[Evaluation of Risk Factors for Immune-Related Adverse Events Associated with Treatment with Immune Checkpoint Inhibitors].

OBJECTIVE: Risk factors for immune-related adverse events(irAEs)associated with immune checkpoint inhibitors(ICIs) remain to be obscure. Therefore, we evaluated the patient background and clinical findings to identify risk factors for the development of irAEs. METHODS: The subjects consisted of 86 patients treated with ICIs between August 2018 and March 2020. They were classified into 2 groups who developed irAEs(irAE group)and did not develop irAEs(non-irAE group). RESULTS: The median age of the subjects was 70 years(39-84 years), and there were 65 males. The underlying disease was non-small cell lung cancer in 51 patients, gastric cancer in 14, renal cell cancer in 9, urothelial cancer in 11, and MSI-high small bowel cancer in 1. The irAE group, in whom treatment with ICIs was discontinued, included 16 patients(18.6%), and the non-irAE group included 70 patients(81.4%). The median number of treatment cycles was 8(1-91), and the median treatment period was 4 months(1-45 months). Evaluation in our hospital revealed no significant background factors, such as gender, age, or the treatment period, as risk factors for the development of eras. Lung disorders were frequently observed after the third-line treatment and in patients with non-small cell lung cancer. CONCLUSION: At present, the prediction of the development of irAEs is difficult. Careful follow-up observation and early irAEs management are important. In addition, further studies are necessary to identify risk factors for the development of irAEs.

Distribution of pituitary adenylate cyclase-activating polypeptide 2 in zebrafish brain.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multipotent neuropeptide with an amino acid sequence that is well conserved among vertebrates. In teleosts, including zebrafish, the PACAP gene (adcyap1) has been duplicated to yield adcyap1a (coding PACAP1) and adcyap1b (coding PACAP2). This study aims to determine the distribution of these PACAPs and their mRNAs in zebrafish. We generated a zebrafish PACAP2-specific antibody. Using real-time PCR, we observed that adcyap1b mRNA was primarily localized in the brain, with the highest level in the telencephalon, followed by the diencephalon. Using immunostaining of brain tissue samples, PACAP2 immunoreactivity was observed mainly in the telencephalon, hypothalamus, and cerebellum, and the immunopositive fibers formed a line to the habenula. PACAP2-immunopositive cells were observed in the ventral and dorsal regions of the telencephalon and in the hypothalamic nucleus of the diencephalon in the colchicine-injected brain. This distribution of PACAP2 suggests its involvement in higher brain functions in teleosts, such as learning and cognition, as well as instinctive behaviors such as feeding and emotional regulation.