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37 results on '"Zukowska, Magdalena"'

1. Mixed Reality Versus 3D Printing in Presurgical Visualization of Soft and Hard Tissues: Selected Cases

Author

Górski, Filip, Smolarek, Emilia, Żukowska, Magdalena, Okła, Maciej, Goos, Gerhard, Series Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Yung, Moti, Editorial Board Member, De Paolis, Lucio Tommaso, editor, Arpaia, Pasquale, editor, and Sacco, Marco, editor

Published
2024
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2. Automated Design and Virtual Fitting of 3D Printed Bicycle Prostheses for Children

Author

Górski, Filip, Denysenko, Yuliia, Kuczko, Wiesław, Żukowska, Magdalena, Chaari, Fakher, Series Editor, Gherardini, Francesco, Series Editor, Ivanov, Vitalii, Series Editor, Haddar, Mohamed, Series Editor, Cavas-Martínez, Francisco, Editorial Board Member, di Mare, Francesca, Editorial Board Member, Kwon, Young W., Editorial Board Member, Tolio, Tullio A. M., Editorial Board Member, Trojanowska, Justyna, Editorial Board Member, Schmitt, Robert, Editorial Board Member, Xu, Jinyang, Editorial Board Member, Machado, Jose, editor, Soares, Filomena, editor, Ottaviano, Erika, editor, Valášek, Petr, editor, Reddy D., Mallikarjuna, editor, Perondi, Eduardo André, editor, and Basova, Yevheniia, editor

Published
2024
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3. Personalized Mechatronic Lower Limb Orthosis

Author

Rybarczyk, Justyna, Dorna, Piotr, Górski, Filip, Kuczko, Wiesław, Żukowska, Magdalena, Chaari, Fakher, Series Editor, Gherardini, Francesco, Series Editor, Ivanov, Vitalii, Series Editor, Haddar, Mohamed, Series Editor, Cavas-Martínez, Francisco, Editorial Board Member, di Mare, Francesca, Editorial Board Member, Kwon, Young W., Editorial Board Member, Tolio, Tullio A. M., Editorial Board Member, Trojanowska, Justyna, Editorial Board Member, Schmitt, Robert, Editorial Board Member, Xu, Jinyang, Editorial Board Member, Machado, Jose, editor, Soares, Filomena, editor, Yildirim, Sahin, editor, Vojtěšek, Jiří, editor, Rea, Pierluigi, editor, Gramescu, Bogdan, editor, and Hrybiuk, Olena O., editor

Published
2024
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4. Development of 3D Printed Low-Cost Individualized Actuated Upper Limb Prostheses

Author

Górski, Filip, Marciniak, Agnieszka, Wichniarek, Radosław, Kuczko, Wiesław, Żukowska, Magdalena, Rybarczyk, Justyna, Chaari, Fakher, Series Editor, Gherardini, Francesco, Series Editor, Ivanov, Vitalii, Series Editor, Haddar, Mohamed, Series Editor, Cavas-Martínez, Francisco, Editorial Board Member, di Mare, Francesca, Editorial Board Member, Kwon, Young W., Editorial Board Member, Tolio, Tullio A. M., Editorial Board Member, Trojanowska, Justyna, Editorial Board Member, Schmitt, Robert, Editorial Board Member, Xu, Jinyang, Editorial Board Member, Gorski, Filip, editor, Păcurar, Răzvan, editor, Roca González, Joaquín F., editor, and Rychlik, Michał, editor

Published
2024
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5. Virtual Design Process of Customized 3D Printed Modular Upper Limb Prostheses

Author

Górski, Filip, Gapsa, Jakub, Kupaj, Aleksandra, Kuczko, Wiesław, Żukowska, Magdalena, Zawadzki, Przemysław, Chaari, Fakher, Series Editor, Gherardini, Francesco, Series Editor, Ivanov, Vitalii, Series Editor, Haddar, Mohamed, Series Editor, Cavas-Martínez, Francisco, Editorial Board Member, di Mare, Francesca, Editorial Board Member, Kwon, Young W., Editorial Board Member, Tolio, Tullio A. M., Editorial Board Member, Trojanowska, Justyna, Editorial Board Member, Schmitt, Robert, Editorial Board Member, Xu, Jinyang, Editorial Board Member, Gorski, Filip, editor, Păcurar, Răzvan, editor, Roca González, Joaquín F., editor, and Rychlik, Michał, editor

