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| 1 | Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by azoxymethane in mice显示文摘AIM:To investigate the causal relationship between hypoadiponectinemia and colorectal carcinogenesis in in vivo experimental model,and to determine the con-tribution of adiponectin defi ciency to colorectal cancer development and proliferation.METHODS:We examined the influence of adiponectin defi ciency on colorectal carcinogenesis induced by the administration of azoxymethane(AOM)(7.5 mg/kg,in-traperitoneal injection once a week for 8 wk),by using adiponectin-knockout(KO) mice.RESULTS:At 53 wk after the fi rst AOM treatment,KOmice developed larger and histologically more progres-sive colorectal tumors with greater frequency com-pared with wild-type(WT) mice,although the tumor incidence was not different between WT and KO mice.KO mice showed increased cell proliferation of colorec-tal tumor cells,which correlated with the expression levels of cyclooxygenase-2(COX-2) in the colorectal tumors.In addition,KO mice showed higher incidence and frequency of liver tumors after AOM treatment.Thirteen percent of WT mice developed liver tumors,and these WT mice had only a single tumor.In contrast,50% of KO mice developed liver tumors,and 58% of these KO mice had multiple tumors.CONCLUSION:Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by AOM in mice.This study strongly suggests that hypoadiponectinemia could be involved in the pathogenesis for colorectal cancer and liver tumor in human subjects. | Tamao Nishihara Miyako Baba Morihiro Matsuda Masahiro Inoue Yasuko Nishizawa Atsunori Fukuhara Hiroshi Araki Shinji Kihara Tohru Funahashi Shinji Tamura Norio Hayashi Hiroyasu Iishi Iichiro Shimomura | 2008 | World Journal of Gastroenterology2008，14，42： | 12 |
| 2 | Progress in researches about focal adhesion kinase in gastrointestinal tract显示文摘Focal adhesion kinase(FAK)is a 125-kDa non-receptor protein tyrosine.Growth factors or the clustering of integrins facilitate the rapid phosphorylation of FAK at Tyr-397 and this in turn recruits Src-family protein tyrosine kinases,resulting in the phosphorylation of Tyr-576 and Tyr-577 in the FAK activation loop and full catalytic FAK activation.FAK plays a critical role in the biological processes of normal and cancer cells including the gastrointestinal tract.FAK also plays an important role in the restitution,cell survival and apoptosis and carcinogenesis of the gastrointestinal tract.FAK is over-expressed in cancer cells and its over-expression and elevated activities are associated with motility and invasion of cancer cells.FAK has been proposed as a potential target in cancer therapy.Small molecule inhibitors effectively inhibit the kinase activity of FAK and show a potent inhibitory effect for the proliferation and migration of tumor cells,indicating a high potential for application in cancer therapy. | Hui Fang Hao Yoshio Naomoto Xiao-Hong Bao Nobuyuki Watanabe Kazufumi Sakurama Kazuhiro Noma Yasuko Tomono Takuya Fukazawa Yasuhiro Shirakawa Tomoki Yamatsuji Junji Matsuoka Munenori Takaoka | 2009 | World Journal of Gastroenterology2009，15，47： | 8 |
