Article
Oncology
Kathleen A. O'Leary, Debra E. Rugowski, Michael P. Shea, Ruth Sullivan, Amy R. Moser, Linda A. Schuler
Summary: Prolactin (PRL) collaborates with Apc(Min/+) to increase tumor incidence and modulate cancer stem cell activity through Notch-driven signals, shedding light on mechanisms whereby PRL elevates risk of breast cancer.
Review
Biochemistry & Molecular Biology
Qiyun Xiao, Johannes Werner, Nachiyappan Venkatachalam, Kim E. Boonekamp, Matthias P. Ebert, Tianzuo Zhan
Summary: Targeting cancer hallmarks is crucial for improving anti-cancer treatment, but cross-talk between signaling pathways often leads to resistance. This article provides an overview of the molecular interactions between the p53 and Wnt pathways in cancer, including complex feedback loops and reciprocal transactivation, as well as the mutational landscape of genes associated with these pathways.
Article
Pathology
Sonja Chen, Sara Gallant, Michael J. Cunningham, Caroline D. Robson, Alanna J. Church, Antonio R. Perez-Atayde, Alyaa Al-Ibraheemi
Summary: This study describes 8 cases of sinonasal myxoma (SNM) and analyzes the clinical and biological differences compared to desmoid fibromatosis. The findings expand the understanding of SNM and highlight its differences from desmoid fibromatosis in histology, clinical characteristics, and genetics.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yuan Guo, Yan-Rong Zhao, Huan Liu, Yang Xin, Jian-Zhi Yu, Yun-Jin Zang, Qing-guo Xu
Summary: The study identified EHMT2 as a critical factor in the development of hepatocellular carcinoma, showing that elevated EHMT2 expression promotes tumorigenesis and activates the Wnt-beta-catenin signaling pathway. EHMT2 was found to epigenetically silence the APC promoter through methylation, and the specific inhibitor UNC0642 demonstrated anti-tumorigenesis effects in HCC, suggesting it as a potential candidate for targeted drug therapy.
CELL AND BIOSCIENCE
(2021)
Article
Multidisciplinary Sciences
Line Mygland, Shoshy Alam Brinch, Martin Frank Strand, Petter Angell Olsen, Aleksandra Aizenshtadt, Kaja Lund, Nina Therese Solberg, Max Lycke, Tor Espen Thorvaldsen, Sandra Espada, Dorna Misaghian, Christian M. Page, Oleg Agafonov, Stale Nygard, Nai-Wen Chi, Eva Lin, Jenille Tan, Yihong Yu, Mike Costa, Stefan Krauss, Jo Waaler
Summary: Small-molecule tankyrase 1 and tankyrase 2 (TNKS1/2) inhibitors have shown to be effective antitumor agents in specific tumor cell lines, with the ability to inhibit key signaling pathways and reduce expression of crucial oncogenes, ultimately impairing cell growth. Additionally, these inhibitors induce the accumulation of beta-catenin degradasomes containing TNKS1/2, which interact with YAP and angiomotin proteins, leading to attenuation of YAP signaling. Further research is needed to fully evaluate the potential of TNKS inhibitors in cancer treatment.
Review
Biochemistry & Molecular Biology
Sarah Koushyar, Valerie S. Meniel, Toby J. Phesse, Helen B. Pearson
Summary: Aberrant activation of the Wnt pathway is closely related to tumor formation, progression, and therapeutic resistance in prostate cancer. Targeting the Wnt pathway for prostate cancer treatment has shown potential efficacy. However, the functional consequences of activating the Wnt pathway during different stages of prostate cancer progression are still unclear. Preclinical research on targeting Wnt signaling in the treatment of prostate cancer is crucial for identifying effective treatment strategies and improving patient care.
Review
Biochemistry & Molecular Biology
Mutsuko Kukimoto-Niino, Mikako Shirouzu, Tesshi Yamada
Summary: TNIK is a promising therapeutic target for colorectal cancer due to its role in regulating the Wnt/β-catenin signaling pathway. In this study, structural insights into TNIK inhibitors targeting the ATP-binding site are presented.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Anja Kafka, Anja Bukovac, Emilija Brglez, Ana-Marija Jarmek, Karolina Poljak, Petar Brlek, Kamelija Zarkovic, Niko Njiric, Nives Pecina-Slaus
Summary: This study investigated genetic and epigenetic changes as well as protein expression levels of negative regulators of Wnt signaling in human astrocytomas. The results emphasize the importance of methylation in Wnt signaling regulation, and suggest that large deletions of the APC gene and effects of beta-catenin and GSK3 beta play key roles in astrocytoma evolution. Further studies are needed to understand the clinical and therapeutic relevance of these molecular alterations.
