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Journal articles on the topic 'Thomas Kraus'

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Published: 4 June 2025

Last updated: 23 June 2025

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1

Kraus, Thomas. "Weiterentwicklung der arbeitsmedizinischen Vorsorge (Interview)." ASU Arbeitsmedizin Sozialmedizin Umweltmedizin 2023, no. 04 (2023): 213–15. http://dx.doi.org/10.17147/asu-1-266298.

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Zur aktuellen Thematik über die ganzheitliche arbeitsmedizinische Vorsorge und die neue AMR 3.3 führt ASU ein Gespräch mit Prof. Dr. Thomas Kraus (TK), dem Präsidenten der Deutschen Gesellschaft für Arbeitsmedizin und Umweltmedizin (DGAUM), und Dr. Wolfgang Panter (WP), dem Präsidenten des Verbands Deutscher Betriebs- und Werksärzte (VDBW).

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2

Köbler, Gerhard. "Die Aachener Stadtrechnungen des 15. Jahrhunderts, bearb. v. Kraus, Thomas R." Zeitschrift der Savigny-Stiftung für Rechtsgeschichte: Germanistische Abteilung 122, no. 1 (2005): 641–42. http://dx.doi.org/10.7767/zrgga.2005.122.1.641.

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3

van Emde Boas, Evert. "Emotion, Memory, Meaning, Directions: A Response to Kirsten Marie Hartvigsen and Thomas J. Kraus." Biblical Interpretation 29, no. 4-5 (2021): 616–30. http://dx.doi.org/10.1163/15685152-29040009.

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Abstract This response article reviews the contributions of Kirsten Marie Hartvigsen and Thomas Kraus to this special issue, and uses them as the basis for a discussion of some theoretical and methodological issues relevant to cognitive narratology and cognitive literary studies more broadly. Without offering substantial answers itself, the response poses questions concerning (i) the compatibility of different scientific frameworks used in cognitive models of characterization, particularly in the light of currently dominant ‘4ea’ models of cognition (there is a particular focus on the relationship between affective and (other) cognitive aspects of reader response, and on the role of memory); and (ii) the adaptability of cognitive models to dealing with “synthetic” and “thematic” (as opposed to “mimetic”) aspects of literary character. A brief conclusion argues for two-way traffic between the cognitive sciences and literary criticism.

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Schmid, U. "New Testament Manuscripts: Their Texts and Their World. Edited by THOMAS J. KRAUS and TOBIAS NICKLAS." Journal of Theological Studies 59, no. 1 (2008): 254–56. http://dx.doi.org/10.1093/jts/flm186.

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5

Colín, Miguel Flores. "Early Christian Manuscripts. Examples of Applied method and Approach by Tobias Nicklas and Thomas J. Kraus, (Ed.)." Mayéutica 36, no. 82 (2010): 458–60. http://dx.doi.org/10.5840/mayeutica2010368211.

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6

Holmes, Michael W. "Early Christian Manuscripts: Examples of Applied Method and Approach - Edited by Thomas J. Kraus and Tobias Nicklas." Religious Studies Review 37, no. 3 (2011): 209. http://dx.doi.org/10.1111/j.1748-0922.2011.01536_3.x.

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7

Delmaire, Bernard. "Thomas Kraus , Regesten des Reichsstadt Aachen , Vierter Band, 1366-1380 , Düsseldorf, Droste Verlag, 2002, xliii -542 p." Revue du Nord 371, no. 3 (2007): XVI. http://dx.doi.org/10.3917/rdn.371.0647p.

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Kraus, Virginia. "Editorial [Hot Topic: Waiting for Action on the Osteoarthritis Front (Guest Editors: Virginia Byers Kraus and Thomas Aigner)]." Current Drug Targets 11, no. 5 (2010): 518–20. http://dx.doi.org/10.2174/138945010791011974.

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9

PEARCE, SARAH. "Benjamin Schliesser, Jan Rüggemeier, Thomas J. Kraus and Jörg Frey (eds), Alexandria: Hub of the Hellenistic World." Journal of Jewish Studies 75, no. 1 (2024): 184–88. http://dx.doi.org/10.3828/jjs.2024.75.1.184.

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10

Ehrman, Bart. "Thomas J. Kraus & Tobias Nicklas (eds.). Das Petrusevangelium und die Petrusapokalypse. Die griechischen Fragmente mit deutscher und englischer Übersetzung." Vigiliae Christianae 61, no. 1 (2007): 103–5. http://dx.doi.org/10.1163/004260307x164511.

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11

Strauch, Dieter. "Regesten der Reichsstadt Aachen (einschließlich des Aachener Reiches und der Reichsabtei Burtscheid), Band 3 1351-1365, bearb. v. Thomas R. Kraus." Zeitschrift der Savigny-Stiftung für Rechtsgeschichte: Germanistische Abteilung 118, no. 1 (2001): 560–61. http://dx.doi.org/10.7767/zrgga.2001.118.1.560.

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Köbler, Gerhard. "Regesten der Reichsstadt Aachen (einschließlich des Aachener Reiches und der Reichsabtei Burtscheid), Band 5 1381-1395, bearb. v., Thomas R. Kraus." Zeitschrift der Savigny-Stiftung für Rechtsgeschichte: Germanistische Abteilung 123, no. 1 (2006): 510–11. http://dx.doi.org/10.7767/zrgga.2006.123.1.510.

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Dormandy, Michael. "Book of Seven Seals: The Peculiarity of Revelation, its Manuscripts, Attestation, and Transmission, written by Thomas J. Kraus and Michael Sommer." Novum Testamentum 59, no. 3 (2017): 330–31. http://dx.doi.org/10.1163/15685365-12341563.

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14

Whitaker, G. H. "Thomas P. Halton, Stella O'Leary: Classical Scholarship: an Annotated Bibliography. Pp. xx + 396. White Plains, New York: Kraus International, 1986. $110 (paper, $45)." Classical Review 37, no. 2 (1987): 334–35. http://dx.doi.org/10.1017/s0009840x00111370.

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15

Parker, D. "Gospel Fragments: The 'Unknown Gospel' on Papyrus Egerton 2, by TOBIAS NICKLAS; Papyrus Oxyrhynchus 840, by MICHAEL J. KRUGER; Other Gospel Fragments, by THOMAS J. KRAUS." Journal of Theological Studies 61, no. 1 (2010): 286–88. http://dx.doi.org/10.1093/jts/flp120.

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16

Doll, Jürgen. "Rückzug in die „Bücher von gestern“." Austriaca 82, no. 1 (2016): 63–72. http://dx.doi.org/10.3406/austr.2016.5068.

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Returning to the “Books of Yesterday”. Jean Améry’s nostalgic look at the Austrian literature of the turn of the century and the First Republic. Jean Améry, who had been driven out from Austria as a Jew in 1938, and later deported to Auschwitz, had to witness how much Austrian politics, the judicial system, the population as a whole after the war struggled to repress or at least to minimize Austrian co-responsibility in the Nazi crimes. Even though he was in some way still attached to his lost homeland, he felt only disgust for his contemporary Austria. To this avid reader turning to the literature of the period before the disaster became the only solution – the literature from the turn of the century and the First Republic, which for him represented the apogee of Austrian literature. From reading authors such as Schnitzler, Karl Kraus, Musil or Joseph Roth he could regain his youth and a bit of his lost love for his own country. At the same time they offered him the opportunity to trace the peculiarity of Austrian literature. This he believes he finds in “morbus austriacus”, this predilection for melancholy, death, and decline that to a lesser or greater extent characterizes the works of all significant Austrian writers. Even though he considered contemporary literature in general in a rather negative light, he still makes an exception for Ingeborg Bachmann and Thomas Bernhard, who seduced him by their Austrian tone that seemed so familiar to him, by including them in the tradition of “morbus austriacus”, a disease in which the death instinct is dominant, the Eros however not quite extinguished.

