Impaired degradation followed by enhanced recycling of epidermal growth factor receptor caused by hypo-phosphorylation of tyrosine 1045 in RBE cells

信州大学博士（医学）・学位論文・平成24年6月11日授与（甲第929号）・桂安萍Background: Since cholangiocarcinoma has a poor prognosis, several epidermal growth factor receptor (EGFR)-targeted therapies with antibody or small molecule inhibitor treatment have been proposed. However, their effect remains limited. The present study sought to understand the molecular genetic characteristics of cholangiocarcinoma related to EGFR, with emphasis on its degradation and recycling. Methods: We evaluated EGFR expression and colocalization by immunoblotting and immunofluorescence, cell surface EGFR expression by fluorescence-activated cell sorting (FACS), and EGFR ubiquitination and protein binding by immunoprecipitation in the human cholangiocarcinoma RBE and immortalized cholangiocyte MMNK-1 cell lines. Monensin treatment and Rab11a depletion by siRNA were adopted for inhibition of EGFR recycling. Results: Upon stimulation with EGF, ligand-induced EGFR degradation was impaired and the expression of phospho-tyrosine 1068 and phospho-p44/42 MAPK was sustained in RBE cells as compared with MMNK-1 cells. In RBE cells, the process of EGFR sorting for lysosomal degradation was blocked at the early endosome stage, and non-degradated EGFR was recycled to the cell surface. A disrupted association between EGFR and the E3 ubiquitin ligase c-Cbl, as well as hypo-phosphorylation of EGFR at tyrosine 1045 (Tyr1045), were also observed in RBE cells. Conclusion: In RBE cells, up-regulation of EGFR Tyr1045 phosphorylation is a potentially useful molecular alteration in EGFR-targeted therapy. The combination of molecular-targeted therapy determined by the characteristics of individual EGFR phosphorylation events and EGFR recycling inhibition show promise in future treatments of cholangiocarcinoma.ArticleBMC Cancer. 2012, 12:179journal articl

Gastric Composite Tumor of Alpha Fetoprotein-Producing Carcinoma/Hepatoid Adenocarcinoma and Endocrine Carcinoma with Reference to Cellular Phenotypes

Alpha-fetoprotein-producing carcinoma (AFPC)/hepatoid adenocarcinoma (HAC) and neuroendocrine carcinoma (NEC) are uncommon in the stomach. Composite tumors consisting of these carcinomas and their histologic phenotypes are not well known. Between 2002 and 2007, to estimate the prevalence of composite tumors consisting of tubular adenocarcinoma, AFPC/HAC and NEC, we reviewed specimens obtained from 294 consecutive patients treated surgically for gastric cancer. We examined histological phenotype of tumors of AFPC or NEC containing the composite tumor by evaluating immunohistochemical expressions of MUC2, MUC5AC, MUC6, CDX2, and SOX2. Immunohistochemically, AFPC/HAC dominantly showed the intestinal or mixed phenotype, and NEC frequently showed the gastric phenotype. In the composite tumor, the tubular and hepatoid components showed the gastric phenotype, and the neuroendocrine component showed the mixed type. The unique composite tumor predominantly showed the gastric phenotype, and the hepatoid and neuroendocrine components were considered to be differentiated from the tubular component

Changes in pollinator fauna affect altitudinal variation of floral size in a bumblebee-pollinated herb

Geographic trait variations are often caused by locally different selection regimes. As a steep environmental cline along altitude strongly influences adaptive traits, mountain ecosystems are ideal for exploring adaptive differentiation over short distances. We investigated altitudinal floral size variation of Campanula punctata var. hondoensis in 12 populations in three mountain regions of central Japan to test whether the altitudinal floral size variation was correlated with the size of the local bumblebee pollinator and to assess whether floral size was selected for by pollinator size. We found apparent geographic variations in pollinator assemblages along altitude, which consequently produced a geographic change in pollinator size. Similarly, we found altitudinal changes in floral size, which proved to be correlated with the local pollinator size, but not with altitude itself. Furthermore, pollen removal from flower styles onto bees (plant's male fitness) was strongly influenced by the size match between flower style length and pollinator mouthpart length. These results strongly suggest that C. punctata floral size is under pollinator-mediated selection and that a geographic mosaic of locally adapted C. punctata exists at fine spatial scale.ArticleECOLOGY AND EVOLUTION. 4(17):3395-3407 (2014)journal articl

