Search

Your search keyword '"Szombath, G."' showing total 8 results
Start Over Author "Szombath, G." Search Limiters Available in Library Collection
8 results on '"Szombath, G."'

1. Common gene variants within 3'-untranslated regions as modulators of multiple myeloma risk and survival

Author

Melaiu, O., Macauda, A., Sainz, J., Calvetti, D., Facioni, M.S., Maccari, G., Horst, R. ter, Netea, M.G., Li, Y., Grząśko, N., Moreno, V., Jurczyszyn, A., Jerez, A., Watek, M., Varkonyi, J., Garcia-Sanz, R., Kruszewski, M., Dudziński, M., Kadar, K., Jacobsen, S.E. Hove, Mazur, G., Andersen, V., Rybicka, M., Zawirska, D., Raźny, M., Zaucha, J.M., Ostrovsky, O., Iskierka-Jazdzewska, E., Reis, R.M., Stępień, A., Beider, K., Nagler, A., Druzd-Sitek, A., Marques, H., Martìnez-Lopez, J., Lesueur, F., Avet-Loiseau, H., Vangsted, A.J., Krawczyk-Kulis, M., Butrym, A., Jamroziak, K., Dumontet, C., Vogel, U., Rymko, M., Pelosini, M., Subocz, E., Szombath, G., Sarasquete, M.E., Silvestri, R., Morani, F., Landi, S., Campa, D., Canzian, F., Gemignani, F., Melaiu, O., Macauda, A., Sainz, J., Calvetti, D., Facioni, M.S., Maccari, G., Horst, R. ter, Netea, M.G., Li, Y., Grząśko, N., Moreno, V., Jurczyszyn, A., Jerez, A., Watek, M., Varkonyi, J., Garcia-Sanz, R., Kruszewski, M., Dudziński, M., Kadar, K., Jacobsen, S.E. Hove, Mazur, G., Andersen, V., Rybicka, M., Zawirska, D., Raźny, M., Zaucha, J.M., Ostrovsky, O., Iskierka-Jazdzewska, E., Reis, R.M., Stępień, A., Beider, K., Nagler, A., Druzd-Sitek, A., Marques, H., Martìnez-Lopez, J., Lesueur, F., Avet-Loiseau, H., Vangsted, A.J., Krawczyk-Kulis, M., Butrym, A., Jamroziak, K., Dumontet, C., Vogel, U., Rymko, M., Pelosini, M., Subocz, E., Szombath, G., Sarasquete, M.E., Silvestri, R., Morani, F., Landi, S., Campa, D., Canzian, F., and Gemignani, F.

Abstract

Contains fulltext : 232394.pdf (Publisher’s version ) (Closed access), We evaluated the association between germline genetic variants located within the 3'-untranlsated region (polymorphic 3'UTR, ie, p3UTR) of candidate genes involved in multiple myeloma (MM). We performed a case-control study within the International Multiple Myeloma rESEarch (IMMEnSE) consortium, consisting of 3056 MM patients and 1960 controls recruited from eight countries. We selected p3UTR of six genes known to act in different pathways relevant in MM pathogenesis, namely KRAS (rs12587 and rs7973623), VEGFA (rs10434), SPP1 (rs1126772), IRF4 (rs12211228) and IL10 (rs3024496). We found that IL10-rs3024496 was associated with increased risk of developing MM and with a worse overall survival of MM patients. The variant allele was assayed in a vector expressing eGFP chimerized with the IL10 3'-UTR and it was found functionally active following transfection in human myeloma cells. In this experiment, the A-allele caused a lower expression of the reporter gene and this was also in agreement with the in vivo expression of mRNA measured in whole blood as reported in the GTEx portal. Overall, these data are suggestive of an effect of the IL10-rs3024496 SNP on the regulation of IL10 mRNA expression and it could have clinical implications for better characterization of MM patients in terms of prognosis.

