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Articles 49501 - 49530 of 742408
Full-Text Articles in Entire DC Network
Russ 308.80: Russian Cinema And Culture, Clint B. Walker
Russ 308.80: Russian Cinema And Culture, Clint B. Walker
University of Montana Course Syllabi, 2021-2025
No abstract provided.
Ahrc 150.01: Respiratory Care Laboratory I, Paul J. Crockford
Ahrc 150.01: Respiratory Care Laboratory I, Paul J. Crockford
University of Montana Course Syllabi, 2021-2025
No abstract provided.
Enst 396.00: Supervised Internship (Peas), Caroline M. Stephens
Enst 396.00: Supervised Internship (Peas), Caroline M. Stephens
University of Montana Course Syllabi, 2021-2025
No abstract provided.
Biom 327.01: Vector-Borne Diseases: Public Health Perspectives, Brent J. Ryckman
Biom 327.01: Vector-Borne Diseases: Public Health Perspectives, Brent J. Ryckman
University of Montana Course Syllabi, 2021-2025
No abstract provided.
Csci 444.01: Data Visualization, Jesse V. Johnson
Csci 444.01: Data Visualization, Jesse V. Johnson
University of Montana Course Syllabi, 2021-2025
No abstract provided.
Nrsm 475.01: Environment And (International) Development, Hilary Faxon
Nrsm 475.01: Environment And (International) Development, Hilary Faxon
University of Montana Course Syllabi, 2021-2025
No abstract provided.
Nrsm 591.10: Environment And (International) Development, Hilary Faxon
Nrsm 591.10: Environment And (International) Development, Hilary Faxon
University of Montana Course Syllabi, 2021-2025
No abstract provided.
Kin 499.01: Capstone Research, Matthew W. Bundle
Kin 499.01: Capstone Research, Matthew W. Bundle
University of Montana Course Syllabi, 2021-2025
No abstract provided.
Vol. 27, No. 2: Masthead, Water Law Review
Vol. 27, No. 2: Full Issue, Water Law Review
Vol. 53, No. 1: Table Of Contents, Denver Journal Of International Law & Policy
Vol. 53, No. 1: Table Of Contents, Denver Journal Of International Law & Policy
Denver Journal of International Law & Policy
No abstract provided.
Vol. 53, No. 1: Full Issue, Denver Journal Of International Law & Policy
Vol. 53, No. 1: Full Issue, Denver Journal Of International Law & Policy
Denver Journal of International Law & Policy
No abstract provided.
Proteomic Profile Of The Icam1 Pk56m Hfpef Risk Variant, Pedro Giro, Mallory Filipp, Michael J Zhang, Ethan D Moser, Edward B Thorp, Prarthana J Dalal, Ravi V Shah, Patrick T Ellinor, Jonathan W Cunningham, Sean J Jurgens, Arjun Sinha, Laura Rasmussen-Torvik, Jorge Kizer, Kent D Taylor, Philip Greenland, Bruce M Psaty, Russell P Tracy, Lin Yee Chen, Amil M Shah, Bing Yu, Sanjiv J Shah, Ravi B Patel
Proteomic Profile Of The Icam1 Pk56m Hfpef Risk Variant, Pedro Giro, Mallory Filipp, Michael J Zhang, Ethan D Moser, Edward B Thorp, Prarthana J Dalal, Ravi V Shah, Patrick T Ellinor, Jonathan W Cunningham, Sean J Jurgens, Arjun Sinha, Laura Rasmussen-Torvik, Jorge Kizer, Kent D Taylor, Philip Greenland, Bruce M Psaty, Russell P Tracy, Lin Yee Chen, Amil M Shah, Bing Yu, Sanjiv J Shah, Ravi B Patel
Faculty, Staff and Student Publications
A common missense variant in ICAM1 among African American individuals (rs5491; pK56M) has been associated with risk of heart failure with preserved ejection fraction (HFpEF), but the pathways that lead to HFpEF among those with this variant are not clear. In this analysis of 92 circulating proteins and their associated networks, we identified 7 circulating inflammatory proteins associated with rs5491 among >600 African American individuals. Using weighted coexpression network analysis, 3 protein networks were identified, one of which was associated with rs5491. This protein network was most highly represented by members of the tumor necrosis receptor superfamily. The rs5491 variant …
The Link Between People's Social Perceptions Of Cultivated Meat Eaters And Their Acceptance Of Cultivated Meat, Xiaoyu Dai, Angela K. Y. Leung, Mark Chong
The Link Between People's Social Perceptions Of Cultivated Meat Eaters And Their Acceptance Of Cultivated Meat, Xiaoyu Dai, Angela K. Y. Leung, Mark Chong
