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1. Checkpoint Inhibitor Monotherapy in Potentially Trial-Eligible or Trial-Ineligible Patients With Metastatic NSCLC in the German Prospective CRISP Registry Real-World Cohort (AIO-TRK-0315)

Author

Ababei, Juliana, Alt, Jürgen, Ammon, Andreas, Anhuf, Jürgen, Azeh, Ivo, Bauer, Stefan, Behringer, Dirk, Berger, Winfried, Bernhardt, Christiane, Bertram, Mathias, Boesche, Michael, Bohnet, Sabine, Bruch, Harald-Robert, Brückl, Wolfgang, Burkhard-Meier, Ulrike, Christopoulos, Petros, Däßler, Klaus-Ulrich, de Wit, Maike, Dechow, Tobias, Depenbusch, Reinhard, Dietze, Lutz, Dommach, Markus, Dörfel, Steffen, Eberhardt, Wilfried, Elender, Corinna, Elsel, Wolfgang, Emde, Till-Oliver, Faehling, Martin, Fietz, Thomas, Fischer, Jürgen R., Flieger, Dimitri, Freidt, Anke, Freier, Werner, Frenzel, Christian, Fuchs, Florian, Fuchs, Roswitha, Gaska, Tobias, Gleiber, Wolfgang, Grah, Christian, Griesinger, Frank, Grohé, Christian, Groschek, Matthias, Güldenzoph, Björn, Günther, Andreas, Haas, Siegfried, Hackenthal, Matthias, Hagen, Volker, Hahn, Lars, Hannig Carla, Verena, Hansen, Richard, Harich, Hanns-Detlev, Heilmann, Monika, Heinrich, Kathrin, Hering-Schubert, Christiane, Heßling, Jörg, Hoffknecht, Petra, Hortig, Patricia, Hübner, Gerdt, Hummel, Horst-Dieter, Hutzschenreuter, Ulrich, Illmer, Thomas, Innig, Georg, Jaeschke, Bastian, Junghanß, Christian, Kaiser, Ulrich, Kamal, Haytham, Kambartel, Kato, Kern, Jens, Kimmich, Martin, Kingreen, Dorothea, Kirchen, Heinz, Klausmann, Martine, Klein, Ortwin, Kokowski, Konrad, Körber, Wolfgang, Kortsik, Cornelius, Koschel, Dirk, Krämer, Benoit, Krammer-Steiner, Beate, Laack, Eckart, Lamberti, Christof, Leistner, Rumo David, Losem, Christoph, Lück, Andreas, Maintz, Christoph, Martin, Kerstin, Medgenberg, Dirk, Metzenmacher, Martin, Meyer zum Büschenfelde, Christian, Meyn, Philipp, Moorahrend, Enno, Müller, Annette, Müller, Lothar, Neise, Michael, Nückel, Holger, Nusch, Arnd, Overbeck, Tobias, Pelz, Henning, Petersen, Volker, Peuser, Bettina, Plath, Margarete, Randerath, Winfried J., Rauh, Jacqueline, Reck, Martin, Reichert, Dietmar, Reinmuth, Niels, Reiser, Marcel, Repp, Roland, Reschke, Daniel, Rittmeyer, Achim, Rodemer, Yolanda, Sackmann, Sandra, Sadjadian, Parvis, Sandner, Reiner, Sauer, Annette, Schäfer, Harald, Schaudt, Christoph, Schlag, Rudolf, Schmidt, Burkhard, Schmitz, Stephan, Schröder, Jan, Schroeder, Michael, Schulze, Mathias, Schumann, Christian, Schütte, Wolfgang, Schwaiblmair, Martin, Schwindt Peter, Florian, Sebastian, Martin, Seese, Bernd, Seipelt, Gernot, Sorgenfrei, Thomas, Steiff, Johannes, Steiniger, Heike, Trarbach, Tanja, Tufman, Amanda, Uhlig, Jens, Vehling-Kaiser, Ursula, von der Heyde, Eyck, von Verschuer, Ulla, Waller, Cornelius, Wehler, Thomas, Weißenborn, Georg, Weißinger, Florian, Wermke, Martin, Wesseler, Claas, Wiegand, Jörg, Wilhelm, Stefan, Wilke, Jochen, Zahn, Mark-Oliver, Zaiss, Matthias, Zeth, Matthias, Eberhardt, Wilfried E.E., Brueckl, Wolfgang M., Jänicke, Martina, Fleitz, Annette, Zacharias, Stefan, Hipper, Annette, Groth, Annika, Weichert, Wilko, and Thomas, Michael

Published
2024
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2. Structure-function studies of the UV-B photoreceptor UVR8 in Arabidopsis thaliana

Author

Heilmann, Monika

Subjects
583, QK Botany
Abstract

UV-B radiation is an integral component of natural sunlight reaching the Earth’s surface. Although being a potentially harmful and damaging agent, UV-B is a key environmental signal for plants initiating diverse responses that affect their metabolism, development and viability. The majority of these responses involve the differential regulation of gene expression and all require accurate perception of the effective light quality by a photoreceptor. The recent identification of UV RESISTANCE LOCUS8 (UVR8) as a UV B photoreceptor has been an important milestone in plant UV B research (Rizzini et al., 2011; Christie et al., 2012; Wu et al., 2012). The aim of this study was to investigate how the structure of the UVR8 protein determines its function in the UV-B response in Arabidopsis.