Published
2021

2. Cardiopoietic cell therapy for advanced ischemic heart failure : results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Author

Bartunek, Jozef, Terzic, Andre, Davison, Beth A, Filippatos, Gerasimos S, Radovanovic, Slavica, Beleslin, Branko, Merkely, Bela, Musialek, Piotr, Wojakowski, Wojciech, Andreka, Peter, Horvath, Ivan G, Katz, Amos, Dolatabadi, Dariouch, El Nakadi, Badih, Arandjelovic, Aleksandra, Edes, Istvan, Seferovic, Petar M, Obradovic, Slobodan, Vanderheyden, Marc, Jagic, Nikola, Petrov, Ivo, Atar, Shaul, Halabi, Majdi, Gelev, Valeri L, Shochat, Michael K, Kasprzak, Jaroslaw D, Sanz Ruiz, Ricardo, Heyndrickx, Guy R, Nyolczas, Noémi, Legrand, Victor, Guédès, Antoine, Heyse, Alex, Moccetti, Tiziano, Fernandez Aviles, Francisco, Jimenez Quevedo, Pilar, Bayes Genis, Antoni, Hernandez Garcia, Jose Maria, Ribichini, Flavio, Gruchala, Marcin, Waldman, Scott A, Teerlink, John R, Gersh, Bernard J, Povsic, Thomas J, Henry, Timothy D, Metra, Marco, Hajjar, Roger J, Tendera, Michal, Behfar, Atta, Alexandre, Bertrand, Seron, Aymeric, Stough, Wendy Gattis, Sherman, Warren, Cotter, Gad, Wijns, W. i. l. l. i. a. m. Collaborators Clinical investigators, Dens, sites Belgium: Ziekenhuis Oost Limburg: J., Dupont, M., Mullens, W., Janssens, M., Dolatabadi, Hoˆpital Civil de Charleroi: D., De Bruyne, Y., Lalmand, J., Dubois, P., El Nakadi, B., Aminian, A., De Vuyst, E., Gurnet, P., Gujic, M., Blankoff, I., Guedes, CHU Mont Godinne UCL: A., Gabriel, L., Seldrum, S., Doyen, C., Andre´, M., Heyse, AZ Glorieux: A., Van Durme, F., Verschuere, J., Legrand, Domaine Universitaire du Sart Tilman: V., Gach, O., D’Orio, V., Davin, L., Lancellotti, P., Baudoux, E., Ancion, A., Dulgheru, R., Vanderheyden, OLV Ziekenhuis Aalst – Cardiologie: M., Bartunek, J., Wijns, W., Verstreken, S., Penicka, . M., Gelev, P. Meeus Bulgaria: Tokuda Hospital Sofia: V., Zheleva Kichukova, I., Parapunova, R., Melamed, R., Sardovski, S., Radev, O., Yordanov, A., Radinov, A., Nenov, D., Amine, I., Petrov, City Hospital Clinic Cardiology Center: I., Kichukov, K., Nikitasov, L., Stankov, Z., Stoyanov, H., Tasheva Dimitrova, I., Angelova, M., Dimitrov, E., Minchev, M., Garvanski, I., Botev, C., Polomski, P., Alexandrovska University Hospital, Vassilev, Sofia: D., Karamfiloff, K., Tarnovska Kadreva, R., Vladimirova, L., Dimitrov, G., Hadzhiev, E., Tzvetkova, G., Andreka, . M. Atanasova Hungary: Gottsegen Gyo¨ rgy Orszagos Kardiologiai Inte´zet: P., Fontos, G., Fabian, J., Csepregi, A., Uzonyi, G., Gelei, A., Edes, Debreceni Egyetem Orvos e´s Ege´szse´gtudomanyi Centrum Altalanos Orvostudomanyi Kar Kardiologia Inte´zet: I., Balogh, L., Vajda, G., Darago, A., Gergely, S., Fulop, T., Jenei, C., Horvath, Pe´csi Tudomanyegyetem Klinikai Ko¨zpont Szıvgyogyaszati Klinika: I., Magyari, B., Nagy, A., Cziraki, A., Faludi, R., Kittka, B., Alizadeh, H., Merkely, Semmelweis Egyetem Varosmajori Szıv e´s Ergyogyaszati Klinika: B., Geller, L., Farkas, P., Szombath, G., Foldes, G., Skopal, J., Kovacs, A., Kosztin, A., Gara, E., Sydo, N., Nyolczas, MH Ege´szse´gu¨gyi Ko¨zpont Kardiologiai Osztaly: N., Kerecsen, G., Korda, A., Kiss, . M., Borsanyi, T., Polgar, B., Muk, B., Sharif, Z. Bari Ireland: HRB Clinical Research Facility: F., Atar, Y. M. Smyth Israel:Western Galilee Hospital: S., Shturman, A., Akria, L., Kilimnik, M., Brezins, M., Halabi, Ziv Medical Center: M., Dally, N., Goldberg, A., Aehab, K., Rosenfeld, I., Levinas, T., Saleem, D., Katz, Barzilai Medical Center: A., Plaev, T., Drogenikov, T., Nemetz, A., Barshay, Y., Jafari, J., Orlov, I., Nazareth Hospital EMMS: M. Omory, N. Kogan Nielsen, Shochat, Hillel Yaffe Medical Center: M., Shotan, A., Frimerman, A., Meisel, S., Asif, A., Sofer, O., Blondheim, D. S., Vazan, A., Metra, L. Arobov Italy: