Ayano M.,Kyushu University |
Tsukamoto H.,Kyushu University |
Kohno K.,National Kyushu Medical Center |
Ueda N.,Miyazaki Prefectural Miyazaki Hospital |
And 7 more authors.
Journal of Immunology | Year: 2015
Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular damage and fibrosis of the skin and internal organs. Because activated and oligoclonally expanded CD8+ T cells can be detected in peripheral blood and lungs of SSc patients, effector memory CD8+ T cells may play a critical role for organ involvement in SSc; however, the pathogenic functions of effector memory CD8+ T cells remain incompletely understood. In this study, we performed DNA microarray analysis of the sort-purified effector memory CD8+ T cells from SSc patients and healthy controls, and showed that the expression of genes related to immune response and cell adhesion, including CD226 (also known as DNAX accessory molecule-1 [DNAM-1]), was significantly altered. Moreover, detailed analysis of CD226 revealed that CD226highCD8+ T cells were increased in SSc patients (mean, 50.7%) compared with healthy controls (32.9%) and were appreciably associated with the severity of skin sclerosis and interstitial lung disease. Furthermore, CD226+CD8+T cells produced higher amount of various cytokines than CD226- ones, and CD226highCD8+ T cells from SSc patients showed upregulated IL-13 production and positive correlation with the cytotoxic capacity of CD8+ T cells against HUVECs. Finally, the neutralization of CD226 in CD8+ T cells impaired costimulation, cytokine productions, and cytolysis against HUVECs. These findings indicate that upregulated CD226 expression on CD8+ T cells reflects disease severity and is involved in SSc pathogenesis via the production of various cytokines, including profibrotic IL-13 and endothelial cell injury, and that CD226 may be a useful target in the treatment of SSc. Copyright © 2015 by The American Association of Immunologists, Inc.
Nisa H.,Kyushu University |
Kono S.,Kyushu University |
Yin G.,Kyushu University |
Toyomura K.,Kyushu University |
And 13 more authors.
BMC Cancer | Year: 2010
Background: It is uncertain whether smoking is related to colorectal cancer risk. Cytochrome P-450 CYP1A1, glutathione-S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1) are important enzymes in the metabolism of tobacco carcinogens, and functional genetic polymorphisms are known for these enzymes. We investigated the relation of cigarette smoking and related genetic polymorphisms to colorectal cancer risk, with special reference to the interaction between smoking and genetic polymorphism.Methods: We used data from the Fukuoka Colorectal Cancer Study, a population-based case-control study, including 685 cases and 778 controls who gave informed consent to genetic analysis. Interview was conducted to assess lifestyle factors, and DNA was extracted from buffy coat.Results: In comparison with lifelong nonsmokers, the odds ratios (OR) of colorectal cancer for <400, 400-799 and ≥800 cigarette-years were 0.65 (95% confidence interval [CI], 0.45-0.89), 1.16 (0.83-1.62) and 1.14 (0.73-1.77), respectively. A decreased risk associated with light smoking was observed only for colon cancer, and rectal cancer showed an increased risk among those with ≥400 cigarette-years (OR 1.60, 95% CI 1.04-2.45). None of the polymorphisms under study was singly associated with colorectal cancer risk. Of the gene-gene interactions studied, the composite genotype of CYP1A1*2A or CYP1A1*2C and GSTT1 polymorphisms was associated with a decreased risk of colorectal cancer, showing a nearly statistically significant (Pinteraction= 0.06) or significant interaction (Pinteraction= 0.02). The composite genotypes of these two polymorphisms, however, showed no measurable interaction with cigarette smoking in relation to colorectal cancer risk.Conclusions: Cigarette smoking may be associated with increased risk of rectal cancer, but not of colon cancer. The observed interactions between CYP1A1 and GSTT1 polymorphisms warrant further confirmation. © 2010 Nisa et al; licensee BioMed Central Ltd.
Joshi A.M.,Kyushu University |
Budhathoki S.,Kyushu University |
Ohnaka K.,Kyushu University |
Mibu R.,Kyushu University |
And 8 more authors.
