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| 1 | Cetuximab plus FOLFOX6 or FOLFIRI in metastatic colorectal cancer: CECOG trial显示文摘AIM: To investigate efficacy and safety of cetuximab combined with two chemotherapy regimens in patients with unresectable metastatic colorectal cancer (mCRC). METHODS: Randomized patients received cetuximab with 5-fluorouracil (5-FU), folinic acid (FA) and oxaliplatin (FOLFOX) 6 (arm A, n = 74) or 5-FU, FA and irinotecan (FOLFIRI) (arm B, n = 77). KRAS mutation status was determined retrospectively in a subset of tumors (n = 117). RESULTS: No significant difference was found between treatment arms A and B in the progression-free survival (PFS) rate at 9 mo, 45% vs 34%; median PFS, 8.6 mo vs 8.3 mo [hazard ratio (HR) = 1.06]; overall response rate (ORR) 43% vs 45% [odds ratio (OR) = 0.93] and median overall survival (OS), 17.4 mo vs 18.9 mo (HR = 0.98). Patients with KRAS wild-type tumors demonstrated improved PFS (HR = 0.55, P = 0.0051), OS, (HR = 0.62, P = 0.0296) and ORR (53% vs 36%) and in arm A, improved PFS (HR = 0.49, P = 0.0196), OS (HR = 0.48, P = 0.0201) and ORR (56%vs 30%), compared with patients with KRAS mutated tumors. In arm B no significant differences were found in efficacy by KRAS mutation status. Treatment in arms A and B was generally well tolerated. CONCLUSION: This study confirms that combinations of cetuximab with FOLFOX6 or FOLFIRI are effective and significantly improve clinical outcome in KRAS wild-type compared with KRAS mutated mCRC. | Janja Ocvirk Thomas Brodowicz Fritz Wrba Tudor E Ciuleanu Galina Kurteva Semir Beslija Ivan Koza Zsuzsanna Pápai Diethelm Messinger Ugur Yilmaz Zsolt Faluhelyi Suayib Yalcin Demetris Papamichael Miklós Wenczl Zrinka Mrsic-Krmpotic Einat Shacham-Shmueli Damir Vrbanec Regina Esser Werner Scheithauer Christoph C Zie-linski | 2010 | World Journal of Gastroenterology2010，16，25： | 17 |
| 2 | Vanishing bile duct syndrome in human immunodeficiency virus infected adults:A report of two cases显示文摘Vanishing bile duct syndrome(VBDS) is a group of rare disorders characterized by ductopenia,the progressive destruction and disappearance of intrahepatic bile ducts leading to cholestasis.Described in association with medications,autoimmune disorders,cancer,transplantation,and infections,the specific mechanisms of disease are not known.To date,only 4 cases of VBDS have been reported in human immunodeficiency virus(HIV) infected patients.We report 2 additional cases of HIV-associated VBDS and review the features common to the HIV-associated cases.Presentation includes hyperbilirubinemia,normal liver imaging,and negative viral and autoimmune hepatitis studies.In HIV-infected subjects,VBDS occurred at a range of CD4+ T-cell counts,in some cases following initiation or change in antiretroviral therapy.Lymphoma was associated with two cases;nevirapine,antibiotics,and viral co-infection were suggested as etiologies in the other cases.In HIV-positive patients with progressive cholestasis,early identification of VBDS and referral for transplantation may improve outcomes. | Ana Paula Oppenheimer Christopher Koh Mary McLaughlin John C Williamson Thomas D Norton Jennifer Laudadio Theo Heller David E Kleiner Kevin P High Caryn G Morse | 2013 | World Journal of Gastroenterology2013，19，1： | 8 |
| 3 | Colonoscopy surveillance for high risk polyps does not always prevent colorectal cancer显示文摘AIM To determine the frequency and risk factors for colorectal cancer(CRC) development among individuals with resected advanced adenoma(AA)/traditional serrated adenoma(TSA)/advanced sessile serrated adenoma(ASSA). METHODS Data was collected from medical records of 14663 subjects found to have AA, TSA, or ASSA at screening or surveillance colonoscopy. Patients with inflammatory bowel disease or known genetic predisposition for CRC were excluded from the study. Factors associated with CRC developing after endoscopic management of high risk polyps were calculated in 4610 such patients who had at least one surveillance colonoscopy within 10 years following the original polypectomy of the incident advanced polyp. RESULTS84/4610(1.8%) patients developed CRC at the polypectomy site within a median of 4.2 years(mean 4.89 years), and 1.2%(54/4610) developed CRC in a region distinct from the AA/TSA/ASSA resection site within a median of 5.1 years(mean 6.67 years). Approximately, 30%(25/84) of patients who developed CRC at the AA/TSA/ASSA site and 27.8%(15/54) of patients who developed CRC at another site had colonoscopy at recommended surveillance intervals. Increasing age; polyp size; male sex; right-sided location; high degree of dysplasia; higher number of polyps resected; and piecemeal