Search

Your search keyword '"Unger, Kristian"' showing total 571 results
Start Over Author "Unger, Kristian"
571 results on '"Unger, Kristian"'

101. Additional file 2 of Transcriptome network of the papillary thyroid carcinoma radiation marker CLIP2

Author

Selmansberger, Martin, Michna, Agata, Braselmann, Herbert, Höfig, Ines, Schorpp, Kenji, Weber, Peter, Natasa Anastasov, Zitzelsberger, Horst, Hess, Julia, and Unger, Kristian

Abstract

Additional file 2: SI Figure 2. A) number of direct CLIP2 interactors in the GNA reconstructed from gene set 4, dependent on the edge probability cut-off in the GeneNet method. Red dashed line indicates the selected cut-off of 0.5 B) Edge-list of the 1st neighborhood of CLIP2 reconstructed from gene set 4. pcor = partial correlation coefficient, node 1/2 = gene names of nodes, pval = p-value of partial correlation test, qval = q-values (positive false discovery rate), prob = edge probability black line: selected cut-off of 0.5 C) Degree distribution of the GNA generated from gene set 4 and a probability cut-off of 0.5 in the GeneNet reconstruction method. The degree distribution (approximately) follows a power law and thereby represents on attribute of a scale-free network.

Published
2020
Full Text
View/download PDF

102. Additional file 1 of Single-center versus multi-center data sets for molecular prognostic modeling: a simulation study

Author

Samaga, Daniel, Hornung, Roman, Braselmann, Herbert, Hess, Julia, Zitzelsberger, Horst, Belka, Claus, Anne-Laure Boulesteix, and Unger, Kristian

Subjects
Computer Science::Formal Languages and Automata Theory
Abstract

Additional file 1 Supplementary simulations. Further plots of the three simulation scenarios, adding “frequency of non-empty signatures”, “mean signature length” and performance scores free from empty signatures (i.e., performance of data usage setting, given a candidate signature was discovered.

Published
2020
Full Text
View/download PDF

103. Tumor DNA‐methylome derived epigenetic fingerprint identifies HPV‐negative head and neck patients at risk for locoregional recurrence after postoperative radiochemotherapy.

Author

Tawk, Bouchra, Wirkner, Ute, Schwager, Christian, Rein, Katrin, Zaoui, Karim, Federspil, Philippe A., Adeberg, Sebastian, Linge, Annett, Ganswindt, Ute, Hess, Julia, Unger, Kristian, Tinhofer, Ingeborg, Budach, Volker, Lohaus, Fabian, Krause, Mechthild, Guberina, Maja, Stuschke, Martin, Balermpas, Panagiotis, Rödel, Claus, and Grosu, Anca L.

Subjects
MICROARRAY technology, CHEMORADIOTHERAPY, DNA microarrays, PROGNOSIS, OVERALL survival, DNA methylation, SQUAMOUS cell carcinoma
Abstract

Biomarkers with relevance for loco‐regional therapy are needed in human papillomavirus negative aka HPV(−) head and neck squamous cell carcinoma (HNSCC). Based on the premise that DNA methylation pattern is highly conserved, we sought to develop a reliable and robust methylome‐based classifier identifying HPV(−) HNSCC patients at risk for loco‐regional recurrence (LR) and all‐event progression after postoperative radiochemotherapy (PORT‐C). The training cohort consisted of HPV‐DNA negative HNSCC patients (n = 128) homogeneously treated with PORT‐C in frame of the German Cancer Consortium—Radiation Oncology Group (DKTK‐ROG) multicenter biomarker trial. DNA Methylation analysis was performed using Illumina 450 K and 850 K‐EPIC microarray technology. The performance of the classifier was integrated with a series of biomarkers studied in the training set namely hypoxia‐, 5‐microRNA (5‐miR), stem‐cell gene‐expression signatures and immunohistochemistry (IHC)‐based immunological characterization of tumors (CD3/CD8/PD‐L1/PD1). Validation occurred in an independent cohort of HPV(−) HNSCC patients, pooled from two German centers (n = 125). We identified a 38‐methylation probe‐based HPV(−) Independent Classifier of disease Recurrence (HICR) with high prognostic value for LR, distant metastasis and overall survival (P < 10−9). HICR remained significant after multivariate analysis adjusting for anatomical site, lymph node extracapsular extension (ECE) and size (T‐stage). HICR high‐risk tumors were enriched for younger patients with hypoxic tumors (15‐gene signature) and elevated 5‐miR score. After adjustment for hypoxia and 5‐miR covariates, HICR maintained predicting all endpoints. HICR provides a novel mean for assessing the risk of LR in HPV(−) HNSCC patients treated with PORT‐C and opens a new opportunity for biomarker‐assisted stratification and therapy adaptation in these patients. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

104. Increased replication stress and R-loop accumulation in EGFRvIII-expressing glioblastoma present new therapeutic opportunities.

