Serum immune modulators during the first cycle of anti-PD-1 antibody therapy in non-small cell lung cancer: Perforin as a biomarker.

BACKGROUND: Currently used biomarkers for immunotherapy are inadequate because they are only based on tumor properties. In view of microenvironment changes by tumors, host immunity should be considered, which may result in identifying more accurate and easily detectable biomarkers for daily clinical practice. Here, we assessed serum immune-modulating factor levels for the response to anti-PD-1 antibodies during the first cycle in non-small cell lung cancer (NSCLC) patients. METHODS: Serum was collected from patients with advanced NSCLC treated with nivolumab or pembrolizumab at several time points during the first cycle. We applied the enzyme-linked immunosorbent assays (ELISAs) and multiplex assays to measure the levels of immune modulators. RESULTS: A total of 40 patients treated with nivolumab and 26 patients treated with pembrolizumab were studied. By ELISA, serum perforin, but not granzyme B, was measured in all samples. By multiplex assay, 10 immune modulators, including granzyme B, were measured in some, but not all, samples. Serum baseline perforin levels were strongly associated with increased progression-free survival (PFS) and overall survival (OS) times. Sequential changes in perforin levels during the first cycle were weakly associated with the clinical outcome. CONCLUSIONS: Serum baseline perforin levels may be used to predict the prognosis of NSCLC patients treated with anti-PD-1 antibody therapy. KEY POINTS: To identify a useful predictive marker for anti-PD-1 antibody therapy, using blood samples might be helpful. Serum baseline perforin levels were closely associated with prognosis with anti-PD-1 antibody therapy in non-small cell lung cancer.

Construction of reporter gene assays using CWP and PDR mutant yeasts for enhanced detection of various sex steroids.

BACKGROUND: Sex steroid hormone receptors are classified into three classes of receptors: estrogen receptors (ER) α and ß, androgen receptor (AR), and progesterone receptor (PR). They belong to the nuclear receptor superfamily and activate their downstream genes in a ligand-dependent manner. Since sex steroid hormones are involved in a wide variety of physiological processes and cancer development, synthetic chemical substances that exhibit sex steroid hormone activities have been applied as pharmaceuticals and consumed in large amounts worldwide. They are potentially hazardous contaminants as endocrine disruptors in the environment because they may induce inappropriate gene expression mediated by sex steroid hormone receptors in vivo. RESULTS: To develop simple reporter gene assays with enhanced sensitivity for the detection of sex steroid hormones, we newly established mutant yeast strains lacking the CWP and PDR genes encoding cell wall mannoproteins and plasma membrane drug efflux pumps, respectively, and expressing human ERα, ERß, AR, and PR. Reporter gene assays with mutant yeast strains responded to endogenous and synthetic ligands more strongly than those with wild-type strains. Sex steroid hormone activities in some pharmaceutical oral tablets and human urine were also detectable in these yeast assays. CONCLUSIONS: Yeast reporter gene assay systems for all six steroid hormone receptors, including previously established glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) assay yeasts, are now available. Environmental endocrine disrupters with steroid hormone activity will be qualitatively detectable by simple and easy procedures. The yeast-based reporter gene assay will be valuable as a primary screening tool to detect and evaluate steroid hormone activities in various test samples. Our assay system will strongly support the detection of agonists, antagonists, and inverse agonists of steroid hormone receptors in the field of novel drug discovery and assessments of environmental pollutants.

Reexamination of mood-mediation hypothesis of background-music-dependent effects in free recall.

The present study reexamined the mood-mediation hypothesis for explaining background-music-dependent effects in free recall. Experiments 1 and 2 respectively examined tempo- and tonality-dependent effects in free recall, which had been used as evidence for the mood-mediation hypothesis. In Experiments 1 and 2, undergraduates (n = 75 per experiment) incidentally learned a list of 20 unrelated words presented one by one at a rate of 5 s per word and then received a 30-s delayed oral free-recall test. Throughout the study and test sessions, a piece of music was played. At the time of test, one third of the participants received the same piece of music with the same tempo or tonality as at study, one third heard a different piece with the same tempo or tonality, and one third heard a different piece with a different tempo or tonality. Note that the condition of the same piece with a different tempo or tonality was excluded. Furthermore, the number of sampled pieces of background music was increased compared with previous studies. The results showed neither tempo- nor tonality-dependent effects, but only a background-music-dependent effect. Experiment 3 (n = 40) compared the effects of background music with a verbal association task and focal music (only listening to musical selections) on the participants' moods. The results showed that both the music tempo and tonality influenced the corresponding mood dimensions (arousal and pleasantness). These results are taken as evidence against the mood-mediation hypothesis. Theoretical implications are discussed.