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| 1 | Compound Danshen injection improves endotoxin-induced microcirculatory disturbance in rat mesentery显示文摘AIM: To investigate the effect of compound Danshen injection on lipopolysaccharide (LPS)-induced rat mesenteric microcirculatory dysfunctions and the underlying possible mechanism by an inverted intravital microscope and high-speed video camera system. METHODS: LPS was continuously infused through the jugular artery of male Wistar rats at the dose of 2 mg/kg per hour. Changes in mesenteric microcirculation,such as diameters of arterioles and venules,velocity of RBCs in venules,leukocyte rolling,adhesion and emigration,free radicals released from post-capillary venules,FITC- albumin leakage and mast cell degranulation,were observed through an inverted intravital microscope assisted with CCD camera and SIT camera. Meanwhile,the expression of adhesion molecules CD11b/CD18 and the production of free radical in neutrophils,and the expression of intercellular adhesion molecule 1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs) were quantified by flow cytometry (FACS) in vitro. RESULTS: The continuous infusion with LPS resulted in a number of responses in microcirculation,including a significant increase in the positive region of venulestained with Monastral blue B,rolling and adhesion of leukocytes,production of oxygen radical in venular wall,albumin efflux and enhanced mast cell degranulation in vivo,all of which,except for the leukocyte rolling,were attenuated by the treatment with compound Danshen injection. Experiments performed in vitro further revealed that the expression of CD11b/CD18 and the production of oxygen free radical in neutrophils,and the expression of ICAM-1 in HUVECs were increased by exposure to LPS,and they were attenuated by compound Danshen injection. CONCLUSION: These results suggest that compound Danshen injection is an efficient drug with multi-targeting potential for improving the microcirculatory disturbance. | Jing-Yan Han Yoshinori Horie Soichiro Miura, Yasutada Akiba Jun Guo Dan Li Jing-Yu Fan Yu-Ying Liu Bai-He Hu Li-Hua An Xin Chang Man Xu De-An Guo Kai Sun Ji-Ying Yang Shu-Ping Fang Ming-Ji Xian Masahiro Kizaki Hiroshi Nagata Toshifumi Hibi | 2007 | World Journal of Gastroenterology2007，13，26： | 26 |
| 2 | Human platelets inhibit liver fibrosis in severe combined immunodeficiency mice显示文摘AIM:To investigate the role of human platelets in liver fibrosis.METHODS:Severe combined immunodeficiency(SCID)mice were administered CCl4and either phosphate-buffered saline(PBS group)or human platelet transfusions(hPLT group).Concentrations of hepatocyte growth factor(HGF),matrix metallopeptidases(MMP)-9,and transforming growth factor-β(TGF-β)in the liver tissue were compared between the PBS and the hPLT groups by enzyme-linked immunosorbent assay(ELISA)and Western blotting.The effects of a human platelet transfusion on liver fibrosis included the fibrotic area,hydroxyproline content,and-smooth muscle actin(α-SMA)expression,which were evaluated by picrosirius red staining,ELISA,and immunohistochemical staining using an anti-mouse-SMA antibody,respectively.Phosphorylations of mesenchymal-epithelial transition factor(Met)and SMAD3,downstream signals of HGF and TGF-β,were compared between the two groups by Western blotting and were quantified using densitometry.