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| 1 | Non-invasive diagnosis of liver fibrosis and cirrhosis显示文摘The evaluation and follow up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, during the last 20 years, it has become evident that this 'gold-standard' is imperfect; even according to its proponents, it is only 'the best' among available methods. Attempts at uncovering non-invasive diagnostic tools have yielded multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and can be repeated essentially as often as required. Most are much less expensive than liver biopsy. Consequently, their use is growing, and in some countries the number of biopsies performed, at least for routine evaluation of hepatitis B and C, has declined sharply. However, the accuracy and diagnostic value of most, if not all, of these methods remains controversial. In this review for the practicing physician, we analyze established and novel biomarkers and physical techniques. We may be witnessing in recent years the beginning of the end of the first phase for the development of non-invasive markers. Early evidence suggests that they might be at least as good as liver biopsy. Novel experimental markers and imaging techniques could produce a dramatic change in diagnosis in the near future. | Yoav Lurie Muriel Webb Ruth Cytter-Kuint Shimon Shteingart Gerardo Z Lederkremer | 2015 | World Journal of Gastroenterology2015，21，41： | 36 |
| 2 | Beneficial effects of naringenin in liver diseases: Molecular mechanisms显示文摘Liver diseases are caused by different etiological agents, mainly alcohol consumption, viruses, drug intoxication or malnutrition. Frequently, liver diseases are initiated by oxidative stress and inflammation that lead to the excessive production of extracellular matrix(ECM), followed by a progression to fibrosis, cirrhosis and hepatocellular carcinoma(HCC). It has been reported that some natural products display hepatoprotective properties. Naringenin is a flavonoid with antioxidant, antifibrogenic, anti-inflammatory and anticancer properties that is capable of preventing liver damage caused by different agents. The main protective effects of naringenin in liver diseases are the inhibition of oxidative stress, transforming growth factor(TGF-β) pathway and the prevention of the transdifferentiation of hepatic stellate cells(HSC), leading to decreased collagen synthesis. Other effects include the inhibition of the mitogen activated protein kinase(MAPK), toll-like receptor(TLR) and TGF-β non-canonical pathways, the inhibition of which further results in a strong reduction in ECM synthesis and deposition. In addition, naringenin has shown beneficial effects on nonalcoholic fatty liver disease(NAFLD) through the regulation of lipid metabolism, modulating the synthesis and oxidation of lipids and cholesterol. Moreover, naringenin protects from HCC, since it inhibits growth factors such as TGF-β and vascular endothelial growth factor(VEGF), inducing apoptosis and regulating MAPK pathways. Naringenin is safe and acts by targeting multiple proteins. However, it possesses low bioavailability and high intestinal metabolism. In this regard, formulations, such as nanoparticles or liposomes, have been developed to improve naringenin bioavailability. We conclude that naringenin should be considered in the future as an important candidate in the treatment of different liver diseases. | Erika Hernández-Aquino Pablo Muriel | 2018 | World Journal of Gastroenterology2018，24，16： | 31 |