| 3 | Bisphenol A in combination with TNF-a selectively induces Th2 cell-promoting dendritic cells in vitro with an estrogen-like activity显示文摘Bisphenol A(BPA)is a monomer used in manufacturing a wide range of chemical products,including epoxy resins and polycarbonate.BPA,an important endocrine disrupting chemical that exerts estrogen-like activities,is detectable at nanomolar levels in human serum worldwide.The pregnancy associated doses of 17b-estradiol(E2)plus tumor-necrosis factor-a(TNF-a)induce distorted maturation of human dendritic cells(DCs)that result in an increased capacity to induce T helper(Th)2 responses.The current study demonstrated that the presence of BPA during DC maturation influences the function of human DCs,thereby polarizing the subsequent Th response.In the presence of TNF-a,BPA treatment enhanced the expression of CC chemokine ligand 1(CCL1)in DCs.In addition,DCs exposed to BPA/TNF-a produced higher levels of IL-10 relative to those of IL-12p70 on CD40 ligation,and preferentially induced Th2 deviation.BPA exerts the same effect with E2 at the same dose(0.01–0.1 mM)with regard to DC-mediated Th2 polarization.These findings imply that DCs exposed to BPA will provide one of the initial signals driving the development and perpetuation of Th2-dominated immune response in allergic reactions. | Hongchuan Guo Tianyi Liu Yasushi Uemura Shunchang Jiao Deqing Wang Zilin Lin Yayoi Narita Motoharu Suzuki Narumi Hirosawa Yasuko Ichihara Osamu Ishihara Hirosato Kikuchi Yasushi Sakamoto Satoru Senju Qiuhang Zhang Feng Ling | 2010 | Cellular & Molecular Immunology2010，7，3： | 6 |
| 4 | Narrow-band imaging observation of colorectal lesions using NICE classification to avoid discarding significant lesions显示文摘AIM: To assess the risk of failing to detect diminutive and small colorectal cancers with the 'resect and discard' policy.METHODS: Patients who received colonoscopy and polypectomy were recruited in the retrospective study. Probable histology of the polyps was predicted by six colonoscopists by the use of NICE classification. The incidence of diminutive and small colorectal cancersand their endoscopic features were assessed. RESULTS: In total, we found 681 cases of diminutive(1-5 mm) lesions in 402 patients and 197 cases of small(6-9 mm) lesions in 151 patients. Based on pathology of the diminutive and small polyps, 105 and 18 were non-neoplastic polyps, 557 and 154 were low-grade adenomas, 18 and 24 were high-grade adenomas or intramucosal/submucosal(SM) scanty invasive carcinomas, 1 and 1 were SM deeply invasive carcinoma, respectively. The endoscopic features of invasive cancer were classified as NICE type 3 endoscopically.CONCLUSION: The risk of failing to detect diminutive and small colorectal invasive cancer with the 'resect and discard' strategy might be avoided through the use of narrow-band imaging observation with the NICE classification scheme and magnifying endoscopy. | Santa Hattori Mineo Iwatate Wataru Sano Noriaki Hasuike Hidekazu Kosaka Taro Ikumoto Masahito Kotaka Akihiro Ichiyanagi Chikara Ebisutani Yasuko Hisano Takahiro Fujimori Yasushi Sano | 2014 | World Journal of Gastrointestinal Endoscopy2014，6，12： | 5 |
| 5 | Glutamine depletion induces murine neonatal melena with increased apoptosis of the intestinal epithelium显示文摘AIM:To investigate the possible biological outcome and effect of glutamine depletion in neonatal mice and rodent intestinal epithelial cells.METHODS:We developed three kinds of artificial milk with different amounts of glutamine;Complete amino acid milk (CAM),which is based on maternal mouse milk,glutamine-depleted milk (GDM),and glutaminerich milk (GRM).GRM contains three-fold more glutamine than CAM.Eighty-seven newborn mice were divided into three groups and were fed with either of CAM,GDM,or GRM via a recently improved nipple-bottle system for seven days.After the feeding period,the mice were subjected to macroscopic and microscopic observations by immunohistochemistry for 5-bromo-2'deoxyuridine (BrdU) and Ki-67 as markers of cell proliferation,and for cleaved-caspase-3 as a marker of apoptosis.Moreover,IEC6 rat intestinal epithelial cells were cultured in different concentrations of glutamine and were subject to a 