TY - JOUR AU - Révész, Csaba AU - Kaucsár, Tamás AU - Godó, Mária AU - Bocskai, Krisztián AU - Krenács, Tibor AU - Mócsai, Attila AU - Szénási, Gábor AU - Hamar, Péter TI - Neutrophils and NADPH Oxidases Are Major Contributors to Mild but Not Severe Ischemic Acute Kidney Injury in Mice JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 5 PG - 17 SN - 1661-6596 DO - 10.3390/ijms25052948 UR - https://m2.mtmt.hu/api/publication/34728797 ID - 34728797 AB - Upregulation of free radical-generating NADPH oxidases (NOX), xanthine oxidoreductase (XOR), and neutrophil infiltration-induced, NOX2-mediated respiratory burst contribute to renal ischemia–reperfusion injury (IRI), but their roles may depend on the severity of IRI. We investigated the role of NOX, XOR, and neutrophils in developing IRI of various severities. C57BL/6 and Mcl-1ΔMyelo neutrophil-deficient mice were used. Oxidases were silenced by RNA interference (RNAi) or pharmacologically inhibited. Kidney function, morphology, immunohistochemistry and mRNA expression were assessed. After reperfusion, the expression of NOX enzymes and XOR increased until 6 h and from 15 h, respectively, while neutrophil infiltration was prominent from 3 h. NOX4 and XOR silencing or pharmacological XOR inhibition did not protect the kidney from IRI. Attenuation of NOX enzyme-induced oxidative stress by apocynin and neutrophil deficiency improved kidney function and ameliorated morphological damage after mild but not moderate/severe IRI. The IR-induced postischemic renal functional impairment (BUN, Lcn-2), tubular necrosis score, inflammation (TNF-α, F4/80), and decreases in the antioxidant enzyme (GPx3) mRNA expression were attenuated by both apocynin and neutrophil deficiency. Inhibition of NOX enzyme-induced oxidative stress or the lack of infiltration by NOX2-expressing neutrophils can attenuate reperfusion injury after mild but not moderate/severe renal IR. LA - English DB - MTMT ER - TY - JOUR AU - Hamar, Péter AU - Schvarcz, Csaba András AU - Danics, Lea AU - Krenács, Tibor AU - Leroy Viana, Pedro Henrique AU - Nagy, Á. AU - Szász, A. AU - Benyó, Zoltán TI - Mutiplex Analysis of Modulated Electro-Hyperthermia-Induced Local Acute Phase Protein Production in Mouse TNBC Model JF - MOLECULAR ONCOLOGY J2 - MOL ONCOL VL - 17 PY - 2023 IS - S1 SP - 468 EP - 469 PG - 2 SN - 1574-7891 UR - https://m2.mtmt.hu/api/publication/34726330 ID - 34726330 LA - English DB - MTMT ER - TY - JOUR AU - Schvarcz, Csaba András AU - Danics, Lea AU - Forika, Gertrud AU - Leroy Viana, Pedro Henrique AU - Krenács, Tibor AU - Benyó, Zoltán AU - Vancsik, Tamás AU - Hamar, Péter TI - Synergism between methotrexate and modulated electro-hyperthermia is mediated by H19 lnc-RNA JF - MOLECULAR ONCOLOGY J2 - MOL ONCOL VL - 17 PY - 2023 IS - (S1) SP - 459 EP - 460 PG - 2 SN - 1574-7891 UR - https://m2.mtmt.hu/api/publication/34725681 ID - 34725681 LA - English DB - MTMT ER - TY - JOUR AU - Almási, Szintia AU - Nagy, Ágnes AU - Krenács, Tibor AU - Lantos, Tamás AU - Zombori, Tamás AU - Cserni, Gábor TI - The prognostic value of stem cell markers in triple-negative breast cancer JF - PATHOLOGY AND ONCOLOGY RESEARCH J2 - PATHOL ONCOL RES VL - 29 PY - 2023 PG - 13 SN - 1219-4956 DO - 10.3389/pore.2023.1611365 UR - https://m2.mtmt.hu/api/publication/34504527 ID - 34504527 AB - Among the many consecutive theories of cancer, the stem cell theory is currently the most accepted one. Cancer stem cells are located in small niches with specific environment, renew themselves and are believed to be responsible for many recurrences. They can be highlighted with stem cell markers, but often these markers also label tumor cells, and this may represent a phenotypical change associated with prognosis. In this study, we attempted to match tumor outcomes with the expression of the following stem cell markers: ALDH1, AnnexinA1, CD44, CD117, CD166, Nanog and oct-4. Tissue microarray blocks from triple-negative breast cancers were immunostained for the listed markers, and their expression by the majority of tumor