| 3 | Quantitative analysis using ELISA of vascular endothelial growth factor and basic fibroblast growth factor in human colorectal cancer,liver metastasis of colorectal cancer and hepatocellular carcinoma显示文摘TO THE EDITOR Angiogenesis consists of the sprouting of capillaries from pre-existing vessels . It is well-known that tumor growth is angiogenesis-dependent. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) stimulated vascular endothelial cell proliferation and are involved in the neoplastic angiogenesis of several types of tumors including those of the intestinal tract.Authors usually investigated VEGF and bFGF protein expressions using immunohistochemistry or Western blotting and VEGF and bFGF transcripts using reverse transcriptase polymerase chain reaction (RT-PCR). We recently reported in a previous issue of the World Journal of Gastroenterology that cirrhotic liver tissue levels of these two | Muriel Mathonnet Bernard Descottes Denis Valleix Francois Labrousse Véronique Truffinet Yves Denizot | 2006 | World Journal of Gastroenterology2006，12，23： | 27 |
| 4 | 空间碎片天基主动清除技术发展现状及趋势显示文摘随着国内外航天发射任务逐年增多,大量在轨滞留的失效航天器将成为未来空间资源有效利用所面临的一个严峻挑战。空间碎片天基主动清除技术是从根源上对空间资源化利用与安全处置的措施,将提升和加强近地空间的可持续循环利用。本文明晰了空间碎片天基主动清除的概念,分析了空间碎片天基主动清除技术的发展历程,提出了其发展过程中面临的非合作目标相对导航、协调控制和捕获方式及装置等主要问题,为我国空间碎片天基主动清除技术的发展提出了有益参考。 | 曹喜滨 李峰 张锦绣 Richard Muriel | 2015 | 国防科技大学学报2015，37，4： | 25 |
| 5 | Effect of resistance training on non-alcoholic fatty-liver disease a randomized-clinical trial显示文摘AIM:To evaluate the effect of resistance training(RT)on non alcoholic liver disease(NAFLD)patients.METHODS:A randomized clinical trial enrolling NAFLD patients without secondary liver disease(e.g.,without hepatitis B virus,hepatitis C virus or excessive alcohol consumption).Patients were randomly allocated either to RT,three times weekly,for 3 mo or a control arm consisting of home stretching.The RT included leg press,chest press,seated rowing,latissimus pull down etc.with 8-12 repetitions,3 sets for each exercise,for a total duration of 40 min.Hepatic ultrasound,fasting blood tests,anthropometrics and body composition by dual energy X-ray absorptiometry were assessed.At baseline and follow-up,patients filled out a detailed semi-quantitative food frequency questionnaire reporting their habitual nutritional intake.Steatosis was quantified by the hepatorenal-ultrasound index(HRI)representing the ratio between the brightness level of the liver and the right kidney.The HRI has been previously demonstrated to be highly reproducible and was validated against liver biopsy and proton magnetic resonance spectroscopy.RESULTS:Eighty two patients with primary NAFLD were randomized to receive 3 mo of either RT or stretching.After dropout or exclusion from analysis because of protocol violation(weight change>3 kg),thirty three patients in the RT arm and 31 in the stretching arm completed the study per protocol.All baseline characteristics were similar for the two treatment groups with respect to demographics,anthropometrics and body composition,blood tests and liver steatosis on imaging.HRI score was reduced significantly in the RT arm as compared to the stretching arm(-0.25±0.37 vs-0.05±0.28,P=0.017).The RT arm had a significantly higher reduction in total,trunk and android fat with increase in lean body mass.There was no correlation between the reduction in HRI in the RT arm and weight change during the study,but it was positively correlated with the change in trunk fat(r=0.37,P=0.048).The RT arm had a significant reduction in serum ferritin and total cholesterol.There was no significant difference between arms in dietary changes and these did not correlate with HRI change.CONCLUSION:Three months RT improves hepatic fat content accompanied by favorable changes in body composition and ferritin.RT may serve as a complement to treatment of NAFLD. | Shira Zelber-Sagi Assaf Buch Hanny Yeshua Nahum Vaisman Muriel Webb Gil Harari Ofer Kis Naomi Fliss-Isakov Elena Izkhakov Zamir Halpern Erwin Santo Ran Oren Oren Shibolet | 2014 | World Journal of Gastroenterology2014，20，15： | 17 |