A. O. Spedali Civili di Brescia: M., Bonadei, I., Inama, L., Chiari, E., Lombardi, C., Magatelli, M., Russo, D., Lazzarini, V., Carubelli, V., Vassanelli, AOUI Verona – Borgo Trento Hospital: C., Ribichini, Flavio Luciano, Bergamini, C., Krampera, Mauro, Cicoria, M. A., Zanolla, L., Dalla Mura, D., Gambaro, A., Rossi, A., Pesarini Poland: Jagiellonian University Department of Cardiac, G., Musialek, Vascular Diseases at John Paul II Hospital in Krakow: P., Mazurek, A., Drabik, L., Ka˛dzielski, A., Walter, Z., Dzieciuch Rojek, M., Rubis, P., Plazak, . W., Tekieli, L., Podolec, J., Orczyk, W., Sutor, U., Zmudka, K., Olszowska, M., Podolec, P., Gruchala, Uniwersyteckie Centrum Kliniczne: M., Ciecwierz, D., Mielczarek, M., Burakowski, S., Chmielecki, M., Zielinska, M., Frankiewicz, A., Wdowczyk, J., Stopczynska, I., Bellwon, J., Mosakowska, K., Nadolna, R., Wroblewska, J., Rozmyslowska, M., Rynkiewicz, M., Marciniak, I., Raczak, G., Tarnawska, M., Taszner, M., Kasprzak, Bieganski Hospital: J., Plewka, M., Fiutowska, D., Rechcinski, T., Lipiec, P., Sobczak, M., Weijner Mik, P., Wraga, M., Krecki, R., Markiewicz, M., Haval Qawoq, D., Wojakowski, Gornosla˛skie Centrum Medyczne Sla˛skie j. Akademii Medycznej: W., Ciosek, J., Dworowy, S., Gaszewska Zurek, E., Ochala, A., Cybulski, W., Jadczyk, T., Wanha, W., Parma, Z., Kozlowski, M., Dzierzak, M., Markiewicz Serbia: Clinical Hospital Center Zvezdara, M., Arandjelovic, Cardiology Clinic: A., Sekularac, N., Boljevic, D., Bogdanovic, A., Zivkovic, S., Cvetinovic, N., Loncar, G., Clinical Centre of Serbia, Beleslin, Cardiology Clinic: B., Nedeljkovic, M., Trifunovic, D., Giga, V., Banovic, M., Nedeljkovic, I., Stepanovic, J., Vukcevic, V., Djordjevic Dikic, A., Dobric, M., Obrenovic Kircanski, B., Seferovic, Cardiology Clinic: P., Orlic, D., Tesic, M., Petrovic, O., Milinkovic, I., Simeunovic, D., Jagic, Clinical Center of Kragujevac: N., Tasic, M., Nikolic, D., Miloradovic, V., Djurdjevic, P., Sreckovic, M., Zornic, N., Clinical Hospital Center Bezanijska Kosa, Radovanovic, Cardiology Department: S., Saric, J., Hinic, S., Djokovic, A., Ðordevic, S., Bisenic, V., Markovic, O., Stamenkovic, S., Malenkovic, V., Tresnjak, J., Misic, G., Cotra, D., Tomovic, L., Vuckovic, V., Clinic of Emergency Internal Medicine, Obradovic, Military Medical Academy: S., Jovic, Z., Vukotic, S., Markovic, D., Djenic, N., Ristic Andjelkov, A., Bayes Genis, D. Ljubinka Spain: Hospital Universitario Germans Trias I. Pujol: A., Rodriguez Leor, O., Labata, C., Vallejo, N., Ferrer, E., Batlle, M., Fernandez Aviles, Hospital General Universitario Gregorio Mara~non: F., Sanz Ruiz, R., Casado, A., Loughlin, G., Zatarain, E., Anguita, J., Ferna ndez Santos, M. E., Pascual, C., Bermejo, J., Hernandez Garcia, Hospital Clinico Universitario Virgen de la Victoria: J. M., Jimenez Navarro, M., Dominguez, A., Carrasco, F., Mu~noz, A., Garcia Pinilla, J. M., Ruiz, J., Queipo de Llano, M. P., Hernandez, A., Fernandez, A., Jimenez Quevedo, Hospital Clinico San Carlos: P., Guerra, R., Biagioni, C., Gonzalez, R. A., Gomez deDiego, J. J., Mansson Broberg, L. Perez de Isla Sweden: Karolinska University Hospital: A., Sylve´n, C., Leblanc, K., Winter, R., Blomberg, P., Gunyeli, E., Ruck, A., Silva, C., Fo¨rstedt Switzerland: CardioCentro Ticino, J., Moccetti, Switzerland: T., Rossi, M., Pasotti, E., Petrova, I., Crljenica, C., Monti, C., Murzilli, R., Su¨rder, D., Moccetti, M., Turchetto, L., Locicero, V., Chiumiento, L., Maspoli, S., Mombelli, M., Anesini, A., Biggiogero, M., Ponti, G., Camporini, C., Polledri, S., Hill, G. Dolci United Kingdom: Kings College Hospital: J., Plymen, C., Amin Youssef, G., Mcdonagh, T., Drasar, E., Mijovic, A., Jouhra, F., Mcloman, D., Dworakowski, R., Webb, I., Byrne, J., and Potter, V.