Research Collection School of Social Sciences
Low consumer acceptance emerges as one important barrier to the introduction of cultivated meat, a novel food which offers an opportunity for more sustainable and ethical meat production. Due to the motives for impression management and self-esteem, one factor that could contribute to people's acceptance of cultivated meat is their perceptions of other individuals who consume cultivated meat. In the current research, two online survey studies with 393 Singaporean undergraduate students and 401 American adults were conducted to explore the perceptions of cultivated meat eaters. In both studies, participants were randomly assigned to read one of three profiles that described …
Review Of Publicly Accessible Behavioral Threat Assessment And Management Program Guides, Erin M. Kearns, Callie Vitro, Sarah Schappert
Review Of Publicly Accessible Behavioral Threat Assessment And Management Program Guides, Erin M. Kearns, Callie Vitro, Sarah Schappert
Reports, Projects, and Research
Across the country, Behavioral Threat Assessment and Management (BTAM) teams exist in communities, education settings, workplaces, and other environments with the aim to assess potential concerns, connect individuals with resources they need, and prevent violence. Despite the prevalence of BTAM teams, there is little available guidance on how to setup and implement these teams in communities. The Review of BTAM Program Setup and Implementation Guides Report is one deliverable in a larger project to (a) evaluate the effectiveness of the DHS I&A NTER Program Office’s Master Trainer Program (MTP) in meeting its objectives, and (b) provide research and recommendations to …
A Chance To See Me: Exploring Black Males’ Perspectives On Public Education Regarding The School-To-Prison Pipeline, Renee Duffaut
A Chance To See Me: Exploring Black Males’ Perspectives On Public Education Regarding The School-To-Prison Pipeline, Renee Duffaut
JWU Dissertations & Theses
In the United States, race undeniably remains at the heart of the educational experiences of Black males. For decades, researchers have studied how schools systemically “push out” and reroute Black males to prison at a disproportionate rate by enforcing inequitable discipline policies and practices (Annamma et al., 2019; Leung-Gagné, 2022; Scott et al., 2017; Skiba et al., 2011). Black children are disciplined for minor infractions at higher rates than any other ethnic group which increases their likelihood of becoming caught up in the School-to-Prison Pipeline (Amemiya et al., 2020). Forty-two percent of youths in juvenile justice placement are Black, even …
Meta-Analysis Identifies Key Genes And Pathways Implicated In Benzo[A]Pyrene Exposure Response, Mingze Zhu, Jooyeon Hwang, Chao Xu
Meta-Analysis Identifies Key Genes And Pathways Implicated In Benzo[A]Pyrene Exposure Response, Mingze Zhu, Jooyeon Hwang, Chao Xu
Faculty, Staff and Student Publications
Introduction: Benzo[a]pyrene (B[a]P) is a carcinogenic polycyclic aromatic hydrocarbon that poses significant risks to human health. B[a]P influences cellular processes via intricate interactions; however, a comprehensive understanding of B[a]P's effects on the transcriptome remains elusive. This study aimed to conduct a comprehensive analysis focused on identifying relevant genes and signaling pathways affected by B[a]P exposure and their impact on human gene expression.
Methods: We searched the Gene Expression Omnibus database and identified four studies involving B[a]P exposure in human cells (T lymphocytes, hepatocellular carcinoma cells, and C3A cells). We utilized two approaches for differential expression analysis: the LIMMA package and …
A Criminal Résumé: Bc’S Unjust Disclosure Of Non-Conviction Information, Nermin Karim
A Criminal Résumé: Bc’S Unjust Disclosure Of Non-Conviction Information, Nermin Karim
UBC Law Review
No abstract provided.
