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E2FBP1 antagonizes the p16^(INK4A)-Rb tumor suppressor machinery for growth suppression and cellular senescence by regulating promyelocytic leukemia protein stability

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International Journal of Oral Science 2011年第4期3卷 200-208页

作者： Yayoi Fukuyo Akiko Takahashi Eiji Hara Nobuo horikoshi Tej K. Pandita Takuma Nakajima Department of Immunology Tulane National Primate Research Center Section of Bacterial Pathogenesis Graduate School Tokyo Medical and Dental University Division of Cancer Biology The Cancer Institute Japanese Foundation for Cancer Research Division of Molecular Radiation Biology Department of Radiation Oncology University of Texas Southwestern Medical Center

Cellular senescence is an irreversible cell cycle arrest triggered by the activation of oncogenes or mitogenic signaling as well as the enforced expression of tumor suppressors such as p53, p16INK4A and promyelocytic leukemia protein （PML） in normal cells. E2F-binding protein 1 （E2FBP1）, a transcription regulator for E2F, induces PML reduction and suppresses the formation of PML-nuclear bodies, whereas the down-regulation of E2FBP1 provokes the PML-dependent premature senescence in human normal fibroblasts. Here we report that the depletion of E2FBP1 induces the accumulation of PML through the Ras-dependent activation of MAP kinase signaling. The cellular levels of p16INK4A and p53 are elevated during premature senescence induced by depletion of E2FBP1, and the depletion of p16INK4A, but not p53 rescued senescent cells from growth arrest. Therefore, the premature senescence induced by E2FBP1 depletion is achieved through the pl6INK4A-Rb pathway. Similar to human normal fibroblasts, the growth inhibition induced by E2FBP1 depletion is also observed in human tumor cells with intact p16INK4A and Rb. These results suggest that E2FBP1 functions as a critical antagonist to the pI6INK4A-Rb tumor suppressor machinery by regulating PML stability.

关键词： E2F-binding protein 1 senescence cell cycle ubiquitin promyelocytic leukemia protein

Measurement of shear wave velocities coupled with an evaluation of elasticity using ARFI elastography in diagnosis of papillary thyroid carcinoma

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Open Journal of Clinical Diagnostics 2013年第4期3卷 178-182页

作者： Ryuhei Okada Masami Suzuki Koji Takeuchi Hiroyuki horikoshi Atsunobu Tsunoda Department of Head and Neck Surgery Gunma Prefectural Cancer Center Gunma Japan Department of Otolaryngology Tokyo Medical and Dental University Tokyo Japan Department of Radiological Diagnosis Gunma Prefectural Cancer Center Gunma Japan

This study aimed to evaluate the diagnostic value of measuring the shear wave velocities (Vs) of thyroid nodules in diagnosis of the thyroid carcinoma. Using Virtual Touch Tissue Quantification (VTTQ) of acoustic radiation force impulse (ARFI) elastography (ACUSON S2000®, Siemens Medical Solutions, Mountain View, CA, USA), we measured the Vs of thyroid nodules in 39 nodules from 34 patients (four males and 30 females) before surgery. Elasticity itself was also estimated by VTTI (Virtual Touch Tissue Imaging) using ARFI. The average Vs of normal thyroid tissue was 2.24 ± 0.68 m/s. Twenty-three out of 39 nodules showed an average 2.52 ± 1.33 m/s. However, 16 other nodules showed “*** m/s”. These 16 nodules showed either “black” or “honeycomb” patterns of elasticity in VTTI. This value suggested that the Vs of these nodules were too fast or heterogenous to measure by this device. After the surgery, the pathologies of these nodules were revealed to be papillary carcinoma (21 cases), adenomatous goiter (11), follicular carcinoma (4), follicular adenoma (2) and follicular lymphoma (1). Five papillary carcinomas were found within adenomatous goiters. Nodules from four follicular carcinomas showed average Vs of 1.92 ± 0.48 m/s, while two follicular adenomas and follicular lymphoma showed 2.19 ± 0.06 and 2.34 m/s respectively. Nodules of adenomatous goiter showed 2.14 ± 0.60 m/s. On the other hand, nodules from five out of 21 papillary carcinomas showed average Vs of 4.00 ± 2.37 m/s. In the nodules of 16 papillary carcinomas, Vs were measured as “*** m/s” and this value was only observed in nodules of papillary carcinoma. These data reflected high and/or heterogenous elasticity of papillary carcinoma, in other words, the tissue of papillary carcinoma was hard and/or heterogenous. It was notable that the Vs value of “*** m/s” strongly suggested papillary carcinoma.