Published
2013

3. Prognostic factors in non-small-cell lung cancer: insights from the German crisp registry

Author

Griesinger, Frank, Hummel, Horst-Dieter, Schäfer, Harald, de Wit, Maike, Kaiser, Ulrich, Kern, Jens, Jänicke, Martina, Spring, Lisa, Zacharias, Stefan, Kaiser-Osterhues, Anja, Groth, Annika, Hipper, Annette, Zaun, Gregor, Müller, Lothar, Uhlig, Jens, Thomas, Michael, Sebastian, Martin, Eberhardt, Wilfried, Ababei, Juliana, Alt, Jürgen, Ammon, Andreas, Anhuf, Jürgen, Azeh, Ivo, Bauer, Stefan, Behringer, Dirk, Berger, Winfried, Bernhardt, Christiane, Bertram, Mathias, Boesche, Michael, Bohnet, Sabine, Bruch, Harald-Robert, Brückl, Wolfgang, Burkhard-Meier, Ulrike, Christopoulos, Petros, Däßler, Klaus-Ulrich, Dechow, Tobias, Depenbusch, Reinhard, Dietze, Lutz, Dommach, Markus, Dörfel, Steffen, Elender, Corinna, Elsel, Wolfgang, Emde, Till-Oliver, Faehling, Martin, Fietz, Thomas, Fischer, Jürgen R., Flieger, Dimitri, Freidt, Anke, Freier, Werner, Frenzel, Christian, Fuchs, Florian, Fuchs, Roswitha, Gaska, Tobias, Gleiber, Wolfgang, Grah, Christian, Grohé, Christian, Groschek, Matthias, Güldenzoph, Björn, Günther, Andreas, Haas, Siegfried, Hackenthal, Matthias, Hagen, Volker, Hahn, Lars, Hannig, Carla Verena, Hansen, Richard, Harich, Hanns-Detlev, Heilmann, Monika, Heinrich, Kathrin, Hering-Schubert, Christiane, Heßling, Jörg, Hoffknecht, Petra, Hortig, Patricia, Hübner, Gerdt, Hutzschenreuter, Ulrich, Illmer, Thomas, Innig, Georg, Jaeschke, Bastian, Junghanß, Christian, Kamal, Haytham, Kambartel, Kato, Kimmich, Martin, Kingreen, Dorothea, Kirchen, Heinz, Klausmann, Martine, Klein, Ortwin, Kokowski, Konrad, Körber, Wolfgang, Kortsik, Cornelius, Koschel, Dirk, Krämer, Benoit, Krammer-Steiner, Beate, Laack, Eckart, Lamberti, Christof, Leistner, Rumo David, Losem, Christoph, Lück, Andreas, Maintz, Christoph, Martin, Kerstin, Medgenberg, Dirk, Metzenmacher, Martin, Meyer zum Büschenfelde, Christian, Meyn, Philipp, Moorahrend, Enno, Müller, Annette, Neise, Michael, Nückel, Holger, Nusch, Arnd, Overbeck, Tobias, Pelz, Henning, Petersen, Volker, Peuser, Bettina, Plath, Margarete, Randerath, Winfried J., Rauh, Jacqueline, Reck, Martin, Reichert, Dietmar, Reinmuth, Niels, Reiser, Marcel, Repp, Roland, Reschke, Daniel, Rittmeyer, Achim, Rodemer, Yolanda, Sackmann, Sandra, Sadjadian, Parvis, Sandner, Reiner, Sauer, Annette, Schaudt, Christoph, Schlag, Rudolf, Schmidt, Burkhard, Schmitz, Stephan, Schröder, Jan, Schroeder, Michael, Schulze, Mathias, Schumann, Christian, Schütte, Wolfgang, Schwaiblmair, Martin, Schwindt, Peter Florian, Seese, Bernd, Seipelt, Gernot, Sorgenfrei, Thomas, Steiff, Johannes, Steiniger, Heike, Trarbach, Tanja, Tufman, Amanda, Vehling-Kaiser, Ursula, von der Heyde, Eyck, von Verschuer, Ulla, Waller, Cornelius, Wehler, Thomas, Weißenborn, Georg, Weißinger, Florian, Wermke, Martin, Wesseler, Claas, Wiegand, Jörg, Wilhelm, Stefan, Wilke, Jochen, Zahn, Mark-Oliver, Zaiss, Matthias, and Zeth, Matthias

