進行膀胱癌に高発現するGPNMBを標的とした環状ペプチドの開発

科学研究費助成事業 研究成果報告書：若手研究(B)2016-2017課題番号 : 16K2012

Atorvastatin improves disease activity of nonalcoholic steatohepatitis partly through its tumour necrosis factor-alpha-lowering property

Background: We have previously found that atorvastatin decreases liver injury markers in patients with nonalcoholic steatohepatitis. However, how atorvastatin treatment ameliorates the disease activity in nonalcoholic steatohepatitis patients remains unknown. Aims: We examined here which anthropometric, metabolic and inflammatory variables were improved and related with amelioration of disease activity in atorvastatin-treated nonalcoholic steatohepatitis patients. Methods: Forty-two biopsy-proven nonalcoholic steatohepatitis patients with dyslipidemia were enrolled. Patients were treated with atorvastatin (10 mg/day) for 12 months. Results: Atorvastatin significantly decreased liver transaminase, gamma-glutamyl transpeptidase, low-density lipoprotein-cholesterol, triglycerides, type IV collagen, and tumour necrosis factor-alpha levels, whilst it increased adiponectin and high-density lipoprotein-cholesterol. Atorvastatin improved nonalcoholic fatty liver disease activity score and increased liver to spleen density ratio. Multiple stepwise regression analysis revealed that gamma-glutamyl transpeptidase, tumour necrosis factor-alpha and liver to spleen density ratio ( inversely) were independently associated with nonalcoholic fatty liver disease activity score. Aspartate aminotransferase, low-density lipoprotein-cholesterol and nonalcoholic fatty liver disease activity score were independent determinants of decreased liver to spleen density ratio. Conclusion: The present study suggests that atorvastatin improves the disease activity of nonalcoholic steatohepatitis partly via its tumour necrosis factor-alpha-lowering property. (C) 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved

Suppression of Interferon-induced Oligo-2\u27, 5\u27-adenylate Synthetase Induction in Human Hepatoma Cell Line, Li-7

Induction of oligo-2\u27, 5\u27-adenylate synthetase (2-5AS) activity by interferon (IFN) was investigated in a human hepatoma cell line, Li-7 cells. Little induction of 2-5AS activity by IFN was demonstrated in Li-7 cells in comparison with other types of cell lines including Ramos, NC-37, FL, Co-3. Furthermore, failure to induce 2-5AS was much clearer in old-cultured cells. Cell growth inhibition by IFN was demonstrated in only high titers of IFN (>10? IU/ml), in which the enzyme had one hundred fold higher activity than that of untreated cells. Poor induction of 2-5AS was in part the result of some inhibitor presented in cellular extracts of Li-7 cells and the decreased level of 2-5AS mRNA transcription

ReMagicMirror: Action Learning Using Human Reenactment with the Mirror Metaphor

MMM 2017: 23rd International Conference on Multimedia Modeling, Jan 4-6, 2017, Reykjavik, Iceland,We propose ReMagicMirror, a system to help people learn actions (e.g., martial arts, dances). We first capture the motions of a teacher performing the action to learn, using two RGB-D cameras. Next, we fit a parametric human body model to the depth data and texture it using the color data, reconstructing the teacher’s motion and appearance. The learner is then shown the ReMagicMirror system, which acts as a mirror. We overlay the teacher’s reconstructed body on top of this mirror in an augmented reality fashion. The learner is able to intuitively manipulate the reconstruction’s viewpoint by simply rotating her body, allowing for easy comparisons between the learner and the teacher. We perform a user study to evaluate our system’s ease of use, effectiveness, quality, and appeal

Effect of Interferon on Cells Persistently Infected with Human T Cell Leukemia Virus (HTLV-I)

Spontaneous production of interferon-gamma (IFN- γ) was shown in four (MT-1, MT-2, SMT-1 and HUT 102) of five human T-lymphoblastoid cell lines persistently infected with human T cell leukemea virus type I (MT-1, MT-2, SMT-1, HUT 102 and OKM-2). These four cell lines were not susceptible to the antivirus effect of IFN. In contrast, the multiplication of vesicular stomatitis virus (VSV) was restricted in the nonproducer cell line of IFN, OKM-2 cells by treatment of IFN- α or IFN- γ. Anti-proliferation effect of IFN w as investigated in producer cell line of IFN (MT-2 and SMT-1) and non-producer cell line of IFN (OKM-2). The growth of MT-2 cells was not affected by IFN- α or by IFN- γ. However, SMT-1 and OKM-2 cells were affected by treatment with externally added IFN-α

Efficacy of surgical management for recurrent intrahepatic cholangiocarcinoma: A multi-institutional study by the Okayama Study Group of HBP surgery

