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Metabolic reprogramming is a hallmark of cancer. The main aim of this work is to integrate a genome-scale metabolic description of tumor cells into a tumor growth model that accounts for the spatiotemporally heterogeneous tumor microenvironment, in order to study the effects of microscopic characteristics on tumor evolution. A lactate maximization metabolic strategy that allows near optimal growth solution, while maximizing lactate secretion, is assumed. The proposed sub-cellular metabolic model is then incorporated into a hybrid discrete-continuous model of tumor growth. We produced several phenotypes by applying different constraints and optimization criteria in the metabolic model and explored the tumor evolution of the various phenotypes in different vasculature conditions and ECM densities. At first, we showed that the metabolic capabilities of phenotypes depending on resource availability can vary in a counter-intuitive manner. We then showed that i) tumor population, morphology and spread are affected differently in different conditions, allowing thus phenotypes to be superior than others in different conditions and that ii) polyclonal tumors consisting of different phenotypes can exploit their different metabolic capabilities to enhance further tumor evolution. The proposed framework comprises a proof-of-concept demonstration showing the importance of considering the metabolic capabilities of phenotypes on predicting tumor evolution. The proposed framework allows the incorporation of context-specific and patient-specific data for the study of personalized tumor evolution and therapy efficacy, linking genome to metabolic capabilities and tumor dynamics.
This article was published in the following journal.
Name: IEEE journal of biomedical and health informatics
The tumor microenvironment presents physical, immunologic, and metabolic barriers to durable immunotherapy responses. We have recently described roles for both T cell metabolic insufficiency as well a...
Hypoxia is an important factor in malignant tumors, and glycolysis is a major metabolic contributor in their development. Glycolytic enzymes have gained increasing attention as potential therapeutic t...
Mathematical modeling provides the predictive ability to understand the metabolic reprogramming and complex pathways that mediate cancer cells' proliferation. We present a mathematical model using a m...
The biosynthetic capabilities of microbes underlie their growth and interactions, playing a prominent role in microbial community structure. For large, diverse microbial communities, prediction of the...
The mechanisms by which regulatory T cells (Tregs) migrate to and function within the hypoxic tumor microenvironment are unclear. Our studies indicate that specific ablation of hypoxia-inducible fact...
The aim of this study is to systematically Analyse the metabolome in capillary blood of healthy men and women at rest and during defined standardized physical activity under normobaric nor...
This study is aiming to evaluate the retentive forces in PEEK framework RPD compared to Cobalt-Chrome framework RPD during attachment/detachment cycles in mandibular kennedy class I edentu...
To evaluate two different techniques of cross linking: standard epithelium off (CXL epi off) versus trans-epithelial (CXL epi on) cross linking in patient with progressive keratoconus.
To determine the effect of an amino acid on bacterial glycolytic acid formation in human interdental plaque.
the purpose of this study is to compare the efficacy and safety of a new method of corneal cross-linking that uses UV-A irradiation intensity of 9mW/cm2 for 7 minutes to well-known Accele...
A framework for development and promotion of common data formats and exchange protocols linked in a way that can be read directly by computers. Semantic Web is a platform for sharing and reusing data across application, enterprise, and community boundaries, by linking concepts rather than just documents.
A rho GTP-binding protein that is prenylated (see PROTEIN PRENYLATION) at its C-terminus and cycles between the cytoplasm and plasma membrane, linking receptor signaling pathways with assembly of FOCAL ADHESIONS; STRESS FIBERS; and contractile ring formation during CYTOKINESIS. It is overexpressed in proliferating and metastatic tumor cells.
A measure of the functional capabilities of the heart, lungs and muscles, relative to the demands of specific exercise routines such as running or cycling.
A human liver tumor cell line used to study a variety of liver-specific metabolic functions.
Acquired or inborn metabolic diseases that produce brain dysfunction or damage. These include primary (i.e., disorders intrinsic to the brain) and secondary (i.e., extracranial) metabolic conditions that adversely affect cerebral function.
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...
An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produc...