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World Journal of Gastroenterology 2005年第20期11卷 3065-3069页

作者： Takahiro Nemoto Shunichiro Kubota Hideyuki ishida Nobuo Murata Daijo Hashimoto Department of Physiological Chemistry and Metabolism Graduate School of Medicine The University of Tokyo 7-3-1 Hongo Bunkyo-kuTokyo 113-0033 Japan Department of Physiological Chemistry and Metabolism Graduate School of Medicine The University of Tokyo 7-3-1 Hongo Bunkyo-kuTokyo 113-0033 Japan Department of Life Sciences Graduate School of Arts and Sciences The University of Tokyo 3-8-1 KomabaMeguro-ku Tokyo 153-8902 Japan Department of Surgery Saitama Medical Center Saitama Medical School 1981 Tsujido-machi Kamoda Kawagoe City Saitama 350-8550 Japan

AIM: To investigate the expressions of omithine decarboxylase (ODC), MMP-2, and Erk, and their relationship in human colon tumors.METHODS: ODC activity, MMP-2 expression, and mitogenactivated protein (MAP) kinase activity (Erk phosphorylation) were determined in 58 surgically removed human colon tumors and their adjacent normal tissues, using [1-14C]-ornithine as a substrate, ELISA assay, and Western blotting, respectively.RESULTS: ODC activity, MMP-2 expression, and Erk phosphorylation were significantly elevated in colon tumors, compared to those in adjacent normal tissues. A significant correlation was observed between ODC activities and MMP-2 levels.CONCLUSION: This is the first report showing a significant correlation between ODC activities and MMP-2 levels in human colon tumors. As MMP-2 is involved in cancer invasion and metastasis, and colon cancer overexpresses ODC, suppression of ODC expression may be a rational approach to treat colon cancer which overexpresses ODC.

关键词：鸟氨酸脱羧酶分裂素活性蛋白蛋白激酶金属蛋白酶-2 结肠肿瘤

Diagnostic problems in two-dimensional shear wave elastography of the liver

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World Journal of Radiology 2020年第5期12卷 76-86页

作者： Hiroko Naganuma Hideaki ishida Atsushi Uno Hiroshi Nagai Hidekatsu Kuroda Masahiro Ogawa Department of Gastroenterology Yokote Municipal HospitalYokote 0138602AkitaJapan Department of Gastroenterology Akita Red Cross HospitalKamikitatesaruta 0101495AkitaJapan Department of Gastroenterology Oomori Municipal HospitalYokote 0130525AkitaJapan New Generation Imaging Laboratory Tokyo 1680065Japan Division of Gastroenterology and Hepatology Iwate Medical UniversityMorioka 0200023IwateJapan Department of Gastroenterology and Hepatology Nihon University HospitalChiyoda 1018309TokyoJapan

Two-dimensional shear wave elastography(2D-SWE)is used in the clinical setting for observation of the liver.Unfortunately,a wide spectrum of artifactual images are frequently encountered in 2D-SWE,the precise mechanisms of which remain incompletely understood.This review was designed to present many of the artifactual images seen in 2D-SWE of the liver and to analyze them by computer simulation models that support clinical observations.Our computer simulations yielded the following suggestions:(1)When performing 2D-SWE in patients with chronic hepatic disease,especially liver cirrhosis,it is recommended to measure shear wave values through the least irregular hepatic surface;(2)The most useful 2D-SWE in patients with focal lesion will detect lesions that are poorly visible on B-mode ultrasound and will differentiate true tumors from pseudo-tumors(e.g.,irregular fatty change);and(3)Measurement of shear wave values in the area posterior to a focal lesion must be avoided.