Published
2024
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6. Assessment of the Usefulness of Additively Manufactured Anatomical Models in the Process of Preoperative Support and Education

Author

Żukowska, Magdalena, Górski, Filip, Wichniarek, Radosław, Kuczko, Wiesław, Buczkowska-Andruszko, Agata, Banaszewski, Jacek, Chaari, Fakher, Series Editor, Gherardini, Francesco, Series Editor, Ivanov, Vitalii, Series Editor, Haddar, Mohamed, Series Editor, Cavas-Martínez, Francisco, Editorial Board Member, di Mare, Francesca, Editorial Board Member, Kwon, Young W., Editorial Board Member, Tolio, Tullio A. M., Editorial Board Member, Trojanowska, Justyna, Editorial Board Member, Schmitt, Robert, Editorial Board Member, Xu, Jinyang, Editorial Board Member, Gorski, Filip, editor, Păcurar, Răzvan, editor, Roca González, Joaquín F., editor, and Rychlik, Michał, editor

Published
2024
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7. Rapid Manufacturing of Individualized Supplies for Eye Socket Reconstructive Surgery

Author

Żukowska, Magdalena, Boberska, Daria, Górski, Filip, Okła, Maciej, Kacprzyk, Janusz, Series Editor, Gomide, Fernando, Advisory Editor, Kaynak, Okyay, Advisory Editor, Liu, Derong, Advisory Editor, Pedrycz, Witold, Advisory Editor, Polycarpou, Marios M., Advisory Editor, Rudas, Imre J., Advisory Editor, Wang, Jun, Advisory Editor, Gzik, Marek, editor, Paszenda, Zbigniew, editor, Piętka, Ewa, editor, Tkacz, Ewaryst, editor, Milewski, Krzysztof, editor, and Jurkojć, Jacek, editor

Published
2024
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8. Automated Design and 3D Printing Of Therapeutic Wrist Hand Orthosis

Author

Górski, Filip, Żukowska, Magdalena, Kuczko, Wiesław, Wichniarek, Radosław, Siwiec, Sabina, Kacprzyk, Janusz, Series Editor, Gomide, Fernando, Advisory Editor, Kaynak, Okyay, Advisory Editor, Liu, Derong, Advisory Editor, Pedrycz, Witold, Advisory Editor, Polycarpou, Marios M., Advisory Editor, Rudas, Imre J., Advisory Editor, Wang, Jun, Advisory Editor, Gzik, Marek, editor, Paszenda, Zbigniew, editor, Piętka, Ewa, editor, Tkacz, Ewaryst, editor, Milewski, Krzysztof, editor, and Jurkojć, Jacek, editor

Published
2024
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9. Study of Individualized Leg Orthoses Made by 3D Printing of Composite Material

Author

Rybarczyk, Justyna, Kuczko, Wiesław, Wichniarek, Radosław, Górski, Filip, Żukowska, Magdalena, Kacprzyk, Janusz, Series Editor, Gomide, Fernando, Advisory Editor, Kaynak, Okyay, Advisory Editor, Liu, Derong, Advisory Editor, Pedrycz, Witold, Advisory Editor, Polycarpou, Marios M., Advisory Editor, Rudas, Imre J., Advisory Editor, Wang, Jun, Advisory Editor, Gzik, Marek, editor, Paszenda, Zbigniew, editor, Piętka, Ewa, editor, Tkacz, Ewaryst, editor, Milewski, Krzysztof, editor, and Jurkojć, Jacek, editor

Published
2024
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10. Non-canonical functions of SNAIL drive context-specific cancer progression

Author

Paul, Mariel C., Schneeweis, Christian, Falcomatà, Chiara, Shan, Chuan, Rossmeisl, Daniel, Koutsouli, Stella, Klement, Christine, Zukowska, Magdalena, Widholz, Sebastian A., Jesinghaus, Moritz, Heuermann, Konstanze K., Engleitner, Thomas, Seidler, Barbara, Sleiman, Katia, Steiger, Katja, Tschurtschenthaler, Markus, Walter, Benjamin, Weidemann, Sören A., Pietsch, Regina, Schnieke, Angelika, Schmid, Roland M., Robles, Maria S., Andrieux, Geoffroy, Boerries, Melanie, Rad, Roland, Schneider, Günter, and Saur, Dieter

Published
2023
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11. Methodology of the Rapid Manufacturing of an Individualized Anatomical Model of the Tongue with a Tumor for the Preparation of an Organ Reconstruction Operation