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)2H-5-tetrazolio]-1,3-benzene disulfonate cell proliferation assay,flow cytometry,and western blotting to examine the biological effect of glutamine on cell growth and apoptosis.RESULTS:During the feeding period,we found colonic hemorrhage in six of 28 GDM-fed mice (21.4%),but not in the GRM-fed mice,with no differences in body weight gain between each group.Microscopic examination showed destruction of microvilli and the disappearance of glycocalyx of the intestinal wall in the colon epithelial tissues taken from GDM-fed mice.Intake of GDM reduced BrdU incorporation (the average percentage of BrdU-positive staining;GRM:13.8%,CAM:10.7%,GDM:1.14%,GRM vs GDM:P < 0.001,CAM vs GDM:P < 0.001) and Ki-67 labeling index (the average percentage of Ki67-positive staining;GRM:24.5%,CAM:22.4% GDM:19.4%,GRM vs GDM:P=0.001,CAM vs GDM:P =0.049),suggesting that glutamine depletion inhibited cell proliferation of intestinal epithelial cells.Glutamine deprivation further caused the deformation of the nuclear membrane and the plasma membrane,accompanied by chromatin degeneration and an absence of fat droplets from the colonic epithelia,indicating that the cells underwent apoptosis.Moreover,immunohistochemical analysis revealed the appearance of cleaved caspase-3 in colonic epithelial cells of GDM-fed mice.Finally,when IEC6 rat intestinal epithelial cells were cultured without glutamine,cell proliferation was significantly suppressed after 24 h (relative cell growth;4 mmol/L:100.0% ± 36.1%,0 mmol/L:25.3% ± 25.0%,P < 0.05),with severe cellular damage.The cells underwent apoptosis,accompanied by increased cell population in sub-G0 phase (4 mmol/L:1.68%,0.4 mmol/L:1.35%,0 mmol/L:5.21%),where dying cells are supposed to accumulate.CONCLUSION:Glutamine is an important alimentary component for the maintenance of intestinal mucosa.Glutamine deprivation can cause instability of the intestinal epithelial alignment by increased apoptosis. | Takayuki Motoki Yoshio Naomoto Junji Hoshiba Yasuhiro Shirakawa Tomoki Yamatsuji Junji Matsuoka Munenori Takaoka Yasuko Tomono Yasuhiro Fujiwara Hiroshi Tsuchita Mehmet Gunduz Hitoshi Nagatsuka Noriaki Tanaka Toshiyoshi Fujiwara | 2011 | World Journal of Gastroenterology2011，17，6： | 4 |
| 6 | Implications of hepatic dysfunction in Kawasaki disease:Time-related changes in aspartate aminotransferase, alanine aminotransferase,total bilirubin,and C-reactive protein levels显示文摘Importance:The cause of the hepatic dysfunction that commonly accompanies Kawasaki disease(KD)remains unclear.Objective:We tried to clarify the cause of the hepatic dysfunction.Methods:A total of 381 consecutive patients with acute KD,who had undergone inpatient treatment with intravenous immunoglobulin until the 7th day of illness,were divided into a group of 199 patients with an alanine aminotransferase(ALT)level≥40 IU/L on admission(group I),a group of 52 patients with an ALT level≥40 IU/L at some point after admission(group II),and a group of 130 patients with ALT levels consistently<40 IU/L throughout hospitalization(group III).Aspartate aminotransferase(AST),ALT,total bilirubin(T-Bil),and C-reactive protein(CRP)levels were analyzed over time,and time-courses were compared.results:In the initial stage of illness,in group I,AST,ALT,T-Bil peaked on days 1-3,and AST tended to improve significantly on the 4th day(P<0.001).T-Bil improved on day 5(P<0.01),and ALT improved significantly on day 6(P<0.001).CRP increased every day up to day 6(P<0.001).In group II,AST and ALT increased after admission,and thereafter CRP increased,then decreased.The frequency of use of aspirin and aspirin doses did not differ significantly in the three groups.Interpretation:Recovery from liver dysfunction occurred in the initial stage of illness in group I-within the period of CRP exacerbation,which is an indicator of systemic inflammation. | Yasuhiko Tomita Takashi Fukaya Yasuko Yamaura Rie Tsujiguchi Haruko Muratani Maki Shimaya | 2019 | Pediatric Investigation2019，3，1： | 3 |