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling.Furthermore,the accumulation of human platelets in the liver 2 h after platelet transfusion was compared between normal and fibrotic livers by immunohistochemical staining using an anti-human CD41 antibody.RESULTS:The fibrotic area and hydroxyproline content in the liver were both significantly lower in the hPLT group when compared to the PBS group(fibrotic area,1.7%±0.6%vs 2.5%±0.6%,P=0.03;hydroxyproline content,121±26 ng/g liver vs 156±47 ng/g liver,P=0.04).There was less α-smooth muscle actin staining in the hPLT group than in the PBS group(0.5%±0.1%vs 0.8%±0.3%,P=0.02).Hepatic expression levels of mouse HGF and MMP-9were significantly higher in the hPLT group than in the PBS group(HGF,109±13 ng/g liver vs 88±22 ng/g liver,P=0.03;MMP-9,113%±7%/GAPDH vs 92%±11%/GAPDH,P=0.04).In contrast,the concentration of mouse TGF-β in the liver tissue was significantly lower in the hPLT group than in the PBS group(22±5ng/g liver vs 39±6 ng/g liver,P=0.02).Phosphorylation of Met was more prevalent in the hPLT group than in the PBS group(37%±4%/GAPDH vs 20%±8%/GAPDH,P=0.03).Phosphorylation of SMAD3was weaker in the hPLT group than in the PBS group(60%±12%/GAPDH vs 84%±12%/GAPDH,P=0.1),although this difference was not significant.Furthermore,a lower rate of hepatocyte apoptosis was observed in the hPLT group than in the PBS group(5.9%±1.7%vs 2.9%±2.1%,P=0.02).Significant human platelet accumulation was observed in the fibrotic liver tissues,whereas few platelets accumulated in the normal liver.CONCLUSION:Human platelets inhibit liver fibrosis in SCID mice.Increased concentration of HGF in the liver suppresses hepatic stellate cell activation,induces MMPs,and inhibits hepatocyte apoptosis. | Kazuhiro Takahashi Soichiro Murata Kiyoshi Fukunaga Nobuhiro Ohkohchi | 2013 | World Journal of Gastroenterology2013，19，32： | 17 |
| 3 | Rifaximin ameliorates hepatic encephalopathy and endotoxemia without affecting the gut microbiome diversity显示文摘AIM To determine the efficacy of rifaximin for hepatic encephalopathy(HE) with the linkage of gut microbiome in decompensated cirrhotic patients.METHODS Twenty patients(12 men and 8 women; median age, 66.8 years; range, 46-81 years) with decompensated cirrhosis(Child-pugh score > 7) underwent cognitive neuropsychological testing, endotoxin analysis, and fecal microbiome assessment at baseline and after 4 wk of treatment with rifaximin 400 mg thrice a day. HE was determined by serum ammonia level and number connection test(NCT)-A. Changes in whole blood endotoxin activity(EA) was analyzed by endotoxinactivity assay. Fecal microbiome was assessed by 16 S ribosome RNA(rR NA) gene sequencing.RESULTS Treatment with rifaximin for 4 wk improved hyperammonemia(from 90.6 ± 23.9 μg/d L to 73.1 ± 33.1 μg/dL; P < 0.05) and time required for NCT(from 68.2 ± 17.4 s to 54.9 ± 20.3 s; P < 0.05) in patients who had higher levels at baseline. Endotoxin activity was reduced(from 0.43 ± 0.03 to 0.32 ± 0.09; P < 0.05) in direct correlation with decrease in serum ammonia levels(r = 0.5886, P < 0.05). No statistically significant differences were observed in the diversity estimator(Shannon diversity index) and major components of the gut microbiome between the baseline and after treatment groups(3.948 ± 0.548 at baseline vs 3.980 ± 0.968 after treatment; P = 0.544), but the relative abundances of genus Veillonella and Streptococcus were lowered.CONCLUSION Rifaximin significantly improved cognition and reduced endotoxin activity without significantly affecting the composition of the gut microbiome in patients with decompensated cirrhosis. | Kosuke Kaji Hiroaki Takaya Soichiro Saikawa Masanori Furukawa Shinya Sato Hideto Kawaratani Mitsuteru Kitade Kei Moriya Tadashi Namisaki Takemi Akahane Akira Mitoro Hitoshi Yoshiji | 2017 | World Journal of Gastroenterology2017，23，47： | 14 |
