FDR-gem plus S-1 with RT for pancreatic cancer

Purpose: This study was conducted to identify the maximum-tolerated dose (MTD) of fixed-dose-rate gemcitabine (FDR-gem) administered concurrently with S-1 and radical radiation for locally advanced pancreatic cancer (LAPC) and to provide efficacy and safety data. Methods: Patients with unresectable pancreatic cancer confined to the pancreatic region were treated with FDR-gem (300-400mg/m2, 5mg/m2/min) on days 1, 8, 22, 29 and 60mg/m2 of S-1 orally on days 1-14, 22-35. A total radiation dose of 50.4 Gy (1.8 Gy/day, 28fractions) was delivered concurrently. Results: Twenty-five patients were enrolled; all were evaluable for toxicity assessment. In phase I, eight patients were treated in sequential cohorts of three to five patients per dose level. The MTD was reached at level 2, and dose-limiting toxicities were neutropenia and thrombocytopenia. The recommended doses were 300mg/m2 of gemcitabine and 60mg/m2 of S-1 daily. The overall response rate was 25% and disease control rate (partial response plus stable disease) was 92%. The progression-free survival was 11.0 months. The median overall survival and 1-year survival rate were 16.0 months and 73%, respectively. Conclusion: The combination of FDR-gem and S-1 with radiation is a feasible regimen that shows favorable antitumor activity with an acceptable safety profile in patients with LAPC

体組成と脈波伝播速度からみた思春期女性の生活習慣病危険因子の検討

We reviewed what kind of factors became lifestyle-related diseases risk factors in girls at puberty. The purpose of this study was to gather data for the primary prevention of lifestyle-related diseases. Subjects were 57 basically healthy girls at the age of puberty，from seventh grade to twelfth grade. We measured body composition including bone density of the whole body using Dual Energy X-ray Absorptiometry. We used form PWV/ABI（Omron Colin Co.，Ltd.，Japan）for the measurement of Pulse Wave Velocity. It became clear that there was a danger of elevated baPWV values in girls whose percentage of body fat and soft tissue fat rate were low. On the other hand，it became clear that bone mineral density（BMD）was likely high in subjects whose percentage of body fat and soft tissue fat rate were high. It is thought that a higher-than-standard percent of body fat becomes an advantage for elevated bone density. From these results，it was concluded that lifestyle-related disease risk factors for girls at puberty with a high rate of body fat are low

思春期女性の踵骨骨評価値に対する利き足の影響に関する検討

When I perform bone evaluation by supersonic wave measurement，I only evaluate the right foot without considering the subject’s laterality，or potential differences between right and left foot bone density. Puberty is the period during which bone density rises，and during which the influence of mechanical stress is considered great，and evaluation of the right foot has been considered sufficient to clarify this effect. From the viewpoint of general health and prevention of osteoporosis we must measure one’s bone density in puberty， raise the peak bone mass，and maintain it. The present experiment was performed to clarify what kind of influence laterality of foot and exercise habits had on the bone density of the right calcaneus. Exercise habits did not have much influence on the bone density rise if the right foot was non-dominant. However，a meaningful connection was recognized between exercise habits and bone density rise if the right foot was dominant. From these results，it was thought that the measurement of calcaneus bone density by a supersonic wave method in puberty is more effective if the dominant foot is used

若年女性の生活習慣と脂質代謝の関連に関する検討

The purpose of this study is to review the factors influencing lipid metabolism of young women in terms of both exercise and nutrition. From the side of nutrition，we reviewed how lipid metabolism is influenced by taking a commercial fish oil supplement（LIQUAMEN）. Total cholesterol deteriorated significantly by taking LIQUAMEN. Improvement of lipid metabolism by LIQUAMEN was suggested. The value of HDL-cholesterol，adiponectin，and leptin were significantly lower in the group of living activity strength Ⅱ while the values of TG and TNF-α increased significantly. This result suggested the possibility that lipid metabolism deteriorated in subjects whose activity was below a certain amount. It also suggested the possibility that lipid metabolism improved in those whose activity was above a certain amount. In the body fat-to-weight ratio， the living activity strengthⅢ・ Ⅳ group showed a significantly lower tendency compared to the group of living activity strength Ⅱ and the group of living activity strengthⅢ・ Ⅳ . This finding suggested that if activity was greater than a certain amount，the body fat-to-weight ratio tended to be comparatively low

