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1004 Publications visible to you, out of a total of 1004
Sevoflurane and Isoflurane-Pharmacokinetics, Hemodynamic Stability and Cardio-protective Effects During Cardiopulmonary Bypass
Genetical Statistics and Systems Biology

Abstract

Not specified

Authors: David Freiermuth, Berend Mets, Daniel Bolliger, Oliver Reuthebuch, Thomas Doebele, Markus Scholz, Michael Gregor, Marcel Haschke, Manfred Seeberger, Jens Fassl

Date Published: 1st Dec 2017

Publication Type: Journal article

Cholesterol esterification in plasma as a biomarker for liver function and prediction of mortality
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND Advanced stages of liver cirrhosis lead to a dramatically increased mortality. For valid identification of these patients suitable biomarkers are essential. The most important biomarkers for …r liver function are bilirubin and prothrombin time expressed as International Normalized Ratio (INR). However, the influence of several anticoagulants on the prothrombin time limits its diagnostic value. Aim of this study was the evaluation of cholesterol esterification (CE) fraction (esterified cholesterol vs. total cholesterol) as an alternative biomarker for liver synthesis and mortality prediction. Under physiological conditions the CE fraction in blood is closely regulated by lecithin-cholesterol acyltransferase (LCAT) which is produced in the liver. METHODS One hundred forty-two patients with liver disease clinically considered for orthotopic liver transplant for different indications were enrolled in the study. One patient was excluded because of the intake of a direct oral factor Xa inhibitor which has a strong impact on prothrombin time. RESULTS Results of CE fraction were in good agreement with INR (R(2) = 0.73; p \textless 0.001). In patients who died or survived within three months mean CE fraction was 56% vs. 74% (p \textless 0.001) and mean INR was 2.0 vs. 1.3 (p \textless 0.001), respectively. The predictive value of CE fraction for three-month mortality risk was higher compared to INR (p = 0.04). Results for one-year mortality were comparable. CONCLUSIONS The cholesterol esterification fraction is a valid biomarker for liver synthesis and allows reliable prediction of mortality. In contrast to INR, it is independent of anticoagulation and other analytical limitations of coagulation tests.

Authors: Thorsten Kaiser, Benedict Kinny-Köster, Michael Bartels, Thomas Berg, Markus Scholz, Cornelius Engelmann, Daniel Seehofer, Susen Becker, Uta Ceglarek, Joachim Thiery

Date Published: 1st Dec 2017

Publication Type: Journal article

Epidermal Growth Factor Receptor Variant III (EGFRvIII) Positivity in EGFR-Amplified Glioblastomas: Prognostic Role and Comparison between Primary and Recurrent Tumors.
GGN - German Glioma Network

Abstract (Expand)

Purpose: Approximately 40% of all glioblastomas have amplified the EGFR gene, and about half of these tumors express the EGFRvIII variant. The prognostic role of EGFRvIII in EGFR-amplified glioblastoma … patients and changes in EGFRvIII expression in recurrent versus primary glioblastomas remain controversial, but such data are highly relevant for EGFRvIII-targeted therapies.Experimental Design:EGFR-amplified glioblastomas from 106 patients were assessed for EGFRvIII positivity. Changes in EGFR amplification and EGFRvIII status from primary to recurrent glioblastomas were evaluated in 40 patients with EGFR-amplified tumors and 33 patients with EGFR-nonamplified tumors. EGFR single-nucleotide variants (SNV) were assessed in 27 patients. Data were correlated with outcome and validated in 150 glioblastoma patients from The Cancer Genome Atlas (TCGA) consortium.Results: Sixty of 106 EGFR-amplified glioblastomas were EGFRvIII-positive (56.6%). EGFRvIII positivity was not associated with different progression-free or overall survival. EGFRvIII status was unchanged at recurrence in 35 of 40 patients with EGFR-amplified primary tumors (87.5%). Four patients lost and one patient gained EGFRvIII positivity at recurrence. None of 33 EGFR-nonamplified glioblastomas acquired EGFR amplification or EGFRvIII at recurrence. EGFR SNVs were frequent in EGFR-amplified tumors, but were not linked to survival.Conclusions: EGFRvIII and EGFR SNVs are not prognostic in EGFR-amplified glioblastoma patients. EGFR amplification is retained in recurrent glioblastomas. Most EGFRvIII-positive glioblastomas maintain EGFRvIII positivity at recurrence. However, EGFRvIII expression may change in a subset of patients at recurrence, thus repeated biopsy with reassessment of EGFRvIII status is recommended for patients with recurrent glioblastoma to receive EGFRvIII-targeting agents. Clin Cancer Res; 23(22); 6846-55. (c)2017 AACR.

