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| 1 | TRAIL-induced apoptosis of hepatocellular carcinoma cells is augmented by targeted therapies显示文摘AIM:To analyze the effect of chemotherapeutic drugs and specific kinase inhibitors,in combination with the death receptor ligand tumor necrosis factor-related apoptosis inducing ligand(TRAIL),on overcoming TRAIL resistance in hepatocellular carcinoma(HCC)and to study the efficacy of agonistic TRAIL antibodies,as well as the commitment of antiapoptotic BCL-2 proteins, in TRAIL-induced apoptosis. METHODS:Surface expression of TRAIL receptors (TRAIL-R1-4)and expression levels of the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL were analyzed by flow cytometry and Western blotting,respectively. Knock-down of MCL-1 and BCL-xL was performed by transfecting specific small interfering RNAs.HCC cellswere treated with kinase inhibitors and chemotherapeutic drugs.Apoptosis induction and cell viability were analyzed via flow cytometry and 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS:TRAIL-R1 and-R2 were profoundly expressed on the HCC cell lines Huh7 and Hep-G2. However,treatment of Huh7 and Hep-G2 with TRAIL and agonistic antibodies only induced minor apoptosis rates.Apoptosis resistance towards TRAIL could be considerably reduced by adding the chemotherapeutic drugs 5-fluorouracil and doxorubicin as well as the kinase inhibitors LY294002[inhibition of phosphoinositol- 3-kinase(PI3K)],AG1478(epidermal growth factor receptor kinase),PD98059(MEK1),rapamycin(mam- malian target of rapamycin)and the multi-kinase inhibitor Sorafenib.Furthermore,the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL play a major role in TRAIL resistance:knock-down by RNA interference increased TRAIL-induced apoptosis of HCC cells.Additionally, knock-down of MCL-1 and BCL-xL led to a significant sensitization of HCC cells towards inhibition of both c-Jun N-terminal kinase and PI3K.CONCLUSION:Our data identify the blockage of survival kinases,combination with chemotherapeutic drugs and targeting of antiapoptotic BCL-2 proteins as promising ways to overcome TRAIL resistance in HCC. | Bruno Christian Koehler Toni Urbanik Binje Vick Regina Johanna Boger Steffen Heeger Peter R Galle Marcus Schuchmann Henning Schulze-Bergkamen | 2009 | World Journal of Gastroenterology2009，15，47： | 9 |
| 2 | Adding pegylated interferon to a current nucleos(t)ide therapy leads to HBsAg seroconversion in a subgroup of patients with chronic hepatitis B显示文摘 | Jens M. Kittner Martin F. Sprinzl Annette Grambihler Arndt Weinmann J?rn M. Schattenberg Peter R. Galle Marcus Schuchmann | 2012 | Journal of Clinical Virology2012，，1： | 2 |
| 3 | Efficacy of SpyGlass^(TM)-directed biopsy compared to brush cytology in obtaining adequate tissue for diagnosis in patients with biliary strictures显示文摘AIM: To evaluate the diagnostic yield(inflammatory activity) and efficiency(size of the biopsy specimen) of SpyGlassTM-guided biopsy vs standard brush cytology in patients with and without primary sclerosing cholangitis(PSC).METHODS: At the University Medical Center Mainz, Germany, 35 consecutive patients with unclear biliarylesions(16 patients) or long-standing PSC(19 patients) were screened for the study. All patients underwent a physical examination, lab analyses, and abdominal ultrasound. Thirty-one patients with non-PSC strictures or with PSC were scheduled to undergo endoscopic retrograde cholangiography(ERC) and subsequent per-oral cholangioscopy(POC). Standard ERC was initially performed, and any lesions or strictures were localized. POC was performed later during the same session. The Boston Scientific SpyGlass SystemTM(Natick, MA, United States) was used for choledochoscopy. The biliary tree was visualized, and suspected lesions or strictures were biopsied, followed by brush cytology of the same area. The study endpoints(for both techniques) were the degree of inflammation, tissue specimen size, and the patient populations(PSC vs non-PSC). Inflammatory changes were divided into three categories: none, low activity, and high activity. The specimen quantity was rated as low, moderate, or sufficient.RESULTS: SpyGlassTM imaging and brush cytology with material retrieval were performed in 29 of 31(93.5%) patients(23 of the 29 patients were male). The median patient age was 45 years(min, 20 years; max, 76 years). Nineteen patients had known PSC, and 10 showed non-PSC strictures. No procedure-related complications were encountered. However, for both methods, tissues could only be retrieved from 29 pa-tients. In cases of inflammation of the biliary tract, the diagnostic yield of the SpyGlassTM-directed biopsies was greater than that using brush cytology. More tissue material was obtained for the biopsy method than for the brush cytology method(P = 0.021). The biopsies showed significantly more inflammatory characteristics and greater inflammatory activity compared to the cy-tological investigation(P = 0.014). The greater quantity of tissue samples proved useful for both PSC and non-PSC patients.CONCLUSION: SpyGlassTM imaging can be recom-mended for proper inflammatory diagnosis in PSC pa-tients. However, its value in diagnosing dysplasia wasnot addressed in this study and requires further investi-gation. | Johannes Wilhelm Rey Torsten Hansen Sebastian Dümcke Achim Tresch Katja Kramer Peter Robert Galle Martin Goetz Marcus Schuchmann Ralf Kiesslich Arthur Hoffman | 2014 | World Journal of Gastrointestinal Endoscopy2014，6，4： | 2 |
