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| 1 | Metformin does not improve survival in patients with hepatocellular carcinoma显示文摘AIM:To assess whether metformin,which has a chemopreventive effect in chronic liver disease,has any chemotherapeutic effect in hepatocellular carcinoma.METHODS:This was a retrospective study of 701 patients with newly diagnosed hepatocellular carcinoma(HCC)seen between January 2005 and June 2011 at Mayo Clinic,Rochester,Minnesota.This patient cohort was a part of the global HCC BRIDGE study,which is a large longitudinal study of HCC determining the realworld experience of HCC characteristics,management and patient outcomes.We defined significant metformin exposure as continuation of this agent at least 90d beyond diagnosis of HCC,and compared survival of diabetic patients on metformin to diabetic patients not on metformin and non-diabetics.RESULTS:Our cohort was 72.9%male,with a mean±SD age of 62.6±12.3 years.The most common etiologies of liver disease were hepatitis C(34%),alcoholic liver disease(29%),fatty liver disease(15%)and hepatitis B(9%).By univariate analysis,using diabetics not on metformin as the reference group,diabetic patients with HCC on metformin had no survival advantage,with a HR(95%CI)of 1.0(0.8-1.3).Non-diabetic HCC patients also did not appear to have a survival advantage as compared to diabetic HCC patients not on metformin,as demonstrated by a HR(95%CI)of1.1(0.7-1.7).Diabetics on metformin beyond 90 d after HCC diagnosis had a longer median survival at 34.2 mo,as compared to 25.5 mo among diabetic patients who were not on metformin or had discontinued metformin within 90 d after HCC diagnosis.This finding was likely due to potential survival bias among those who lived long enough to receive metformin.CONCLUSION:Although the literature suggests a chemotherapeutic effect in other malignancies,our study demonstrates no survival benefit to the use of metformin in diabetic patients with HCC. | Mamatha Bhat Roongruedee Chaiteerakij William S Harmsen Cathy D Schleck Ju Dong Yang Nasra H Giama Terry M Therneau Gregory J Gores Lewis R Roberts | 2014 | World Journal of Gastroenterology2014，20，42： | 11 |
| 2 | Model combining pre-transplant tumor biomarkers and tumor size shows more utility in predicting hepatocellular carcinoma recurrence and survival than the BALAD models显示文摘AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver transplant.METHODS BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein(AFP), Lens culinaris agglutinin-reactive AFP(AFP-L3), and des-gammacarboxyprothrombin(DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios(HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42(1.18-5.00), 1.86(0.98-3.52), and 2.83(1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48(1.15-1.91) and 1.59(1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45(1.06-1.98) and 1.38(1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65,0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant(S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter(S-LAD). | Nicha Wongjarupong Gabriela M Negron-Ocasio Roongruedee Chaiteerakij Benyam D Addissie Essa A Mohamed Kristin C Mara William S Harmsen J Paul Theobald Brian E Peters Joseph G Balsanek Melissa M Ward Nasra H Giama Sudhakar K Venkatesh Denise M Harnois Michael R Charlton Hiroyuki Yamada Alicia Algeciras-Schimnich Melissa R Snyder Terry M Therneau Lewis R Roberts | 2018 | World Journal of Gastroenterology2018，24，12： | 5 |