| 7 | Polymorphisms of microsomal triglyceride transfer protein gene and manganese superoxide dismutase gene in non-alcoholic steatohepatitis显示文摘 | Chikako Namikawa Zhang Shu-Ping John Raynor Vyselaar Yasuko Nozaki Yoshihisa Nemoto Masafumi Ono Naoaki Akisawa Toshiji Saibara Makoto Hiroi Hideaki Enzan Saburo Onishi | 2004 | Journal of Hepatology2004，，5： | 3 |
| 8 | Single-port laparoscopic hepatectomy: technique, safety, and feasibility in a clinical case series显示文摘 | Masayasu Aikawa Mitsuo Miyazawa Kojun Okamoto Yasuko Toshimitsu Katsuya Okada Yosuke Ueno Shigeki Yamaguchi Isamu Koyama | 2012 | Surgical Endoscopy2012，，6： | 3 |
| 9 | Spermatogenesis in aged rats after prenatal 3,3′,4,4′,5-pentachlorobiphenyl exposure显示文摘 | Shin Wakui Fumio Takagi Tomoko Muto Kiyofumi Yokoo Shyou Hirono Yasuko Kobayashi Kinji Shirota Fumiaki Akahori Yoshihiko Suzuki Hiroshi Hano Hitoshi Endou Yoshikatsu Kanai | 2007 | Toxicology2007，，2： | 3 |
| 10 | Platelet‐derived growth factor receptor α‐positive cells in the tunica muscularis of human colon显示文摘 | Masaaki Kurahashi Yasuko Nakano Grant W. Hennig Sean M. Ward Kenton M. Sanders | 2012 | J. Cell. Mol. Med2012，，7： | 2 |
| 11 | Vascular endothelial dysfunction in cirrhosis显示文摘 | Yasuko Iwakiri Roberto J. Groszmann | 2007 | Journal of Hepatology2007，，5： | 2 |
| 12 | Radiation-induced autophagy is associated with LC3 and its inhibitionsensitizes malignant glioma cells显示文摘 | Hideaki Ito Shigeru Daido Takao Kanzawa Seiji Kondo Yasuko Kondo | 2005 | International Journal of Oncology2005，，5： | 2 |
| 13 | Broad antiretroviral activity and resistance profile of the novel human immunodeficiency virus integrase inhibitor elvitegravir (JTK-303/GS-9137 ) 显示文摘 | Kazuya S Eiichi K Yasuko S | 2008 | J Virol2008，82，2： | 1 |
| 14 | Local extension of pancreatic carcinoma: assessment with thin-section helical CT versus with breath-hold fast MR imaging ROC analysis显示文摘 | Taiji N Yamashita Y Yasuko A | 1999 | Radiology1999，212，2： | 1 |
| 15 | Clinical usefulness of frac- tional exhaled nitric oxide for diagnosing prolonged cough 显示文摘 | Suguru S Junpei S Yasuko S | 2008 | Respir Med2008，102，10： | 1 |
| 16 | Slow-release of potassium from potassium silicate fertilizer显示文摘 | Yasuko Yao Kaoru Satoh Tatsuhito Takahashi | 2005 | Journal of Science of Soil and Fertilizer in Japan2005，76，6： | 1 |
| 17 | Improving the oral bioavilability of albendazole in rabbits by the solid dispersion technique显示文摘 | Nanori Kohri Yasuko Yamayoshi Xin H | 1999 | J Pharm Pharmacol1999，51，： | 1 |
| 18 | Oral administration of FAK inhibitor TAE226 inhibits the progression of peritoneal dissemination of colorectal cancer显示文摘 | Hui-fang Hao Munenori Takaoka Xiao-hong Bao Zhi-gang Wang Yasuko Tomono Kazufumi Sakurama Toshiaki Ohara Takuya Fukazawa Tomoki Yamatsuji Toshiyoshi Fujiwara Yoshio Naomoto | 2012 | Biochemical and Biophysical Research Communications2012，，： | 1 |
| 19 | Impact of genetic insights into calpain biology显示文摘 | Hiroyuki S Shoji H Yasuko O | 2011 | J Biochem2011，150，1： | 1 |
| 20 | Genetic variants in PCSK9 in the Japanese population: Rare genetic variants in PCSK9 might collectively contribute to plasma LDL cholesterol levels in the general population显示文摘 | Yasuko Miyake Rina Kimura Yoshihiro Kokubo Akira Okayama Hitonobu Tomoike Taku Yamamura Toshiyuki Miyata | 2007 | Atherosclerosis2007，，： | 1 |
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