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5,844 results on '"Ulrich, M."'

261. Prädikative und präsymptomatische Diagnostik spätmanifestierender Erkrankungen: Empfehlungen zur Testung einwilligungsfähiger Minderjähriger

Author

Ulrich M. Gassner, Heiner Fangerau, Florian Braune, and Janet Opper

Abstract

During recent years, prediction has reached ever wider areas of medicine. This development includes the prenatal, predictive and pre-symptomatic diagnosing of diseases which manifest themselves later in life. Since a cure for a number of the diseases in question is currently not available and cannot be expected in the near future, the problem arises of how to deal with the expected findings of such diagnoses appropriately. Both in clinical application and in research, the question occurs of how to adequately address the expectations of patients and their families with regard to prognostics. In particular, predictive and pre-symptomatic diagnostics in children and adolescents poses challenges because children’s ability to consent to medical tests is even more difficult to assess than adults’. This volume offers an analysis and recommendations regarding predictive diagnostics for late onset diseases in children. Its recommendations are the result of a project funded by the German Federal Ministry of Education and Research. In addition to content analyses of existing research literature, they are based on interviews with individuals who sought or wanted genetic counselling and on interviews with physicians who are experts in human genetics.

Published
2023

263. Virotherapy in Germany—Recent Activities in Virus Engineering, Preclinical Development, and Clinical Studies

Author

Dirk M. Nettelbeck, Mathias F. Leber, Jennifer Altomonte, Assia Angelova, Julia Beil, Susanne Berchtold, Maike Delic, Jürgen Eberle, Anja Ehrhardt, Christine E. Engeland, Henry Fechner, Karsten Geletneky, Katrin Goepfert, Per Sonne Holm, Stefan Kochanek, Florian Kreppel, Lea Krutzke, Florian Kühnel, Karl Sebastian Lang, Antonio Marchini, Markus Moehler, Michael D. Mühlebach, Ulrike Naumann, Roman Nawroth, Jürg Nüesch, Jean Rommelaere, Ulrich M. Lauer, and Guy Ungerechts

Subjects
oncolytic virus, virotherapy, research in Germany, virus engineering, virus targeting, therapeutic transgene, Microbiology, QR1-502
Abstract

Virotherapy research involves the development, exploration, and application of oncolytic viruses that combine direct killing of cancer cells by viral infection, replication, and spread (oncolysis) with indirect killing by induction of anti-tumor immune responses. Oncolytic viruses can also be engineered to genetically deliver therapeutic proteins for direct or indirect cancer cell killing. In this review—as part of the special edition on “State-of-the-Art Viral Vector Gene Therapy in Germany”—the German community of virotherapists provides an overview of their recent research activities that cover endeavors from screening and engineering viruses as oncolytic cancer therapeutics to their clinical translation in investigator-initiated and sponsored multi-center trials. Preclinical research explores multiple viral platforms, including new isolates, serotypes, or fitness mutants, and pursues unique approaches to engineer them towards increased safety, shielded or targeted delivery, selective or enhanced replication, improved immune activation, delivery of therapeutic proteins or RNA, and redirecting antiviral immunity for cancer cell killing. Moreover, several oncolytic virus-based combination therapies are under investigation. Clinical trials in Germany explore the safety and potency of virotherapeutics based on parvo-, vaccinia, herpes, measles, reo-, adeno-, vesicular stomatitis, and coxsackie viruses, including viruses encoding therapeutic proteins or combinations with immune checkpoint inhibitors. These research advances represent exciting vantage points for future endeavors of the German virotherapy community collectively aimed at the implementation of effective virotherapeutics in clinical oncology.

Published
2021
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264. Global-scale evidence for the refractory nature of riverine black carbon

Author

Coppola, Alysha I., Wiedemeier, Daniel B., Galy, Valier, Haghipour, Negar, Hanke, Ulrich M., Nascimento, Gabriela S., Usman, Muhammed, Blattmann, Thomas M., Reisser, Moritz, Freymond, Chantal V., Zhao, Meixun, Voss, Britta, Wacker, Lukas, Schefuß, Enno, Peucker-Ehrenbrink, Bernhard, Abiven, Samuel, Schmidt, Michael W. I., and Eglinton, Timothy I.

