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Clinical relevance of cancer genome sequencing

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World Journal of Gastroenterology 2013年第13期19卷 2011-2018页

作者： Chee Seng Ku David N Cooper Dimitrios H Roukos Department of Medical Epidemiology and Biostatistics Karolinska Institute institute of Medical Genetics School of MedicineCardiff University Department of Surgery Ioannina University School of Medicine Centre for Biosystems and Synthetic Genomic Network Medicine Centre for BioSystems and Genomic Network MedicineIoannina University

The arrival of both high-throughput and bench-top next-generation sequencing technologies and sequence enrichment methods has revolutionized our approach to dissecting the genetic basis of cancer. These technologies have been almost invariably employed in wholegenome sequencing (WGS) and whole-exome sequencing (WES) studies. Both WGS and WES approaches have been widely applied to interrogate the somatic mutational landscape of sporadic cancers and identify novel germline mutations underlying familial cancer syndromes. The clinical implications of cancer genome sequencing have become increasingly clear, for example in diagnostics. In this editorial, we present these advances in the context of research discovery and discuss both the clinical relevance of cancer genome sequencing and the challenges associated with the adoption of these genomic technologies in a clinical setting.

关键词： Next-generation sequencing Exome Cancer Diagnostics Familial cancer syndrome Somatic mutation

Diabetes--Role of epigenetics,genetics,and physiological factors

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中南大学学报（医学版） 2009年第9期34卷 837-845页

作者： Sreerama Krupanidhi Saikiran K. Sedimbi Ganesan Vaishnav Sreerama Sai Madhukar Carani B. Sanjeevi Department of Biosciences Sri Sathya Sai University Prasanthi Nilayam 515134 India Department of Molecular Immunogenetics Karolinska Institute Stockholm 17176 Sweden Department of Bioinformatics Sathyabama University Chennai 600019 India

Cells of organ systems are endowed with a relatively similar genome while epigenome niches keep varying chronologically and defined explicitly in the respective *** genome of an individual is always influenced by parental,embryonic,tissue-specific,and environmental epigenomes and the same must have been the possible reason for invariable inquiries relating to familial,environmental and life style patterns in the preliminary investigations of diabetic *** methylation of lysine residues of histones and cytosines of CpG islands of promoter DNA impede the transcription of genes and homocysteine is the metabolic key player of methyl *** and COX7A1 are the 2 examples in the present review to elucidate the epigenetic influence on the onset of *** are additional promising cellular components influencing both at transcriptional and translational levels and promoting either in favour or against(i.e.,feed back) TFs,signaling factors and proteins through their pliotropic effects and thus are reported to regulate cellular ***-124a and miR-9 are primarily endemic to nervous tissue and they are now being exploited in islets for their function in executing exocytosis of insulin,which of course is one of the fundamental canons of ***-375 persuades beta cells for glucose-induced insulin gene *** current approach to evaluate the constellation of genes and their products involved in diabetes in huge number of samples through GWA studies may unravel intricacies involved in the management of diabetes and its associated consequences.

关键词：糖尿病临床治疗疗效遗传学

Renal cell carcinoma escapes NK cell-mediated immune surveillance through the downregulation of DNAM-1

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Cancer Communications 2023年第7期43卷 855-859页

作者： Veronika Kremer Shi Yong Neo Yaxuan Liu Yi Chen Arnika Kathleen Wagner Ying Yang Ziqing Chen Christina Seitz Nicholas Patrick Tobin Maarten Alexander Ligtenberg Evren Alici Xinsong Chen Felix Haglund Barbara Seliger Ulrika Harmenberg Eugenia Colón Ann-Helén Scherman Plogell Lisa Lei Liu Andreas Lundqvist Department of Oncology-Pathology Karolinska InstitutetStockholmSweden Singapore Immunology Network Agency for ScienceTechnology and ResearchSingaporeSingapore Department of Medicine Columbia University Irving Medical CenterNew YorkUSA Department of Medicine Huddinge Karolinska InstitutetStockholmSweden Department of Molecular Biology Princeton UniversityNew JerseyUSA institute of Environmental Medicine Karolinska InstitutetStockholmSweden Department of Molecular Oncology The Netherlands Cancer InstituteAmsterdamNetherlands institute for Medical Immunology Martin-Luther University Halle-WittenbergHalleGermany institute of Translational Immunology Medical School Theodor FontaneBrandenburg an der Havel14770and Fraunhofer Institute for Cell Therapy and ImmunologyLeipzigGermany Department ofWomen’s and Children’s Health Karolinska Institutet and S:t Göran’s Hospital-UnilabsStockholmSweden Department of Urology Stockholm South General HospitalStockholmSweden

Dear Editor,The activating receptor DNAX accessory molecule-1(DNAM-1)plays an important role in T and natural killer(NK)cell-mediated cytotoxicity via the interaction with its ligands poliovirus receptor(PVR,CD155)and Nectin-2(CD112).Compared with peripheral blood NK cells,tumor-infiltrating NK cells show reduced expression of DNAM-1 across several solid tumors,including ovarian and breast cancer resulting in impaired NK cell *** studies reported an inverse correlation between DNAM-1 expression and its ligands in leukemic blasts and ovarian cancer[1].