Japanese Journal of Clinical Oncology | Year: 2011
Objective: Tumor protein p53 gene and its negative regulator, murine double minute 2 homolog are important components for cell-cycle arrest and apoptosis. An arginine-to-proline substitution at codon 72 in the p53 gene is reported to decrease apoptotic potential, while a thymine-to-guanine polymorphism at nucleotide 309, named SNP309, of murine double minute 2 gene increases transcription of the gene. These two polymorphisms therefore may be of importance in colorectal carcinogenesis. The relation of these polymorphisms to colorectal cancer risk was addressed in the Fukuoka Colorectal Cancer Study. Methods: We genotyped the two polymorphisms in 685 incident cases of colorectal cancer and 778 community controls by the polymerase chain reaction-restriction fragment length polymorphism method. Statistical adjustment was made for sex and age. Results: The proline allele of p53 gene and the guanine allele of SNP309 were each associated with a small, statistically non-significant increase in the odds ratio of colorectal cancer; the adjusted odds ratio (95% confidence interval) for arginine/proline and proline/proline genotypes combined versus arginine/arginine genotype of p53 gene was 1.23 (0.99-1.52) and that for thymine/guanine and guanine/guanine genotypes combined versus thymine/thymine genotype of SNP309 was 1.27 (0.98-1.63). Individuals harboring the proline allele of p53 gene and the guanine allele of SNP309 showed an odds ratio of 1.67 (95% confidence interval, 1.11-2.51). Conclusions: Codon 72 polymorphism of p53 and SNP309 in combination may confer an increased risk of colorectal cancer. © The Author (2010). Published by Oxford University Press. All rights reserved.
Yoshida D.,Fukuoka Teishin Hospital |
Ikeda Y.,Fukuoka Teishin Hospital |
Ikeda Y.,National Kyushu Medical Center |
Waki K.,Fukuoka Teishin Hospital |
And 5 more authors.
Surgery Today | Year: 2012
Purpose The clinicopathological features of colon cancer differ between proximal and distal sites; however, the influence of tumor location on liver metastasis has not been fully examined. The aim of this study was to evaluate the differences in the features of liver metastasis between proximal and distal colon cancer. Methods The clinicopathological data from 931 colon cancer patients who were treated surgically were examined retrospectively using a multivariate analysis. Results The incidence of synchronous liver metastasis was 7.1% (31/438) in proximal colon patients and 11.6% (57/493) in distal colon patients. Both univariate and multivariate analyses showed distal colon cancer to be a risk factor for synchronous liver metastasis. Conclusion The incidence of synchronous liver metastasis differs between proximal and distal colon cancer. © Springer 2011.
Breast ultrasound elastography and magnetic resonance imaging of fibrotic changes of breast disease: Correlations between elastography findings and pathologic and short tau inversion recovery imaging results, including the enhancement ratio and apparent diffusion coefficient
Matsubayashi R.N.,Breast Care Center |
Matsubayashi R.N.,Clinical Research Institute |
Imanishi M.,National Hospital Organization Kumamoto Medical Center |
Nakagawa S.,Breast Care Center |
And 7 more authors.
Journal of Computer Assisted Tomography | Year: 2015
PURPOSE: Ultrasound (US) elastography provides information regarding tissue hardness and is expected to become a novel diagnostic tool for breast disease. In contrast, magnetic resonance (MR) images reflect the tissue characteristics. Fibrosis of the stroma of breast diseases may affect their hardness. We investigated the correlation among elasticity score (ES) and signal intensity of short Tau inversion recovery MR images, enhancement ratio, apparent diffusion coefficient (ADC), and the fibrosis in the breast lesions. MATERIALS AND METHODS: We reviewed the findings of US elastography and MR imaging from 41 consecutive patients with breast lesions (25 invasive ductal carcinoma, 3 fibroadenoma, 1 phyllodes tumor, 2 ductal hyperplasia, 2 primary malignant lymphoma, 3 mastopathy, 1 metastasis, 1 tubular adenoma, 1 ductal carcinoma in situ, 1 diabetic mastopathy, and 1 intraductal papilloma). In each patient, elastography images were classified based on Tsukuba ES. We calculated the ratio of signal intensity of the lesion to the muscle on short Tau inversion recovery images (L/M ratio), enhancement ratio of early to precontrast and early to delayed images, and ADC for each lesion. The ES and MR findings were correlated with the degree of fibrosis (based on Masson trichrome stain). RESULTS: The ES significantly correlated with the L/M ratio (P = 0.0306) and the ADC (P = 0.0256). The stromal fibrosis also correlated with ES (P = 0.0023), the L/M ratio (P = 0.0344), and enhancement ratio of the early-to-delayed images (P = 0.049). CONCLUSIONS: The ES and L/M ratio are correlated significantly with each other, and they are correlated with the fibrosis. These results suggest that they will provide the information on the fibrosis and may help the diagnosis of breast lesions. © 2015 Wolters Kluwer Health, Inc. All rights reserved.