Author

Żukowska, Magdalena, Jezińska, Renata, Górski, Filip, Kuczko, Wiesław, Wichniarek, Radosław, Banaszewski, Jacek, Buczkowska-Andruszko, Agata, Cavas-Martínez, Francisco, Editorial Board Member, Chaari, Fakher, Series Editor, di Mare, Francesca, Editorial Board Member, Gherardini, Francesco, Series Editor, Haddar, Mohamed, Editorial Board Member, Ivanov, Vitalii, Series Editor, Kwon, Young W., Editorial Board Member, Trojanowska, Justyna, Editorial Board Member, Gorski, Filip, editor, Rychlik, Michał, editor, and Păcurar, Răzvan, editor

Published
2022
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12. Design and Additive Manufacturing of an Individualized Specialized Leg Orthosis

Author

Górski, Filip, Rybarczyk, Justyna, Zawadzki, Przemysław, Kuczko, Wiesław, Wierzbicka, Natalia, Żukowska, Magdalena, Siwiec, Sabina, Cavas-Martínez, Francisco, Editorial Board Member, Chaari, Fakher, Series Editor, di Mare, Francesca, Editorial Board Member, Gherardini, Francesco, Series Editor, Haddar, Mohamed, Editorial Board Member, Ivanov, Vitalii, Series Editor, Kwon, Young W., Editorial Board Member, Trojanowska, Justyna, Editorial Board Member, Gorski, Filip, editor, Rychlik, Michał, editor, and Păcurar, Răzvan, editor

Published
2022
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13. Evaluation of a Prototype System of Automated Design and Rapid Manufacturing of Orthopaedic Supplies

Author

Górski, Filip, Wichniarek, Radosław, Kuczko, Wiesław, Żukowska, Magdalena, Rybarczyk, Justyna, Lulkiewicz, Monika, Cavas-Martínez, Francisco, Editorial Board Member, Chaari, Fakher, Series Editor, di Mare, Francesca, Editorial Board Member, Gherardini, Francesco, Series Editor, Haddar, Mohamed, Editorial Board Member, Ivanov, Vitalii, Series Editor, Kwon, Young W., Editorial Board Member, Trojanowska, Justyna, Editorial Board Member, Gorski, Filip, editor, Rychlik, Michał, editor, and Păcurar, Răzvan, editor

Published
2022
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14. Selective multi-kinase inhibition sensitizes mesenchymal pancreatic cancer to immune checkpoint blockade by remodeling the tumor microenvironment

Author

Falcomatà, Chiara, Bärthel, Stefanie, Widholz, Sebastian A., Schneeweis, Christian, Montero, Juan José, Toska, Albulena, Mir, Jonas, Kaltenbacher, Thorsten, Heetmeyer, Jeannine, Swietlik, Jonathan J., Cheng, Jing-Yuan, Teodorescu, Bianca, Reichert, Oliver, Schmitt, Constantin, Grabichler, Kathrin, Coluccio, Andrea, Boniolo, Fabio, Veltkamp, Christian, Zukowska, Magdalena, Vargas, Angelica Arenas, Paik, Woo Hyun, Jesinghaus, Moritz, Steiger, Katja, Maresch, Roman, Öllinger, Rupert, Ammon, Tim, Baranov, Olga, Robles, Maria S., Rechenberger, Julia, Kuster, Bernhard, Meissner, Felix, Reichert, Maximilian, Flossdorf, Michael, Rad, Roland, Schmidt-Supprian, Marc, Schneider, Günter, and Saur, Dieter

Published
2022
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15. Environmental Impact of Additive Manufacturing for Individual Supplies

Author

Górski, Filip, Osiński, Filip, Wierzbicka, Natalia, Żukowska, Magdalena, Cavas-Martínez, Francisco, Series Editor, Chaari, Fakher, Series Editor, Gherardini, Francesco, Series Editor, Haddar, Mohamed, Series Editor, Ivanov, Vitalii, Series Editor, Kwon, Young W., Series Editor, Trojanowska, Justyna, Series Editor, Tonkonogyi, Volodymyr, editor, Oborskyi, Gennadii, editor, Grabchenko, Anatolii, editor, Pavlenko, Ivan, editor, Edl, Milan, editor, Kuric, Ivan, editor, and Dasic, Predrag, editor

Published
2021
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16. Automated Design of Customized 3D-Printed Wrist Orthoses on the Basis of 3D Scanning