Author

Struve, Nina, Hoffer, Konstantin, Weik, Anna-Sophie, Riepen, Britta, Krug, Leonie, Cetin, Meryem H., Burmester, Jasmin, Ott, Leonie, Liebing, Jana, Gatzemeier, Fruzsina, Müller-Goebel, Justus, Gerbach, Mirja, Bußmann, Lara, Parplys, Ann Christin, Unger, Kristian, Mansour, Wael Y., Schüller, Ulrich, Rieckmann, Thorsten, Petersen, Cordula, and Rothkamm, Kai

Published
2022
Full Text
View/download PDF

106. MCL1 Is Required for Maintenance of Intestinal Homeostasis and Prevention of Carcinogenesis in Mice

Author

Healy, Marc E., primary, Boege, Yannick, additional, Hodder, Michael C., additional, Böhm, Friederike, additional, Malehmir, Mohsen, additional, Scherr, Anna-Lena, additional, Jetzer, Jasna, additional, Chan, Lap Kwan, additional, Parrotta, Rossella, additional, Jacobs, Kurt, additional, Clerbaux, Laure-Alix, additional, Kreutzer, Susanne, additional, Campbell, Andrew, additional, Gilchrist, Ella, additional, Gilroy, Kathryn, additional, Rodewald, Ann-Katrin, additional, Honcharova-Biletska, Hanna, additional, Schimmer, Roman, additional, Vélez, Karelia, additional, Büeler, Simone, additional, Cammareri, Patrizia, additional, Kalna, Gabriela, additional, Wenning, Anna S., additional, McCoy, Kathy D., additional, Gomez de Agüero, Mercedes, additional, Schulze-Bergkamen, Henning, additional, Klose, Christoph S.N., additional, Unger, Kristian, additional, Macpherson, Andrew J., additional, Moor, Andreas E., additional, Köhler, Bruno, additional, Sansom, Owen J., additional, Heikenwälder, Mathias, additional, and Weber, Achim, additional

Published
2020
Full Text
View/download PDF

108. Establishment and Validation of an Individualized Cell Cycle Process-Related Gene Signature to Predict Cancer-Specific Survival in Patients with Bladder Cancer

Author

Shi, Run, primary, Bao, Xuanwen, additional, Rogowski, Paul, additional, Schäfer, Christian, additional, Schmidt-Hegemann, Nina-Sophie, additional, Unger, Kristian, additional, Lu, Shun, additional, Sun, Jing, additional, Buchner, Alexander, additional, Stief, Christian, additional, Belka, Claus, additional, and Li, Minglun, additional

Published
2020
Full Text
View/download PDF

109. Utility of gene expression studies in relation to radiation exposure and clinical outcomes: thyroid cancer in the Ukrainian-American cohort and late health effects in a MAYAK worker cohort

Author

Abend, Michael, primary, Pfeiffer, Ruth M., additional, Port, Matthias, additional, Hatch, Maureen, additional, Bogdanova, Tetyana, additional, Tronko, Mykola D., additional, Mabuchi, Kiyohiko, additional, Azizova, Tamara, additional, Unger, Kristian, additional, Braselmann, Herbert, additional, Ostheim, Patrick, additional, and Brenner, Alina V., additional

Published
2020
Full Text
View/download PDF

111. Improved risk stratification in younger IDH wild-type glioblastoma patients by combining a 4-miRNA signature with MGMT promoter methylation status

Author

Unger, Kristian, primary, Fleischmann, Daniel F, additional, Ruf, Viktoria, additional, Felsberg, Jörg, additional, Piehlmaier, Daniel, additional, Samaga, Daniel, additional, Hess, Julia, additional, Suresh, Marian Preetham, additional, Mittelbronn, Michel, additional, Lauber, Kirsten, additional, Budach, Wilfried, additional, Sabel, Michael, additional, Rödel, Claus, additional, Reifenberger, Guido, additional, Herms, Jochen, additional, Tonn, Jörg-Christian, additional, Zitzelsberger, Horst, additional, Belka, Claus, additional, and Niyazi, Maximilian, additional

Published
2020
Full Text
View/download PDF

113. RET/PTC Rearrangement Occurring in Primary Peritoneal Carcinoma

Author

Flavin, Richard, Jackl, Gerhard, Finn, Stephen, Smyth, Paul, Ring, Martina, OʼRegan, Esther, Cahill, Susanne, Unger, Kristian, Denning, Karen, Li, Jinghuan, Aherne, Sinead, Tallini, Giovanni, Gaffney, Eoin, OʼLeary, J. J., Zitzelsberger, Horst, and Sheils, Orla

Published
2009

114. Improved outcome prediction across data sources through robust parameter tuning

Author

Schüller, Nicole, Boulesteix, Anne-Laure, Bischl, Bernd, Unger, Kristian, and Hornung, Roman

Subjects
Prediction, Robust modeling, Tuning parameter value optimization, Batch effects
Abstract

In many application areas, prediction rules trained based on high-dimensional data are subsequently applied to make predictions for observations from other sources, but they do not always perform well in this setting. This is because data sets from different sources can feature (slightly) differing distributions, even if they are, in principle, similar in terms of population and definitions of the variables. In the context of high-dimensional data and beyond, most prediction methods involve one or several tuning parameters. Their values are commonly chosen by maximizing the cross-validated prediction performance within the training data. This procedure, however, implicitly presumes that the data to which the prediction rule will be ultimately applied, follow the same distribution as the training data. If this is not the case, less complex prediction rules that slightly underfit the training data may be preferable. Indeed, a tuning parameter does not only control the degree of adjustment of a prediction rule to the training data, but also, more generally, the degree of adjustment to the distribution of the training data. On the basis of this idea, in this paper we compare various approaches including new procedures for choosing tuning parameter values that lead to better generalizing prediction rules than those obtained based on cross-validation. Most of these tuning approaches use an external validation data set. In our extensive comparison study based on a large collection of 15 transcriptomic real data sets, tuning on external data and robust tuning with tuned robustness parameter are the two approaches leading to better generalizing prediction rules. All R code written to produce and evaluate our results is available online.