Published
2018
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267. Chemovirotherapy of Pancreatic Adenocarcinoma by Combining Oncolytic Vaccinia Virus GLV-1h68 with nab-Paclitaxel Plus Gemcitabine

Author

Eike Binz, Susanne Berchtold, Julia Beil, Martina Schell, Christine Geisler, Irina Smirnow, and Ulrich M. Lauer

Subjects
pancreatic cancer, vaccinia virus, chemovirotherapy, virotherapy, immunotherapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Oncolytic viruses have proven their therapeutic potential against a variety of different tumor entities both in vitro and in vivo. Their ability to selectively infect and lyse tumor cells, while sparing healthy tissues, makes them favorable agents for tumor-specific treatment approaches. Particularly, the addition of virotherapeutics to already established chemotherapy protocols (so-called chemovirotherapy) is of major interest. Here we investigated the in vitro cytotoxic effect of the oncolytic vaccinia virus GLV-1h68 combined with dual chemotherapy with nab-paclitaxel plus gemcitabine in four human pancreatic adenocarcinoma cell lines (AsPc-1, BxPc-3, MIA-PaCa-2, and Panc-1). This chemovirotherapeutic protocol resulted in enhanced tumor cell killing in two tumor cell lines compared to the respective monotherapies. We were thereby able to show that the combination of oncolytic vaccinia virus GLV-1h68 with nab-paclitaxel and gemcitabine has great potential in the chemovirotherapeutic treatment of advanced pancreatic adenocarcinoma. However, the key to a successful combinatorial chemovirotherapeutic treatment seems to be a profound viral replication, as tumor cell lines that were non-responsive to the combination therapy exhibited a reduced viral replication in the presence of the chemotherapeutics. This finding is of special significance when aiming to achieve a virus-mediated induction of a profound and long-lasting antitumor immunity.

Published
2017
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268. Regulation of drug metabolism and toxicity by multiple factors of genetics, epigenetics, lncRNAs, gut microbiota, and diseases: a meeting report of the 21st International Symposium on Microsomes and Drug Oxidations (MDO)

Author

Ai-Ming Yu, Magnus Ingelman-Sundberg, Nathan J. Cherrington, Lauren M. Aleksunes, Ulrich M. Zanger, Wen Xie, Hyunyoung Jeong, Edward M. Morgan, Peter J. Turnbaugh, Curtis D. Klaassen, Aadra P. Bhatt, Matthew R. Redinbo, Pengying Hao, David J. Waxman, Li Wang, and Xiao-bo Zhong

Subjects
Drug metabolism and toxicity, Genetics, Epigenetics, Gut microbiota, Long non-coding RNAs, Disease, Personalized medication, Therapeutics. Pharmacology, RM1-950
Abstract

Variations in drug metabolism may alter drug efficacy and cause toxicity; better understanding of the mechanisms and risks shall help to practice precision medicine. At the 21st International Symposium on Microsomes and Drug Oxidations held in Davis, California, USA, in October 2–6, 2016, a number of speakers reported some new findings and ongoing studies on the regulation mechanisms behind variable drug metabolism and toxicity, and discussed potential implications to personalized medications. A considerably insightful overview was provided on genetic and epigenetic regulation of gene expression involved in drug absorption, distribution, metabolism, and excretion (ADME) and drug response. Altered drug metabolism and disposition as well as molecular mechanisms among diseased and special populations were presented. In addition, the roles of gut microbiota in drug metabolism and toxicology as well as long non-coding RNAs in liver functions and diseases were discussed. These findings may offer new insights into improved understanding of ADME regulatory mechanisms and advance drug metabolism research.

Published
2017
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269. Phase I study of VSV-GP (BI 1831169) as monotherapy or combined with ezabenlimab in advanced and refractory solid tumors

Author

Mercedes Porosnicu, Anne-Marie Quinson, Kate Crossley, Stephan Luecke, and Ulrich M Lauer

Subjects
Oncolytic Virotherapy, Oncolytic Viruses, Cancer Research, Clinical Trials, Phase I as Topic, Oncology, Cell Line, Tumor, Neoplasms, Antibodies, Monoclonal, Humans, General Medicine, Immune Checkpoint Inhibitors, Glycoproteins
Abstract

