相分離法による高分子多孔膜の形成の熱力学とその膜の2,3の性質

取得学位：博士(工学)，学位授与番号：博乙第153号，学位授与年月日：平成10年3月25日,学位授与年：199

The apelin‑apelin receptor signaling pathway in fibroblasts is involved in tumor growth via p53 expression of cancer cells

Cancer-associated fibroblasts (CAFs) are pivotal in tumor progression. TP53-deficiency in cancer cells is associated with robust stromal activation. The apelin-apelin receptor (APJ) system has been implicated in suppressing fibroblast-to-myofibroblast transition in non-neoplastic organ fibrosis. The present study aimed to elucidate the oncogenic role of the apelin-APJ system in tumor fibroblasts. APJ expression and the effect of APJ suppression in fibroblasts were investigated for p53 status in cancer cells using human cell lines (TP53-wild colon cancer, HCT116, and Caco-2; TP53-mutant colon cancer, SW480, and DLD-1; and colon fibroblasts, CCD-18Co), resected human tissue samples of colorectal cancers, and immune-deficient nude mouse xenograft models. The role of exosomes collected by ultracentrifugation were also analyzed as mediators of p53 expression in cancer cells and APJ expression in fibroblasts. APJ expression in fibroblasts co-cultured with p53-suppressed colon cancer cells (HCT116sh p53 cells) was significantly lower than in control colon cancer cells (HCT116sh control cells). APJ-suppressed fibroblasts treated with an antagonist or small interfering RNA showed myofibroblast-like properties, including increased proliferation and migratory abilities, via accelerated phosphorylation of Sma- and Mad-related protein 2/3 (Smad2/3). In addition, xenografts of HCT116 cells with APJ-suppressed fibroblasts showed accelerated tumor growth. By contrast, apelin suppressed the upregulation of phosphorylated Smad2/3 in fibroblasts. MicroRNA 5703 enriched in exosomes derived from HCT116sh p53 cells inhibited APJ expression, and inhibition of miR-5703 diminished APJ suppression in fibroblasts caused by cancer cells. APJ suppression from a specific microRNA in cancer cell-derived exosomes induced CAF-like properties in fibroblasts. Thus, the APJ system in fibroblasts in the tumor microenvironment may be a promising therapeutic target.Saiki H., Hayashi Y., Yoshii S., et al. The apelin‑apelin receptor signaling pathway in fibroblasts is involved in tumor growth via p53 expression of cancer cells. International Journal of Oncology 63, 139 (2023); https://doi.org/10.3892/ijo.2023.5587

Specific Regulation of T Helper Cell 1–mediated Murine Colitis by CEACAM1

Carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) is a cell surface molecule that has been proposed to negatively regulate T cell function. We have shown that CEACAM1 is associated with specific regulation of T helper cell (Th)1 pathways, T-bet–mediated Th1 cytokine signaling, and Th1-mediated immunopathology in vivo. Mice treated with anti–mouse CEACAM1-specific monoclonal antibody (mAb) CC1 during the effector phase exhibited a reduced severity of trinitrobenzene sulfonic acid colitis in association with decreased interferon (IFN)-γ production. Although oxazolone colitis has been reported as Th2 mediated, mice treated with the CC1 mAb or a CEACAM1-Fc chimeric protein exhibited a reduced severity of colitis in association with a significant reduction of IFN-γ and T-bet activation, whereas signal transducer and activator of antigen 4 activation was unaffected. Both interleukin-4 and IFN-γ gene–deficient mice exhibited less severe colitis induction by oxazolone. Direct ligation of T cells in vitro with the murine hepatitis virus spike protein, a natural ligand for the N-domain of CEACAM1, inhibited the differentiation of naive cells into Th1 but not Th2 cells and activation of Th1 but not Th2 cytokine production. These results indicate that CEACAM1 isoforms are a novel class of activation-induced cell surface molecules on T cells that function in the specific regulation of Th1-mediated inflammation such as that associated with inflammatory bowel disease

Multiwalled carbon nanotubes grown in hydrogen atmosphere : An x-ray diffraction study

X-ray diffraction study of multiwalled carbon nanotube (MWNT) grown by arc discharge in hydrogen atmosphere is presented. It is found that the thermal-expansion coefficient along the radial direction of MWNT is widely distributed in a range from 1.6×10-5 K-1 to 2.6×10-5 K-1, indicating the existence of both of Russian doll MWNT and highly defective MWNT. Russian doll MWNT is suggested to have the outer diameter less than ∼100  Å . Thicker MWNT's are typically highly defective, and may have the jelly roll (scroll) or defective polygonal structure consisting of flat graphite domains

Narrow-band imaging with magnifying endoscopy for Peyer's patches is useful in predicting the recurrence of remissive patients with ulcerative colitis

Background/AimsPeyer's patches (PPs) are aggregates of lymphoid follicles that are mainly located in the distal ileum; they play a major role in mucosal immunity. We recently reported that patients with ulcerative colitis (UC) have alterations in PPs that can be detected using narrow-band imaging with magnifying endoscopy (NBI-ME). However, the usefulness of NBI-ME in UC treatment as a whole is still unknown.MethodsWe collected NBI-ME images of PPs from 67 UC patients who had undergone ileocolonoscopy. We evaluated changes in the villi using the "villi index," which is based on three categories: irregular formation, hyperemia, and altered vascular network pattern. The patients were divided into two groups on the basis of villi index: low (L)- and high (H)-types. We then determined the correlation between morphological alteration of the PPs and various clinical characteristics. In 52 patients who were in clinical remission, we also analyzed the correlation between NBI-ME findings of PPs and clinical recurrence.ResultsThe time to clinical recurrence was significantly shorter in remissive UC patients with H-type PPs than in those with L-type PPs (P<0.01). Moreover, PP alterations were not correlated with age, sex, disease duration, clinical activity, endoscopic score, or extent of disease involvement. Multivariate analysis revealed that the existence of H-type PPs was an independent risk factor for clinical recurrence (hazard ratio, 3.3; P<0.01).ConclusionsUC patients with morphological alterations in PPs were at high risk of clinical relapse. Therefore, to predict the clinical course of UC, it may be useful to evaluate NBI-ME images of PPs