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Gathercole, Simon. "Thomas J. Kraus, Michael J. Kruger and Tobias Nicklas (eds) Gospel Fragments, Oxford Early Christian Gospel Texts (Oxford: Oxford University Press, 2009), pp. xx + 304. $150.00/£75.00 (hbk)." Scottish Journal of Theology 65, no. 1 (2012): 105–7. http://dx.doi.org/10.1017/s0036930610000256.

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Gussone, Monika. "Regesten der Reichsstadt Aachen (einschließlich des Aachener Reiches und der Reichsabtei Burtscheid), Bd. 7: Nachträge 1251–1400, bearb. v. Thomas R. Kraus. (Publikationen der Gesellschaft für Rheinische Geschichtskunde XLVII)." Annalen des Historischen Vereins für den Niederrhein 216, no. 1 (2013): 264–66. http://dx.doi.org/10.7788/annalen-2013-0118.

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Gussone, Monika. "Regesten der Reichsstadt Aachen (einschließlich des Aachener Reiches und der Reichsabtei Burtscheid), Bd. 7: Nachträge 1251–1400, bearb. v. Thomas R. Kraus. (Publikationen der Gesellschaft für Rheinische Geschichtskunde XLVII)." Annalen des Historischen Vereins für den Niederrhein 216, no. 1 (2013): 264–66. http://dx.doi.org/10.7788/annalen-2014-0118.

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Gussone, Monika. "Regesten der Reichsstadt Aachen (einschließlich des Aachener Reiches und der Reichsabtei Burtscheid), Bd. 7: Nachträge 1251–1400, bearb. v. Thomas R. Kraus. (Publikationen der Gesellschaft für Rheinische Geschichtskunde XLVII)." Annalen des Historischen Vereins für den Niederrhein 216, no. 1 (2013): 264–66. http://dx.doi.org/10.7788/annalen-2014-216-0118.

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Gussone, Monika. "Thomas R. Kraus: Aachen von den Anfängen bis zur Gegenwart, Bd. 3.1: Stadtwerdung – Ereignisse 1138 bis 1500 (Veröffentlichungen des Stadtarchivs Aachen 15; Beihefte der Zeitschrift des Aachener Geschichtsvereins 9)." Annalen des Historischen Vereins für den Niederrhein 218, no. 1 (2015): 282–85. http://dx.doi.org/10.7788/annalen-2015-0112.

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22

Andrew, Alex M. "HETEROGENEOUS AGENT SYSTEMS, by V.S. Subrahmanian, Piero Bonatti, Jürgen Dix, Thomas Etier, Sarit Kraus, Fatma Ozcan and Robert Ross, MIT Press, Cambridge, Mass., 2000, xiv+580pp., ISBN 0-262-19436-8 (Hardback, £39.95)." Robotica 19, no. 4 (2001): 459–62. http://dx.doi.org/10.1017/s0263574701223492.

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23

Gout, Johann, Yazid J. Resheq, Jessica Lindenmayer, et al. "Abstract C053: Pancreatic cancer patient-derived organoids, preclinical tools for therapeutic profiling, patient response prediction, and tumor evolution." Cancer Research 84, no. 17_Supplement_2 (2024): C053. http://dx.doi.org/10.1158/1538-7445.pancreatic24-c053.

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Abstract Pancreatic cancer (PC) is characterized by an aggressive biology and an exceptionally high tumor heterogeneity that causes considerable variations in response to chemotherapies, targeted agents, and immunotherapies. Patient-derived organoids (PDOs) accurately reflect parental tumor biological and molecular features and may represent powerful preclinical avatars to predict drug response and support clinical decision-making. We generated a living organoid biobank of &gt;100 PC PDO lines from treatment-naïve and pretreated primary tumor and metastases with a reliable efficacy (60.8%), and previously developed a pharmacotyping-guided prediction model to prognosticate patient therapy response in an initial feasibility trial (Beutel AK et al, 2021). Real-life chemotherapy responses in 46 patients (for a total of 93 therapy lines) matched to pharmacotyping-informed predictions with overall 73.1% accuracy, 85.4% sensitivity (responsiveness), and 63.5% specificity (non-responsiveness). Overall, our model allowed a successful drug-response prediction in naïve patients with an accuracy of 73.0% and 70.0% for first and second-line regimens. Prediction power was nevertheless lower in pretreated and heavily pretreated patients with a precision of 68.2% and 50.0% for subsequent chemotherapy lines, respectively. Interestingly, PDO-based pharmacotyping also precisely predicted patient clinical outcome in the neoadjuvant and adjuvant settings, with respective accuracies of 83.3% and 71.4%. Retrospective analysis of patient clinical data in palliative setting finally showed that the administration of a regimen predicted to be efficient ultimately translated into a significantly longer progression-free survival. Implementing automation and drug screening miniaturization to our workflow also significantly enhanced our process capacity, reduced time before pharmacotyping, and improved compliance to internal quality controls. Tracking clonal evolution in longitudinal biopsies (a set of seven PDO pairs derived from the same patients at two distinct timepoints) revealed lower mutational burden and therapy-driven genetic alterations upon progression. Notably, this approach revealed a CHEK2-mutated patient responded over time to PARP inhibitor maintenance therapy, aligning with our predictions and underscoring the robustness of our method. Single nucleus-resolved RNA and ATAC-seq analysis of a unique longitudinally-collected case uncovered transcriptomic and epigenetic dynamics associated with an oncogenic FGFR2 fusion and with a subsequent resistance-mediating mutation upon targeted treatment with FGFR2 inhibitors. Particularly, FGFR2 constitutive activation correlated with aberrant epigenetic trace and transcription programs of downstream targets as PI3K-AKT and RAS family members and of RNA polymerase II transcription machinery. Here, we report a robust and clinically-relevant preclinical tool for drug-response prediction, one more step towards a PDO therapeutic profiling-guided personalized medicine in clinical routine. Citation Format: Johann Gout, Yazid J Resheq, Jessica Lindenmayer, Julian D Schwab, Elodie Roger, Johann M Kraus, Thomas Ettrich, Alica K Beutel, Lukas Perkhofer, Hans A Kestler, Thomas Seufferlein, Alexander Kleger. Pancreatic cancer patient-derived organoids, preclinical tools for therapeutic profiling, patient response prediction, and tumor evolution [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C053.

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24

Hocquet, Jean-Claude. "Regesten der Reichsstadt Aachen (einschließlich des Aachener Reiches und der Reichsabtei Burtscheid) , Bd 3 : 1351-1365 , bearb. von Thomas R. KRAUS (Publikationen der Gesellschaft für Rheinische Geschichtskunde, 47), Dröste, Düsseldorf, 1999, XLII, 474 S." Revue du Nord 341, no. 3 (2001): IV. http://dx.doi.org/10.3917/rdn.341.0617d.

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25

Gussone, Monika. "Thomas R. Kraus (Hrsg.): Aachen von den Anfängen bis zur Gegenwart, Bd. 1: Die natürlichen Grundlagen. Von der Vorgeschichte bis zu den Karolingern. (Veröffentlichungen des Stadtarchivs Aachen 13; Beihefte der Zeitschrift des Aachener Geschichtsvereins 7)." Annalen des Historischen Vereins für den Niederrhein 216, no. 1 (2013): 252–56. http://dx.doi.org/10.7788/annalen-2013-0113.

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Gussone, Monika. "Thomas R. Kraus (Hrsg.): Aachen von den Anfängen bis zur Gegenwart, Bd. 1: Die natürlichen Grundlagen. Von der Vorgeschichte bis zu den Karolingern. (Veröffentlichungen des Stadtarchivs Aachen 13; Beihefte der Zeitschrift des Aachener Geschichtsvereins 7)." Annalen des Historischen Vereins für den Niederrhein 216, no. 1 (2013): 252–56. http://dx.doi.org/10.7788/annalen-2014-0113.

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Gussone, Monika. "Thomas R. Kraus (Hrsg.): Aachen von den Anfängen bis zur Gegenwart, Bd. 1: Die natürlichen Grundlagen. Von der Vorgeschichte bis zu den Karolingern. (Veröffentlichungen des Stadtarchivs Aachen 13; Beihefte der Zeitschrift des Aachener Geschichtsvereins 7)." Annalen des Historischen Vereins für den Niederrhein 216, no. 1 (2013): 252–56. http://dx.doi.org/10.7788/annalen-2014-216-0113.