Subjects
Pulmonary and Respiratory Medicine, Medizin
Abstract

IntroductionUnderstanding prognosis, especially long-term outcome, in advanced nonsmall cell lung cancer (NSCLC) is crucial to inform patients, guide treatment and plan supportive and palliative care.MethodsPrognostic factors influencing overall survival (OS) and progression-free survival (PFS) in 2082 patients with wild-type (WT)-NSCLC (629 M1a, 249 M1b, 1204 M1c) are reported. Patients were included in the prospective German CRISP registry recruiting in >150 centres. Analysis for pre-therapeutic factors was based on results from Cox proportional hazard models.ResultsCurrent M-descriptors of the Union for International Cancer Control-8 staging system were validated: M1a and M1b patients had significantly longer median time to events compared to M1c (OS/PFS 16.4/7.2 months, 17.8/6.7 months and 10.9/5.4 months, respectively). OS and PFS were influenced by number and location of metastatic organ systems. M1c and four or more metastatic organs involved had shorter OS and PFS than M1c with one to three organs (OS hazard ratio (HR) 1.69, pConclusionIn this large observational dataset, we further defined factors for outcome in WT-NSCLC, including increased number of involved metastatic organ systems and liver metastases, as those with overall poorer prognosis and reduced survival chance.

Published
2022

10. Corrigendum to “Biomarker testing in non-small cell lung cancer in routine care: Analysis of the first 3,717 patients in the German prospective, observational, nation-wide CRISP registry (AIO-TRK-0315)” [Lung Cancer 152 (2021) 174–184]

Author

Griesinger, Frank, primary, Eberhardt, Wilfried, additional, Nusch, Arnd, additional, Reiser, Marcel, additional, Zahn, Mark-Oliver, additional, Maintz, Christoph, additional, Bernhardt, Christiane, additional, Losem, Christoph, additional, Stenzinger, Albrecht, additional, Heukamp, Lukas C., additional, Büttner, Reinhard, additional, Marschner, Norbert, additional, Jänicke, Martina, additional, Fleitz, Annette, additional, Spring, Lisa, additional, Sahlmann, Jörg, additional, Karatas, Aysun, additional, Hipper, Annette, additional, Weichert, Wilko, additional, Heilmann, Monika, additional, Sadjadian, Parvis, additional, Gleiber, Wolfgang, additional, Grah, Christian, additional, Waller, Cornelius F., additional, Reck, Martin, additional, Rittmeyer, Achim, additional, Christopoulos, Petros, additional, Sebastian, Martin, additional, and Thomas, Michael, additional

Published
2021
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11. Biomarker testing in non-small cell lung cancer in routine care: Analysis of the first 3,717 patients in the German prospective, observational, nation-wide CRISP registry (AIO-TRK-0315) (vol 152, pg 174, 2021)

Author

Griesinger, Frank, Eberhardt, Wilfried, Nusch, Arnd, Reiser, Marcel, Zahn, Mark-Oliver, Maintz, Christoph, Bernhardt, Christiane, Losem, Christoph, Stenzinger, Albrecht, Heukamp, Lukas C., Buettner, Reinhard, Marschner, Norbert, Jaenicke, Martina, Fleitz, Annette, Spring, Lisa, Sahlmann, Joerg, Karatas, Aysun, Hipper, Annette, Weichert, Wilko, Heilmann, Monika, Sadjadian, Parvis, Gleiber, Wolfgang, Grah, Christian, Waller, Cornelius F., Reck, Martin, Rittmeyer, Achim, Christopoulos, Petros, Sebastian, Martin, Thomas, Michael, Griesinger, Frank, Eberhardt, Wilfried, Nusch, Arnd, Reiser, Marcel, Zahn, Mark-Oliver, Maintz, Christoph, Bernhardt, Christiane, Losem, Christoph, Stenzinger, Albrecht, Heukamp, Lukas C., Buettner, Reinhard, Marschner, Norbert, Jaenicke, Martina, Fleitz, Annette, Spring, Lisa, Sahlmann, Joerg, Karatas, Aysun, Hipper, Annette, Weichert, Wilko, Heilmann, Monika, Sadjadian, Parvis, Gleiber, Wolfgang, Grah, Christian, Waller, Cornelius F., Reck, Martin, Rittmeyer, Achim, Christopoulos, Petros, Sebastian, Martin, and Thomas, Michael

Published
2021

12. Biomarker testing in non-small cell lung cancer in routine care: Analysis of the first 3,717 patients in the German prospective, observational, nation-wide CRISP Registry (AIO-TRK-0315)

Author

Griesinger, Frank, Eberhardt, Wilfried, Nusch, Arnd, Reiser, Marcel, Zahn, Mark-Oliver, Maintz, Christoph, Bernhardt, Christiane, Losem, Christoph, Stenzinger, Albrecht, Heukamp, Lukas C., Buettner, Reinhard, Marschner, Norbert, Jaenicke, Martina, Fleitz, Annette, Spring, Lisa, Sahlmann, Joerg, Karatas, Aysun, Hipper, Annette, Weichert, Wilko, Heilmann, Monika, Sadjadian, Parvis, Gleiber, Wolfgang, Grah, Christian, Waller, Cornelius F., Reck, Martin, Rittmeyer, Achim, Christopoulos, Petros, Sebastian, Martin, Thomas, Michael, Griesinger, Frank, Eberhardt, Wilfried, Nusch, Arnd, Reiser, Marcel, Zahn, Mark-Oliver, Maintz, Christoph, Bernhardt, Christiane, Losem, Christoph, Stenzinger, Albrecht, Heukamp, Lukas C., Buettner, Reinhard, Marschner, Norbert, Jaenicke, Martina, Fleitz, Annette, Spring, Lisa, Sahlmann, Joerg, Karatas, Aysun, Hipper, Annette, Weichert, Wilko, Heilmann, Monika, Sadjadian, Parvis, Gleiber, Wolfgang, Grah, Christian, Waller, Cornelius F., Reck, Martin, Rittmeyer, Achim, Christopoulos, Petros, Sebastian, Martin, and Thomas, Michael

