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Persistent CXCR4 expression after preoperative chemoradiotherapy predicts early recurrence and poor prognosis in esophageal cancer

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World Journal of Gastroenterology 2006年第47期12卷 7585-7590页

作者： Kenji Koishi Reigetsu Yoshikawa Tohru Tsujimura Tomoko Hashimoto-Tamaoki Syoudou kojima Hidenori Yanagi Takehira Yamamura Yoshinori Fujiwara Second Department of Surgery Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Second Department of Surgery Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Institute for Advanced Medical Sciences Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Second Department of Pathology Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Institute for Advanced Medical Sciences Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Department of Genetics Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan

AIM: To study the effect of CXC chemokine receptor-4 (CXCR4) expression on disease progression and prognosis in esophageal cancer. METHODS: CXCR4 expression was evaluated in 37 patients with histologically confirmed esophageal squamous carcinomas (ESCC) undergoing preoperative chemoradiotherapy (CRT) by immunohistochemical staining. RESULTS: Eleven out of 37 ESCC patients showed a pathological complete response (CR) after CRT. CXCR4 protein expression was observed in cell cytoplasms of 13 tumors, and null expression was seen in 13 tumors. Distant recurrence was significantly more common in patients with positive CXCR4 expression (P = 0.0318). After a median follow-up time of 31.6 mo, 19 patients progressed (12 of 19 expressed positive CXCR4) and 11 died (10 of 11 expressed positive CXCR4). Overall survival was significantly correlated with lymph node metastasis (952.1 ± 53.8 d in negative group vs 475.1 ± 56.2 d in positive group, P = 0.023), distant metastasis (874.0 ± 60.4 d in negative group vs 434.9 ± 75.2 d in positive group, P = 0.014) and CRT (811.5 ± 51.2 d in responder group vs 459.6 ± 94.0 d in non-responder group, P = 0.00038) and further with an absence ofCXCR4 expression or no residual tumor (959.8 ± 51.0 d in null expression or no tumor group vs 412.0 ± 57.1 d in positive expression group, P = 0.0001). CONCLUSION: Persistent positive CXCR4 expression is implicated in tumor aggressiveness and poor prognosis in ESCC after CRT, and preoperative CRT may improve the prognosis of ESCC via CXCL12-CXCR4 signaling pathway.

关键词： CXC chemokine receptor-4 Metastasis Chemoradiotherapy Esophageal cancer

Serial changes in expression of functionally clustered genes in progression of liver fibrosis in hepatitis C patients

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World Journal of Gastroenterology 2008年第13期14卷 2010-2022页

作者： yoshiyuki Takahara Mitsuo Takahashi Qing-Wei Zhang Hirotaka Wagatsuma Maiko Mori Akihiro Tamori Susumu Shiomi Shuhei Nishiguchi Exploratory & Applied Pharmaceutical Research Department Pharmaceutical Company Ajinomoto Co. Inc. 1-1 Suzuki-cho Kawasaki-ku Kawasaki 210-8681 Japan Department of Nuclear Medicine Graduate School of Medicine Osaka City University Osaka Japan Division of Hepatobiliary and Pancreatic Diseases Department of Internal Medicine Hyogo College of Medicine Nishinomiya Japan

AIM: To investigate the relationship of changes in expression of marker genes in functional categories or molecular networks comprising one functional category or multiple categories in progression of hepatic fibrosis in hepatitis C (HCV) patients. METHODS: Marker genes were initially identified using DNA microarray data from a rat liver fibrosis model. The expression level of each fibrosis associated marker gene was analyzed using reverse transcription-polymerase chain reaction (RT-PCR) in clinical biopsy specimens from HCV-positive patients (n = 61). Analysis of changes in expression patterns and interactions of marker genes in functional categories was used to assess the biological mechanism of fibrosis. RESULTS: The profile data showed several biological changes associated with progression of hepatic fibrosis. Clustered genes in functional categories showed sequential changes in expression. Several sets of clustered genes, including those related to the extracellular matrix (ECM), inflammation, lipid metabolism, steroid metabolism, and some transcription factors important for hepatic biology showed expression changes in the immediate early phase (F1/F2) of fibrosis. Genes associated with aromatic amino acid (AA) metabolism, sulfur-containing AA metabolism and insulin/ Wnt signaling showed expression changes in the middle phase (F2/F3), and some genes related to glucose metabolism showed altered expression in the late phase of fibrosis (F3/F4). Therefore, molecular networks showing serial changes in gene expression are present in liver fibrosis progression in hepatitis C patients. CONCLUSION: Analysis of gene expression profiles from a perspective of functional categories or molecular networks provides an understanding of disease and suggests new diagnostic methods. Selected marker genes have potential utility for biological identification of advanced fibrosis.

