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Alterations of glutathione S-transferase and matrix metalloproteinase-9 expressions are early events in esophageal carcinogenesis

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World Journal of Gastroenterology 2007年第5期13卷 676-682页

作者： Laszlo Herszenyi Istvan Hritz Istvan Pregun Ferenc Sipos Mark Juhasz Bela molnar zsolt Tulassay 2nd Department of Medicine Semmelweis University Hungarian Academy of Science Clinical Gastroenterology Research Unit Budapest Hungary

AIM: To investigate the role of glutathione S-transferase (GST) and matrix metalloproteinase-9 (MMP-9) expres-sions in the development and progression of reflux es-ophagitis-Barrett’s metaplasia-dysplasia-adenocarcinoma sequence in the ***: GST and MMP-9 expressions were analyzed in 51 paraffin-embedded tissue samples by immunohisto-chemistry including patients with reflux esophagitis (n = 7), Barrett’s metaplasia (n = 14), Barrett and esophagi-tis (n = 8), Barrett and dysplasia (n = 7), esophageal adenocarcinoma (n = 8) and a control group without any histological changes (n = 7). Immunostaining was determined semiquantitatively. Statistical analysis with one-way ANOVA, LSD test and correlation analysis were performed. P value of red ***: GST expression was significantly higher while MMP-9 expression was significantly lower in control group compared to Barrett’s metaplasia and the other groups. No major changes were observed between Bar-rett, esophagitis, and Barrett and concomitant esophagi-tis. Barrett and concomitant dysplasia, and adenocarci-noma revealed a significant lower expression of GST and higher levels of MMP-9 compared to all other groups. Adenocarcinoma showed almost no expression of GST and significantly higher levels of MMP-9 than Barrett and concomitant dysplasia. Alterations of GST and MMP-9 were inversely correlated (r = - 0.82).CONCLUSION: Decreased GST and increased ex-pression of MMP-9 in Barrett’s metaplasia-dysplasia-adenocarcinoma sequence as compared to normal tissue suggest their association with esophageal tumorigenesis. Loss of GST and gain of MMP-9 in Barrett with dyspla-sia compared to non-dysplastic metaplasia indicate that these alterations may be early events in carcinogenesis. Quantification of these parameters in Barrett’s esopha-gus might be useful to identify patients at higher risk for progression to cancer.

关键词： Glutathione S-transferase Matrix metallo-proteinase-9 Barrett's metaplasia Esophagus Adenocarcinoma Dysplasia

Successful elimination of extended-spectrum beta-lactamase (ESBL)-producing nosocomial bacteria at a neonatal intensive care unit

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World Journal of Pediatrics 2017年第3期13卷 210-216页

作者： Borbála Szél zsolt reiger Edit Urbán Andrea Lázár Krisztina Mader Ivelina Damjanova Kamilla Nagy Gyula Tálosi Infection Control Unit University of SzegedHungary Department of Pediatrics University of SzegedHungary Institute of Clinical Microbiology University of SzegedHungary Department of Bacteriology National Center for EpidemiologyHungary

Background:Extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria are highly dangerous to *** our Neonatal Intensive Care Unit (NICU),the presence of these bacteria became so threatening in 2011 that immediate intervention was ***:This study was conducted during a nearly two-year period consisting of three phases:retrospective (9 months),educational (3 months) and prospective (9 months).Based on retrospective data analysis,a complex management plan was devised involving the introduction of the INSUrE protocol,changes to the antibiotic regimen,microbiological screening at short intervals,progressive feeding,a safer bathing protocol,staff hand hygiene training and continuous monitoring of the number of newly infected and newly colonized *** these intervals,a total of 355 patients were ***:Both ESBL-producing Enterobacter cloaceae and Klebsiella pneumoniae were found (in both patients and environmental samples).In the prospective period a significant reduction could be seen in the average number of both colonized (26/167 patients;P=0.029) and infected (3/167 patients;P=0.033) patients compared to data from the retrospective period regarding colonized (72/188 patients) and infected (9/188 patients) *** was a decrease in the average number of patientdays (from 343.72 to 292.44 days per months),though this difference is not significant (P=0.058).During the prospective period,indirect hand hygiene compliance showed a significant increase (from the previous 26.02 to 33.6 hand hygiene procedures per patient per hospital day,Pre rolled back successfully in a multi-step effort that required an interdisciplinary approach.