removal were associated with an increased risk for CRC developmentat the same site as the index polyp. Increasing age; right-sided location; higher number of polyps resected and sessile endoscopic appearance of the index AA/TSA/ASSA were significantly associated with an increased risk for CRC development at a different site. CONCLUSION Recognition that CRC may develop following AA/TSA/ASSA removal is one step toward improving our practice efficiency and preventing a portion of CRC related morbidity and mortality. | Mohamad A Mouchli Lidia Ouk Marianne R Scheitel Alisha P Chaudhry Donna Felmlee-Devine Diane E Grill Shahrooz Rashtak Panwen Wang Junwen Wang Rajeev Chaudhry Thomas C Smyrk Ann L Oberg Brooke R Druliner Lisa A Boardman | 2018 | World Journal of Gastroenterology2018，24，8： | 5 |
| 4 | Meeting report:a hard look at the state of enamel research显示文摘The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines(ENAMEL) Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National Institute of Dental and Craniofacial Research(NIDCR). Discussion topics included model organisms, stem cells/cell lines, and tissues/3 D cell culture/organoids. Scientists from a number of disciplines,representing institutions from across the United States, gathered to discuss advances in our understanding of enamel, as well as future directions for the field. | ophir d klein olivier duverger wendy shaw rodrigo s lacruz derk joester janet moradian-oldak megan k pugach j timothy wright sarah e millar ashok b kulkarni john d bartlett thomas gh diekwisch pamela den besten james p simmer | 2017 | International Journal of Oral Science2017，9，4： | 3 |
| 5 | Wrist Fractures显示文摘 | Douglas P Hanel Marci D Jones Thomas E Trumble | 2002 | Orthopedic Clinics of North America2002，，1： | 3 |
| 6 | Macrophage secretory products induce an inflammatory phenotype in hepatocytes显示文摘AIM:To investigate the influence of macrophages on hepatocyte phenotype and function.METHODS:Macrophages were differentiated from THP-1 monocytes via phorbol myristate acetate stimulation and the effects of monocyte or macrophageconditioned medium on HepG2 mRNA and protein expression determined.The in vivo relevance of these findings was confirmed using liver biopsies from 147 patients with hepatitis C virus(HCV)infection.RESULTS:Conditioned media from macrophages,but not monocytes,induced a transient morphological change in hepatocytes associated with upregulation of vimentin(7.8±2.5-fold,P=0.045)and transforming growth factor(TGF)-β1(2.6±0.2-fold,P<0.001)and downregulation of epithelial cadherin(1.7±0.02-fold,P=0.017)mRNA expression.Microarray analysis revealed significant upregulation of lipocalin-2(17-fold,P <0.001)and pathways associated with inflammation,and substantial downregulation of pathways related to hepatocyte function.In patients with chronic HCV,realtime polymerase chain reaction and immunohistochemistry confirmed an increase in lipocalin-2 mRNA(F0 1.0 ±0.3,F1 2.2±0.2,F2 3.0±9.3,F3/4 4.0±0.8,P= 0.003)and protein expression(F1 1.0±0.5,F2 1.3± 0.4,F3/4 3.6±0.4,P=0.014)with increasing liver injury.High performance liquid chromatography-tandem mass spectrometry analysis identified elevated levels of matrix metalloproteinase(MMP)-9 in macrophageconditioned medium,and a chemical inhibitor of MMP-9 attenuated the change in morphology and mRNA expression of TGF-β1(2.9±0.2 vs 1.04±0.1,P<0.001) in macrophage-conditioned media treated HepG2 cells.In patients with chronic HCV infection,hepatic mRNA expression of CD163(F0 1.0±0.2,F1/2 2.8±0.3,F3/4 5.3±1.0,P=0.001)and MMP-9(F0 1.0±0.4,F1/2 2.8±0.3,F3/4 4.1±0.8,P=0.011)was significantly associated with increasing stage of fibrosis.CONCLUSION:Secreted macrophage products alter the phenotype and function of hepatocytes,with increased expression of inflammatory mediators,suggesting that hepatocytes actively participate in liver injury. | Michelle Melino Victoria L Gadd Gene V Walker Richard Skoien Helen D Barrie Dinesh Jothimani Leigh Horsfall Alun Jones Matthew J Sweet Gethin P Thomas Andrew D Clouston Julie R Jonsson Elizabeth E Powell | 2012 | World Journal of Gastroenterology2012，18，15： | 3 |
