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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 | Contribution of TLR signaling to the pathogenesis of colitisassociated cancer in inflammatory bowel disease显示文摘In the intestine a balance between proinflammatory and repair signals of the immune system is essential for the maintenance of intestinal homeostasis. The innate immunity ensures a primary host response to microbial invasion, which induces an inflammatory process to localize the infection and prevent systemic dissemination of pathogens. The key elements of this process are the germline encoded pattern recognition receptors inclu-ding Toll-like receptors(TLRs). If pathogens cannot be eliminated, they may elicit chronic inflammation, which may be partly mediated via TLRs. Additionally, chronic inflammation has long been suggested to trigger tissue tumorous transformation. Inflammation, the seventh hallmark of cancer, may affect all phases of tumor development, and evade the immune system. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability. Furthermore, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Colorectal cancers in inflammatory bowel disease patients are considered typical examples of inflammation-related cancers. Although data regarding the role of TLRs in the pathomechanism of cancer-as-sociated colitis are rather conflicting, functionally these molecules can be classified as 'largely antitumorigenic' and 'largely pro-tumorigenic' with the caveat that the underlying signaling pathways are mainly context(i.e., organ-, tissue-, cell-) and ligand-dependent. | Ferenc Sipos István Fri Miklós Constantinovits Zsolt Tulassay Gyrgyi Mzes | 2014 | World Journal of Gastroenterology2014，20，36： | 9 |
| 3 | Aging related methylation influences the gene expression of key control genes in colorectal cancer and adenoma显示文摘AIM To analyze colorectal carcinogenesis and age-related DNA methylation alterations of gene sequences associated with epigenetic clock CpG sites. METHODS In silico DNA methylation analysis of 353 epigenetic clock Cp G sites published by Steve Horvath was performed using methylation array data for a set of 123 colonic tissue samples [64 colorectal cancer(CRC), 42 adenoma, 17 normal; GEO accession number: GSE48684]. Among the differentially methylated agerelated genes, secreted frizzled related protein 1(SFRP1) promoter methylation was further investigated in colonic tissue from 8 healthy adults, 19 normal children, 20 adenoma and 8 CRC patients using bisulfite-specific PCR followed by methylation-specific high resolution melting(MS-HRM) analysis. m RNA expression of age-related 'epigenetic clock' genes was studied using Affymetrix HGU133 Plus2.0 whole transcriptome data of 153 colonic biopsy samples(49 healthy adult, 49 adenoma, 49 CRC, 6 healthy children)(GEO accession numbers: GSE37364, GSE10714, GSE4183, GSE37267). Whole promoter methylation analysis of genes showing inverse DNA methylationgene expression data was performed on 30 colonic samples using methyl capture sequencing.RESULTS Fifty-seven age-related Cp G sites including hypermethylated PPP1R16 B, SFRP1, SYNE1 and hypomethylated MGP, PIPOX were differentially methylated between CRC and normal tissues(P < 0.05, ?β≥ 10%). In the adenoma vs normal comparison, 70 CpG sites differed significantly, including hypermethylated DKK3, SDC2, SFRP1, SYNE1 and hypomethylated CEMIP, SPATA18(P < 0.05, ?β≥ 10%). In MS-HRM analysis, the SFRP1 promoter region was significantly hypermethylated in CRC(55.0% ± 8.4 %) and adenoma tissue samples(49.9% ± 18.1%) compared to normal adult(5.2% ± 2.7%) and young(2.2% ± 0.7%) colonic tissue(P < 0.0001). DNA methylation of SFRP1 promoter was slightly, but significantly increased in healthy adults compared to normal young samples(P < 0.02). This correlated with significantly increased SFRP1 m RNA levels in children compared to normal adult samples(P < 0.05). In CRC tissue the mR NA expression of 117 agerelated genes were changed, while in adenoma samples 102 genes showed differential expression compared with normal colonic tissue(P < 0.05, logF C > 0.5). The change of expression for several genes including SYNE1, CLEC3 B, LTBP3 and SFRP1, followed the same pattern in aging and carcinogenesis, though not for all genes(e.g., MGP). CONCLUSION Several age-related DNA methylation alterations can be observed during CRC development and progression affecting the m RNA expression of certain CRC- and adenoma-related key control genes. | Orsolya Galamb Alexandra Kalmár Barbara Kinga Barták árpád V Patai Katalin Leiszter Bálint Péterfia Barnabás Wichmann Gábor Valcz Gábor Veres Zsolt Tulassay Béla Molnár | 2016 | World Journal of Gastroenterology2016，22，47： | 7 |