Published
2019
Full Text
View/download PDF

119. Matching of array CGH and gene expression microarray features for the purpose of integrative genomic analyses

Author

van Wieringen Wessel N, Unger Kristian, Leday Gwenaël GR, Krijgsman Oscar, de Menezes Renée X, Ylstra Bauke, and van de Wiel Mark A

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background An increasing number of genomic studies interrogating more than one molecular level is published. Bioinformatics follows biological practice, and recent years have seen a surge in methodology for the integrative analysis of genomic data. Often such analyses require knowledge of which elements of one platform link to those of another. Although important, many integrative analyses do not or insufficiently detail the matching of the platforms. Results We describe, illustrate and discuss six matching procedures. They are implemented in the R-package sigaR (available from Bioconductor). The principles underlying the presented matching procedures are generic, and can be combined to form new matching approaches or be applied to the matching of other platforms. Illustration of the matching procedures on a variety of data sets reveals how the procedures differ in the use of the available data, and may even lead to different results for individual genes. Conclusions Matching of data from multiple genomics platforms is an important preprocessing step for many integrative bioinformatic analysis, for which we present six generic procedures, both old and new. They have been implemented in the R-package sigaR, available from Bioconductor.

Published
2012
Full Text
View/download PDF

121. MicroRNA expression patterns in oral squamous cell carcinoma: hsa‐mir‐99b‐3p and hsa‐mir‐100‐5p as novel prognostic markers for oral cancer

Author

Jakob, Mark, primary, Mattes, Lena M., additional, Küffer, Stefan, additional, Unger, Kristian, additional, Hess, Julia, additional, Bertlich, Mattis, additional, Haubner, Frank, additional, Ihler, Friedrich, additional, Canis, Martin, additional, Weiss, Bernhard G., additional, and Kitz, Julia, additional

Published
2019
Full Text
View/download PDF

124. Generation of focal mutations and large genomic deletions in the pancreas using inducible in vivo genome editing

Author

Mishra, Amrendra, primary, Emamgholi, Fatemeh, additional, Erlangga, Zulrahman, additional, Hartleben, Björn, additional, Unger, Kristian, additional, Wolff, Katharina, additional, Teichmann, Ulrike, additional, Kessel, Michael, additional, Woller, Norman, additional, Kühnel, Florian, additional, Dow, Lukas E, additional, Manns, Michael P, additional, Vogel, Arndt, additional, Lowe, Scott W, additional, Saborowski, Anna, additional, and Saborowski, Michael, additional

Published
2019
Full Text
View/download PDF

125. A Five-MicroRNA Signature Predicts Survival and Disease Control of Patients with Head and Neck Cancer Negative for HPV Infection

Author

Hess, Julia, primary, Unger, Kristian, additional, Maihoefer, Cornelius, additional, Schüttrumpf, Lars, additional, Wintergerst, Ludmila, additional, Heider, Theresa, additional, Weber, Peter, additional, Marschner, Sebastian, additional, Braselmann, Herbert, additional, Samaga, Daniel, additional, Kuger, Sebastian, additional, Pflugradt, Ulrike, additional, Baumeister, Philipp, additional, Walch, Axel, additional, Woischke, Christine, additional, Kirchner, Thomas, additional, Werner, Martin, additional, Werner, Kristin, additional, Baumann, Michael, additional, Budach, Volker, additional, Combs, Stephanie E., additional, Debus, Jürgen, additional, Grosu, Anca-Ligia, additional, Krause, Mechthild, additional, Linge, Annett, additional, Rödel, Claus, additional, Stuschke, Martin, additional, Zips, Daniel, additional, Zitzelsberger, Horst, additional, Ganswindt, Ute, additional, Henke, Michael, additional, and Belka, Claus, additional

Published
2019
Full Text
View/download PDF

126. Murine Liver Organoids as a Genetically Flexible System to Study Liver Cancer In Vivo and In Vitro

Author

Saborowski, Anna, primary, Wolff, Katharina, additional, Spielberg, Steffi, additional, Beer, Benedikt, additional, Hartleben, Björn, additional, Erlangga, Zulrahman, additional, Becker, Diana, additional, Dow, Lukas E., additional, Marhenke, Silke, additional, Woller, Norman, additional, Unger, Kristian, additional, Schirmacher, Peter, additional, Manns, Michael P., additional, Marquardt, Jens U., additional, Vogel, Arndt, additional, and Saborowski, Michael, additional

Published
2019
Full Text
View/download PDF

127. Induction of apoptosis in ovarian cancer cells by miR-493-3p directly targeting AKT2, STK38L, HMGA2, ETS1 and E2F5

Author

Kleemann, Michael, primary, Schneider, Helga, additional, Unger, Kristian, additional, Bereuther, Jeremias, additional, Fischer, Simon, additional, Sander, Philip, additional, Marion Schneider, E., additional, Fischer-Posovszky, Pamela, additional, Riedel, Christian U., additional, Handrick, René, additional, and Otte, Kerstin, additional