| 7 | Senescent human hepatocytes express a unique secretory phenotype and promote macrophage migration显示文摘AIM:To develop a model of stress-induced senescence to study the hepatocyte senescence associated secretory phenotype(SASP).METHODS:Hydrogen peroxide treatment was used to induce senescence in the human Hep G2 hepatocyte cell line.Senescence was confirmed by cytochemical staining for a panel of markers including Ki67,p21,heterochromatin protein 1β,and senescence-associated-β-galactosidase activity.Senescent hepatocytes were characterised by gene expression arrays and quantitative polymerase chain reaction(q PCR),and conditioned media was used in proteomic analyses,a human chemokine protein array,and cell migration assays to characterise the composition and function of the hepatocyte SASP.RESULTS:Senescent hepatocytes induced classical markers of senescence(p21,heterochromatin protein1β,and senescence-associated-β-galactosidase activity);and downregulated the proliferation marker,Ki67.Hepatocyte senescence induced a 4.6-fold increase in total secreted protein(P=0.06)without major alterations in the protein profile.Senescence-induced genes were identified by microarray(Benjamini Hochbergcorrected P<0.05);and,consistent with the increase in secreted protein,gene ontology analysis revealed a significant enrichment of secreted proteins among inducible genes.The hepatocyte SASP included characteristic factors such as interleukin(IL)-8 and IL-6,as well as novel components such as SAA4,IL-32and Fibrinogen,which were validated by q PCR and/or chemokine protein array.Senescent hepatocyteconditioned medium elicited migration of inflammatory(granulocyte-macrophage colony stimulating factor,GM-CSF-derived),but not non-inflammatory(CSF-1-derived)human macrophages(P=0.022),which could contribute to a pro-inflammatory microenvironment in vivo,or facilitate the clearance of senescent cells.CONCLUSION:Our novel model of hepatocyte senescence provides insights into mechanisms by which senescent hepatocytes may promote chronic liver disease pathogenesis. | Katharine M Irvine Richard Skoien Nilesh J Bokil Michelle Melino Gethin P Thomas Dorothy Loo Brian Gabrielli Michelle M Hill Matthew J Sweet Andrew D Clouston Elizabeth E Powell | 2014 | World Journal of Gastroenterology2014，20，47： | 2 |
| 8 | Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial显示文摘 | Thomas E Hutson Vladimir Lesovoy Salman Al-Shukri Viktor P Stus Oleg N Lipatov Angel H Bair Brad Rosbrook Connie Chen Sinil Kim Nicholas J Vogelzang | 2013 | Lancet Oncology2013，，13： | 2 |
| 9 | Sciatic nerve injuries in revision total hip arthroplasty 显示文摘 | Peters Lance E Buly Sculco Thomas P | 2001 | Techniques in Orthopaedics2001，16，3： | 2 |
| 10 | Optical diagnosis of small colorectal polyps at routine colonoscopy (Detect InSpect ChAracterise Resect and Discard; DISCARD trial): a prospective cohort study显示文摘 | Ana Ignjatovic James E East Noriko Suzuki Margaret Vance Thomas Guenther Brian P Saunders | 2009 | Lancet Oncology2009，，： | 2 |
| 11 | Three dimensional transonic aeroelasticity using proper orthogonal decompo- sition-based reduced order models显示文摘 | Thomas J P Dowell E H Hall K C | 2003 | Journal of Aircraft2003，40，3： | 1 |
| 12 | Improved acid neutralisation capacity assessment of iron carbonates by titration and theoretical calculation显示文摘 | Weber P A Thomas J E Skinner W M | 2004 | Applied Geochemistry2004，19，： | 1 |
| 13 | Robust analysis of the yeast proteome under 50 kDa by molecular-massbased fractionation and top-down mass spectrometry显示文摘 | Kellie J F Catherman A D Durbin K R Tran J C Tipton J D Norris J L Witkowski C E 2nd Thomas P M Kelleher N L | | 0，，01： | 1 |
| 14 | Perceived stress, intemal resources,and social support as determinants of mental health among young adults显示文摘 | Patrick A B Chamot E Thomas V P | 2004 | Quality Life Res2004，13，6： | 1 |
| 15 | Seawater corrosion behavior of laser surface modified Inconel 625 alloy 显示文摘 | Cooper K P Slebodnick P Thomas E D | 1996 | Materials Science Engineering1996，206，： | 1 |
| 16 | Isokinetic evealuation of rotational strength in normal shouler and shoulders with impingment syndrome 显示文摘 | Leroux J1 Codine P Thomas E | 1994 | Clin Orthop Relat Res1994，30，4： | 1 |
| 17 | Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells 显示文摘 | Thomas P Pang Y Filardo E J | 2005 | Endocrinology2005，146，2： | 1 |
| 18 | Late paleocene to eocene paleocenography of the equatorial pacific ocean: stable isotopes recorded at ocean drilling program site 865, allison guyot显示文摘 | Zachos J C Thomas E Parrow M Paul C K Kelly D C Silva I P Sliter W V Lohmann K C | 1995 | Paleoceanography1995，10，： | 1 |
| 19 | Effects of porcine circovims Type 2 (PCV2) maternal antibodies on experimental infection of piglets with PCV2 clinical and diagnostic laboratory immunology显示文摘 | McKeown N E Opriessnig T Thomas P | 2005 | 12:1 347-1 3512005，12，： | 1 |
| 20 | Tackling antibiotic resistance显示文摘 | Bush K Courvalin P Dantas G Davies J Eisenstein B Huovinen P Jacoby GA Kishony R Kreiswirth BN Kutter E Lerner SA Levy S Lewis K Lomovskaya O Miller JH Mobashery S Piddock LJ Projan S Thomas CM Tomasz A Tulkens PM Walsh TR Watson JD Witkowski J Witte W Wr | | 0，，： | 1 |
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