Characteristics of Patent Ductus Arteriosus in Congenital Rubella Syndrome

This study investigated the characteristics of congenital rubella syndrome (CRS)-associated cardiac complications, particularly patent ductus arteriosus (PDA). We reviewed the medical records of patients with CRS who were admitted to the Children’s Hospital 1 in Vietnam between December 2010 and December 2012, and patients with CRS who underwent PDA transcatheter occlusion therapy at the cardiology department between December 2009 and December 2015. We compared the characteristics of PDA treated with transcatheter closure between children with CRS (CRS-PDA) and those without CRS (non-CRS-PDA) who underwent PDA transcatheter closure between July 2014 and December 2015. One-hundred-and-eight children with CRS were enrolled. Cardiac defects (99%), cataracts (72%), and hearing impairment (7%) were detected. Fifty CRS-PDA and 290 non-CRS-PDA patients were examined. CRS-PDA patients had smaller median birthweight (p < 0.001), more frequent pulmonary (p < 0.001) and aortic stenosis (p < 0.001), higher main pulmonary artery pressure, and higher aortic pressure in systole/diastole (p < 0.001 for each) than did non-CRS-PDA patients. The proportion of tubular-type PDA was higher in CRS-PDA patients (16%) than in non-CRS-PDA patients (3%) (p = 0.020). Tubular-type PDA was frequently seen in patients with CRS and accompanied by pulmonary/systemic hypertension and pulmonary/aortic stenosis; in these patients, more cautious device selection is needed for transcatheter PDA closure

Sequential therapies after atezolizumab plus bevacizumab or lenvatinib first-line treatments in hepatocellular carcinoma patients

Introduction: The aim of this retrospective proof-of-concept study was to compare different second-line treatments for patients with hepatocellular carcinoma and progressive disease (PD) after first-line lenvatinib or atezolizumab plus bevacizumab.Materials and methods: A total of 1381 patients had PD at first-line therapy. 917 patients received lenvatinib as first-line treatment, and 464 patients atezolizumab plus bevacizumab as first-line.Results: 49.6% of PD patients received a second-line therapy without any statistical difference in overall survival (OS) between lenvatinib (20.6 months) and atezolizumab plus bev-acizumab first-line (15.7 months; p = 0.12; hazard ratio [HR] = 0.80). After lenvatinib first-line, there wasn't any statistical difference between second-line therapy subgroups (p = 0.27; sorafenib HR: 1; immunotherapy HR: 0.69; other therapies HR: 0.85). Patients who under-went trans-arterial chemo-embolization (TACE) had a significative longer OS than patients who received sorafenib (24.7 versus 15.8 months, p &lt; 0.01; HR = 0.64). After atezolizumab plus bevacizumab first-line, there was a statistical difference between second-line therapy subgroups (p &lt; 0.01; sorafenib HR: 1; lenvatinib HR: 0.50; cabozantinib HR: 1.29; other therapies HR: 0.54). Patients who received lenvatinib (17.0 months) and those who under-went TACE (15.9 months) had a significative longer OS than patients treated with sorafenib (14.2 months; respectively, p = 0.01; HR = 0.45, and p &lt; 0.05; HR = 0.46).Conclusion: Approximately half of patients receiving first-line lenvatinib or atezolizumab plus bevacizumab access second-line treatment. Our data suggest that in patients progressed to atezolizumab plus bevacizumab, the systemic therapy able to achieve the longest survival is lenvatinib, while in patients progressed to lenvatinib, the systemic therapy able to achieve the longest survival is immunotherapy

Deep Rooting in Winter Wheat: Rooting Nodes of Deep Roots in Two Cultivars with Deep and Shallow Root Systems

Deep rooting of wheat has been suggested that it influences the tolerance to various environmental stresses. In this study, the nodes from which the deepest penetrated roots had emerged were examined in winter wheat. The wheat was grown in long tubes with or without mechanical stress and in large root boxes. The length and growth angle of each axile root were examined to analyze the difference in the vertical distribution of the roots between the two wheat cultivars, one with a deep and one with a shallow root system. In Shiroganekomugi, a Japanese winter wheat cultivar with a shallow root system, the rooting depths of the seminal and nodal roots decreased as the rooting nodes advanced acropetally. Six out of nine deepest roots were seminal root in the non-mechanical stress conditions. In Mutsubenkei, a Japanese winter wheat cultivar with a deep root system, grown in root boxes, not only the seminal roots but also the coleoptilar and the first nodal roots penetrated to a depth of more than 1.3 m in the root box, and became the deepest roots. In both cultivars, the seminal roots became the deepest roots under the mechanical stress conditions. There were no clear tendencies in the root growth angles among the rooting nodes in the wheat root system. This indicates that the length of the axile roots can explain the differences in the rooting depths among axile roots in a wheat root system. On the other hand, the axile roots of Mutsubenkei elongated significantly more vertically than those of Shiroganekomugi. This suggests that not only seminal but also nodal roots exhibit strong positive gravitropism and penetrate deeply in a cultivar with a deep root system. In wheat cultivars, it is likely that the extent of its Root Depth Index results partly from the gravitropic responses of both seminal and nodal roots