| 3 | Pancreatic cancer: Are 'liquid biopsies' ready for prime-time?显示文摘Pancreatic cancer is a disease that carries a poor prognosis. Accurate tissue diagnosis is required. Tumours contain a high content of stromal tissue and therefore biopsies may be inconclusive. Circulating tumour cells(CTCs) have been investigated as a potential 'liquid biopsy' in several malignancies and have proven to be of prognostic value in breast, prostate and colorectal cancers. They have been detected in patients with localised and metastatic pancreatic cancer with sensitivities ranging from 38%-100% using a variety of platforms. Circulating tumour DNA(ct DNA) has also been detected in pancreas cancer with a sensitivity ranging from 26%-100% in studies across different platforms and using different genetic markers. However, there is no clear consensus on which platform is the most effective for detection, nor which genetic markers are the most useful to use. Potential roles of liquid biopsies include diagnosis, screening, guiding therapies and prognosis. The presence of CTCs or ct DNA has been shown to be of prognostic value both at diagnosis and after treatment in patients with pancreatic cancer. However, more prospective studies are required before this promising technology is ready for adoption into routine clinical practice. | Alexandra R Lewis Juan W Valle Mairead G Mc Namara | 2016 | World Journal of Gastroenterology2016，22，32： | 5 |
| 4 | Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study显示文摘 | Shamir R Mehta Salim Yusuf Ron JG Peters Michel E Bertrand Basil S Lewis Madhu K Natarajan Klas Malmberg Hans-Jürgen Rupprecht Feng Zhao Susan Chrolavicius Ingrid Copland Keith AA Fox | 2001 | The Lancet . 2001 (9281)2001，，9281： | 4 |
| 5 | Stress Proteins (HSPs): Method of Detection and Their use as an Environmental Biomarker显示文摘 | Lewis S Handy R D | 1999 | Ecotoxicology1999，8，： | 2 |
| 6 | Evaluation of contact resistance for isotropic electrically conductive adhesives 显示文摘 | Gaynes M A Lewis R H | 1995 | IEEE Trans Compon Packg Manuf Tech Part B1995，18，3： | 2 |
| 7 | Novel diet-related mouse model of colon cancer parallels human colon cancer显示文摘AIM:To investigate the close parallels between our novel diet-related mouse model of colon cancer and human colon cancer.METHODS:Twenty-two wild-type female mice(ages 6-8 wk)were fed the standard control diet(AIN-93G)and an additional 22 female mice(ages 6-8 wk)were fed the control diet supplemented with 0.2%deoxycho-lic acid[diet+deoxycholic acid(DOC)]for 10 mo.Tu-mors occurred in the colons of mice fed diet+DOC and showed progression to colon cancer[adenocarcinoma(AC)].This progression is through the stages of tubular adenoma(TA),TA with high grade dysplasia or ad-enoma with sessile serrated morphology,intramucosal AC,AC stage T1,and AC stage T2.The mouse tumors were compared to human tumors at the same stages by histopathological analysis.Sections of the small and large intestines of mice and humans were evaluated for glandular architecture,cellular and nuclear morphology including cellular orientation,cellular and nuclear atyp-ia,pleomorphism,mitotic activity,frequency of goblet cells,crypt architecture,ulceration,penetration of crypts through the muscularis mucosa and presence of malignant crypts in the muscularis propria.In addition,preserved colonic tissues from genetically similar male mice,obtained from a prior experiment,were analyzed by immunohistochemistry.The male mice had been fed the control diet or diet+DOC.Four molecular markers were evaluated:8-OH-dG,DNA repair protein ERCC1,autophagy protein beclin-1 and the nuclear location of beta-catenin in the stem cell region of crypts.Also,male mice fed diet+DOC plus 0.007%chlorogenic acid(diet+DOC+CGA)were evaluated for ERCC1,beclin-1 and nuclear location of beta-catenin.RESULTS:Humans with high levels of diet-relatedDOC in their colons are at a substantially increased riskof developing colon cancer.The mice fed diet+DOChad levels of DOC in their colons comparable to that ofhumans on a high fat diet.The 22 mice without addedDOC in their diet had no colonic tumors while 20 ofthe 22 mice(91%)fed diet+DOC developed colonictumors.Furthermore,the tumors in 10 of these mice(45%of mice)included an adenocarcinoma.All micewere free of cancers of the small