Association of Baseline Serum Levels of CXCL5 With the Efficacy of Nivolumab in Advanced Melanoma

Anti-programmed cell death protein 1 (PD1) antibodies are in wide use for the treatment of various cancers. PD1 antibody-based immunotherapy, co-administration of nivolumab and ipilimumab, is one of the optimal immunotherapies, especially in advanced melanoma with high tumor mutation burden. Since this combined therapy leads to a high frequency of serious immune-related adverse events (irAEs) in patients with advanced melanoma, biomarkers are needed to evaluate nivolumab efficacy to avoid serious irAEs caused by ipilimumab. This study analyzed baseline serum levels of CXCL5, CXCL10, and CCL22 in 46 cases of advanced cutaneous melanoma treated with nivolumab. Baseline serum levels of CXCL5 were significantly higher in responders than in non-responders. In contrast, there were no significant differences in baseline serum levels of CXCL10 and CCL22 between responders and non-responders. These results suggest that baseline serum levels of CXCL5 may be useful as a biomarker for identifying patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy

Serum Level of Soluble CD163 May Be a Predictive Marker of the Effectiveness of Nivolumab in Patients With Advanced Cutaneous Melanoma

Antibodies against programmed cell death protein 1, such as nivolumab and pembrolizumab, are widely used for treating various cancers, including advanced melanoma. Nivolumab significantly prolongs survival in patients with metastatic melanoma, and sequential administration with lipilimumab may improve outcomes when switched at the appropriate time. Biomarkers are therefore needed to evaluate nivolumab efficacy soon after first administration. This study analyzed serum levels of soluble cluster of differentiation 163 (sCD163) in 59 cases of advanced cutaneous melanoma and 16 cases of advanced mucosal melanoma treated using nivolumab. Serum levels of sCD163 were significantly increased after 6 weeks in responders compared to non-responders after initial administration of nivolumab for cutaneous melanoma. In contrast, no significant difference between responders and non-responders was seen among patients with non-cutaneous melanoma. These results suggest that sCD163 may be useful as a biomarker for selecting patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy

A possible mechanism of horseback riding on dynamic trunk alignment

The study aimed to clarify the regularity of the motions of horse's back, rider's pelvis and spine associated with improvement of rider's dynamic trunk alignment. The study used a crossover design, with exercise using the horseback riding simulator (simulator hereafter) as the control condition. The experiments were conducted at Tokyo University of Agriculture Bio-therapy Center. The sample consisted of 20 healthy volunteers age 20–23 years. Participants performed 15-min sessions of horseback riding with a Hokkaido Pony and exercise using the simulator in experiments separated by ≥2 weeks. Surface electromyography (EMG) after horseback riding revealed decreased activity in the erector spinae. Exploratory data analysis of acceleration and angular velocity inferred associations between acceleration (Rider's neck/longitudinal axis [Y hereafter]) and angular velocity (Horse saddle/Y) as well as angular velocity (Rider's pelvis/Y) and angular velocity (Horse saddle/Y). Acceleration (Rider's neck/Y) tended to be associated with angular velocity (Rider's pelvis/Y). Surface EMG following exercise revealed decreased activity in the rectus abdominis and erector spinae after the simulator exercise. Horseback riding improved the rider's dynamic trunk alignment with a clear underlying mechanism, which was not observed with the simulator

Magnetic Properties of Shandite-Phase Co3−xFexSn2S2(x=0–1.0)\mathrm{Co_{3− x}Fe_{x}Sn_{2}S_{2}(x = 0–1.0)} Obtained with High Pressure Synthesis

In situ high-pressure (HP) and high-temperature (HT) energy dispersive X-ray diffraction of shandite-phase Co$_{3− x}$Fe$_x$Sn$_2$S$_2$ was carried out in the pressure range of 0–11 GPa and temperature range from room temperature to 1673 K. The Fe solubility limit xmax rises from below 0.6 up to 1.0 following HP and HT heat treatments. The ferromagnetic transition temperatures (TC) of Co$_{3− x}$Fe$_x$Sn$_2$S$_2$ decreases with x, and TC changes from 175(5) K (x = 0) to 68(3) K (x = 1), and this result is in qualitative agreement with theoretical calculations using the density functional theory with a pseudopotential. These results indicate that HP and HT techniques enable us to expand the solubility limits and magnetic phase diagrams in sulfides

Serum levels of soluble CD163 and CXCL5 may be predictive markers for immune-related adverse events in patients with advanced melanoma treated with nivolumab: a pilot study

Antibodies against PD-1, such as nivolumab and pembrolizumab, are widely used in the treatment of various cancers including advanced melanoma. The anti-PD-1 Ab significantly prolongs survival in patients with metastatic melanoma, and its administration in combination with local or systemic therapy may also lead to improved outcomes. Although anti-PD-1 Ab-based combined therapy might be effective for the treatment of advanced melanoma, the associated risk of irAEs is an important consideration. Therefore, being able to predict irAEs is of great interest to oncologists. The purpose of this study was to evaluate the value of using serum levels of sCD163 and CXCL5 to predict irAEs in patients with advanced melanoma who were administered nivolumab. To this end, we analyzed these serum levels in 46 cases of advanced melanoma treated with nivolumab. In addition, the tumor stroma was evaluated by immunohistochemistry and immunofluorescence. We measured the serum levels of sCD163 and CXCL5 on day 0 (immediately before nivolumab administration) and day 42. The serum absolute levels of sCD163 were significantly increased in patients who developed AEs (p = 0.0018). Although there was no significant difference in serum levels of CXCL5, the absolute value of CXCL5 could at least be a supportive marker for the increased absolute levels of serum sCD163. This study suggests that sCD163 and CXCL5 may serve as possible prognostic biomarkers for irAEs in patients with advanced melanoma treated with nivolumab

Anti-proliferative protein Tob negatively regulates CPEB3 target by recruiting Caf1 deadenylase

Shortening of the 3′ poly(A) tail by deadenylation promotes mRNA decay. Here, the authors show that the anti-proliferative protein Tob binds to the cytoplasmic polyadenylation element-binding protein CPEB3 and recruits the deadenylase Caf1 to target mRNAs to promote deadenylation and mRNA turnover