Published
2018
Full Text
View/download PDF

128. A prognostic mRNA expression signature of four 16q24.3 genes in radio(chemo)therapy‐treated head and neck squamous cell carcinoma (HNSCC)

Author

Wintergerst, Ludmila, primary, Selmansberger, Martin, additional, Maihoefer, Cornelius, additional, Schüttrumpf, Lars, additional, Walch, Axel, additional, Wilke, Christina, additional, Pitea, Adriana, additional, Woischke, Christine, additional, Baumeister, Philipp, additional, Kirchner, Thomas, additional, Belka, Claus, additional, Ganswindt, Ute, additional, Zitzelsberger, Horst, additional, Unger, Kristian, additional, and Hess, Julia, additional

Published
2018
Full Text
View/download PDF

130. X-change symposium: status and future of modern radiation oncology-from technology to biology.

Author

Corradini, Stefanie, Niyazi, Maximilian, Verellen, Dirk, Valentini, Vincenzo, Walsh, Seán, Grosu, Anca-L., Lauber, Kirsten, Giaccia, Amato, Unger, Kristian, Debus, Jürgen, Pieters, Bradley R., Guckenberger, Matthias, Senan, Suresh, Budach, Wilfried, Rad, Roland, Mayerle, Julia, and Belka, Claus

Subjects
POSITRON emission tomography, PROTON therapy, RADIOBIOLOGY, BIOLOGY, RADIATION, COMPUTERS in medicine, RESEARCH funding, RADIOTHERAPY, TUMORS, ONCOLOGY
Abstract

Future radiation oncology encompasses a broad spectrum of topics ranging from modern clinical trial design to treatment and imaging technology and biology. In more detail, the application of hybrid MRI devices in modern image-guided radiotherapy; the emerging field of radiomics; the role of molecular imaging using positron emission tomography and its integration into clinical routine; radiation biology with its future perspectives, the role of molecular signatures in prognostic modelling; as well as special treatment modalities such as brachytherapy or proton beam therapy are areas of rapid development. More clinically, radiation oncology will certainly find an important role in the management of oligometastasis. The treatment spectrum will also be widened by the rational integration of modern systemic targeted or immune therapies into multimodal treatment strategies. All these developments will require a concise rethinking of clinical trial design. This article reviews the current status and the potential developments in the field of radiation oncology as discussed by a panel of European and international experts sharing their vision during the "X-Change" symposium, held in July 2019 in Munich (Germany). [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

131. Utility of gene expression studies in relation to radiation exposure and clinical outcomes: thyroid cancer in the Ukrainian-American cohort and late health effects in a MAYAK worker cohort.

Author

Abend, Michael, Pfeiffer, Ruth M., Port, Matthias, Hatch, Maureen, Bogdanova, Tetyana, Tronko, Mykola D., Mabuchi, Kiyohiko, Azizova, Tamara, Unger, Kristian, Braselmann, Herbert, Ostheim, Patrick, and Brenner, Alina V.

Subjects
RADIATION exposure, THYROID cancer, GENE expression, RADIATION protection, GAMMA rays
Abstract

We herein report on changes in gene expression after radiation exposure to iodine-131 from the Chernobyl accident in the Ukrainian-American thyroid cohort and to external gamma ray or internal plutonium exposure in the Mayak Production Association radiation workers. Taking advantage of access to tissue samples from the thyroid cancer cases in the Ukrainian-American cohort, our group tried to identify candidate genes to discriminate spontaneously occurring thyroid cancers from thyroid cancers caused by radiation exposure. We also examined gene expression changes in normal and cancerous thyroid tissue in relation to iodine-131 dose separately. Gene expression changes in the peripheral blood of radiation exposed Mayak workers were examined to elucidate the dose-to-gene and gene-to-health (e.g. cardiovascular disease) relationships. Results of both projects are discussed under the aspect of dose-response relationships (dose-to-gene) and clinical outcome relationships (gene-to-effect) in light of how mechanistic data can be translated into actionable knowledge for radiation protection or clinical purposes. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

132. Direct conversion of human fibroblasts into therapeutically active vascular wall-typical mesenchymal stem cells.

Author

Steens, Jennifer, Unger, Kristian, Klar, Lea, Neureiter, Anika, Wieber, Karolin, Hess, Julia, Jakob, Heinz G., Klump, Hannes, and Klein, Diana

Subjects
*MESENCHYMAL stem cells, *FIBROBLASTS, *STEM cells, *GENETIC code, *CARDIOVASCULAR diseases
Abstract