关键词： ARFI Elastography Thyroid Thyroid Nodule

Acylcarnitine: Useful biomarker for early diagnosis of hepatocellular carcinoma in non-steatohepatitis patients

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World Journal of Gastrointestinal Oncology 2019年第10期11卷 887-897页

作者： Hiroaki Takaya Tadashi Namisaki Mitsuteru Kitade Naotaka Shimozato Kosuke Kaji Yuki Tsuji Keisuke Nakanishi Ryuichi Noguchi Yukihisa Fujinaga Yasuhiko Sawada Soichiro Saikawa Shinya Sato Hideto Kawaratani Kei Moriya Takemi Akahane Hitoshi yoshiji Third Department of Internal Medicine Nara Medical University

BACKGROUND Early diagnosis of hepatocellular carcinoma(HCC)is necessary to improve the prognosis of ***,the currently available tumor biomarkers are insufficient for the early detection of *** is essential in fatty acid metabolic pathways.A recent study reported that a high level of acylcarnitine may serve as a useful biomarker for the early diagnosis of HCC in steatohepatitis(SH)*** contrast,another study reported that the level of acetylcarnitine(AC2)-one of the acylcarnitine species-in non-SH patients with HCC was decreased vs that reported in those without *** To investigate the usefulness of acylcarnitine as a biomarker for the early diagnosis of HCC in non-SH *** Thirty-three non-SH patients(14 with HCC and 19 without HCC)were enrolled in this *** samples were obtained from patients at the time of *** levels of acylcarnitine and AC2 in the serum were determined through tandem mass *** levels of vascular endothelial growth factor(VEGF)and VEGF receptor 2(VEGFR-2)were determined by enzymelinked immunosorbent *** and multivariate analyses were used to determine early diagnostic factors of *** The level of acylcarnitine was significantly lower in non-SH patients with HCC vs those without HCC(P<0.05).In contrast,the level of lens culinaris agglutininreactive fraction ofα-fetoprotein(AFP)-AFP-L3%-was significantly higher in non-SH patients with HCC vs those without HCC(P<0.05).However,the levels of total carnitine,free carnitine,AFP,des-γ-carboxy prothrombin,VEGF,and VEGFR-2 were not different between patients with and without *** multivariate analysis showed that a low level of acylcarnitine was the only independent factor for the early diagnosis of *** patients with a low level of AC2 had a significantly higher level of VEGF vs those with a high level of AC2(P<0.05).CONCLUSION The metabolic pathways of fatty acids may differ between SH HCC and non-SH HCC

关键词： Acylcarnitine Acetylcarnitine Biomarker Hepatocellular carcinoma Angiogenesis Carnitine palmitoyltransferase 1 Oxidative stress

A Study on Diagnostic Assist Systems of Chronic Obstructive Pulmonary Disease from Medical Images by Deep Learning

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Journal of Computer and Communications 2018年第1期6卷 21-31页

作者： Toru Kimura Takashi Kawakami Akihiro Kikuchi Ryosuke Ooev Masaki Akiyama Hiroyuki horikoshi Faculty of Engineering Hokkaido University of Science Sapporo Japan Department of Radiology Gunma Prefecture Cancer Center Gunma Japan

In this paper, we propose new diagnostic assist systems of medical images using deep learning algorithms. Specifically, we aim to develop a diagnostic support system for the very early stage of chronic obstructive pulmonary disease (COPD) based on the CT images. It is said that COPD is a disease that develops due to long-term smoking, and it is said that there are a large number of latent onset reserve forces. By discovering this COPD in the very early period 0 and improving the living conditions, subsequent severity can be avoided in many cases, so a system that will help diagnosis by professional radiologists is needed. We show the some experimental results examined by the constructed system.