cells (diffuse positivity) was correlated with prognosis. Of the 106 tumors investigated, diffuse positivity was seen in 7 (ALDH1), 33 (AnnexinA1), 53 (CD44), 44 (CD117 membranous only), 49 (CD117), 72 (CD166), 19 (Nanog), and 11 (oct-4) cases. With a median follow-up of 83 months, ALDH1 and CD117 expression was associated with DFS, whereas CD44, CD117 and CD166 were associated with OS estimates, based on Kaplan-Meier analyses. In the multivariate Cox proportional hazard models (including the examined markers and clinicopathological data which had a statistical impact in the univariate analysis), the pN category and the lack of ALDH1 expression were independent prognosticators for DFS, and the pN category and diffuse CD44 staining were independent prognosticators for OS. In the multivariate analysis including all of the examined clinicopathological data and markers, only CD117 showed a statistical impact on OS. We failed to demonstrate a prognostic impact for most stem cell markers tested in triple-negative breast cancer, but lack of ALDH1 staining and CD44 expression appears as of prognostic value, requiring further examination in independent studies. LA - English DB - MTMT ER - TY - JOUR AU - Varga, Ákos AU - Németh, István Balázs AU - Kemény, Lajos AU - Varga, János AU - Tiszlavicz, László AU - Kumar, D. AU - Dodd, S. AU - Simpson, A.W.M. AU - Buknicz, Tünde AU - Beynon, R. AU - Simpson, D. AU - Krenács, Tibor AU - Dockray, G.J. AU - Varro, A. TI - Elevated serum gastrin is associated with melanoma progression: putative role in increased migration and invasion of melanoma cells JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 23 PG - 16 SN - 1661-6596 DO - 10.3390/ijms242316851 UR - https://m2.mtmt.hu/api/publication/34443653 ID - 34443653 LA - English DB - MTMT ER - TY - JOUR AU - Sárközy, Márta AU - Watzinger, Simon AU - Kovács, Zsuzsanna AU - Acar, Eylem AU - Márványkövi, Fanni AU - Szűcs, Gergő AU - Lauber, Gülsüm Yilmaz AU - Galla, Zsolt AU - Siska, Andrea AU - Földesi, Imre AU - Fintha, Attila AU - Kriston, András AU - Kovács, Ferenc AU - Horváth, Péter AU - Kővári, Bence AU - Cserni, Gábor AU - Krenács, Tibor AU - Szabó, Petra Lujza AU - Szabó, Gábor Tamás AU - Monostori, Péter AU - Zins, Karin AU - Abraham, Dietmar AU - Csont, Tamás Bálint AU - Pokreisz, Peter AU - Podesser, Bruno K. AU - Kiss, Attila TI - Neuregulin-1β Improves Uremic Cardiomyopathy and Renal Dysfunction in Rats JF - JACC:BASIC TO TRANSLATIONAL SCIENCE J2 - JACC-BASIC TRANSL SC VL - 8 PY - 2023 IS - 9 SP - 1160 EP - 1176 PG - 17 SN - 2452-302X DO - 10.1016/j.jacbts.2023.03.003 UR - https://m2.mtmt.hu/api/publication/33941648 ID - 33941648 LA - English DB - MTMT ER - TY - JOUR AU - Gurbi, Bianka AU - Brauswetter, Diána AU - Pénzes, Kinga AU - Varga, Attila AU - Krenács, Tibor AU - Dános, Kornél AU - Birtalan, Ede AU - Tamás, László AU - Csala, Miklós TI - MEK Is a Potential Indirect Target in Subtypes of Head and Neck Cancers JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 3 PG - 19 SN - 1661-6596 DO - 10.3390/ijms24032782 UR - https://m2.mtmt.hu/api/publication/33610921 ID - 33610921 N1 - Export Date: 13 May 2023 AB - The poor prognosis of head-and-neck squamous cell carcinoma (HNSCC) is partly due to the lack of reliable prognostic and predictive markers. The Ras/Raf/MEK/ERK signaling pathway is often activated by overexpressed epidermal growth factor receptor (EGFR) and stimulates the progression of HNSCCs. Our research was performed on three human papillomavirus (HPV)-negative HNSCC-cell lines: Detroit 562, FaDu and SCC25. Changes in cell viability upon EGFR and/or MEK inhibitors were measured by the MTT method. The protein-expression and phosphorylation profiles of the EGFR-initiated signaling pathways were assessed using Western-blot analysis. The EGFR expression and pY1068-EGFR levels were also studied in the patient-derived HNSCC samples. We found significant differences between the sensitivity of the tumor-cell lines used. The SCC25 line was found to be the most sensitive to the MEK inhibitors, possibly