Review
Cell Biology
Wibke Groenewald, Anders H. H. Lund, David Michael Gay
Summary: It is well known that mutations in the WNT-signalling pathway are significant in cancer development. Understanding the role and occurrence of these mutations within the pathway is crucial for developing effective therapeutic strategies. Some cancers have mutations at the receptor level of the pathway, while others have mutations in the cytoplasmic segment, leading to ligand-dependent or ligand-independent pathway activation, respectively. This review explores the driving mutations in cancer and the available therapeutic interventions for each type of mutation, and also discusses a potential new therapeutic avenue targeting the translational apparatus downstream from WNT signalling.
Article
Biochemistry & Molecular Biology
Janson Tse, Ryan O'Keefe, Angela Rigopolous, Annalisa L. E. Carli, Jo Waaler, Stefan Krauss, Matthias Ernst, Michael Buchert
Summary: Specific signalling thresholds of the WNT/beta-catenin pathway affect embryogenesis and tissue homeostasis. Currently, there is a lack of specific in vivo assays to evaluate inhibitors of WNT/beta-catenin signalling. We present a simple in vivo assay to assess the efficacy and bioavailability of candidate compounds.
Review
Cell Biology
Ishita S. Hiremath, Arul Goel, Sudha Warrier, Alan Prem Kumar, Gautam Sethi, Manoj Garg
Summary: The Wnt/β-catenin signaling pathway is crucial for various physiological processes and implicated in the development of several cancers. Different regulators of the pathway play essential roles in cancer development.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lingchen Fu, Jia Fan, Sudipa Maity, Grant McFadden, Yixin Shi, Wei Kong
Summary: PD-L1 interacts with Frizzled 6 receptor to activate beta-catenin signaling and increase the expression of stem cell markers, thereby maintaining and expanding the population of cancer stem cells. Blocking PD-L1 function can inhibit tumor progression by reducing the CSC population.
Article
Oncology
Jiri Svec, Monika Stastna, Lucie Janeckova, Dusan Hrckulak, Martina Vojtechova, Jakub Onhajzer, Vitezslav Kriz, Katerina Galuskova, Eva Sloncova, Jan Kubovciak, Lucie Pfeiferova, Jan Hrudka, Radoslav Matej, Petr Waldauf, Lukas Havluj, Michal Kolar, Vladimir Korinek
Summary: TROP2 is overexpressed in colorectal cancer and is associated with negative prognostic factors such as lymph node metastases and poor tumor differentiation. Its expression is regulated by the Wnt/β-catenin signaling pathway and YAP.
Article
Oncology
Huajun Han, Laurie A. Davidson, Martha Hensel, Grace Yoon, Kerstin Landrock, Clinton Allred, Arul Jayaraman, Ivan Ivanov, Stephen H. Safe, Robert S. Chapkin
Summary: The study reveals the protective role of AhR signaling in genetically induced colon tumorigenesis at least by suppressing Wnt signaling and provides rationale for the AhR as a therapeutic target for cancer prevention and treatment.
MOLECULAR CANCER RESEARCH
(2021)
Article
Medicine, Research & Experimental
Zheng Qin, Yupei Li, Jiameng Li, Luojia Jiang, Zhuyun Zhang, Kaixi Chang, Qinbo Yang, Shanshan Chen, Ruoxi Liao, Baihai Su
Summary: This study found that exosomal STAT1 derived from HP-treated HUVECs can promote VSMC calcification. Activation of the Wnt/beta-catenin pathway may be a potential mechanism of exosome-promoted VSMC calcification.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2022)
Article
Mathematics, Applied
Meraj Alam, H. M. Byrne, G. P. Raja Sekhar
Summary: This article introduces a mathematical model for describing hydrodynamics and deformation mechanics in solid tumors embedded or adjacent to healthy tissues. The model accounts for the deformability of tumor and normal tissue regions, as well as the nonlinearity caused by heterogeneous and deformation-dependent physiological transport parameters. The study establishes the existence of a unique weak solution and its continuity with respect to the given data using Galerkin and weak convergence methods.