| 4 | Comparison of different lymph node staging systems in prognosis of gastric cancer:a bi-institutional study from Hungary显示文摘Objective: The Union for International Cancer Control(UICC) Node(N) classification is the most common used staging method for the prognosis of gastric cancer. It demands adequate, at least 16 lymph nodes(LNs) to be dissected; therefore different staging systems were invented.Methods: Between March 2005 and March 2010, 164 patients were evaluated at the Department of General Surgery in the Kenézy Gyula Hospital and at the Department of General, Thoracic and Vascular Surgery in the Kaposi Mór Hospital. The 6th, 7th and 8th UICC N-staging systems, the number of examined LNs, the number of harvested negative LNs, the metastatic lymph node ratio(MLR) and the log odds of positive LNs(LODDS) were determined to measure their 5-year survival rates and to compare them to each other.Results: The overall 5-year survival rate for all patients was 55.5% with a median overall survival time of 102 months. The tumor stage, gender, UICC N-stages, MLR and the LODDS were significant prognostic factors for the 5-year survival with univariate analysis. The 6th UICC N-stage did not follow the adequate risk in comparing N2 vs. N0 and N3 vs. N0 with multivariate investigation. Comparison of performances of the residual N classifications proved that the LODDS system was first in the prediction of prognosis during the evaluation of all patients and in cases with less than 16 harvested LNs. The MLR gave the best prognostic prediction when adequate(more than or equal to 16) lymphadenectomy was performed.Conclusions: We suggest the application of LODDS system routinely in western patients and the usage of MLR classification in cases with extended lymphadenectomy. | dezso tóth adrienn bíró zsolt varga miklós torok péterárkosy | 2017 | Chinese Journal of Cancer Research2017，29，4： | 4 |
| 5 | Impact of proteolytic enzymes in colorectal cancer development and progression显示文摘Tumor invasion and metastasis is a highly complicated, multi-step phenomenon. In the complex event of tumor progression, tumor cells interact with basement membrane and extracellular matrix components. Proteolytic enzymes(proteinases) are involved in the degradation of extracellular matrix, but also in cancer invasion and metastasis. The four categories of proteinases(cysteine-, serine-, aspartic-, and metalloproteinases) are named and classified according to the essential catalytic component in their active site. We and others have shown that proteolytic enzymes play a major role not only in colorectal cancer(CRC) invasion and metastasis, but also in malignant transformation of precancerous lesions into cancer. Tissue and serumplasma antigen concentrations of proteinases might be of great value in identifying patients with poor prognosis in CRC. Our results, in concordance with othersindicate the potential tumor marker impact of proteinases for the early diagnosis of CRC. In addition, proteinases may also serve as potential target molecules for therapeutic agents. | László Herszényi Loránd Barabás István Hritz Gábor István Zsolt Tulassay | 2014 | World Journal of Gastroenterology2014，20，37： | 3 |
| 6 | Surgical stress and cytoskeletal changes in lens epithelial cells following manual and femtosecond laser-assisted capsulotomy显示文摘AIM:To study the effect of mechanical stress on the cytoskeleton in lens epithelial cells following conventional phacoemulsification surgery(CPS)and femtosecond laserassisted cataract surgery(FLACS).METHODS:The cytoskeleton of the epithelial cells of the anterior lens capsules(ALC)removed by CPS and FLACS was examined by immunohistochemistry.Expression of the intermediate filament,glial fibrillary acidic protein(GFAP),and glutamine synthetase(GS)immunoreactivity were detected.In order to map the actin network of cells,fluorescently labeled phalloidin was used.The samples were examined using confocal laser scanning microscopy.RESULTS:GFAP expression was visible in a larger number of the epithelial cells after CPS compared to FLACS.In CPS sample’s epithelial cells,GFAP immunoreactivity indicated robust morphological change.Regarding the actin filaments,the presence of tubular elements connecting epithelial cells,regular actin pattern and marked cortical network after CPS were found.Following FLACS,the actin cytoskeleton of the epithelial cells remained densely structured,and the tubular elements were undetectable,however,the above-mentioned regular actin pattern and the marked cortical network were visible.CONCLUSION:The conventional removal of the ALC induces more robust changes of the cytoskeleton of the lens epithelial cells. | ANDrea Krisztina Sükosd Krisztina Szabadfi Edina Szabó-Meleg Beáta Gáspár Pavel Stodulka Gyorgy SétálóJr Róbert Gábriel Miklós Nyitrai Zsolt Biró Hajnalka Abrahám | 2020 | International Journal of Ophthalmology(English edition)2020，13，6： | 2 |