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Schild, Wolfgang. "Thomas Krause, Geschichte des Strafvollzugs." Zeitschrift der Savigny-Stiftung für Rechtsgeschichte: Germanistische Abteilung 118, no. 1 (2001): 784–85. http://dx.doi.org/10.7767/zrgga.2001.118.1.784.

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Seelbach, Ulrich. "STEFAN BAUMGARTNER: Reise zum Heiligen Grab 1498 mit Herzog Heinrich dem Frommen von Sachsen. Hrsg. von Thomas Kraus. Mit einer Biographie von Lotte Kurras. - Göppingen: Kümmerle 1986. (= Göppinger Arbeiten zur Germanistik. 445.) 72 S., 8 Bll. Abbildungen." Daphnis 17, no. 2 (1988): 394–97. http://dx.doi.org/10.1163/18796583-90000441.

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30

Herold, Heiko. "Jürgen Kraus und Thomas Müller, Die deutschen Kolonial- und Schutztruppen von 1889 bis 1918. Geschichte, Uniformierung und Ausrüstung, Wien: Militaria 2009, 579 S. (= Kataloge des Bayerischen Armeemuseums Ingolstadt, 7), EUR 99,00 [ISBN 978-3-902526-24-3]." Militaergeschichtliche Zeitschrift 77, no. 1 (2018): 228–30. http://dx.doi.org/10.1515/mgzs-2018-0035.

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31

Liermann, Christiane, Susanne Krauß, and Edgar Göll. "Allgemeines und Überblicksdarstellungen, Festschriften, neue Zeitschriften." Das Historisch-Politische Buch (HPB) 65, no. 3 (2017): 231–34. http://dx.doi.org/10.3790/hpb.65.3.231.

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David Gilmour: Auf der Suche nach Italien. Eine Geschichte der Menschen, Städte und Regionen von der Antike bis zur Gegenwart (Christiane Liermann) Ewald Frie, Mischa Meier (Hg.): Aufruhr – Katastrophe – Konkurrenz – Zerfall. Bedrohte Ordnungen als Thema der Kulturwissenschaften (Susanne Krauß) Alexander Amberger, Thomas Möbius (Hg.): Auf Utopias Spuren. Utopie und Utopieforschung (Edgar Göll)

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Rich, Thomas H., David W. Krause, Peter Trusler, et al. "Second specimen of Corriebaatar marywaltersae from the Lower Cretaceous of Australia confirms its multituberculate affinities." Acta Palaeontologica Polonica 67, no. 1 (2022): 115–34. https://doi.org/10.4202/app.00924.2021.

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Rich, Thomas H., Krause, David W., Trusler, Peter, White, Matt A., Kool, Lesley, Evans, Alistair R., Morton, Steven, Vickers-Rich, Patricia (2022): Second specimen of Corriebaatar marywaltersae from the Lower Cretaceous of Australia confirms its multituberculate affinities. Acta Palaeontologica Polonica 67 (1): 115-134, DOI: 10.4202/app.00924.2021, URL: http://dx.doi.org/10.4202/app.00924.2021

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Demmler, Kathrin, and Dagmar Hoffmann. "Medien und Narrative - Die Kraft des Erzählens in mediatisierten Welten." merz | medien + erziehung 64, no. 4 (2020): 6–7. http://dx.doi.org/10.21240/merz/2020.4.6.

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Medien sind von jeher Erzähl-, Erlebnis- und Inszenierungsräume, die sich – so die Ausgangsthese – durch Digitalisierungsprozesse verändern, da sich unter anderem Angebote ausdifferenzieren, erweitern, neujustieren und zunehmend durch Nutzer*innen (mit)gestaltet werden. Nutzende fungieren nicht nur als Geschichtenleser*innen, sondern auch als Geschichtenerzähler*innen (Tophinke 2017). Produktions-, Nutzungs- und Aneignungsweisen von medial vermittelten Narrationen haben sich einerseits strukturell durch neue Formate und Plattformen und nicht zuletzt Streamingdienste gewandelt. Andererseits haben sich inhaltlich-dramaturgisch sowie ästhetisch neue Erzählweisen/-strategien in Film und Serien, auf Blogs, in Sozialen Netzwerken und vor allem auf Bild- und Videoportalen herausgebildet. Sie sind zu wichtigen Erzählkontexten avanciert, wobei die kulturelle Praxis des Erzählens sich mitunter den Umgebungen anpasst und sich die Erzähler*innen teilweise ihrem Publikum unterwerfen, dieses ‚empowern‘ und mobilisieren, erinnern oder auch verstören können. Es finden sich spontane, offene Erzählungen aber auch geschlossene. Manche haben Snippetcharakter. Man denke etwa an Instagram-Storys, Memes und Tweets. Erzählmedium ist sowohl Schriftlichkeit als auch Bildlichkeit in Form von Fotos, Filmen und kurzen Videos, die nur marginal beschrieben und kommentiert oder mit Hashtags versehen werden (Tophinke 2017; Wagner 2019). Letztere ermöglichen Themensetzungen, anlass- und issuebezogene Kollektivierungen von Nutzer*innen im Sinne einer „Neogemeinschaft“ (Reckwitz 2017, S. 262) sowie auch Resonanzräume, die kritisch nicht selten affektiv aufgeladen sind, Hate- und Counterspeech hervorbringen. Das vorliegende Heft beschäftigt sich mit fiktionalen und dokumentarischen, interaktiven sowie multimedialen Erzählformen in Netzumgebungen. Der erste Beitrag von Christina Schachtner thematisiert narrative Selbstkonstruktionen in mediatisierten Lebenswelten. Ausgehend von der Metatheorie der Mediatisierung und dem phänomenologischen Lebensweltansatz gilt es, die Selbsterzählungen von Blogger*innen und Netzakteur*innen, die die Autorin interviewt hat, im Hinblick auf ihr Selbstbildungspotenzial einzuordnen. So verweisen nicht allein dominierende Narrationen, sondern auch narrative Puzzleteile, sogenannte „Narrationsnester“ (Kraus 2000), immer auf das eigene Selbst, das heißt auf Selbstentwürfe und das Bedürfnis nach einem kohärenten Identitätsgefühl. Wie es sich anfühlt, verschiedenen Kulturen anzugehören, an zwei weit voneinander entfernten Orten zu leben und zu arbeiten, weiß der Theologe und Linguist Alexander Görlach nur zu gut. Kathrin Demmler hat ihn zu den aktuellen politischen Themen und der Prägung durch populäre Narrative interviewt. Judith Ackermann, Leyla Dewitz und Alexandra Makulik interessieren sich für die Potenziale der App TikTok im Hinblick auf die individuelle und gesellschaftliche Bewältigung der Corona-Pandemie. Die Autorinnen werteten 100 Videos unter #corona inhaltsanalytisch aus und identifizier-ten zentrale Narrative. Als Ergebnis halten sie unter anderem fest, dass die Videos Krisenbewältigung, Angstreduktion und Stressregulation bei den Nutzer*innen ermöglichen. Ausgangspunkt der Überlegungen von Florian Schultz-Pernice ist das Plakat der Fridays-for-Future-Bewegung mit dem Satz: „Dinosaurier dachten auch, sie hätten Zeit.“ Diskutiert werden neben der Kernbotschaft auch die Mittel und Strategien der Narrativierung, die seiner Ansicht nach ein besonderes Potenzial haben, eine der anthropozänen Konfiguration angemessene Bildungsbewegung anzuregen. Historischen Narrativen in Film und Fernsehen widmet sich Andrea Kluxen. Sie setzt sich mit der Frage auseinander, wie und ob Filme oder Fernsehbeiträge zu historischen Themen uns helfen, Geschichte zu verstehen oder unser Geschichtsbewusstsein verfälschen. Abschließend setzt sich die Autorin mit dem Film selbst als historisches Dokument auseinander und betont seine Bedeutung für die Wissenschaft. Florian Krauß und Julian Kinghorst beschäftigen sich in ihrem Beitrag mit digitalen Jugendnarrativen in der deutschen Fernsehfiktion. Anhand der Serien DRUCK, Wir sind jetzt und How to Sell Drugs Online (Fast) arbeiten die Autoren heraus, wie von Jugend erzählt wird. Demzufolge greifen alle drei Produktionen nicht nur narrationstypische Muster des Teen TV auf, sondern repräsentieren auch digitale Medienpraktiken und spiegeln so inhaltlich ihre Online-Distribution wider. Einen Blick aus der Praxis auf Narrative werfen Jonas Lutz und Thomas Kupser in ihrem Beitrag am Beispiel von PARLAMENSCH. In diesem Projekt waren junge Filmemacher*innen gefordert, sich mit Demokratie aus der Perspektive unterschiedlicher Protagonist*innen auseinanderzusetzen. Die Beiträge zeigen die große Bedeutung, die Narrative in der Aufbereitung und Rezeption von Themen mit Medien spielen. Kaum ein Medienbeitrag, in dem nicht Narrative zitiert, neue Geschichten erzählt und Bezüge zu bekannten Narrativen hergestellt werden. Insbesondere bei den von jungen Menschen selbst erstellten Medienbeiträgen ist die Auseinandersetzung mit bekannten Rollen und Bildern häufig grundlegend. Somit kann die Befassung mit medialen Narrativen sowohl zu einer spannenden Reflexion der eigenen Vorlieben und Bilder beitragen als auchein Ansatzpunkt für die pädagogische Arbeit sein.

