The role of the bias in Th-subset 1/2/17 on pathogenesis of atopic dermatitis

課題番号：2059133

The benefit of a sentinel lymph node biopsy and adjuvant therapy in thick (>4 mm) melanoma: multicenter, retrospective study of 291 Japanese patients

The benefit of a sentinel lymph node (SLN) biopsy and adjuvant therapy for patients with thick (>4 mm) melanoma has not been well studied in the Asian population. We examined the benefit of an SLN biopsy and adjuvant therapy on prognosis in Japanese patients with thick melanoma. A review of the melanoma database collected from 26 institutions in Japan identified 291 patients with thick melanoma between 2005 and 2010. Univariate and multivariate analyses were performed to evaluate the factors predictive of the overall survival (OS) and the disease-free survival (DFS). Of the 242 patients with thick melanoma who underwent an SLN biopsy, the results for 96 (40%) were positive. On multivariate analysis, increased Breslow thickness (relative risk, 1.11; 95% confidence interval, 1.05–1.17; P=0.0002) and SLN metastasis (2.14; 1.04–4.43; P=0.040) were associated with a poor OS. Increased Breslow thickness (1.11; 1.04–1.18; P =0.0018), ulceration (3.11; 1.25–7.72; P=0.014), satellitosis (3.89; 1.62–9.31; P=0.0023), and SLN metastasis (2.24; 1.16–4.36; P=0.017) were associated with DFS. Adjuvant chemotherapy had no impact on either OS or DFS. Adjuvant use of a monthly dermal injection of interferon-β (IFN-β) was associated with a improvement in both OS (0.34; 0.17–0.67; P=0.0022) and DFS (0.42; 0.20–0.86; P=0.018). An SLN biopsy provided useful prognostic information and the adjuvant use of IFN-β improved both OS and DFS in Japanese patients with thick melanoma. These results were consistent with those of previous studies carried out on a white population. Therefore, we suggest that an SLN biopsy and adjuvantIFN should be considered for patients with thick melanoma irrespective of the Breslow thickness or ethnicity

Cytokine biomarkers to predict antitumor responses to nivolumab suggested in a phase 2 study for advanced melanoma

Promising antitumor activities of nivolumab, a fully humanized IgG4 inhibitor antibody against the programmed death-1 protein, were suggested in previous phase 1 studies. The present phase 2, single-arm study (JAPIC-CTI #111681) evaluated the antitumor activities of nivolumab and explored its predictive correlates in advanced melanoma patients at 11 sites in Japan. Intravenous nivolumab 2 mg/kg was given repeatedly at 3-week intervals to 35 of 37 patients enrolled from December 2011 to May 2012 until they experienced unacceptable toxicity, disease progression, or complete response. Primary endpoint was objective response rate. Serum levels of immune modulators were assessed at multiple time points. As of 21 October 2014, median response duration, median progression-free survival, and median overall survival were 463 days, 169 days, and 18.0 months, respectively. The overall response rate and 1- and 2-year survival rates were 28.6%, 54.3%, and 42.9%, respectively. Thirteen patients remained alive at the end of the observation period and no deaths were drug related. Grade 3–4 drug-related adverse events were observed in 31.4% of patients. Pretreatment serum interferon-γ, and interleukin-6 and -10 levels were significantly higher in the patients with objective tumor responses than in those with tumor progression. In conclusion, giving repeated i.v. nivolumab had potent and durable antitumor effects and a manageable safety profile in advanced melanoma patients, strongly suggesting the usefulness of nivolumab for advanced melanoma and the usefulness of pretreatment serum cytokine profiles as correlates for predicting treatment efficacy

Single nucleotide polymorphism-based genome-wide linkage analysis in Japanese atopic dermatitis families

<p>Abstract</p> <p>Background</p> <p>Atopic dermatitis develops as a result of complex interactions between several genetic and environmental factors. To date, 4 genome-wide linkage studies of atopic dermatitis have been performed in Caucasian populations, however, similar studies have not been done in Asian populations. The aim of this study was to identify chromosome regions linked to atopic dermatitis in a Japanese population.</p> <p>Methods</p> <p>We used a high-density, single nucleotide polymorphism genotyping assay, the Illumina BeadArray Linkage Mapping Panel (version 4) comprising 5,861 single nucleotide polymorphisms, to perform a genome-wide linkage analysis of 77 Japanese families with 111 affected sib-pairs with atopic dermatitis.</p> <p>Results</p> <p>We found suggestive evidence for linkage with 15q21 (LOD = 2.01, NPL = 2.87, <it>P </it>= .0012) and weak linkage to 1q24 (LOD = 1.26, NPL = 2.44, <it>P </it>= .008).</p> <p>Conclusion</p> <p>We report the first genome-wide linkage study of atopic dermatitis in an Asian population, and novel loci on chromosomes 15q21 and 1q24 linked to atopic dermatitis. Identification of novel causative genes for atopic dermatitis will advance our understanding of the pathogenesis of atopic dermatitis.</p

<所内学術研究成果報告>H. 「環境保全・地球環境温暖化防止をターゲットとする新パルプ資源ケナフの栽培と利用に関する研究」

本研究は, エコマテリアルとしての非木材繊維資源に最も適切である一年生植物ケナフ(Hibiscus cannabinus L.)の栽培とその利用を目的に, 1993年より開始した研究である。従来の成果は, すでに本年報1992,\u2794,\u2795,\u2796,\u2797,\u2798,および\u2799年に報告した。特に従来のケナフ栽培の成果の総決算として, 1998年より平塚市および平塚ケナフ普及協会との共同研究が行われてきた。特に, 平塚市では休耕田対策としてケナフの栽培を推奨し, 現在, 栽培したケナフのパルプ化と紙製造を行って市政に還元している。この現状はさらに展開し, 平塚市のみならず日本全国にその輪が広がり大きな活動となっている。これらの栽培や利用は最も基礎的な指導と, より学術的な研究成果の提供が常に必要であり, この点を最も重要な課題としている。さらに, 環境教育に対する展開を学校, 公民館などを中心に行い, 2000年度は, 平塚キャンパスで市内6小学校の生徒28名のケナフ教育を行った。まお, 研究室内では, 栽培研究の他に, a)種子の発芽阻害実験, b)海水による阻害実験, c)生長に伴うクロロフィル量および水分量の測定実験, d)光合成測定実験, e)花の成分(色素)研究, f)葉など各器官の成分研究などを行っている。取り扱った種類も, ローゼル(H. sabdariffa L.)類も加えると30種に近い