Authors: J. Felsberg, B. Hentschel, K. Kaulich, D. Gramatzki, A. Zacher, B. Malzkorn, M. Kamp, M. Sabel, M. Simon, M. Westphal, G. Schackert, J. C. Tonn, T. Pietsch, A. von Deimling, M. Loeffler, G. Reifenberger, M. Weller

Date Published: 15th Nov 2017

Publication Type: Journal article

Human Diseases: brain glioblastoma multiforme

Feasibility of structured endurance training and Mediterranean diet in BRCA1 and BRCA2 mutation carriers - an interventional randomized controlled multicenter trial (LIBRE-1).
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

BACKGROUND: Women with pathogenic BRCA germline mutations have an increased risk for breast and ovarian cancer that seems to be modified by life-style factors. Though, randomized trials investigating … the impact of lifestyle interventions on cancer prevention and prognosis in BRCA carriers are still missing. METHODS: We implemented a multicenter, prospective randomized controlled trial in BRCA1/2 patients, comparing a lifestyle intervention group (IG) with a control group (CG) with the primary aim to prove feasibility. Intervention comprised a structured, individualized endurance training alongside nutrition education based on the Mediterranean diet (MD) for 3 months, plus monthly group training and regular telephone contact during the subsequent 9 months. The CG attended one session on healthy nutrition and the benefits of physical activity. Primary endpoints were feasibility, acceptance and satisfaction over 12 months. Furthermore, effects on physical fitness, diet profile, body mass index (BMI), quality of life and perceived stress were investigated. RESULTS: Sixty-eight participants (mean age 41, mean BMI 23.2 kg/m(2)) were enrolled, of whom 55 (81%, 26 IG, 29 CG) completed 12 months. 73% (n = 26) participated in at least 70% of all intervention sessions. Predictors for drop-outs (19%; n = 13) or non-adherence (27%; n = 7) were not found. 73% rated the program highly and 80% would participate again. Severe adverse events did not occur. Positive effects in the IG compared to the CG were observed for secondary endpoints: BMI, MD eating pattern and stress levels. CONCLUSIONS: This lifestyle intervention was feasible, safe and well accepted. Positive results on eating habits, physical fitness and stress levels warrant a larger randomized trial. TRIAL REGISTRATION: The study has been retrospectively registered at ClinicalTrials.gov (reference: NCT02087592 ) on March 12, 2014. The first patient was included on February 24, 2014.

Authors: M. Kiechle, R. Dukatz, M. Yahiaoui-Doktor, A. Berling, M. Basrai, V. Staiger, U. Niederberger, N. Marter, J. Lammert, S. Grill, K. Pfeifer, K. Rhiem, R. K. Schmutzler, M. Laudes, M. Siniatchkin, M. Halle, S. C. Bischoff, C. Engel

Date Published: 10th Nov 2017

Publication Type: Not specified

Human Diseases: hereditary breast ovarian cancer syndrome

Model-based optimization of G-CSF treatment during cytotoxic chemotherapy.
Genetical Statistics and Systems Biology

Abstract (Expand)