Dynamically Integrated Transport Approach for High-Energy Nuclear Collisions at High Baryon Density

To explore the structure of the QCD phase diagram in high baryon density domain, several high-energy nuclear collision experiments in a wide range of beam energies are currently performed or planned using many accelerator facilities. In these experiments search for a first-order phase transition and the QCD critical point is one of the most important topics. To find the signature of the phase transition, experimental data should be compared to appropriate dynamical models which quantitatively describe the process of the collisions. In this study we develop a new dynamical model on the basis of the non-equilibrium hadronic transport model JAM and 3+1D hydrodynamics. We show that the new model reproduce well the experimental beam-energy dependence of hadron yields and particle ratio by the partial thermalization of the system in our core-corona approach.Comment: 4 pages, 3 figures; contribution to the proceedings of the 8th International Conference on Quarks and Nuclear Physics (QNP2018), Tsukuba, November 13-17, 201

CRYSTAL GROWTH OF RARE EARTH COMPOUNDS IN CLOSED SYSTEM

Remarkable improvements have been made on the crystal growth of rare earth pnictides and chalchogenides by the development of new growth technique and the construction of several new equipments for the crystal growth such as electron beam welding system of tungsten crucible provided with large glove box and vacuum HF furnace. This system has really worked on obtaining excellent quality of single crystals and made easier to explore unknown materials of rare earth compounds. Interesting and attractive physical properties of these compounds were obtained from the crystals produced by this system and contributed to extend a new scope of the heavy Fermion physics

Exopolysaccharides From Streptococcus thermophilus ST538 Modulate the Antiviral Innate Immune Response in Porcine Intestinal Epitheliocytes

It was reported that exopolysaccharides (EPSs) from lactobacilli are able to differentially modulate mucosal antiviral immunity. Although research has described the ability of EPSs derived from Streptococcus thermophilus to modulate the mucosal immune system, their impact on antiviral immunity was less explored. In this work, we investigated the capacity of the EPS-producing S. thermophilus ST538 to modulate the innate antiviral immune response triggered by the activation of the Toll-like receptor 3 (TLR3) in porcine intestinal epitheliocytes (PIE cells). Moreover, in order to study the immunomodulatory potential of S. thermophilus ST538 EPS, we successfully developed two mutant strains through the knockout of the epsB or epsC genes. High-performance liquid chromatography and scanning electron microscopy studies demonstrated that the wild type (WT) strain produced as high as 595 μg/ml of EPS in the skim milk medium, while none of the mutant strains (S. thermophilus ΔepsB and ΔepsC) were able to produce EPS. Studies in PIE cells demonstrated that the EPS of S. thermophilus ST538 is able to significantly improve the expression of interferon β (IFN-β), interleukin 6 (IL-6), and C-X-C motif chemokine 10 (CXCL10) in response to TLR3 stimulation. The role of EPS in the modulation of antiviral immune response in PIE cells was confirmed by comparative studies of cell free culture supernatants and fermented skim milks obtained from S. thermophilus ΔepsB and ΔepsC. These results suggest that S. thermophilus ST538 could be used as an immunobiotic strain for the development of new immunologically functional foods, which might contribute to improve resistance against viral infections.Fil: Mizuno, Akira. Tohoku University; JapónFil: Tomotsune, Kae. Tohoku University; JapónFil: Islam, Md Aminul. Tohoku University; JapónFil: Funabashi, Ryutaro. Tohoku University; JapónFil: Albarracín, Leonardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Tohoku University; Japón. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología; ArgentinaFil: Ikeda Ohtsubo, Wakako. Tohoku University; JapónFil: Aso, Hisashi. Tohoku University; JapónFil: Takahashi, Hideki. Tohoku University; JapónFil: Kimura, Katsunori. Meiji Co.; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Tohoku University; JapónFil: Sasaki, Yasuko. Meiji University; JapónFil: Kitazawa, Haruki. Tohoku University; Japó

Estimation of additional secondary factor of LORAN-C around Izu Oshima Island

東京水産大学海洋システム工学講座東京水産大学海洋システム工学講座東京水産大学研究練習船神鷹丸東京水産大学研究練習船神鷹丸東京水産大学研究練習船神鷹

Distribution and behavior of bottom water in Tokyo Bay in summer : Role of wind on outflow of poor oxygen water

東京水産大学練習船東京水産大学環境システム学講座東京水産大学練習船東京水産大学環境システム学講座東京水産大学練習船東京水産大学環境システム学講