due to the lack of feedback Akt activation through EGFR. By contrast, this feedback activation had an important role in the FaDu cells. The observed insensitivity of the Detroit 562 cells to the MEK inhibitors might have been caused by their PIK3CA mutation. Among HNSCC cell lines, EGFR-initiated signaling pathways are particularly versatile. An ERK/EGFR feedback loop can lead to Akt-pathway activation upon MEK inhibition, and it is related not only to increased amounts of EGFR but also to the elevation of pY1068-EGFR levels. The presence of this mechanism may justify the combined application of EGFR and MEK inhibitors. LA - English DB - MTMT ER - TY - JOUR AU - Székely, Tamás AU - Wichmann, Barnabás AU - Maros, Máté Előd AU - Csizmadia, Annamária AU - Bödör, Csaba AU - Timár, Botond AU - Krenács, Tibor TI - Myelofibrosis progression grading based on type-I and type-III collagen and fibrillin-1 expression boosted by whole slide image analysis JF - HISTOPATHOLOGY J2 - HISTOPATHOLOGY VL - 82 PY - 2023 IS - 4 SP - 622 EP - 632 PG - 11 SN - 0309-0167 DO - 10.1111/his.14846 UR - https://m2.mtmt.hu/api/publication/33293071 ID - 33293071 AB - Aims The progression of primary myelofibrosis is characterized by ongoing extracellular matrix deposition graded based on ?reticulin? and ?collagen? fibrosis as revealed by Gomori's silver impregnation. Here we studied the expression of the major extracellular matrix proteins of fibrosis in relation to diagnostic silver grading supported by image analysis. Methods and Results By using automated immunohistochemistry, here we demonstrate, that the expression of both type-I and type-III collagens, and fibrillin-1 by bone marrow stromal cells can reveal the extracellular matrix scaffolding in line with myelofibrosis progression as classified by silver grading. ?Reticulin? fibrosis indicated by type-III collagen expression and ?collagen? fibrosis featured by type-I collagen expression were parallel rather than sequential events. This is line with the proposed role of type-III collagen in regulating type-I collagen fibrillogenesis. The uniformly strong firbillin-1 immune signals offered the best interrater agreements and the highest statistical correlations with silver grading of the 3 markers, which was robustly confirmed by automated whole slide digital image analysis using a machine learning-based algorithm. The progressive upregulation of fibrillin-1 during myelofibrosis may result from a negative feedback loop since fibrillin microfibrils sequester TGF-? the major promoter of fibrosis. This can also reduce TGF-? induced RANKL levels which would stimulate osteoclastogenesis and thus can support osteosclerosis in advanced myelofibrosis. Conclusions Through the in situ detection of these extracellular matrix proteins our results verify the molecular pathobiology of fibrosis during myelofibrosis progression. In particular, fibrillin-1 immunohistochemistry with or without image analysis can complement diagnostic silver grading at decent cell morphology. LA - English DB - MTMT ER - TY - CHAP AU - Kiss, Éva AU - Hajdú, Anett AU - Forika, Gertrud AU - Dank, Magdolna AU - Krenács, Tibor AU - Németh, Zsuzsanna ED - Gurunathan, Dr. Ramesh TI - Investigating the Effect of Dietary Methyl-Donor Intake and Other Lifestyle Factors on Cancer Patients in Hungary T2 - Current Innovations in Medicine and Medical Science Vol. 8 PB - BP International CY - Petaling Jaya SN - 9789355479617 PY - 2022 SP - 31 EP - 52 PG - 22 DO - 10.9734/bpi/cimms/v8/3466A UR - https://m2.mtmt.hu/api/publication/33290290 ID - 33290290 LA - English DB - MTMT ER - TY - JOUR AU - Fónyad, László AU - Csizmadia, Annamária AU - Krenács, Tibor AU - Székely, Tamás AU - Micsik, Tamás AU - Fintha, Attila AU - Molnár, Béla AU - Rácz, Gergely TI - Patológia határok nélkül: Digitális patológia - telepatológia JF - KLINIKAI ONKOLÓGIA J2 - KLINIKAI ONKOLÓGIA VL - 9 PY - 2022 IS - 3 SP - 301 EP - 318 PG - 18 SN - 2064-5058 UR - https://m2.mtmt.hu/api/publication/33169627 ID - 33169627 LA - Hungarian DB - MTMT ER -