Dataset Information

Restraint and Social Isolation Stressors Differentially Regulate Adaptive Immunity and Tumor Angiogenesis in a Breast Cancer Mouse Model.

ABSTRACT: The ability of stress to induce immune suppression is widely recognized, but the mechanisms underlying the effects of stress on the adaptive immune system during tumor progression are not completely understood. To study the effect of stress on the immune system in vivo, we used a preclinical immunocompetent mouse model bearing 4T1 mammary adenocarcinoma cells. Mice were randomized into 4 groups, including social isolation (SI), acute restraint stress (aRRS), chronic restraint stress (cRRS), or no stress (NS). We found that SI significantly decreased the number of tumor-bearing mice still alive at the end of protocol (28 days), compared to NS mice. Although we did not detect significant changes in primary tumor volume, we observed a significant increase in the endothelial marker CD31 in primary tumors of SI mice and in lung metastases in SI and RRS mice. Survival decline in SI mice was associated with significant decreases in splenic CD8 cells and in activated T cells. From a mechanistic standpoint, RRS increased expression of FOXP3, CXCL-10, and granzyme B in mouse tumors, and the effects were reversed by propranolol. Our data demonstrate that various forms of stress differentially impact adaptive immunity and tumor angiogenesis, and negatively impact survival.

SUBMITTER: Budiu RA

PROVIDER: S-EPMC5464739 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Restraint and Social Isolation Stressors Differentially Regulate Adaptive Immunity and Tumor Angiogenesis in a Breast Cancer Mouse Model.

Budiu Raluca A RA Vlad Anda M AM Nazario Linda L Bathula Chandra C Cooper Kristine L KL Edmed Jessica J Thaker Premal H PH Urban Julie J Kalinski Pawel P Lee Adrian V AV Elishaev Esther L EL Conrads Thomas P TP Flint Melanie S MS

Cancer and clinical oncology 20161111 1

The ability of stress to induce immune suppression is widely recognized, but the mechanisms underlying the effects of stress on the adaptive immune system during tumor progression are not completely understood. To study the effect of stress on the immune system <i>in vivo</i>, we used a preclinical immunocompetent mouse model bearing 4T1 mammary adenocarcinoma cells. Mice were randomized into 4 groups, including social isolation (SI), acute restraint stress (aRRS), chronic restraint stress (cRRS ...[more]

PMID: 28603578

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Project description:Objective Using population-based simulations and machine-learning algorithms to develop an adaptive restraint system that accounts for occupant anthropometry variations to further enhance safety balance throughout the whole population. Methods Two thousand MADYMO full frontal impact crash simulations at 35 mph using two validated vehicle/restraint models representing a sedan and an SUV along with a parametric occupant model were conducted based on the maximal projection design of experiments, which considers varying occupant covariates (sex, stature, and body mass index) and vehicle restraint design variables (three for airbag, three for safety belt, and one for knee bolster). A Gaussian-process-based surrogate model was trained to rapidly predict occupant injury risks and the associated uncertainties. An optimization framework was formulated to seek the optimal adaptive restraint design policy that minimizes the population injury risk across a wide range of occupant sizes and shapes while maintaining a low difference in injury risks among different occupant subgroups. The effectiveness of the proposed method was tested by comparing the population-wise injury risks under the adaptive design policy and the traditional state-of-the-art design. Results Compared to the traditional state-of-the-art design for midsize males, the optimal design policy shows the potential to further reduce the joint injury risk (combining head, chest, and lower extremity injury risks) among the whole population in the sedan and SUV models. Specifically, the two subgroups of vulnerable occupants including tall obese males and short obese females had higher reductions in injury risks. Conclusions This study lays out a method to adaptively adjust vehicle restraint systems to improve safety balance. This is the first study where population-based crash simulations and machine-learning methods are used to optimize adaptive restraint designs for a diverse population. Nevertheless, this study shows the high injury risks associated with obese and female occupants, which can be mitigated via restraint adaptability.

Dataset Information

Restraint and Social Isolation Stressors Differentially Regulate Adaptive Immunity and Tumor Angiogenesis in a Breast Cancer Mouse Model.

Publications

Restraint and Social Isolation Stressors Differentially Regulate Adaptive Immunity and Tumor Angiogenesis in a Breast Cancer Mouse Model.

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