关键词： Hepatitis C Liver fibrosis Marker gene Gene expression RT-PCR Molecular network Metabolism Transcription factor Diagnosis

Severe hypercholesterolemia associated with primary biliary cirrhosis in a 44-year-old Japanese woman

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World Journal of Gastroenterology 2004年第17期10卷 2607-2608页

作者： Tatsuo Kanda Osamu Yokosuka Hiroshige kojima Fumio Imazeki Keiich Nagao Ichiro Tatsuno Yasushi Saito Hiromitsu Saisho First Department of Medicine Chiba University School of MedicineChiba 260-8670Japan Health Sciences CenterChiba UniversityChiba 260-8670Japan Health Sciences Center Chiba UniversityChiba 260-8670Japan Second Department of Medicine Chiba University School of MedicineChiba 260-8670Japan

A 44-year-old woman developed jaundice and was diagnosed as stage Ⅱ of primary biliary cirrhosis(PBC).She showed a severely high total cholesterol *** article focuses on atypical presentations of PBC and the need to ... 详细信息

关键词： Adult Cholesterol Female Humans Hypercholesterolemia Japan Liver Cirrhosis, Biliary Severity of Illness Index

Pneumatosis cystoides intestinalis associated with massive free air mimicking perforated diffuse peritonitis

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World Journal of Gastroenterology 2008年第43期14卷 6753-6756页

作者： Yoichi Sakurai Masahiro Hikichi Jun Isogaki Shinpei Furuta Risaburo Sunagawa Kazuki Inaba yoshiyuki Komori Ichiro Uyama Department of Surgery Fujita Health University School of MedicineToyoake Aichi 470-1192Japan

While pneumatosis cystoides intestinalis （PCI） is a rare disease entity associated with a wide variety of gastrointestinal and non-gastrointestinal disorders, PCI associated with massive intra- and retroperitoneal free air is extremely uncommon, and is difficult to diagnose differentially from perforated peritonitis. We present two cases of PCI associated with massive peritoneal free air and/or retroperitoneal air that mimicked perforated peritonitis. These cases highlight the clinical importance of PCI that mimics perforated peritonitis, which requires emergency surgery. Preoperative imaging modalities and diagnostic laparoscopy are useful to make an accurate diagnosis.

关键词： Pneumatosis cystoides intestinalis Perforated peritonitis Corticosteroid therapy Peritonealfree air

Gene expression profiles of hepatic cell-type specific marker genes in progression of liver fibrosis

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World Journal of Gastroenterology 2006年第40期12卷 6473-6499页

作者： yoshiyuki Takahara Mitsuo Takahashi Hiroki Wagatsuma Fumihiko Yokoya Qing-Wei Zhang Mutsuyo Yamaguchi Hiroyuki Aburatani Norifumi Kawada Exploratory and Applied Pharmaceutical Research Department Pharmaceutical Company Ajinomoto Co. Inc Kawasaki 210-8681 Japan Biochemical Information project BiolT Business Development Group Fujitsu Limited Tokyo Japan Center for Collaborative Research Research Center for Advanced Science and Technology the University of Tokyo Tokyo Japan Department of Hepatology Graduate School of Medicine Osaka City University Osaka Japan

AIM: To determine the gene expression profile data for the whole liver during development of dimethylni-trosamine (DMN)-induced hepatic ***: Marker genes were identified for different types of hepatic cells, including hepatic stellate cells (HSCs), Kupffer cells (including other inflammatory cells), and hepatocytes, using independent temporal DNA microarray data obtained from isolated hepatic cells. RESULTS: The cell-type analysis of gene expression gave several key results and led to formation of three hypotheses: (1) changes in the expression of HSC-specific marker genes during fibrosis were similar to gene expression data in in vitro cultured HSCs, suggesting a major role of the self-activating characteristics of HSCs in formation of fibrosis; (2) expression of mast cell-specific marker genes reached a peak during liver fibrosis, suggesting a possible role of mast cells in formation of fibrosis; and (3) abnormal expression of hepatocyte-specific marker genes was found across several metabolic pathways during fibrosis, including sulfur-containing amino acid metabolism, fatty acid metabolism, and drug metabolism, suggesting a mechanistic relationship between these abnormalities and symptoms of liver fibrosis. CONCLUSION: Analysis of marker genes for specific hepatic cell types can identify the key aspects of fibro-genesis. Sequential activation of inflammatory cells and the self-supporting properties of HSCs play an important role in development of fibrosis.