Patients with advanced, recurrent or metastatic cancer have poor prognosis despite treatment advancements. Vesicular stomatitis virus (VSV)-glycoprotein (GP; BI 1831169) is a chimeric VSV with its neurotropic glycoprotein G replaced by the non-neurotropic GP of the lymphocytic choriomeningitis virus. This live, recombinant oncolytic virus has demonstrated preclinical efficacy as a viral-based immunotherapy due to its interferon-dependent tumor specificity, potent oncolysis and stimulation of antitumor immune activity. Co-administration of the immune checkpoint inhibitor, ezabenlimab (BI 754091), alongside VSV-GP may synergistically enhance antitumor immune activity. Here, we describe the rationale and design of the first-in-human, phase I, dose-escalation study of VSV-GP alone and in combination with the immune checkpoint inhibitor ezabenlimab in patients with advanced, metastatic or relapsed and refractory solid tumors (NCT05155332).There is a need to develop new treatments for people living with cancer. Immunotherapy is a type of medicine that works by helping the body’s natural defenses, known as the immune system, to destroy cancer cells. There are different types of immunotherapies such as oncolytic viruses (OVs) and immune checkpoint inhibitors (ICIs). OVs are viruses that may help destroy cancer cells while leaving normal cells unharmed. They work by replicating within cancer cells; this causes them to burst and release more of the virus which then infects nearby cancer cells and activates the body’s immune system. ICIs may be able to work together with OVs to amplify this effect. Vesicular stomatitis virus (VSV)-glycoprotein (GP) is a type of OV that has been shown to effectively destroy cancer cells in animal studies. This first-in-human study will investigate VSV-GP on its own and in combination with an ICI called ezabenlimab for the treatment of late-stage cancer or cancer that has spread to multiple parts of the body. Here, we describe the background and design of this study in progress which aims to find out if VSV-GP alone or in combination with ezabenlimab is effective against cancer, the suitable dose and if any side effects occur. Trial Registration Number: NCT05155332 (ClinicalTrials.gov).

Published
2022

270. Synergy of Analytical Approaches Enables a Robust Assessment of the Brazil Mystery Oil Spill

Author

Christopher M. Reddy, Robert K. Nelson, Ulrich M. Hanke, Xingqian Cui, Roger E. Summons, David L. Valentine, Ryan P. Rodgers, Martha L. Chacón-Patiño, Sydney F. Niles, Carlos E.P. Teixeira, Luis E.A. Bezerra, Rivelino M. Cavalcante, Marcelo O. Soares, André H.B. Oliveira, Helen K. White, Robert F. Swarthout, Karin L. Lemkau, and Jagoš R. Radović

Subjects
Fuel Technology, General Chemical Engineering, Energy Engineering and Power Technology
Published
2022

272. Abstract CT119: A first-in-human phase 1 study of LOXO-435, a potent, highly isoform-selective FGFR3 inhibitor in advanced solid tumors with FGFR3 alterations (trial in progress)

Author

Iyer, Gopa, primary, Siefker-Radtke, Arlene, additional, Milowsky, Matthew, additional, Shore, Neal, additional, Gao, Xin, additional, Reimers, Melissa A., additional, Hahn, Noah, additional, Cosman, Rasha, additional, Matsubara, Nobuaki, additional, Necchi, Andrea, additional, Robbrecht, Debbie, additional, Vinceneux, Armelle, additional, Grande, Enrique, additional, Lee, Jae-Lyun, additional, Zhang, Tian, additional, Guren, Tormod, additional, Lauer, Ulrich M., additional, Sarfaty, Michal, additional, Eigl, Bernhard, additional, Hussain, Syed, additional, Zhao, Xiang, additional, Balar, Arjun V., additional, Francese, Kaitlyn, additional, Widau, Ryan, additional, and Garmezy, Benjamin, additional

Published
2023
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274. Supplementary Figure 1 from Differential Induction of Apoptosis and Senescence by the DNA Methyltransferase Inhibitors 5-Azacytidine and 5-Aza-2′-Deoxycytidine in Solid Tumor Cells

Author

Venturelli, Sascha, primary, Berger, Alexander, primary, Weiland, Timo, primary, Essmann, Frank, primary, Waibel, Michaela, primary, Nuebling, Tina, primary, Häcker, Sabine, primary, Schenk, Martin, primary, Schulze-Osthoff, Klaus, primary, Salih, Helmut R., primary, Fulda, Simone, primary, Sipos, Bence, primary, Johnstone, Ricky W., primary, Lauer, Ulrich M., primary, and Bitzer, Michael, primary