Cell-based therapies using adult stem cells are promising options for the treatment of a number of diseases including autoimmune and cardiovascular disorders. Among these, vascular wall-derived mesenchymal stem cells (VW-MSCs) might be particularly well suited for the protection and curative treatment of vascular damage because of their tissue-specific action. Here we report a novel method for the direct conversion of human skin fibroblasts towards MSCs using a VW-MSC-specific gene code (HOXB7, HOXC6 and HOXC8) that directs cell fate conversion bypassing pluripotency. This direct programming approach using either a self-inactivating (SIN) lentiviral vector expressing the VW-MSC-specific HOX-code or a tetracycline-controlled Tet-On system for doxycycline-inducible gene expressions of HOXB7, HOXC6 and HOXC8 successfully mediated the generation of VW-typical MSCs with classical MSC characteristics in vitro and in vivo. The induced VW-MSCs (iVW-MSCs) fulfilled all criteria of MSCs as defined by the International Society for Cellular Therapy (ISCT). In terms of multipotency and clonogenicity, which are important specific properties to discriminate MSCs from fibroblasts, iVW-MSCs behaved like primary ex vivo isolated VW-MSCs and shared similar molecular and DNA methylation signatures. With respect to their therapeutic potential, these cells suppressed lymphocyte proliferation in vitro, and protected mice against vascular damage in a mouse model of radiation-induced pneumopathy in vivo, as well as ex vivo cultured human lung tissue. The feasibility to obtain patient-specific VW-MSCs from fibroblasts in large amounts by a direct conversion into induced VW-MSCs could potentially open avenues towards novel, MSC-based therapies. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

133. Functional interplay of Epstein-Barr virus oncoproteins in a mouse model of B cell lymphomagenesis.

Author

Sommermann, Thomas, Tomoharu Yasuda, Ronen, Jonathan, Wirtz, Tristan, Weber, Timm, Sack, Ulrike, Caeser, Rebecca, Jingwei Zhang, Xun Li, Van Trung Chu, Jauch, Anna, Unger, Kristian, Hodson, Daniel J., Akalin, Altuna, and Rajewsky, Klaus

Subjects
B cells, B cell differentiation, EPSTEIN-Barr virus, PLASMA cells, CELL transformation
Abstract

Epstein-Barr virus (EBV) is a B cell transforming virus that causes B cell malignancies under conditions of immune suppression. EBV orchestrates B cell transformation through its latent membrane proteins (LMPs) and Epstein-Barr nuclear antigens (EBNAs). We here identify secondary mutations in mouse B cell lymphomas induced by LMP1, to predict and identify key functions of other EBV genes during transformation. We find aberrant activation of early B cell factor 1 (EBF1) to promote transformation of LMP1-expressing B cells by inhibiting their differentiation to plasma cells. EBV EBNA3A phenocopies EBF1 activities in LMP1-expressing B cells, promoting transformation while inhibiting differentiation. In cells expressing LMP1 together with LMP2A, EBNA3A only promotes lymphomagenesis when the EBNA2 target Myc is also overexpressed. Collectively, our data support a model where proproliferative activities of LMP1, LMP2A, and EBNA2 in combination with EBNA3A-mediated inhibition of terminal plasma cell differentiation critically control EBV-mediated B cell lymphoma-genesis. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

134. Generation of focal mutations and large genomic deletions in the pancreas using inducible in vivo genome editing.

Author

Mishra, Amrendra, Emamgholi, Fatemeh, Erlangga, Zulrahman, Hartleben, Björn, Unger, Kristian, Wolff, Katharina, Teichmann, Ulrike, Kessel, Michael, Woller, Norman, Kühnel, Florian, Dow, Lukas E, Manns, Michael P, Vogel, Arndt, Lowe, Scott W, Saborowski, Anna, and Saborowski, Michael

Subjects
GENOME editing, UBIQUITIN ligases, GENETIC models, EMBRYONIC stem cells, PANCREAS, ONCOLOGY
Abstract

Beyond the nearly uniform presence of KRAS mutations, pancreatic cancer is increasingly recognized as a heterogeneous disease. Preclinical in vivo model systems exist, but with the advent of precision oncology, murine models with enhanced genetic flexibility are needed to functionally annotate genetic alterations found in the human malignancy. Here, we describe the generation of focal gene disruptions and large chromosomal deletions via inducible and pancreas-specific expression of Cas9 in adult mice. Experimental mice are derived on demand directly from genetically engineered embryonic stem cells, without the need for further intercrossing. To provide initial validation of our approach, we show that disruption of the E3 ubiquitin ligase Rnf43 accelerates Kras G12D -dependent tumourigenesis. Moreover, we demonstrate that this system can be used to rapidly interrogate the impact of complex cancer-associated alleles through the generation of a previously unstudied 1.2 megabase deletion surrounding the CDKN2A and CDKN2B tumour suppressors. Thus, our approach is capable of reproducibly generating biallelic and precise loss of large chromosomal fragments that, in conjunction with mutant Kras , leads to development of pancreatic ductal adenocarcinoma with full penetrance. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

135. Copy number aberrations from Affymetrix SNP 6.0 genotyping data—how accurate are commonly used prediction approaches?

Author

Pitea, Adriana, Kondofersky, Ivan, Sass, Steffen, Theis, Fabian J, Mueller, Nikola S, and Unger, Kristian

Subjects
FORECASTING, CONFOUNDING variables, DATA analysis, CANCER research, TUMORS
Abstract