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Krause, Meredith A., Thomas Koster, Bryan N. MacNeill, et al. "Diversity and abundance of dragonflies and damselflies in Tampa Bay, Florida." Florida Entomologist 103, no. 2 (2020): 392–96. https://doi.org/10.1653/024.103.0312.

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Krause, Meredith A., Koster, Thomas, MacNeill, Bryan N., Zydek, Daniel J., Ogburn, Nicholas T., Sharpin, Jonathan, Shell, Robert, Lajeunesse, Marc J. (2020): Diversity and abundance of dragonflies and damselflies in Tampa Bay, Florida. Florida Entomologist 103 (2): 392-396, DOI: 10.1653/024.103.0312, URL: https://bioone.org/journals/florida-entomologist/volume-103/issue-3/024.103.0312/Diversity-and-Abundance-of-Dragonflies-and-Damselflies-in-Tampa-Bay/10.1653/024.103.0312.full

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Piovanelli, Pierluigi. "Comptes rendus / Reviews of books: Das Petrusevangelium und die Petrusapokalypse. Die griechischen Fragmente mit deutscher und englischer Ubersetzung Thomas J. Kraus et Tobias Nicklas Collection « Die Griechischen Christlichen Schrifsteller der ersten Jahrunderte » Neue Folge, Band 11 (« Neutestamentliche Apocryphen » 1) Berlin et New York, Walter de Gruyter, 2004. x + 155 p." Studies in Religion/Sciences Religieuses 34, no. 2 (2005): 281–83. http://dx.doi.org/10.1177/000842980503400213.

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Dexheimer, Thomas S., Nathan P. Coussens, Thomas E. Silvers, et al. "Abstract 1675: Evaluation of combination strategies with RAS-targeted inhibitors in multi-cell type spheroids." Cancer Research 85, no. 8_Supplement_1 (2025): 1675. https://doi.org/10.1158/1538-7445.am2025-1675.

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Abstract RAS genes are among the most frequently mutated oncogenes in cancer. Though previously considered undruggable, agents have recently been developed that specifically target RAS. The agents can be categorized as (1) those that selectively target specific RAS oncoproteins and (2) pan-RAS inhibitors that target a wide range of RAS alterations, including oncogenic variants and amplifications. This study evaluated the activity of four novel RAS-targeted inhibitors in combination with other targeted agents in thirty solid tumor cell lines of diverse cancer types. These included twenty-six patient-derived cancer cell lines from the NCI Patient-Derived Models Repository (https://pdmr.cancer.gov/) and four established cell lines. The cells were grown as multi-cell type (mct) tumor spheroids from 60% malignant cells, 25% endothelial cells, and 15% mesenchymal stem cells. All agents were tested at concentrations up to the clinical Cmax value, if known or 10 µM. As single agents, the KRAS-G12C inhibitors RMC-6291 and divarasib, along with the KRAS-G12D inhibitor MRTX-1133, demonstrated selective activity against the mct tumor spheroids harboring the targeted variants. In contrast, the pan-RAS(ON) inhibitor RMC-6236 demonstrated activity against the mct tumor spheroids harboring a range of KRAS variants or wild-type KRAS. When used in combination, each of the four RAS-targeted inhibitors exhibited strong synergistic effects with SHP2 inhibitors as determined by the Bliss independence model and reductions in cell viability and spheroid volume. In tumor models harboring different KRAS variants, the pan-RAS(ON) inhibitor showed increased cytotoxicity with the MEK inhibitor cobimetinib, as well as PI3K-AKT-mTOR pathway inhibitors, such as inavolisib (PI3Kα), ipatasertib (AKT), and sapanisertib (mTORC1/2). When the same agents were combined with variant-specific KRAS inhibitors similar effects were observed in mct tumor spheroids carrying the corresponding RAS variant. These preclinical findings might provide guidance for the selection of combination regimens with KRAS inhibitors to improve clinical efficacy. Funded by NCI Contract No. 75N91019D00024. Citation Format: Thomas S. Dexheimer, Nathan P. Coussens, Thomas E. Silvers, Eric M. Jones, Naoko Takebe, James H. Doroshow, Beverly A. Teicher. Evaluation of combination strategies with RAS-targeted inhibitors in multi-cell type spheroids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1675.

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Takebe, Naoko, Thomas Dexheimer, Thomas Silvers, et al. "Abstract 1054: RAS-pathway inhibitors (Sotorasib, MRTX-1257, TNO-155, BI-3406) in a Complex Spheroid Combination Screen with PDMR Cell Lines." Cancer Research 82, no. 12_Supplement (2022): 1054. http://dx.doi.org/10.1158/1538-7445.am2022-1054.

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Abstract The KRAS G12C selective inhibitors, sotorasib and MRTX-1257, as well as the SHP-2 inhibitor TNO-155 and the SOS-1 inhibitor were assayed alone and in combination with approved and investigational anticancer agents in complex spheroids including tumor cells, endothelial cells (HUVEC) and mesenchymal stem cells (MSCs). The cell lines were from the PDMR collection (https://pdmr.cancer.gov/models/database.htm). The Ras mutation status of each line was known and included KRAS G12C (5 lines), KRAS G12D (7 lines) and 8 lines which were RAS WT or harbored other RAS mutations. The high concentration range of each agent was near the clinical Cmax for the drug or was 10 μM and decreased in half-logs covering a 3-log range. The complex spheroids were established for 3 days before drug(s) were added. Seven days after drug exposure the experiment was terminated with CellTiter-Glo 3D. Cell viability was determined relative to a vehicle treated control and IC50 values were calculated from concentration response curves. The concentration response for sotorasib and MRTX-1257 (except for concentrations 3 μM or higher) inhibitors were shallow to flat. The 4 KRAS G12C mutant line were most sensitive to sotorasib and MRTX-1257 with the KRAS G12C mutant pancreatic cancer line being the next most sensitive. A similar pattern was observed with the SHP-2 inhibitor TNO-155; however, there was no selectivity for the KRAS G12C mutant lines in response to the SOS-1 inhibitor BI-3406. There was heterogeneity in the occurrence of additivity/synergy amongst the KRAS G12C mutant lines in the combination studies likely indicating that factors in addition to KRAS mutations influenced response. The most successful combination was TNO-155 plus ipatasertib which resulted in more than 1-log of cell kill in 9 of 20 lines including the 5 KRAS G12C mutant lines. Venetoclax in combination with the RAS pathway inhibitors was active in 4 of the 5 KRAS G12C lines as was the combination of sapanisertib and TNO-155. TNO-155 in combination with sotorasib, MRTX-1257 or BI-3406 was highly active in the LG0567-F671 NSCLC harboring KRAS G12C. The response of the RAS mutant lines to the combinations was compared with the response of RAS WT lines to the same combinations. Often at the higher concentrations of the drugs/investigational agents, lines without RAS mutations are responsive. Next steps include PDX studies with the same tumor models. This project was funded in part with federal funds from the NCI, NIH, under contract no. HHSN261200800001E. Citation Format: Naoko Takebe, Thomas Dexheimer, Thomas Silvers, Rene Delosh, Julie Laudeman, Siddhartha Paul, Russell Reinhardt, Chad Ogle, Joel Morris, Nathan Coussens, James H. Doroshow, Beverly A. Teicher. RAS-pathway inhibitors (Sotorasib, MRTX-1257, TNO-155, BI-3406) in a Complex Spheroid Combination Screen with PDMR Cell Lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1054.