| 4 | Biomarkers for individualized dosage adjustments in immunosuppressive therapy using calcineurin inhibitors after organ transplantation显示文摘Calcineurin inhibitors (CNIs), such as cyclosporine A and tacrolimus, are widely used immunosuppressive agents for the prevention of post-transplantation rejection and have improved 1-year graft survival rates by up to 90%. However, CNIs can induce severe reactions, such as acute or chronic allograft nephropathy, hypertension, and neurotoxicity. Because CNIs have varied bioavailabilities, narrow therapeutic ranges, and individual propensities for toxic effects, therapeutic drug monitoring is necessary for all CNIs. Identifying the genetic polymorphisms in drug-metabolizing enzymes will help to determine personalized dosage regimens for CNIs, as CNIs are substrates for CYP3A5 and P-glycoprotein (P-gp, MDR1). CNIs are often concomitantly administered with voriconazole or proton pump inhibitors (PPIs), giving rise to drug interaction problems. Voriconazole and PPIs can increase the blood concentrations of CNIs, and both are primarily metabolized by CYP2C19. Thus, it is expected that interactions between CNIs and voriconazole or PPI would be affected by CYP2C19 and CYP3A5 polymorphisms. CNI-induced acute kidney injury (AKI) is a serious complication of transplantations. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) are noninvasive urinary biomarkers that are believed to be highly sensitive to CNI-induced AKI. In this article, we review the adverse events and pharmacokinetics of CNIs and the biomarkers related to CNIs, including CYP3A5, CYP2C19, MDR1, NGAL, and KIM-1. We hope that these data will help to identify the optimal biomarkers for monitoring CNI-based immunosuppressive therapy after organ transplantation. | Rao Fu Soichiro Tajima Kimitaka Suetsugu Hiroyuki Watanabe Nobuaki Egashira Satohiro Masuda | 2019 | Acta Pharmacologica Sinica2019，40，2： | 10 |
| 5 | Prognostic value of postoperative complication for early recurrence after curative resection of hepatocellular carcinoma显示文摘Background: Postoperative complications may adversely affect oncological outcomes. The aim of this study was to evaluate the impact of postoperative complications on early-phase recurrence after curative resection for hepatocellular carcinoma(HCC).Methods: We included 145 HCC patients who underwent initial and curative resection between January2004 and December 2013. Postoperative complications of grade III or higher based on Clavien–Dindo classification were defined as clinically relevant postoperative complications. Recurrence within two years after hepatectomy was defined as early-phase recurrence.Results: Thirty-eight patients(26%) developed postoperative complications. The only predictive factor for postoperative complication was longer operative duration(P = 0.037). The disease-specific survival rate of patients with complication was lower than that of patients without complications(P = 0.015). Earlyphase recurrence was observed in 20/38(53%) patients who suffered postoperative complications and36/107(34%) patients with no complications, which was statistically significant(P = 0.039). Multivariate analysis identified four factors contributing to early-phase recurrence: high serum AFP level(P = 0.042),multiple tumors(P < 0.001), poor differentiation(P = 0.036) and presence of postoperative complication(P = 0.039).Conclusions: Postoperative complication is an independent prognostic factor for early-phase recurrence after curative resection of HCC. Close observation of patients with postoperative complications may be a necessary treatment strategy for HCC. | Masataka Amisaki Hiroaki Saito Naruo Tokuyasu Teruhisa Sakamoto Soichiro Honjo Yoshiyuki Fujiwara | 2018 | Hepatobiliary & Pancreatic Diseases International2018，17，4： | 10 |