intestine.Histopatho-logically,the colonic tumor types in the mice werevirtually identical to those in humans.In humans,char-acteristic aberrant changes in molecular markers can be detected both in field defects surrounding cancers(from which cancers arise)and within cancers.In thecolonic tissues of mice fed diet+DOC similar changesin biomarkers appeared to occur.Thus,8-OH-dG wasincreased,DNA repair protein ERCC1 was decreased,autophagy protein beclin-1 was increased and,in thestem cell region at the base of crypts there was sub-stantial nuclear localization of beta-catenin as well asincreased cytoplasmic beta-catenin.However,in micefed diet+DOC+CGA(with reduced frequency ofcancer)and evaluated for ERCC1,beclin-1,and beta-catenin in the stem cell region of crypts,mouse tissueshowed amelioration of the aberrancies,suggestingthat chlorogenic acid is protective at the molecular levelagainst colon cancer.This is the first diet-related modelof colon cancer that closely parallels human progressionto colon cancer,both at the histomorphological level aswell as in its molecular profile.CONCLUSION:The diet-related mouse model of coloncancer parallels progression to colon cancer in humans,and should be uniquely useful in model studies of pre-vention and therapeutics. | Anil R Prasad Shilpa Prasad Huy Nguyen Alexaner Facista Cristy Lewis Beryl Zaitlin Harris Bernstein Carol Bernstein | 2014 | World Journal of Gastrointestinal Oncology2014，6，7： | 2 |
| 8 | Necessary and sufficient for delayindependent stability of linear autonomous system显示文摘 | LEWIS R W ANDSON B D O | 1980 | IEEE Trans on Automat Contr1980，25，： | 2 |
| 9 | Hepatitis C Virus Infects the Endothelial Cells of the Blood-Brain Barrier显示文摘 | Nicola F. Fletcher Garrick K. Wilson Jacinta Murray Ke Hu Andrew Lewis Gary M. Reynolds Zania Stamataki Luke W. Meredith Ian A. Rowe Guangxiang Luo Miguel A. Lopez–Ramirez Thomas F. Baumert Babette Weksler Pierre–Olivier Couraud Kwang Sik Kim Ignacio A. R | 2012 | Gastroenterology2012，，3： | 2 |
| 10 | Selective Deactivation of Gibberellins below the Shoot Apex is Critical to Flowering but Not to Stem Elongation of Lolium显示文摘赤霉素(气体) 在 GA1 的合成在植物高度和基因块引起戏剧的增加解释相形见绌 Mendel 的豌豆。为 flowering,是 GA5 重要在长天(LD ) 应答的草, Lolium。当我们这里出现,因为他们被 C-2 hydroxylation 在射击顶下面撤销, GA1 和 GA4 为 flowering 在他们的有效性被限制。相反,因为它的结构的保护, GA5 是有效的。切除植物的射击尖端很快降级[14C ] GA1,[14C ] GA4,并且[14C ] GA20 (>80% 在 6 ? h ) ,然而并非[14C ] GA5。偶然,编码二 2-oxidases 的基因和通常认为的 1617-epoxidase 最就在射击顶下面被表示(< 3 ? 公里) 。进一步击倒不成熟的茎(> 4 ? 公里) ,这些 GA 释放基因的表示被减少,那么允许 GA1 和 GA4 支持接近顶点的茎延伸。随后, GA 降级在花地导致的射击尖端和这些气体衰退能为花的开发变得活跃。稳定 GA4 的结构的变化证实在 florigenicity 和限制 GA 2-hydroxylation 之间的连接(例如 2-hydroxylation 和 C-2 di-methylation ) 。另外,一个 2-oxidase 禁止者(Trinexapac 乙醇) 提高了应用 GA4 的活动,作为做了在 16,17-dihydro 气体或在 C-13 hydroxylation 以后限制 C-16,17 epoxidation。总的来说,就在射击顶下面的 GA1 和 GA4 的释放有效地在 Lolium 限制他们的 florigenicity,相反地,与 GA5,对释放的 C-2 和 C-13 保护允许它的高 florigenicity。思索地,在草的射击顶的 GA 存取的如此的差别可能为把花的正式就职与开花期出现分开是重要的并且能因此在草食动物 predation 的条件下面影响他们的幸存。 | Rod W. King Lewis N. Mander Torben Asp Colleen R MacMillan Cheryl A. Blundell Lloyd T. Evans | 2008 | Molecular Plant2008，1，2： | 2 |
| 11 | 轿车柴油机进气门与座圈磨损机理的研究显示文摘采用台式试验装置来研究轿车柴油机进气门与座圈的磨损机理,所用的台式试验装置按模拟进气门与座圈的负荷环境和接触条件而设计的。研究表明进气门与座圈的磨损问题包括两种不同的机理:气门关闭时的落座冲击和燃烧压力作用下气门在座圈上的滑动。研究表明,磨损的主要机理与各种关键的工作状态有关,例如气门的关闭速度、燃烧负荷、气门相对气门座的不对中性以及气门和座圈的材料选择等。 | Lewis R Dwyer-Joyce R S Josey G 史大德 | 2000 | 国外内燃机2000，，4： | 2 |
