116 results on '"Krenacs T"'
Search Results
2. DNA fragmentation and caspase-independent programmed cell death by modulated electrohyperthermia
- Author
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Meggyeshazi, N., Andocs, G., Balogh, L., Balla, P., Kiszner, G., Teleki, I., Jeney, A., and Krenacs, T.
- Published
- 2014
- Full Text
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3. Collagen XVII is expressed in malignant but not in benign melanocytic tumors and it can mediate antibody induced melanoma apoptosis
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Krenacs, T., Kiszner, G., Stelkovics, E., Balla, P., Teleki, I., Nemeth, I., Varga, E., Korom, I., Barbai, T., Plotar, V., Timar, J., and Raso, E.
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- 2012
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4. Prognostic significance of claudin expression changes in breast cancer with regional lymph node metastasis
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Szasz, A. M., Tokes, A. M., Micsinai, M., Krenacs, T., Jakab, Cs., Lukacs, L., Nemeth, Zs., Baranyai, Zs., Dede, K., Madaras, L., and Kulka, J.
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- 2011
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5. Morphological and immunophenotypic features of primary and metastatic giant cell tumour of bone
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Alberghini, M., Kliskey, K., Krenacs, T., Picci, P., Kindblom, L., Forsyth, R., and Athanasou, N. A.
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- 2010
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6. The Potential of Digital Microscopy in Breast Pathology
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Krenacs, T., Zsakovics, I., Diczhazi, Cs., Ficsor, L., Varga, V. S., and Molnar, B.
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- 2009
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7. Suppression of Metastatic Melanoma Growth in Lung by Modulated Electro-Hyperthermia Monitored by a Minimally Invasive Heat Stress Testing Approach in Mice
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Thomas, M. J., Major, E., Benedek, A., Horvath, I., Mathe, D., (0000-0002-8733-4286) Bergmann, R., Szasz, A. M., Krenacs, T., Benyo, Z., Thomas, M. J., Major, E., Benedek, A., Horvath, I., Mathe, D., (0000-0002-8733-4286) Bergmann, R., Szasz, A. M., Krenacs, T., and Benyo, Z.
- Abstract
Modulated electro-hyperthermia (mEHT) is a novel complementary therapy in oncology which is based on the higher conductivity and permittivity of cancerous tissues due to their enhanced glycolytic activity and ionic content compared to healthy normal tissues. We aimed to evaluate the potential of mEHT, inducing local hyperthermia, in the treatment of pulmonary metastatic melanoma. Our primary objective was the optimization of mEHT for targeted lung treatment as well as to identify the mechanism of its potential anti-tumor effect in the B16F10 mouse melanoma pulmonary metastases model while investigating the potential treatment-related side effects of mEHT on normal lung tissue. Repeated treatment of tumor-bearing lungs with mEHT induced significant anti-tumor effects as demonstrated by the lower number of tumor nodules and the downregulation of Ki67 expression in treated tumor cells. mEHT treatment provoked significant DNA double-strand breaks indicated by the increased expression of phosphorylated H2AX protein in treated tumors, although treatment-induced elevation of cleaved/activated caspase-3 expression was insignificant, suggesting the minimal role of apoptosis in this process. The mEHT-related significant increase in p21waf1 positive tumor cells suggested that p21waf1-mediated cell cycle arrest plays an important role in the anti-tumor effect of mEHT on melanoma metastases. Significantly increased CD3+, CD8+ T-lymphocytes, and F4/80+CD11b+ macrophage density in the whole lung and tumor of treated animals emphasizes the mobilizing capability of mEHT on immune cells. In conclusion, mEHT can reduce the growth potential of melanoma, thus offering itself as a complementary therapeutic option to chemo- and/or radiotherapy.
- Published
- 2020
8. How we process trephine biopsy specimens: epoxy resin embedded bone marrow biopsies
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Krenacs, T., Bagdi, E., Stelkovics, E., Bereczki, L., and Krenacs, L.
- Subjects
Bone marrow examination -- Methods ,Bone marrow -- Biopsy ,Bone marrow -- Methods ,Health - Published
- 2005
9. The immunophenotype of osteoclasts and macrophage polykaryons
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Maggiani, F, Forsyth, R, Hogendoorn, P C W, Krenacs, T, and Athanasou, N A
- Published
- 2011
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10. 3.P.12 MORPHOLOGICAL AND IMMUNOPHENOTYPIC FEATURES OF METASTATIC GIANT CELL TUMOURS OF BONE: CLUES TO PATHOGENESIS
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Alberghini, M., Kliskey, K., Krenacs, T., Picci, P., and Athanasou, N. A.
- Published
- 2010
11. Regeneration of Rabbit Cornea Following Excimer Laser Photorefractive Keratectomy: a Study on Gap Junctions, Epithelial Junctions and Epidermal Growth Factor Receptor Expression in Correlation with Cell Proliferation
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Ratkay-Traub, I., Hopp, B., Bor, Zs., Dux, L., Becker, D.L., and Krenacs, T.
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- 2001
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12. Cell cycle regulatory protein expression in multinucleated giant cells: Do they proliferate?