| 4 | Precipitation of metal oxide nanoparticles using a miniemulsion technique显示文摘A method to precipitate nanoparticles using a miniemulsion technique is described, in which miniemulsion droplets between 100 and 1000 nm in size serve as nanoreactors enabling both the control of particle formation and particle growth. The application of miniemulsion droplets to synthesise nanoparticles comprises three advantages: first, the size of the precipitated particles is limited by the reactant concentration within the emulsion droplet; second, particle agglomeration is prevented as nanoparticle collision outside the nanoreactor is avoided; and third, easy technical scale up can be realized by increasing emulsion volume and thus the number of nanoreactors, while local conditions within the reactors are not changed. The miniemulsion technique is an easy scalable process which allows defined synthesis of particles by precipitation reactions. The miniemulsion technique involves first the preparation of a stable water-in- oil miniemulsion by high pressure homogenisation. Whereas a water soluble reactant is provided within the aqueous droplets, another oil- as well as water-soluble reactant can be introduced to the emulsion after homogenisation. The precipitation reaction is induced by the diffusion of the second reactant into the emulsion droplet. Together with this contribution, a method is described and discussed which uses a high pressure homogenisation process to produce stable water-in-oil miniemulsions serving as a reaction medium to precipitate metal oxides. | Marion Winkelmann Heike Petra Schuchmann | 2011 | Particuology2011，9，5： | 2 |
| 5 | Effects of dexamethasone and celecoxib on calcium homeostasis and expression of cyclooxygenase-2 mRNA in MG-63 human osteosarcoma cells显示文摘 | Wiontzek M Matziolis G Schuchmann S | 2006 | Clin Exp Rheumatol2006，24，4： | 1 |
| 6 | Dietary fiber in extru- ded cereals : limitations and opportunities 显示文摘 | Robin F Schuchmann H P Palzer F | 2012 | Trends in Food Science & Technology2012，28，： | 1 |
| 7 | Sonolysis of aqueous 4-nitrophenol at low and high pH显示文摘 | Tauber A Schuchmann H P Sonntag C V | 2000 | Ultrasonics Sonochemistry2000，7，1： | 1 |
| 8 | Structure of and diffusion in O/W/O double emulsions by CLSM and NMR-comparison with W/O/W显示文摘 | BERNEWITZ R SCHMIDT US SCHUCHMANN HP | 2014 | Colloids Surf A:Physicochem Eng Aspects2014，458，： | 1 |
| 9 | Dietary fiber in extruded cereals:Limitations and opportunities显示文摘 | Robin F Schuchmann H P Palzer S | 2012 | Trends in Food Science & Technology2012，28，1： | 1 |
| 10 | Immune-mediated liver injury显示文摘 | Herkel J Schuchmann M Tiegs G | 2005 | J Hepatol2005，42，6： | 1 |
| 11 | Experimental fe- brile sezures are precipitated by a hyperthermia-induced re- spiratory alkalosiys显示文摘 | Schuchmann S Schmitz D Rivera C | 2006 | Nat Med2006，12，7： | 1 |
| 12 | thermal processing of carrots:Lycopene stability and isomerisation with regard to antioxidant potential显示文摘 | Mayer-Miebach E Behsnilian D Regier M Schuchmann H P | 2005 | Food Research International2005，，38： | 1 |
| 13 | Suppres- sion of Mcl-1 via RNA interference sensitizes human hepatocellular carcinoma ceils towards apoptosis induction 显示文摘 | Schulze-Bergkamen H Fleischer B Schuchmann M | 2006 | BMC Cancer2006，2，6： | 1 |
| 14 | apoptosis in liver disease显示文摘 | Schattenberg JM Galle PR Schuchmann M | 2006 | Liver lnt2006，26，8： | 1 |
| 15 | Apoptosis in liver disease显示文摘 | Schattenberg JM Galle PR Schuchmann M | 2006 | Liver Int2006，26，8： | 1 |
| 16 | Persistent hiccups during rehabilitation hospitalization:three case reports and review of the literature显示文摘 | Schuchmann JA Browne BA | 2007 | American Journal of Physical Medicine & Rehabilitation2007，86，12： | 1 |
| 17 | Cell death and hep- atocarcinogenesis: dysregulation of apoptosis signaling pathways显示文摘 | Schattenberg J M Schuchmann M Galle P R | 2011 | J Gas- troenterol Hepatol2011，26，1： | 1 |
| 18 | Attenuated total reflection infrared (ATR-IR)spectroscopy of a water-in-oil emulsion显示文摘 | KIEFER J FRANK K SCHUCHMANN HP | 2011 | Appl Spectrosc2011，65，9： | 1 |
| 19 | How to decide about liver transplantation in patients with hepatocellular carci- noma:size and number of lesions or response to TACE? 显示文摘 | Otto G Schuchmann M Hoppe-Lotichius M | 2013 | J Hepatol2013，59，： | 1 |
| 20 | Differential scanning calorimetry (DSC)in multiple W/O/W emulsions显示文摘 | SCHUCH A KOHLER K SCHUCHMANN HP | 2013 | J Therm Anal Calorim2013，111，3： | 1 |
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