| 6 | Sex hormones in the modulation of irritable bowel syndrome显示文摘Compelling evidence indicates sex and gender differences in epidemiology,symptomatology,pathophysiology,and treatment outcome in irritable bowel syndrome(IBS).Based on the female predominance as well as the correlation between IBS symptoms and hormonal status,several models have been proposed to examine the role of sex hormones in gastrointestinal(GI)function including differences in GI symptoms expression in distinct phases of the menstrual cycle,in pre-and post-menopausal women,during pregnancy,hormonal treatment or after oophorectomy.Sex hormones may influence peripheral and central regulatory mechanisms of the brain-gut axis involved in the pathophysiology of IBS contributing to the alterations in visceral sensitivity,motility,intestinal barrier function,and immune activation of intestinal mucosa.Sex differences in stress response of the hypothalamic-pituitary-adrenal axis and autonomic nervous system,neuroimmune interac-tions triggered by stress,as well as estrogen interactions with serotonin and corticotropin-releasing factor signaling systems are being increasingly recognized.A concept of'microgenderome'related to the potential role of sex hormone modulation of the gut microbiota is also emerging.Significant differences between IBS female and male patients regarding symptomatology and comorbidity with other chronic pain syndromes and psychiatric disorders,together with differences in efficacy of serotonergic medications in IBS patients confirm the necessity for more sex-tailored therapeutic approach in this disorder. | Agata Mulak Yvette Taché Muriel Larauche | 2014 | World Journal of Gastroenterology2014，20，10： | 14 |
| 7 | 斯德哥尔摩的拥挤收费政策——政策实施5年后的效果、接受度及经验启示显示文摘根据2006年拥挤收费政策试运行结束后的公民投票结果,2007年,斯德哥尔摩正式实施了该政策。讨论了其至2011年6月首个5年内的政策实施效果。结果表明,受到外部因素影响,由收费引起的交通减少量随时间推移稍有增加。2008年的清洁汽车免税措施可显著提高销售量。结合最新研究成果和瑞典的经验,讨论了公众接受度和政治接受度。得到的结论是:拥挤收费对交通系统的主客观影响,以及环境和政治态度,是公众支持拥挤收费的基础;同时,为了获得政治支持,必须要进行体制改革、解决权力问题。最后,简要讨论了拥挤收费的实施对瑞典交通规划进程的可能影响。 | Maria Brjesson Jonas Eliasson Muriel B.Hugsson Karin Brundell-Freij 刘莹 蔡静 | 2012 | 城市交通2012，10，2： | 10 |
| 8 | Naringenin prevents experimental liver fibrosis by blocking TGFβ-Smad3 and JNK-Smad3 pathways显示文摘AIM To study the molecular mechanisms involved in the hepatoprotective effects of naringenin(NAR)on carbon tetrachloride(CCl4)-induced liver fibrosis.METHODS Thirty-two male Wistar rats(120-150 g)were randomly divided into four groups:(1)a control group(n=8)that received 0.7%carboxy methyl-cellulose(NAR vehicle)1 m L/daily p.o.;(2)a CCl4 group(n=8)that received 400 mg of CCl4/kg body weight i.p.3 times a week for 8 wk;(3)a CCl4+NAR(n=8)group that received 400 mg of CCl4/kg body weight i.p.3times a week for 8 wk and 100 mg of NAR/kg body weight daily for 8 wk p.o.;and(4)an NAR group(n=8)that received 100 mg of NAR/kg body weight daily for 8 wk p.o.After the experimental period,animals were sacrificed under ketamine and xylazine anesthesia.Liver damage markers such as alanine aminotransferase(ALT),alkaline phosphatase(AP),γ-glutamyl transpeptidase(γ-GTP),reduced glutathione(GSH),glycogen content,lipid peroxidation(LPO)and collagen content were measured.The enzymatic activity of glutathione peroxidase(GPx)was assessed.Liver histopathology was performed utilizing Masson’s trichrome and hematoxylin-eosin stains.Zymography assays for MMP-9 and MMP-2 were carried out.Hepatic TGF-β,α-SMA,CTGF,Col-I,MMP-13,NF-κB,IL-1,IL-10,Smad7,Smad3,p Smad3 and p JNK proteins were detected via western blot.RESULTS NAR administration prevented increases in ALT,AP,γ-GTP,and GPx enzymatic activity;depletion of GSH and glycogen;and increases in LPO and collagen produced by chronic CCl4 intoxication(P<0.05).Liver histopathology showed a decrease in collagen deposition when rats received NAR in addition to CCl4.Although zymography assays