关键词： impaired cancer killer

Long Term Effects of Radiation-Induced Osteonecrosis of the Pelvis Caused Complete Failure of Total Hip Arthroplasty

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Surgical Science 2012年第7期3卷 373-375页

作者： Tigist Wodaje Per Wretenberg Department of Molecular Medicine and Surgery Section of Orthopaedics Karolinska Institute and Karolinska University Hospital Stockholm Sweden

This case report describe severe osteonecrosis of the pelvis more than 30 years after radiation due to ovarian cancer. As orthopedic surgeon it is important to ask about previous radiation to the pelvis in case of tot... 详细信息

关键词： Osteonecrosis Hip Radiation

Trunk Kinematics and Centre of Pressure Displacement during Lateral Lifting and Lowering

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中国运动医学杂志 2006年第4期25卷 428-434页

作者： Huang Qiangmin Alf Thorstensson Andrew Cresswell Department of Sports Science Shanghai Institute of Physical EducationShanghaiChina 200438 Departments of Neuroscience Karolinska Institute and Sport and Health Sciences University College of Physical Education and Sports Stockholm Sweden

Lateral bending of the trunk has been specifically identified as a high risk factor for lower back disorders. However, few studies have presented in vivo kinematic data of the trunk while performing functional lateral bending tasks. Five healthy male subjects performed lateral lifting and lowering tasks under loading condition ranging from light (2kg) to 100 % of a maximum (ML) at a controlled velocity. Single lowering tasks were also performed at 125% and 150% of ML. Video based movement analysis was used to determine kinematics of the trunk, pelvis, shoulders and neck in the frontal plane. Centre of pressure (COP) data was also obtained from a force platform on which the subjects stood when performing the lifting and lowering tasks. Kinematics of the trunk revealed a smooth and relatively large change in angular displacement (between 69°to 55°) toward the unloaded side during the lifting phase. Trunk angular displacement significantly decreased with increasing lifting load. The trunk was additionally divided into four segments representing the lower and upper lumbar regions and the lower and upper thoracic regions. The greatest displacement in these segments took place at the upper lumbar and lower thoracic regions (ranging from 29°to 22°and 23°to 17°, respectively) with the least displacement occurring in the lower lumbar and upper thoracic regions (approx. 6° and 5°, respectively). Both the upper lumbar and lower thoracic segments showed significant decreases in angular displacement with increasing load. During the single lowering trials the trunk rotated toward the loaded side with slightly less magnitude to that recorded during the lowering phase of the heaviest lifting and lowering conditions. Angular displacements of the upper lumbar and lower thoracic segments also decreased with increasing load in single lowering. Identified changes in the COP displacement were also correlated to increasing lifting and lowering load. The main findings of this study indicat

关键词：运动分析运动医学侧弯曲侧提升

Cystic tumors of the pancreas: Opportunities and risks

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World Journal of Gastrointestinal Pathophysiology 2015年第2期6卷 29-32页

作者： Marco Del Chiaro Caroline Verbeke Pancreatic Surgery Unit Division of Surgery Department of Clinical Science Intervention and Technology (CLINTEC) Karolinska Institute at Center for Digestive Diseases Karolinska University Hospital Department of Pathology Institute of Clinical Medicine University of Oslo Department of Pathology Karolinska Institute

Pancreatic cystic neoplasms(PCNs) are a high prevalence disease. It is estimated that about 20% of the general population is affected by PCNs. Some of those lesions can progress till cancer, while others behave in a benign fashion. In particular intraductal papillary mucinousneoplasms of the pancreas can be considered as the pancreatic analogon to colonic polyps. Treatment of these precursor lesions at an early stage can potentially reduce pancreas cancer mortality and introduce a new "era" of preemptive pancreatic surgery. However, only few of those lesions have an aggressive behavior. The accuracy of preoperative diagnosis, i.e., the distinction between the various PCNs is around 60%, and the ability to predict the future outcome is also less accurate. For this reason, a significant number of patients are currently over-treated with an unnecessary, high-risk surgery. Furthermore, the majority of patients with PCN are on life-long follow-up with imaging modality, which has huge cost implications for the Health Care System for limited benefits considering that a significant proportion of PCNs are or behave like benign lesions. The current guidelines for the diagnosis and management of PCNs are more based on expert opinion than on evidence. For all those reasons, the management of cystic tumors of the pancreas remains a controversial area of pancreatology. On one hand, the detection of PCNs and the surgical treatment of pre-cancerous neoplasms can be considered a big opportunity to reduce pancreatic cancer related mortality. On the other hand, PCNs are associated with a considerable risk of under- or over- treatment of patients and incur high costs for the Health Care System.