Author

Górski, Filip, Zawadzki, Przemysław, Wichniarek, Radosław, Kuczko, Wiesław, Żukowska, Magdalena, Wesołowska, Izabela, Wierzbicka, Natalia, Ceccarelli, Marco, Series Editor, Hernandez, Alfonso, Editorial Board Member, Huang, Tian, Editorial Board Member, Takeda, Yukio, Editorial Board Member, Corves, Burkhard, Editorial Board Member, Agrawal, Sunil, Editorial Board Member, Okada, Hiroshi, editor, and Atluri, Satya N., editor

Published
2020
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17. Rating of Polymers for Low-Cost Rapid Manufacturing of Individualized Anatomical Models Used in Presurgical Planning

Author

Żukowska, Magdalena, Górski, Filip, Hamrol, Adam, Ceccarelli, Marco, Series Editor, Hernandez, Alfonso, Editorial Board Member, Huang, Tian, Editorial Board Member, Takeda, Yukio, Editorial Board Member, Corves, Burkhard, Editorial Board Member, Agrawal, Sunil, Editorial Board Member, Okada, Hiroshi, editor, and Atluri, Satya N., editor

Published
2020
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18. Rapid Manufacturing and Virtual Prototyping of Pre-surgery Aids

Author

Żukowska, Magdalena, Górski, Filip, Bromiński, Gabriel, Magjarevic, Ratko, Editor-in-Chief, Ładyżyński, Piotr, Series Editor, Ibrahim, Fatimah, Series Editor, Lacković, Igor, Series Editor, Rock, Emilio Sacristan, Series Editor, Lhotska, Lenka, editor, Sukupova, Lucie, editor, and Ibbott, Geoffrey S., editor

Published
2019
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19. Low-Cost 3D Printing in Innovative VR Training and Prototyping Solutions

Author

Buń, Paweł, Górski, Filip, Wichniarek, Radosław, Kuczko, Wiesław, Żukowska, Magdalena, Kacprzyk, Janusz, Series Editor, Pal, Nikhil R., Advisory Editor, Bello Perez, Rafael, Advisory Editor, Corchado, Emilio S., Advisory Editor, Hagras, Hani, Advisory Editor, Kóczy, László T., Advisory Editor, Kreinovich, Vladik, Advisory Editor, Lin, Chin-Teng, Advisory Editor, Lu, Jie, Advisory Editor, Melin, Patricia, Advisory Editor, Nedjah, Nadia, Advisory Editor, Nguyen, Ngoc Thanh, Advisory Editor, Wang, Jun, Advisory Editor, Burduk, Anna, editor, Chlebus, Edward, editor, Nowakowski, Tomasz, editor, and Tubis, Agnieszka, editor

Published
2019
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21. Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes

Author

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

Subjects
Phenotypes -- Research, Cell culture -- Research, Pancreatic cancer -- Genetic aspects -- Physiological aspects, Biological research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The poor correlation of mutational landscapes with phenotypes limits our understanding of the pathogenesis and metastasis of pancreatic ductal adenocarcinoma (PDAC). Here we show that oncogenic dosage-variation has a critical role in PDAC biology and phenotypic diversification. We find an increase in gene dosage of mutant KRAS in human PDAC precursors, which drives both early tumorigenesis and metastasis and thus rationalizes early PDAC dissemination. To overcome the limitations posed to gene dosage studies by the stromal richness of PDAC, we have developed large cell culture resources of metastatic mouse PDAC. Integration of cell culture genomes, transcriptomes and tumour phenotypes with functional studies and human data reveals additional widespread effects of oncogenic dosage variation on cell morphology and plasticity, histopathology and clinical outcome, with the highest Kras[sup.MUT] levels underlying aggressive undifferentiated phenotypes. We also identify alternative oncogenic gains (Myc, Yap1 or Nfkb2), which collaborate with heterozygous Kras[sup.MUT] in driving tumorigenesis, but have lower metastatic potential. Mechanistically, different oncogenic gains and dosages evolve along distinct evolutionary routes, licensed by defined allelic states and/or combinations of hallmark tumour suppressor alterations (Cdkn2a, Trp53, Tgf-pathway). Thus, evolutionary constraints and contingencies direct oncogenic dosage gain and variation along defined routes to drive the early progression of PDAC and shape its downstream biology. Our study uncovers universal principles of Ras-driven oncogenesis that have potential relevance beyond pancreatic cancer., Author(s): Sebastian Mueller [1, 2]; Thomas Engleitner [1, 2, 3]; Roman Maresch [1, 2, 3]; Magdalena Zukowska [1, 2]; Sebastian Lange [1, 2]; Thorsten Kaltenbacher [1, 2, 3]; Bjrn Konukiewitz [...]