关键词： hand hygiene INSUrE protocol interdisciplinary approach neonates polyresistance

Systematic review of the old and new concepts in the epithelial-mesenchymal transition of colorectal cancer

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World Journal of Gastroenterology 2016年第30期22卷 6764-6775页

作者： Simona Gurzu Camelia Silveanu Annamaria Fetyko Vlad Butiurca zsolt Kovacs Ioan Jung Department of Pathology University of Medicine and Pharmacy of Tirgu-Mures Department of Surgery University of Medicine and Pharmacy of Tirgu-Mures Departments of Genetics and Biochemistry University of Medicine and Pharmacy of Tirgu-Mures

Epithelial-to-mesenchymal transition(EMT) is defined as the transformation of an epithelial cell into a spindle cell with the loss of membrane E-cadherin expression and the gain of mesenchymal markers positivity. In the field of colorectal cancer(CrC), first data about EMT was published in 1995 and more than 400 papers had been written up to March 2016. Most of them are focused on the molecular pathways and experimentally-proved chemoresistance. In the present article, an update in the field of EMT in CrC based on the review of the literature and personal experience of the authors is presented. The information about the molecular and immunohistochemical(IHC) particularities of these processes and their possible role in the prognosis of CrC were also up-dated. This article focuses on the IHC quantification of the EMT, the immunoprofile of tumor buds and on the relation between EMT, angiogenesis, and stem cells activation. The EMT-induced chemoresistance vs chemotherapyor radiotherapy-induced EMT and cellular senescence was also synthesized for both conventional and targeted therapy. As a future perspective, the EMTangiogenesis-stemness link could be used as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management of patients with CrC. Association of dexamethasone and angiotensin converting enzyme inhibitors combined with conventional chemotherapies could have clinical benefits in patients with CrC. The main conclusion is that, although many studies have been published, the EMT features are still incompletely elucidated and newly discovered EMT markers provide confusing data in understanding this complicated process, which might have significant clinical impact.

关键词： Angiogenesis Colorectal cancer Budding Epithelial-mesenchymal transition Chemoresistance

Symmetric carbon tetramers forming spin qubits in hexagonal boron nitride

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npj Computational Materials 2023年第1期9卷 407-416页

作者： zsolt Benedek rohit Babar Ádám Ganyecz Tibor Szilvási Örs Legeza Gergely Barcza Viktor Ivády Strongly Correlated Systems Lendület research Group Wigner Research Centre for PhysicsPO Box 49H-1525 BudapestHungary MTA-ELTE Lendület“Momentum”NewQubit research Group Pázmány PéterSétány 1/A1117 BudapestHungary Department of Chemical and Biological Engineering The University of AlabamaTuscaloosaAL 35487USA Institute for Advanced Study Technical University of MunichLichtenbergstrasse 2a85748 GarchingGermany Department of Physics of Complex Systems Eötvös Loránd UniversityEgyetem tér 1-3H-1053 BudapestHungary Department of Physics Chemistry and BiologyLinköping UniversitySE-58183 LinköpingSweden

Point defect quantum bits in semiconductors have the potential to revolutionize sensing at atomic ***,vacancy-related defects are at the forefront of high spatial resolution and low-dimensional *** the other hand,it is expected that impurity-related defect structures may give rise to new features that could further advance quantum sensing in low ***,we study the symmetric carbon tetramer clusters in hexagonal boron nitride and propose them as spin qubits for *** utilize periodic-DFT and quantum chemistry approaches to reliably and accurately predict the electronic,optical,and spin properties of the studied *** show that the nitrogen-centered symmetric carbon tetramer gives rise to spin state-dependent optical signals with strain-sensitive intersystem crossing ***,the weak hyperfine coupling of the defect to their spin environments results in a reduced electron spin resonance linewidth that can enhance sensitivity.

