BackgroundPreclinical studies have implicated excess release of catecholamines and prostaglandins in the mediation of prometastatic processes during surgical treatment of cancer. In this study, we tested the combined perioperative blockade of these pathways in patients with colorectal cancer (CRC).MethodsIn a randomized, double‐blind, placebo‐controlled biomarker trial involving 34 patients, the β‐blocker propranolol and the COX2‐inhibitor etodolac were administered for 20 perioperative days, starting 5 days before surgery. Excised tumors were subjected to whole genome messenger RNA profiling and transcriptional control pathway analyses.ResultsDrugs were well‐tolerated, with minor complications in both the treatment group and the placebo group. Treatment resulted in a significant improvement (P < .05) of tumor molecular markers of malignant and metastatic potential, including 1) reduced epithelial‐to‐mesenchymal transition, 2) reduced tumor infiltrating CD14+ monocytes and CD19+ B cells, and 3) increased tumor infiltrating CD56+ natural killer cells. Transcriptional activity analyses indicated a favorable drug impact on 12 of 19 a priori hypothesized CRC‐related transcription factors, including the GATA, STAT, and EGR families as well as the CREB family that mediates the gene regulatory impact of β‐adrenergic– and prostaglandin‐signaling. Alterations observed in these transcriptional activities were previously associated with improved long‐term clinical outcomes. Three‐year recurrence rates were assessed for long‐term safety analyses. An intent‐to‐treat analysis revealed that recurrence rates were 12.5% (2/16) in the treatment group and 33.3% (6/18) in the placebo group (P = .239), and in protocol‐compliant patients, recurrence rates were 0% (0/11) in the treatment group and 29.4% (5/17) in the placebo group (P = .054).ConclusionsThe favorable biomarker impacts and clinical outcomes provide a rationale for future randomized placebo‐controlled trials in larger samples to assess the effects of perioperative propranolol/etodolac treatment on oncological clinical outcomes.

Although older adults rarely outperform young adults on learning tasks, here they surpassed their younger counterparts both on answering more semantic-memory general-information questions correctly, but also on correcting their mistakes. While both young and older adults exhibited a ‘hypercorrection effect,’ correcting their high-confidence errors more than their low-confidence errors, the effect was larger for young adults. Whereas older adults corrected high-confidence errors to the same extent as did young adults they outdid the young in also correcting their low-confidence errors. Their event related potentials (ERPs) point to an attentional explanation: both groups showed a strong attention-related P3a in conjunction with high-confidence error feedback, but the older adults also showed strong P3a’s to low-confidence error feedback. Indeed, the older adults were able to rally their attentional resources to learn the true answers regardless of their original confidence in the error and regardless of their familiarity with the answers.

The field of psychoneuroimmunology (PNI) examines interactions among psychological and behavioral states, the brain, and the immune system. Research in PNI has elegantly documented effects of stress at multiple levels of the neuro‐immune network, with profound implications for both physical and mental health. In this review, we consider how the neuro‐immune network might be influenced by “positive” psychological and behavioral states, focusing on positive affect, eudaimonic well‐being, physical activity, and sleep. There is compelling evidence that these positive states and behaviors are associated with changes in immune activity in the body, including reductions in peripheral inflammatory processes relevant for physical health. Growing evidence from animal models also suggests effects of positive states on immune cells in the brain and the blood‐brain barrier, which then impact critical aspects of mood, cognition, and behavior. Tremendous advances are being made in our understanding of neuro‐immune dynamics; one of the central goals of this review is to highlight recent preclinical research in this area and consider how we can leverage these findings to investigate and cultivate a healthy neuro‐immune network in humans.

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