Development Of Extruded Puffed Snack Utilizing Carrot Pomace, Bean Flour, And Rice Starch As Primary Ingredients, Julia Zoe
Master's Theses
Every year, the carrot industry worldwide wastes up to 50% of carrots as raw material due to processing (Šeregelj et al., 2020). When carrots are juiced, the remaining fibrous pulp is often discarded as carrot pomace. In order to redirect this food waste, the first objective of this research was to optimize formulations for an extruded puffed snack that is most similar to commercially available puffed snacks, utilizing baby lima bean flour and carrot pomace
Hardness (kg), cross-sectional expansion ratio, bulk density (g/cm3), moisture content (%), water activity, specific mechanical energy (kJ/kg), carotenoid concentration (ppm), and total dietary …
Survey Of Soilborne Pathogens Infecting Strawberry In Oxnard, California & Effect Of Planting Date And Chill Treatment On Yield Of Strawberry, Samantha Z. Simard
Survey Of Soilborne Pathogens Infecting Strawberry In Oxnard, California & Effect Of Planting Date And Chill Treatment On Yield Of Strawberry, Samantha Z. Simard
Master's Theses
Survey to quantify the frequency of the five main pathogens (Macrophomina phaseolina, Fusarium oxysporum f. sp. fragariae races 1 and 2, Verticillium dahliae, and Phytophthora spp.) infecting strawberry in the Oxnard growing district of California. M. phaseolina was the most prevalent pathogen detected in diseased plants in the Oxnard growing district, present in 67.6% of samples positive for at least one pathogen. F. oxysporum f. sp. fragariae race 1 (35.3%), V. dahlia (8.8%), F. oxysporum f. sp. fragariae race 2 (5.9%) and Phytophthora spp. (2.9%) followed at lower prevalence. Associations were found between fewer drip irrigation lines …
Contributions Of White Adipose Tissue To Energy Requirements For Female Reproduction, Elizabeth S Anaya, Evelyn L De Groot, John P Lydon, Stephanie A Pangas, Sean M Hartig
Contributions Of White Adipose Tissue To Energy Requirements For Female Reproduction, Elizabeth S Anaya, Evelyn L De Groot, John P Lydon, Stephanie A Pangas, Sean M Hartig
Faculty, Staff and Students Publications
Body composition impacts female fertility and there are established relationships between adipose tissue and the reproductive system. Maintaining functional adipose tissue is vital for meeting the energetic demands during the reproductive process, from ovulation to delivery and lactation. White adipose tissue (WAT) shows plastic responses to daily physiology and secretes diverse adipokines that affect the hypothalamic-pituitary-ovarian axis, but many other interorgan interactions remain to be determined. This review summarizes the current state of research on the dialogue between WAT and the female reproductive system, focusing on the impact of this crosstalk on ovarian and endometrial factors essential for fecundity.
Transcriptional Coactivation Of Nrf2 Signaling In Cardiac Fibroblasts Promotes Resistance To Oxidative Stress, Lisa K Mcclendon, Rainer B Lanz, Anil Panigrahi, Kristan Gomez, Michael J Bolt, Min Liu, Fabio Stossi, Michael A Mancini, Clifford C Dacso, David M Lonard, Bert W O'Malley
Transcriptional Coactivation Of Nrf2 Signaling In Cardiac Fibroblasts Promotes Resistance To Oxidative Stress, Lisa K Mcclendon, Rainer B Lanz, Anil Panigrahi, Kristan Gomez, Michael J Bolt, Min Liu, Fabio Stossi, Michael A Mancini, Clifford C Dacso, David M Lonard, Bert W O'Malley
Faculty, Staff and Students Publications
We recently discovered that steroid receptor coactivators (SRCs) SRCs-1, 2 and 3, are abundantly expressed in cardiac fibroblasts (CFs) and their activation with the SRC small molecule stimulator MCB-613 improves cardiac function and dramatically lowers pro-fibrotic signaling in CFs post-myocardial infarction. These findings suggest that CF-derived SRC activation could be beneficial in the mitigation of chronic heart failure after ischemic insult. However, the cardioprotective mechanisms by which CFs contribute to cardiac pathological remodeling are unclear. Here we present studies designed to identify the molecular and cellular circuitry that governs the anti-fibrotic effects of an MCB-613 derivative, MCB-613-10-1, in CFs. We …
Women’S Health And Kidney Protective Medications, Mythri Shankar, Sehrish Ali, Silvi Shah
Women’S Health And Kidney Protective Medications, Mythri Shankar, Sehrish Ali, Silvi Shah
Faculty, Staff and Students Publications
Purpose of review: We discuss the sex-based differences in the pharmacokinetics and pharmacodynamics of kidney protective medications and their implications on women's health.
