Dataset Information

Modeling leukocyte-leukocyte non-contact interactions in a lymph node.

ABSTRACT: The interaction among leukocytes is at the basis of the innate and adaptive immune-response and it is largely ascribed to direct cell-cell contacts. However, the exchange of a number of chemical stimuli (chemokines) allows also non-contact interaction during the immunological response. We want here to evaluate the extent of the effect of the non-contact interactions on the observed leukocyte-leukocyte kinematics and their interaction duration. To this aim we adopt a simplified mean field description inspired by the Keller-Segel chemotaxis model, of which we report an analytical solution suited for slowly varying sources of chemokines. Since our focus is on the non-contact interactions, leukocyte-leukocyte contact interactions are simulated only by means of a space dependent friction coefficient of the cells. The analytical solution of the Keller-Segel model is then taken as the basis of numerical simulations of interactions between leukocytes and their duration. The mean field interaction force that we derive has a time-space separable form and depends on the chemotaxis sensitivity parameter as well as on the chemokines diffusion coefficient and their degradation rate. All these parameters affect the distribution of the interaction durations. We draw a successful qualitative comparison between simulated data and sets of experimental data for DC-NK cells interaction duration and other kinematic parameters. Remarkably, the predicted percentage of the leukocyte-leukocyte interactions falls in the experimental range and depends (~25% increase) upon the chemotactic parameter indicating a non-negligible direct effect of the non-contact interaction on the leukocyte interactions.

SUBMITTER: Gritti N

PROVIDER: S-EPMC3810259 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Modeling leukocyte-leukocyte non-contact interactions in a lymph node.

Gritti Nicola N Caccia Michele M Sironi Laura L Collini Maddalena M D'Alfonso Laura L Granucci Francesca F Zanoni Ivan I Chirico Giuseppe G

PloS one 20131028 10

The interaction among leukocytes is at the basis of the innate and adaptive immune-response and it is largely ascribed to direct cell-cell contacts. However, the exchange of a number of chemical stimuli (chemokines) allows also non-contact interaction during the immunological response. We want here to evaluate the extent of the effect of the non-contact interactions on the observed leukocyte-leukocyte kinematics and their interaction duration. To this aim we adopt a simplified mean field descrip ...[more]

PMID: 24204669

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Project description:BackgroundCurrent practice is to perform a completion axillary lymph node dissection (ALND) for breast cancer patients with tumor-involved sentinel lymph nodes (SLNs), although fewer than half will have non-sentinel node (NSLN) metastasis. Our goal was to develop new models to quantify the risk of NSLN metastasis in SLN-positive patients and to compare predictive capabilities to another widely used model.MethodsWe constructed three models to predict NSLN status: recursive partitioning with receiver operating characteristic curves (RP-ROC), boosted Classification and Regression Trees (CART), and multivariate logistic regression (MLR) informed by CART. Data were compiled from a multicenter Northern California and Oregon database of 784 patients who prospectively underwent SLN biopsy and completion ALND. We compared the predictive abilities of our best model and the Memorial Sloan-Kettering Breast Cancer Nomogram (Nomogram) in our dataset and an independent dataset from Northwestern University.Results285 patients had positive SLNs, of which 213 had known angiolymphatic invasion status and 171 had complete pathologic data including hormone receptor status. 264 (93%) patients had limited SLN disease (micrometastasis, 70%, or isolated tumor cells, 23%). 101 (35%) of all SLN-positive patients had tumor-involved NSLNs. Three variables (tumor size, angiolymphatic invasion, and SLN metastasis size) predicted risk in all our models. RP-ROC and boosted CART stratified patients into four risk levels. MLR informed by CART was most accurate. Using two composite predictors calculated from three variables, MLR informed by CART was more accurate than the Nomogram computed using eight predictors. In our dataset, area under ROC curve (AUC) was 0.83/0.85 for MLR (n = 213/n = 171) and 0.77 for Nomogram (n = 171). When applied to an independent dataset (n = 77), AUC was 0.74 for our model and 0.62 for Nomogram. The composite predictors in our model were the product of angiolymphatic invasion and size of SLN metastasis, and the product of tumor size and square of SLN metastasis size.ConclusionWe present a new model developed from a community-based SLN database that uses only three rather than eight variables to achieve higher accuracy than the Nomogram for predicting NSLN status in two different datasets.

Project description:BackgroundThe current preferred approach for surgical mediastinal staging of non-small-cell lung carcinoma is video-assisted mediastinoscopy. An alternative technique in which lymph nodes are resected instead of biopsied is video-assisted mediastinoscopic lymphadenectomy (VAMLA) that is suggested to be superior in detecting N2 disease. Yet, evidence is conflicting and furthermore limited by sample size. The objective was to compare mediastinal staging through VAMLA and video-assisted mediastinoscopy.MethodsA single-center cohort study was conducted. All consecutive patients that underwent surgical mediastinal staging of non-small-cell lung carcinoma by VAMLA (2011 to 2018) were compared to historic video-assisted mediastinoscopy controls (2007 to 2011). Patients with negative surgical mediastinal staging underwent subsequent anatomical resection with systematic regional lymphadenectomy. Primary outcome was the sensitivity and negative predictive value for detecting N2 disease.ResultsTwo-hundred-sixty-nine video-assisted mediastinoscopic lymphadenectomies and 118 video-assisted mediastinoscopies were performed. The prevalence of N2 disease was 20% and 26% respectively in the VAMLA and video-assisted mediastinoscopy group, while the rate of unforeseen pN2 resulting from lymph node dissection during anatomical resection was 4% and 11%, respectively. Invasive staging using VAMLA demonstrated superior sensitivity of 0.82 and a negative predictive value of 0.96 when compared to video-assisted mediastinoscopy (0.62 and 0.89, respectively), offering a 64% decrease in risk of unforeseen pN2 following anatomical resection. However, VAMLA is also associated with a 75% risk increase on complications (P=0.36).ConclusionsWe conclude that performing invasive mediastinal lymph node assessment for staging of non-small-cell lung carcinoma, VAMLA should be the preferred technique with superior sensitivity and negative predictive value in detecting N2 disease. Though, VAMLA is also associated with an increased risk of complications.

Dataset Information

Modeling leukocyte-leukocyte non-contact interactions in a lymph node.

Publications

Modeling leukocyte-leukocyte non-contact interactions in a lymph node.

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