Published
2023
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275. Supplementary Table 1 from Differential Induction of Apoptosis and Senescence by the DNA Methyltransferase Inhibitors 5-Azacytidine and 5-Aza-2′-Deoxycytidine in Solid Tumor Cells

Author

Venturelli, Sascha, primary, Berger, Alexander, primary, Weiland, Timo, primary, Essmann, Frank, primary, Waibel, Michaela, primary, Nuebling, Tina, primary, Häcker, Sabine, primary, Schenk, Martin, primary, Schulze-Osthoff, Klaus, primary, Salih, Helmut R., primary, Fulda, Simone, primary, Sipos, Bence, primary, Johnstone, Ricky W., primary, Lauer, Ulrich M., primary, and Bitzer, Michael, primary

Published
2023
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276. Supplementary Figure Legend from Differential Induction of Apoptosis and Senescence by the DNA Methyltransferase Inhibitors 5-Azacytidine and 5-Aza-2′-Deoxycytidine in Solid Tumor Cells

Author

Venturelli, Sascha, primary, Berger, Alexander, primary, Weiland, Timo, primary, Essmann, Frank, primary, Waibel, Michaela, primary, Nuebling, Tina, primary, Häcker, Sabine, primary, Schenk, Martin, primary, Schulze-Osthoff, Klaus, primary, Salih, Helmut R., primary, Fulda, Simone, primary, Sipos, Bence, primary, Johnstone, Ricky W., primary, Lauer, Ulrich M., primary, and Bitzer, Michael, primary

Published
2023
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277. Supplementary Figure 2 from Differential Induction of Apoptosis and Senescence by the DNA Methyltransferase Inhibitors 5-Azacytidine and 5-Aza-2′-Deoxycytidine in Solid Tumor Cells

Author

Venturelli, Sascha, primary, Berger, Alexander, primary, Weiland, Timo, primary, Essmann, Frank, primary, Waibel, Michaela, primary, Nuebling, Tina, primary, Häcker, Sabine, primary, Schenk, Martin, primary, Schulze-Osthoff, Klaus, primary, Salih, Helmut R., primary, Fulda, Simone, primary, Sipos, Bence, primary, Johnstone, Ricky W., primary, Lauer, Ulrich M., primary, and Bitzer, Michael, primary

Published
2023
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278. Supplementary Figure 4 from Differential Induction of Apoptosis and Senescence by the DNA Methyltransferase Inhibitors 5-Azacytidine and 5-Aza-2′-Deoxycytidine in Solid Tumor Cells

Author

Venturelli, Sascha, primary, Berger, Alexander, primary, Weiland, Timo, primary, Essmann, Frank, primary, Waibel, Michaela, primary, Nuebling, Tina, primary, Häcker, Sabine, primary, Schenk, Martin, primary, Schulze-Osthoff, Klaus, primary, Salih, Helmut R., primary, Fulda, Simone, primary, Sipos, Bence, primary, Johnstone, Ricky W., primary, Lauer, Ulrich M., primary, and Bitzer, Michael, primary

Published
2023
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279. Supplementary Figure 3 from Differential Induction of Apoptosis and Senescence by the DNA Methyltransferase Inhibitors 5-Azacytidine and 5-Aza-2′-Deoxycytidine in Solid Tumor Cells

Author

Venturelli, Sascha, primary, Berger, Alexander, primary, Weiland, Timo, primary, Essmann, Frank, primary, Waibel, Michaela, primary, Nuebling, Tina, primary, Häcker, Sabine, primary, Schenk, Martin, primary, Schulze-Osthoff, Klaus, primary, Salih, Helmut R., primary, Fulda, Simone, primary, Sipos, Bence, primary, Johnstone, Ricky W., primary, Lauer, Ulrich M., primary, and Bitzer, Michael, primary

Published
2023
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280. Data from Differential Induction of Apoptosis and Senescence by the DNA Methyltransferase Inhibitors 5-Azacytidine and 5-Aza-2′-Deoxycytidine in Solid Tumor Cells