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Schmidt, Klaus J. "Andrej Krause Zur Analogie bei Cajetan und Thomas von Aquin. Eine Analyse." Bochumer Philosophisches Jahrbuch für Antike und Mittelalter 5 (December 31, 2000): 272–75. http://dx.doi.org/10.1075/bpjam.5.27sch.

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Foley, Kevin P., Chenghao Ying, Yaya Wang, et al. "Abstract 1649: Chemically induced chaperone-mediated protein degradation (CHAMP) of KRAS(G12C)." Cancer Research 83, no. 7_Supplement (2023): 1649. http://dx.doi.org/10.1158/1538-7445.am2023-1649.

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Abstract Covalent KRAS(G12C) inhibitors have recently shown promising efficacy in the clinic. However, the rapid development of drug resistance compromises their long-term benefits, indicating the need for additional approaches to treat KRAS-mutated cancers. Targeted protein degradation represents one such potential approach. We have therefore explored applying Chaperone-mediated Protein Degradation (CHAMP) technology to degrade KRAS(G12C) protein. CHAMPs are heterobifunctional small molecules that mediate protein degradation by inducing proximity between a target protein and the HSP90 chaperone complex, resulting in target ubiquitination and degradation by the proteasome. Due HSP90 being highly activated in cancer cells, CHAMPs also preferentially accumulate in tumors relative to normal tissues, resulting in an improved therapeutic index relative to typical inhibitors. In order to chemically induce KRAS(G12C) degradation, CHAMP compounds were synthesized by covalently coupling KRAS(G12C)- and HSP90-binding moieties through a short linker. CHAMP treatment of KRAS(G12C)-mutated cell lines resulted in formation of a KRAS(G12C)-CHAMP-HSP90 ternary complex and subsequent proteasome-dependent KRAS(G12C) degradation and inhibition of cell proliferation. In contrast, combination treatment with KRAS(G12C) and HSP90 inhibitors did not result in substantial KRAS(G12C) degradation. Importantly, CHAMPs retained potency in cell line models of resistance to covalent KRAS(G12C) inhibitors. Further, in mouse xenograft models, CHAMPs displayed prolonged pharmacokinetics in tumors relative to plasma and normal tissues and strongly inhibited tumor growth at tolerated doses. Based on these findings, KRAS(G12C)-degrading CHAMPs represents a promising approach to the treatment of KRAS(G12C)-mutated cancers. Citation Format: Kevin P. Foley, Chenghao Ying, Yaya Wang, Yan Dai, Zhiyong Wang, Jinhua Li, Zimo Yang, Yuetong Sun, Hao Xin Zhou, Thomas L. Prince, Guoqiang Wang, Weiwen Ying. Chemically induced chaperone-mediated protein degradation (CHAMP) of KRAS(G12C) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1649.

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Tuckett, Christopher. "Das Evangelium nach Petrus. Text, Kontexte, Intertexte. Edited by Thomas J. Kraus and Tobias Nicklas. (Texte und Untersuchungen zur Geschichte der altchristlichen Literatur. Archiv für die Ausgabe der Griechischen Christlichen Schiftsteller der ersten Jahrhunderte (TU), 158.) Pp. viii+384. Berlin–New York: Walter de Gruyter, 2007. €98. 978 3 11 019313 8; 0082 3589." Journal of Ecclesiastical History 59, no. 4 (2008): 721–23. http://dx.doi.org/10.1017/s0022046908004661.

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Endrino, Ines Pulido, Laura gunder, Qiyue Luan, et al. "Abstract 1932: Overcoming acquired resistance to KRAS(G12D) inhibition using a KRAS-HSP90 hetero-bifunctional small molecule therapeutic agent." Cancer Research 84, no. 6_Supplement (2024): 1932. http://dx.doi.org/10.1158/1538-7445.am2024-1932.

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Abstract KRAS mutations are highly prevalent across many different cancer types. Recent advancements in KRAS-targeted drugs, such as the FDA-approved KRAS(G12C) inhibitors sotorasib and adagrasib for NSCLC patients, have shown great promise in the clinic. Nonetheless, these new agents fail to address other mutations, such as KRAS(G12D), which overall is the most common KRAS mutation in cancers, being found in 37% of pancreatic ductal adenocarcinomas, 12.5% of colorectal cancers and 4.9% of lung adenocarcinomas. Recently, MRTX1133 has been described as a selective, non-covalent inhibitor of KRAS(G12D) that shows promising preclinical efficacy and is undergoing clinical testing. However, based on prior clinical experience with sotorasib and adagrasib, acquired resistance to MRTX1133 may reasonably be anticipated. In fact, we find that KRAS(G12D)-mutated cell lines and a patient-derived organoid model exhibit varying degrees of inherent resistance to MRTX1133. To examine the consequences of blocking KRAS signaling, we employed a KRAS(G12D)-specific PROTAC, which simulated the effects of KRAS deletion. This demonstrated that receptor tyrosine kinase (RTK) activation could compensate for loss of KRAS signaling and was a key de novo resistance mechanism. This suggests that combination therapies may need to be individually tailored to treat patients resistant to KRAS(G12D)-targeted therapies. Additionally, we developed MRTX1133 resistant cells by culturing sensitive AsPC-1 pancreatic cancer cells in gradually increasing concentrations of the inhibitor. The resulting resistant cells displayed a complex RTK activation profile compared to parental cells. To counteract this, we employed KRAS(G12D)-CHAMP RNK08179, a hetero-bifunctional small molecule agent that simultaneously targets both KRAS(G12D) and HSP90, an RTK-regulating chaperone protein. RNK08179 effectively suppressed both KRAS signaling and RTK activation in MRTX1133-resistant cancer models, overcoming the compensatory resistance mechanisms observed with MRTX1133 alone. These findings highlight the potential of KRAS-CHAMPs as a novel, effective treatment strategy for KRAS-driven cancers, particularly those resistant to KRAS(G12D) inhibitors. Citation Format: Ines Pulido Endrino, Laura gunder, Qiyue Luan, Chenghao Ying, Zimo Yang, Jinhua Li, Yaya Wang, Yuetong Sun, Chuhe Liu, Yan Dai, Haoxin Zhou, Malek Massad, Ian Papautsky, Thomas L. Prince, Guoqiang Wang, Kevin P. Foley, Weiwen Ying. Overcoming acquired resistance to KRAS(G12D) inhibition using a KRAS-HSP90 hetero-bifunctional small molecule therapeutic agent [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1932.

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Brückner, Burkhart. "Animal Magnetism, Psychiatry and Subjective Experience in Nineteenth-Century Germany: Friedrich Krauß and hisNothschrei." Medical History 60, no. 1 (2015): 19–36. http://dx.doi.org/10.1017/mdh.2015.66.