关键词： Deep Learning CT Images Diagnostic Assist Systems Chronic Obstructive Pulmonary Disease

Crosstalk between angiogenesis, cytokeratin-18, and insulin resistance in the progression of non-alcoholic steatohepatitis

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World Journal of Gastroenterology 2009年第41期15卷 5193-5199页

作者： Mitsuteru Kitade Hitoshi yoshiji Ryuichi Noguchi Yasuhide Ikenaka Kosuke Kaji Yusaku Shirai Masaharu Yamazaki Masahito Uemura Junichi Yamao Masao Fujimoto Akira Mitoro Masahisa Toyohara Masayoshi Sawai Motoyuki Yoshida Chie Morioka Tatsuhiro Tsujimoto Hideto Kawaratani Hiroshi Fukui Third Department of Internal Medicine Nara Medical University

AIM: To elucidate the possible crosstalk between angiogenesis, cytokeratin-18 (CK-18), and insulin resistance (IR) especially in patients with non-alcoholic steatohepatitis (NASH).METHODS: Twenty-eight patients with NASH and 11 with simple fatty liver disease (FL) were enrolled in this study and underwent clinicopathological examination. The measures of angiogenesis, CK-18, and IR employed were CD34-immunopositive vessels, CK-18immunopositive cells, and homeostasis model assessment of IR (HOMA-IR), respectively. The correlations of these factors with NASH were ***: Significant development of hepatic neovascularization was observed only in NASH, whereas almost no neovascularization could be observed in FL and healthy liver. The degree of angiogenesis was almost parallel to liver fibrosis development, and both parameters were positively correlated. Similarly, CK-18expression and HOMA-R were signifi cantly increased in NASH as compared with FL and healthy liver. Furthermore, CK-18 and HOMA-IR were also positively correlated with the degree of neovascularization. CONCLUSION: These results indicate that the crosstalk between angiogenesis, CK-18, and IR may play an important role in the onset and progression of NASH.

关键词： Angiogenesis Cytokeratin-18 Fatty liver Insulin resistance Non-alcoholic steatohepatitis Liver fibrosis

Influence of the period between onset of IgA nephropathy and medical intervention on renal prognosis

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Health 2011年第8期3卷 518-523页

作者： Keiko Okazaki, Yusuke Suzuki Takashi Kobayashi Fumiko Kodama Satoshi horikoshi Yasuhiko Tomino 不详

Background. The clinical course of IgA nephropathy (IgAN) is highly variable. In order to verify the necessity of early medical intervention in IgAN patients, the present study investigated the clinical impact of the duration between disease onset and first medical intervention on renal prognosis. Methods. We enrolled 57 patients diagnosed with IgAN on the basis of biopsy performed at our hospital. The medical records of these patients were traceable to the last 10 years, during which they had not undergone dialysis or treatment at any other hospital. On the basis of histological assessment of prognosis, these patients were classified according to the Japanese guidelines into the following groups: groups I, good prognosis;group II, relatively good prognosis;group III, relatively poor prognosis;and group IV, poor prognosis. We investigated the correlation between the duration of disease onset and the first consultation with a nephrologist and the rate of increase in serum creatinine over a 10 year period. In addition to the abovementioned patients, 6 patients with IgAN who underwent dialysis within the 10 years were separately evaluated. These patients came under the poor prognosis category;i.e., they belonged to group IV. Results. The duration between disease onset and medical consultation was significantly longer in younger patients or in those with asymptomatic proteinuria at onset when compared to that in older patients or in those with other urinary abnormalities. There was a significant correla tion between this duration and renal prognosis, particularly in group III patients. Although the duration between onset and consultation was not correlated to the serum creatinine level at the time of first medical intervention, urinary protein level among group IV patients at the time of first consultation was significantly higher in patients with dialysis than that in those without dialysis. Conclusions. Early medical intervention may lead to a better renal prognosis,

关键词： IgA Nephropathy Medical Intervention Diagnosis Prognosis

Decreased phagocytic activity of Kupffer cells in a rat nonalcoholic steatohepatitis model

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World Journal of Gastroenterology 2008年第39期14卷 6036-6043页

作者： Tatsuhiro Tsujimoto Hideto Kawaratani Toshiyuki Kitazawa Toshiko Hirai Hajime Ohishi Mitsuteru Kitade Hitoshi yoshiji Masahito Uemura Hiroshi Fukui Third Department of Internal Medicine Nara Medical University840 Shijo-choKashiharaNara 634-8522Japan Department of Endoscopy and Ultrasound Nara Medical University840 Shijo-choKashiharaNara 634-8522Japan

