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Hepatocellular carcinoma: Therapy and prevention

World Journal of Gastroenterology 2005年第47期11卷 7391-7400页

作者： Hubert E blum department of Medicine Ⅱ University of FreiburgD-79106 FreiburgGermany

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. despite these scientific advances and the implementation of measures for the early detection of HCC in patients at risk, patient survival has not improved during the last three decades. This is due to the advanced stage of the disease at the time of clinical presentation and limited therapeutic options. The therapeutic options fall into five main categories: surgical interventions including tumor resection and liver transplantation, percutaneous interventions including ethanol injection and radiofrequency thermal ablation, transarterial interventions including embolization and chemoembolization, radiation therapy and drugs as well as gene and immune therapies. These therapeutic strategies have been evaluated in part in randomized controlled clinical trials that are the basis for therapeutic recommendations. Though surgery, percutaneous and transarterial interventions are effective in patients with limited disease (1-3 lesions, ＜5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis more than 80% patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care. In order to reduce the morbidity and mortality of HCC, early diagnosis and the development of novel systemic therapies for advanced disease, including drugs, gene and immune therapies as well as primary HCC prevention are of paramount importance. Furthermore, secondary HCC prevention after successful therapeutic interventions needs to be improved in order to make an impact on the survival of patients with HCC. New technologies, including gene expression profiling and proteomic analyses, should allow to further elucida

关键词： HCC resection Liver transplantation Percutaneous ethanol injection Radiofrequency thermal ablation Transarterial embolization or chemoembolization Chemotherapy Gene therapy Immune therapy Prevention

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Significant methodologic variations in calculating renal function changes following kidney tumor surgery:A quality reporting issue?

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World Journal of Clinical Oncology 2015年第5期6卷 89-91页

作者： Ruth d blum Jay d Raman division of Urology Penn State Milton S.Hershey Medical Center

Renal tumor surgery places patients at increased risk for chronic kidney disease(CKd). Accurate quantification of kidney function changes before and after surgery is essential to determine the magnitude of decline attributable to an index procedure. Current literature, however, highlights heterogeneity and inconsistencies in measurement techniques thereby contributing to ambiguity amongst studies. Further efforts are necessary to standardize reporting of kidney function outcomes related to renal surgery.

关键词： Radical nephrectomy Partial nephrectomy Nephroureterectomy Glomerular filtration rate Chronic kidney disease

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Effect of ultrasonic vibration-assisted laser surface melting and texturing of Ti-6Al-4V ELI alloy on surface properties

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Journal of Materials Science & Technology 2019年第2期35卷 295-302页

作者： Sourabh Biswas S.Habib Alavi Bhishma Sedai Frank d.blum Sandip P.Harimkar School of Mechanical and Aerospace Engineering Oklahoma State University department of Chemistry Oklahoma State University

Ultrasonic vibration-assisted laser surface processing that involves application of vertical ultrasonic vibrations to the Ti-6 Al-4 V alloy substrates while being irradiated with a CO_2 laser was performed for the development of laser melted and textured surfaces with potential applications in biomedical *** laser processing resulted in very consistent repeating undulating grooved surfaces, and the undulations were significantly more pronounced in the samples processed with higher ultrasonic power *** phase evolution, studied by x-ray diffraction, confirmed that the laser processing triggered transformation of globular α→ acicular α and martensitic α' as well as increased amounts of retained α phases,which were also reflected in the microscopic analysis. The surface texture developed by laser processing resulted in increased surface wettability with increasing ultrasonic power output. The textured surfaces exhibited marked decrease in coefficients of friction during sliding wear testing performed under simulated body fluid due to lubricant entrainment within the textured grooves. The texturing also resulted in significant reduction in surface contact area during the wear process, which considerably reduced the overall wear rates due to abrasive wear.