Abstract

Objectives: An increasing number of treatment-determining biomarkers has been identified in non-small cell lung cancer (NSCLC) and molecular testing is recommended to enable optimal individualized treatment. However, data on implementation of these recommendations in the real-world setting are scarce. This study presents comprehensive details on the frequency, methodology and results of biomarker testing of advanced NSCLC in Germany. Patients and methods: This analysis included 3,717 patients with advanced NSCLC (2,921 non-squamous; 796 squamous), recruited into the CRISP registry at start of systemic therapy by 150 German sites between December 2015 and June 2019. Evaluated were the molecular biomarkers EGFR, ALK, ROS1, BRAF, KRAS, MET, TP53, RET, HER2, as well as expression of PD-L1. Results: In total, 90.5 % of the patients were tested for biomarkers. Testing rates were 92.2 % (non-squamous), 70.7 % (squamous) and increased from 83.2 % in 2015/16 to 94.2% in 2019. Overall testing rates for EGFR, ALK, ROS1, and BRAF were 72.5 %, 74.5 %, 66.1 %, and 53.0 %, respectively (non-squamous). Testing rates for PD-L1 expression were 64.5 % (non-squamous), and 58.5 % (squamous). The most common testing methods were immunohistochemistry (68.5 % non-squamous, 58.3 % squamous), and next-generation sequencing (38.7 % nonsquamous, 14.4 % squamous). Reasons for not testing were insufficient tumor material or lack of guideline recommendations (squamous). No alteration was found in 37.8 % (non-squamous), and 57.9 % (squamous), respectively. Most common alterations in non-squamous tumors (all patients/all patients tested for the respective biomarker): KRAS (17.3 %/39.2 %), TP53 (14.1 %/51.4 %), and EGFR (11.0 %/15.1 %); in squamous tumors: TP53 (7.0 %/69.1 %), MET (1.5 %/11.1 %), and EGFR (1.1 %/4.4 %). Median PFS (non-squamous) was 8.7 months (95 % CI 7.4-10.4) with druggable EGFR mutation, and 8.0 months (95 % CI 3.9-9.2) with druggable ALK alterations. Conclusion: Testing rates i

Published
2021

13. Corrigendum to 'Biomarker testing in non-small cell lung cancer in routine care: Analysis of the first 3,717 patients in the German prospective, observational, nation-wide CRISP registry (AIO-TRK-0315)' [Lung Cancer 152 (2021) 174–184]

Author

Griesinger, Frank, Eberhardt, Wilfried E. E., Nusch, Arnd, Reiser, Marcel, Zahn, Mark-Oliver, Maintz, Christoph, Bernhardt, Christiane, Losem, Christoph, Stenzinger, Albrecht, Heukamp, Lukas, Büttner, Reinhard, Marschner, Sebastian, Jänicke, Martina, Fleitz, Annette, Spring, Lisa, Sahlmann, Jörg, Karatas, Aysun, Hipper, Annette, Weichert, Wilko, Heilmann, Monika, Sadjadian, Parvis, Gleiber, Wolfgang, Grah, Christian, Waller, Cornelius, Reck, Martin, Rittmeyer, Achim, Christopoulos, Petros, Sebastian, Martin, Thomas, Michael, Griesinger, Frank, Eberhardt, Wilfried E. E., Nusch, Arnd, Reiser, Marcel, Zahn, Mark-Oliver, Maintz, Christoph, Bernhardt, Christiane, Losem, Christoph, Stenzinger, Albrecht, Heukamp, Lukas, Büttner, Reinhard, Marschner, Sebastian, Jänicke, Martina, Fleitz, Annette, Spring, Lisa, Sahlmann, Jörg, Karatas, Aysun, Hipper, Annette, Weichert, Wilko, Heilmann, Monika, Sadjadian, Parvis, Gleiber, Wolfgang, Grah, Christian, Waller, Cornelius, Reck, Martin, Rittmeyer, Achim, Christopoulos, Petros, Sebastian, Martin, and Thomas, Michael

Published
2021

15. Biomarker testing in non-small cell lung cancer in routine care: Analysis of the first 3,717 patients in the German prospective, observational, nation-wide CRISP Registry (AIO-TRK-0315)