APPLICABLE ANALYSIS
(2022)
Article
Biology
Anna Sher, Steven A. Niederer, Gary R. Mirams, Anna Kirpichnikova, Richard Allen, Pras Pathmanathan, David J. Gavaghan, Piet H. van der Graaf, Denis Noble
Summary: This article discusses the challenges in model development and assessment in Quantitative Systems Pharmacology (QSP). QSP requires incorporating mathematical descriptions of complex physiology and drug targets into models, while also developing robust and predictive models. However, there is no standard for model development and assessment in QSP, leading to potential miscommunication and misapplication within the modeling community.
BULLETIN OF MATHEMATICAL BIOLOGY
(2022)
Article
Computer Science, Interdisciplinary Applications
Ehsan Taghizadeh, Helen M. Byrne, Brian D. Wood
Summary: In this study, a combination of formal upscaling and data-driven machine learning was used to explicitly close nonlinear transport and reaction process in multiscale tissues. The neural network trained to model the closure problem exhibited good generalizability and high fidelity in predicting the effectiveness factor for tissues with different scale and complexity. This approach not only resulted in an upscaled nonlinear PDE but also identified important source terms for closure and improved the accuracy of the models predicting correction factors.
JOURNAL OF COMPUTATIONAL PHYSICS
(2022)
Article
Multidisciplinary Sciences
Bernadette J. Stolz, Jakob Kaeppler, Bostjan Markelc, Franziska Braun, Florian Lipsmeier, Ruth J. Muschel, Helen M. Byrne, Heather A. Harrington
Summary: This article showcases how topological data analysis can be used to characterize the geometric, spatial, and temporal organization of vascular networks. The proposed method captures multiscale features and vessel connectivity, enabling quantification of abnormal structural features and variation in vascular networks. The authors validate the method through analysis of images collected using different imaging modalities, and quantify the effects of antibody modulation and radiotherapy on vascular architecture.
Article
Biology
Gopikrishnan C. C. Remesan, Jennifer A. A. Flegg, Helen M. M. Byrne
Summary: In vitro experiments demonstrate the impact of mechanical interactions between tumour cells and the surrounding tissue in a gelatinous medium, as well as the local levels of diffusible nutrients, on tumour growth dynamics. A mathematical model is presented to describe these experiments, revealing the influence of mechanical deformations in the hydrogel on tumour growth. Variations in the hydrogel's mechanical properties affect the tumour's equilibrium size, with soft hydrogels favoring nutrient availability and larger tumour size, while stiff hydrogels can eliminate tumours due to increased mechanical resistance. The model analysis identifies parameter regimes in which the hydrogel contributes to tumour elimination.
JOURNAL OF MATHEMATICAL BIOLOGY
(2023)
Article
Biology
Dominic G. Whittaker, Alejandra D. Herrera-Reyes, Maurice Hendrix, Markus R. Owen, Leah R. Band, Gary R. Mirams, Kirsty J. Bolton, Simon P. Preston
Summary: This article discusses the importance of epidemic models in policy-making during the SARS-CoV-2 pandemic. Model-based projections and inferences have influenced public health responses, especially regarding non-pharmaceutical interventions. The study shows that mis-specifying distributions representing host infectiousness and infection-to-death times in simpler models can lead to significant errors in inferred quantities relevant to policy-making. Bayesian uncertainty quantification is considered and applied to synthetic and real data, emphasizing the misleading nature of neglecting uncertainty.
JOURNAL OF THEORETICAL BIOLOGY
(2023)
Article
Biology
Heyrim Cho, Allison L. Lewis, Kathleen M. Storey, Helen M. Byrne
Summary: This article investigates the inference of interaction types between two tumor cell lines using the Lotka-Volterra model. Three experimental designs are evaluated for identifiability and predictive power of the model. The study also highlights the need for caution when interpreting parameter estimates for the spatially-averaged Lotka-Volterra model calibrated against data from a spatially-resolved cellular automaton model.
JOURNAL OF THEORETICAL BIOLOGY
(2023)
Article
Biology
Giulia L. Celora, Helen M. Byrne, P. G. Kevrekidis
Summary: This study presents a mathematical model that describes the evolution of tumour heterogeneity in a tissue slice oxygenated by a single blood vessel. The model considers the phenotype of tumour cells, which determines their proliferative capacity, apoptosis propensity, and response to treatment. Numerical simulations reveal the multiple steady states of the system and the role of tissue oxygen levels in the efficacy of radiation protocols commonly used in the clinic.