AIM: To investigate Kupffer cell dynamics and phagocytic activity,using a rat nonalcoholic steatohepatitis (NASH) model. METHODS: Male F344 rats were fed either a control diet or a choline-deficient L-amino acid-defined (CDAA) diet,followed by contrast enhanced ultrasonography (CEUS) using Levovist. The uptake of latex beads by the Kupffer cells was determined by fluorescent microscopy. The status of the Kupffer cells was compared between the two groups,using the immunohistochemical staining technique. RESULTS: After 4 or more wk of the CDAA diet,CEUS examination revealed a decrease in the signal intensity,20 min after intravenous Levovist. Fluorescent microscopic examination showed that the uptake of latex beads by the Kupffer cells was reduced at week 1 and 2 in the study group,compared with the controls,with no further reduction after 3 wk. Immunohistochemical staining revealed no significant difference in the Kupffer cell counts between the control group and the CDAA group. CONCLUSION: CEUS examination using Levovist demonstrated reduced contrast effect and phagocytic activity in the liver parenchymal phase,although the Kupffer cell numbers were unchanged,indicating reduced phagocytic function of the Kupffer cells in the rat NASH model. We believe that CEUS examination using Levovist is a useful screening modality,which can detect NASH in fatty liver patients.

关键词： Nonalcoholic steatohepatitis Kupffer cells Contrast enhanced ultrasonography Levovist Ultrasound contrast agent Phagocytic activity

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中桥

Activation of c-Yes in hepatocellular carcinoma: A preliminary study

城市环境设计 2024年第1期147卷 168-173页

作者：宫原贤次名城俊树田中浩介今井博康 Adrien Fritz 堀越圭晋中尾孝佑 SS

中桥是一座步行桥，代表了隈研吾事务所自2013年开始参与南三陆市复兴设计的努力。桥身连接南三陆市Sun Sun商业街和复兴祈愿公园（前身是防灾办公室），成为一个祈祷的场所。中桥以不同形式连接了不同空间。从前防灾办公室穿过桥梁，...

中桥是一座步行桥，代表了隈研吾事务所自2013年开始参与南三陆市复兴设计的努力。桥身连接南三陆市Sun Sun商业街和复兴祈愿公园（前身是防灾办公室），成为一个祈祷的场所。中桥以不同形式连接了不同空间。从前防灾办公室穿过桥梁，会到达上山八幡宫神社。在日本神社中，道路与神社之间的桥梁被用来区分和联系人界与神界。中桥优雅的桥拱与神社前典型的太鼓桥相似。

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来源：博看期刊

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World Journal of Gastroenterology 2006年第35期12卷 5743-5745页

作者： Han Feng Tsutomu Masaki Takako Nonomura Asahiro Morishita Gong Jian Seiji Nakai Akihiro Deguchi Naohito Uchida Takashi Himoto Hisakazu Iwama Hisashi Usuki Hisao Wakabayashi Kunihiko Izuishi Hitoshi yoshiji Kazutaka Kurokohchi Shigeki Kuriyama Third Departmentof Internal Medicine Kagawa Medical University 1750-1 Ikenobe Miki-cho Kita-gun Kagawa 761-0793 Japan Information Technology Center Kagawa Medical University 1750-1 Ikenobe Miki-cho Kita-gun Kagawa 761-0793 Japan Department of Gastroenterological Surgery Kagawa Medical University 1750-1 Ikenobe Miki-cho Kita-gun Kagawa 761-0793 Japan Third Department of Internal Medicine Nara Medical University 840 Shijo-cho Kashihara Nara 634-8522 Japan Department of Gastroenterology KKR Takamatsu Hospital 4-18 Tenjinmae Takamatsu Kagawa 760-0018 Japan

Hepatocellular carcinoma （HCC） is thought to develop through a multistep process. A long history of viral hepatitis or prolonged exposure to environmental toxins predisposes liver cells to mutations of the genes critical in the control of hepatocyte growth. In fact, both activation of cellular oncogenes and inactivation of tumorsuppressor genes are involved in the development of HCC. Activation of oncogenes by hepatitis virus integration has been shown in the woodchuck animal model, although the significance of this finding in human hepatocarcinogenesis is still under investigation. Tyrosine kinases, though a minor class of cellular protein, represent a major class of oncogenes. These tyrosine kinases are classified into two major groups.

关键词： Hepatocellular carcinoma Tyrosine kinase c-Yes Oncogene