Published
2018
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22. Supplementary Figures and Methods from Genetic Screens Identify a Context-Specific PI3K/p27Kip1 Node Driving Extrahepatic Biliary Cancer

Author

Falcomatà, Chiara, primary, Bärthel, Stefanie, primary, Ulrich, Angelika, primary, Diersch, Sandra, primary, Veltkamp, Christian, primary, Rad, Lena, primary, Boniolo, Fabio, primary, Solar, Myriam, primary, Steiger, Katja, primary, Seidler, Barbara, primary, Zukowska, Magdalena, primary, Madej, Joanna, primary, Wang, Mingsong, primary, Öllinger, Rupert, primary, Maresch, Roman, primary, Barenboim, Maxim, primary, Eser, Stefan, primary, Tschurtschenthaler, Markus, primary, Mehrabi, Arianeb, primary, Roessler, Stephanie, primary, Goeppert, Benjamin, primary, Kind, Alexander, primary, Schnieke, Angelika, primary, Robles, Maria S., primary, Bradley, Allan, primary, Schmid, Roland M., primary, Schmidt-Supprian, Marc, primary, Reichert, Maximilian, primary, Weichert, Wilko, primary, Sansom, Owen J., primary, Morton, Jennifer P., primary, Rad, Roland, primary, Schneider, Günter, primary, and Saur, Dieter, primary

Published
2023
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23. Data from Genetic Screens Identify a Context-Specific PI3K/p27Kip1 Node Driving Extrahepatic Biliary Cancer

Author

Falcomatà, Chiara, primary, Bärthel, Stefanie, primary, Ulrich, Angelika, primary, Diersch, Sandra, primary, Veltkamp, Christian, primary, Rad, Lena, primary, Boniolo, Fabio, primary, Solar, Myriam, primary, Steiger, Katja, primary, Seidler, Barbara, primary, Zukowska, Magdalena, primary, Madej, Joanna, primary, Wang, Mingsong, primary, Öllinger, Rupert, primary, Maresch, Roman, primary, Barenboim, Maxim, primary, Eser, Stefan, primary, Tschurtschenthaler, Markus, primary, Mehrabi, Arianeb, primary, Roessler, Stephanie, primary, Goeppert, Benjamin, primary, Kind, Alexander, primary, Schnieke, Angelika, primary, Robles, Maria S., primary, Bradley, Allan, primary, Schmid, Roland M., primary, Schmidt-Supprian, Marc, primary, Reichert, Maximilian, primary, Weichert, Wilko, primary, Sansom, Owen J., primary, Morton, Jennifer P., primary, Rad, Roland, primary, Schneider, Günter, primary, and Saur, Dieter, primary

Published
2023
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24. Supplementary Table 1 from Genetic Screens Identify a Context-Specific PI3K/p27Kip1 Node Driving Extrahepatic Biliary Cancer

Author

Falcomatà, Chiara, primary, Bärthel, Stefanie, primary, Ulrich, Angelika, primary, Diersch, Sandra, primary, Veltkamp, Christian, primary, Rad, Lena, primary, Boniolo, Fabio, primary, Solar, Myriam, primary, Steiger, Katja, primary, Seidler, Barbara, primary, Zukowska, Magdalena, primary, Madej, Joanna, primary, Wang, Mingsong, primary, Öllinger, Rupert, primary, Maresch, Roman, primary, Barenboim, Maxim, primary, Eser, Stefan, primary, Tschurtschenthaler, Markus, primary, Mehrabi, Arianeb, primary, Roessler, Stephanie, primary, Goeppert, Benjamin, primary, Kind, Alexander, primary, Schnieke, Angelika, primary, Robles, Maria S., primary, Bradley, Allan, primary, Schmid, Roland M., primary, Schmidt-Supprian, Marc, primary, Reichert, Maximilian, primary, Weichert, Wilko, primary, Sansom, Owen J., primary, Morton, Jennifer P., primary, Rad, Roland, primary, Schneider, Günter, primary, and Saur, Dieter, primary