showed that CCl4 produced an increase in MMP-9 and MMP-2gelatinase activity;interestingly,NAR administration was associated with normal MMP-9 and MMP-2 activity(P<0.05).The anti-inflammatory,antinecrotic and antifibrotic effects of NAR may be attributed to its ability to prevent NF-κB activation and the subsequent production of IL-1 and IL-10(P<0.05).NAR completely prevented the increase in TGF-β,α-SMA,CTGF,Col-1,and MMP-13 proteins compared with the CCl4-treated group(P<0.05).NAR prevented Smad3phosphorylation in the linker region by JNK since this flavonoid blocked this kinase(P<0.05).CONCLUSION NAR prevents CCl4 induced liver inflammation,necrosis and fibrosis,due to its antioxidant capacity as a free radical inhibitor and by inhibiting the NF-κB,TGF-β-Smad3 and JNK-Smad3 pathways. | Erika Hernández-Aquino Natanael Zarco Sael Casas-Grajales Erika Ramos-Tovar Rosa E Flores-Beltrán Jonathan Arauz Mineko Shibayama Liliana Favari Víctor Tsutsumi José Segovia Pablo Muriel | 2017 | World Journal of Gastroenterology2017，23，24： | 10 |
| 9 | Capsule endoscopy in non-steroidal anti-inflammatory drugs-enteropathy and miscellaneous,rare intestinal diseases显示文摘Despite significant advances over the last decade, mucosal lesions of the small bowel are poorly detected by imaging studies such as CT scan, MRI-enteroclysis and contrast-enhanced abdominal ultrasound. Capsule endoscopy (CE) has dramatically changed the diagnostic approach to intestinal diseases. Moreover, the use of CE can be extended to include other conditions. However, it is diffi cult to assess the positive influence of CE on patient outcomes in conditions involving a small number of patients, or in critically ill and diff icult to examine patients. CE has the advantage of diagnosing intestinal lesions and of directing the use of double balloon enteroscopy (DBE) in order to obtain biopsy specimens. Moreover, CE allows repeated assessment in chronic conditions, especially to detect relapse of an infectious disease. | Gerard Gay Michel Delvaux Muriel Frederic | 2008 | World Journal of Gastroenterology2008，14，34： | 9 |
| 10 | Comparison of fatty liver index with noninvasive methods for steatosis detection and quantification显示文摘AIM:To compare noninvasive methods presently used for steatosis detection and quantification in nonalcoholic fatty liver disease(NAFLD).METHODS:Cross-sectional study of subjects from the general population,a subgroup from the First Israeli National Health Survey,without excessive alcohol consumption or viral hepatitis.All subjects underwent anthropometric measurements and fasting blood tests.Evaluation of liver fat was performed using four noninvasive methods:the SteatoTest;the fatty liver index(FLI);regular abdominal ultrasound(AUS);and the hepatorenal ultrasound index(HRI).Two of the noninvasive methods have been validated vs liver biopsy and were considered as the reference methods:the HRI,the ratio between the median brightness level of the liver and right kidney cortex;and the SteatoTest,a biochemical surrogate marker of liver steatosis.The FLI is calculated by an algorithm based on triglycerides,body mass index,γ-glutamyl-transpeptidase and waist circumference,that has been validated only vs AUS.FLI < 30 rules out and FLI ≥ 60 rules in fatty liver.RESULTS:Three hundred and thirty-eight volunteers met the inclusion and exclusion criteria and had valid tests.The prevalence rate of NAFLD was 31.1% according to AUS.The FLI was very strongly correlated with SteatoTest(r = 0.91,P < 0.001) and to a lesser but significant degree with HRI(r = 0.55,P < 0.001).HRI and SteatoTest were significantly correlated(r = 0.52,P < 0.001).The κ between diagnosis of fatty liver by SteatoTest(≥ S2) and by FLI(≥ 60) was 0.74,which represented good agreement.The sensitivity of FLI vs SteatoTest was 85.5%,specificity 