Author

Griesinger, Frank, primary, Eberhardt, Wilfried, additional, Nusch, Arnd, additional, Reiser, Marcel, additional, Zahn, Mark-Oliver, additional, Maintz, Christoph, additional, Bernhardt, Christiane, additional, Losem, Christoph, additional, Stenzinger, Albrecht, additional, Heukamp, Lukas C., additional, Büttner, Reinhard, additional, Marschner, Norbert, additional, Jänicke, Martina, additional, Fleitz, Annette, additional, Spring, Lisa, additional, Sahlmann, Jörg, additional, Karatas, Aysun, additional, Hipper, Annette, additional, Weichert, Wilko, additional, Heilmann, Monika, additional, Sadjadian, Parvis, additional, Gleiber, Wolfgang, additional, Grah, Christian, additional, Waller, Cornelius F., additional, Reck, Martin, additional, Rittmeyer, Achim, additional, Christopoulos, Petros, additional, Sebastian, Martin, additional, and Thomas, Michael, additional

Published
2021
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17. Checkpoint Inhibitor Monotherapy in Potentially Trial-Eligible or Trial-Ineligible Patients With Metastatic NSCLC in the German Prospective CRISP Registry Real-World Cohort (AIO-TRK-0315)

Author

Griesinger, Frank, Sebastian, Martin, Brueckl, Wolfgang M., Hummel, Horst-Dieter, Jaeschke, Bastian, Kern, Jens, Wesseler, Claas, Jänicke, Martina, Fleitz, Annette, Zacharias, Stefan, Hipper, Annette, Groth, Annika, Weichert, Wilko, Dörfel, Steffen, Petersen, Volker, Schröder, Jan, Wilke, Jochen, Eberhardt, Wilfried E.E., Thomas, Michael, Ababei, Juliana, Alt, Jürgen, Ammon, Andreas, Anhuf, Jürgen, Azeh, Ivo, Bauer, Stefan, Behringer, Dirk, Berger, Winfried, Bernhardt, Christiane, Bertram, Mathias, Boesche, Michael, Bohnet, Sabine, Bruch, Harald-Robert, Brückl, Wolfgang, Burkhard-Meier, Ulrike, Christopoulos, Petros, Däßler, Klaus-Ulrich, de Wit, Maike, Dechow, Tobias, Depenbusch, Reinhard, Dietze, Lutz, Dommach, Markus, Dörfel, Steffen, Eberhardt, Wilfried, Elender, Corinna, Elsel, Wolfgang, Emde, Till-Oliver, Faehling, Martin, Fietz, Thomas, Fischer, Jürgen R., Flieger, Dimitri, Freidt, Anke, Freier, Werner, Frenzel, Christian, Fuchs, Florian, Fuchs, Roswitha, Gaska, Tobias, Gleiber, Wolfgang, Grah, Christian, Griesinger, Frank, Grohé, Christian, Groschek, Matthias, Güldenzoph, Björn, Günther, Andreas, Haas, Siegfried, Hackenthal, Matthias, Hagen, Volker, Hahn, Lars, Hannig Carla, Verena, Hansen, Richard, Harich, Hanns-Detlev, Heilmann, Monika, Heinrich, Kathrin, Hering-Schubert, Christiane, Heßling, Jörg, Hoffknecht, Petra, Hortig, Patricia, Hübner, Gerdt, Hummel, Horst-Dieter, Hutzschenreuter, Ulrich, Illmer, Thomas, Innig, Georg, Jaeschke, Bastian, Junghanß, Christian, Kaiser, Ulrich, Kamal, Haytham, Kambartel, Kato, Kern, Jens, Kimmich, Martin, Kingreen, Dorothea, Kirchen, Heinz, Klausmann, Martine, Klein, Ortwin, Kokowski, Konrad, Körber, Wolfgang, Kortsik, Cornelius, Koschel, Dirk, Krämer, Benoit, Krammer-Steiner, Beate, Laack, Eckart, Lamberti, Christof, Leistner, Rumo David, Losem, Christoph, Lück, Andreas, Maintz, Christoph, Martin, Kerstin, Medgenberg, Dirk, Metzenmacher, Martin, Meyer zum Büschenfelde, Christian, Meyn, Philipp, Moorahrend, Enno, Müller, Annette, Müller, Lothar, Neise, Michael, Nückel, Holger, Nusch, Arnd, Overbeck, Tobias, Pelz, Henning, Petersen, Volker, Peuser, Bettina, Plath, Margarete, Randerath, Winfried J., Rauh, Jacqueline, Reck, Martin, Reichert, Dietmar, Reinmuth, Niels, Reiser, Marcel, Repp, Roland, Reschke, Daniel, Rittmeyer, Achim, Rodemer, Yolanda, Sackmann, Sandra, Sadjadian, Parvis, Sandner, Reiner, Sauer, Annette, Schäfer, Harald, Schaudt, Christoph, Schlag, Rudolf, Schmidt, Burkhard, Schmitz, Stephan, Schröder, Jan, Schroeder, Michael, Schulze, Mathias, Schumann, Christian, Schütte, Wolfgang, Schwaiblmair, Martin, Schwindt Peter, Florian, Sebastian, Martin, Seese, Bernd, Seipelt, Gernot, Sorgenfrei, Thomas, Steiff, Johannes, Steiniger, Heike, Trarbach, Tanja, Tufman, Amanda, Uhlig, Jens, Vehling-Kaiser, Ursula, von der Heyde, Eyck, von Verschuer, Ulla, Waller, Cornelius, Wehler, Thomas, Weißenborn, Georg, Weißinger, Florian, Wermke, Martin, Wesseler, Claas, Wiegand, Jörg, Wilhelm, Stefan, Wilke, Jochen, Zahn, Mark-Oliver, Zaiss, Matthias, and Zeth, Matthias

