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Ellagic acid induces apoptosis through inhibition of nuclear factor κB in pancreatic cancer cells

World Journal of Gastroenterology 2008年第23期14卷 3672-3680页

作者： Mouad Edderkaoui Irina Odinokova Izumi ohno Ilya Gukovsky Vay Liang W Go Stephen J Pandol Anna S Gukovskaya Department of Medicine Veterans Affairs Greater Los Angeles Healthcare System and University of CaliforniaLos Angeles CA 90073CaliforniaUnited States Institute of Theoretical and Experimental Biophysics Russian Academy of SciencesPushchinoMoscow Region 142290Russia

AIM： To determine the effect of ellagic acid on apoptosis and proliferation in pancreatic cancer cells and to determine the mechanism of the pro-survival effects of ellagic acid.METHODS： The effect of ellagic acid on apoptosis was assessed by measuring Phosphatidylserine externalization, caspase activity, mitochondrial membrane potential and DNA fragmentation; and proliferation by measuring DNA thymidine incorporation. Mitochondrial membrane potential was measured in permeabilized cells, and in isolated mitochondria. Nuclear factor κB （NF-κB） activity was measured by electromobility shift assay （EMSA）. RESULTS： We show that ellagic acid, a polyphenolic compound in fruits and berries, at concentrations 10 to 50 mmol/L stimulates apoptosis in human pancreatic adenocarcinoma cells. Further, ellagic acid decreases proliferation by up to 20-fold at 50 mmol/L. Ellagic acid stimulates the mitochondrial pathway of apoptosis associated with mitochondrial depolarization, cytochrome C release, and the downstream caspase activation. Ellagic acid does not directly affect mitochondria. Ellagic acid dose-dependently decreased NF-κB binding activity. Furthermore, inhibition of NF-κB activity using IkB wild type plasmid prevented the effect of ellagic acid on apoptosis. CONCLUSION： Our data indicate that ellagic acid stimulates apoptosis through inhibition of the prosurvival transcription factor NF-κB.

关键词： Ellagic acid Nuclear factor-κB Apoptosis Pancreatic cancer

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Immunohistochemical Study of Serum Proteins in Normal and Cadmium-Treated Mouse Testis by in vivo Cryotechnique

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Journal of Reproduction and Contraception 2005年第3期16卷 137-146页

作者： Nobuo TERADA Nobuhiko ohno Yasuhisa FUJII Shinichi ohno Department of Anatomy Interdisciplinary Graduate School of Medicine and Engineering University of Yamanashi Yamanashi 409-3898 Japan

Objective To investigate time-dependent changes of serum proteins permeability in the normal and cadmium（Cd）-treated mouse testis, reflecting tight junctional （TJ） barriers of Sertoli cells Methods The serum proteins, albumin and immunoglobulin-G（IgG）, in the seminiferous tubules were firstly immobilized by the “in vivo cryotechnique”, in which the dynamic blood circulation was always kept. The cryofixed testicular tissues were then processed for the freeze-substitution method, and embedded in the paraffin wax. Serial sections of 5μm thickness were immunostained by anti-mouse albumin or IgG antibody with peroxidase immunostaining, and also stained with hematoxylin-eosine （HE）for morphological observation. Results In normal seminiferous tubules, albumin immunoreaction products were localized around peritubular myoid cells and among Leydig cells, as well as in blood vessels. They were also localized as arch-like patterns around some spermatogonia in basal compartments. The number of the immunopositive arch structures was different according to developmental stages of the seminiferous cycle, judging from the arrangement of germ cells by HE-staining. The patterns of localization of IgG immunostaining in normal mouse testis were similar to that of albumin. In 24 h after Cd-treatment, some enlarged spaces and vesicular formation in the seminiferous epithelium were observed on the paraffin sections by HE-staining. The albumin or IgGimmunolocalization was seen not only in the basal compartments, but also in the adluminal compartments between *** and germ cells. Conclusion The structural changes of inter-Sertoli TJ barriers in vivo, such as different immunostaining patterns of serum proteins between the normal and Cd-treated mouse seminiferous tubules, could be clearly detected by the “in vivo cryotechnique” with albumin or IgG immunohistochemistry.