Subjects
0301 basic medicine, Male, Cardiopoiesis, Cardiovascular disease, Disease severity, Marker, Precision medicine, Regenerative medicine, Stem cell, Target population, Adult, Aged, Double-Blind Method, Female, Heart Failure, Humans, Mesenchymal Stem Cell Transplantation, Middle Aged, Myocardial Ischemia, Prospective Studies, Treatment Outcome, Young Adult, Cardiology and Cardiovascular Medicine, Cell- and Tissue-Based Therapy, mesenchymal stem-cells, 030204 cardiovascular system & hematology, Cardiorespiratory Medicine and Haematology, outcomes, Fast-Track Clinical Research, Sudden cardiac death, 0302 clinical medicine, Ischemia, cardiovascular disease, Clinical endpoint, target population, CHART Program, Ejection fraction, bone-marrow, Heart Failure/Cardiomyopathy, 3. Good health, Cohort, Cardiology, Fast Track, disease severity, delivery, medicine.medical_specialty, precision medicine, Clinical Sciences, regenerative medicine, 03 medical and health sciences, cardiopoiesis, Internal medicine, medicine, Adverse effect, marker, disease, business.industry, medicine.disease, mortality, Confidence interval, Clinical trial, stem cell, Editor's Choice, 030104 developmental biology, predictors, Cardiovascular System & Hematology, Heart failure, business
Abstract