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Friedrich Krauß (1791–1868) is the author ofNothschrei eines Magnetisch-Vergifteten[Cry of Distress by a Victim of Magnetic Poisoning] (1852), which has been considered one of the most comprehensive self-narratives of madness published in the German language. In this 1018-page work Krauß documents his acute fears of ‘mesmerist’ influence and persecution, his detainment in an Antwerp asylum and his encounter with various illustrious physicians across Europe. Though in many ways comparable to other prominent nineteenth-century first-person accounts (eg. John Thomas Perceval’s 1838Narrative of the Treatment Experienced by a Gentlemanor Daniel Paul Schreber’s 1903Memoirs of my Nervous Illness), Krauß’s story has received comparatively little scholarly attention. This is especially the case in the English-speaking world. In this article I reconstruct Krauß’s biography by emphasising his relationship with physicians and his under-explored stay at the asylum. I then investigate the ways in which Krauß appropriated nascent theories about ‘animal magnetism’ to cope with his disturbing experiences. Finally, I address Krauß’s recently discovered calligraphic oeuvre, which bears traces of his typical fears all the while showcasing his artistic skills. By moving away from the predominantly clinical perspective that has characterised earlier studies, this article reveals how Friedrich Krauß sought to make sense of his experience by selectively appropriating both orthodox and non-orthodox forms of medical knowledge. In so doing, it highlights the mutual interaction of discourses ‘from above’ and ‘from below’ as well as the influence of broader cultural forces on conceptions of self and illness during that seminal period.

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Chikkanna, Dinesh, Madhu Aeluri, Leena Khare, et al. "Abstract 7017: Discovery and development of a highly co-operative and potent pan-KRAS degrader." Cancer Research 85, no. 8_Supplement_1 (2025): 7017. https://doi.org/10.1158/1538-7445.am2025-7017.

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Abstract KRAS is one of the most frequently mutated oncogenes in various cancers. KRAS G12D mutation is prevalent in 39% of pancreatic ductal adenocarcinoma (PDAC), 27% of colorectal cancer, 11% of non-small cell lung adenocarcinoma as well as in a subset of other solid tumors. KRAS G12V mutation is found in 31% of PDAC, 20% of colorectal cancer and 19% of non-small cell lung adenocarcinoma. KRASG12C mutations are found in 41% of non-small cell lung adenocarcinoma and 3-5% of colorectal cancers. Despite recent advances in small molecule KRAS inhibitors, a majority of KRAS alterations are not yet addressed. Further, in cases where inhibitors are available, resistance rapidly emerges. Eliminating all mutant KRAS using a targeted protein degradation approach may lead to superior efficacy relative to inhibiting the protein. We have identified a series of degraders through structure-based drug design and our Directed Neo-substrate Degrader (DNsD) approach, with very high co-operativity, potent pan-KRAS degradation activity and a desirable pharmacokinetic profile. The high co-operativity of pan-KRAS degraders was confirmed though Surface Plasmon Resonance (SPR) analysis. These degraders demonstrated significant degradation of KRAS in multiple KRAS mutant cell lines and showed mechanistic activity via the modulation of pERK levels leading to significant anti-proliferative activity. The KRAS degraders were found to be selective against HRAS and NRAS which was also confirmed using global proteomic analysis. Further, the development candidate molecule demonstrated significant and dose dependent tumor growth inhibition in multiple KRAS mutant xenograft models which was accompanied by sustained KRAS degradation. Notably, the development candidate compound has demonstrated excellent PK and tolerability in rodent and non-rodent tox species. IND enabling studies are ongoing to support clinical development. Citation Format: Dinesh Chikkanna, Madhu Aeluri, Leena Khare, Ravindra MV, Debajyoti Basak, Uday Bhat, Suraj T. Gore, Narmatha V, Shailesh V. Jadhav, K Y. Vasantha, Sivapriya Marappan, Megha Goyal, R N. Raghavendra, Amit A. Dhudashiya, Kiran Aithal, T Jagadeesh Kumar, D S. Suhas, K B. Charamanna, P Dharani, R Naveenkumar, Rahul B. Chavan , Randeep Bokalial, D S. Samiulla, Subhendu Mukherjee, Thomas Antony, Kavitha Nellore, Rajesh Eswarappa, Girish Chandrappa Daginakatte, Sanjeev Giri, Susanta Samajdar, Murali Ramachandra. Discovery and development of a highly co-operative and potent pan-KRAS degrader [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7017.

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Black, Cheryl, James Parsons, Anthony Thomas, et al. "Abstract 1127: Preclinical development of safe and effective T cell receptors specific for mutant KRAS G12D peptide." Cancer Research 83, no. 7_Supplement (2023): 1127. http://dx.doi.org/10.1158/1538-7445.am2023-1127.

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Abstract Adoptive T cell therapy (ACT) has demonstrated activity in solid tumors but requires further optimization to become a reproducibly effective treatment. T cell receptor (TCR)-engineered T cells recognize peptides derived from intracellular and surface proteins presented in the context of MHC class I. Targeting mutated oncogenic drivers addresses some of the major obstacles of this modality, in that the antigenic epitope is: 1) tumor-specific, 2) essential for tumor survival, and 3) derived from a stably expressed protein. KRAS is the most frequently mutated gene in human cancers with alterations in codon 12 associated with poor clinical outcomes in a high proportion of colon, lung and pancreatic cancers, as well as many others. To isolate TCRs specific for the peptide derived from the KRAS G12D mutation presented in the context of HLA-A*11:01, one of the most common HLA alleles worldwide, we employed our high-throughput in vitro TCR discovery platform. CD8+ T cells were isolated from healthy donors and co-cultured with autologous antigen-presenting cells exogenously-loaded with mutant KRAS peptides encompassing the G12D mutation. The highest avidity T cells were subsequently identified and enriched by fluorescence-based cell sorting and the corresponding TCR genes isolated by single-cell sequencing and inserted into a lentiviral expression vector. TCR candidates were transduced into primary T cells and prioritized based on functional avidity and specificity (response to titrated peptide-loaded presenting cells and tumor cells endogenously expressing the KRAS G12D antigen) and cytotoxicity (in vitro tumor cell killing assays). X-Scan studies, in which each residue of the reference KRAS G12D peptide was systematically substituted by all other amino acids, revealed a highly restrictive TCR recognition motif, suggesting limited risk of promiscuous off-target activation. We engineered both CD4+ and CD8+ T cells to lentivirally-express candidate TCRs in addition to the genes encoding the CD8αβ co-receptor to enhance TCR-HLA class I avidity in CD4+ T cells, with the aim of creating a coordinated CD4 and CD8 T cell response to the same tumor target to promote increased T cell activity and persistence while minimizing T cell exhaustion. Transduced CD4+ T cells were functional and could be demonstrated to provide help to CD8+ T cells, supporting tumor elimination in several experimental models. In summary, we report a TCR gene therapy approach targeting mutant KRAS G12D-containing peptides with a coordinated CD4 and CD8 T cell response that has a promising efficacy and safety profile. Our work to date supports the planned clinical development of this novel TCR-engineered T cell therapy for treating KRAS-mutant solid tumors. Citation Format: Cheryl Black, James Parsons, Anthony Thomas, Allison P. Drain, Santosh Narayan, Joshua Francis, Xingyue He, Ankit Gupta, Jessica Webb, Thomas M. Schmitt, Philip D. Greenberg, Gary Shapiro, Loïc Vincent. Preclinical development of safe and effective T cell receptors specific for mutant KRAS G12D peptide [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1127.

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Coussens, Nathan P., Thomas S. Dexheimer, Phillip R. Sanchez, et al. "Abstract 1674: Combinatorial screen with standard of care and selected anticancer agents identifies multiple combinations with activity against a panel of patient-derived colorectal organoids." Cancer Research 85, no. 8_Supplement_1 (2025): 1674. https://doi.org/10.1158/1538-7445.am2025-1674.