Copy number aberrations (CNAs) are known to strongly affect oncogenes and tumour suppressor genes. Given the critical role CNAs play in cancer research, it is essential to accurately identify CNAs from tumour genomes. One particular challenge in finding CNAs is the effect of confounding variables. To address this issue, we assessed how commonly used CNA identification algorithms perform on SNP 6.0 genotyping data in the presence of confounding variables. We simulated realistic synthetic data with varying levels of three confounding variables—the tumour purity, the length of a copy number region and the CNA burden (the percentage of CNAs present in a profiled genome)—and evaluated the performance of OncoSNP, ASCAT, GenoCNA, GISTIC and CGHcall. Furthermore, we implemented and assessed CGHcall*, an adjusted version of CGHcall accounting for high CNA burden. Our analysis on synthetic data indicates that tumour purity and the CNA burden strongly influence the performance of all the algorithms. No algorithm can correctly find lost and gained genomic regions across all tumour purities. The length of CNA regions influenced the performance of ASCAT, CGHcall and GISTIC. OncoSNP, GenoCNA and CGHcall* showed little sensitivity. Overall, CGHcall* and OncoSNP showed reasonable performance, particularly in samples with high tumour purity. Our analysis on the HapMap data revealed a good overlap between CGHcall, CGHcall* and GenoCNA results and experimentally validated data. Our exploratory analysis on the TCGA HNSCC data revealed plausible results of CGHcall, CGHcall* and GISTIC in consensus HNSCC CNA regions. Code is available at https://github.com/adspit/PASCAL. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

136. EpCAM ectodomain EpEX is a ligand of EGFR that counteracts EGF-mediated epithelial-mesenchymal transition through modulation of phospho-ERK1/2 in head and neck cancers

Author

Pan, Min, primary, Schinke, Henrik, additional, Luxenburger, Elke, additional, Kranz, Gisela, additional, Shakhtour, Julius, additional, Libl, Darko, additional, Huang, Yuanchi, additional, Gaber, Aljaž, additional, Pavšič, Miha, additional, Lenarčič, Brigita, additional, Kitz, Julia, additional, Jakob, Mark, additional, Schwenk-Zieger, Sabina, additional, Canis, Martin, additional, Hess, Julia, additional, Unger, Kristian, additional, Baumeister, Philipp, additional, and Gires, Olivier, additional

Published
2018
Full Text
View/download PDF

137. Abstract 391: Evolutionary trajectories andKRASgene dosage define pancreatic cancer phenotypes

Author

Mueller, Sebastian, primary, Engleitner, Thomas, additional, Maresch, Roman, additional, Zukowska, Magdalena, additional, Lange, Sebastian, additional, Kaltenbacher, Thorsten, additional, Konukiewitz, Björn, additional, Öllinger, Rupert, additional, Zwiebel, Maximilian, additional, Strong, Alex, additional, Yen, Hsi-Yu, additional, Banerjee, Ruby, additional, Louzada, Sandra, additional, Fu, Beiyuan, additional, Seidler, Barbara, additional, Götzfried, Juliana, additional, Schuck, Kathleen, additional, Hassan, Zonera, additional, Schönhuber, Nina, additional, Klein, Sabine, additional, Veltkamp, Christian, additional, Friedrich, Mathias, additional, Rad, Lena, additional, Barenboim, Maxim, additional, Ziegenhain, Christoph, additional, Hess, Julia, additional, Dovey, Oliver M., additional, Eser, Stefan, additional, Parekh, Swati, additional, Constantino-Casas, Fernando, additional, Rosa, Jorge de la, additional, Sierra, Marta I., additional, Fraga, Mario, additional, Mayerle, Julia, additional, Klöppel, Günter, additional, Schmid, Roland M., additional, Cadiñanos, Juan, additional, Liu, Pentao, additional, Vassiliou, George, additional, Weichert, Wilko, additional, Steiger, Katja, additional, Enard, Wolfgang, additional, Yang, Fengtang, additional, Unger, Kristian, additional, Schneider, Günter, additional, Varela, Ignacio, additional, Bradley, Allan, additional, Saur, Dieter, additional, and Rad, Roland, additional

Published
2018
Full Text
View/download PDF

138. A genomic copy number signature predicts radiation exposure in post‐ C hernobyl breast cancer

Author

Wilke, Christina M., primary, Braselmann, Herbert, additional, Hess, Julia, additional, Klymenko, Sergiy V., additional, Chumak, Vadim V., additional, Zakhartseva, Liubov M., additional, Bakhanova, Elena V., additional, Walch, Axel K., additional, Selmansberger, Martin, additional, Samaga, Daniel, additional, Weber, Peter, additional, Schneider, Ludmila, additional, Fend, Falko, additional, Bösmüller, Hans C., additional, Zitzelsberger, Horst, additional, and Unger, Kristian, additional

Published
2018
Full Text
View/download PDF

139. Expression of miRNA‐26b‐5p and its target TRPS1 is associated with radiation exposure in post‐Chernobyl breast cancer

Author

Wilke, Christina M., primary, Hess, Julia, additional, Klymenko, Sergiy V., additional, Chumak, Vadim V., additional, Zakhartseva, Liubov M., additional, Bakhanova, Elena V., additional, Feuchtinger, Annette, additional, Walch, Axel K., additional, Selmansberger, Martin, additional, Braselmann, Herbert, additional, Schneider, Ludmila, additional, Pitea, Adriana, additional, Steinhilber, Julia, additional, Fend, Falko, additional, Bösmüller, Hans C., additional, Zitzelsberger, Horst, additional, and Unger, Kristian, additional