关键词： Two-dimensional shear wave elastography Ultrasound Artifacts Liver cirrhosis Liver tumor Computer simulation model

HsfAld, a Protein Identified via FOX Hunting Using Thellungiella salsuginea cDNAs Improves Heat Tolerance by Regulating Heat-Stress-Responsive Gene Expression

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Molecular Plant 2013年第2期6卷 411-422页

作者： Yukari Higashi Naohiko Ohama Tomoko Ishikawa Taku Katori Ayaka Shimura Kazuya Kusakabe Kazuko Yamaguchi-Shinozaki Junko ishida Maho Tanaka Motoaki Seki Kazuo Shinozaki Yoichi Sakata Takahisa Hayashi Teruaki Taji Department of Bio-Science Tokyo University of Agriculture 1-1-1 Sakuragaoka Setagaya Tokyo 156-8502 Japan Graduate School of Agriculture and Life Sciences University of Tokyo Tokyo 113-8657 Japan RIKEN Yokohama Institute 1-7-22 Suehiro-cho Tsururni-ku Yokohama 230-0045 Japan

Thellungiella salsuginea （formerly T. halophila）, a species closely related to Arabidopsis （Arabidopsis thali-ana）, is tolerant not only to high salt levels, but also to chilling, freezing, and ozone. Here, we report that T. salsuginea also shows greater heat tolerance than Arabidopsis. We identified T. salsuginea HsfAld （TsHsfAld） as a gene that can confer marked heat tolerance on Arabidopsis. TsHsfAld was identified via Full-length cDNA Over-eXpressing gene （FOX） hunt-ing from among a collection of heat-stress-related T. salsuginea cDNAs. Transgenic Arabidopsis overexpressing TsHsfAld showed constitutive up-regulation of many genes in the Arabidopsis AtHsfA1 regulon under normal growth tempera-ture. in Arabidopsis mesophyll protoplasts, TsHsfAld was localized in both the nucleus and the cytoplasm. TsHsfAld also interacted with AtHSP90, which negatively regulates AtHsfAls by forming HsfA1-HSP90 complexes in the cytoplasm. It is likely that the partial nuclear localization of TsHsfAld induced the expression of the AtHsfAld regulon in the transgenic plants at normal temperature. We also discovered that transgenic Arabidopsis plants overexpressing AtHsfAldwere more heat-tolerant than wild-type plants and up-regulated the expression of the HsfAld regulon, as was observed in TsHsfAld-overexpressing plants. We propose that the products of both TsHsfAld and AtHsfAld function as positive regulators of Arabidopsis heat-stress response and would be useful for the improvement of heat-stress tolerance in other plants.

关键词： Thellungiella salsuginea heat-stress tolerance HsfA1 FOX hunting.

Irinotecan, a key chemotherapeutic drug for metastatic colorectal cancer

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World Journal of Gastroenterology 2015年第43期21卷 12234-12248页

作者： Ken-ichi Fujita Yutaro Kubota Hiroo ishida Yasutsuna Sasaki Institute of Molecular Oncology Showa University Department of Medical Oncology Showa University School of Medicine

Irinotecan hydrochloride is a camptothecin derivative that exerts antitumor activity against a variety of tumors. SN-38 produced in the body by carboxylesterase is the active metabolite of irinotecan. After irinotecan was introduced for the treatment of metastatic colorectal cancer(CRC) at the end of the last century,survival has improved dramatically. Irinotecan is now combined with 5-fluorouracil,oxaliplatin and several molecularly-targeted anticancer drugs,resulting in the extension of overall survival to longer than 30 mo. Severe,occasionally life-threatening toxicity occurs sporadically,even in patients in relatively good condition who have a low risk of chemotherapyinduced toxicity,often causing the failure of irinotecanbased chemotherapy. Clinical pharmacological studies have revealed that such severe toxicity is related to exposure to SN-38 and genetic polymorphisms in UDPglucuronosyltransferase 1A1 gene. The large interand intra-patient variability in systemic exposure to SN-38 is determined not only by genetic factors but also by physiological and environmental factors. This review first summarizes the roles of irinotecan in chemotherapy for metastatic CRC and then discusses the optimal dosing of irinotecan based on the aforementioned factors affecting systemic exposure to SN-38,with the ultimate goal of achieving personalized irinotecan-based chemotherapy.