Recent findings: A critical examination of adverse drug reactions highlights the underrepresentation of women in clinical trials for kidney and cardiovascular protective drugs, such as SGLT2 inhibitors, ACE inhibitors, and endothelin receptor antagonists. This underscores the need for sex-specific analyses in clinical studies to accurately assess medication efficacy and safety.
Summary: The research demonstrates that women are more likely to experience adverse events and less likely to benefit from certain treatments, emphasizing the urgent need for healthcare …
Multi-Institutional Audit Of Flash And Conventional Dosimetry With A 3d Printed Anatomically Realistic Mouse Phantom, M Ramish Ashraf, Stavros Melemenidis, Kevin Liu, Veljko Grilj, Jeannette Jansen, Brett Velasquez, Luke Connell, Joseph B Schulz, Claude Bailat, Aaron Libed, Rakesh Manjappa, Suparna Dutt, Luis Soto, Brianna Lau, Aaron Garza, William Larsen, Lawrie Skinner, Amy S Yu, Murat Surucu, Edward E Graves, Peter G Maxim, Stephen F Kry, Marie-Catherine Vozenin, Emil Schüler, Billy W Loo
Multi-Institutional Audit Of Flash And Conventional Dosimetry With A 3d Printed Anatomically Realistic Mouse Phantom, M Ramish Ashraf, Stavros Melemenidis, Kevin Liu, Veljko Grilj, Jeannette Jansen, Brett Velasquez, Luke Connell, Joseph B Schulz, Claude Bailat, Aaron Libed, Rakesh Manjappa, Suparna Dutt, Luis Soto, Brianna Lau, Aaron Garza, William Larsen, Lawrie Skinner, Amy S Yu, Murat Surucu, Edward E Graves, Peter G Maxim, Stephen F Kry, Marie-Catherine Vozenin, Emil Schüler, Billy W Loo
Faculty, Staff and Student Publications
Purpose: We conducted a multi-institutional dosimetric audit between FLASH and conventional dose rate (CONV) electron irradiations by using an anatomically realistic 3-dimensional (3D) printed mouse phantom.
Methods and materials: A computed tomography (CT) scan of a live mouse was used to create a 3D model of bony anatomy, lungs, and soft tissue. A dual-nozzle 3D printer was used to print the mouse phantom using acrylonitrile butadiene styrene (∼1.02 g/cm3) and polylactic acid (∼1.24 g/cm3) simultaneously to simulate soft tissue and bone densities, respectively. The lungs were printed separately using lightweight polylactic acid (∼0.64 g/cm3). Hounsfield units (HU), densities, and print-to-print …
Lifr Regulates Cholesterol-Driven Bidirectional Hepatocyte-Neutrophil Cross-Talk To Promote Liver Regeneration, Yalan Deng, Zilong Zhao, Marisela Sheldon, Yang Zhao, Hongqi Teng, Consuelo Martinez, Jie Zhang, Chunru Lin, Yutong Sun, Fan Yao, Michael A Curran, Hao Zhu, Li Ma
Lifr Regulates Cholesterol-Driven Bidirectional Hepatocyte-Neutrophil Cross-Talk To Promote Liver Regeneration, Yalan Deng, Zilong Zhao, Marisela Sheldon, Yang Zhao, Hongqi Teng, Consuelo Martinez, Jie Zhang, Chunru Lin, Yutong Sun, Fan Yao, Michael A Curran, Hao Zhu, Li Ma