Published
2023
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25. A conditional piggyBac transposition system for genetic screening in mice identifies oncogenic networks in pancreatic cancer

Author

Rad, Roland, Rad, Lena, Wang, Wei, Strong, Alexander, Ponstingl, Hannes, Bronner, Iraad F, Mayho, Matthew, Steiger, Katja, Weber, Julia, Hieber, Maren, Veltkamp, Christian, Eser, Stefan, Geumann, Ulf, Öllinger, Rupert, Zukowska, Magdalena, Barenboim, Maxim, Maresch, Roman, Cadiñanos, Juan, Friedrich, Mathias, Varela, Ignacio, Constantino-Casas, Fernando, Sarver, Aaron, ten Hoeve, Jelle, Prosser, Haydn, Seidler, Barbara, Bauer, Judith, Heikenwälder, Mathias, Metzakopian, Emmanouil, Krug, Anne, Ehmer, Ursula, Schneider, Günter, Knösel, Thomas, Rümmele, Petra, Aust, Daniela, Grützmann, Robert, Pilarsky, Christian, Ning, Zemin, Wessels, Lodewyk, Schmid, Roland M, Quail, Michael A, Vassiliou, George, Esposito, Irene, Liu, Pentao, Saur, Dieter, and Bradley, Allan

Published
2015
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26. A next-generation dual-recombinase system for time- and host-specific targeting of pancreatic cancer

Author

Schönhuber, Nina, Seidler, Barbara, Schuck, Kathleen, Veltkamp, Christian, Schachtler, Christina, Zukowska, Magdalena, and Eser, Stefan

Subjects
Recombinases -- Genetic aspects -- Health aspects -- Usage, Gene therapy -- Testing -- Usage -- Health aspects, Gene targeting -- Usage -- Genetic aspects -- Health aspects, Pancreatic cancer -- Development and progression -- Care and treatment -- Genetic aspects
Abstract

The next generation of genetically engineered mouse models of pancreatic cancer involving a new inducible dual-recombinase system that combines Flp-FRT and Cre-loxP. Genetically engineered mouse models (GEMMs) have dramatically improved our understanding of tumor evolution and therapeutic resistance. However, sequential genetic manipulation of gene expression and targeting of the host is almost impossible using conventional Cre-loxP-based models. We have developed an inducible dual-recombinase system by combining flippase-FRT (Flp-FRT) and Cre-loxP recombination technologies to improve GEMMs of pancreatic cancer. This enables investigation of multistep carcinogenesis, genetic manipulation of tumor subpopulations (such as cancer stem cells), selective targeting of the tumor microenvironment and genetic validation of therapeutic targets in autochthonous tumors on a genome-wide scale. As a proof of concept, we performed tumor cell-autonomous and nonautonomous targeting, recapitulated hallmarks of human multistep carcinogenesis, validated genetic therapy by 3-phosphoinositide-dependent protein kinase inactivation as well as cancer cell depletion and show that mast cells in the tumor microenvironment, which had been thought to be key oncogenic players, are dispensable for tumor formation., Author(s): Nina Schönhuber [sup.1] , Barbara Seidler [sup.1] , Kathleen Schuck [sup.1] , Christian Veltkamp [sup.1] , Christina Schachtler [sup.1] , Magdalena Zukowska [sup.1] , Stefan Eser [sup.1] , Thorsten [...]

Published
2014
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28. Genetic Screens Identify a Context-Specific PI3K/p27Kip1 Node Driving Extrahepatic Biliary Cancer

Author

Falcomatà, Chiara, primary, Bärthel, Stefanie, additional, Ulrich, Angelika, additional, Diersch, Sandra, additional, Veltkamp, Christian, additional, Rad, Lena, additional, Boniolo, Fabio, additional, Solar, Myriam, additional, Steiger, Katja, additional, Seidler, Barbara, additional, Zukowska, Magdalena, additional, Madej, Joanna, additional, Wang, Mingsong, additional, Öllinger, Rupert, additional, Maresch, Roman, additional, Barenboim, Maxim, additional, Eser, Stefan, additional, Tschurtschenthaler, Markus, additional, Mehrabi, Arianeb, additional, Roessler, Stephanie, additional, Goeppert, Benjamin, additional, Kind, Alexander, additional, Schnieke, Angelika, additional, Robles, Maria S., additional, Bradley, Allan, additional, Schmid, Roland M., additional, Schmidt-Supprian, Marc, additional, Reichert, Maximilian, additional, Weichert, Wilko, additional, Sansom, Owen J., additional, Morton, Jennifer P., additional, Rad, Roland, additional, Schneider, Günter, additional, and Saur, Dieter, additional