92.6%,positive predictive value(PPV) 74.7%,and negative predictive value(NPV) 96.1%.Most subjects(84.2%) with FLI < 60 had S0 and none had S3-S4.The κ between diagnosis of fatty liver by HRI(≥ 1.5) and by FLI(≥ 60) was 0.43,which represented only moderate agreement.The sensitivity of FLI vs HRI was 56.3%,specificity 86.5%,PPV 57.0%,and NPV 86.1%.The diagnostic accuracy of FLI for steatosis > 5%,as predicted by SteatoTest,yielded an area under the receiver operating characteristic curve(AUROC) of 0.97(95% CI:0.95-0.98).The diagnostic accuracy of FLI for steatosis> 5%,as predicted by HRI,yielded an AUROC of 0.82(95% CI:0.77-0.87).The κ between diagnosis of fatty liver by AUS and by FLI(≥ 60) was 0.48 for the entire sample.However,after exclusion of all subjects with an intermediate FLI score of 30-60,the κ between diagnosis of fatty liver by AUS and by FLI either ≥ 60 or < 30 was 0.65,representing good agreement.Excluding all the subjects with an intermediate FLI score,the sensitivity of FLI was 80.3% and the specificity 87.3%.Only 8.5% of those with FLI < 30 had fatty liver on AUS,but 27.8% of those with FLI ≥ 60 had normal liver on AUS.CONCLUSION:FLI has striking agreement with SteatoTest and moderate agreements with AUS or HRI.However,if intermediate values are excluded FLI has high diagnostic value vs AUS. | Shira Zelber-Sagi Muriel Webb Nimer Assy Laurie Blendis Hanny Yeshua Moshe Leshno Vlad Ratziu Zamir Halpern Ran Oren Erwin Santo | 2013 | World Journal of Gastroenterology2013，19，1： | 8 |
| 11 | Neoadjuvant sorafenib combined with gemcitabine plus oxaliplatin in advanced hepatocellular carcinoma显示文摘This paper reports the first case of a patient with hepatocellular carcinoma with lymph node metastasis treated by sorafenib combined with gemcitabine plus oxaliplatin,with a partial response and normalization of α fetoprotein,which allowed curative surgery.The potential synergy between these three drugs needs to be confirmed,and is currently being investigated in a randomized phase Ⅱ trial. | Nicolas Williet Olivier Dubreuil Tarek Boussaha Isabelle Trouilloud Bruno Landi Martin Housset Muriel Botti Philippe Rougier Jacques Belghiti Julien Taieb | 2011 | World Journal of Gastroenterology2011，17，17： | 8 |
| 12 | Platelet-activating factor in cirrhotic liver and hepatocellular carcinoma显示文摘瞄准:激活血小板的因素(PAF ) 是一个支持 inflammatory 和 angiogenic 类脂化合物调停人。这里,我们试图调查 PAF 的层次, lyso-PAF ( PAF 先锋),磷脂酶 A ( 2 )( PLA ( 2 ),产生 lyso-PAF 的酶的活动), acetylhydrolase 活动(啊哈, PAF 降级的酶)并且在硬变肝和肝细胞癌( HCC )的 PAF 受体( PAF-R )抄本。方法:有 HCC 的 29 个病人在这研究被注册。肝硬化在十四个病人是在场的,七没有肝疾病。织物 PAF 层次被血小板聚集试金调查。Lyso-PAF 在它的化学乙酰化作用以后被估计进 PAF。啊哈被降级决定[(3 ) H ]-PAF。PLA (2 ) 层次被 EIA 估计。PAF-R 抄本用 RT-PCR 被调查。结果:PAF 和 PAF-R 抄本的提高的数量(白血球类型) 1 作为与非肝脏硬化症的相比在肝脏硬化症的纸巾被发现。PAF 和 PAF-R 抄本的更高的数量(织物类型) 1 和 2 作为与非肿瘤纸巾相比在 HCC 纸巾被发现。PLA (2 ) , lyso-PAF 和啊哈层次没在肝脏硬化症的纸巾和 HCC 被改变。结论:当 PAF 的角色在肝生理学当前是未知的时,这研究在在 HCC 期间在硬变肝并且在 angiogenic 反应发现的煽动性的网络建议它的潜在的参与。 | Muriel Mathonnet Bernard Descottes Denis Valleix Véronique Truffinet Franois Labrousse Yves Denizot | 2006 | World Journal of Gastroenterology2006，12，17： | 7 |
| 13 | Role of illness perception and self-efficacy in lifestyle modification among non-alcoholic fatty liver disease patients显示文摘AIM To describe the relationships between non-alcoholic fatty-liver disease(NAFLD) patient's disease consequences and treatment perceptions, self-efficacy, and healthy lifestyle maintenance. METHODS A cross-sectional study among 146 ultrasound diagnosed NAFLD patients who visited the fatty liver clinic at the TelAviv Medical Center. Eighty-seven of these individuals, participated in a clinical trial of physical activity and underwent fasting blood tests, analyzed at the same lab. Exclusion criteria included positivity for serum HBsA g or anti-HCV antibodies; fatty liver suspected to be secondary