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Krenacs, T., Maros, M. E., Sapi, Z., Szendroi, M., Ramses Forsyth, Picci, P., S Benassi, M., Athanasou, N., Supporting clinical sciences, and Experimental Pathology
- Published
- 2017
13. World Congress Integrative Medicine & Health 2017: part two Berlin, Germany. 3-5 May 2017 Abstracts
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Ee, C, Thuraisingam, S, Pirotta, M, French, S, Xue, C, Teede, H, Kristoffersen, AE, Sirois, F, Stub, T, Engler, J, Joos, S, Güthlin, C, Felenda, J, Beckmann, C, Stintzing, F, Evans, R, Bronfort, G, Keefe, D, Taberko, A, Hanson, L, Haley, A, Ma, H, Jolton, J, Yarosh, L, Keefe, F, Nam, J, Ojala, L, Kreitzer, MJ, Fink, C, Kraft, K, Flower, A, Lewith, G, Harman, K, Stuart, B, Bishop, FL, Frawley, J, Füleki, L, Kiss, E, Vancsik, T, Krenacs, T, Funabashi, M, Pohlman, KA, Mior, S, Thiel, H, Hill, MD, Cassidy, DJ, Westaway, M, Yager, J, Hurwitz, E, Kawchuk, GN, O’Beirne, M, Vohra, S, Gaboury, I, Morin, C, Gaertner, K, Torchetti, L, Frei-Erb, M, Kundi, M, Frass, M, Gallo, E, Maggini, V, Comite, M, Sofi, F, Baccetti, S, Vannacci, A, Di Stefano, M, Monechi, MV, Gori, L, Rossi, E, Firenzuoli, F, Mediati, RD, Ballerini, G, Gardiner, P, Lestoquoy, AS, Negash, L, Stillman, S, Shah, P, Liebschutz, J, Adelstein, P, Farrell-Riley, C, Brackup, I, Penti, B, Saper, R, Sampedro, IG, Carvajal, G, Gleiss, A, Gross, MM, Brendlin, D, Röttger, J, Stritter, W, Seifert, G, Grzanna, N, Stange, R, Guendling, PW, Gu, W, Lu, Y, Wang, J, Zhang, C, Bai, H, He, Y, Zhang, X, Zhang, Z, Wang, D, Meng, F, Hagel, A, Albrecht, H, Vollbracht, C, Dauth, W, Hagel, W, Vitali, F, Ganzleben, I, Schultis, H, Konturek, P, Stein, J, Neurath, M, Raithel, M, Krick, B, Haller, H, Klose, P, Dobos, G, Kümmel, S, Cramer, H, Saha, FJ, Kowoll, A, Ebner, B, Berger, B, Choi, K-E, He, L, Wang, H, He, X, Gu, C, Zhang, Y, Zhao, L, Tong, X, Ho, RST, Chung, VCH, Wu, X, Wong, CHL, Wu, JCY, Wong, SYS, Lau, AYL, Sit, RWS, Wong, W, Holmes, M, Bishop, F, Calman, L, Newell, D, Field, J, Htut, WL, Han, D, Choi, DI, Choi, SJ, Kim, HY, Hwang, JH, Huang, CW, Jang, BH, Chen, FP, Ko, SG, Huang, W, Jin, D, Lian, F, Jang, S, Kim, KH, Lee, EK, Sun, SH, Go, HY, Ko, Y, Park, S, Shin, YC, Janik, H, Greiffenhagen, N, Bolte, J, Jaworski, M, Adamus, M, Dobrzynska, A, Jeitler, M, Jaspers, J, von Scheidt, C, Koch, B, Michalsen, A, Steckhan, N, Kessler, C, Huang, W-J, Pang, B, Lian, F-M, Jong, M, Baars, E, Glockmann, A, Hamre, H, Kainuma, M, Murakami, A, Kubota, T, Kobayashi, D, Sumoto, Y, Furusyo, N, Ando, S-I, Shimazoe, T, Kelber, O, Verjee, S, Gorgus, E, Schrenk, D, Kemper, K, Hill, E, Rao, N, Gascon, G, Mahan, J, Kienle, G, Dietrich, J, Schmoor, C, Huber, R, Kim, WH, Ahmed, M, Meggyeshazi, N, Kovago, C, Klaus, AK, Zerm, R, Pranga, D, Ostermann, T, Reif, M, von Laue, HB, Brinkhaus, B, Kröz, M, Recchia, DR, Klein-Laansma, CT, von Hagens, C, Jansen, JP, van Wietmarschen, H, Jong, MC, Sun, S-H, Go, H-Y, Jeon, C-Y, Song, Y-K, Ko, S-G, Koch, AK, Rabsilber, S, Lauche, R, Langhorst, J, Trifunovic-Koenig, M, Koster, E, Delnoij, D, Kroll, L, Weiss, K, Kubo, A, Hendlish, S, Altschuler, A, Connolly, N, Avins, A, Wardle, J, Lee, D, Sibbritt, D, Adams, J, Park, C, Mishra, G, Lechner, J, Lee, I, Chae, Y, Lee, J, Cho, SH, Choi, Y, Lee, JY, Ryu, HS, Yoon, SS, Oh, HK, Hyun, LK, Kim, JO, Yoon, SW, Lee, J-Y, Shin, S-H, Jang, M, Müller, I, Park, S-HJ, Laird, L, Mitchell, S, Li, X, Wang, Y, Zhen, J, Yu, H, Liu, T, Gu, X, Liu, H, Ma, W, Shang, X, Bai, Y, Liu, W, Rooney, C, Smith, A, Lopes, S, Demarzo, M, do