Faculty, Staff and Student Publications
Liver regeneration is under metabolic and immune regulation. Despite increasing recognition of the involvement of neutrophils in regeneration, it is unclear how the liver signals to the bone marrow to release neutrophils after injury and how reparative neutrophils signal to hepatocytes to reenter the cell cycle. Here we report that loss of the liver tumour suppressor Lifr in mouse hepatocytes impairs, whereas overexpression of leukaemia inhibitory factor receptor (LIFR) promotes liver repair and regeneration after partial hepatectomy or toxic injury. In response to physical or chemical damage to the liver, LIFR from hepatocytes promotes the secretion of cholesterol and CXCL1 …
A Guideline On The Molecular Ecosystem Regulating Ferroptosis, Enyong Dai, Xin Chen, Andreas Linkermann, Xuejun Jiang, Rui Kang, Valerian E Kagan, Hülya Bayir, Wan Seok Yang, Ana J Garcia-Saez, Maria S Ioannou, Tobias Janowitz, Qitao Ran, Wei Gu, Boyi Gan, Dmitri V Krysko, Xiaofeng Zhu, Jiayi Wang, Stefan Krautwald, Shinya Toyokuni, Yangchun Xie, Florian R Greten, Qing Yi, Joel Schick, Jiao Liu, Dmitry I Gabrilovich, Jinbao Liu, Herbert J Zeh, Donna D Zhang, Minghua Yang, Juan Iovanna, Manfred Kopf, Timon E Adolph, Jen-Tsan Chi, Changfeng Li, Hidenori Ichijo, Michael Karin, Vijay G Sankaran, Weiping Zou, Lorenzo Galluzzi, Ashley I Bush, Binghui Li, Gerry Melino, Eric H Baehrecke, Michael T Lotze, Daniel J Klionsky, Brent R Stockwell, Guido Kroemer, Daolin Tang
A Guideline On The Molecular Ecosystem Regulating Ferroptosis, Enyong Dai, Xin Chen, Andreas Linkermann, Xuejun Jiang, Rui Kang, Valerian E Kagan, Hülya Bayir, Wan Seok Yang, Ana J Garcia-Saez, Maria S Ioannou, Tobias Janowitz, Qitao Ran, Wei Gu, Boyi Gan, Dmitri V Krysko, Xiaofeng Zhu, Jiayi Wang, Stefan Krautwald, Shinya Toyokuni, Yangchun Xie, Florian R Greten, Qing Yi, Joel Schick, Jiao Liu, Dmitry I Gabrilovich, Jinbao Liu, Herbert J Zeh, Donna D Zhang, Minghua Yang, Juan Iovanna, Manfred Kopf, Timon E Adolph, Jen-Tsan Chi, Changfeng Li, Hidenori Ichijo, Michael Karin, Vijay G Sankaran, Weiping Zou, Lorenzo Galluzzi, Ashley I Bush, Binghui Li, Gerry Melino, Eric H Baehrecke, Michael T Lotze, Daniel J Klionsky, Brent R Stockwell, Guido Kroemer, Daolin Tang
Faculty, Staff and Student Publications
Ferroptosis, an intricately regulated form of cell death characterized by uncontrolled lipid peroxidation, has garnered substantial interest since this term was first coined in 2012. Recent years have witnessed remarkable progress in elucidating the detailed molecular mechanisms that govern ferroptosis induction and defence, with particular emphasis on the roles of heterogeneity and plasticity. In this Review, we discuss the molecular ecosystem of ferroptosis, with implications that may inform and enable safe and effective therapeutic strategies across a broad spectrum of diseases.