| 7 | Relationship between diabetes mellitus and cataract in Hungary显示文摘AIM:To examine the coexistence of diabetes mellitus(DM)and cataract in Hungary.The effects of DM on the cataract surgical results were also in the focus of analysis.METHODS:Statistical data analysis of the results of the Rapid Assessment of Avoidable Blindness with Diabetic Retinopathy(RAAB+DR)module conducted in Hungary in 2015.This cross-sectional,population-based,national survey included 3523 people aged 50 years and over.Participants of the survey were examined on-site.Visual acuity,main cause for visual impairment(using direct and indirect ophthalmoscopes),in case of best corrected visual acuity(BCVA)≤0.5 and blood glucose level(random test with glucometer)were examined.RESULTS:The prevalence of cataract was 23.4%,and DM was 20.0%.The occurrence of cataract steadily increased with age.Among the examined participants with DM,the prevalence of cataract was significantly(P=0.012)higher(+35%)than that in non-diabetic subjects(29.5%vs 21.8%).Following aging(OR=15.2%,P<0.001),DM proved to be the most independent influencing risk factor(OR=49.9%,P<0.001).The presence of DM was neither an influencing factor for complications of cataract surgery,nor for postoperative visual acuity.CONCLUSION:DM appears to be one of the main risk factors for developing cataract.Other risk factors,such as age,sex and environment also play an influencing role.Diabetes does not seem to affect the occurrence of cataract surgical complications. | Anita Pék Dorottya Szabó Gábor LászlóSándor Gábor Tóth András Papp Zoltán Zsolt Nagy Hans Limburg János Németh | 2020 | International Journal of Ophthalmology(English edition)2020，13，5： | 2 |
| 8 | Elevated insulin-like growth factor 1 receptor, hepatocyte growth factor receptor and telomerase protein expression in mild ulcerative colitis显示文摘 | Ferenc Sipos Orsolya Galamb László Herszényi Béla Molnár Norbert Solymosi Tamás Zágoni Lajos Berczi Zsolt Tulassay | 2008 | Scandinavian Journal of Gastroenterology2008，，3： | 2 |
| 9 | Association of hepatocyte-derived growth factor receptor/caudal type homeobox 2 co-expression with mucosal regeneration in active ulcerative colitis显示文摘AIM:To characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived growth factor receptor(HGFR)-expressing cells in active ulcerative colitis(UC).METHODS:On the whole 38 peripheral blood samples and 38 colonic biopsy samples from 18 patients with histologically proven active UC and 20 healthy control subjects were collected.After preparing tissue microarrays and blood smears HGFR,caudal type homeobox 2(CDX2),prominin-1(CD133) and Musashi-1conventional and double fluorescent immunolabelings were performed.Immunostained samples were digitalized using high-resolution Mirax Desk instrument,and analyzed with the Mirax TMA Module software.For semiquantitative counting of immunopositive lamina propria(LP) cells 5 fields of view were counted at magnification x 200 in each sample core,then mean ± SD were determined.In case of peripheral blood smears,30 fields of view with 100 μm diameter were evaluated in every sample and the number of immunopositive cells(mean ± SD) was determined.Using 337 nm UVA Laser MicroDissection system at least 5000 subepithelial cells from the lamina propria were collected.Gene expression analysis of HGFR,CDX2,CD133,leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5),Musashi-1 and cytokeratin20(CK20) were performed in both laser-microdisscted samples and blood samples by using real time reverse transcription polymerase chain reaction(RT-PCR).RESULTS:By performing conventional and double fluorescent immunolabelings confirmed by RT-PCR,higher number of HGFR(blood:6.7 ± 1.22 vs 38.5 ±3.18;LP:2.25 ± 0.85 vs 9.22 ± 0.65;P < 0.05),CDX2(blood:0 vs 0.94 ± 0.64;LP:0.75 ± 0.55 vs 2.11± 0.75;P < 0.05),CD133(blood:1.1 ± 0.72 vs 8.3± 1.08;LP:11.1 ± 0.85 vs 26.28 ± 1.71;P < 0.05)and Musashi-1(blood and LP:0 vs scattered) positive cells were detected in blood and lamina propria of UC samples as compared to controls.HGFR/CDX2(blood:0 vs 1± 0.59;LP:0.8 ± 0.69 vs 2.06 ± 0.72,P < 0.05)and Musashi-1/CDX2(blood and LP:0 vs scattered) coexpressions were found in blood and lamina propria of UC samples.HGFR/CD133 and CD133/CDX2 coexpressions appeared only in UC lamina propria samples.CDX2,Lgr5 and Musashi-1 expressions in UC blood samples were not accompanied by CK20 mRNA expression.CONCLUSION:In active UC,a portion of circulating HGFR-expressing cells are committed to the epithelial lineage,and may participate in mucosal regeneration by undergoing mesenchymal-to-epithelial transition. | Ferenc Sipos Miklós Constantinovits Gábor Valcz Zsolt Tulassay Gy?rgyi M?zes | 2015 | World Journal of Gastroenterology2015，21，28： | 2 |