Abstract

Patients with metastatic NSCLC (mNSCLC) treated with immune checkpoint inhibitors in clinical practice may often not meet the strict inclusion criteria of clinical trials. Our aim was to assess the trial eligibility of patients with mNSCLC treated with pembrolizumab monotherapy in real-world and to compare the outcome of “trial-ineligible” and “potentially trial-eligible” patients.

Published
2024
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18. Dimer/monomer status and in vivo function of salt-bridge mutants of the plant UV-B photoreceptor UVR8

Author

Heilmann, Monika, Velanis, Christos N., Cloix, Catherine, Smith, Brian O., Christie, John M., and Jenkins, Gareth I.

Abstract

UV RESISTANCE LOCUS8 (UVR8) is a photoreceptor for ultraviolet-B (UV-B) light that initiates photomorphogenic responses in plants. UV-B photoreception causes rapid dissociation of dimeric UVR8 into monomers that interact with CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1) to initiate signal transduction. Experiments with purified UVR8 show that the dimer is maintained by salt-bridge interactions between specific charged amino acids across the dimer interface. However, little is known about the importance of these charged amino acids in determining dimer/monomer status and UVR8 function in plants. Here we evaluate the use of different methods to examine dimer/monomer status of UVR8 and show that mutations of several salt-bridge amino acids affect dimer/monomer status, interaction with COP1 and photoreceptor function of UVR8 in vivo. In particular, the salt-bridges formed between arginine 286 and aspartates 96 and 107 are key to dimer formation. Mutation of arginine 286 to alanine impairs dimer formation, interaction with COP1 and function in vivo, whereas mutation to lysine gives a weakened dimer that is functional in vivo, indicating the importance of the positive charge of the arginine/lysine residue for dimer formation. Notably, a UVR8 mutant in which aspartates 96 and 107 are conservatively mutated to asparagine is strongly impaired in dimer formation but mediates UV-B responses in vivo with a similar dose-response relationship to wild-type. The UV-B responsiveness of this mutant does not correlate with dimer formation and monomerisation, indicating that monomeric UVR8 has the potential for UV-B photoreception, initiating signal transduction and responses in plants.

Published
2016

20. Evolutionary conservation of structure and function of the UVR8 photoreceptor from the liverwort Marchantia polymorpha and the moss Physcomitrella patens.

Author

Soriano, Gonzalo, Cloix, Catherine, Heilmann, Monika, Núñez‐Olivera, Encarnación, Martínez‐Abaigar, Javier, and Jenkins, Gareth I.

Subjects
PLANT photoreceptors, MARCHANTIA polymorpha, PHYSCOMITRELLA patens, ARABIDOPSIS, GENE expression
Abstract

The ultraviolet-B ( UV-B) photoreceptor UV RESISTANCE LOCUS 8 ( UVR8) mediates photomorphogenic responses to UV-B in Arabidopsis through differential gene expression, but little is known about UVR8 in other species. Bryophyte lineages were the earliest diverging embryophytes, thus being the first plants facing the UV-B regime typical of land. We therefore examined whether liverwort and moss species have functional UVR8 proteins and whether they are regulated similarly to Arabidopsis UVR8., We examined the expression, dimer/monomer status, cellular localisation and function of Marchantia polymorpha and Physcomitrella patens UVR8 in experiments with bryophyte tissue and expression of green fluorescent protein ( GFP)- UVR8 fusions in Nicotiana leaves and transgenic Arabidopsis., P. patens expresses two UVR8 genes that encode functional proteins, whereas the single M. polymorpha UVR8 gene expresses two transcripts by alternative splicing that encode functional UVR8 variants. P. patens UVR8 proteins form dimers that monomerise and accumulate in the nucleus following UV-B exposure, similar to Arabidopsis UVR8, but M. polymorpha UVR8 has weaker dimers and the proteins appear more constitutively nuclear., We conclude that liverwort and moss species produce functional UVR8 proteins. Although there are differences in expression and regulation of P. patens and M. polymorpha UVR8, the mechanism of UVR8 action is strongly conserved in evolution. [ABSTRACT FROM AUTHOR]

Published
2018
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27. Proton-Coupled Electron Transfer Constitutes the Photoactivation Mechanism of the Plant Photoreceptor UVR8.

Author

Mathis, Tilo, Heilmann, Monika, Pandit, Anjali, Jingyi Zhu, Ravensbergen, Janneke, Kloz, Miroslav, Yinan Fu, Smith, Brian O., Christie, John M., Jenkins, Gareth I., and Kennis, John T. M.

