Dataset Information

A persistent invasive phenotype in post-hypoxic tumor cells is revealed by fate mapping and computational modeling.

ABSTRACT: Hypoxia is a critical factor in solid tumors that has been associated with cancer progression and aggressiveness. We recently developed a hypoxia fate mapping system to trace post-hypoxic cells within a tumor for the first time. This approach uses an oxygen-dependent fluorescent switch and allowed us to measure key biological features such as oxygen distribution, cell proliferation, and migration. We developed a computational model to investigate the motility and phenotypic persistence of hypoxic and post-hypoxic cells during tumor progression. The cellular behavior was defined by phenotypic persistence time, cell movement bias, and the fraction of cells that respond to an enhanced migratory stimulus. This work combined advanced cell tracking and imaging techniques with mathematical modeling, to reveal that a persistent invasive migratory phenotype that develops under hypoxia is required for cellular escape into the surrounding tissue, promoting the formation of invasive structures ("plumes") that expand toward the oxygenated tumor regions.

SUBMITTER: Rocha HL

PROVIDER: S-EPMC8449249 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A persistent invasive phenotype in post-hypoxic tumor cells is revealed by fate mapping and computational modeling.

Rocha Heber L HL Godet Inês I Kurtoglu Furkan F Metzcar John J Konstantinopoulos Kali K Bhoyar Soumitra S Gilkes Daniele M DM Macklin Paul P

iScience 20210804 9

Hypoxia is a critical factor in solid tumors that has been associated with cancer progression and aggressiveness. We recently developed a hypoxia fate mapping system to trace post-hypoxic cells within a tumor for the first time. This approach uses an oxygen-dependent fluorescent switch and allowed us to measure key biological features such as oxygen distribution, cell proliferation, and migration. We developed a computational model to investigate the motility and phenotypic persistence of hypoxi ...[more]

PMID: 34568781

Similar Datasets

Project description:IntroductionCatheter ablation of persistent AF has not been consistently successful in terminating AF or preventing arrhythmia recurrences. Non-invasive Electrocardiographic Imaging (ECGI) can help to understand recurrences by mapping the mechanisms of pre-ablation AF and comparing them with the patterns of recurrent arrhythmias in the same patient.MethodsSeventeen persistent AF patients underwent ECGI before their first catheter ablation. Time-domain activation maps and phase progression maps were obtained on the bi-atrial epicardium. Location of arrhythmogenic drivers were annotated on the bi-atrial anatomy. Activation and phase movies were examined to understand the wavefront dynamics during AF. Eight patients recurred within 12 months of ablation and underwent a follow-up ECGI. Driver locations and movies were compared for pre- and post-ablation AF.ResultsA total of 243 focal drivers were mapped during pre-ablation AF. 62% of the drivers were mapped in the left atrium (LA). The pulmonary vein region harbored most of the drivers (43%). 35% of the drivers were mapped in the right atrium (RA). 59% (10/17) and 53% (9/17) of patients had repetitive sources in the left pulmonary veins (LPV) and left atrial appendage (LAA), and the lower half of RA, respectively. All patients had focal drivers. 29% (5/17) of patients had macro-reentry waves. 24% (4/17) of patients had rotors. Activation patterns during persistent AF varied from single macro-reentry to complex activity with multiple simultaneous wavefronts in both atria, resulting in frequent wave collisions. A total of 76 focal driver activities were mapped in 7/8 patients during recurrence. 59% of the post-ablation AF drivers were mapped in the LA. The pulmonary vein region harbored 50% of total drivers. 39% of sources were mapped in the RA. AF complexity remained similar post-ablation. 58% (44/76) of pre-ablation sources persisted during recurrence. 38% (3/8) of patients had macro-reentry and one patient had rotors.ConclusionECGI provides patient-specific information on mechanisms of persistent AF and recurrent arrhythmia. More than half pre-ablation sources repeated during post-ablation recurrence. This study provides direct evidence for drivers that persist days and months after the ablation procedure. Patient-tailored bi-atrial ablation is needed to successfully target persistent AF and prevent recurrence. ECGI can potentially predict recurrence and assist in choice of therapy.

Project description:There are a variety of difficulties in evaluating clinical cardiac mapping systems, most notably the inability to record the transmembrane potential throughout the entire heart during patient procedures which prevents the comparison to a relevant "gold standard". Cardiac mapping systems are comprised of hardware and software elements including sophisticated mathematical algorithms, both of which continue to undergo rapid innovation. The purpose of this study is to develop a computational modeling framework to evaluate the performance of cardiac mapping systems. The framework enables rigorous evaluation of a mapping system's ability to localize and characterize (i.e., focal or reentrant) arrhythmogenic sources in the heart. The main component of our tool is a library of computer simulations of various dynamic patterns throughout the entire heart in which the type and location of the arrhythmogenic sources are known. Our framework allows for performance evaluation for various electrode configurations, heart geometries, arrhythmias, and electrogram noise levels and involves blind comparison of mapping systems against a "silver standard" comprised of computer simulations in which the precise transmembrane potential patterns throughout the heart are known. A feasibility study was performed using simulations of patterns in the human left atria and three hypothetical virtual catheter electrode arrays. Activation times (AcT) and patterns (AcP) were computed for three virtual electrode arrays: two basket arrays with good and poor contact and one high-resolution grid with uniform spacing. The average root mean squared difference of AcTs of electrograms and those of the nearest endocardial action potential was less than 1 ms and therefore appears to be a poor performance metric. In an effort to standardize performance evaluation of mapping systems a novel performance metric is introduced based on the number of AcPs identified correctly and those considered spurious as well as misclassifications of arrhythmia type; spatial and temporal localization accuracy of correctly identified patterns was also quantified. This approach provides a rigorous quantitative analysis of cardiac mapping system performance. Proof of concept of this computational evaluation framework suggests that it could help safeguard that mapping systems perform as expected as well as provide estimates of system accuracy.

Dataset Information

A persistent invasive phenotype in post-hypoxic tumor cells is revealed by fate mapping and computational modeling.

Publications

A persistent invasive phenotype in post-hypoxic tumor cells is revealed by fate mapping and computational modeling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets