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| 1 | The effect of adenovirus expressing wild-type p53 on 5-fluorouracil chemosensitivity is related to p53 status in pancreatic cancer cell lines显示文摘AIM: There are conflicting data about p53 function on cellular sensitivity to the cytotoxic action of 5-fluorouracil (5-FU).Therefore the objective of this study was to determine the combined effects of adenovirus-mediated wild-type (wt) p53 gene transfer and 5-FU chemotherapy on pancreatic cancer cells with different p53 gene status.METHODS: Human pancreatic cancer cell lines Capan-1^p53mut,Capan-2^p53wt, FAMPAC^p53mut, PANG1^p53mut, and rat pancreatic cancer cell lines AS^p53wt and DSL6A^p53null were used for in vitro studies. Following infection with different ratios of Adp53-particles (MOI) in combination with 5-FU, proliferation of tumor cells and apoptosis were quantified by cell proliferation assay (WST-1) and FACS (PI-staining). In addition, DSL6A syngeneic pancreatic tumor cells were inoculated subcutaneously in to Lewis rats for in vivostudies.Tumor size, apoptosis (TUNEL) and survival were determined.RESULTS: Ad-p53 gene transfer combined with 5-FU significantly inhibited tumor cell proliferation and substantially enhanced apoptosis in all four cell lines with an alteration in the p53 gene compared to those two cell lines containing wt-p53. In vivo experiments showed the most effective tumor regression in animals treated with Ad-p53 plus 5-FU. Both in vitroand in vivoanalyses revealed that a sublethal dose of Ad-p53 augmented the apoptotic response induced by 5-FU.CONCLUSION: Our results suggest that Ad-p53 may synergistically enhance 5-FU-chemosensitivity most strikingly in pancreatic cancer cells lacking p53 function. These findings illustrate that the anticancer efficacy of this combination treatment is dependent on the p53 gene status of the target tumor cells. | Sven Eisold Michael Linnebacher EduardRyschich DaliborAntolovic UlfHinz Ernst Klar Jan Schmidt | 2004 | World Journal of Gastroenterology2004，10，24： | 14 |
| 2 | Identification of differentially expressed genes after partial rat liver ischemia/reperfusion by suppression subtractive hybridization显示文摘AIM: To identify potential diagnostic target genes in early reperfusion periods following warm liver ischemia before irreversible liver damage occurs.METHODS: We used two strategies (SSH suppression subtractive hybridization and hybridization of cDNA arrays)to determine early changes in gene expression profiles in a rat model of partial WI/R, comparing postischemic and adjacent nonischemic liver lobes. Differential gene expression was verified (WT/R; 1 h/2 h) and analyzed in more detail after warm ischemia (1 h) in a reperfusion time kinetics (0, 1, 2 and 6 h) and compared to untreated livers by Northern blot hybridizations. Protein expression was examined on Western blots and by immunohistochemistry for four differentially expressed target genes (Hsp70,Hsp27, Gadd45a and IL-1rl).RESULTS: Thirty-two individual WI/R target genes showing altered RNA levels after confirmation by Northern blot analyzes were identified. Among them, six functionally uncharacteristic expressed sequences and 26 known genes (12 induced in postischemic liver lobes, 14 with higher transcriptional expression in adjacent nonischemic liver lobes). Functional categories of the verified marker genes indicate on the one hand cellular stress and tissue damage but otherwise activation of protective cellular reactions (AP-1 transcription factors, apoptosis related genes, heat shock genes). In order to assign the transcriptional status to the biological relevant protein level we demonstrated that Hsp70, Hsp27, Gadd45a and IL-1rI were clearly up-regulated comparing postischemic and untreated rat livers, suggesting their involvement in the WI/R context.CONCLUSION: This study unveils a WI/R response gene set that will help to explore molecular pathways involved in the tissue damage after WI/R. In addition, these genes especially Hsp70and Gadd45a might represent promising new candidates indicating WI/R liver damage. | Christine Fallsehr Christina Zapletal Michael Kremer Resit Demir Magnus von Knebel Doeberitz Ernst Klar | 2005 | World Journal of Gastroenterology2005，11，9： | 4 |
| 3 | Direct and relaxation methods for soil-structure interaction due to tunneling显示文摘This paper deals with the problem of tunneling effects on existing buildings. The direct solution,using the condensation method,is presented. This method allows the structural and geotechnical engineers to treat the problem separately and then assemble a relatively small matrix that can be solved directly,even within a spreadsheet. There are certain concerns that the resultant matrix may be ill-conditioned when the structure is very stiff. This paper suggests an alternative method that essentially relaxes the system from an infinitely rigid structure solution. As such,it does not encounter the problems associated with stiff systems. The two methods are evaluated for an example problem of tunneling below a framed structure. It is found that while the direct method may fail to predict reasonable values when the structure is extremely rigid,the alternative method is stable. The relaxation method can therefore be used in cases where there are concerns about the reliability of a direct solution. | Assaf KLAR Itai ELKAYAM | 2010 | Journal of Zhejiang University-Science A(Applied Physics & Engineering)2010，11，1： | 3 |