关键词： hexagonal boron quantum

Interaction of arylsulfatases A and B with maspin: A possible explanation for dysregulation of tumor cell metabolism and invasive potential of colorectal cancer

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World Journal of Clinical Cases 2019年第23期7卷 3990-4003页

作者： zsolt Kovacs Ioan Jung Krisztina Szalman Laura Banias Tivadar Jr Bara Simona Gurzu Department of Pathology University of MedicinePharmacySciences and Technology“George Emil Palade”Targu Mures 530149Romania Department of Internal Medicine University of MedicinePharmacySciences and Technology“George Emil Palade”Targu Mures 530149Romania Department of Surgery University of MedicinePharmacyScience and Technology“George Emil Palade”Tirgu Mures 530149Romania research Center(CCAMF) University of MedicinePharmacySciences and TechnologyTargu Mures 540139Romania

BACKGrOUND Although it has been shown that arylsulfatases are lost in colorectal cancer(CrC)cell lines,their exact role in the carcinogenesis and behavior of this cancer was not *** data about the correlation between serum and immunohistochemical(IHC)level of arylsulfatases(ArSA,ArSB)in patients with CrC were published *** To evaluate the possible prognostic value of ArSA and/or ArSB in CrC,at circulating and protein *** The present study included 45 consecutive patients who were prospectively diagnosed with *** IHC stains(protein expression)ArSA,ArSB and maspin expression were *** these markers,cytoplasmic expression was taken into *** gene expression study,circulating mrNA was isolated from all patients,before surgery.A group of 45 healthy patients without inflammatory or tumor pathologies was used as control *** transcription and Taqman Gene Expression Array were used for ArSB gene *** The preoperative circulating rNA level of the ArSB gene was significantly decreased in patients with CrC(rQred with the control group(rQ>1).A more significant decrease(rQrred in ulcero-infiltrative maspinpositive adenocarcinomas,with a higher degree of tumor budding,diagnosed in locally advanced stages(pT3/4).ArSA/maspin immunopositivity indicated a higher risk for lymph node metastasis,while triple positivity for maspin/ArSA/ArSB and ArSB gene expression levelre indicators of CrC aggressive behavior,independent of lymph node *** The significant independent negative prognostic factors of CrC are the ulceroinfiltrative aspect,high budding degree,triple positivity for maspin,ArSA and ArSB,and low ArSB gene expression.

关键词： Arylsulfatase Maspin Colorectal cancer ArSB gene Blood Tissue

Paradoxical expression pattern of the epithelial mesenchymal transition-related biomarkers CD44, SLUG, N-cadherin and VSIG1/Glycoprotein A34 in gastrointestinal stromal tumors

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World Journal of Gastrointestinal Oncology 2017年第11期9卷 436-443页

作者： Attila Kovecsi Simona Gurzu Zoltan Szentirmay zsolt Kovacs Tivadar Jr Bara Ioan Jung Department of Pathology University of Medicine and Pharmacy research Center University of Medicine and Pharmacy Department of Pathology National Institute of Oncology Department of Biochemistry University of Medicine and Pharmacy Department of Surgery University of Medicine and Pharmacy

AIM To evaluate the immunohistochemical(IHC) expression of five biomarkers, commonly involved in epithelial mesenchymal/mesenchymal epithelial transition(EMT/MET), in gastrointestinal stromal tumors(GISTs). METHODS In 80 consecutive GISTs the IHC examinations were performed using the EMT-related antibodies E-cadherin,N-cadherin, SLUG, V-set and immunoglobulin domain containing 1(VSIG1) and CD44. rESULTS The positivity rate was 88.75% for SLUG, 83.75% for VSIG1, 36.25% for CD44 and 10% for N-cadherin. No correlation was noted between the examined markers and clinicopathological parameters. Nuclear positivity for SLUG and VSIG1 was observed in all cases with distant metastasis. The extra-gastrointestinal stromal tumors(e-GISTs) expressed nuclear positivity for VSIG1 and SLUG, with infrequent positivity for N-cadherin and CD44. The low overall survival was mainly dependent on VSIG1 negativity(P = 0.01) and nuclear positivity for SLUG and/or CD44. CONCLUSION GIST aggressivity may be induced by nuclear upregulation of SLUG and loss or cytoplasm-to-nuclear translocation of VSIG1. SLUG and VSIG1 may act as activated nuclear transcription factors. The CD44, but not N-cadherin, might also have an independent prognostic value in these tumors. The role of the EMT/MET-related transcription factors in the evolution of GISTs, should be revisited with a larger dataset. This is the first study exploring the IHC pattern of VSIG1 in GISTs.