Author

Venturelli, Sascha, primary, Berger, Alexander, primary, Weiland, Timo, primary, Essmann, Frank, primary, Waibel, Michaela, primary, Nuebling, Tina, primary, Häcker, Sabine, primary, Schenk, Martin, primary, Schulze-Osthoff, Klaus, primary, Salih, Helmut R., primary, Fulda, Simone, primary, Sipos, Bence, primary, Johnstone, Ricky W., primary, Lauer, Ulrich M., primary, and Bitzer, Michael, primary

Published
2023
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281. Figure S4 from Phase I Study of Oncolytic Vaccinia Virus GL-ONC1 in Patients with Peritoneal Carcinomatosis

Author

Lauer, Ulrich M., primary, Schell, Martina, primary, Beil, Julia, primary, Berchtold, Susanne, primary, Koppenhöfer, Ursula, primary, Glatzle, Jörg, primary, Königsrainer, Alfred, primary, Möhle, Robert, primary, Nann, Dominik, primary, Fend, Falko, primary, Pfannenberg, Christina, primary, Bitzer, Michael, primary, and Malek, Nisar P., primary

Published
2023
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282. Table S1 from Phase I Study of Oncolytic Vaccinia Virus GL-ONC1 in Patients with Peritoneal Carcinomatosis

Author

Lauer, Ulrich M., primary, Schell, Martina, primary, Beil, Julia, primary, Berchtold, Susanne, primary, Koppenhöfer, Ursula, primary, Glatzle, Jörg, primary, Königsrainer, Alfred, primary, Möhle, Robert, primary, Nann, Dominik, primary, Fend, Falko, primary, Pfannenberg, Christina, primary, Bitzer, Michael, primary, and Malek, Nisar P., primary

Published
2023
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283. Data from Specific Elimination of CD133+ Tumor Cells with Targeted Oncolytic Measles Virus

Author

Bach, Patricia, primary, Abel, Tobias, primary, Hoffmann, Christopher, primary, Gal, Zoltan, primary, Braun, Gundula, primary, Voelker, Iris, primary, Ball, Claudia R., primary, Johnston, Ian C.D., primary, Lauer, Ulrich M., primary, Herold-Mende, Christel, primary, Mühlebach, Michael D., primary, Glimm, Hanno, primary, and Buchholz, Christian J., primary

Published
2023
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284. Supplementary Figure 4 from Liver Cancer Protease Activity Profiles Support Therapeutic Options with Matrix Metalloproteinase–Activatable Oncolytic Measles Virus

Author

Mühlebach, Michael D., primary, Schaser, Thomas, primary, Zimmermann, Martina, primary, Armeanu, Sorin, primary, Hanschmann, Kay-Martin O., primary, Cattaneo, Roberto, primary, Bitzer, Michael, primary, Lauer, Ulrich M., primary, Cichutek, Klaus, primary, and Buchholz, Christian J., primary

Published
2023
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285. Supplementary Figure 3 from Liver Cancer Protease Activity Profiles Support Therapeutic Options with Matrix Metalloproteinase–Activatable Oncolytic Measles Virus

Author

Mühlebach, Michael D., primary, Schaser, Thomas, primary, Zimmermann, Martina, primary, Armeanu, Sorin, primary, Hanschmann, Kay-Martin O., primary, Cattaneo, Roberto, primary, Bitzer, Michael, primary, Lauer, Ulrich M., primary, Cichutek, Klaus, primary, and Buchholz, Christian J., primary

Published
2023
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286. Supplementary Figure 6 from Liver Cancer Protease Activity Profiles Support Therapeutic Options with Matrix Metalloproteinase–Activatable Oncolytic Measles Virus

Author

Mühlebach, Michael D., primary, Schaser, Thomas, primary, Zimmermann, Martina, primary, Armeanu, Sorin, primary, Hanschmann, Kay-Martin O., primary, Cattaneo, Roberto, primary, Bitzer, Michael, primary, Lauer, Ulrich M., primary, Cichutek, Klaus, primary, and Buchholz, Christian J., primary

Published
2023
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288. Supplementary Figure Legends 1-6 from Liver Cancer Protease Activity Profiles Support Therapeutic Options with Matrix Metalloproteinase–Activatable Oncolytic Measles Virus

Author

Mühlebach, Michael D., primary, Schaser, Thomas, primary, Zimmermann, Martina, primary, Armeanu, Sorin, primary, Hanschmann, Kay-Martin O., primary, Cattaneo, Roberto, primary, Bitzer, Michael, primary, Lauer, Ulrich M., primary, Cichutek, Klaus, primary, and Buchholz, Christian J., primary