| 6 | Post-operative albumin-bilirubin grade predicts long-term outcomes among Child–Pugh grade A patients with hepatocellular carcinoma after curative resection显示文摘Background: Although Child–Pugh grade A patients with hepatocellular carcinoma(HCC) are candidates for curative resection, some may have a poor prognosis. The albumin-bilirubin(ALBI) grade, a measure of liver function based on albumin and bilirubin, has the potential to detect Child–Pugh grade A HCC patients with poor prognosis. Because components of the ALBI grade can be measured easily even after surgery, we explored the predictive values of ALBI in patient prognosis after HCC resection. Methods: In this retrospective case-control study, we included 136 HCC patients who underwent curative resection between January 2004 and December 2013 at our hospital. ALBI grade was calculated from laboratory data recorded the day before surgery and at post-operative day 5. Results: Pre-and post-operative ALBI grade predicted patients' long-term outcomes( P = 0.020 and P < 0.001, respectively, for overall survival, and P = 0.012 and P = 0.015, respectively, for recurrence-free survival). Post-operative ALBI grade was associated with patients' surgical factors of repeated hepatic resection( P = 0.012), intra-operative bleeding( P = 0.006), and surgery duration( P = 0.033). Furthermore, post-operative ALBI grade, rather than pre-operative ALBI grade, was an independent predictive factor of long-term outcome of Child–Pugh grade A patients with HCC. Conclusions: Post-operative ALBI grade is useful to predict the prognosis in patients after HCC resection. | Masataka Amisaki Ei Uchinaka Masaki Morimoto Naruo Tokuyasu Teruhisa Sakamoto Soichiro Honjo Hiroaki Saito Yoshiyuki Fujiwara | 2018 | Hepatobiliary & Pancreatic Diseases International2018，17，6： | 9 |
| 7 | 电火花加工间隙流场的三维仿真研究显示文摘间隙流场中加工屑的分布是影响火花放电频率和放电点分布的重要因素,并直接关系到加工速度与加工精度,对间隙流场中加工屑分布情况进行研究是提高加工速度、加工精度的重要途径之一。该研究在对间隙流场中工作液和加工屑的运动进行理论分析的基础上,建立间隙流场的三维仿真模型,进行电极上下往复运动过程中间隙流场和加工屑运动的仿真计算,验证实验的结果证明了仿真方法的正确性。 | 张杰 韩福柱 Isago Soichiro | 2008 | 电加工与模具2008，，2： | 8 |
| 8 | Acquired amegakaryocytic thrombocytopenia previously diagnosed as idiopathic thrombocytopenic purpura in a patient with hepatitis C virus infection显示文摘We report the first case of a patient with hepatitis C virus(HCV) infection and idiopathic thrombocytopenic purpura(ITP), who later developed acquired amegakaryocytic thrombocytopenia(AAMT), with autoantibodies to the thrombopoietin(TPO) receptor(c-Mpl). A 64-year-old woman, with chronic hepatitis C, developed severe thrombocytopenia and was diagnosed with ITP. She died of liver failure. Autopsy revealed cirrhosis and liver carcinoma. In the bone marrow, a marked reduction in the number of megakaryocytes was observed, while other cell lineages were preserved. Therefore, she was diagnosed with AAMT. Additionally, autoantibodies to c-Mpl were detected in her serum. Autoantibodies to c-Mpl are one of the causes of AAMT, acting through inhibition of TPO function, megakaryocytic maturation, and platelet formation. HCV infection induces several autoantibodies. HCV infection might also induce autoantibodies to c-Mpl, resulting in the development of AAMT. This mechanism may be one of the causes of thrombocytopenia in patients with HCV infection. | Shojiro Ichimata Mikiko Kobayashi Kohei Honda Soichiro Shibata Akihiro Matsumoto Hiroyuki Kanno | 2017 | World Journal of Gastroenterology2017，23，35： | 8 |
| 9 | Programmed cell death-1 inhibitor-related sclerosing cholangitis:A systematic review显示文摘BACKGROUND Programmed cell death-1(PD-1)inhibitor has been indicated for many types of malignancies.However,these inhibitors also cause immune-related adverse events.Hepatobiliary disorder is a phenotype of immune-related adverse event affecting 0%–4.5%of patients treated with PD-1 inhibitors.Recent studies have reported PD-1 inhibitor-related sclerosing cholangitis(SC);however,the associated clinical and pathological features are unclear.AIM To evaluate the clinical and pathological features of PD-1 inhibitor-related SC through a systematic review of the literature.METHODS The