JOURNAL OF THEORETICAL BIOLOGY
(2023)
Article
Biology
Rahil Sachak-Patwa, Erin I. Lafferty, Claude J. Schmit, Robin N. Thompson, Helen M. Byrne
Summary: This article studies a hierarchy of ordinary differential equation models that describe the within-host viral kinetics of influenza infections, where the IR model explicitly accounts for an immune response to the virus, while the simpler TEIV and TV models do not. It is shown that the parameters values of the IR model can be determined when fitting it to experimental murine data considering the viral load, fraction of dead cells, and immune response levels. However, if only viral load data are available, we can estimate parameters of the TEIV and TV models but not the IR model. These results are supported by a structural and practical identifiability analysis. The study concludes that a simple target-cell limited model, such as the TV model, can reproduce influenza infection dynamics and distinguish between hosts with differing immune responses, if only viral load data are available.
JOURNAL OF THEORETICAL BIOLOGY
(2023)
Article
Biology
Keith L. Chambers, Mary R. Myerscough, Helen M. Byrne
Summary: Athersclerotic plaques are formed by lipid accumulation in artery walls, driven by chronic inflammatory response. The impact of blood LDL/HDL levels on plaque composition and lipid distribution in plaque macrophages remains unexplored. In this study, we develop a lipid-structured mathematical model to investigate this impact and find that plaque lipid content is sensitive to the influx of LDL relative to HDL capacity. The macrophage lipid distribution evolves in a wave-like manner towards an equilibrium profile, and lipid accumulation may severely impair macrophage uptake.
MATHEMATICAL BIOSCIENCES
(2023)
Article
Computer Science, Interdisciplinary Applications
Chon Lok Lei, Michael Clerx, David J. Gavaghan, Gary R. Mirams
Summary: This article discusses a method of automatically designing experimental protocols to identify cell-specific maximum conductance values in cardiac cellular electrophysiology research. The results show that this approach can not only better identify model parameters and improve model predictive power, but also shorten the experimental duration.
COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
(2023)
Article
Medicine, Research & Experimental
Daria Stepanova, Helen M. Byrne, Philip K. Maini, Tomas Alarcon
Summary: Angiogenesis is a complex biological process involving the formation of new blood vessels by endothelial cells. Theoretical modeling has contributed to our understanding of this process, but current models based on the snail-trail hypothesis may not fully capture the role of cell mixing. This review focuses on the phenomenon of cell mixing during angiogenic sprouting and discusses its functional role in theoretical models.
WIRES MECHANISMS OF DISEASE
(2023)
Review
Medicine, Research & Experimental
Aditi Agrawal, Ken Wang, Liudmila Polonchuk, Jonathan Cooper, Maurice Hendrix, David J. Gavaghan, Gary R. Mirams, Michael Clerx
Summary: The L-type calcium current (ICaL) plays a critical role in cardiac electrophysiology. However, there is a large variability in the predictions of different ICaL models, and it is unclear which model is best suited for specific applications. Further experimental and modeling work is needed to reduce the competing theories and develop a consensus ICaL model.
WIRES MECHANISMS OF DISEASE
(2023)
Article
Multidisciplinary Sciences
Dominic G. Whittaker, Jiahui Wang, Joseph G. Shuttleworth, Ravichandra Venkateshappa, Jacob M. Kemp, Thomas W. Claydon, Gary R. Mirams
Summary: Mathematical models of voltage-gated ion channels play a crucial role in research and applications, but determining the appropriate complexity and structure of these models is challenging. This study utilizes the MBAM method to simplify ion channel models, resulting in models with fewer parameters while still retaining good predictive capability.
JOURNAL OF THE ROYAL SOCIETY INTERFACE
(2022)
Article
Physics, Fluids & Plasmas
Jakub Kory, Philip K. Maini, Joe M. Pitt-Francis, Helen M. Byrne
Summary: When blood flows through vessel networks, the width of the cell-free layer (CFL) near the vessel wall impacts the blood rheology and oxygen delivery. Existing methods based on the analysis of forces acting on red blood cells (RBCs) are challenging due to the complexity of blood interactions. In this study, we propose a two-step approach to derive a functional relationship between CFL width and vessel properties, which shows promising results in agreement with in vivo data.