Subjects
*OXIDATION-reduction reaction, *PHOTOACTIVATION, *PLANT photoreceptors, *TRYPTOPHAN, *CHARGE exchange, *DIMERS
Abstract

UVR8 is a novel UV-B photoreceptor that regulates a range of plant responses and is already used as a versatile optogenetic tool. Instead of an exogenous chromophore, UVR8 uniquely employs tryptophan side chains to accomplish UV-B photoreception. UV-B absorption by homodimeric UVR8 induces monomerization and hence signaling, but the underlying photodynamic mechanisms are not known. Here, by using a combination of time-resolved fluorescence and absorption spectroscopy from femto- to microseconds, we provide the first experimental evidence for the UVR8 molecular signaling mechanism. The results indicate that tryptophan residues at the dimer interface engage in photoinduced proton coupled electron transfer reactions that induce monomerization. [ABSTRACT FROM AUTHOR]

Published
2015
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30. Structure-function studies of the UV-B photoreceptor UVR8 in Arabidopsis thaliana

Author

Heilmann, Monika and Heilmann, Monika

Abstract

UV-B radiation is an integral component of natural sunlight reaching the Earth’s surface. Although being a potentially harmful and damaging agent, UV-B is a key environmental signal for plants initiating diverse responses that affect their metabolism, development and viability. The majority of these responses involve the differential regulation of gene expression and all require accurate perception of the effective light quality by a photoreceptor. The recent identification of UV RESISTANCE LOCUS8 (UVR8) as a UV B photoreceptor has been an important milestone in plant UV B research (Rizzini et al., 2011; Christie et al., 2012; Wu et al., 2012). The aim of this study was to investigate how the structure of the UVR8 protein determines its function in the UV-B response in Arabidopsis.

31. Structure-function studies of the UV-B photoreceptor UVR8 in Arabidopsis thaliana

Author

Heilmann, Monika and Heilmann, Monika

Abstract

UV-B radiation is an integral component of natural sunlight reaching the Earth’s surface. Although being a potentially harmful and damaging agent, UV-B is a key environmental signal for plants initiating diverse responses that affect their metabolism, development and viability. The majority of these responses involve the differential regulation of gene expression and all require accurate perception of the effective light quality by a photoreceptor. The recent identification of UV RESISTANCE LOCUS8 (UVR8) as a UV B photoreceptor has been an important milestone in plant UV B research (Rizzini et al., 2011; Christie et al., 2012; Wu et al., 2012). The aim of this study was to investigate how the structure of the UVR8 protein determines its function in the UV-B response in Arabidopsis.

32. Structure-function studies of the UV-B photoreceptor UVR8 in Arabidopsis thaliana

Author

Heilmann, Monika and Heilmann, Monika

Abstract

UV-B radiation is an integral component of natural sunlight reaching the Earth’s surface. Although being a potentially harmful and damaging agent, UV-B is a key environmental signal for plants initiating diverse responses that affect their metabolism, development and viability. The majority of these responses involve the differential regulation of gene expression and all require accurate perception of the effective light quality by a photoreceptor. The recent identification of UV RESISTANCE LOCUS8 (UVR8) as a UV B photoreceptor has been an important milestone in plant UV B research (Rizzini et al., 2011; Christie et al., 2012; Wu et al., 2012). The aim of this study was to investigate how the structure of the UVR8 protein determines its function in the UV-B response in Arabidopsis.

33. Severe Syndrome of Inappropriate Antidiuretic Hormone Secretion with Docetaxel Treatment in Metastatic Breast Cancer.

Author

Langer-Nitsche, Christiane, Lück, Hans-Joachim, and Heilmann, Monika

Subjects
DOCETAXEL, BREAST cancer, DRUG therapy, DRUG side effects
Abstract

Presents the case of an elderly woman with metastatic breast cancer who developed severe syndrome of inappropriate antidiuretic hormone secretion (SIADH) during treatment with docetaxel. First reported case of SIADH related to taxine chemotherapy in breast cancer; Change of the antineoplastic regimen to an oral treatment with an aromatase inhibitor.