Published
2023
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289. Supplementary Figure 5 from Liver Cancer Protease Activity Profiles Support Therapeutic Options with Matrix Metalloproteinase–Activatable Oncolytic Measles Virus

Author

Mühlebach, Michael D., primary, Schaser, Thomas, primary, Zimmermann, Martina, primary, Armeanu, Sorin, primary, Hanschmann, Kay-Martin O., primary, Cattaneo, Roberto, primary, Bitzer, Michael, primary, Lauer, Ulrich M., primary, Cichutek, Klaus, primary, and Buchholz, Christian J., primary

Published
2023
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290. Supplementary Figure 1 from Liver Cancer Protease Activity Profiles Support Therapeutic Options with Matrix Metalloproteinase–Activatable Oncolytic Measles Virus

Author

Mühlebach, Michael D., primary, Schaser, Thomas, primary, Zimmermann, Martina, primary, Armeanu, Sorin, primary, Hanschmann, Kay-Martin O., primary, Cattaneo, Roberto, primary, Bitzer, Michael, primary, Lauer, Ulrich M., primary, Cichutek, Klaus, primary, and Buchholz, Christian J., primary

Published
2023
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291. Supplementary Figures 1-8 from Specific Elimination of CD133+ Tumor Cells with Targeted Oncolytic Measles Virus

Author

Bach, Patricia, primary, Abel, Tobias, primary, Hoffmann, Christopher, primary, Gal, Zoltan, primary, Braun, Gundula, primary, Voelker, Iris, primary, Ball, Claudia R., primary, Johnston, Ian C.D., primary, Lauer, Ulrich M., primary, Herold-Mende, Christel, primary, Mühlebach, Michael D., primary, Glimm, Hanno, primary, and Buchholz, Christian J., primary

Published
2023
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292. Supplementary Tables 1-4 from Liver Cancer Protease Activity Profiles Support Therapeutic Options with Matrix Metalloproteinase–Activatable Oncolytic Measles Virus

Author

Mühlebach, Michael D., primary, Schaser, Thomas, primary, Zimmermann, Martina, primary, Armeanu, Sorin, primary, Hanschmann, Kay-Martin O., primary, Cattaneo, Roberto, primary, Bitzer, Michael, primary, Lauer, Ulrich M., primary, Cichutek, Klaus, primary, and Buchholz, Christian J., primary

Published
2023
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293. Supplementary Methods and Materials from Liver Cancer Protease Activity Profiles Support Therapeutic Options with Matrix Metalloproteinase–Activatable Oncolytic Measles Virus

Author

Mühlebach, Michael D., primary, Schaser, Thomas, primary, Zimmermann, Martina, primary, Armeanu, Sorin, primary, Hanschmann, Kay-Martin O., primary, Cattaneo, Roberto, primary, Bitzer, Michael, primary, Lauer, Ulrich M., primary, Cichutek, Klaus, primary, and Buchholz, Christian J., primary

Published
2023
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294. Supplementary Figure 2 from Liver Cancer Protease Activity Profiles Support Therapeutic Options with Matrix Metalloproteinase–Activatable Oncolytic Measles Virus

Author

Mühlebach, Michael D., primary, Schaser, Thomas, primary, Zimmermann, Martina, primary, Armeanu, Sorin, primary, Hanschmann, Kay-Martin O., primary, Cattaneo, Roberto, primary, Bitzer, Michael, primary, Lauer, Ulrich M., primary, Cichutek, Klaus, primary, and Buchholz, Christian J., primary

Published
2023
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296. Comparative metagenomics reveals host-specific functional adaptation of intestinal microbiota across hominids

Author

Rühlemann, MC, primary, Bang, C, additional, Gogarten, JF, additional, Hermes, BM, additional, Groussin, M, additional, Waschina, S, additional, Poyet, M, additional, Ulrich, M, additional, Akoua-Koffi, C, additional, Deschner, T, additional, Muyembe-Tamfum, JJ, additional, Robbins, MM, additional, Surbeck, M, additional, Wittig, RM, additional, Zuberbühler, K, additional, Baines, JF, additional, Leendertz, FH, additional, and Franke, A, additional

Published
2023
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298. Ultramafic-hosted volcanogenic massive sulfide deposits: an overlooked subclass of VMS deposits?