Altres ajuts: This work was supported by Celyad, SA (Mont-Saint-Guibert, Belgium). Celyad has received research grants from the Walloon Region (Belgium, DG06 funding). Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort. This multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n = 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving > 24 million mesenchymal stem cells (n = 315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n = 157) or sham procedure (n = 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n = 151 sham). The primary efficacy endpoint was a Finkelstein–Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann–Whitney estimator 0.54, 95% confidence interval [CI] 0.47–0.61 [value > 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200–370 mL (60% of patients) (Mann–Whitney estimator 0.61, 95% CI 0.52–0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death. The primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted.

Published
2017

3. Impact of polymorphic variation at 7p15.3, 3p22.1 and 2p23.3 loci on risk of multiple myeloma

Author

Martino, A., Campa, D., Canzian, F., Jamroziak, K., Szemraj-Rogucka, Z., Reis, R.M., Marques, H., Sainz, J., Jurado, M., Ríos, R., Buda, G., Orciuolo, E., Petrini, M., García-Sanz, R., Lesueur, F., Moreno, V., Szemraj, J., Tjønneland, A., Overvad, K., Vangsted, A.J., Vogel, Ulla Birgitte, Mikala, G., Kádár, K., Szombath, G., Varkonyi, J., Dumontet, C., Gemignani, F., Rossi, A.M., Landi, S., Houlston, R.S., Hemminki, K., Martino, A., Campa, D., Canzian, F., Jamroziak, K., Szemraj-Rogucka, Z., Reis, R.M., Marques, H., Sainz, J., Jurado, M., Ríos, R., Buda, G., Orciuolo, E., Petrini, M., García-Sanz, R., Lesueur, F., Moreno, V., Szemraj, J., Tjønneland, A., Overvad, K., Vangsted, A.J., Vogel, Ulla Birgitte, Mikala, G., Kádár, K., Szombath, G., Varkonyi, J., Dumontet, C., Gemignani, F., Rossi, A.M., Landi, S., Houlston, R.S., and Hemminki, K.

Published
2012

4. The Potential Use of THP-1, a Monocytic Leukemia Cell Line, to Predict Immune-Suppressive Potency of Human Bone-Marrow Stromal Cells (BMSCs) In Vitro: A Pilot Study.

Author

Ren J, Szombath G, Vitale-Cross L, Stroncek DF, Robey PG, Hajdara A, Szalayova I, Mayer B, Martin D, Mezey E, and Nemeth K

Subjects
Humans, Pilot Projects, Interleukin-10, Cell Line, Stromal Cells, Bone Marrow, Leukemia, Monocytic, Acute
Abstract

Adoptive transfer of cultured BMSCs was shown to be immune-suppressive in various inflammatory settings. Many factors play a role in the process, but no master regulator of BMSC-driven immunomodulation was identified. Consequently, an assay that might predict BMSC product efficacy is still unavailable. Below, we show that BMSC donor variability can be monitored by IL-10 production of monocytes/macrophages using THP-1 cells (immortalized monocytic leukemia cells) co-cultured with BMSCs. Using a mixed lymphocyte reaction (MLR) assay, we also compared the ability of the different donor BMSCs to suppress T-cell proliferation, another measure of their immune-suppressive ability. We found that the BMSCs from a donor that induced the most IL-10 production were also the most efficient in suppressing T-cell proliferation. Transcriptome studies showed that the most potent BMSC batch also had higher expression of several known key immunomodulatory molecules such as hepatocyte growth factor (HGF), PDL1, and numerous members of the PGE2 pathway, including PTGS1 and TLR4. Multiplex ELISA experiments revealed higher expression of HGF and IL6 by the most potent BMSC donor. Based on these findings, we propose that THP-1 cells may be used to assess BMSC immunosuppressive activity as a product characterization assay.