Role of macrophage autophagy in postoperative pain and inflammation in mice

Abstract Background Postoperative pain and inflammation are significant complications following surgery. Strategies that aim to prevent excessive inflammation without hampering natural wound-healing are required for the management of postoperative pain and inflammation. However, the knowledge of the mechanisms and target pathways involved in these processes is lacking. Recent studies have revealed that autophagy in macrophages sequesters pro-inflammatory mediators, and it is therefore being recognized as a crucial process involved in regulating inflammation. In this study, we tested the hypothesis that autophagy in macrophages plays protective roles against postoperative pain and inflammation and investigated the underlying mechanisms. Methods Postoperative pain was induced by plantar incision under isoflurane anesthesia in mice lacking macrophage autophagy (Atg5flox/flox LysMCre +) and their control littermates (Atg5flox/flox). Mechanical and thermal pain sensitivity, changes in weight distribution, spontaneous locomotor activity, tissue inflammation, and body weight were assessed at baseline and 1, 3, and 7 days after surgery. Monocyte/macrophage infiltration at the surgical site and inflammatory mediator expression levels were evaluated. Results Atg5flox/flox LysMCre + mice compared with the control mice exhibited lower mechanical and thermal pain thresholds and surgical/non-surgical hindlimb weight-bearing ratios. The augmented neurobehavioral symptoms observed in the Atg5flox/flox LysMCre + mice were associated with more severe paw inflammation, higher pro-inflammatory mediator mRNA expression, and more monocytes/macrophages at the surgical site. Conclusion The lack of macrophage autophagy augmented postoperative pain and inflammation, which were accompanied by enhanced pro-inflammatory cytokine secretion and surgical-site monocyte/macrophage infiltration. Macrophage autophagy plays a protective role in postoperative pain and inflammation and can be a novel therapeutic target

Meningiomas in patients with neurofibromatosis type 2 predominantly comprise ‘immunogenic subtype’ tumours characterised by macrophage infiltration

Abstract Although recent molecular analyses revealed that sporadic meningiomas have various genetic, epigenetic, and transcriptomic profiles, meningioma in patients with neurofibromatosis type 2 (NF2) have not been fully elucidated. This study investigated meningiomas' clinical, histological, and molecular characteristics in NF2 patients. A long-term retrospective follow-up (13.5 ± 5.5 years) study involving total 159 meningiomas in 37 patients with NF2 was performed. Their characteristics were assessed using immunohistochemistry (IHC), bulk-RNA sequencing, and copy number analysis. All variables of meningiomas in patients with NF2 were compared with those in 189 sporadic NF2-altered meningiomas in 189 patients. Most meningiomas in NF2 patients were stable, and the mean annual growth rate was 1.0 ± 1.8 cm3/year. Twenty-eight meningiomas (17.6%) in 25 patients (43.1%) were resected during the follow-up period. WHO grade I meningiomas in patients with NF2 were more frequent than in sporadic NF2-altered meningiomas (92.9% vs. 80.9%). Transcriptomic analysis for patients with NF2/sporadic NF2-altered WHO grade I meningiomas (n = 14 vs. 15, respectively) showed that tumours in NF2 patients still had a higher immune response and immune cell infiltration than sporadic NF2-altered meningiomas. Furthermore, RNA-seq/IHC-derived immunophenotyping corroborated this enhanced immune response by identifying myeloid cell infiltration, particularly in macrophages. Clinical, histological, and transcriptomic analyses of meningiomas in patients with NF2 demonstrated that meningiomas in NF2 patients showed less aggressive behaviour than sporadic NF2-altered meningiomas and elicited a marked immune response by identifying myeloid cell infiltration, particularly of macrophages