Author

Patten, C. G. C., Coltat, Remí, Junge, M., Peillod, A., Ulrich, M., Manatschal, G., Kolb, J., Patten, C. G. C., Coltat, Remí, Junge, M., Peillod, A., Ulrich, M., Manatschal, G., and Kolb, J.

Abstract

Volcanogenic massive sulfide (VMS) deposits form or are recorded throughout most of Earth history from the Archean to present day. The discovery of actively forming hydrothermal deposits on the seafloor has been critical for understanding these systems. Extensive seafloor exploration led to discovery of very diverse seafloor massive sulfide (SMS) deposits in most of oceanic crust-related tectonic environments such as mid-oceanic ridges (MOR), back-arcs, island-arcs and fore-arcs matching those found in the geological record on land. During the last two decades, however, seafloor exploration highlighted a still poorly defined sub-group of VMS deposits on land: the so called ultramafic-hosted SMS deposits (UM-SMS; [1]). These deposits form mainly in slow to ultraslow spreading MOR environments with little magmatic activity [1]. They show strong structural control and are located at or in the vicinity of low-angle detachment faults such as oceanic core complexes [1]. They are hosted in variably altered ultramafic rocks and are enriched in precious (Au-Ag), critical (Co) and base metals (Cu-Zn-Ni). Compared with other types of VMS deposits, they are commonly thought to be scarce in the geological record because they are unlikely to be tectonically emplaced during collision as they form in MOR environments, generally far away from accreting margins. Patten et al. [2] argue that UM-VMS deposits are more common than previously thought in the geological record. There are often referred after some key localities, such as Outokumpu-type [3] and Main Ural Fault-type [4], but a coherent and thorough review of these deposit is lacking. The UM-VMS deposits occur in complex tectonic settings, which are sometimes misinterpreted (e.g. as tectonic mélange), their origin is often disputed (e.g. hydrothermally overprinted magmatic Ni-Cu massive sulfide) or overlooked (classified as end member of mafic-type VMS) and orogenic overprint can hinder their primary seafloor-related features.

Published
2023

299. A New Panel-Based Next-Generation Sequencing Method for ADME Genes Reveals Novel Associations of Common and Rare Variants With Expression in a Human Liver Cohort

Author

Kathrin Klein, Roman Tremmel, Stefan Winter, Sarah Fehr, Florian Battke, Tim Scheurenbrand, Elke Schaeffeler, Saskia Biskup, Matthias Schwab, and Ulrich M. Zanger

Subjects
ADME, next generation sequencing, pharmacogenomics, eQTL analysis, rare variants, Genetics, QH426-470
Abstract

We developed a panel-based NGS pipeline for comprehensive analysis of 340 genes involved in absorption, distribution, metabolism and excretion (ADME) of drugs, other xenobiotics, and endogenous substances. The 340 genes comprised phase I and II enzymes, drug transporters and regulator/modifier genes within their entire coding regions, adjacent intron regions and 5′ and 3′UTR regions, resulting in a total panel size of 1,382 kbp. We applied the ADME NGS panel to sequence genomic DNA from 150 Caucasian liver donors with available comprehensive gene expression data. This revealed an average read-depth of 343 (range 27–811), while 99% of the 340 genes were covered on average at least 100-fold. Direct comparison of variant annotation with 363 available genotypes determined independently by other methods revealed an overall accuracy of >99%. Of 15,727 SNV and small INDEL variants, 12,022 had a minor allele frequency (MAF) below 2%, including 8,937 singletons. In total we found 7,273 novel variants. Functional predictions were computed for coding variants (n = 4,017) by three algorithms (Polyphen 2, Provean, and SIFT), resulting in 1,466 variants (36.5%) concordantly predicted to be damaging, while 1,019 variants (25.4%) were predicted to be tolerable. In agreement with other studies we found that less common variants were enriched for deleterious variants. Cis-eQTL analysis of variants with (MAF ≥ 2%) revealed significant associations for 90 variants in 31 genes after Bonferroni correction, most of which were located in non-coding regions. For less common variants (MAF < 2%), we applied the SKAT-O test and identified significant associations to gene expression for ADH1C and GSTO1. Moreover, our data allow comparison of functional predictions with additional phenotypic data to prioritize variants for further analysis.

Published
2019
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