PURPOSE: Although G-CSF is widely used to prevent or ameliorate leukopenia during cytotoxic chemotherapies, its optimal use is still under debate and depends on many therapy parameters such as dosing … and timing of cytotoxic drugs and G-CSF, G-CSF pharmaceuticals used and individual risk factors of patients. METHODS: We integrate available biological knowledge and clinical data regarding cell kinetics of bone marrow granulopoiesis, the cytotoxic effects of chemotherapy and pharmacokinetics and pharmacodynamics of G-CSF applications (filgrastim or pegfilgrastim) into a comprehensive model. The model explains leukocyte time courses of more than 70 therapy scenarios comprising 10 different cytotoxic drugs. It is applied to develop optimized G-CSF schedules for a variety of clinical scenarios. RESULTS: Clinical trial results showed validity of model predictions regarding alternative G-CSF schedules. We propose modifications of G-CSF treatment for the chemotherapies 'BEACOPP escalated' (Hodgkin's disease), 'ETC' (breast cancer), and risk-adapted schedules for 'CHOP-14' (aggressive non-Hodgkin's lymphoma in elderly patients). CONCLUSIONS: We conclude that we established a model of human granulopoiesis under chemotherapy which allows predictions of yet untested G-CSF schedules, comparisons between them, and optimization of filgrastim and pegfilgrastim treatment. As a general rule of thumb, G-CSF treatment should not be started too early and patients could profit from filgrastim treatment continued until the end of the chemotherapy cycle.

Authors: S. Schirm, C. Engel, S. Loibl, M. Loeffler, M. Scholz

Date Published: 6th Nov 2017

Publication Type: Journal article

Autoimmunity and autoinflammation: A systems view on signaling pathway dysregulation profiles.
LHA - Leipzig Health Atlas

Abstract (Expand)

INTRODUCTION: Autoinflammatory and autoimmune disorders are characterized by aberrant changes in innate and adaptive immunity that may lead from an initial inflammatory state to an organ specific damage. … These disorders possess heterogeneity in terms of affected organs and clinical phenotypes. However, despite the differences in etiology and phenotypic variations, they share genetic associations, treatment responses and clinical manifestations. The mechanisms involved in their initiation and development remain poorly understood, however the existence of some clear similarities between autoimmune and autoinflammatory disorders indicates variable degrees of interaction between immune-related mechanisms. METHODS: Our study aims at contributing to a holistic, pathway-centered view on the inflammatory condition of autoimmune and autoinflammatory diseases. We have evaluated similarities and specificities of pathway activity changes in twelve autoimmune and autoinflammatory disorders by performing meta-analysis of publicly available gene expression datasets generated from peripheral blood mononuclear cells, using a bioinformatics pipeline that integrates Self Organizing Maps and Pathway Signal Flow algorithms along with KEGG pathway topologies. RESULTS AND CONCLUSIONS: The results reveal that clinically divergent disease groups share common pathway perturbation profiles. We identified pathways, similarly perturbed in all the studied diseases, such as PI3K-Akt, Toll-like receptor, and NF-kappa B signaling, that serve as integrators of signals guiding immune cell polarization, migration, growth, survival and differentiation. Further, two clusters of diseases were identified based on specifically dysregulated pathways: one gathering mostly autoimmune and the other mainly autoinflammatory diseases. Cluster separation was driven not only by apparent involvement of pathways implicated in adaptive immunity in one case, and inflammation in the other, but also by processes not explicitly related to immune response, but rather representing various events related to the formation of specific pathophysiological environment. Thus, our data suggest that while all of the studied diseases are affected by activation of common inflammatory processes, disease-specific variations in their relative balance are also identified.

Authors: A. Arakelyan, L. Nersisyan, D. Poghosyan, L. Khondkaryan, A. Hakobyan, H. Loffler-Wirth, E. Melanitou, H. Binder

Date Published: 4th Nov 2017

Publication Type: Not specified

Association analysis identifies 65 new breast cancer risk loci
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer … risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P \textless 5 \times 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