review,conducted using electronic databases in PubMed,was restricted to the period from January 2014 to September 2019 and focused on case reports/series on PD-1 inhibitor-related SC published in English.We scanned the references of the selected literature to identify any further relevant studies.Six cases previously studied by us,including three that have not yet been published,were included in this review.RESULTS Thirty-one PD-1 inhibitor-related SC cases were evaluated.Median age of patients was 67 years(range,43–89),with a male to female ratio of 21:10.The main disease requiring PD-1 inhibitor treatment was non-small cell lung cancer.Agents that caused PD-1 inhibitor-related SC were nivolumab(19 cases),pembrolizumab(10 cases),avelumab(1 case),and durvalumab(1 case).The median number of cycles until PD-1 inhibitor-related SC onset was 5.5(range,1–27).Abdominal pain or discomfort(35.5%,11/31)was the most frequent symptom.Blood serum tests identified liver dysfunction with a notable increase in biliary tract enzymes relative to hepatic enzymes,and a normal level of serum immunoglobulin G4.Biliary dilation without obstruction(76.9%,20/26),diffuse hypertrophy of the extrahepatic biliary tract(90.5%,19/21),and multiple strictures of the intrahepatic biliary tract(30.4%,7/23)were noted.In 11/23(47.8%)cases,pathological examination indicated that CD8+T cells were the dominant inflammatory cells in the bile duct or peribiliary tract.Although corticosteroids were mainly used for PD inhibitor-related SC treatment,the response rate was 11.5%(3/26).CONCLUSION Some clinical and pathological features of PD-1 inhibitor-related SC were revealed.To establish diagnostic criteria for PD-1 inhibitor-related SC,more cases need to be evaluated. | Takumi Onoyama Yohei Takeda Taro Yamashita Wataru Hamamoto Yuri Sakamoto Hiroki Koda Soichiro Kawata Kazuya Matsumoto Hajime Isomoto | 2020 | World Journal of Gastroenterology2020，26，3： | 7 |
| 10 | Intestinal Behcet's disease with esophageal ulcers and colonic longitudinal ulcers显示文摘因为食道、回肠结肠的打外面的溃疡的周期性的口头的 aphthous,红斑象 nodosum 一样爆发,生殖器的溃疡,和内视镜的调查结果的历史,肠的 Behcet 在一个 38 岁的女人的疾病与结肠的纵的溃疡被诊断。食道的损害和结肠的纵的溃疡很少在肠的 Behcet 的疾病被看见。没有任何不利效果,食管和 ileocolon 的溃疡与氢化尼松和 mesalazine 与处理的 3 wk 愈合了。Mesalazine 可以减少氢化尼松的全部的剂量要求了治疗疾病。 | Soichiro Fujiwara Ichiro Shimizu Momoko Ishikawa Kohzo Uehara Hirofumi Yamamoto Michiyo Okazaki Takahiro Horie Arata luchi Susumu Ito | 2006 | World Journal of Gastroenterology2006，12，16： | 7 |
| 11 | Generation of insulin-producing β-like cells from human iPS cells in a defined and completely xeno-free culture system显示文摘因为他们的区别能力,人的导致的 pluripotent 茎(臀部) 细胞为生产胰岛素的胰腺的细胞的产生被认为潜在的来源。在这研究,我们开发了一个五步的 xeno 免费的文化系统高效地在 vitro 区分臀部房间进生产胰岛素的房间。我们发现高少量集中为明确地首先导致区别进胰腺、十二指肠的 homeobox-1 (PDX1 ) 是关键的积极胰腺的祖先然后进 neurogenin 3 (NGN3 ) 表示胰腺的内分泌的祖先,当压制区别进肝或肠的房间时。我们也发现 3-isobutyl-1-methylxanthine (IBMX ) 的联合, exendin-4,和菸碱为进胰岛素的区别是重要的表示了各种各样的胰腺的房间标记的单人赛积极的房间。最尤其是,区分的房间包含了响应各种各样的胰岛素促泌素和葡萄糖的高水平被释放的内长的 C 肽水池。因此,我们的结果表明在 xeno 免费的条件下面产生导出臀部的胰腺的房间的可行性并且加亮他们的潜力与类型 1 糖尿病对待病人。 | Hussain Md. Shahjalal Nobuaki Shiraki Daisuke Sakano Kazuhide Kikawa Soichiro Ogaki Hideo Baba Kazuhiko Kume Shoen Kume | 2014 | Journal of Molecular Cell Biology2014，8，5： | 6 |
| 12 | 电火花线切割拐角加工精度的实时预测显示文摘提出了一种电火花线切割加工拐角加工精度的实时预测方法,并为此建立了实时预测系统。系统根据实时采集的放电能量等加工参数,通过电极丝振动解析及数控轨迹与电极丝位置关系的分析,可得出电极丝形变量与加工误差,从而可将拐角加工形状实时地再现于计算机上,实现了拐角加工精度的实时预测。 | 周晓光 荆晓雪 韩福柱 Isago Soichiro | 2008 | 电加工与模具2008，，3： | 6 |