Background The prognosis of intrahepatic cholangiocarcinoma (ICC) has been poor, because of the high recurrence rate even after curative surgery. This study aimed to evaluate the prognostic impact of surgical resection of recurrent ICC. Patients and methods A total of 345 cases of ICC who underwent hepatectomy with curative intent in 17 institutions were retrospectively analyzed, focusing on recurrence patterns and treatment modalities for recurrent ICC. Results Median survival time and overall 5-year recurrence-free survival rate were 17.8 months and 28.5%, respectively. Recurrences (n = 223) were classified as early (recurrence at 1 year, n = 92). Median survival time was poorer for early recurrence (16.3 months) than for late recurrence (47.7 months,p<0.0001). Treatment modalities for recurrence comprised surgical resection (n = 28), non-surgical treatment (n = 134), and best supportive care (BSC) (n = 61). Median and overall 1-/5-year survival rates after recurrence were 39.5 months and 84.6%/36.3% for surgical resection, 14.3 months and 62.5%/2.9% for non-surgical treatment, and 3 months and 4.8%/0% for BSC, respectively (p<0.0001). Multivariate analysis identified early recurrence, simultaneous intra- and extrahepatic recurrence, and surgical resection of recurrence as significant prognostic factors. In subgroup analyses, surgical resection may have positive prognostic impacts on intra- and extrahepatic recurrences, and even on early recurrence. However, simultaneous intra- and extrahepatic recurrence may not see any survival benefit from surgical management. Conclusion Surgical resection of recurrent ICC could improve survival after recurrence, especially for patients with intra- or extrahepatic recurrence as resectable oligo-metastases

Regulation of Pancreatic β Cell Mass by Cross-Interaction between CCAAT Enhancer Binding Protein β Induced by Endoplasmic Reticulum Stress and AMP-Activated Protein Kinase Activity

During the development of type 2 diabetes, endoplasmic reticulum (ER) stress leads to not only insulin resistance but also to pancreatic beta cell failure. Conversely, cell function under various stressed conditions can be restored by reducing ER stress by activating AMP-activated protein kinase (AMPK). However, the details of this mechanism are still obscure. Therefore, the current study aims to elucidate the role of AMPK activity during ER stress-associated pancreatic beta cell failure. MIN6 cells were loaded with 5-amino-1-ϐ-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) and metformin to assess the relationship between AMPK activity and CCAAT enhancer binding protein ϐ (C/EBPϐ) expression levels. The effect of C/EBPϐ phosphorylation on expression levels was also investigated. Vildagliptin and metformin were administered to pancreatic beta cell-specific C/EBPϐ transgenic mice to investigate the relationship between C/EBPϐ expression levels and AMPK activity in the pancreatic islets. When pancreatic beta cells are exposed to ER stress, the accumulation of the transcription factor C/EBPϐ lowers the AMP/ATP ratio, thereby decreasing AMPK activity. In an opposite manner, incubation of MIN6 cells with AICAR or metformin activated AMPK, which suppressed C/EBPϐ expression. In addition, administration of the dipeptidyl peptidase-4 inhibitor vildagliptin and metformin to pancreatic beta cell-specific C/EBPϐ transgenic mice decreased C/EBPϐ expression levels and enhanced pancreatic beta cell mass in proportion to the recovery of AMPK activity. Enhanced C/EBPϐ expression and decreased AMPK activity act synergistically to induce ER stress-associated pancreatic beta cell failure

TP53 codon 72 polymorphism is associated with FGFR3 and RAS mutation in non-muscle-invasive bladder cancer

ObjectiveTP53, a well-known tumor-suppressor gene in bladder carcinogenesis, has a functional single-nucleotide polymorphism on codon 72. The aim of this study was to elucidate the association between TP53 codon 72 polymorphism and somatic mutations in bladder cancer.Material and methodsGermline TP53 codon 72 polymorphism and somatic mutations of 50 cancer-associated genes were analyzed in 103 bladder cancer patients (59 non-muscle-invasive and 44 muscle-invasive), using Taqman genotyping assay and target sequencing, respectively. The expression of FGF-FGFR signaling pathway genes was analyzed by RNA sequencing of frozen tissue.ResultsThe allele frequency of TP53 codon 72 in our cohort was 37, 42, and 21% for Arg/Arg, Arg/Pro, and Pro/Pro, respectively. Interestingly, the prevalence of FGFR3 mutation was higher in patients with the Arg allele, whereas that of the RAS mutation was higher in patients without the Arg allele. The same association was seen in non-muscle-invasive bladder cancer (NMIBC) patients and no differences were observed in muscle-invasive bladder cancer patients. In NMIBC, FGFR1 expression was higher in patients without the Arg allele and FGFR3 expression was higher in patients with the Arg allele.ConclusionThe germline TP53 codon 72 polymorphism was associated with mutations of FGFR3 or RAS and expression of FGFR1 and FGFR3 in NMIBC. These findings provide new insight into the molecular mechanisms underlying the influence of the genetic background on carcinogenesis in bladder cancer