Published
2000
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34. Autoren

Author

Adam, Olaf, Ahrens, Katrin, Allolio, Bruno, Andreas, Stephan, Anker, Stefan, Arends, Jann, Assmann, Gerd, Becker, Klaus, Berg, Aloys, Bergmann, Karl E., Bergmann, Renate, Berthold, Heiner K., Bischoff, Stephan C., Böhles, Hansjosef, Bösch, Dennis, Bremer, Karl, Busse, Martin W., Dellweg, Dominic, Druml, Wilfried, Dudenhausen, Joachim W., Ehrenreich, Hannelore, Eis, Dieter, Ellrott, Thomas, Erckenbrecht, Joachim F., Ernst, Jan Peter, Exner, Martin, Faustin, Vivien, Flieger, Robert, Forth, Wolfgang, Friebe, Holger, Gärtner, Roland, Großklaus, Rolf, Grunewald, R. Willi, Gundert-Remy, Ursula, Hahn, Andreas, Hasenfuß, Gerd, Hauner, Hans, Haustein, Knut-Olaf, Hebebrand, Johannes, Heilmann, Monika, Hense, Hans-Werner, Hermann, Hans-Peter, Hertfelder, Hans-Jörg, Heseker, Helmut, Hesse, Albrecht, Hölscher, Arnulf H., Hüfner, Michael, Husemann, Bernhard J., Huth, Walter, Jany, Klaus-Dieter, Jordan, Angelika, Kaufmann, Frank, Karaus, Michael, Keil, Ulrich, Keller, Ulrich, Kiener, Claudia, Knecht, Stefan, Koch, Horst, Kohnhorst, Marie-Luise, Köhrle, Josef, Koletzko, Berthold, König, Daniel, Köhler, Dieter, Korenke, Georg-Christoph, Krampe, Henning, Kreymann, Georg, Lakomek, Max, Langenbach, Michael, Lankisch, Paul Georg, Leitzmann, Claus, Lembcke, Bernhard, Löser, Christian, Lübke, Heinrich Josef, Lueg, Andreas, Machold, Heike, Maurer, Britta, Mausberg, Rainer F., Meiners, Thomas, Melchior, Jean-Claude, Nauck, Michael, Neumann, Daniela, Niggemann, Bodo, Oberritter, Helmut, Oelschläger, Christian, Ollenschläger, Günter, Ott, Klaus, Peters, Achim, Pfeiffer, F.H. Andreas, Pöschl, Gudrun, Pudel, Volker, Püschel, Gerhard P., Rathmann, Wolfgang, Reich, Günter, Richter, Gerd, Ring, Johannes, Ringelstein, E. Bernd, Röbl, Markus, Rosenthal, Kathrin, Schauder, Peter, Schlierf, Günter, Schmitz, Jörg Erik, Schneider, Roland, Schusdziarra, Volker, Schwenk, Achim, Seitz, Helmut K., Siener, Roswitha, Stein, Jürgen, Stickel, Felix, Stippel, Dirk, Stöckli, Rolf, Stöckmann, Fritz, Ströhle, Alexander, Subic-Wrana, Claudia, Szliska, Christiane, Tegtbur, Uwe, Toeller, Monika, Trümper, Lorenz, Vocks, Elisabeth, Volkert, Dorothee, Wächtershäuser, Astrid, Wahn, Ulrich, Wahrburg, Ursel, Werfel, Thomas, Wieland, Eberhard, Wirth, Alfred, Wolters, Maike, Wulf, Gerald, Zidek, Walter, Zunft, Hans-Joachim F., Inoue, H., Kling, C., Pöschl, G., Posselt, H.-G., Rasche, K., Richter, W.O., Rosenthal, K., Rost†, R., Schulte-Werninghaus, G., Schwanitz, H.J., Sonntag, H.-G, and Thul, P.

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35. Dimer/monomer status and in vivo function of salt-bridge mutants of the plant UV-B photoreceptor UVR8.

Author

Heilmann M, Velanis CN, Cloix C, Smith BO, Christie JM, and Jenkins GI

Subjects
Arabidopsis genetics, Arabidopsis radiation effects, Arabidopsis Proteins genetics, Chromosomal Proteins, Non-Histone genetics, Gene Expression Regulation, Plant genetics, Gene Expression Regulation, Plant radiation effects, Mutation, Ubiquitin-Protein Ligases, Ultraviolet Rays, Arabidopsis metabolism, Arabidopsis Proteins metabolism, Chromosomal Proteins, Non-Histone metabolism
Abstract

UV RESISTANCE LOCUS8 (UVR8) is a photoreceptor for ultraviolet-B (UV-B) light that initiates photomorphogenic responses in plants. UV-B photoreception causes rapid dissociation of dimeric UVR8 into monomers that interact with CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1) to initiate signal transduction. Experiments with purified UVR8 show that the dimer is maintained by salt-bridge interactions between specific charged amino acids across the dimer interface. However, little is known about the importance of these charged amino acids in determining dimer/monomer status and UVR8 function in plants. Here we evaluate the use of different methods to examine dimer/monomer status of UVR8 and show that mutations of several salt-bridge amino acids affect dimer/monomer status, interaction with COP1 and photoreceptor function of UVR8 in vivo. In particular, the salt-bridges formed between arginine 286 and aspartates 96 and 107 are key to dimer formation. Mutation of arginine 286 to alanine impairs dimer formation, interaction with COP1 and function in vivo, whereas mutation to lysine gives a weakened dimer that is functional in vivo, indicating the importance of the positive charge of the arginine/lysine residue for dimer formation. Notably, a UVR8 mutant in which aspartates 96 and 107 are conservatively mutated to asparagine is strongly impaired in dimer formation but mediates UV-B responses in vivo with a similar dose-response relationship to wild-type. The UV-B responsiveness of this mutant does not correlate with dimer formation and monomerisation, indicating that monomeric UVR8 has the potential for UV-B photoreception, initiating signal transduction and responses in plants., (© 2016 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

Published
2016
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36. [In Process Citation].

Author

Heilmann M

Subjects
Female, Germany, Humans, Male, Sex Factors, Conflict, Psychological, Harassment, Non-Sexual, Interprofessional Relations, Workplace
Published
2014
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