关键词： Laser texturing Laser melting Ultrasonic vibrations Wear

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Hepatitis C virus infection and apoptosis

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World Journal of Gastroenterology 2007年第36期13卷 4865-4872页

作者： Richard Fischer Thomas Baumert Hubert E blum department of InternalMedicine II University of Freiburg Germany Inserm U748 Service d’Hépatogastro-entérologie Hpitaux Universitaires de Strasbourg Strasbourg France

Apoptosis is central for the control and elimination of viral infections. In chronic hepatitis C virus (HCV) infection, enhanced hepatocyte apoptosis and upregulation of the death inducing ligands Cd95/Fas, TRAIL and TNFα occur. Nevertheless, HCV infection persists in the majority of patients. The impact of apoptosis in chronic HCV infection is not well understood. It may be harmful by triggering liver fibrosis, or essential in interferon (IFN) induced HCV elimination. For virtually all HCV proteins, pro- and anti-apoptotic effects have been described, especially for the core and NS5A protein. To date, it is not known which HCV protein affects apoptosis in vivo and whether the infectious virions act pro- or anti- apoptotic. With the availability of an infectious tissue culture system, we now can address pathophysiologically relevant issues. This review focuses on the effect of HCV infection and different HCV proteins on apoptosis and of the corresponding signaling cascades.

关键词： Hepatitis C Spoptosis TRAIL Cd95/Fas TNFα Perforin

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Pseudomonas exotoxin antisense RNA selectively kills hepatitis B virus infected cells

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World Journal of Gastroenterology 2008年第18期14卷 2810-2817页

作者： Peter Hafkemeyer Ulrich Brinkmann Elizabeth Brinkmann Ira Pastan Hubert E blum Thomas F Baumert department of Medicine Ⅱ University Hospital Freiburg Hugstetterstrasse 55 Freiburg D-79106 Germany Roche diagnostics Nonnenwald 2 Penzberg D-82377 Germany National Cancer Institute National Institutes of Health Bethesda United States Inserm unit 748 Université Louis Pasteur 3 Rue Koeberle Strasbourg F-67000 France

AIM: To present an approach for selectively killing retrovirus-infected cells that combines the toxicity of Pseudomonas exotoxin (PE) and the presence of reverse transcriptase (RT) in infected cells. METHOdS: PE antisense toxin RNA has palindromic stem loops at its 5' and 3' ends enabling self-primed generation of cdNA in the presence of RT. The RT activity expressed in retrovirus-infected cells converts "antisense-toxin-RNA" into a lethal toxin gene exclusively in these cells. RESULTS: Using cotransfection studies with PE-expressing RNAs and β-gal expressing reporter plasmids, we show that, in HepG2 and HepG2.2.15 hepatoma cells as well as in duck hepatitis B virus (dHBV) infected cells, HBV or dHBV-polymerase reverse transcribe a lethal cdNA copy of an antisense toxin RNA, which is composed of sequences complementary to a PE gene and eukaryotic transcription and translation signals. CONCLUSION: This finding may have important implications as a novel therapeutic strategy aimed at the elimination of HBV infection.

关键词： Gene therapy Pseudomonas exotoxin Retrovirus Reverse transcription

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When starvation therapy meets chemodynamic therapy

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ChemPhysMater 2022年第4期1卷 264-280页

作者： Nicholas Thomas blum Lianhua Fu Jing Lin Peng Huang Marshall Laboratory of Biomedical Engineering International Cancer CenterLaboratory of Evolutionary Theranostics(LET)School of Biomedical EngineeringHealth Science CenterShenzhen UniversityShenzhen 518060China

In recent years,starvation-primed chemodynamic therapies(ST-CdT)have become a hot topic in the wake of many discoveries related to the aberrant metabolism of cancer cells and their resistance to traditional chemother-apies,as well as altered redox signaling within tumor *** platforms are in a unique position to exploit these interrelated phenomena to realize a therapeutic effect;few therapeutic modalities are able to deliver multiple drugs simultaneously outside of nanotechnology,a basic requirement when striving to exploit a complex,interactive system such as a cancer *** this review,the pertinent mechanisms of ST and CdT,as well as the important interactions between these two therapies,are *** outline how these therapies may work synergistically or antagonistically,depending on both the therapeutic design and the system of reactions ***,specific applications that nanotechnology is particularly well-suited are given,which may offer improvement over clinical *** considerations are important,as nanotechnology has historically encountered great difficulty in clinical translation.