Published
2021
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30. 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
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32. Myosin kinase of molluscan smooth muscle: regulation by binding of calcium to the substrate and inhibition of myorod and twitchin phosphorylation by myosin

Author

Sobieszek, Apolinary, Sarg, Bettina, Lindner, Herbert, Matusovsky, Oleg S., and Zukowska, Magdalena

Subjects
Ammonium sulphate -- Chemical properties, Mollusks -- Physiological aspects, Mollusks -- Genetic aspects, Phosphorylation -- Analysis, Phosphotransferases -- Chemical properties, Phosphotransferases -- Structure, Biological sciences, Chemistry
Abstract

Ammonium sulfate fractionation and divalent cation precipitation were applied to purify major contractile proteins from relaxed actomyosin extracted from molluscan catch muscle myofibrils, as a supramolecular complex composed of twitchin (TW), myosin (MY), and myorod (MR). The phosphorylation of twitchin by PKA-like kinase and the phosphorylation of myosin and myorod by myosin-associated kinase were found to play crucial role in the development of the catch state.

Published
2010

33. A conditional piggyBac transposition system for genetic screening in mice identifies oncogenic networks in pancreatic cancer

Author

Rad, Roland, primary, Rad, Lena, additional, Wang, Wei, additional, Strong, Alexander, additional, Ponstingl, Hannes, additional, Bronner, Iraad F, additional, Mayho, Matthew, additional, Steiger, Katja, additional, Weber, Julia, additional, Hieber, Maren, additional, Veltkamp, Christian, additional, Eser, Stefan, additional, Geumann, Ulf, additional, Öllinger, Rupert, additional, Zukowska, Magdalena, additional, Barenboim, Maxim, additional, Maresch, Roman, additional, Cadiñanos, Juan, additional, Friedrich, Mathias, additional, Varela, Ignacio, additional, Constantino-Casas, Fernando, additional, Sarver, Aaron, additional, ten Hoeve, Jelle, additional, Prosser, Haydn, additional, Seidler, Barbara, additional, Bauer, Judith, additional, Heikenwälder, Mathias, additional, Metzakopian, Emmanouil, additional, Krug, Anne, additional, Ehmer, Ursula, additional, Schneider, Günter, additional, Knösel, Thomas, additional, Rümmele, Petra, additional, Aust, Daniela, additional, Grützmann, Robert, additional, Pilarsky, Christian, additional, Ning, Zemin, additional, Wessels, Lodewyk, additional, Schmid, Roland M, additional, Quail, Michael A, additional, Vassiliou, George, additional, Esposito, Irene, additional, Liu, Pentao, additional, Saur, Dieter, additional, and Bradley, Allan, additional

Published
2014
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34. Evolutionary routes and KRASdosage define pancreatic cancer phenotypes

Author

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

Abstract

The poor correlation of mutational landscapes with phenotypes limits our understanding of the pathogenesis and metastasis of pancreatic ductal adenocarcinoma (PDAC). Here we show that oncogenic dosage-variation has a critical role in PDAC biology and phenotypic diversification. We find an increase in gene dosage of mutant KRASin human PDAC precursors, which drives both early tumorigenesis and metastasis and thus rationalizes early PDAC dissemination. To overcome the limitations posed to gene dosage studies by the stromal richness of PDAC, we have developed large cell culture resources of metastatic mouse PDAC. Integration of cell culture genomes, transcriptomes and tumour phenotypes with functional studies and human data reveals additional widespread effects of oncogenic dosage variation on cell morphology and plasticity, histopathology and clinical outcome, with the highest KrasMUTlevels underlying aggressive undifferentiated phenotypes. We also identify alternative oncogenic gains (Myc, Yap1or Nfkb2), which collaborate with heterozygous KrasMUTin driving tumorigenesis, but have lower metastatic potential. Mechanistically, different oncogenic gains and dosages evolve along distinct evolutionary routes, licensed by defined allelic states and/or combinations of hallmark tumour suppressor alterations (Cdkn2a, Trp53, Tgfβ-pathway). Thus, evolutionary constraints and contingencies direct oncogenic dosage gain and variation along defined routes to drive the early progression of PDAC and shape its downstream biology. Our study uncovers universal principles of Ras-driven oncogenesis that have potential relevance beyond pancreatic cancer.