关键词： Liver fibrosis Gene expression Microarray Dimethylnitrosamine Marker genes Hepatic stellate cell Kupffer cell Hepatocytes Metabolic pathway

Hypoxia-inducible factor 1 alpha and vascular endothelial growth factor overexpression in ischemic colitis

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World Journal of Gastroenterology 2005年第10期11卷 1535-1539页

作者： Tomoyuki Okuda Takeshi Azuma Masahiro Ohtani Ryuho Masaki yoshiyuki Ito Yukinao Yamazaki Shigeji Ito Masaru Kuriyama Second Department of Internal Medicine Department of Endoscopic Medicine Department of Internal Medicine

AIM: To examine the etiology and pathophysiology in human ischemic colitis from the viewpoint of ischemic factors such as hypoxia-inducible factor 1 alpha (HIF-1 alpha and vascular endothelial growth factor (VEGF). METHODS: Thirteen patients with ischemic colitis and 21 normal controls underwent colonoscopy. The follow-up colonoscopy was performed in 8 patients at 7 to 10 d after the occurrence of ischemic colitis. Biopsy samples were subjected to real-time RT-PCR and immunohistochemistry to detect the expression of HIF-1 alpha and VEGF. RESULTS: HIF-1 alpha and VEGF expression were found in the normal colon tissues by RT-PCR and immunohistochemistry. HIF-1 alpha and VEGF were overexpressed in the lesions of ischemic colitis. Overexpressed HIF-1 alpha and VEGF RNA quickly decreased to the normal level in the scar regions at 7 to 10 d after the occurrence of ischemic colitis. CONCLUSION: Constant expression of HIF-1 alpha and VEGF in normal human colon tissue suggested that HIF-1 alpha and VEGF play an important role in maintaining tissue integrity. We confirmed the ischemic crisis in ischemic colitis at the molecular level, demonstrating overexpression of HIF-1 alpha and VEGF in ischemic lesions. These ischemic factors may play an important role in the pathophysiology of ischemic colitis.

关键词： Ischemic colitis HIF-1 alpha VEGF

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陆壳的生成：与赞歧岩类的联系

科学通报 2008年第9期53卷 977-990页

作者： yoshiyuki Tatsumi Institute for Research on Earth Evolution (IFREE) Japan Agency for Marine-Earth Science and Technology (JAMSTEC) Yokosuka 237-0061Japan

陆壳的平均成分为中性,而某些典型岛弧岩浆岩也具中性的化学组成,因而,人们认为陆壳应产生于古老的会聚板块边界.中性陆壳形成的一个可能机制是直接产生于上地幔的安山质熔体.产于日本西南Setouchi火山岩带的赞歧岩类包括高镁安山岩(HM... 详细信息

陆壳的平均成分为中性,而某些典型岛弧岩浆岩也具中性的化学组成,因而,人们认为陆壳应产生于古老的会聚板块边界.中性陆壳形成的一个可能机制是直接产生于上地幔的安山质熔体.产于日本西南Setouchi火山岩带的赞歧岩类包括高镁安山岩(HMA),是俯冲板片熔融及其后的熔体-地幔相互作用的结果.该岩类形成于特殊构造环境(例如,热的岩石圈俯冲进入异常热的上地幔),这种环境可能在太古代时业已存在.富水的高镁安山岩岩浆很可能在地壳内固结形成高镁安山质岩体,然后这些岩体重熔产生了分异的赞歧岩类.目前,高镁安山岩岩浆的形成和分异可能正发生于Izu-Bonin Mariana(IBM)弧-沟系.这是因为:(1)IBM演化初始阶段以高镁安山岩岩浆作用为特征(2)IBM中地壳的波速VP与总体陆壳的波速一致.对具高镁安山质深成岩的VP估计也支持了这一点,但也不能排除英云闪长质岩在该岛弧中部地壳的存在.因此,陆壳的形成也有可能由幔源玄武质岩浆分异而产生.