| 12 | Papillary thyroid cancer and inflammatory bowel disease:Is there a relationship?显示文摘AIM:To formally study age of diagnosis of papillary thyroid cancer(PTC) in inflammatory bowel disease(IBD) patients and evaluate the prevalence of PTC in IBD patients compared to a control population.pothesis that patients with IBD are more likely to be diagnosed with PTC than a control population.A retrospective cohort analysis was performed using the University of Pennsylvania Health System's electronic database.Outpatients from 1998-2009 were included in the search,and patients in the cohort were selected based on ICD-9 codes.Inclusion criteria included the diagnosis of Crohn's disease(CD) or ulcerative colitis(UC) and the concurrent diagnosis of thyroid cancer in comparison to a control population.Using these methods 912 patients with CD and 1774 with UC were compared to 1638 diverticulitis and 19 447 asthma controls.Statistics were performed using corrected chisquare analysis.The primary outcome for this study was the diagnosis of PTC.Approval to conduct this study was obtained by the Institutional Review Board at the University of Pennsylvania.RESULTS:The mean age was 47.5 years(range:18-102 years) and 66% patients were female.An analysis of variance model was used to compare the age of PTC diagnosis between the CD,UC,asthma and diverticulitis groups,and a statistically significant difference in age at PTC diagnosis was noted across all groups(F = 6.35,df = 3,P = 0.0006).The age of PTC diagnosis in CD patients was statistically significantly lower than UC,asthma,and diverticulitis patients(average PTC diagnosis age for CD 25,UC 49,asthma 45,diverticulitis 63).After covarying for sex and age in 2009,the difference in age at PTC diagnosis remained statistically significant(F = 4.13,df = 3,P = 0.0089).A total of 86 patients were diagnosed with PTC.Nine patients(0.5%) with UC were diagnosed with PTC.Patients with UC were not shown to be more likely to develop PTC [odds ratio(OR):1.544,95%CI 0.767-3.108] compared to asthma controls.Four patients(0.4%) with CD were diagnosed with PTC.Patients with CD were not shown to be more likely to develop PTC(OR:1.334,95%CI 0.485-3.672) compared to a control population with asthma.Nine patients(0.5%) with a history of diverticulitis were diagnosed with PTC.Patients with diverticulitis were not shown to be more likely to develop PTC(OR:1.673,95%CI 0.831-3.368) compared to asthma controls.Patients with CD or UC were not less likely to develop PTC compared to those with diverticulitis(CD OR:0.80,95%CI 0.25-2.60;UC OR:0.92,95%CI 0.37-2.33).None of the patients used immunosuppressant medications prior to the diagnosis of PTC(azathioprine,6-mercaptopurine,and methotrexate).CONCLUSION:There is a significant difference in age of diagnosis of PTC in patients with CD compared to patients with UC and the control populations studied. | Irene S Sonu Wojciech Blonski Ming Valerie Lin James Lewis Faten Aberra Gary R Lichtenstein | 2013 | World Journal of Gastroenterology2013，19，7： | 2 |
| 13 | SNPs as windows on evolution显示文摘 | Lewis R | | 0，，： | 2 |
| 14 | Gain saturation in silica-fibre Raman amplifier 显示文摘 | LEWIS S A E CHERNIKOV S V TAYLOR J R | 1999 | Electron Lett1999，35，11： | 2 |
| 15 | Effect of two opposing changes in photoperiod upon age at first egg and related traits in layer - hybrid pullets 显示文摘 | Lewis P D Perry G C Morris T R | 2003 | Journal of Agricultural Science Cambridge2003，140，： | 1 |
| 16 | Video - assisted thoracic surgical resection of malignant lung tumors 显示文摘 | Lewis R J Caccavale R J Sisler GE | 1992 | Thorac Cardiovasc Surg1992，104，6： | 1 |
| 17 | Thiazolo pyrimidines: 1 : synthesis and anti-human cytomegalovirus (HCMV) activity in-vitro of certain alkyl derivatives显示文摘 | Lewis A F Revankar G R Fennewald S M | 1995 | J Heterocycl Chem1995，32，20： | 1 |
| 18 | Prevalence of anxiety and depression in patients with severe COPD: similar high levels with and without LTOT 显示文摘 | LEWIS K E ANNANDALE J A SYKES R N | 2007 | COPD2007，4，4： | 1 |
| 19 | A role for the AKT1 potassium channel in plant nutrition显示文摘 | Hirsch R E Lewis B D Spalding E P | 1998 | Science1998，280，： | 1 |
| 20 | Synthesis of new bis (acetylide)-substituted fluorene derivatives and their bimetallic and polymeric complexes显示文摘 | Lewis J Raithby P R Wong W Y | 1998 | J Organomet Chem1998，556，： | 1 |
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