, biogenesis, and mechanism of target recognition, examining how these processes are altered in tumorigenesis. Given the critical role miRNAs play in tumorigenesis processes and their disease specific expression, they hold potential as therapeutic targets and novel biomarkers.

680 citations