关键词：高镁安山岩赞歧岩类玻安岩板片熔融陆壳

Identification of individuals with non-alcoholic fatty liver disease by the diagnostic criteria for the metabolic syndrome

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World Journal of Gastroenterology 2012年第13期18卷 1508-1516页

作者： Masahide Hamaguchi Noriyuki Takeda Takao kojima Akihiro Ohbora Takahiro Kato Hiroshi Sarui Michiaki Fukui Chisato Nagata Jun Takeda Immunology Frontier Research Center at Osaka University Osaka 5650871Japan Department of Endocrinology and Metabo lism Murakami Memorial HospitalAsahi UniversityGifu 5008523Japan Department of Gastroenterology Murakami Memorial HospitalAsahi UniversityGifu 5008523Japan Department of Endocrinology and Metabolism Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyoto 6028566Japan Department of Epidemiology and Preventive Medicine Graduate School of MedicineGifu UniversityGifu 5008523Japan Department of Diabetes and Endocrinology Division of Molecule and StructureGraduate School of MedicineGifu UniversityGifu 5008523Japan

AIM:To clarify the efficiency of the criterion of metabolic syndrome to detecting non-alcoholic fatty liver disease(NAFLD).METHODS:Authors performed a cross-sectional study involving participants of a medical health checkup program including abdominal *** study involved 11 714 apparently healthy Japanese men and women,18 to 83 years of *** was defined by abdominal ultrasonography without an alcohol intake of more than 20 g/d,known liver disease,or current use of *** revised criteria of the National Cholesterol Education Program Adult Treatment PanelⅢ were used to characterize the metabolic ***:NAFLD was detected in 32.2%(95%CI:31.0%-33.5%)of men(n=1874 of 5811)and in 8.7%(95%CI:8.0%-9.5%)of women(n=514 of 5903).Among obese people,the prevalence of NAFLD was as high as 67.3%(95%CI:64.8%-69.7%)in men and 45.8%(95%CI:41.7%-50.0%)in *** NAFLD was thought of as being the liver phenotype of metabolic syndrome,the prevalence of the metabolic syndrome among subjects with NAFLD was low both in men and women.66.8%of men and 70.4%of women with NAFLD were not diagnosed with the metabolic syndrome.48.2%of men with NAFLD and 49.8%of women with NAFLD weren't overweight[body mass index(BMI)≥25 kg/m2].In the same way,68.6%of men with NAFLD and 37.9%of women with NAFLD weren't satisfied with abdominal classification(≥90 cm for men and≥80 cm for women).Next,authors defined it as positive at screening for NAFLD when participants satisfied at least one criterion of metabolic *** sensitivity of the definition"at least 1 criterion"was as good as 84.8%in men and 86.6%in *** subjects by BMI,the sensitivity was higher in obese men and women than in non-obese men and women(92.3%vs 76.8%in men,96.1%vs 77.0%in women,respectively).CONCLUSION:Authors could determine NAFLD effectively in epidemiological study by modifying the usage of the criteria for metabolic syndrome.

关键词： Nonalcoholic fatty liver Metabolic syndrome Population based study Methodology

Japanese herbal medicine, Saiko-keishi-to, prevents gut ischemia/reperfusion-induced liver injury in rats via nitric oxide

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World Journal of Gastroenterology 2004年第15期10卷 2241-2244页

作者： Yoshinori Horie Mikio Kajihara Shuka Mori yoshiyuki Yamagishi Hiroyuki Kimura Hironao Tamai Shinzo Kato Hiromasa Ishii Department of Internal Medicine School of MedicineKeio UniversityTokyo 160-8582Japan

AIM:To determine whether Saiko-keishi-to(TJ-10),a Japanese herbal medicine,could protect liver injury induced by gut ischemia/reperfusion(I/R),and to investigate the role of NO. METHODS:Male Wistar rats were exposed to 30-min gut isohemia followed by 60 min of *** microscopy was used to monitor leukocyte *** tumor necrosis factor(TNF)levels and alanine aminotransferase (ALT)activities were ***-10 1 g/(kg.d)was intragastrically administered to rats for 7 d.A NO synthase inhibitor was administered. RESULTS:In control rats,gut I/R elicited increases in the number of stationary leukocytes,and plasma TNF levels and ALT activities were mitigated by pretreatment with *** with the NO synthase inhibitor diminished the protective effects of TJ-10 on leukostasis in the liver,and the increase of plasma TNF levels and ALT *** with TJ-10 increased plasma nitrite/nitrate levels. CONCLUSION:TJ-10 attenuates the gut I/R-induced hepatic microvascular dysfunction and sequential hepatocellular injury via enhancement of NO production.

关键词： Liver Circulation Animals Drugs, Chinese Herbal Liver Diseases control Male Nitric Oxide Rats Rats, Wistar Reperfusion Injury Research Support, Non-U.S. Gov't