关键词： immunohistochemistry in vivo cryotechnique serum proteins testis cadmium

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Pharmacy residency system in Gunma University Hospital

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Asian Journal of Pharmaceutical Sciences 2016年第1期11卷 215-216页

作者： Asami Matsushita Daisuke Nagano Mikako Shimone kyoko Obayashi Takuya Araki Koujirou Yamamoto Department of Pharmacy Gunma University Hospital3-39-15 Showa-machiMaebashi 371-8511Japan Department of Clinical Pharmacology Gunma University Graduate School of Medicine3-39-22 Showa-machiMaebashi 371-8511Japan

Recently,undergraduate and postgraduate pharmaceutical education systems have been changing greatly in *** 2006,undergraduate pharmacist program was changed from 4 years course to 6 years course to train higher-quality pharmacists who can deal with the changes in the progression of medical technology and meet social demands for medication safety[1].As a postgraduate training system,pharmacy residency system was started in several hospital in 2002,and around 35 hospitals have pharmacy residency system at 2015[2].

关键词： Pharmacy residency system Postgraduate pharmaceutical program Teaching program Japanese pharmacy

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Intraarterial and intravenous contrast enhanced CT and MR imaging of multi-step hepatocarcinogenesis defining the early stage of hepatocellular carcinoma development

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Hepatoma Research 2020年第6期6卷 107-120页

作者： Satoshi Kobayashi Kazuto Kozaka Toshifumi Gabata Osamu matsui Tetsuya Minami Department of Quantum Medical Technology Kanazawa University Graduate School of Medical SciencesKanazawa 920-0942Japan Department of Radiology Kanazawa University Graduate School of Medical SciencesKanazawa 920-8641Japan Department of Radiology Kanazawa Medical UniversityUchinada 920-0293Japan

Liver cancer is the second leading cause of cancer deaths in men worldwide,and the 6th and 7th cause of cancer deaths in men and women in developed countries.70%-90%of primary liver cancer is hepatocellular *** B or C viruses and chronic inflammation due to alcohol intake are the main risk factors for hepatocellular *** of the key approaches for the early detection of hepatocellular carcinoma is to understand the specific imaging findings of liver nodules in the multi-step hepatocrcinogenesis *** this article,we review the imaging findings of multistep hepatocarcinogenesis,with a focus on the early detection of malignant,cirrhotic nodules with CT and MRI.

关键词： Hepatocellular carcinoma multistep hepatocarcinogenesis early hepatocellular carcinoma dysplastic nodule CT MRI

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Characteristics of superficial esophageal squamous cell carcinomas undetectable with narrow-band imaging endoscopy

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Gastroenterology Report 2021年第5期9卷 402-407,I0001页

作者： Shingo Ono Akira Dobashi Hiroto Furuhashi Akio Koizumi Hiroaki matsui Yuko Hara Kazuki Sumiyama Department of Endoscopy The Jikei University School of MedicineTokyoJapan

Background The detection rate of narrow-band imaging(NBI)for superficial esophageal squamous cell carcinoma(SESCC),including high-grade intraepithelial neoplasia,is significantly higher than that of white-light ***,there are SESCCs that are undetectable by NBI but detectable by Lugol chromoendoscopy(LCE)and the characteristics of these SESCCs are still ***,this study aimed to clarify the characteristics of SESCC that are undetectable using *** Patients with current SCC or a history of SCC in the head and neck or in the esophagus were *** inspection of the esophagus was initiated by NBI,followed by *** were taken of all suspected SESCC lesions during NBI observation and Lugol-voiding lesions(LVLs)that were irregularly shaped and>5mmand/or pink in color during LCE *** characteristics of SESCC that were undetectable with NBI were statistically *** Overall,147 lesions in 105 cases were histologically diagnosed as *** in 15 cases were NBI-undetectable lesions,all of which were macroscopic flat type(0-IIb).The median sizes of the NBI-undetectable lesions and NBI-detectable lesions were both 15mm(P=0.47).Multivariate analysis revealed independent factors for NBI-undetectable lesions such as numerous irregularly shaped LVLs(odds ratio[OR]:4.94,95%confidence interval[CI]:1.39–17.5,P<0.05)and anterior wall position(OR:4.99,95%CI:1.58–15.8,P<0.05).Conclusions The detection of SESCCs with NBI is challenging when lesions are morphologically completely flat,in cases with numerous irregularly shaped LVLs,and if located at the anterior wall.