Mitochondrial Complex I Promotes Kidney Cancer Metastasis, Divya Bezwada, Luigi Perelli, Nicholas P Lesner, Ling Cai, Bailey Brooks, Zheng Wu, Hieu S Vu, Varun Sondhi, Daniel L Cassidy, Stacy Kasitinon, Sherwin Kelekar, Feng Cai, Arin B Aurora, Mckenzie Patrick, Ashley Leach, Rashed Ghandour, Yuanyuan Zhang, Duyen Do, Phyllis Mcdaniel, Jessica Sudderth, Dennis Dumesnil, Sara House, Tracy Rosales, Alan M Poole, Yair Lotan, Solomon Woldu, Aditya Bagrodia, Xiaosong Meng, Jeffrey A Cadeddu, Prashant Mishra, Javier Garcia-Bermudez, Ivan Pedrosa, Payal Kapur, Kevin D Courtney, Craig R Malloy, Giannicola Genovese, Vitaly Margulis, Ralph J Deberardinis
Mitochondrial Complex I Promotes Kidney Cancer Metastasis, Divya Bezwada, Luigi Perelli, Nicholas P Lesner, Ling Cai, Bailey Brooks, Zheng Wu, Hieu S Vu, Varun Sondhi, Daniel L Cassidy, Stacy Kasitinon, Sherwin Kelekar, Feng Cai, Arin B Aurora, Mckenzie Patrick, Ashley Leach, Rashed Ghandour, Yuanyuan Zhang, Duyen Do, Phyllis Mcdaniel, Jessica Sudderth, Dennis Dumesnil, Sara House, Tracy Rosales, Alan M Poole, Yair Lotan, Solomon Woldu, Aditya Bagrodia, Xiaosong Meng, Jeffrey A Cadeddu, Prashant Mishra, Javier Garcia-Bermudez, Ivan Pedrosa, Payal Kapur, Kevin D Courtney, Craig R Malloy, Giannicola Genovese, Vitaly Margulis, Ralph J Deberardinis
Faculty, Staff and Student Publications
Most kidney cancers are metabolically dysfunctional1-4, but how this dysfunction affects cancer progression in humans is unknown. We infused 13C-labelled nutrients in over 80 patients with kidney cancer during surgical tumour resection. Labelling from [U-13C]glucose varies across subtypes, indicating that the kidney environment alone cannot account for all tumour metabolic reprogramming. Compared with the adjacent kidney, clear cell renal cell carcinomas (ccRCCs) display suppressed labelling of tricarboxylic acid (TCA) cycle intermediates in vivo and in ex vivo organotypic cultures, indicating that suppressed labelling is tissue intrinsic. [1,2-13C]acetate and [U-13C]glutamine infusions in patients, coupled with measurements of respiration in isolated human …
Magnetic Particle Imaging Enables Nonradioactive Quantitative Sentinel Lymph Node Identification: Feasibility Proof In Murine Models, Olivia C Sehl, Kelvin Guo, Abdul Rahman Mohtasebzadeh, Petrina Kim, Benjamin Fellows, Marcela Weyhmiller, Patrick W Goodwill, Max Wintermark, Stephen Y Lai, Paula J Foster, Joan M Greve
Magnetic Particle Imaging Enables Nonradioactive Quantitative Sentinel Lymph Node Identification: Feasibility Proof In Murine Models, Olivia C Sehl, Kelvin Guo, Abdul Rahman Mohtasebzadeh, Petrina Kim, Benjamin Fellows, Marcela Weyhmiller, Patrick W Goodwill, Max Wintermark, Stephen Y Lai, Paula J Foster, Joan M Greve
Faculty, Staff and Student Publications
Background: Sentinel lymph node biopsy (SLNB) is an important cancer diagnostic staging procedure. Conventional SLNB procedures with 99mTc radiotracers and scintigraphy are constrained by tracer half-life and, in some cases, insufficient image resolution. Here, we explore an alternative magnetic (nonradioactive) image-guided SLNB procedure.
Purpose: To demonstrate that magnetic particle imaging (MPI) lymphography can sensitively, specifically, and quantitatively identify and map sentinel lymph modes (SLNs) in murine models in multiple regional lymphatic basins.