关键词： Pancreatic cystic neoplasms Mucinous cystic neoplasia Preemptive pancreatic surgery Pancreas Intraductal papillary mucinous neoplasia

In silico Proteome-wide Amino aCid and Elemental Composition (PACE) Analysis of Expression Proteomics Data Provides A Fingerprint of Dominant Metabolic Processes

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Genomics, Proteomics & Bioinformatics 2013年第4期11卷 219-229页

作者： David M. Good Anwer Mamdoh Harshavardhan Budamgunta Roman A. Zubarev Division of Physiological Chemistry I Department of Medical Biochemistry and Biophysics Karolinska InstituteSE17177 Stockholm Sweden Science for Life Laboratory SE17121 Solna Sweden

Proteome-wide Amino aCid and Elemental composition （PACE） analysis is a novel and informative way of interrogating the proteome. The PACE approach consists of in silico decompo- sition of proteins detected and quantified in a proteomics experiment into 20 amino acids and five elements （C, H, N, O and S）, with protein abundances converted to relative abundances of amino acids and elements. The method is robust and very sensitive; it provides statistically reliable differ- entiation between very similar proteomes. In addition, PACE provides novel insights into prote- ome-wide metabolic processes, occurring, e.g., during cell starvation. For instance, both Escherichia coli and Synechocystis down-regulate sulfur-rich proteins upon sulfur deprivation, but E. coli preferentially down-regulates cysteine-rich proteins while Synechocystis mainly down- regulates methionine-rich proteins. Due to its relative simplicity, flexibility, generality and wide applicability, PACE analysis has the potential of becoming a standard analytical tool in proteomics.

关键词： Shotgun proteomics Mass spectrometry LC-MS/MS Data reduction Cyanobacterium Arginine deprivation

New therapeutic perspectives in Type 1 Diabetes: dietary interventions prevent β cell-autoimmunity by modifying the gut metabolic environment

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Cellular & Molecular Immunology 2017年第12期14卷 951-953页

作者： Chiara Sorini Ilaria Cosorich Marika Falcone Immunology and Allergy Unit Department of MedicineKarolinska InstitutetStockholmSweden Experimental Diabetes Unit-DRI Division of ImmunologyTransplantation and Infectious DiseasesIRCCS San Raffaele Scientific InstituteMilanItaly

The gut microbiota plays a key role in the pathogenesis of autoimmune diseases such as Type 1 Diabetes(T1D),but the mechanism underlying this modulation is yet to be *** paper highlights the crucial role of the microbiota-induced gut metabolic profile,rather than the presence of single bacterial strains,in T1D *** importantly,it provides the first evidence that dietary interventions can modulate the autoimmune pathogenesis of T1D by altering the gut metabolic environment.

关键词： Diabetes autoimmune pathogenesis

Labor Induction with Transcervical Catheter versus Oral Misoprostol in Primiparous Women and Women with an Unripe Cervix

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Open Journal of Obstetrics and Gynecology 2015年第14期5卷 819-826页

作者： Anna Thorbiornson Tomislav Vladic Ylva Vladic Stjernholm Medical Educational Programme in Gynecology and Obstetrics Karolinska University Hospital and Karolinska Institute Stockholm Sweden Department of Women’s and Children’s Health Karolinska University Hospital Stockholm Sweden

Objective: To compare labor induction with transcervical catheter to oral misoprostol treatment in primiparous women and women with an unripe cervix, who are at high risk for unsuccessful labor induction. Study Design: A retrospective study was carried out in a university hospital in Sweden. Primary outcomes were vaginal birth within 24 hours and the cesarean section rate. Secondary outcomes were the induction to vaginal delivery interval, chorioamnionitis and neonatal asphyxia. Results: Vaginal birth within 24 hours was obtained more frequently after catheter compared with misoprostol in primiparous women (p 0.05). The induction to vaginal delivery interval was 8 - 12 hours shorter after catheter (p < 0.001). The rates of chorioamnionitis and newborns with an Apgar score 0.05). Conclusion: Labor induction with transcervical catheter resulted in a higher rate of vaginal birth within 24 hours and an 8 - 12 hour shorter induction to vaginal delivery interval compared to treatment with oral misoprostol. This was obtained without increasing the rates of cesarean section, chorioamnionitis or neonatal asphyxia.

关键词： Cervical Ripening Transcervical Catheter Oral Misoprostol Vaginal Birth Cesarean Section