| 13 | Association between endotoxemia and histological features of nonalcoholic fatty liver disease显示文摘AIM To assess whether surrogate biomarkers of endotoxemia were correlated with the histological features ofnonalcoholic fatty liver disease(NAFLD).METHODS One hundred twenty-six NAFLD patients who had undergone percutaneous liver biopsy were enrolled. Serum lipopolysaccharide(LPS)-binding protein(LBP) and anti-endotoxin core immunoglobulin G(Endo Cab Ig G) antibody concentrations at the time of liver biopsy were measured using the enzyme-linked immunosorbent assays to examine for relationships between biomarker levels and histological scores. RESULTS Serum LBP concentration was significantly increased in nonalcoholic steatohepatitis(NASH) patients as compared with nonalcoholic fatty liver(NAFL) subjects and was correlated with steatosis(r = 0.38, P < 0.0001) and ballooning scores(r = 0.23, P = 0.01), but not with the severity of lobular inflammation or fibrosis. Multivariate linear regression analysis revealed that LBP was associated with steatosis score and circulating C-reactive protein, aspartate aminotransferase, and fibrinogen levels. Serum Endo Cab Ig G concentration was comparable between NASH and NAFL patients. No meaningful correlations were detected between Endo Cab Ig G and histological findings. CONCLUSION LBP/Endo Cab Ig G were not correlated with lobular inflammation or fibrosis. More accurate LPS biomarkers are required to stringently assess the contribution of endotoxemia to conventional NASH. | Hiroyuki Kitabatake Naoki Tanaka Naoyuki Fujimori Michiharu Komatsu Ayaka Okubo Kyogo Kakegawa Takefumi Kimura Ayumi Sugiura Tomoo Yamazaki Soichiro Shibata Yuki Ichikawa Satoru Joshita Takeji Umemura Akihiro Matsumoto Masayoshi Koinuma Kenji Sano Toshifumi Aoyama Eiji Tanaka | 2017 | World Journal of Gastroenterology2017，23，4： | 5 |
| 14 | Nomograms for colorectal cancer:A systematic review显示文摘AIM: To assist in the selection of suitable nomograms for obtaining desired predictions in daily clinicalpractice.METHODS: We conducted electronic searches for journal articles on colorectal cancer(CRC)-associated nomograms using the search terms colon/rectal/colorectal/nomogram. Of 174 articles initially found, we retrieved 28 studies in which a nomogram for CRC was developed.RESULTS: We discuss the currently available CRCassociated nomograms, including those that predict the oncological prognosis, the short-term outcome of treatments, such as surgery or neoadjuvant chemoradiotherapy, and the future development of CRC. Developing nomograms always presents a dilemma. On the one hand, the desire to cover as wide a patient range as possible tends to produce nomograms that are too complex and yet have C-indexes that are not sufficiently high. Conversely, confining the target patients might impair the clinical applicability of constructed nomograms.CONCLUSION: The information provided in this review should be of use in selecting a nomogram suitable for obtaining desired predictions in daily clinical practice. | Kazushige Kawai Eiji Sunami Hironori Yamaguchi Soichiro Ishihara Shinsuke Kazama Hiroaki Nozawa Keisuke Hata Tomomichi Kiyomatsu Junichiro Tanaka Toshiaki Tanaka Takeshi Nishikawa Joji Kitayama Toshiaki Watanabe | 2015 | World Journal of Gastroenterology2015，21，41： | 5 |
| 15 | Oncological problems in pancreatic cancer surgery显示文摘尽管有更复杂的诊断技术的发展,胰腺的癌还没在早阶段被检测了。外科的切除术为痊愈或长期的幸存提供唯一的机会。切除术率在外科的技术和广泛的外科的申请由于最近的进展增加了。然而,手术后的预后由于通常发生的肝转移,本地复发和腹传播是差的。最近的分子生物的研究在胰腺的癌症澄清了秘密转移,微转移和系统病。在胰腺的癌症外科的几个 oncological 问题在现在的评论被讨论。 | Akimasa Nakao Tsutomu Fujii Hiroyuki Sugimoto Naohito Kanazumi Shuji Nomoto Yasuhiro Kodera Soichiro Inoue Shin Takeda | 2006 | World Journal of Gastroenterology2006，12，28： | 5 |