关键词： Irinotecan Metastatic colorectal cancer Survival a

Visualizing the hepatic vascular architecture using superb microvascular imaging in patients with hepatitis C virus: A novel technique

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World Journal of Gastroenterology 2016年第26期22卷 6057-6064页

作者： Hidekatsu Kuroda Tamami Abe Keisuke Kakisaka Yudai Fujiwara Yuichi Yoshida Akio Miyasaka Kazuyuki ishida Hideaki ishida Tamotsu Sugai Yasuhiro Takikawa Division of Hepatology Department of Internal Medicine Iwate Medical University School of Medicine Department of Molecular Diagnostic Pathology Iwate Medical University Center of Diagnostic Ultrasound Akita Red Cross Hospital

AIM: To identify the hepatic vascular architecture of patients with hepatitis C virus(HCV) using superb microvascular imaging(SMI) and investigate the use of SMI in the evaluation of liver fibrosis.METHODS: SMI was performed in 100 HCV patients. SMI images were classified into five types according to the vascular pattern, and these patterns were compared with the fibrosis stage. Moreover, the images were analyzed to examine vascularity by integrating the number of SMI signals in the region of interest ROI [number of vascular trees(VT)]. The number of VT, fibrosis stage, serum parameters of liver function, and CD34 expression were investigated.RESULTS: There was a significant difference between SMI distribution pattern and fibrosis stage(P < 0.001). The mean VT values in each of the fibrosis stages were as follows: 26.69 ± 7.08 in F0, 27.72 ± 9.32 in F1, 36.74 ± 9.23 in F2, 37.36 ± 5.32 in F3, and 58.14 ± 14.08 in F4. The VT showed excellent diagnostic ability for F4 [area under the receiver operator characteristic(AUROC): 0.911]. The VT was significantly correlated with the CD34 labeling index(r = 0.617, P < 0.0001).CONCLUSION: SMI permitted the detailed delineation of the vascular architecture in chronic liver disease. SMI appears to be a reliable tool for noninvasively detecting significant fibrosis or cirrhosis in HCV patients.

关键词： Superb microvascular imaging Number of vascular trees Chronic liver disease Ultrasound Liver fibrosi

Effects of Propolis on Peripheral White Cells, Antioxidative Activity and Tumor Growth in Irradiated mice

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Journal of Traditional Chinese Medicine 2006年第4期26卷 299-305页

作者： Takashi Nakamura Yuka Itokawa Kwang-Ho Cho Jung-Sook Choi Ikukatsu Suzuki Toshihoro Miura Torao ishida Yeunhwa Gu Graduate School of Health Science Suzuka University of Medical Science Japan Gyeongdo provincial college Kyoungbook korea Department of Radiological Science Catholic University of Deagu College of Health Science Deagu Korea Hi-tech Research Center Suzuka University of Medical Science Japan

The effect of continuous water-soluble propolis administration on radioactivity-induced reduction of hemocytes, and the antioxidant and antitumor effects were investigated. Following a 1-week adjustment period, water-soluble propolis was administered intraperitoneally to male ICR mice at a dose of 100 mg/kg every other day for 2 weeks. Following administration, 2 Gy whole-body irradiation was performed and the counts of leukocytes, lymphocytes, and granulocytes and monocytes in the peripheral blood were determined 1, 3, 7, 15 and 30 days after irradiation. In the second experiment, water-soluble propolis was similarly administered to the mice for 2 weeks after a 1-week adjustment period, and 2 Gy whole-body irradiation was performed. The antioxidant effects in hemocytes were then investigated using 2,2’-azobis(2-amidinopropane) dihydrochloride (AAPH), a radical generator. In the third experiment, 1×106 Sarcoma-180 cells were inoculated into the right thigh of mice, which were divided into four groups: control, water-soluble propolis-treated, 6 Gy irradiated and water-soluble propolis-treated + 6 Gy irradiated groups, and changes in tumor size were measured for 20 days. Results show that administration of water-soluble propolis inhibits the reduction of hemocytes caused by whole-body irradiation, enhances antioxidant effects against radioactivity, and inhibits tumor growth.

关键词：蜂胶肿瘤生长照射损伤病理

Effects of the Chinese Herbal Medicine Based on Hachimi-jio-gan in Male Rats with the Adenine-Induced Osteopenia

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Journal of Traditional Chinese Medicine 2005年第3期25卷 226-232页

作者： Takeshi Ogirima Kaori Tano Masayuki Kanehara Ming Gao Xiuyun Wang Yi Guo Yanjun Zhang Liping Guo Torao ishida Graduate School of Health Science suzuka University of Medical Science 1001-1 Kishioka Suzuka Mie Pref. 510-0293 Japan Graduate School of Health Science Institute of Traditional Chinese Medicine Suzuka University ofMedical Science 1001-1 Kishioka Suzuka Mie Pref. 510-0293 Japan Graduate School of Health Science Suzuka University of Medical Science 1001-1 Kishioka Suzuka Mie Pref. 510-0293 Japan

In the adenine-induced renal failure rats, reversibility of renal failure and recovery of bone mineral density (BMD) by discontinuation of adenine-rich diet were reported: We think that the effect to bone metabolism with medication may be able to be evaluated as reinforcement of the BMD recovery. We have so far investigated the Chinese herbal medicine based on Hachimi-jio-gan (HJG) which are more effective than HJG alone. In this study, we investigated the effects of our Chinese herbal prescription on BMD in the adenine-treated rats compared to that of vitamin D3treatment. Young male rats were administrated 100 mg/ml adenine for 8 weeks, and they showed renal failure and bone loss. The adenine-treated rats were divided into the following 3 groups, that is, the group experienced no treatment (control), the group givenour Chinese herbal medicine (HAO), and the group given vitamin D3 (VD3) medication. It is likely that VD3 medication was less effective for increase of the femoral BMD than increase of the spinal BMD. In contrast, HAO was effective for increase of the femoral BMD. The VD3 group showed low deoxypyridinoline (Dpd: bone resorption maker) as compared to the control group.However, the HAO group showed same or slightly high Dpd. It is suggested that VD3 may increase BMD by reduction of bone resorption, while HAO may show effect on BMD by activating bone metabolism. It is indicated that HAO may become a curative medicine for bone loss because of the different target site from vitamin D3.

关键词：中医药疗法腺嘌呤肾疾病骨密度

Functional foods effective for hepatitis C: Identification of oligomeric proanthocyanidin and its action mechanism

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World Journal of Hepatology 2014年第12期6卷 870-879页

作者： Yo-ichi ishida Masahiko Takeshita Hiroaki Kataoka Department of Molecular and Cellular Biochemistry Meiji Pharmaceutical University Kiyose Tokyo 204-8588 Japan Research Division Minami Nippon Dairy Co-op. Ltd. Miyakonojo Miyazaki 885-0003 Japan Section of Oncopathology and Regenerative Biology Department of Pathology Faculty of Medicine University of Miyazaki Kiyotake Miyazaki 889-1692 Japan

Hepatitis C virus(HCV)is a major cause of viral hepatitis and currently infects approximately 170 million people worldwide.An infection by HCV causes high rates of chronic hepatitis(>75%)and progresses to liver cirrhosis and hepatocellular carcinoma ultimately.HCV can be eliminated by a combination of pegylatedα-interferon and the broad-spectrum antiviral drug ribavirin;however,this treatment is still associated with poor efficacy and tolerability and is often accompanied by serious side-effects.While some novel direct-actingantivirals against HCV have been developed recently,high medical costs limit the access to the therapy in cost-sensitive countries.To search for new natural anti-HCV agents,we screened local agricultural products for their suppressive activities against HCV replication using the HCV replicon cell system in vitro.We found a potent inhibitor of HCV RNA expression in the extracts of blueberry leaves and then identified oligomeric proanthocyanidin as the active ingredient.Further investigations into the action mechanism of oligomeric proanthocyanidin suggested that it is an inhibitor of heterogeneous nuclear ribonucleoproteins(hn RNPs)such as hn RNP A2/B1.In this review,we presented an overview of functional foods and ingredients efficient for HCV infection,the chemical structural characteristics of oligomeric proanthocyanidin,and its action mechanism.