to hepatotoxic drugs; excessive alcohol consumption(≥ 30 g/d in men or ≥ 20 g/d in women) and positive markers of genetic or immune-mediated liver diseases. Patients were asked to complete a selfreport structured questionnaire, assembled by the Israeli Center for Disease Control. Nutrition habits were measured using six yes/no questions(0 = no, 1 = yes) adopted from the national survey questionnaire. Participants in the clinical trial completed a detailed semi-quantitative food frequency questionnaire(FFQ) reporting their habitual nutritional intake during the past year. Self-efficacy was assessed by the Self-Efficacy Scale questionnaire, emotional representation, degree of illness understanding, timeline perception, treatment perception and symptoms were measured by the Brief Illness Perception questionnaire. Illness consequences were measured by the Personal Models of Diabetes Interview questionnaire. A path analysis was performed to describe the interrelationships between the patients' illness perceptions, and assess the extent to which the data fit a prediction of nutritional habits.RESULTS The study sample included 54.1% men, with a mean age of 47.76 ± 11.68 years(range: 20-60) and mean body mass index of 31.56 ± 4.6. The average perceived nutrition habits score was 4.73 ± 1.45 on a scale between 0-6, where 6 represents the healthiest eating habits. Most of the study participants(57.2%) did not feel they fully understood what NAFLD is. Better nutritional habits were positively predicted by the degree of illness understanding(β = 0.26; P = 0.002) and selfefficacy(β = 0.25; P = 0.003). Perceptions of more severe illness consequences were related with higher emotional representation(β = 0.55; P < 0.001), which was related with lower self-efficacy(β =-0.17; P = 0.034). The perception of treatment effectiveness was positively related with self-efficacy(β = 0.32; P < 0.001). In accordance with the correlation between self-efficacy and the perceived nutrition habits score, self-efficacy was also correlated with nutrient intake evaluated by the FFQ; negatively with saturated fat(percent of saturated fat calories from total calories)(r =-0.28, P = 0.010) and positively with fiber(r = 0.22, P = 0.047) and vitamin C intake(r = 0.34, P = 0.002). In a sub analysis of the clinical trial participants, objectively measured compliance to physical activity regimen was positively correlated with the self-efficacy level(r = 0.34, P = 0.046). CONCLUSION Self-efficacy and illness understanding are major determinants of lifestyle-modification among NAFLD patients. This information can assist clinicians in improving compliance with lifestyle changes among these patients. | Shira Zelber-Sagi Shiran Bord Gali Dror-Lavi Matthew Lee Smith Samuel D Towne Jr Assaf Buch Muriel Webb Hanny Yeshua Assy Nimer Oren Shibolet | 2017 | World Journal of Gastroenterology2017，23，10： | 6 |
| 14 | VEGF in hepatocellular carcinoma and surrounding cirrhotic liver tissues显示文摘TO THE EDITORWe read with a great interest the recent work of Deli andcolleagues. in the World Journal of Gastroenterology reportingvascular endothelial growth factor (VEGF) expressionin hepatocellular carcinoma (HCC) and cirrhotic livertissues. This well-documented work shows that VEGFwas significantly higher in surrounding cirrhotic livertissues than in HCC. Authors assessed VEGF expressionusing immunohistochemistry.The | Muriel Mathonnet Bernard Descottes Denis Valleix Francois Labrousse Yves Denizot | 2006 | World Journal of Gastroenterology2006，12，5： | 5 |