| 16 | Anticancer effect of linalool via cancer-specific hydroxyl radical generation in human colon cancer显示文摘AIM To investigate the anticancer mechanisms of the monoterpenoid alcohol linalool in human colon cancer cells.METHODS The cytotoxic effect of linalool on the human colon cancer cell lines and a human fibroblast cell line was examined using the WST-8 assay. The apoptosisinducing effect of linalool was measured using the terminal deoxynucleotidyl transferase d UTP nickend labeling assay and flow cytometry with Annexin V. Oxidative stress was investigated by staining for diphenyl-1-pyrenylphosphine, which is a cellular lipid peroxidation marker, and electron spin resonance spectroscopy. Sixteen SCID mice xenografted with human cancer cells were randomized into 3 groups for in vivo analysis: control and low-dose and high-dose linalool groups. The control group was administered tap water orally every 3 d. The linalool treatment groups were administered 100 or 200 μg/kg linalool solution orally for the same period. All mice were sacrificed under anesthesia 21 d after tumor inoculation, and tumors and organs were collected for immunohistochemistry using an anti-4-hydroxynonenal antibody. Tumor weights were measured and compared between groups. RESULTS Linalool induced apoptosis of cancer cells in vitro, following the cancer-specific induction of oxidative stress, which was measured based on spontaneous hydroxyl radical production and delayed lipid peroxidation. Mice in the high-dose linalool group exhibited a 55% reduction in mean xenograft tumor weight compared with mice in the control group(P < 0.05). In addition, tumor-specific lipid peroxidation was observed in the in vivo model.CONCLUSION Linalool exhibited an anticancer effect via cancerspecific oxidative stress, and this agent has potential for application in colon cancer therapy. | Kenichi Iwasaki Yun-Wen Zheng Soichiro Murata Hiromu Ito Ken Nakayama Tomohiro Kurokawa Naoki Sano Takeshi Nowatari Myra O Villareal Yumiko N Nagano Hiroko Isoda Hirofumi Matsui Nobuhiro Ohkohchi | 2016 | World Journal of Gastroenterology2016，22，44： | 5 |
| 17 | Fibroblasts, an inconspicuous but essential player in colon cancer development and progression显示文摘Tumor microenvironments have a crucial role in cancer initiation and progression, and share many molecular and pathological features with wound healing process. Unless treated, tumors, however, do not heal in contrast to wounds that heal within a limited time framework. Wounds heal in coordination of a myriad of types of cells, particularly endothelial cells, leukocytes, and fibroblasts. Similar sets of cells also contribute to cancer initiation and progression, and as a consequence, anti-cancer treatment strategies have been proposed and tested by targeting endothelial cells and/or leukocytes. Compared with endothelial cells and leukocytes, less attention has been paid to the roles of cancer-associated fibroblasts(CAFs), fibroblasts present in tumor tissues, because their heterogeneity hinders the elucidation on them at cellular and molecular levels. Here, we will discuss the origin of CAFs and their crucial roles in cancer initiation and progression, and the possibility to develop a novel type of anti-cancer treatment by manipulating the migration and functions of CAFs. | Naofumi Mukaida Soichiro Sasaki | 2016 | World Journal of Gastroenterology2016，22，23： | 4 |
| 18 | Mutations of pre-core and basal core promoter before and after hepatitis B e antigen seroconversion显示文摘AIM: To investigate the role of pre-core and basal core promoter(BCP) mutations before and after hepatitis Be antigen(HBe Ag) seroconversion.METHODS: The proportion of pre-core(G1896A) and basal core promoter(A1762T and G1764A) mutant viruses and serum levels of hepatitis B virus(HBV) DNA, hepatitis B surface antigen(HBs Ag), and HB core-related antigen were analyzed in chronic hepatitis B patients before and after HBe Ag seroconversion(n = 25), in those who were persistently HBe Ag positive(n = 18), and in those who were persistently anti-HBe positive(n = 43). All patients were infected with HBV genotype C and were followed for a median of 9 years.RESULTS: Although the pre-core mutant became predominant(24% to 65%, P = 