关键词： ribavirin interferon antiviral replication cirrhosis extracts ultimately currently ingredient suppression

Radioprotective Effect of Lyophyllum Decastes and the Effect on Immunological Functions in Irradiated Mice

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Journal of Traditional Chinese Medicine 2007年第1期27卷 70-75页

作者： Takashi Nakamura Yuka Itokawa Masayuki Tajima Yuuichi Ukawa Kwang-Ho Cho Jung-Sook Choi Torao ishida Yeunhwa Gu Graduate School of Health Science Suzuka University of Medical Science Oji Forest & Product Co. Ltd Department of Radiological Science Catholic University of Deagu College of Heallth Science Gyeongdo Provincial College Hi-tech Research Center Suzuka University of Medical Science

In this study, to explore the radiation protection effects of Lyophyllum Decastes Sing (LDS), a hot distilled-water extract of LDS was orally administered at a dosage of 250mg/kg every other day for a period of 2 weeks in irradiated mice. An automatic blood cell counter was used to measure white blood cells (lymphocytes, monocyte, and granulocytes) one day before X-ray irradiation, and 3 hours, 12 hours, 24 hours, 3 days, 7 days, 15 days and 30 days after irradiation. The Dunnett test was used to examine statistical significance of differences. The peripheral blood cell counts in the Lyophyllum-administered non-irradiation group revealed an increase in the numbers of leukocytes, lymphocytes and monocytes. For 2 Gy whole body radiation, a significant statistical difference was found between the X-ray group and the Lyophyllum plus X-ray group in the numbers of leukocytes, lymphocytes and monocytes. The results suggest that Lyophyllum restrains blood cell-count falling after irradiation, which is probably mediated at least in part by hemopoietic function, and NK and LAK activities seems to play a role in preventing secondary infections associated with irradiation.

关键词：受辐照小白鼠担子菌提取物荷叶离褶伞免疫机能辐射防护作用

Case of gastric neuroendocrine carcinoma showing an interesting tumorigenic pathway

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World Journal of Clinical Cases 2017年第11期5卷 397-402页

作者： Noriyuki Uesugi Ryo Sugimoto Makoto Eizuka Yasuko Fujita Mitsumasa Osakabe Keisuke Koeda Takashi Kosaka Shunichi Yanai Kazuyuki ishida Akira Sasaki Takayuki Matsumoto Tamotsu Sugai Department of Diagnostic Molecular Pathology School of MedicineIwate Medical University Department of Surgery School of MedicineIwate Medical University Division of Gastroenterology Department of Internal MedicineSchool of MedicineIwate Medical University

Here, we report a case of gastric neuroendocrine carcinoma showing an interesting tumorigenic pathway. A 57-year-old Japanese woman presented with epigastric tenderness, and distal gastrectomy was performed. In the surgical specimen, histologically, the tumor tissue was composed of three subtypes of tumor components showing different histological architecture and cellular atypia, diagnosed as neuroendocrine tumor(NET) G2, NET G3, and neuroendocrine carcinoma(NEC) components. Immunohistochemically, the Ki-67-positive rates of NET G2, NET G3, and NEC components were 6.5%, 99.5% and 88.1%, respectively. Although allelic imbalance(AI) on chromosomes 1p, 3p, 8q, TP53, 18q and 22 q was commonly found in all components, AI of 4p was found in NET G3 and NEC components(but not in the NET G2 component). In contrast, AIs of 5q and 9p were found in only the NEC component. Thus, we showed the progression from NET G2 to NEC, via NET G3, within the same tumor.

关键词： stomach neuroendocrine tumor G2 neuroendocrine tumor G3 neuroendocrine carcinoma