Patrocínio Nunes, M, Lorenz, P, Gründemann, C, Heinrich, M, Garcia-Käufer, M, Grunewald, F, Messerschmidt, S, Herrick, A, Gruber, K, Knödler, M, Steinborn, C, Lu, T, Wang, L, Wu, D, Luberto, CM, Hall, DL, Chad-Friedman, E, Lechner, S, Park, ER, Park, E, Goodman, J, Luer, S, Heri, M, von Ammon, K, Landini, I, Lapucci, A, Nobili, S, Mini, E, McDermott, C, Richards, S, Cox, D, Frossell, S, Leydon, G, Eyles, C, Raphael, H, Rogers, R, Selby, M, Adler, C, Allam, J, Bu, X, Zhang, H, Zhang, J, Mikolasek, M, Berg, J, Witt, C, Barth, J, Miskulin, I, Lalic, Z, Miskulin, M, Dumic, A, Sebo, D, Vcev, A, Mohammed, NAA, Im, HB, Mukherjee, A, Kandhare, A, Bodhankar, S, Thakurdesai, P, Munk, N, Evans, E, Froman, A, Kline, M, Bair, MJ, Musial, F, Alræk, T, Hamre, HJ, Björkman, L, Fønnebø, VM, Ni, Q, Tong, X-L, Li, X-L, Liu, W-K, Feng, S, Zhao, X-Y, Zheng, Y-J, Zhao, X-M, Lin, Y-Q, Zhao, T-Y, Phd, HC, Liu, F, Zhao, L-H, Ye, R, Gu, C-J, Peng, W, De Carvalho, D, El-Bayoumi, M, Haig, B, Kelly, K, Wade, DJ, Portalupi, E, Gobo, G, Bellavita, L, Guglielmetti, C, Raak, C, Teuber, M, Molsberger, F, von Rath, U, Reichelt, U, Schwanebeck, U, Zeil, S, Vogelberg, C, Veintimilla, DR, Mery, GT, Villavicencio, MM, Moran, SH, Sachse, C, Gündlin, PW, Sahebkarkhorasani, M, Azizi, H, Schumann, D, Sundberg, T, Leach, MJ, Seca, S, Greten, H, Selliah, S, Shakya, A, Sherbakova, A, Ulrich-Merzenich, G, Abdel-Aziz, H, Sibinga, E, Webb, L, Ellen, J, Skrautvol, K, Nåden, D, Song, R, Grabowska, W, Osypiuk, K, Diaz, GV, Bonato, P, Park, M, Hausdorff, J, Fox, M, Sudarsky, LR, Tarsy, D, Novakowski, J, Macklin, EA, Wayne, PM, Hwang, I, Ahn, S, Lee, M-A, Sohn, MK, Sorokin, O, Heydeck, D, Borchert, A, Hohmann, C-D, Kühn, H, Kirschbaum, C, Stalder, T, Stöckigt, B, Teut, M, Suhr, R, Sulmann, D, Streeter, C, Gerbarg, P, Silveri, M, Brown, R, Jensen, J, Rutert, B, Eggert, A, Längler, A, Holmberg, C, Sun, J, Deng, X, Li, W-Y, Wen, B, Robinson, N, Liu, J-P, Sung, HK, Yang, N, Shin, SM, Jung, H, Kim, YJ, Jung, WS, Park, TY, Suzuki, K, Ito, T, Uchida, S, Kamohara, S, Ono, N, Takamura, M, Yokochi, A, Maruyama, K, Tapia, P, Thabaut, K, Thronicke, A, Steele, M, Matthes, H, Herbstreit, C, Schad, F, Tian, J, Yang, L, Tian, T, Tian, X, Wang, C, Chai, QY, Zhang, L, Xia, R, Huang, N, Fei, Y, Liu, J, Trent, N, Miraglia, M, Dusek, J, Pasalis, E, Khalsa, SB, Trifunovic-König, M, Koch, A, Uebelacker, L, Tremont, G, Gillette, L, Epstein-Lubow, G, Strong, D, Abrantes, A, Tyrka, A, Tran, T, Gaudiano, B, Miller, I, Ullmann, G, Li, Y, Vaidya, S, Marathe, V, Vale, AC, Motta, J, Donadão, F, Valente, AC, Valente, LCC, Ghelman, R, Vesovic, D, Jevdic, D, Jevdic, A, Jevdic, K, Djacic, M, Letic, D, Bozic, D, Markovic, M, Dunjic, S, Ruscuklic, G, Baksa, D, Vrca, K, Vincent, A, Wahner-Roedler, D, Whipple, M, Vogelius, MM, Friesecke, I, Gündling, PW, Mahapatra, S, Hynes, R, Van Rooy, K, Looker, S, Ghosh, A, Bauer, B, Cutshall, S, Walach, H, Flores, AB, Ofner, M, Kastner, A, Schwarzl, G, Schwameder, H, Alexander, N, Strutzenberger, G, Wang, S, Shi, J, Hao, Y, Wu, J, Qiu, Z, Wang, Y-H, Lou, C-J, Watts, S, Wayne, P, Vergara-Diaz, G, Gow, B, Miranda, J, Sudarsky, L, Macklin, E, Wode, K, Bergqvist, J, Bernhardsson, B-M, Nordberg, JH, Sharp, L, Henriksson, R, Woo, Y, Hyun, MK, Wu, H, Wang, T-F, Zhao, Y, Wei, Y, Tian, L, Wang, X, Wu, R, Han, M, Caldwell, PHY, Liu, S, Chai, Q, Guo, Z, Liu, Z, Yang, IJ, Lincha, VR, Ahn, SH, Lee, DU, Shin, HM, Sung, H, Kim, Y, Yap, A, Kwan, YH, Tan, CS, Ibrahim, S, Ang, SB, Yayi, A, Yoo, JE, Yoo, HR, Jang, SB, Lee, HL, Youssef, A, Ezzat, S, Motaal, AA, El-Askary, H, Yu, X, Cui, Y, Yun, Y, Ahn, J-H, Jang, B-H, Kim, K-S, Choi, I, Glinz, A, ten