| 15 | Novel biomarkers and therapeutic targets for optimizing the therapeutic management of melanomas显示文摘Cutaneous malignant melanoma is the most aggressive form of skin cancer with an extremely poor survival rate for the patients diagnosed with locally invasive and metastatic disease states. Intensive research has led in last few years to an improvement of the early detection and curative treatment of primary cutaneous melanomas that are confined to the skin by tumor surgical resection. However, locally advanced and disseminated melanomas are generally resistant to conventional treatments, including ionizing radiation, systemic chemotherapy, immunotherapy and/or adjuvant stem cellbased therapies, and result in the death of patients. The rapid progression of primary melanomas to locally invasive and/or metastatic disease states remains a major obstacle for an early effective diagnosis and a curative therapeutic intervention for melanoma patients. Importantly, recent advances in the melanoma research have led to the identification of different gene products that are often implicated in the malignant transforma-tion of melanocytic cells into melanoma cells, including melanoma stem/progenitor cells, during melanoma initiation and progression to locally advanced and metastatic disease states. The frequent deregulated genes products encompass the oncogenic B-Raf V600 E and N-RasQ 61 R mutants, different receptor tyrosine kinases and developmental pathways such as epidermal growth factor receptor(EGFR), stem cell-like factor(SCF) receptor KIT, hedgehog, Wnt/β-catenin, Notch, stromal cell-derived factor-1(SDF-1)/CXC chemokine receptor-4(CXCR4) and vascular endothelial growth factor(VEGF)/VEGFR receptor. These growth factors can cooperate to activate distinct tumorigenic downstream signaling elements and epithelial-mesenchymal transition(EMT)-associated molecules, including phosphatidylinositol 3'-kinase(PI3K)/Akt/ molecular target of rapamycin(mT OR), nuclear factor-kappaB(NF-κB), macrophage inhibitory cytokine-1(MIC-1), vimentin, snail and twist. Of therapeutic relevance, these deregulated signal transduction components constitute new potential biomarkers and therapeutic targets of great clinical interest for improving the efficacy of current diagnostic and prognostic methods and management of patients diagnosed with locally advanced, metastatic and/or relapsed melanomas. | Murielle Mimeault Surinder K Batra | 2012 | World Journal of Clinical Oncology2012，3，3： | 5 |
| 16 | Hallmarks in colorectal cancer:Angiogenesis and cancer stem-like cells显示文摘Carcinogenesis is a multistep process that requires the accumulation of various genetic and epigenetic aberrations to drive the progressive malignant transformation of normal human cells.Two major hallmarks of carcinogenesis that have been described are angiogenesis and the stem cell characteristic of limitless replicative potential.These properties have been targeted over the past decade in the development of therapeutic treatments for colorectal cancer(CRC),one of the most commonly diagnosed and lethal cancers worldwide.The treatment of solid tumor cancers such as CRC has been challenging due to the heterogeneity of the tumor itself and the chemoresistance of the malignant cells.Furthermore,the same microenvironment that maintains the pool of intestinal stem cells that contribute to the continuous renewal of the intestinal epithelia also provides the necessary conditions for proliferative growth of cancer stem-like cells.These cancer stem-like cells are responsible for the resistance to therapy and cancer recurrence,though they represent less than 2.5%of the tumor mass.The stromal environment surrounding the tumor cells,referred to as the tumor niche,also supports angiogenesis,which supplies the oxygen and nutrients needed for tumor development.Anti-angiogenic therapy,such as with bevacizumab,a monoclonal antibody against vascular-endothelial growth factor,significantly prolongs the survival of metastatic CRC patients.However,such treatments are not completely curative,and a large proportion of patient