关键词： Starvation therapy Chemodynamic therapy Glucose oxidase Reactive oxygen species Cancer

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Comparison of imaging-based and pathological dimensions in pancreatic neuroendocrine tumors

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World Journal of Gastroenterology 2017年第17期23卷 3092-3098页

作者： Salvatore Paiella Harmony Impellizzeri Elisabetta Zanolin Giovanni Marchegiani Marco Miotto Anna Malpaga Riccardo de Robertis Mirko d'Onofrio Borislav Rusev Paola Capelli Sara Cingarlini Giovanni Butturini Maria Vittoria davì Antonio Amodio Claudio BassiAldo Scarpa Roberto Salvia Luca Landoni General and Pancreatic Surgery department Pancreas InstituteUniversity and Hospital Trust of Verona department of Public Health and Community Medicine University and Hospital Trust of Verona department of Radiology Casa di Cura Pederzoli department of Radiology Pancreas InstituteUniversity and Hospital Trust of Verona department of diagnostics and Public Health Section of PathologyUniversity and Hospital Trust of Verona ARC-NET Research Center University and Hospital Trust of Verona department of Oncology Pancreas InstituteUniversity and Hospital Trust of Verona Hepato-bilio-pancreatic Surgery Unit Casa di Cura Pederzoli Section of Endocrinology Medicina Generale e Malattie Aterotrombotiche e DegenerativeDepartment of MedicineUniversity and Hospital Trust of Verona Gastroenterology B department Pancreas InstituteUniversity and Hospital Trust of Verona

AIM To establish the ability of magnetic resonance(MR) and computer tomography(CT) to predict pathologic dimensions of pancreatic neuroendocrine tumors(Pan NET) in a caseload of a tertiary referral *** Patients submitted to surgery for Pan NET at the Surgical Unit of the Pancreas Institute with at least 1 preoperative imaging examination(MR or CT scan) from January 2005 to december 2015 were included and data retrospectively collected. Exclusion criteria were: multifocal lesions, genetic syndromes, microadenomas or mixed tumors, metastatic disease and neoadjuvant therapy. Bland-Altman(BA) and Mountain-Plot(MP) statistics were used to compare size measured by each modality with the pathology size. Passing-Bablok(PB) regression analysis was used to check the agreement between MR and *** Our study population consisted of 292 patients. Seventy-nine(27.1%) were functioning Pan NET. The mean biases were 0.17 ± 7.99 mm, 1 ± 8.51 mm and 0.23 ± 9 mm, 1.2 ± 9.8 mm for MR and CT, considering the overall population and the subgroup of non-functioning-Pan NET, respectively. Limits of agreement(LOA) included the vast majority of observations, indicating a good agreement between imaging and pathology. The MP further confirmed this finding and showed that the two methods are unbiased with respect to each other. Considering ≤ 2 cm non-functioning-Pan NET, no statistical significance was found in the size estimation rate of MR and CT(P = 0.433). PBR analysis did not reveal significant differences between MR, CT and *** MR and CT scan are accurate and interchangeable imaging techniques in predicting pathologic dimensions of Pan NET.

关键词： Pancreatic neoplasms Neuroendocrine tumors Magnetic resonance imaging diagnostic imaging Pathological dimensions

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Chemical Compositions of the Leaf Essential Oils of <i>Aralia spinosa</i>from Three Habitats in Northern Alabama

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American Journal of Plant Sciences 2011年第3期2卷 507-510页

作者： Purva C. davé Bernhard Vogler William N. Setzer 不详

Aralia spinosa leaves were collected from three different habitats in north Alabama. The leaf essential oils were collected by hydrodistillation and analyzed by gas chromatography / mass spectrometry (GC-MS). The most abundant components of A. spinosa essential oils were the sesquiterpenes germacrene d (28.0% - 37.3%), (E)-caryophyllene (8.2% - 15.7%), and α-humulene (1.9% - 4.9%);the monoterpene myrcene (up to 15.1%), and the fatty-acid-derivative (2E)-hexenal (trace to 28.9%). Fatty-acid derivatives and monoterpene hydrocarbons were more abundant in samples from suburban Huntsville than those from “natural” habitats (Monte Sano Mountain, Wheeler National Wildlife Refuge), while sesquiterpene hydrocarbons were more abundant in the natural/wild samples.