Brink, F, Büssing, A, Gutenbrunner, C, Helbrecht, B, Fang, T, Shen, Z, Zhang, R, Wu, F, Li, M, Xuan, X, Shen, X, Ren, K, Berman, B, Zheng, Z, Wan, Y, Ma, X, Dong, F, Zick, S, Harris, R, Bae, GE, Kwon, JN, Lee, HY, Nam, JK, Lee, SD, Lee, DH, Han, JY, Yun, YJ, Lee, JH, Park, HL, Park, SH, Bocci, C, Ivaldi, GB, Vietti, I, Meaglia, I, Guffi, M, Ruggiero, R, Gualea, M, Longa, E, Bonucci, M, Croke, S, Rodriguez, LD, Caracuel-Martínez, JC, Fajardo-Rodríguez, MF, Ariza-García, A, la Fuente, FG-D, Arroyo-Morales, M, Estrems, MS, Gómez, VG, Sabater, MV, Ferreri, R, Bernardini, S, Pulcri, R, Cracolici, F, Rinaldi, M, Porciani, C, Fisher, P, Hughes, J, Mendoza, A, MacPherson, H, Filshie, J, Di Francesco, A, Bernardini, A, Messe, M, Primitivo, V, Iasella, PA, Taminato, M, Alcantara, JDC, De Oliveira, KR, Rodrigues, DCDA, Mumme, JRC, Sunakozawa, OKM, Filho, VO, Goldenberg, J, Day, A, Sasagawa, M, Ward, L, Cooley, K, Gunnarsdottir, T, Hjaltadottir, I, Hajimonfarednejad, M, Hannan, N, Hellsing, R, Andermo, S, Arman, M, von Hörsten, I, Torrielo, PV, Vilaró, CLA, Cabrera, FC, Hui, H, Ziea, E, Tsui, D, Hsieh, J, Lam, C, Chan, E, Jensen, MP, Battalio, SL, Chan, J, Edwards, KA, Gertz, KJ, Day, MA, Sherlin, LH, Ehde, DM, Börner, A, Lee, B, Chang, GT, Menassa, A, Motoo, Y, Müller, J, Rabini, S, Vinson, B, Storr, M, Niemeijer, M, Hoekman, J, Ruijssenaaars, W, Njoku, FC, Norheim, AJ, Okumus, F, Oncu-Celik, H, Ee, C, Thuraisingam, S, Pirotta, M, French, S, Xue, C, Teede, H, Kristoffersen, AE, Sirois, F, Stub, T, Engler, J, Joos, S, Güthlin, C, Felenda, J, Beckmann, C, Stintzing, F, Evans, R, Bronfort, G, Keefe, D, Taberko, A, Hanson, L, Haley, A, Ma, H, Jolton, J, Yarosh, L, Keefe, F, Nam, J, Ojala, L, Kreitzer, MJ, Fink, C, Kraft, K, Flower, A, Lewith, G, Harman, K, Stuart, B, Bishop, FL, Frawley, J, Füleki, L, Kiss, E, Vancsik, T, Krenacs, T, Funabashi, M, Pohlman, KA, Mior, S, Thiel, H, Hill, MD, Cassidy, DJ, Westaway, M, Yager, J, Hurwitz, E, Kawchuk, GN, O’Beirne, M, Vohra, S, Gaboury, I, Morin, C, Gaertner, K, Torchetti, L, Frei-Erb, M, Kundi, M, Frass, M, Gallo, E, Maggini, V, Comite, M, Sofi, F, Baccetti, S, Vannacci, A, Di Stefano, M, Monechi, MV, Gori, L, Rossi, E, Firenzuoli, F, Mediati, RD, Ballerini, G, Gardiner, P, Lestoquoy, AS, Negash, L, Stillman, S, Shah, P, Liebschutz, J, Adelstein, P, Farrell-Riley, C, Brackup, I, Penti, B, Saper, R, Sampedro, IG, Carvajal, G, Gleiss, A, Gross, MM, Brendlin, D, Röttger, J, Stritter, W, Seifert, G, Grzanna, N, Stange, R, Guendling, PW, Gu, W, Lu, Y, Wang, J, Zhang, C, Bai, H, He, Y, Zhang, X, Zhang, Z, Wang, D, Meng, F, Hagel, A, Albrecht, H, Vollbracht, C, Dauth, W, Hagel, W, Vitali, F, Ganzleben, I, Schultis, H, Konturek, P, Stein, J, Neurath, M, Raithel, M, Krick, B, Haller, H, Klose, P, Dobos, G, Kümmel, S, Cramer, H, Saha, FJ, Kowoll, A, Ebner, B, Berger, B, Choi, K-E, He, L, Wang, H, He, X, Gu, C, Zhang, Y, Zhao, L, Tong, X, Ho, RST, Chung, VCH, Wu, X, Wong, CHL, Wu, JCY, Wong, SYS, Lau, AYL, Sit, RWS, Wong, W, Holmes, M, Bishop, F, Calman, L, Newell, D, Field, J, Htut, WL, Han, D, Choi, DI, Choi, SJ, Kim, HY, Hwang, JH, Huang, CW, Jang, BH, Chen, FP, Ko, SG, Huang, W, Jin, D, Lian, F, Jang, S, Kim, KH, Lee, EK, Sun, SH, Go, HY, Ko, Y, Park, S, Shin, YC, Janik, H, Greiffenhagen, N, Bolte, J, Jaworski, M, Adamus, M, Dobrzynska, A, Jeitler, M, Jaspers, J, von