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| 1 | Distinct antifibrogenic effects of erlotinib,sunitinib and sorafenib on rat pancreatic stellate cells显示文摘AIM:To study if three clinically available small molecule kinase inhibitors(SMI),erlotinib,sunitinib and sorafenib,exert antifibrogenic effects on pancreatic stellate cells(PSC)and analyze the basis of their action.METHODS:Cultured rat PSC were exposed to SMI.Cell proliferation and viability were assessed employing 5-bromo-2’-deoxyuridine incorporation assay and flow cytometry,respectively.2-Deoxy-2-[18F]fluoroglucose(18F-FDG)uptake was measured to study metabolic activity.Exhibition of the myofibroblastic PSC phenotype was monitored by immunofluorescence analysis ofα-smooth muscle actin(α-SMA)expression.Levels of mRNA were determined by real-time PCR,while protein expression and phosphorylation were analyzed by immunoblotting.Transforming growth factor-β1 (TGF-β1)levels in culture supernatants were quantified by ELISA.RESULTS:All three SMI inhibited cell proliferation and18F-FDG uptake in a dose-dependent manner and without significant cytotoxic effects.Furthermore,additive effects of the drugs were observed.Immunoblot analysis showed that sorafenib and sunitib,but not erlotinib,efficiently blocked activation of the AKT pathway,while all three drugs displayed little effect on phosphorylation of ERK1/2.Cells treated with sorafenib or sunitinib expressed less interleukin-6 mRNA as well as less collagen type 1 mRNA and protein.Sorafenib was the only drug that also upregulated the expression of matrix metalloproteinase-2 and reduced the secretion of TGF-β1 protein.All three drugs showed insignificant or discordant effects on the mRNA and protein levels ofα-SMA.CONCLUSION:The tested SMI,especially sorafenib,exert inhibitory effects on activated PSC,which should be further evaluated in preclinical studies. | Anne Elsner Falko Lange Brit Fitzner Martin Heuschkel Bernd Joachim Krause Robert Jaster | 2014 | World Journal of Gastroenterology2014，20，24： | 2 |
| 2 | A Practical Guide for the Diagnosis of Primary Enteric Nervous System Disorders显示文摘 | M.G. Sch?ppi A. Staiano P.J. Milla V.V. Smith J.A. Dias R. Heuschkel S. Husby M.L. Mearin A. Papadopoulou F.M. Ruemmele Yvan Vandenplas S. Koletzko | 2013 | Journal of Pediatric Gastroenterology and Nutrition2013，，5： | 2 |
| 3 | Role of small-bowel endoscopy in the management of patients with inflammatory bowel disease: an international OMED–ECCO consensus显示文摘 | A. Bourreille A. Ignjatovic L. Aabakken E. Loftus Jr R. Eliakim M. Pennazio Y. Bouhnik E. Seidman M. Keuchel J. Albert S. Ardizzone S. Bar-Meir R. Bisschops E. Despott P. Fortun R. Heuschkel J. Kammermeier J. Leighton G. Mantzaris D. Moussata S. Lo V. Pau | 2009 | Endoscopy2009，，07： | 1 |
| 4 | Abdominal migraine in children with neurofibromatosis type 1 :A case series and review of gastrointestinal involvement in NF1 显示文摘 | Heuschkel R Kim S Korf B | 2001 | J Pediatr Gastroenterol Nutr2001，33，2： | 1 |
| 5 | Enteral nutrition and corticosteroids in the treatment of acute Crohn's disease in children 显示文摘 | Heuschkel RB Menache CC Megerian JT | 2000 | J Pediatr Gastroenterol Nutr2000，31，1： | 1 |
| 6 | En- teral nutrition and corticosteroids in the treatment of a- cute Crohn~s disease in children显示文摘 | Heuschkel R B Menache C C Megerian J T | 2000 | J Pediatr Gastroen- terol Nutr2000，31，1： | 1 |
| 7 | Guidelines for the management of growth failure in childhood inflammatory bowel disease 显示文摘 | Heuschkel R Salvestrini C Beattie RM Hildebrand H Waiters T Griffiths A | 2008 | Inflamm Bowel Dis2008，14，6： | 1 |
| 8 | Enteral nutrition in Crohn's disease:more than just calories显示文摘 | Heuschkel R | 2004 | J Pediatr Gastroenterol Nutr2004，38，3： | 1 |
| 9 | A three-dimensional multi-electrode array for multi-site stimulation and recording in acute brain slices 显示文摘 | HEUSCHKEL M O FEJTL M RAGGENBASS M | 2002 | J Neurosci Methods2002，114，2： | 1 |
| 10 | New immunologic treatments for inflammatory bowel disease 显示文摘 | HEUSCHKEL RB | 2000 | Curt Opin Gastroenterol2000，16，6： | 1 |
| 11 | Weld metal property selection and control显示文摘 | Heuschkel J | 1973 | Weld J1973，52，： | 1 |
| 12 | Neural recording and stimulation of dissociated hippocampal cultures using microfabricated three-dimensional tip electrode array 显示文摘 | NAM Y WHEELER B C HEUSCHKEL M O | 2006 | J Neurosci Methods2006，155，2： | 1 |
| 13 | Guidelines for the management of growth failure in childhood inflammatory bowel disease 显示文摘 | Heuschkel R Salvestrini C Beattie RM | 2008 | Inflamm Bowel Dis2008，14，6： | 1 |
| 14 | Enteral Nutrition in Children With Crohn’s Disease显示文摘 | Robert B. Heuschkel | 2000 | Journal of Pediatric Gastroenterology and Nutrition2000，，5： | 1 |
| 15 | Weld metal property selection and control显示文摘 | Heuschkel J | 1973 | Welding Journal1973，52，： | 1 |
| 16 | Is the repetitive training of complex hand and arm movements beneficial for motor recovery in stroke patients 显示文摘 | Woldag H Waldmann G Heuschkel G | 2003 | Clin Rehabil2003，17，7： | 1 |
| 17 | Comparison of stratum corneum penetration and localization of a lipophilic model drug applied in an o/w microemulsion and an amphiphilic cream显示文摘 | Teichmann A Heuschkel S Jacobi U | 2007 | Eur J Pharm Biopharm2007，，3： | 1 |
| 18 | Enteral nutrition and corticosteroids in the treatment of acute Crohn's disease in children 显示文摘 | Heuschkel RB Menache CC Megerian JT | 2000 | J Pediatr Gastroenterol Nutr2000，31，1： | 1 |
| 19 | Infliximab Delays but Does Not Avoid the Need for Surgery in Treatment-Resistant Pediatric Crohn’ Disease显示文摘 | N. A. Afzal A. Ozzard S. Keady M. Thomson S. Murch R. Heuschkel | 2007 | Digestive Diseases and Sciences2007，，12： | 1 |
| 20 | Enteral Nutrition and Corticosteroids in the Treatment of Acute Crohn's Disease in Children显示文摘 | Heuschkel R B Menache C C Megerian J T | 2000 | J Pediatr Gastroenterol Nutr2000，31，1： | 1 |
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