关键词： SLUG Glycoprotein A34 N-cadherin V-set and immunoglobulin domain containing gastrointestinal stromal tumors

relation of the IGF/IGF1r system to autophagy in colitis and colorectal cancer

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World Journal of Gastroenterology 2017年第46期23卷 8109-8119页

作者： Ferenc Sipos Hajnal Székely Imre Dániel Kis zsolt Tulassay Gyorgyi Muzes 2nd Department of Internal Medicine Semmelweis University Faculty of Medicine Semmelweis University Molecular Medicine research Group Hungarian Academy of Sciences

Metabolic syndrome(Met S), as a chronic inflammatory disorder has a potential role in the development of inflammatory and cancerous complications of the colonic tissue. The interaction of DNA damage and inflammation is affected by the insulin-like growth factor 1 receptor(IGF1 r) signaling pathway. The IGF1 r pathway has been reported to regulate autophagy, as well, but sometimes through a bidirectional context. Targeting the IGF1 r-autophagy crosstalk could represent a promising strategy for the development of new antiinflammatory and anticancer therapies, and may help for subjects suffering from Met S who are at increased risk of colorectal cancer. However, therapeutic responses to targeted therapies are often shortlived, since a signaling crosstalk of IGF1 r with other receptor tyrosine kinases or autophagy exists, leading to acquired cellular resistance to therapy. From a pharmacological point of view, it is attractive to speculate that synergistic benefits could be achieved by inhibition of one of the key effectors of the IGF1 r pathway, in parallel with the pharmacological stimulation of the autophagy machinery, but cautiousness is also required, because pharmacologic IGF1 r modulation can initiate additional, sometimes unfavorable biologic effects.

关键词： Insulin-like growth factor IGF1r Autophagy Colitis Colorectal cancer Metabolic syndrome

Association of hepatocyte-derived growth factor receptor/caudal type homeobox 2 co-expression with mucosal regeneration in active ulcerative colitis

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World Journal of Gastroenterology 2015年第28期21卷 8569-8579页

作者： Ferenc Sipos Miklós Constantinovits Gábor Valcz zsolt Tulassay Gy?rgyi M?zes 2nd Department of Internal Medicine Semmelweis University Molecular Medicine research Group Hungarian Academy of Sciences

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 *** preparing tissue microarrays and blood smears HGFr,caudal type homeobox 2(CDX2),prominin-1(CD133) and Musashi-1conventional and double fluorescent immunolabelings were *** samples were digitalized using high-resolution Mirax Desk instrument,and analyzed with the Mirax TMA Module *** 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 *** 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 *** 337 nm UVA Laser MicroDissection system at least 5000 subepithelial cells from the lamina propria were *** 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 red) positive cells were detected in blood and lamina propria of UC samples as compared to ***/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 sc

关键词： Hepatocyte-derived growth factor receptor Caudal type homeobox 2 CD133 Musashi-1 Leucinerichrepeat-containing G-protein coupled receptor 5 Ulcerative colitis regeneration

Seroreactivity against Saccharomyces cerevisiae in patients with Crohn's disease and celiac disease

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World Journal of Gastroenterology 2003年第10期9卷 2308-2312页

作者： zsolt Barta István Csíp■ Gábor G.Szabó Gyula Szegedi 3~(nd) Department of Medicine University of DebrecenMóricz Zs.Krt.22.4004 DebrecenHungary

AIM:To explore whether there was anti-Saccharomyces cerevisiae antibodies (ASCA) positivity in our patients with biopsy-confirmed celiac disease. METHODS:A cohort of patients with inflammatory bowel diseases (42 patients with Crohn's disease and 10 patients with ulcerative colitis) and gluten sensitive enteropathy (16 patients) from Debrecen,Hungary were enrolled in the study. The diagnosis was made using the formally accepted criteria. Perinuclear antineutrophil cytoplasmic antibodies (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA), antiendomysium antibodies (EMA),antigliadin antibodies (AGA) and anti human tissue transglutaminase antibodies (tTGA) were investigated. rESULTS:The results showed that ASCA positivity occurred not only in Crohn's disease but also in Celiac disease and in these cases both the IgG and IgA type antibodies were proved. CONCLUSION:It is conceivable that ASCA positivity correlates with the (auto-) immune inflammation of small intestines and it is a specific marker of Crohn's disease.

关键词： Adult Antibodies, Antineutrophil Cytoplasmic Antibodies, Fungal Celiac Disease Cohort Studies Crohn Disease Female Gliadin Humans Immunoglobulin A Immunoglobulin G Male Middle Aged Saccharomyces cerevisiae Seroepidemiologic Studies