关键词： esophageal squamous cell carcinoma narrow-band imaging Lugol chromoendoscopy Lugol-voiding lesions

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Supplementing Conventional Treatment with Pycnogenol(R) May Improve Hepatitis C Virus-Associated Type 2 Diabetes:A Mini Review

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Journal of Clinical and Translational Hepatology 2016年第3期4卷 228-233页

作者： Sayeh Ezzikouri Fatima Zahra Jadid Salsabil Hamdi Lahcen Wakrim kyoko Tsukiyama-Kohara Soumaya Benjelloun Virology Unit Viral Hepatitis Laboratory Institut Pasteur du Maroc Casablanca Morocco Virology Unit Immunovirology Laboratory Institut Pasteur du Maroc Casablanca Morocco Laboratory of Animal Hygiene Joint Faculty of Veterinary MedicineKagoshima University Kagoshima Japan Transboundary Animal Diseases Centre Joint Faculty of Veterinary MedicineKagoshima University Kagoshima Japan

Hepatitis C virus (HCV) infection and type 2 diabetes mellitus (T2DM) present a significant health burden,with increasing complications and mortality rates ***(R) (PYC),a natural product,possesses antidiabetic and antiviral properties that may improve HCV-associated *** this review,we present previously published data on the effectiveness of PYC against HCV replication and *** believe that supplementing conventional treatment with PYC may improve the current HCV therapy,attenuate HCV-associated T2DM,and reduce the risk of complications such as cirrhosis or hepatocellular carcinoma and cardiovascular disease.

关键词： T2DM Hepatitis C Pycnogenol(R) Complementary medicine

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Ratio of mean platelet volume to platelet count is a potential surrogate marker predicting liver cirrhosis

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World Journal of Hepatology 2018年第1期10卷 82-87页

作者： Hiroya Iida Masaki Kaibori Kosuke matsui Morihiko Ishizaki Masanori Kon Department of Surgery Kansai Medical University

AIM To provide a simple surrogate marker predictive of liver cirrhosis(LC).METHODS Specimens from 302 patients who underwent resection for hepatocellular carcinoma between January 2006 and December 2012 were retrospectively analyzed. Based on pathologic findings, patients were divided into groups based on whether or not they had LC. Parameters associated with hepatic functional reserve were compared in these two groups using MannWhitney U-test for univariate analysis. Factors differing significantly in univariate analyses were entered into multivariate logistic regression *** There were significant differences between the LC group(n = 100) and non-LC group(n = 202) in prothrombin activity, concentrations of alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin, cholinesterase, type Ⅳ collagen, hyaluronic acid, indocyanine green retention rate at 15 min, maximal removal rate of technitium-99 m diethylene triamine pentaacetic acid-galactosyl human serum albumin and ratio of mean platelet volume to platelet count(MPV/PLT). Multivariate analysis showed that prothrombin activity, concentrations of alanine aminotransferase, aspartate aminotransferase, total bilirubin and hyaluronic acid, and MPV/PLT ratio were factors independently predictive of LC. The area under the curve value for MPV/PLT was 0.78,with a 0.8 cutoff value having a sensitivity of 65% and a specificity of 78%.CONCLUSION The MPV/PLT ratio, which can be determined simply from the complete blood count, may be a simple surrogate marker predicting LC.

关键词： Mean platelet volume Platelet count Liver cirrhosis Hepatic functional reserve Liver fibrosis

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Recurrence of cholestatic liver disease after living donor liver transplantation

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World Journal of Gastroenterology 2008年第33期14卷 5105-5109页

作者： Sumihito Tamura Yasuhiko Sugawara Junichi Kaneko Junichi Togashi Yuichi matsui Noriyo Yamashiki Norihiro Kokudo Masatoshi Makuuchi Artificial Organ and Transplantation Division Department of Surgery Graduate School of Medicine University of Tokyo7-3-1 Hongo Bunkyo-ku Tokyo 113-8655 Japan Japanese Red Cross Medical Center 4-1-22 Hiroo Shibuya-ku Tokyo 150-8935 Japan

End-stage liver disease, due to cholestatic liver diseases with an autoimmune background such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), is considered a good indication for liver transplantation. Excellent overall patient and graft outcomes, based mostly on the experience from deceased donor liver transplantation (DDLT), have been reported. Due to the limited number of organ donations from deceased donors in most Asian countries, living donor liver transplantation (LDLT) is the mainstream treatment for end-stage liver disease, including that resulting from PBC and PSC. Although the initial experiences with LDLT for PBC and PSC seem satisfactory or comparable to that with DDLT, some aspects, including the timing of transplantation, the risk of recurrent disease, and its long-term clinical implications, require further evaluation. Whether or not the long-term outcomes of LDLT from a biologically related donor are equivalent to that of DDLT requiresfurther observations. The clinical course following LDLT may be affected by the genetic background shared between the recipient and the living related donor.

