A PSMA-targeted Tri-specific Killer Engager enhances NK cell cytotoxicity against prostate cancer.

Natural killer (NK) cell tumor infiltration is associated with good prognosis in patients with metastatic castration-resistant prostate cancer (mCRPC). NK cells recognize and kill targets by a process called natural cytotoxicity. We hypothesized that promoting an antigen-specific synapse with co-activation may enhance NK cell function in mCRPC.

Balanced engagement of activating and inhibitory receptors mitigates human NK cell exhaustion.

NK cell exhaustion is caused by chronic exposure to activating stimuli during viral infection, tumorigenesis, and prolonged cytokine treatment. Evidence suggests that exhaustion may play a role in disease progression. However, relative to T cell exhaustion, the mechanisms underlying NK cell exhaustion and methods of reversing it are poorly understood.

Understanding the stimulus effects of nicotine and bupropion in a drug-drug discriminated goal-tracking task.

Rationale: Bupropion is a non-nicotine medication for smoking cessation that has overlapping stimulus effects with nicotine as demonstrated in drug discrimination studies. Whether these shared stimulus effects will alter acquisition or maintenance of a discrimination between nicotine and bupropion is unknown.

Objective: We sought to test this possibility using the drug discriminated goal-tracking (DGT) task and whether discrimination training history affected generalization and substitution tests.

Menthol blunts the interoceptive discriminative stimulus effects of nicotine in female but not male rats.

Rationale: Menthol is a widely used tobacco constituent that has shown to enhance nicotine's reinforcing effects.

Objective: To determine whether injected menthol also alters nicotine's stimulus effects, we used a drug discrimination task.

Methods: A total of 57 adult Sprague-Dawley rats (28M, 29F) received 20 positive and 20 negative days (intermixed) of discrimination training.

Investigating the interoceptive stimulus effects of injected menthol in rats.

Menthol is a commonly used tobacco constituent that also modulates nicotine reinforcement and metabolism. Little is known about the stimulus effects of menthol that mediate the behavior associated with reinforcement-learning. Our present research explored the interoceptive stimulus effects of intraperitoneally administered menthol in a drug discrimination task.