Published
2023
Full Text
View/download PDF

5. Bone Marrow-Derived Mesenchymal Stromal Cells (MSCs) Modulate the Inflammatory Character of Alveolar Macrophages from Sarcoidosis Patients.

Author

McClain Caldwell I, Hogden C, Nemeth K, Boyajian M, Krepuska M, Szombath G, MacDonald S, Abshari M, Moss J, Vitale-Cross L, Fontana JR, and Mezey E

Abstract

Sarcoidosis is a devastating inflammatory disease affecting many organs, especially the lungs and lymph nodes. Bone marrow-derived mesenchymal stromal cells (MSCs) can "reprogram" various types of macrophages towards an anti-inflammatory phenotype. We wanted to determine whether alveolar macrophages from sarcoidosis subjects behave similarly by mounting an anti-inflammatory response when co-cultured with MSCs. Fifteen sarcoidosis and eight control subjects underwent bronchoscopy and bronchoalveolar lavage (BAL). Unselected BAL cells (70-94% macrophages) were isolated and cultured with and without MSCs from healthy adults. Following stimulation of the cultured cells with lipopolysaccharide, the medium was removed to measure interleukin 10 and tumor necrosis factor alpha (IL-10 and TNF-α). In two additional sarcoidosis subjects, flow cytometry was used to study intracellular cytokines and surface markers associated with alveolar macrophages to confirm the results. Unselected BAL cells from sarcoidosis subjects co-cultured with MSCs showed a reduction in TNF-α (pro-inflammatory M1) and an increase in IL-10 (anti-inflammatory M2) in 9 of 11 samples studied. Control subject samples showed few, if any, differences in cytokine production. Unselected BAL cells from two additional patients analyzed by flow cytometry confirmed a switch towards an anti-inflammatory state (i.e., M1 to M2) after co-culture with MSCs. These results suggest that, similarly to other macrophages, alveolar macrophages also respond to MSC contacts by changing towards an anti-inflammatory phenotype. Based on our results, we hypothesize that mesenchymal stromal cells applied to the airways might alleviate lung inflammation and decrease steroid need in patients with sarcoidosis.

Published
2020
Full Text
View/download PDF

6. Elevated HOX gene expression in acute myeloid leukemia is associated with NPM1 mutations and poor survival.

Author

Nagy Á, Ősz Á, Budczies J, Krizsán S, Szombath G, Demeter J, Bödör C, and Győrffy B

Abstract

Acute myeloid leukemia (AML) is a clonal disorder of hematopoietic progenitor cells and the most common malignant myeloid disorder in adults. Several gene mutations such as in NPM1 (nucleophosmin 1) are involved in the pathogenesis and progression of AML. The aim of this study was to identify genes whose expression is associated with driver mutations and survival outcome. Genotype data (somatic mutations) and gene expression data including RNA-seq, microarray, and qPCR data were used for the analysis. Multiple datasets were utilized as training sets (GSE6891, TCGA, and GSE1159). A new clinical sample cohort (Semmelweis set) was established for in vitro validation. Wilcoxon analysis was used to identify genes with expression alterations between the mutant and wild type samples. Cox regression analysis was performed to examine the association between gene expression and survival outcome. Data analysis was performed in the R statistical environment. Eighty-five genes were identified with significantly altered expression when comparing NPM1 mutant and wild type patient groups in the GSE6891 set. Additional training sets were used as a filter to condense the six most significant genes associated with NPM1 mutations. Then, the expression changes of these six genes were confirmed in the Semmelweis set: HOXA5 ( P  = 3.06E-12, FC = 8.3), HOXA10 ( P  = 2.44E-09, FC = 3.3), HOXB5 ( P  = 1.86E-13, FC = 37), MEIS1 ( P  = 9.82E-10, FC = 4.4), PBX3 ( P  = 1.03E-13, FC = 5.4) and ITM2A ( P  = 0.004, FC = 0.4). Cox regression analysis showed that higher expression of these genes - with the exception of ITM2A - was associated with worse overall survival. Higher expression of the HOX genes was identified in tumors harboring NPM1 gene mutations by computationally linking genotype and gene expression. In vitro validation of these genes supports their potential therapeutic application in AML.