| 10 | NKX2-3 and IRGM variants are associated with diseasesu sceptibility to IBD in Eastern European patients显示文摘AIM: To investigate variants of immunity-related GT-Pase family M (IRGM) and NKX2-3 genes and genotype-phenotype in Eastern European patients with inflammatory bowel disease (IBD).METHODS: We analyzed 1707 Hungarian and Czech subjects with Crohn’s disease (CD) (n = 810, age: 37.1 ± 12.6 years, duration: 10.7 ± 8.4 years) and ulcerative colitis (UC) (n = 428, age: 43.7 ± 15.0 years, duration: 12.6 ± 9.9 years), as well as 469 healthy controls. IRGM rs13361189, NKX2-3 rs10883365 and ECM1 rs13294 polymorphisms were tested by LightCy-cler allele discrimination. Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: NKX2-3 rs10883365 variant allele was as-sociated with increased risk for CD (P = 0.009, OR = 1.24, 95% CI = 1.06-1.48) and UC (P = 0.001, OR = 1.36, 95% CI = 1.13-1.63), whereas variant IRGM allele increased risk for CD (P = 0.029, OR = 1.36, 95% CI = 1.03-1.79). In contrast, ECM1 rs13294 was not associat-ed with either CD or UC. In CD, the variant IRGM allele was associated with a colon-only location (P = 0.02, OR = 1.62, 95% CI = 1.07-2.44), whereas in UC, the ECM1 variant was associated with cutaneous manifestations (P = 0.002, OR = 3.36, 95% CI = 1.48-7.63). Variant alleles did not predict resistance to steroids or azathio-prine, efficacy of infliximab, or need for surgery. CONCLUSION: NKX2-3 and IRGM are susceptibility locifor IBD in Eastern European patients. Further studies are needed to confirm the reported phenotype-genotype associations. | Nora Meggyesi Lajos S Kiss Magdalena Koszarska Martin Bortlik Dana Duricova Laszlo Lakatos Tamas Molnar Martin Lenicek Libor Vítek Istvan Altorjay Maria Papp Zsolt Tulassay Pal Miheller Janos Papp Attila Tordai Hajnalka Andrikovics Milan Lukas Peter Laszlo Lakatos | 2010 | World Journal of Gastroenterology2010，16，41： | 2 |
| 11 | The role of rabbit meat as functional food显示文摘 | Antonella D Z Zsolt S | 2011 | Meat Science2011，88，3： | 1 |
| 12 | Cell therapy for human ischemic heart diseases: Critical review and summary of the clinical experiences显示文摘 | Noemi Pavo Silvia Charwat Noemi Nyolczas András Jakab Zsolt Murlasits Jutta Bergler-Klein Mariam Nikfardjam Imre Benedek Teodora Benedek Imre J. Pavo Bernard J. Gersh Kurt Huber Gerald Maurer Mariann Gy?ngy?si | 2014 | Journal of Molecular and Cellular Cardiology2014，，： | 1 |
| 13 | N-acetylcysteine treatment prevent the progression of multisystem organ failure:A prospective, randomized,placebo-controlled study显示文摘 | Euan S Derek L | 1999 | Crit Care Med1999，27，： | 1 |
| 14 | Springback Analysis of High Strength Dual-phase Steels显示文摘 | Miklós Tisza Zsolt Lukács | 2014 | Procedia Engineering2014，，： | 1 |
| 15 | The relationshi pbetween built - u pareas and the spatial development of the mean maximum urban heat island in debrecen, hungary显示文摘 | Zsolt B A Andrea K S Andor S | 2005 | international journal of climatology2005，25，： | 1 |
| 16 | The role of rabbit meat as functional food显示文摘 | ANTONELLA D Z ZSOLT S | 2011 | Meat Science2011，88，3： | 1 |
| 17 | Abdominal compartment syndrome:The cause or effect of postinjury multiple organ failure显示文摘 | Zsolt B Bruce A Charles S | 2003 | Shock2003，20，6： | 1 |
| 18 | Gastrointestinal stromal tumors:A clinicopathologic and immunohistochemical study of 136 cases显示文摘 | Zsolt O Tamas T Zoltan S | 2005 | Pathol Oncol Res2005，11，1： | 1 |
| 19 | Clinical significance of sentinel lymph node involvement in malignant melanoma显示文摘 | Gabriella Liszkay Gábor Péley István Sinkovics Ilona Péter Zsolt Orosz Zsuzsa Fej?s Béla Horváth István K?ves Katalin Gilde Miklós Kásler | 2003 | Pathology Oncology Research2003，，3： | 1 |
| 20 | Single-exposure dual-energy subtraction chest radiography:detection of pulmonary nodules and masses in clinical practice显示文摘 | Zsolt S F Michael A Seyran Y H | 2008 | Eur Radiol2008，18，1： | 1 |
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