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Abstract Thirty-two patient-derived colorectal organoid models were selected from the NCI’s Patient-Derived Models Repository (https://pdmr.cancer.gov) to serve in a high-throughput screening panel. The models were derived from primary or metastatic tumors of patients with varied ancestries, ranging in age from 32–90 yrs, that were either previously treated or treatment naïve. Variations were determined in microsatellite stability, consensus molecular subtype, and genetics, including clinically relevant oncogenic variants of RAS, BRAF and PIK3CA. A screen was conducted with twenty-two combinations of agents, including SOC and investigational oncology drugs. Organoids were exposed to single agents or combinations at four concentrations covering 2 logs up to the clinical Cmax, if known. Following compound addition, organoid growth was measured by live bright field imaging every 24 h and cell viability was determined by CellTiter-Glo 3D at 48 h and 168 h. Modest responses were observed in most models from the combination of leucovorin with 5-FU; however, &gt;1 log of cytotoxicity was observed in only several models. The panel was more responsive to FOLFOX, which was consistent with the sensitivity of models to oxaliplatin. Responses to TAS-102 varied and &gt;1 log of cytotoxicity was observed in several models. The MEK inhibitor cobimetinib was active in models with wild type KRAS and generally more active in models with oncogenic KRAS. Combination of the BCL-2/BCL-xL inhibitor pelcitoclax plus cobimetinib achieved &gt;1 log of cytotoxicity in most organoid models. Combinations of cobimetinib with the EGFR inhibitors erlotinib, afatinib or cetuximab demonstrated synergy in many organoids according to the Bliss independence model and frequently achieved ≥1 log of cytotoxicity. As a single agent, the KRAS G12D inhibitor MRTX1133 was active against organoid models harboring KRAS G12D. The combination of cobimetinib and MRTX1133 had synergistic activity by Bliss independence in multiple organoid models and frequently achieved &gt;1 log of cytotoxicity. Additionally, combinations of MRTX1133 with an EGFR inhibitor had additive and greater-than-additive cytotoxicity in a range of organoids. The pan-RAS(ON) inhibitor RMC-6236 had substantial single-agent activity against organoid models with wild type KRAS and most models with an oncogenic KRAS variant. In combination with cobimetinib, RMC-6236 demonstrated additive and synergistic cytotoxicity, frequently ≥1 log, in organoid models with BRAF V600E and harboring wild type KRAS or an oncogenic variant. When combined with the pan-PI3K inhibitor copanlisib, RMC-6236 demonstrated substantial synergy, achieving ≥2 logs of cytotoxicity in several organoid models with wild type KRAS. Complimentary PDX studies are in progress. Funded by NCI Contract No. 75N91019D00024 & 75N91020F00032. Citation Format: Nathan P. Coussens, Thomas S. Dexheimer, Phillip R. Sanchez, Thomas Silvers, Eric M. Jones, Bryce M. Butler, John R. Britt, Carmen Allegra, James H. Doroshow, Beverly A. Teicher. Combinatorial screen with standard of care and selected anticancer agents identifies multiple combinations with activity against a panel of patient-derived colorectal organoids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1674.

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Pulido, Ines, Qiyue Luan, Chenghao Yin, et al. "Abstract B093: Treating KRAS(G12D) inhibitor resistance using a KRAS- and HSP90 chaperone-targeted hetero-bispecific small molecule agent." Molecular Cancer Therapeutics 22, no. 12_Supplement (2023): B093. http://dx.doi.org/10.1158/1535-7163.targ-23-b093.

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Abstract KRAS is the most frequently mutated oncoprotein in human cancers. Although long considered “undruggable”, recent breakthroughs in medicinal chemistry have led to FDA-approval of the KRAS(G12C) mutation-specific inhibitors sotorasib and adagrasib for the treatment of KRAS(G12C)-positive non-small cell lung cancer. However, illustrating the need to develop additional novel agents targeting mutated KRAS, the 5-year relative survival rate for pancreatic cancer, which is commonly associated with a variety of different KRAS mutations, is only 12% (all SEER stages) due to poor early detection and a lack of effective treatments. In particular, KRAS(G12D) is the most common KRAS mutation, being found in 37% of pancreatic ductal adenocarcinomas (PDACs), as well as in 12.5% of colorectal cancer and 4.9% of lung adenocarcinoma (LUAD) patients. MRTX1133 is a highly-selective, non-covalent KRAS(G12D) inhibitor that has recently entered a phase 1 clinical trial. However, here we show that exposure of KRAS(G12D)-mutated PDAC (PANC-1 and AsPC-1) and LUAD (SK-LU-1) cell lines and a patient-derived organoid (PDO) PDAC model (RPAN001) to MRTX1133 resulted in varying degrees of in vitro efficacy. Decreased downstream KRAS signaling in the form of reduced phospho-ERK1/2 levels was observed to rapidly recover within 24 hours of treatment with 500 nM MRTX1133. Moreover, this rebound coincided with increased expression of KRAS, NRAS andHRAS mRNAs. Concurrently, activation of the receptor tyrosine kinases (RTKs) EGFR and MET was observed in PANC-1 and SK-LU-1 cells that displayed innate resistance to MRTX1133, while the sensitive AsPC-1 cells showed no such RTK activation. These results suggest that targeting of both KRAS(G12D) and RTKs may be needed to treat KRAS(G12D) inhibitor-resistant cancers. To address this, we employed a novel hetero-bispecific CHAMP molecule, RNK08179, that simultaneously targets both KRAS(G12D) and HSP90, an RTK-regulating chaperone protein. RNK08179 treatment demonstrated a striking reduction in phospho-ERK1/2 levels, RTK activation and cell viability in MRTX1133-resistant PANC-1 and SK-LU-1 cells. Furthermore, similar efficacy was observed in the MRTX1133-resistant RPAN001 PDO model. In summary, RNK08179 displayed promising efficacy in cancer models harboring KRAS(G12D) by suppressing both mutated KRAS and HSP90-supported RTK signaling. Citation Format: Ines Pulido, Qiyue Luan, Chenghao Yin, Zimo Yang, Jinhua Lin, Yaya Wang, Yuetong Sun, Chuche Liu, Haoxin Zhou, Marek Massad, Ian Papautsky, Thomas L. Prince, Guoqiang Wang, Kevin P. Foley, Weiwen Ying, Takeshi Shimamura. Treating KRAS(G12D) inhibitor resistance using a KRAS- and HSP90 chaperone-targeted hetero-bispecific small molecule agent [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B093.

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Rigby, Megan, John Columbus, Vanessa Wall, et al. "Abstract B027: Bioluminescence resonance energy transfer (BRET) as a tool for assessing mutant KRAS-effector affinity and drug efficacy." Molecular Cancer Research 21, no. 5_Supplement (2023): B027. http://dx.doi.org/10.1158/1557-3125.ras23-b027.

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Abstract KRAS mutations occur in roughly 15% of cancer patients, with KRAS G12D, KRAS G12V, and KRAS G12C substitutions constituting the majority of these cases. Cancer types also display puzzling preferences for certain RAS mutations; for instance, 49% of pancreatic ductal carcinomas (PDAC) are driven by KRAS G12D substitutions compared to 35% of colon adenocarcinomas (COAD) and 17% of lung adenocarcinomas (LUAD)1. In contrast, KRAS G12C mutations drive only 3% of PDAC and 10% of COAD, but 41% of LUAD cases1. Some of this discrepancy can be explained by mutagen exposure, as there is evidence that tobacco smoke carcinogens drive the predominance of KRAS G12C mutations in lung cancer. However, it is possible that inherent functional differences between the mutant proteins also contribute to such preferences across cancer types. These oncogenic substitutions do endow subtle and unique differences in biochemical properties, but it is unknown whether this translates to differences in cellular signaling potential. KRAS activates the MAPK and PI3K signaling pathways by binding directly to RAF1 or the p110 catalytic subunit of PI3K. These interactions are important signaling nodes that result in cellular proliferation, survival, movement, differentiation, and immune evasion, and therefore drive cancer when constitutively activated by mutant KRAS. Biochemical assessments of relative effector affinity between KRAS mutants lack crucial elements present in a cellular environment, such as GDP/GTP ratios, membrane interactions, subcellular localization, and engagement with other proteins. Here, we optimize a cell-based Bioluminescent Resonance Energy Transfer (BRET) system in HEK293T cells using NanoLuc- and mVenus-tagged proteins to quantify relative effector affinities between KRAS mutants. We assess the affinities of KRAS4b G12C, KRAS4b G12D, and KRAS4b WT for effectors p110α and RAF1(52-188), along with RAS binding deficient control mutants p110α T208D/K227A and RAF1(52-188)R89L, and show statistical differences in effector engagement between the wildtype and mutant proteins. We also demonstrate the efficacy of this optimized system as a drug screening tool by assessing compounds in clinical development for their ability to disrupt mutant KRAS-effector interactions within a cellular environment. 1Prior IA, Hood FE, Hartley JL. The frequency of Ras mutations in cancer. Cancer Research 2020. Citation Format: Megan Rigby, John Columbus, Vanessa Wall, Dominic Esposito, Thomas Turbyville, Dhirendra Simanshu, Dwight Nissley, Frank McCormick, Anna Maciag. Bioluminescence resonance energy transfer (BRET) as a tool for assessing mutant KRAS-effector affinity and drug efficacy [abstract]. In: Proceedings of the AACR Special Conference: Targeting RAS; 2023 Mar 5-8; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Res 2023;21(5_Suppl):Abstract nr B027.