Scheidt, C, Koch, B, Michalsen, A, Steckhan, N, Kessler, C, Huang, W-J, Pang, B, Lian, F-M, Jong, M, Baars, E, Glockmann, A, Hamre, H, Kainuma, M, Murakami, A, Kubota, T, Kobayashi, D, Sumoto, Y, Furusyo, N, Ando, S-I, Shimazoe, T, Kelber, O, Verjee, S, Gorgus, E, Schrenk, D, Kemper, K, Hill, E, Rao, N, Gascon, G, Mahan, J, Kienle, G, Dietrich, J, Schmoor, C, Huber, R, Kim, WH, Ahmed, M, Meggyeshazi, N, Kovago, C, Klaus, AK, Zerm, R, Pranga, D, Ostermann, T, Reif, M, von Laue, HB, Brinkhaus, B, Kröz, M, Recchia, DR, Klein-Laansma, CT, von Hagens, C, Jansen, JP, van Wietmarschen, H, Jong, MC, Sun, S-H, Go, H-Y, Jeon, C-Y, Song, Y-K, Ko, S-G, Koch, AK, Rabsilber, S, Lauche, R, Langhorst, J, Trifunovic-Koenig, M, Koster, E, Delnoij, D, Kroll, L, Weiss, K, Kubo, A, Hendlish, S, Altschuler, A, Connolly, N, Avins, A, Wardle, J, Lee, D, Sibbritt, D, Adams, J, Park, C, Mishra, G, Lechner, J, Lee, I, Chae, Y, Lee, J, Cho, SH, Choi, Y, Lee, JY, Ryu, HS, Yoon, SS, Oh, HK, Hyun, LK, Kim, JO, Yoon, SW, Lee, J-Y, Shin, S-H, Jang, M, Müller, I, Park, S-HJ, Laird, L, Mitchell, S, Li, X, Wang, Y, Zhen, J, Yu, H, Liu, T, Gu, X, Liu, H, Ma, W, Shang, X, Bai, Y, Liu, W, Rooney, C, Smith, A, Lopes, S, Demarzo, M, do Patrocínio Nunes, M, Lorenz, P, Gründemann, C, Heinrich, M, Garcia-Käufer, M, Grunewald, F, Messerschmidt, S, Herrick, A, Gruber, K, Knödler, M, Steinborn, C, Lu, T, Wang, L, Wu, D, Luberto, CM, Hall, DL, Chad-Friedman, E, Lechner, S, Park, ER, Park, E, Goodman, J, Luer, S, Heri, M, von Ammon, K, Landini, I, Lapucci, A, Nobili, S, Mini, E, McDermott, C, Richards, S, Cox, D, Frossell, S, Leydon, G, Eyles, C, Raphael, H, Rogers, R, Selby, M, Adler, C, Allam, J, Bu, X, Zhang, H, Zhang, J, Mikolasek, M, Berg, J, Witt, C, Barth, J, Miskulin, I, Lalic, Z, Miskulin, M, Dumic, A, Sebo, D, Vcev, A, Mohammed, NAA, Im, HB, Mukherjee, A, Kandhare, A, Bodhankar, S, Thakurdesai, P, Munk, N, Evans, E, Froman, A, Kline, M, Bair, MJ, Musial, F, Alræk, T, Hamre, HJ, Björkman, L, Fønnebø, VM, Ni, Q, Tong, X-L, Li, X-L, Liu, W-K, Feng, S, Zhao, X-Y, Zheng, Y-J, Zhao, X-M, Lin, Y-Q, Zhao, T-Y, Phd, HC, Liu, F, Zhao, L-H, Ye, R, Gu, C-J, Peng, W, De Carvalho, D, El-Bayoumi, M, Haig, B, Kelly, K, Wade, DJ, Portalupi, E, Gobo, G, Bellavita, L, Guglielmetti, C, Raak, C, Teuber, M, Molsberger, F, von Rath, U, Reichelt, U, Schwanebeck, U, Zeil, S, Vogelberg, C, Veintimilla, DR, Mery, GT, Villavicencio, MM, Moran, SH, Sachse, C, Gündlin, PW, Sahebkarkhorasani, M, Azizi, H, Schumann, D, Sundberg, T, Leach, MJ, Seca, S, Greten, H, Selliah, S, Shakya, A, Sherbakova, A, Ulrich-Merzenich, G, Abdel-Aziz, H, Sibinga, E, Webb, L, Ellen, J, Skrautvol, K, Nåden, D, Song, R, Grabowska, W, Osypiuk, K, Diaz, GV, Bonato, P, Park, M, Hausdorff, J, Fox, M, Sudarsky, LR, Tarsy, D, Novakowski, J, Macklin, EA, Wayne, PM, Hwang, I, Ahn, S, Lee, M-A, Sohn, MK, Sorokin, O, Heydeck, D, Borchert, A, Hohmann, C-D, Kühn, H, Kirschbaum, C, Stalder, T, Stöckigt, B, Teut, M, Suhr, R, Sulmann, D, Streeter, C, Gerbarg, P, Silveri, M, Brown, R, Jensen, J, Rutert, B, Eggert, A, Längler, A, Holmberg, C, Sun, J, Deng, X, Li, W-Y, Wen, B, Robinson, N, Liu, J-P, Sung, HK, Yang, N, Shin, SM, Jung, H, Kim, YJ, Jung, WS, Park, TY, Suzuki, K, Ito, T, Uchida, S, Kamohara, S, Ono, N, Takamura, M, Yokochi, A, Maruyama, K, Tapia, P, Thabaut, K, Thronicke, A, Steele, M, Matthes, H, Herbstreit, C, Schad, F, Tian, J, Yang, L, Tian, T, Tian, X, Wang, C, Chai, QY, Zhang, L, Xia, R, Huang, N, Fei, Y, Liu, J, Trent, N, Miraglia, M, Dusek, J, Pasalis, E, Khalsa, SB, Trifunovic-König, M, Koch, A, Uebelacker, L, Tremont, G, Gillette, L, Epstein-Lubow, G, Strong, D, Abrantes, A, Tyrka, A, Tran, T, Gaudiano, B, Miller, I, Ullmann, G, Li, Y, Vaidya, S, Marathe, V, Vale, AC, Motta, J, Donadão, F, Valente, AC, Valente, LCC, Ghelman, R, Vesovic, D, Jevdic, D, Jevdic, A, Jevdic, K, Djacic, M, Letic, D, Bozic, D, Markovic, M, Dunjic, S, Ruscuklic, G, Baksa, D, Vrca, K, Vincent, A, Wahner-Roedler, D, Whipple, M, Vogelius, MM, Friesecke, I, Gündling, PW, Mahapatra, S, Hynes, R, Van Rooy, K, Looker, S, Ghosh, A, Bauer, B, Cutshall, S, Walach, H, Flores, AB, Ofner, M, Kastner, A, Schwarzl, G, Schwameder, H, Alexander, N, Strutzenberger, G, Wang, S, Shi, J, Hao, Y, Wu, J, Qiu, Z, Wang, Y-H, Lou, C-J, Watts, S, Wayne, P, Vergara-Diaz, G, Gow, B, Miranda, J, Sudarsky, L, Macklin, E, Wode, K, Bergqvist, J, Bernhardsson, B-M, Nordberg, JH, Sharp, L, Henriksson, R, Woo, Y, Hyun, MK, Wu, H, Wang, T-F, Zhao, Y, Wei, Y, Tian, L, Wang, X, Wu, R, Han, M, Caldwell, PHY, Liu, S, Chai, Q, Guo, Z, Liu, Z, Yang, IJ, Lincha, VR, Ahn, SH, Lee, DU, Shin, HM, Sung, H, Kim, Y, Yap, A, Kwan, YH, Tan, CS, Ibrahim, S, Ang, SB, Yayi, A, Yoo, JE, Yoo, HR, Jang, SB, Lee, HL, Youssef, A, Ezzat, S, Motaal, AA, El-Askary, H, Yu, X, Cui, Y, Yun, Y, Ahn, J-H, Jang, B-H, Kim, K-S, Choi, I, Glinz, A, ten Brink, F, Büssing, A, Gutenbrunner, C, Helbrecht, B, Fang, T, Shen, Z, Zhang, R, Wu, F, Li, M, Xuan, X, Shen, X, Ren, K, Berman, B, Zheng, Z, Wan, Y, Ma, X, Dong, F, Zick, S, Harris, R, Bae, GE, Kwon, JN, Lee, HY, Nam, JK, Lee, SD, Lee, DH, Han, JY, Yun, YJ, Lee, JH, Park, HL, Park, SH, Bocci, C, Ivaldi, GB, Vietti, I, Meaglia, I, Guffi, M, Ruggiero, R, Gualea, M, Longa, E, Bonucci, M, Croke, S, Rodriguez, LD, Caracuel-Martínez, JC, Fajardo-Rodríguez, MF, Ariza-García, A, la Fuente, FG-D, Arroyo-Morales, M, Estrems, MS, Gómez, VG, Sabater, MV, Ferreri, R, Bernardini, S, Pulcri, R, Cracolici, F, Rinaldi, M, Porciani, C, Fisher, P, Hughes, J, Mendoza, A, MacPherson, H, Filshie, J, Di Francesco, A, Bernardini, A, Messe, M, Primitivo, V, Iasella, PA, Taminato, M, Alcantara, JDC, De Oliveira, KR, Rodrigues, DCDA, Mumme, JRC, Sunakozawa, OKM, Filho, VO, Goldenberg, J, Day, A, Sasagawa, M, Ward, L, Cooley, K, Gunnarsdottir, T, Hjaltadottir, I, Hajimonfarednejad, M, Hannan, N, Hellsing, R, Andermo, S, Arman, M, von Hörsten, I, Torrielo, PV, Vilaró, CLA, Cabrera, FC, Hui, H, Ziea, E, Tsui, D, Hsieh, J, Lam, C, Chan, E, Jensen, MP, Battalio, SL, Chan, J, Edwards, KA, Gertz, KJ, Day, MA, Sherlin, LH, Ehde, DM, Börner, A, Lee, B, Chang, GT, Menassa, A, Motoo, Y, Müller, J, Rabini, S, Vinson, B, Storr, M, Niemeijer, M, Hoekman, J, Ruijssenaaars, W, Njoku, FC, Norheim, AJ, Okumus, F, and Oncu-Celik, H
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- 2017
14. Active TGF-beta Signalling and Decreased Expression of PTEN Separates Angiosarcoma of Bone from Its Soft Tissue Counterpart
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Verbeke, S.L.J., Bertoni, F., Bacchini, P., Oosting, J., Sciot, R., Krenacs, T., Dijke, P. ten, and Bovee, J.V.M.G.