Published
2017
Full Text
View/download PDF

140. NASH limits anti-tumour surveillance in immunotherapy-treated HCC

Author

Pfister, Dominik, Núñez, Nicolás Gonzalo, Pinyol, Roser, Govaere, Olivier, Pinter, Matthias, Szydlowska, Marta, Gupta, Revant, Qiu, Mengjie, Deczkowska, Aleksandra, Weiner, Assaf, Müller, Florian, Sinha, Ankit, Friebel, Ekaterina, Engleitner, Thomas, Lenggenhager, Daniela, Moncsek, Anja, Heide, Danijela, Stirm, Kristin, Kosla, Jan, Kotsiliti, Eleni, Leone, Valentina, Dudek, Michael, Yousuf, Suhail, Inverso, Donato, Singh, Indrabahadur, Teijeiro, Ana, Castet, Florian, Montironi, Carla, Haber, Philipp K., Tiniakos, Dina, Bedossa, Pierre, Cockell, Simon, Younes, Ramy, Vacca, Michele, Marra, Fabio, Schattenberg, Jörn M., Allison, Michael, Bugianesi, Elisabetta, Ratziu, Vlad, Pressiani, Tiziana, D’Alessio, Antonio, Personeni, Nicola, Rimassa, Lorenza, Daly, Ann K., Scheiner, Bernhard, Pomej, Katharina, Kirstein, Martha M., Vogel, Arndt, Peck-Radosavljevic, Markus, Hucke, Florian, Finkelmeier, Fabian, Waidmann, Oliver, Trojan, Jörg, Schulze, Kornelius, Wege, Henning, Koch, Sandra, Weinmann, Arndt, Bueter, Marco, Rössler, Fabian, Siebenhüner, Alexander, Dosso, Sara De, Mallm, Jan-Philipp, Umansky, Viktor, Jugold, Manfred, Luedde, Tom, Schietinger, Andrea, Schirmacher, Peter, Emu, Brinda, Augustin, Hellmut G., Billeter, Adrian, Müller-Stich, Beat, Kikuchi, Hiroto, Duda, Dan G., Kütting, Fabian, Waldschmidt, Dirk-Thomas, Ebert, Matthias Philip, Rahbari, Nuh, Mei, Henrik E., Schulz, Axel Ronald, Ringelhan, Marc, Malek, Nisar, Spahn, Stephan, Bitzer, Michael, Ruiz de Galarreta, Marina, Lujambio, Amaia, Dufour, Jean-Francois, Marron, Thomas U., Kaseb, Ahmed, Kudo, Masatoshi, Huang, Yi-Hsiang, Djouder, Nabil, Wolter, Katharina, Zender, Lars, Marche, Parice N., Decaens, Thomas, Pinato, David J., Rad, Roland, Mertens, Joachim C., Weber, Achim, Unger, Kristian, Meissner, Felix, Roth, Susanne, Jilkova, Zuzana Macek, Claassen, Manfred, Anstee, Quentin M., Amit, Ido, Knolle, Percy, Becher, Burkhard, Llovet, Josep M., and Heikenwalder, Mathias

Abstract

Hepatocellular carcinoma (HCC) can have viral or non-viral causes1–5. Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need6,7. Here we report the progressive accumulation of exhausted, unconventionally activated CD8+PD1+T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded activated CD8+PD1+T cells within tumours but did not lead to tumour regression, which indicates that tumour immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASH–HCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8+PD1+CXCR6+, TOX+, and TNF+T cells. The increase in HCC triggered by anti-PD1 treatment was prevented by depletion of CD8+T cells or TNF neutralization, suggesting that CD8+T cells help to induce NASH–HCC, rather than invigorating or executing immune surveillance. We found similar phenotypic and functional profiles in hepatic CD8+PD1+T cells from humans with NAFLD or NASH. A meta-analysis of three randomized phase III clinical trials that tested inhibitors of PDL1 (programmed death-ligand 1) or PD1 in more than 1,600 patients with advanced HCC revealed that immune therapy did not improve survival in patients with non-viral HCC. In two additional cohorts, patients with NASH-driven HCC who received anti-PD1 or anti-PDL1 treatment showed reduced overall survival compared to patients with other aetiologies. Collectively, these data show that non-viral HCC, and particularly NASH–HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of patients with HCC according to underlying aetiology in studies of immunotherapy as a primary or adjuvant treatment.

Published
2021
Full Text
View/download PDF

141. Additional file 13: Figure S3. of Transcriptomic analyses of the radiation response in head and neck squamous cell carcinoma subclones with different radiation sensitivity: time-course gene expression profiles and gene association networks

Author

Michna, Agata, SchĂśtz, Ulrike, Selmansberger, Martin, Zitzelsberger, Horst, Lauber, Kirsten, Unger, Kristian, and Hess, Julia

Subjects
body regions, nervous system, fungi, sense organs, skin and connective tissue diseases
Abstract

Temporal expression and corresponding fold-changes of gene ERV3-1 after irradiation with 8Â Gy. (PDF 531Â kb)

Published
2016
Full Text
View/download PDF

142. Additional file 2: Table S2. of Transcriptomic analyses of the radiation response in head and neck squamous cell carcinoma subclones with different radiation sensitivity: time-course gene expression profiles and gene association networks

Author

Michna, Agata, SchĂśtz, Ulrike, Selmansberger, Martin, Zitzelsberger, Horst, Lauber, Kirsten, Unger, Kristian, and Hess, Julia

Subjects
stomatognathic diseases
Abstract

Overview on the cytogenetic aberrations in CAL-33 cells. Clonal structural and numerical chromosomal aberrations detected by SKY and copy number changes detected by array CGH are listed. (DOCX 94Â kb)