关键词： Liver transplantation Primary biliary cirrhosis Primary sclerosing cholangitis Living donor Recurrence

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A plant sesquiterpene lactone and its derivative reduce cutaneous side effect of vemurafenib,a BRAF inhibitor drug to treat late stage melanoma

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中国药理学与毒理学杂志 2015年第S1期29卷 90-91页

作者： Meng-ting CHANG Jia-hua FENG kyoko NAKAGAWA-GOTO Kuo-Hsiung LEE Lie-Fen SHYUR Agricultural Biotechnology Research Center Academia Sinica Chinese Taipei 115 Institute of Plant Biology College of Life Science National Taiwan University Chinese Taipei 106 College of Medical Pharmaceutical and Health Sciences Kanazawa University Kakuma-machi Kanazawa 920-1192 Japan Natural Products Research Laboratories Eshelamn School of Phamacy University of North Carclina Chape Hill North Carolina 27599 USA

OBJECTIVE To investigate the pharmacological effect of a plant sesquiterpene lactone(designated D)and its semi-organically synthesized novel derivative(designated S)and the role of lipid mediators,viz.,oxylipins in attenuating vemurafenib-induced cutaneous side *** A DMBA/TPAinduced skin carcinogenesis mouse model mimicking cutaneous side effect caused by vemurafenib was established to evaluate the efficacy of compound D and S in reversal of vemurafenib side *** oxylipin metabolomics platform using UPLC-TQD mass spectrometry coupled with partial least squares-discriminant analysis(PLS-DA)analysis,cell-based assays,and immunochemistry analysis were performed to elucidate the mechanism insights of DET and S compounds and the role of specific oxylipins in skin cancer *** Vemurafenib treatment expedited the skin papillomas formation in DMBA-TPA treated mouse from week 6 to week *** D and S compounds could suppress the vemurafenib side effect and also decrease total papillomas numbers(55% to 72%)and average sizes(66% to 89%).Oxylipins metabolome analysis shows that specific arachidonic acid metabolites may play a role in vemurafenib-induced squamous cell carcinoma or keratoacanthomas formation in mouse skin that can be deregulated by D or S compound ***,S compound can inhibit vemurafenib-induced paradoxical activation of MAP kinases in mouse skin or in NRAS mutant melanoma *** Our results indicate that plant sesquiterpene lactone D and its novel analog can reduce cutaneous side effect of vemurafenib through novel modes of action by inhibiting paradoxical activation of MAP kinases and de-regulating pro-inflammation mediators COX-2 and specific ecosanoid-type of *** study may suggest a novel adjuvant therapy approach in treatment of BRAFV600 Emutant melanoma.

关键词： vemurafenib sesquiterpene lactone two-stage carcin

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A novel large deletion(exons 12,13)and a missense mutation(p.G46R)in the PAH in a Japanese patient with phenylketonuria

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World Journal of Pediatrics 2015年第2期11卷 181-184页

作者： Yoshihiro Maruo Masafumi Suzaki Katsuyuki matsui Yu Mimura Asami Mori Haruo Shintaku Yoshihiro Takeuchi Department of Pediatrics Shiga University of Medical ScienceTsukinowaSetaOtsuShiga 520-2192Japan Central Research Laboratory Shiga University of Medical ScienceTsukinowaSetaOtsuShiga 520-2192Japan Department of Pediatrics Osaka City University Graduate School of MedicineOsakaJapan

Background:Phenylketonuria(PKU)is caused by a defect in phenylalanine hydroxylase(PAH).More than 500 mutations have been reported for the gene encoding ***,approximately l%-5%of these include large deletions and large duplications that cannot be detected by conventional ***:In this report we tried to fully characterize a PAH-deficient *** patient was a 2-year-old Japanese boy who was diagnosed with classical PKU at the time of neonatal screening,which was confirmed by the tetrahydrobiopterin-loading ***-related direct sequencing and multiplex ligation-dependent probe amplification(MLPA)were used to analyze of the PAH of the ***:Using PCR-related direct sequencing method,we could detect only a heterozygous novel missense mutation:p.136G>C(p.G46R).A second mutation was detected by *** patient was heterozygous for a novel large deletion of exons 12 and 13:c.1200-?_1359+?del(EX12_13del).For genetic counseling,an accurate genetic diagnosis is often ***:Through a combination of MLPA and conventional methods,the success rate of PAH mutation identification can be close to 100%.

关键词： large deletion multiplex ligation-dependent probe amplification phenylalanine hydroxylase phenylketonuria

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