Published
2019
Full Text
View/download PDF

7. Multiple Myeloma of the Central Nervous System: 13 Cases and Review of the Literature.

Author

Varga G, Mikala G, Gopcsa L, Csukly Z, Kollai S, Balázs G, Botond T, Wohner N, Horváth L, Szombath G, Farkas P, and Masszi T

Abstract

Central nervous system involvement is a rare complication of multiple myeloma with extremely poor prognosis as it usually fails to respond to therapy. We present 13 cases diagnosed at two centers in Budapest and review the current literature. The majority of our cases presented with high-risk features initially; two had plasma cell leukemia. Repeated genetic tests showed clonal evolution in 3 cases. Treatments varied according to the era, and efficacy was poor as generally reported in the literature. Only one patient is currently alive, with 3-month follow-up, and the patient responded to daratumumab-based treatment. Recent case reports show promising effectivity of pomalidomide and marizomib.

Published
2018
Full Text
View/download PDF

8. The Impact of Acute Matriptase Inhibition in Hepatic Inflammatory Models.

Author

Pomothy J, Szombath G, Rokonál P, Mátis G, Neogrády Z, Steinmetzer T, and Pászti-Gere E

Subjects
Animals, Cell Death drug effects, Hepatocytes drug effects, Hepatocytes metabolism, Hepcidins metabolism, Hydrogen Peroxide metabolism, Interleukin-6 metabolism, Interleukin-8 metabolism, Kupffer Cells drug effects, Kupffer Cells metabolism, Liver drug effects, Male, Oxidative Stress drug effects, Phenylalanine pharmacology, Reactive Oxygen Species metabolism, Swine, Inflammation metabolism, Liver metabolism, Liver Diseases metabolism, Serine Endopeptidases metabolism
Abstract

Purpose. Dysfunction of matriptase-2 can be involved in iron regulatory disorder via downregulation of hepcidin expression. In the present study, we investigated the effects of 3-amidinophenylalanine-derived matriptase inhibitors on porcine hepatic inflammatory cell models. Methods. Hepatocyte-Kupffer cell cocultures (ratio of 2 : 1 and 6 : 1) were treated with four structurally related matriptase inhibitors at 50 μM. Cell cytotoxicity and relative expressions of IL-6 and IL-8 and the levels of hepcidin were determined by MTS and porcine-specific ELISA. The extracellular H2O2 contents were analyzed by Amplex Red method. Results. Matriptase inhibitors at 50 µM for 24 h did not increase cell death rate. The elevated ROS production observed after short-term application of inhibitor MI-441 could be correlated with lowered hepcidin expression. MI-460 could significantly enhance hepcidin levels in the supernatants of cocultures (by 62.21 ± 26.8% in hepatocyte-Kupffer cell, 2 : 1, and by 42.6 ± 14.3% in hepatocyte-Kupffer cell, 6 : 1, cocultures, resp.). No significant changes were found in IL-6 and IL-8 levels in cocultures exposed to matriptase inhibitors. Conclusions. Based on in vitro findings, administration of MI-460 via modulation of hepcidin expression without cytotoxic and oxidative stress inducing properties might be a reliable alternative to treat iron overload in human and veterinary clinical practice.

Published
2016
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results