关键词： Aralia spinosa Araliaceae Leaf Essential Oil Chemical Composition Germacrene d Myrcene (E)-Caryophyllene (2E)-Hexenal

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EGFR and HER2 expression in advanced biliary tract cancer

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World Journal of Gastroenterology 2009年第36期15卷 4511-4517页

作者： Jan Harder Oliver Waiz Florian Otto Michael Geissler Manfred Olschewski Brigitte Weinhold Hubert E blum Annette Schmitt-Graeff Oliver G Opitz department of MedicineⅡ University Medical CenterD-79106 Freiburg Germany Tumorzentrum Ludwig Heilmeyer- Comprehensive Cancer Center Freiburg D-79106 Freiburg Germany Tumorzentrum ZeTuP St.GallenSwitzerland and Department of MedicineⅠUniversity Medical Center D-79106 FreiburgGermany department of Medicine Gastroenterology and OncologyMunicipal Hospital EsslingenGermany department of Medical Biometry und Statistics University of FreiburgD-79106 FreiburgGermany Annette Schmitt-Graeff Institute of PathologyUniversity Medical CenterD-79106 Freiburg Germany

AIM:To analyze the pathogenetic role and potential clinical usefulness of the epidermal growth factor receptor(EGFR)and the human epidermal growth factor receptor 2(HER2)in patients with advanced biliary tract cancer(BTC). METHOdS:EGFR and HER2 expression was studied in biopsy samples from 124 patients(51%women; median age 64.8 years),with advanced BTC diagnosed between 1997 and *** micrometers sections of paraffin embedded tissue were examined by standard, FdA approved *** with scores of 2+or 3+for HER2 expression on immunochemistry were additionally tested for HER2 gene amplification by fluorescence in situ hybridisation(FISH).RESULTS:34/124 patients(27.4%)had gallbladder cancer,47(37.9%)had intrahepatic BTC and 43(34.7%)had extrahepatic or perihilar *** expression was examined in a subset of 56 samples. EGFR expression was absent in 22/56 tumors(39.3%). Of the remaining samples expression was scored as 1+in 12(21.5%),2+in 13(23.2%)and 3+in 9(16%), ***2 expression was as follows:score 0 73/124(58.8%),score 1+27/124(21.8%),score 2+ 21/124(17%)and score 3+4/124(3.2%).HER2 gene amplification was present in 6/124,resulting in an overall amplification rate of 5%. CONCLUSION:Our data suggest that routine testing and therapeutic targeting of HER2 does not seem to be useful in patients with BTC,while targeting EGFR may be promising.

关键词： Cholangiocarcinoma Gallbladder cancer Chemotherapy Targeted therapy

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Interaction of hepatitis C virus envelope glycoprotein E2 with the large extracellular loop of tupaia Cd81

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World Journal of Gastroenterology 2009年第2期15卷 240-244页

作者： Zhan-Fei Tian Hong Shen Xi-Hua Fu Yi-Chun Chen Hubert E blum Thomas F Baumert Xi-Ping Zhao department of Infectious diseases 161 Hospital of PLA Wuhan 430030 Hubei Province China department of Infectious diseases Tongji Hospital Tongji Medical College Huazhong Science & Technology University Wuhan 430030 Hubei Province China department of Medicine II University of Freiburg D-79106 Freiburg Germany Inserm U748 Universit6 Louis Pasteur Service d'Hepatogastroenterologie 3 Rue Koeberle F-67000 Strasbourg France

AIM: To further analyze the interaction of tupaia Cd81 with hepatitis C virus (HCV) envelope protein E2. METHOdS: A tupaia Cd81 large extracellular loop (Cd81 LEL), which binds to HCV E2 protein, was cloned and expressed as a GST-fusion protein, and interaction of HCV E2 protein with a tupaia Cd81 LEL was evaluated by enzyme-linked immunosorbent assay (EIA). RESULTS: Although tupaia and human Cd81 LEL differed in 6 amino acid changes, tupaia Cd81 LEL was strongly recognized by anti-Cd81 antibodies against human Cd81 LEL conformation-dependent epitopes. Investigating LEL Cd81-E2 interactions by EIA, we demonstrated that binding of tupaia Cd81 LEL GST fusion protein to recombinant HCV E2 protein was markedly reduced compared to binding of human Cd81 LEL GST fusion protein to recombinant HCV E2 protein. CONCLUSION: These data suggest that the structural differences in-between the tupaia and human Cd81 may alter the interaction of the large extracellular loop with HCV envelope glycoprotein E2. These findings may be important for the understanding of the mechanisms of binding and entry of HCV to PTHs.

关键词： Hepatitis C virus E2 protein Tupaia Cd81,Bind Enzyme-linked immunosorbent assay

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