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Godfrey, W. G. "Proceedings and Debates of the British Parliaments Respecting North America 1754-1783, Volume IV, January to May 1774, edited by R.C. Simmons and P.D.G. ThomasProceedings and Debates of the British Parliaments Respecting North America 1754-1783, Volume IV, January to May 1774, edited by R.C. Simmons and P.D.G. Thomas. White Plains, N.Y., Kraus International Publications, 1985. xii, 515 pp. $112.00 U.S." Canadian Journal of History 23, no. 2 (1988): 267–68. http://dx.doi.org/10.3138/cjh.23.2.267.

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Law, Brian, Daniel Lu, Priyanka Somanath, James T. Palmer, Taisei Kinoshita, and Thomas Butler. "Abstract 2665: Irreversible menin inhibitor, BMF-219, inhibits the growth of KRAS-mutated solid tumors." Cancer Research 82, no. 12_Supplement (2022): 2665. http://dx.doi.org/10.1158/1538-7445.am2022-2665.

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Abstract Introduction: KRAS (Kirsten rat sarcoma virus) is the most frequently mutated isoform amongst RAS oncogenes in human solid tumors being present in a high percentage of colorectal cancers (CRC), non-small cell lung cancers (NSCLC), and pancreatic cancers. With only one approved KRAS G12C inhibitor for NSCLC, KRAS-driven tumors continue to represent a significant unmet medical need where novel effective therapies are highly desired. Menin is a required co-factor of oncogenic transcriptional proteins with functional interactions that are critical for various malignancies including acute leukemia. We previously reported that BMF-219, a novel irreversible menin inhibitor, exhibits strong potency on acute leukemia (MOLM-13) and KRAS-mutant (MiaPaCa-2) cells. Results from MiaPaCa-2 cells prompted our exploration of the effects of BMF-219 in an expanded panel of KRAS-mutant solid tumors through in vitro and ex vivo preclinical models. Methods: BMF-219, clinical reversible menin inhibitors, or clinically approved KRAS G12C inhibitor, sotorasib, were cultured with CRC, NSCLC, pancreatic cancer cell lines for 4-days. Human ex vivo preclinical models harboring KRAS mutations were cultured with BMF-219 and reversible menin for 6-days. Cell viability was measured using CellTiter Glo and IC50 values were calculated. MiaPaCa-2 cells incubated with BMF-219 were analyzed by RNA-seq on the Illumina NextSeq 550 platform. Results: MiaPaCa-2, a KRAS G12C-mutant cell line, showed marked reduction of KRAS expression levels following 24 hours of BMF-219 treatment at 0.5 µM. An expanded panel of 14 CRC, NSCLC and pancreatic KRAS-mutant cell lines harboring G12C, G12D, G12V, and Q61L revealed single-agent BMF-219 activity after a 4-day treatment. Majority of the cell lines tested exhibited &gt;90% inhibition of growth, independent of KRAS mutation type. Sotorasib reached a maximum of 90-93% growth inhibition in three of eight cell lines. By contrast, BMF-219 inhibited cell viability ≥ 90% in six of eight KRAS G12C lung cancer lines. Human CRC, NSCLC and pancreatic ex vivo preclinical models with G12C, G12D, and G12V KRAS mutations were all sensitive to BMF-219 after a 6-day treatment. Complete abrogation of growth was observed in all samples with IC50 values ranging between 0.2 μM - 0.6 μM. Conclusion: KRAS-mutant CRC, NSCLC, pancreatic cancer cell lines and ex vivo preclinical models are highly sensitive to irreversible menin inhibitor, BMF-219, where clinical reversible menin inhibitors displayed limited activity. High potency of BMF-219 was observed amongst various KRAS-mutant cell lines suggesting that BMF-219 broadly inhibits these tumors. As an irreversible menin inhibitor, BMF-219, manifests advantages over the KRAS-targeted inhibitor sotorasib in multiple cell lines tested, and displays unique potency compared with clinical reversible menin inhibitors in ex vivo preclinical models of CRC, NSCLC, and pancreatic cancer. Citation Format: Brian Law, Daniel Lu, Priyanka Somanath, James T. Palmer, Taisei Kinoshita, Thomas Butler. Irreversible menin inhibitor, BMF-219, inhibits the growth of KRAS-mutated solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2665.

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van Tienen, Laurens Moore, Shadwa Bayoumi, Khaja Muneeruddin, et al. "Abstract B037: Hit-finding by Cysteine-Scanning (HCS): A method for finding druggable pockets." Molecular Cancer Research 21, no. 5_Supplement (2023): B037. http://dx.doi.org/10.1158/1557-3125.ras23-b037.

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Abstract Large-scale cancer sequencing efforts coupled with deep functional genomic interrogation of cancer models provides us an increasingly detailed view of the critical cancer drivers required for persistent growth and survival of cancer cells. Targeting such drivers has provided significant therapeutic benefit to patients across a wide range of cancers, yet progress has been, in large part, confined to the targeting of catalytic domains in kinases. To expand the reach of therapeutics into new classes of therapeutic targets, we need to identify and validate specific mechanisms and pockets to enable drug discovery. To enable this, we are developing a method called Hit-finding by Cysteine-Scanning (HCS) for identifying druggable pockets in proteins of interest. Here, we seek to couple the ability to create systematic variant libraries across proteins of interest with increasingly diverse covalent small molecule/fragment libraries. Thus, HCS involves screening pooled cysteine (cys)-variants against libraries of covalent compounds. To demonstrate the utility of this approach, we applied HCS to systematically screen 189 KRAS-G12D variants. We successfully purified KRAS cys-variant recombinant proteins in pools of seven or eight achieving coverage of 184/189 variants. KRAS variant pools were then screened against a pilot library of 47 covalent compounds with diverse reactivity detecting reactive variant-ligand pairs by intact LC-MS. This allowed us to quantify the accessibility and reactivity across the entire KRAS-G12D protein. The data confirmed the known SII-pocket in KRAS and revealed potentially novel ligand-bound conformations of oncogenic KRAS mutant proteins. In parallel, the same KRAS cys-variant library was generated as a barcoded library in a mammalian expression system. Upon screening this library in intact cells we observed that Sotorasib functionally inhibit the relevant KRAS SII-pocket cys-variants, enabling enrichment of these variants in a negative selection screen. Importantly, binding of a panel of SII-pocket compounds to variant H95C was found to be independent of the KRAS mutant context. Our results indicate that HCS could be a useful tool for the development of inhibitors for currently undruggable oncogenic KRAS mutants as well as potentially other drug targets. Citation Format: Laurens Moore van Tienen, Shadwa Bayoumi, Khaja Muneeruddin, Nancy Leymarie, David Kornfilt, Yuemin Bian, Devishi Kesar, Ruitong Li, Thomas Atack, Alexandra-Mariela Popa, Zuzana Jandova, Philipp Trollmann, Andreas Bergner, Klaus Rumpel, Dirk Kessler, William R. Sellers. Hit-finding by Cysteine-Scanning (HCS): A method for finding druggable pockets [abstract]. In: Proceedings of the AACR Special Conference: Targeting RAS; 2023 Mar 5-8; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Res 2023;21(5_Suppl):Abstract nr B037.

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