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

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.</jats:p

Please address correspondence to Raluca Budiu. Verification of Sentences Containing Anaphoric Metaphors: An ACT-R Computational Model

In a sentence-verification experiment, Budiu and Anderson (2001) found that participants took longer to respond to sentences containing anaphoric metaphors than to corresponding sentences containing literals. We present a computational model of this experiment, based on INP, a more general ACT-R (Anderson &amp; Lebiere, 1998) model of sentence processing that has been used to explain various other linguistic and memory phenomena (Budiu &amp; Anderson, 2000; Budiu, 2001; Budiu &amp; Anderson, in preparation). This model shows that metaphors take longer to be processed because their low similarity to their antecedents generates an initial failure of comprehension; that failure may be resolved through an expensive reevaluation process at the end of the sentence, in light of the supplemental information brought in by the other words in the sentence