Published
2018
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36. Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes

Author

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

Subjects
Male, endocrine system diseases, Carcinogenesis, Gene Dosage, Genes, myc, Cell Cycle Proteins, Evolution, Molecular, Proto-Oncogene Proteins p21(ras), Transforming Growth Factor beta1, Mice, NF-kappa B p52 Subunit, Animals, Humans, Neoplasm Metastasis, Alleles, Cyclin-Dependent Kinase Inhibitor p16, Adaptor Proteins, Signal Transducing, Nuclear Proteins, YAP-Signaling Proteins, Genes, p53, Phosphoproteins, digestive system diseases, 3. Good health, Pancreatic Neoplasms, Phenotype, Mutation, Disease Progression, Female, Transcriptome, Carcinoma, Pancreatic Ductal, Transcription Factors
Abstract

The poor correlation of mutational landscapes with phenotypes limits our understanding of the pathogenesis and metastasis of pancreatic ductal adenocarcinoma (PDAC). Here we show that oncogenic dosage-variation has a critical role in PDAC biology and phenotypic diversification. We find an increase in gene dosage of mutant KRAS in human PDAC precursors, which drives both early tumorigenesis and metastasis and thus rationalizes early PDAC dissemination. To overcome the limitations posed to gene dosage studies by the stromal richness of PDAC, we have developed large cell culture resources of metastatic mouse PDAC. Integration of cell culture genomes, transcriptomes and tumour phenotypes with functional studies and human data reveals additional widespread effects of oncogenic dosage variation on cell morphology and plasticity, histopathology and clinical outcome, with the highest KrasMUTlevels underlying aggressive undifferentiated phenotypes. We also identify alternative oncogenic gains (Myc, Yap1 or Nfkb2), which collaborate with heterozygous KrasMUTin driving tumorigenesis, but have lower metastatic potential. Mechanistically, different oncogenic gains and dosages evolve along distinct evolutionary routes, licensed by defined allelic states and/or combinations of hallmark tumour suppressor alterations (Cdkn2a, Trp53, Tgfβ-pathway). Thus, evolutionary constraints and contingencies direct oncogenic dosage gain and variation along defined routes to drive the early progression of PDAC and shape its downstream biology. Our study uncovers universal principles of Ras-driven oncogenesis that have potential relevance beyond pancreatic cancer.

37. Different positions of tropomyosin isoforms on actin filament are determined by specific sequences of end-to-end overlaps.

Author

Sliwińska M, Zukowska M, Borys D, and Moraczewska J

Subjects
Actins genetics, Animals, Anisotropy, Fluorescence Resonance Energy Transfer, Mutation, Myosins genetics, Protein Binding, Rats, Tropomyosin genetics, Actins metabolism, Myosins metabolism, Tropomyosin metabolism
Abstract

Tropomyosins are dimeric rod-like proteins which polymerize along actin filaments and regulate interactions with other actin-binding proteins. Homologous sequences responsible for the binding of tropomyosin to consecutive actin monomers repeat along tropomyosin and are called actin-binding periods. In this work, the localization of tropomyosin isoforms on actin alone and on actin–myosin complex was evaluated by measuring Förster resonance energy transfer (FRET) distances between a donor (AEDANS) attached to either the N-terminal actin-binding period 1 or to the central actin-binding period 5 and an acceptor (DABMI) bound to actin's Cys374. The recombinant -tropomyosin isoforms–TM2, TM5a, and TM1b9a, used in this study, had various amino acid sequences of the N- and C-termini forming the end-to-end overlap. Although the sequences of actin-binding period 5 of the three isoforms were identical, the donor–acceptor distances calculated for each isoform varied between 38.6 and 41.5 Å. Differences in FRET distances between the three tropomyosin isoforms labeled in actin-binding period 1 varied between 34.8 and 40.2 Å. Rigor binding of myosin heads to actin increased all measured distances. The degree and cooperativity of myosin-induced shift was different for each of the isoforms and actin-binding periods. The structural differences correlate with cooperative regulation of actin-activated S1 ATPase by the three tropomyosins. The results indicate that amino acid sequences of the end-to-end overlap determine specific orientation of tropomyosin isoform on actin. This can be important for steric and cooperative regulation of the actin filament and determine functional specificity of multiple tropomyosin isoforms present in eucaryotic cells., (© 2011 Wiley-Liss, Inc.)

Published
2011
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