tumors retain chemoresistance or show recurrence.This article reviews the current knowledge regarding the molecular phenotype of CRC cancer cells,as well as discusses the mechanisms contributing to their maintenance.Future personalized therapeutic approaches that are based on the interaction of the carcinogenic hallmarks,namely angiogenic and proliferative attributes,could improve survival and decrease adverse effects induced by unnecessary chemotherapy. | Muriel Mathonnet Aurelie Perraud Niki Christou Hussein Akil Carole Melin Serge Battu Marie-Odile Jauberteau Yves Denizot | 2014 | World Journal of Gastroenterology2014，20，15： | 5 |
| 17 | Predictors for incidence and remission of NAFLD in the general population during a seven-year prospective follow-up显示文摘 | Shira Zelber-Sagi Roni Lotan Amir Shlomai Muriel Webb Gil Harrari Assaf Buch Dorit Nitzan Kaluski Zamir Halpern Ran Oren | 2012 | Journal of Hepatology2012，，5： | 4 |
| 18 | Antioxidants in liver health显示文摘Liver diseases are a worldwide medical problem because the liver is the principal detoxifying organ and maintains metabolic homeostasis. The liver metabolizes various compounds that produce free radicals(FR).However, antioxidants scavenge FR and maintain the oxidative/antioxidative balance in the liver. When the liver oxidative/antioxidative balance is disrupted, the state is termed oxidative stress. Oxidative stress leadsto deleterious processes in the liver and produces liver diseases. Therefore, restoring antioxidants is essential to maintain homeostasis. One method of restoring antioxidants is to consume natural compounds with antioxidant capacity. The objective of this review is to provide information pertaining to various antioxidants found in food that have demonstrated utility in improving liver diseases. | Sael Casas-Grajales Pablo Muriel | 2015 | World Journal of Gastrointestinal Pharmacology and Therapeutics2015，6，3： | 4 |
| 19 | Tropomyosin-related kinase B/brain derived-neurotrophicfactor signaling pathway as a potential therapeutic targetfor colorectal cancer显示文摘Colorectal cancer(CRC) is the second most common cause of cancer-related death in western countries. Approximately one-quarter of newly diagnosed patients for CRC have metastases, and a further 40%-50% experience disease recurrence or develop metastases after all standard therapies. Therefore, understanding the molecular mechanisms involved in the progression of CRC and subsequently developing novel therapeutic targets is crucial to improve management of CRC and patients' long-term survival. Several tyrosine kinase receptors have been implicated in CRC development, progression and metastasis, including epidermal growth factor receptor(EGFR) and vascular EGFR. Recently, tropomyosin-related kinase B(Trk B), a tyrosine kinase receptor, has been reported in CRC and found to clearly exert several biological and clinical features, such as tumor cell growth and survival in vitro and in vivo, metastasis formation and poor prognosis. Here we review the significance of Trk B and its ligand brain derived-neurotrophic factor in CRC. We focus on their expression in CRC tumor samples, and their functional roles in CRC cell lines and in in vivo models. Finally we discuss therapeutic approaches that can lead to the development of novel therapeutic agents for treating Trk B-expressing CRC tumors. | Hussein Akil Aurélie Perraud Marie-Odile Jauberteau Muriel Mathonnet | 2016 | World Journal of Gastroenterology2016，22，2： | 3 |
| 20 | Long term nutritional intake and the risk for non-alcoholic fatty liver disease (NAFLD): A population based study显示文摘 | Shira Zelber-Sagi Dorit Nitzan-Kaluski Rebecca Goldsmith Muriel Webb Laurie Blendis Zamir Halpern Ran Oren | 2007 | Journal of Hepatology2007，，5： | 3 |
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