Authors: Kyriaki Michailidou, Sara Lindström, Joe Dennis, Jonathan Beesley, Shirley Hui, Siddhartha Kar, Audrey Lemaçon, Penny Soucy, Dylan Glubb, Asha Rostamianfar, Manjeet K. Bolla, Qin Wang, Jonathan Tyrer, Ed Dicks, Andrew Lee, Zhaoming Wang, Jamie Allen, Renske Keeman, Ursula Eilber, Juliet D. French, Xiao Qing Chen, Laura Fachal, Karen McCue, Amy E. McCart Reed, Maya Ghoussaini, Jason S. Carroll, Xia Jiang, Hilary Finucane, Marcia Adams, Muriel A. Adank, Habibul Ahsan, Kristiina Aittomäki, Hoda Anton-Culver, Natalia N. Antonenkova, Volker Arndt, Kristan J. Aronson, Banu Arun, Paul L. Auer, François Bacot, Myrto Barrdahl, Caroline Baynes, Matthias W. Beckmann, Sabine Behrens, Javier Benitez, Marina Bermisheva, Leslie Bernstein, Carl Blomqvist, Natalia V. Bogdanova, Stig E. Bojesen, Bernardo Bonanni, Anne-Lise Børresen-Dale, Judith S. Brand, Hiltrud Brauch, Paul Brennan, Hermann Brenner, Louise Brinton, Per Broberg, Ian W. Brock, Annegien Broeks, Angela Brooks-Wilson, Sara Y. Brucker, Thomas Brüning, Barbara Burwinkel, Katja Butterbach, Qiuyin Cai, Hui Cai, Trinidad Caldés, Federico Canzian, Angel Carracedo, Brian D. Carter, Jose E. Castelao, Tsun L. Chan, Ting-Yuan David Cheng, Kee Seng Chia, Ji-Yeob Choi, Hans Christiansen, Christine L. Clarke, Margriet Collée, Don M. Conroy, Emilie Cordina-Duverger, Sten Cornelissen, David G. Cox, Angela Cox, Simon S. Cross, Julie M. Cunningham, Kamila Czene, Mary B. Daly, Peter Devilee, Kimberly F. Doheny, Thilo Dörk, Isabel Dos-Santos-Silva, Martine Dumont, Lorraine Durcan, Miriam Dwek, Diana M. Eccles, Arif B. Ekici, A. Heather Eliassen, Carolina Ellberg, Mingajeva Elvira, Christoph Engel, Mikael Eriksson, Peter A. Fasching, Jonine Figueroa, Dieter Flesch-Janys, Olivia Fletcher, Henrik Flyger, Lin Fritschi, Valerie Gaborieau, Marike Gabrielson, Manuela Gago-Dominguez, Yu-Tang Gao, Susan M. Gapstur, José A. García-Sáenz, Mia M. Gaudet, Vassilios Georgoulias, Graham G. Giles, Gord Glendon, Mark S. Goldberg, David E. Goldgar, Anna González-Neira, Grethe I. Grenaker Alnæs, Mervi Grip, Jacek Gronwald, Anne Grundy, Pascal Guénel, Lothar Haeberle, Eric Hahnen, Christopher A. Haiman, Niclas Håkansson, Ute Hamann, Nathalie Hamel, Susan Hankinson, Patricia Harrington, Steven N. Hart, Jaana M. Hartikainen, Mikael Hartman, Alexander Hein, Jane Heyworth, Belynda Hicks, Peter Hillemanns, Dona N. Ho, Antoinette Hollestelle, Maartje J. Hooning, Robert N. Hoover, John L. Hopper, Ming-Feng Hou, Chia-Ni Hsiung, Guanmengqian Huang, Keith Humphreys, Junko Ishiguro, Hidemi Ito, Motoki Iwasaki, Hiroji Iwata, Anna Jakubowska, Wolfgang Janni, Esther M. John, Nichola Johnson, Kristine Jones, Michael Jones, Arja Jukkola-Vuorinen, Rudolf Kaaks, Maria Kabisch, Katarzyna Kaczmarek, Daehee Kang, Yoshio Kasuga, Michael J. Kerin, Sofia Khan, Elza Khusnutdinova, Johanna I. Kiiski, Sung-Won Kim, Julia A. Knight, Veli-Matti Kosma, Vessela N. Kristensen, Ute Krüger, Ava Kwong, Diether Lambrechts, Loic Le Marchand, Eunjung Lee, Min Hyuk Lee, Jong Won Lee, Chuen Neng Lee, Flavio Lejbkowicz, Jingmei Li, Jenna Lilyquist, Annika Lindblom, Jolanta