0.022) in the HBe Ag seroconversion group during follow-up, the proportion of the basal core promoter mutation did not change. Median HBV viral markers were significantly higher in patients without the mutations in an HBe Ag positive status(HBV DNA: P = 0.003; HBs Ag: P < 0.001; HB core-related antigen: P = 0.001). In contrast, HBV DNA(P = 0.012) and HBs Ag(P = 0.041) levels were significantly higher in patients with the pre-core mutation in an anti-HBe positive status.CONCLUSION: There is an opposite association of the pre-core mutation with viral load before and after HBe Ag seroconversion in patients with HBV infection. | Nozomi Kamijo Akihiro Matsumoto Takeji Umemura Soichiro Shibata Yuki Ichikawa Takefumi Kimura Michiharu Komatsu Eiji Tanaka | 2015 | World Journal of Gastroenterology2015，21，2： | 4 |
| 19 | Breakthrough therapy for peritoneal carcinomatosis of gastric cancer:Intraperitoneal chemotherapy with taxanes显示文摘The effect of chemotherapy on peritoneal carcinomatosis(PC) of gastric cancer remains unclear.Recently,the intraperitoneal(IP) administration of taxanes [e.g.,paclitaxel(PTX) and docetaxel(DOC)] during the perioperative period has shown promising results.Herein,we summarized the rationale and methodology for using IP chemotherapy with taxanes and reviewed the clinical results.IP administered taxanes remain in the IP space at an extremely high concentration for 48-72 h.The drug directly infiltrates peritoneal metastatic nodules from the surface and then produces antitumor effects,making it ideal for IP chemotherapy.There are two types of perioperative IP chemotherapy with taxanes: neoadjuvant intraperitoneal and systemic chemotherapy and sequential perioperative intraperitoneal chemotherapy(SPIC).In SPIC,patients receive neoadjuvant IP chemotherapy and the same regimen of IP chemotherapy after cytoreductive surgery(CRS) until disease progression.Usually,a taxane dissolved in 500-1000 m L of saline at ordinary temperature is administered through an IP access port on an outpatient basis.According to phase Ⅰ?studies,the recommended doses(RD) are as follows: IP DOC,45-60 mg/m2; IP PTX [without intravenous(IV) PTX],80 mg/m2; and IP PTX(with IV PTX),20 mg/m2.Phase Ⅱ studies have reported a median survival time of 14.4-24.6 mo with a 1-year overall survival of 67%-78%.A phase Ⅲ study comparing S-1 in combination with IP and IV PTX to S-1 with IV cisplatin started in 2011.The prognosis of patients who underwent CRS was better than that of those who did not; however,this was partly due to selection bias.Although several phase Ⅱ studies have shown promising results,a randomized controlled study is needed to validate the effectiveness of IP chemotherapy with taxanes for PC of gastric cancer. | Hironori Yamaguchi Joji Kitayama Hironori Ishigami Shinsuke Kazama Hiroaki Nozawa Kazushige Kawai Keisuke Hata Tomomichi Kiyomatsu Toshiaki Tanaka Junichiro Tanaka Takeshi Nishikawa Kensuke Otani Koji Yasuda Soichiro Ishihara Eiji Sunami Toshiaki Watanabe | 2015 | World Journal of Gastrointestinal Oncology2015，7，11： | 3 |
| 20 | Erythropoietin -induced proliferation of gastric mucosal cells显示文摘瞄准:在胃的标本上分析红细胞生成素受体的本地化并且用一个猪的胃的上皮的房间文化模型在正常胃的上皮的增长上描绘红细胞生成素的效果。方法:红细胞生成素受体被 RT-PCR,西方的弄污和 immunohistochermistry 检测。有教养的胃的粘膜房间上的红细胞生成素的生长刺激效果被 ELISA 用 bromodeoxyuridine (BrdU ) 决定。结果:红细胞生成素受体在有教养的猪的胃的粘膜上皮细胞上被检测。红细胞生成素受体也在胃的粘膜上皮的底组织化学地被检测。BrdU 试金由红细胞生成素的管理在有教养的猪的胃的粘膜上皮细胞的生长潜力表明了剂量依赖者增加,以及这些效果被反的管理禁止 -- 红细胞生成素抗体(P<0.01 ) 。结论:这些调查结果显示红细胞生成素有一个潜力增殖经由红细胞生成素的胃的粘膜上皮受体。 | Kazuro Itoh Yoshio Sawasaki Kyoko Takeuchi Shingo Kato Nobuhiro Imai Yoichiro Kato Noriyuki Shibata Makio Kobayashi Yoshiyuki Moriguchi Masato Higuchi Fumio Ishihata Yushi Sudoh Soichiro Miura | 2006 | World Journal of Gastroenterology2006，12，2： | 3 |
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