| 4 | Bacteriolytic therapy of experimental pancreatic carcinoma显示文摘AIM:To investigate the effectiveness of Clostridium novyi(C.novyi)-NT spores for the treatment of established subcutaneous pancreatic tumor in the syngeneic,immunocompetent Panc02/C57Bl/6 model. METHODS:C.novyi-NT spores were applied intravenously to animals carrying established pancreatic tumors of three different sizes.Systemic immune responses in peripheral blood and spleen were examined by flow cytometry.Supplementary,cytotoxic activity of lymphocytes against syngeneic tumor targets was analyzed. RESULTS:Application of spores identified,that(1) small tumors(<150 mm 3 )were completely unaffected (n=10);(2)very large tumors(>450 mm3)responded with substantial necrosis followed by shrinkage and significant lethality most likely due to tumor lysis syndrome (n=6);and(3)an optimal treatment window exists for tumors of approximately 250 mm 3 (n=21).In this latter group,all tumor-bearing animals had complete tu-mor regression and remained free of tumor recurrence. In subsequent tumor rechallenge experiments a significant delay in tumor growth compared to the initial tumor cell inoculation was observed(tumor volume at day 28:197.8±87.3 mm 3 vs 500.1±50.9 mm3,P<0.05). These effects were accompanied by systemic activation of immune response mechanisms predominantly mediated by the innate arm of the immune system. CONCLUSION:The observed complete tumor regression is encouraging and shows that immunotherapy with C.novyi-NT is an interesting strategy for the treatment of pancreatic carcinomas of defined sizes. | Claudia Maletzki Michael Gock Ulrike Klier Ernst Klar Michael Linnebacher | 2010 | World Journal of Gastroenterology2010，16，28： | 3 |
| 5 | A hardening load transfer function for rock bolts and its calibration using distributed fiber optic sensing显示文摘Confinement of rock bolts by the surrounding rock formation has long been recognized as a positive contributor to the pull-out behavior,yet only a few experimental works and analytical models have been reported,most of which are based on the global rock bolt response evaluated in pull-out tests.This paper presents a laboratory experimental setup aiming to capture the rock formation effect,while using distributed fiber optic sensing to quantify the effect of the confinement and the reinforcement pull-out behavior on a more local level.It is shown that the behavior along the sample itself varies,with certain points exhibiting stress drops with crack formation.Some edge effects related to the kinematic freedom of the grout to dilate are also observed.Regardless,it was found that the mid-level response is quite similar to the average response along the sample.The ability to characterize the variation of the response along the sample is one of the many advantages high-resolution fiber optic sensing allows in such investigations.The paper also offers a plasticity-based hardening load transfer function,representing a'slice'of the anchor.The paper describes in detail the development of the model and the calibration/determination of its parameters.The suggested model captures well the coupled behavior in which the pull-out process leads to an increase in the confining stress due to dilative behavior. | Assaf Klar Ori Nissim Itai Elkayam | 2023 | Journal of Rock Mechanics and Geotechnical Engineering2023，15，11： | 2 |
| 6 | Outcome prediction for individual intensive care patients: Useful, misused, or abused?显示文摘 | S. Lemeshow J. Klar D. Teres | 1995 | Intensive Care Medicine1995，，9： | 2 |
| 7 | Genetic models for handedness,brain lateralization,schizophrenia,and manic-depression显示文摘 | Klar AJ | 1999 | Schizophr Res1999，39，3： | 1 |
| 8 | Interpolymer complexation and its effect on bioadhesive strength and dissolution characteris-tics of buccal drug delivery system 显示文摘 | Gupta A Gary S Klar PK | 1994 | Drug Dev Ind Pharm1994，20，3： | 1 |
| 9 | Distributed performance monitoring: methods, tools, and applications 显示文摘 | Hofmann R Klar P Mohr B | 1994 | IEEE Transactions on Parallel and Distributed Systems1994，5，6： | 1 |
| 10 | New pathophysiologic knowledge about acute pancreatitis显示文摘 | Klar E Werner J | 2000 | Chirurg2000，71，3： | 1 |
| 11 | Compact design for high precision machine tools 显示文摘 | BRECHER C UTSCH P KLAR R | 2010 | International Journal of Machine Tools & Manufacture2010，50，4： | 1 |
| 12 | Soil-pipe interaction due to tunnel- ling:comparison between Winkler and elastic continuum solu- tions显示文摘 | KLAR A VOSTER T E | 2005 | Geotechnique2005，55，8： | 1 |
| 13 | Breaking Abbe' s diffraction resolution limit in fluorescence microscopy with stimulated emission depletion beams of various shapes 显示文摘 | T A Klar E Engel S W Hell | 2001 | Phys Rev E2001，64，06： | 1 |
| 14 | Good prediction of the likelihood for sentinel lymph node metastasis by using the MSKCC nomogram in a german breast cancer population 显示文摘 | Klar M Foeldi M Gitsch G | 2009 | Ann Surg Oncol2009，16，5： | 1 |
| 15 | Mortality probability models for patients in the intensive care unit for 48 or 72h:a prospective multicenter study显示文摘 | Lemeshow S Klar J Teres D | 1994 | Crit Care Med1994，22，： | 1 |
| 16 | Soil-pipe interaction due to tunnelling: comparison between Winkler and elastic continuum solutions显示文摘 | KLAR A VORSTER T E B SOGA K | 2005 | G6otechnique2005，55，6： | 1 |
| 17 | Outcome prediction for individual intensive care patients:useful,misused,or abused?显示文摘 | Lemeshow S Klar J Teres D | 1995 | Intensive Care Med1995，21，： | 1 |
| 18 | Soil-pipe interaction due to tunnelling: comparison between Winkler and elastic continuum solutions显示文摘 | KLAR A VORSTER T E B SOGA K | 2005 | Geotechnique2005，55，6： | 1 |
| 19 | General inhibition of renocortical cyclooxygenase-2 expression by the renin-angiotensin system显示文摘 | Castrop H Klar J Wagner C | 2003 | Am J Physiol Renal Physiol2003，284，： | 1 |
| 20 | Isovolemic:hemodilution with dextran 60 as treament of pancreatic ischemia in acute pancreatitis显示文摘 | Klar E Foitzik T Buhr H | | 0，，： | 1 |
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