Lissowska, Wing-Yee Lo, Sibylle Loibl, Jirong Long, Artitaya Lophatananon, Jan Lubinski, Craig Luccarini, Michael P. Lux, Edmond S. K. Ma, Robert J. MacInnis, Tom Maishman, Enes Makalic, Kathleen E. Malone, Ivana Maleva Kostovska, Arto Mannermaa, Siranoush Manoukian, JoAnn E. Manson, Sara Margolin, Shivaani Mariapun, Maria Elena Martinez, Keitaro Matsuo, Dimitrios Mavroudis, James McKay, Catriona McLean, Hanne Meijers-Heijboer, Alfons Meindl, Primitiva Menéndez, Usha Menon, Jeffery Meyer, Hui Miao, Nicola Miller, Nur Aishah Mohd Taib, Kenneth Muir, Anna Marie Mulligan, Claire Mulot, Susan L. Neuhausen, Heli Nevanlinna, Patrick Neven, Sune F. Nielsen, Dong-Young Noh, Børge G. Nordestgaard, Aaron Norman, Olufunmilayo I. Olopade, Janet E. Olson, Håkan Olsson, Curtis Olswold, Nick Orr, V. Shane Pankratz, Sue K. Park, Tjoung-Won Park-Simon, Rachel Lloyd, Jose I. A. Perez, Paolo Peterlongo, Julian Peto, Kelly-Anne Phillips, Mila Pinchev, Dijana Plaseska-Karanfilska, Ross Prentice, Nadege Presneau, Darya Prokofyeva, Elizabeth Pugh, Katri Pylkäs, Brigitte Rack, Paolo Radice, Nazneen Rahman, Gadi Rennert, Hedy S. Rennert, Valerie Rhenius, Atocha Romero, Jane Romm, Kathryn J. Ruddy, Thomas Rüdiger, Anja Rudolph, Matthias Ruebner, Emiel J. T. Rutgers, Emmanouil Saloustros, Dale P. Sandler, Suleeporn Sangrajrang, Elinor J. Sawyer, Daniel F. Schmidt, Rita K. Schmutzler, Andreas Schneeweiss, Minouk J. Schoemaker, Fredrick Schumacher, Peter Schürmann, Rodney J. Scott, Christopher Scott, Sheila Seal, Caroline Seynaeve, Mitul Shah, Priyanka Sharma, Chen-Yang Shen, Grace Sheng, Mark E. Sherman, Martha J. Shrubsole, Xiao-Ou Shu, Ann Smeets, Christof Sohn, Melissa C. Southey, John J. Spinelli, Christa Stegmaier, Sarah Stewart-Brown, Jennifer Stone, Daniel O. Stram, Harald Surowy, Anthony Swerdlow, Rulla Tamimi, Jack A. Taylor, Maria Tengström, Soo H. Teo, Mary Beth Terry, Daniel C. Tessier, Somchai Thanasitthichai, Kathrin Thöne, Rob A. E. M. Tollenaar, Ian Tomlinson, Ling Tong, Diana Torres, Thérèse Truong, Chiu-Chen Tseng, Shoichiro Tsugane, Hans-Ulrich Ulmer, Giske Ursin, Michael Untch, Celine Vachon, Christi J. van Asperen, David van den Berg, Ans M. W. van den Ouweland, Lizet van der Kolk, Rob B. van der Luijt, Daniel Vincent, Jason Vollenweider, Quinten Waisfisz, Shan Wang-Gohrke, Clarice R. Weinberg, Camilla Wendt, Alice S. Whittemore, Hans Wildiers, Walter Willett, Robert Winqvist, Alicja Wolk, Anna H. Wu, Lucy Xia, Taiki Yamaji, Xiaohong R. Yang, Cheng Har Yip, Keun-Young Yoo, Jyh-Cherng Yu, Wei Zheng, Ying Zheng, Bin Zhu, Argyrios Ziogas, Elad Ziv, Sunil R. Lakhani, Antonis C. Antoniou, Arnaud Droit, Irene L. Andrulis, Christopher I. Amos, Fergus J. Couch, Paul D. P. Pharoah, Jenny Chang-Claude, Per Hall, David J. Hunter, Roger L. Milne, Montserrat García-Closas, Marjanka K. Schmidt, Stephen J. Chanock, Alison M. Dunning, Stacey L. Edwards, Gary D. Bader, Georgia Chenevix-Trench, Jacques Simard, Peter Kraft, Douglas F. Easton

Date Published: 1st Nov 2017

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

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