Materials and methods: Iron oxide nanoparticles were administered intradermally to healthy C57BL/6 mice (male, 12-week-old, n = 5). The nanoparticles (0.675 mg Fe/kg) were injected into the tongue, …
Co-Targeting Sos1 Enhances The Antitumor Effects Of Krasg12c Inhibitors By Addressing Intrinsic And Acquired Resistance, Venu Thatikonda, Hengyu Lyu, Sabine Jurado, Kaja Kostyrko, Christopher A Bristow, Christoph Albrecht, Donat Alpar, Heribert Arnhof, Oliver Bergner, Karin Bosch, Ningping Feng, Sisi Gao, Daniel Gerlach, Michael Gmachl, Melanie Hinkel, Simone Lieb, Astrid Jeschko, Annette A Machado, Thomas Madensky, Ethan D Marszalek, Mikhila Mahendra, Gabriella Melo-Zainzinger, Jessica M Molkentine, Philipp A Jaeger, David H Peng, Robyn L Schenk, Alexey Sorokin, Sandra Strauss, Francesca Trapani, Scott Kopetz, Christopher P Vellano, Mark Petronczki, Norbert Kraut, Timothy P Heffernan, Joseph R Marszalek, Mark Pearson, Irene C Waizenegger, Marco H Hofmann
Co-Targeting Sos1 Enhances The Antitumor Effects Of Krasg12c Inhibitors By Addressing Intrinsic And Acquired Resistance, Venu Thatikonda, Hengyu Lyu, Sabine Jurado, Kaja Kostyrko, Christopher A Bristow, Christoph Albrecht, Donat Alpar, Heribert Arnhof, Oliver Bergner, Karin Bosch, Ningping Feng, Sisi Gao, Daniel Gerlach, Michael Gmachl, Melanie Hinkel, Simone Lieb, Astrid Jeschko, Annette A Machado, Thomas Madensky, Ethan D Marszalek, Mikhila Mahendra, Gabriella Melo-Zainzinger, Jessica M Molkentine, Philipp A Jaeger, David H Peng, Robyn L Schenk, Alexey Sorokin, Sandra Strauss, Francesca Trapani, Scott Kopetz, Christopher P Vellano, Mark Petronczki, Norbert Kraut, Timothy P Heffernan, Joseph R Marszalek, Mark Pearson, Irene C Waizenegger, Marco H Hofmann
Faculty, Staff and Student Publications
Combination approaches are needed to strengthen and extend the clinical response to KRASG12C inhibitors (KRASG12Ci). Here, we assessed the antitumor responses of KRASG12C mutant lung and colorectal cancer models to combination treatment with a SOS1 inhibitor (SOS1i), BI-3406, plus the KRASG12C inhibitor, adagrasib. We found that responses to BI-3406 plus adagrasib were stronger than to adagrasib alone, comparable to adagrasib with SHP2 (SHP2i) or EGFR inhibitors and correlated with stronger suppression of RAS-MAPK signaling. BI-3406 plus adagrasib treatment also delayed the emergence of acquired resistance and elicited antitumor responses from adagrasib-resistant models. Resistance to KRASG12Ci seemed to be driven by …
Mechanisms That Clear Mutations Drive Field Cancerization In Mammary Tissue, Marta Ciwinska, Hendrik A Messal, Hristina R Hristova, Catrin Lutz, Laura Bornes, Theofilos Chalkiadakis, Rolf Harkes, Nathalia S M Langedijk, Stefan J Hutten, Renée X Menezes, Jos Jonkers, Stefan Prekovic, Grand Challenge Precision Consortium, Benjamin D Simons, Colinda L G J Scheele, Jacco Van Rheenen
Mechanisms That Clear Mutations Drive Field Cancerization In Mammary Tissue, Marta Ciwinska, Hendrik A Messal, Hristina R Hristova, Catrin Lutz, Laura Bornes, Theofilos Chalkiadakis, Rolf Harkes, Nathalia S M Langedijk, Stefan J Hutten, Renée X Menezes, Jos Jonkers, Stefan Prekovic, Grand Challenge Precision Consortium, Benjamin D Simons, Colinda L G J Scheele, Jacco Van Rheenen
Faculty, Staff and Student Publications
Oncogenic mutations are abundant in the tissues of healthy individuals, but rarely form tumours1-3. Yet, the underlying protection mechanisms are largely unknown. To resolve these mechanisms in mouse mammary tissue, we use lineage tracing to map the fate of wild-type and Brca1-/-;Trp53-/- cells, and find that both follow a similar pattern of loss and spread within ducts. Clonal analysis reveals that ducts consist of small repetitive units of self-renewing cells that give rise to short-lived descendants. This offers a first layer of protection as any descendants, including oncogenic mutant cells, are constantly lost, thereby limiting the spread of mutations to …