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Male ,Pathology ,soft tissue tumor ,DNA Mutational Analysis ,Soft Tissue Neoplasms ,Kaplan-Meier Estimate ,bone tumor ,Phosphatidylinositol 3-Kinases ,Transforming Growth Factor beta ,Angiosarcoma ,Child ,Aged, 80 and over ,Tissue microarray ,biology ,Retinoblastoma ,Middle Aged ,Prognosis ,Europe ,immunohistochemistry ,Female ,Signal Transduction ,Adult ,medicine.medical_specialty ,Adolescent ,Class I Phosphatidylinositol 3-Kinases ,Hemangiosarcoma ,Down-Regulation ,Bone Neoplasms ,Pathology and Forensic Medicine ,Diagnosis, Differential ,Young Adult ,Cyclin D1 ,Predictive Value of Tests ,Biomarkers, Tumor ,medicine ,Humans ,PTEN ,neoplasms ,PI3K/AKT/mTOR pathway ,Aged ,angiosarcoma ,business.industry ,CD117 ,PTEN Phosphohydrolase ,Endoglin ,medicine.disease ,digestive system diseases ,Tissue Array Analysis ,Mutation ,vascular tumor ,biology.protein ,business - Abstract
Angiosarcomas constitute a heterogeneous group of highly malignant vascular tumors. Angiosarcoma of bone is rare and poorly characterized. For angiosarcoma of soft tissue, some pathways seem to be involved in tumor development. Our aim was to evaluate the role of these pathways in angiosarcoma of bone. We collected 37 primary angiosarcomas of bone and used 20 angiosarcomas of soft tissue for comparison. Immunohistochemistry was performed on constructed tissue microarrays to evaluate expression of CDKN2A, TP53, PTEN, BCL2, CDK4, MDM2, cyclin D1, β-catenin, transforming growth factor-β (TGF-β), CD105, phospho-Smad1, phospho-Smad2, hypoxia-inducible factor-1α, plasminogen activator inhibitor type 1 (PAI-1), VEGF, CD117 and glucose transporter--1. PIK3CA was screened for hotspot mutations in 19 angiosarcomas. In nearly 55% of the angiosarcoma of bone, the retinoblastoma (Rb) pathway was affected. Loss of CDKN2A expression was associated with a significantly worse prognosis. No overexpression of TP53 or MDM2 was found, suggesting that the TP53 pathway is not important in angiosarcoma of bone. Angiosarcoma of bone showed highly active TGF-β signaling with immunoreactivity for phospho-Smad2 and PAI-1. Although the phosphatidylinositol 3-kinase (PI3K)/Akt pathway seems to be active in both tumor groups, different mechanisms were involved: 41% of angiosarcoma of bone showed a decrease in expression of PTEN, whereas in angiosarcoma of soft tissue overexpression of KIT was found (90%). PIK3CA hotspot mutations were absent. In conclusion, the Rb pathway is involved in tumorigenesis of angiosarcoma of bone. The PI3K/Akt pathway is activated in both angiosarcoma of bone and soft tissue, however, with a different cause; PTEN expression is decreased in angiosarcoma of bone, whereas angiosarcomas of soft tissue show overexpression of KIT. Our findings support that angiosarcomas are a heterogeneous group of vascular malignancies. Both angiosarcoma of bone and soft tissue may benefit from therapeutic strategies targeting the PI3K/Akt pathway. However, interference with TGF-β signaling may be specifically relevant in angiosarcoma of bone.
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- 2013
15. Selective in situ protein expression profiles correlate with distinct phenotypes of basal cell carcinoma and squamous cell carcinoma of the skin
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Stelkovics, E., Kiszner, G., Meggyeshazi, N., Korom, I., Varga, E., Nemeth, I., Molnar, J., Marczinovits, I., and Krenacs, T.
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integumentary system ,5 - Ciencias puras y naturales::57 - Biología::576 - Biología celular y subcelular. Citología [CDU] ,Squamous cell carcinoma ,Skin cancer ,neoplasms - Abstract
Non-melanoma skin cancer is the most common malignancy that shows increasing incidence due to our cumulative exposure to ultraviolet irradiation. Its major subtypes, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) differ in pathobiology, phenotype and clinical behavior, which must be reflected at the molecular level. In this study, protein expression profiles of BCC and SCC were tested in tissue microarrays and correlated with that of actinic keratosis, Bowen’s disease, seborrheic keratosis and normal epidermis by detecting 22 proteins involved in cell interactions, growth, cell cycle regulation or apoptosis. The significantly more reduced collagen XVII, CD44v6, pan-Desmoglein levels and more evident E-Cadherin delocalization in BCC compared to SCC correlated with the de novo dermal invasion of BCC against the progressive invasion from in situ lesions in SCC development. EGFR was also expressed at a significantly higher level in SCC than in BCC. The upregulated cell communication protein connexin43 in BCC could contribute to the protection of BCC from metastatic invasion. Elevated cell replication in BCC was underlined by the increased topoisomerase IIa and reduced p21waf1 and p27kip1 positive cells fractions compared to SCC. Compared to differentiated keratinocytes, caspase-8 and -9 were equally upregulated in skin carcinoma subtypes for either mediating apoptosis induction or immune escape of tumor cells. Hierarchical cluster analysis grouped SCC and actinic keratosis cases exclusively together in support of their common origin and malignant phenotype. BCC cases were also clustered fully together. Differentially expressed proteins reflect the distinct pathobiology of skin carcinoma subtypes and can serve as surrogate markers in doubtful cases.