Published
2016
Full Text
View/download PDF

143. Additional file 3: Figure S1. of Transcriptomic analyses of the radiation response in head and neck squamous cell carcinoma subclones with different radiation sensitivity: time-course gene expression profiles and gene association networks

Author

Michna, Agata, SchĂśtz, Ulrike, Selmansberger, Martin, Zitzelsberger, Horst, Lauber, Kirsten, Unger, Kristian, and Hess, Julia

Abstract

Analyses of proliferation rates and cell cycle distribution. Proliferation curves of the CAL-33 parental cell line and the subclones SP and RP are shown in panel (A). Doubling times were determined in the exponential growth phase by semi-log regression. Cell cycle analyses were performed under exponential growth conditions (B). The dynamics of G2-arrest upon irradiation at 4Â Gy are shown in figure panel (C). (PDF 318Â kb)

Published
2016
Full Text
View/download PDF

144. Additional file 5: Table S4. of Transcriptomic analyses of the radiation response in head and neck squamous cell carcinoma subclones with different radiation sensitivity: time-course gene expression profiles and gene association networks

Author

Michna, Agata, SchĂśtz, Ulrike, Selmansberger, Martin, Zitzelsberger, Horst, Lauber, Kirsten, Unger, Kristian, and Hess, Julia

Subjects
sense organs
Abstract

Technical validation of microarray data. Eight of the differentially expressed genes detected with the microarray technology were arbitrarily chosen for technical validation by qRT-PCR. Correlation analysis results (Spearmanâ s rho coefficient) and fold-changes (microarray and qRT-PCR) are shown. Asterisks (*) indicate fold-change values for genes detected as differentially expressed by microarray analysis. (DOCX 52Â kb)

Published
2016
Full Text
View/download PDF

145. A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development

Author

Boege, Yannick, primary, Malehmir, Mohsen, additional, Healy, Marc E., additional, Bettermann, Kira, additional, Lorentzen, Anna, additional, Vucur, Mihael, additional, Ahuja, Akshay K., additional, Böhm, Friederike, additional, Mertens, Joachim C., additional, Shimizu, Yutaka, additional, Frick, Lukas, additional, Remouchamps, Caroline, additional, Mutreja, Karun, additional, Kähne, Thilo, additional, Sundaravinayagam, Devakumar, additional, Wolf, Monika J., additional, Rehrauer, Hubert, additional, Koppe, Christiane, additional, Speicher, Tobias, additional, Padrissa-Altés, Susagna, additional, Maire, Renaud, additional, Schattenberg, Jörn M., additional, Jeong, Ju-Seong, additional, Liu, Lei, additional, Zwirner, Stefan, additional, Boger, Regina, additional, Hüser, Norbert, additional, Davis, Roger J., additional, Müllhaupt, Beat, additional, Moch, Holger, additional, Schulze-Bergkamen, Henning, additional, Clavien, Pierre-Alain, additional, Werner, Sabine, additional, Borsig, Lubor, additional, Luther, Sanjiv A., additional, Jost, Philipp J., additional, Weinlich, Ricardo, additional, Unger, Kristian, additional, Behrens, Axel, additional, Hillert, Laura, additional, Dillon, Christopher, additional, Di Virgilio, Michela, additional, Wallach, David, additional, Dejardin, Emmanuel, additional, Zender, Lars, additional, Naumann, Michael, additional, Walczak, Henning, additional, Green, Douglas R., additional, Lopes, Massimo, additional, Lavrik, Inna, additional, Luedde, Tom, additional, Heikenwalder, Mathias, additional, and Weber, Achim, additional

Published
2017
Full Text
View/download PDF

147. Kupffer Cell-Derived Tnf Triggers Cholangiocellular Tumorigenesis through JNK due to Chronic Mitochondrial Dysfunction and ROS

Author

Yuan, Detian, primary, Huang, Shan, additional, Berger, Emanuel, additional, Liu, Lei, additional, Gross, Nina, additional, Heinzmann, Florian, additional, Ringelhan, Marc, additional, Connor, Tracy O., additional, Stadler, Mira, additional, Meister, Michael, additional, Weber, Julia, additional, Öllinger, Rupert, additional, Simonavicius, Nicole, additional, Reisinger, Florian, additional, Hartmann, Daniel, additional, Meyer, Rüdiger, additional, Reich, Maria, additional, Seehawer, Marco, additional, Leone, Valentina, additional, Höchst, Bastian, additional, Wohlleber, Dirk, additional, Jörs, Simone, additional, Prinz, Marco, additional, Spalding, Duncan, additional, Protzer, Ulrike, additional, Luedde, Tom, additional, Terracciano, Luigi, additional, Matter, Matthias, additional, Longerich, Thomas, additional, Knolle, Percy, additional, Ried, Thomas, additional, Keitel, Verena, additional, Geisler, Fabian, additional, Unger, Kristian, additional, Cinnamon, Einat, additional, Pikarsky, Eli, additional, Hüser, Norbert, additional, Davis, Roger J., additional, Tschaharganeh, Darjus F., additional, Rad, Roland, additional, Weber, Achim, additional, Zender, Lars, additional, Haller, Dirk, additional, and Heikenwalder, Mathias, additional

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results