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

Aftershock Distribution of the 1993 M6.6 Earthquake Off Noto Peninsula and its Relation to Tectonic Features

An M6.6 earthquake occurred on February 7,1993, around a sea rise extending southwest-northeast direction off the northeastern tip of Noto Peninsula. The hypocenters of the mainshock and aftershocks were located using telemetered data from university stations. The aftershocks during the first two days are concentrated in the narrow active fault zone along the northwest side of the rise. Other concentrations occurred along active faults on the southeast side of the rise. Most of the focal depths are 10-15km, consistent with the interpretation of T phases and pP phases recorded at some stations. Northwestward dipping 3-dimensional distributions for large aftershocks suggest two possible fault planes, which coincide well with the two fault planes of the CMT solution. The gross nature of the seismic fault is of a thrust type, which contradicts the strike slip solution estimated from the initial motions. The Noto region is part of the tectonic zone along the eastern margin of the Japan Sea, where zonal shortening due to compression is predominant as in the Japan Sea coast region in northern Honshu, Japan. The alignment of aftershocks along the topographic lineaments and submarine active faults may reflect this tectonism.1993年2月7日の能登半島沖地震は,禄剛崎沖の南西から北東へ伸びる海底の高まり付近で発生した.この余震の分布をできるだけ精密に求めるため京大防災研上宝観測所と東大地震研信越地震観測所の観測網のデータを統合して震源計算した.この地域の構造はきわめて不均質であり,その影響を極力さけるためもっとも震源域に近い観測点を用いて地震決定を行なった

Degeneration of patellar cartilage in patients with recurrent patellar dislocation following conservative treatment: evaluation with delayed gadolinium-enhanced magnetic resonance imaging of cartilage

ObjectiveTo examine the characteristics of cartilage degeneration in patients with recurrent patellar dislocation (RPD) following conservative treatment using delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC).DesignThis study evaluated three groups of knees: group I, 35 knees from both knees of patients with bilateral RPD and dislocated side knees of patients with unilateral RPD; group II, 15 non-dislocated side knees of patients with unilateral RPD; and group III, 20 knees from both knees of healthy volunteers. Differences in post-contrast T1 [T1(Gd)] of cartilage at both medial and lateral facets between groups I, II and III were analyzed. For group I, possible relationships were evaluated between T1(Gd) of cartilage and patient age, length of time between the initial dislocation and MRI and the total number of dislocations between the initial dislocation and MRI for both medial and lateral facets.ResultsThe mean T1(Gd) of cartilage at medial facets for groups I, II and III were 411+- 46 ms, 465 +- 38 ms and 490 +- 29 ms, respectively; there were significant differences between these means (P < 0.05). The mean T1(Gd) of cartilage at lateral facets for groups I, II and III were 426 +- 53 ms, 466 +- 45 ms and 510 +- 36 ms, respectively; there were also significant differences between these means (P < 0.05). Significant correlations were observed between T1(Gd) of cartilage for both medial and lateral facets and length of time between the initial dislocation and MRI (P < 0.05). No other correlations were significant.ConclusiondGEMRIC may be a useful method to monitor glycosaminoglycan concentration in patients with RPD following conservative treatment