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Open AccessVirtual clinical trials via a QSP immuno-oncology model to simulate the response to a conditionally activated PD-L1 targeting antibody in NSCLC
Recently, immunotherapies for antitumoral response have adopted conditionally activated molecules with the objective of reducing systemic toxicity. Amongst these are conditionally activated antibodies, such as...
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Article
Open AccessChemokine-derived oncolytic peptide induces immunogenic cancer cell death and significantly suppresses tumor growth
Chemokinostatin-1 (CKS1) is a 24-mer peptide originally discovered as an anti-angiogenic peptide derived from the CXCL1 chemokine. Here, we demonstrate that CKS1 acts not only as an anti-angiogenic peptide but...
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Open AccessExperiment-based computational model predicts that IL-6 classic and trans-signaling exhibit similar potency in inducing downstream signaling in endothelial cells
Inflammatory cytokine mediated responses are important in the development of many diseases that are associated with angiogenesis. Targeting angiogenesis as a prominent strategy has shown limited effects in man...
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Open AccessSpatial transcriptomics analysis of neoadjuvant cabozantinib and nivolumab in advanced hepatocellular carcinoma identifies independent mechanisms of resistance and recurrence
Novel immunotherapy combination therapies have improved outcomes for patients with hepatocellular carcinoma (HCC), but responses are limited to a subset of patients. Little is known about the inter- and intra-...
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Open AccessGenerating immunogenomic data-guided virtual patients using a QSP model to predict response of advanced NSCLC to PD-L1 inhibition
Generating realistic virtual patients from a limited amount of patient data is one of the major challenges for quantitative systems pharmacology modeling in immuno-oncology. Quantitative systems pharmacology (...
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Open AccessA systems biology model of junctional localization and downstream signaling of the Ang–Tie signaling pathway
The Ang–Tie signaling pathway is an important vascular signaling pathway regulating vascular growth and stability. Dysregulation in the pathway is associated with vascular dysfunction and numerous diseases tha...
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Open AccessA Quantitative Systems Pharmacology Model of T Cell Engager Applied to Solid Tumor
Cancer immunotherapy has recently drawn remarkable attention as promising results in the clinic have shown its ability to improve the overall survival, and T cells are considered to be one of the primary effec...
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Article
Open AccessMechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma
Hepatocyte growth factor (HGF) signaling through its receptor Met has been implicated in hepatocellular carcinoma tumorigenesis and progression. Met interaction with integrins is shown to modulate the downstre...
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Open AccessA QSP Model for Predicting Clinical Responses to Monotherapy, Combination and Sequential Therapy Following CTLA-4, PD-1, and PD-L1 Checkpoint Blockade
Over the past decade, several immunotherapies have been approved for the treatment of melanoma. The most prominent of these are the immune checkpoint inhibitors, which are antibodies that block the inhibitory ...
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Open AccessA Computational Model of Neoadjuvant PD-1 Inhibition in Non-Small Cell Lung Cancer
Immunotherapy and immune checkpoint blocking antibodies such as anti-PD-1 are approved and significantly improve the survival of advanced non-small cell lung cancer (NSCLC) patients, but there has been little ...
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Open AccessTumor Ensemble-Based Modeling and Visualization of Emergent Angiogenic Heterogeneity in Breast Cancer
There is a critical need for new tools to investigate the spatio-temporal heterogeneity and phenotypic alterations that arise in the tumor microenvironment. However, computational investigations of emergent in...
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Open AccessAuthor Correction: Deciphering microvascular changes after myocardial infarction through 3D fully automated image analysis
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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Open AccessSimultaneous blockade of IL-6 and CCL5 signaling for synergistic inhibition of triple-negative breast cancer growth and metastasis
Metastatic triple-negative breast cancer (TNBC) is a heterogeneous and incurable disease. Numerous studies have been conducted to seek molecular targets to treat TNBC effectively, but chemotherapy is still the...
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Open AccessDeciphering microvascular changes after myocardial infarction through 3D fully automated image analysis
The microvasculature continuously adapts in response to pathophysiological conditions to meet tissue demands. Quantitative assessment of the dynamic changes in the coronary microvasculature is therefore crucia...
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Open AccessAn agent-based model of triple-negative breast cancer: the interplay between chemokine receptor CCR5 expression, cancer stem cells, and hypoxia
Triple-negative breast cancer lacks estrogen, progesterone, and HER2 receptors and is thus not possible to treat with targeted therapies for these receptors. Therefore, a greater understanding of triple-negati...
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Open AccessThe Angiogenic Secretome in VEGF overexpressing Breast Cancer Xenografts
The plasticity of cancer cells and the fluidity of the tumor microenvironment continue to present major challenges in the comprehensive understanding of cancer that is essential to design effective treatments....
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Open AccessA multiscale computational model predicts distribution of anti-angiogenic isoform VEGF165b in peripheral arterial disease in human and mouse
Angiogenesis is the growth of new blood vessels from pre-existing microvessels. Peripheral arterial disease (PAD) is caused by atherosclerosis that results in ischemia mostly in the lower extremities. Clinical...
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Open AccessEffects of endothelial cell proliferation and migration rates in a computational model of sprouting angiogenesis
Angiogenesis, the recruitment of new blood vessels, is a critical process for the growth, expansion, and metastatic dissemination of develo** tumors. Three types of cells make up the new vasculature: tip cel...
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Multi-scale Modeling in Clinical Oncology: Opportunities and Barriers to Success
Hierarchical processes spanning several orders of magnitude of both space and time underlie nearly all cancers. Multi-scale statistical, mathematical, and computational modeling methods are central to designin...
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Multiscale Modeling in the Clinic: Drug Design and Development
A wide range of length and time scales are relevant to pharmacology, especially in drug development, drug design and drug delivery. Therefore, multiscale computational modeling and simulation methods and parad...