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- 2013
16. 590 G protein-coupled oestrogen receptor (GPER) is expressed in melanoma and may predict survival benefit
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Fábián, M., Balogh, P., Rencz, F., Brodszky, V., Hársing, J., Krenács, T., Németh, K., and Kárpáti, S.
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- 2017
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17. 342: Modulated electrohyperthermia induced immunogenic cell death specific signals in colorectal adenocarcinoma model
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Meggyeshazi, N., primary, Andocs, G., additional, Kovago, C., additional, Balogh, L., additional, and Krenacs, T., additional
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- 2014
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18. Gap junction intercellular communication is likely to be involved in regulation of stroma-dependent proliferation of hemopoietic stem cells
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Ploemacher, Rob, Mayen, AEM (Angelique), de Koning, JP (John), Krenacs, T, Rosendaal, M, and Hematology
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- 2000
19. 1438 POSTER Claudin-4/E-cadherin Index to Predict Prognosis in Breast Cancer
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Szasz, A., primary, Gyorffy, B., additional, Nemeth, Z., additional, Krenacs, T., additional, Baranyai, Z., additional, Harsanyi, L., additional, Dank, M., additional, Madaras, L., additional, Tokes, A.M., additional, and Kulka, J., additional
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- 2011
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20. Lymphoid aggregates may contribute to the migration and epithelial commitment of bone marrow-derived cells in colonic mucosa
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Valcz, G., primary, Krenacs, T., additional, Sipos, F., additional, Patai, A. V., additional, Wichmann, B., additional, Leiszter, K., additional, Toth, K., additional, Balogh, Z., additional, Csizmadia, A., additional, Hagymasi, K., additional, Masszi, T., additional, Molnar, B., additional, and Tulassay, Z., additional
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- 2011
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21. Specific expression of PAD4 and citrullinated proteins in lung cancer is not associated with anti-CCP antibody production
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Baka, Z., primary, Barta, P., additional, Losonczy, G., additional, Krenacs, T., additional, Papay, J., additional, Szarka, E., additional, Sarmay, G., additional, Babos, F., additional, Magyar, A., additional, Geher, P., additional, Buzas, E. I., additional, and Nagy, G., additional
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- 2011
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22. Optical delineation of human malignant melanoma using second harmonic imaging of collagen
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Thrasivoulou, C., primary, Virich, G., additional, Krenacs, T., additional, Korom, I., additional, and Becker, D. L., additional
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- 2011
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23. Increased serum PAD4 and RF in lung cancer is not associated with anti CCP antibody production
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Baka, Z., primary, Barta, P., additional, Losonczy, G., additional, Krenacs, T., additional, Papay, J., additional, Szarka, E., additional, Sarmay, G., additional, Magyar, A., additional, Buzas, E., additional, Falus, A., additional, and Nagy, G., additional
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- 2011
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24. Prognostic significance of claudin expression changes in breast cancer with regional lymph node metastasis
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Szasz, A. M., primary, Tokes, A. M., additional, Micsinai, M., additional, Krenacs, T., additional, Jakab, Cs., additional, Lukacs, L., additional, Nemeth, Zs., additional, Baranyai, Zs., additional, Dede, K., additional, Madaras, L., additional, and Kulka, J., additional
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- 2010
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25. Morphological and immunophenotypic features of primary and metastatic giant cell tumour of bone
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Alberghini, M., primary, Kliskey, K., additional, Krenacs, T., additional, Picci, P., additional, Kindblom, L., additional, Forsyth, R., additional, and Athanasou, N. A., additional
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- 2009
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26. Proteomic Profiling of Breast Carcinomas Based on Claudin Expression Pattern.
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Szasz, A., primary, Szasz, A., additional, Micsinai, M., additional, Tokes, A., additional, Madaras, L., additional, Krenacs, T., additional, and Kulka, J., additional
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- 2009
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27. The Potential of Digital Microscopy in Breast Pathology
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Krenacs, T., primary, Zsakovics, I., additional, Diczhazi, Cs., additional, Ficsor, L., additional, Varga, V. S., additional, and Molnar, B., additional
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- 2008
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28. Assessment of malignant melanoma using non-linear second harmonic generation imaging
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Virich, G., primary, Krenacs, T., additional, Ragoowansi, R., additional, Moir, G., additional, Becker, D., additional, and Thrasivoulou, C., additional
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- 2007
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29. Refractory sprue: Report of 2 cases without previous history of celiac disease
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Gurbity Palfi, T, primary, Krenacs, L, additional, Bagdi, E, additional, Krenacs, T, additional, Piukovics, K, additional, and Kiss, J, additional
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- 2004
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30. An antiserum reacts with an evolutionary conserved region in the ε subunit of the T-cell receptor—CD3 complex in phylogenetically distant species
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Kurucz, E., primary, Glavits, R., additional, Krenacs, L., additional, Krenacs, T., additional, Ocsovszky, I., additional, Keresztes, G., additional, Monostori, E., additional, and Ando, I., additional
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- 1993
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31. 344 Cell-cycle Phase Specific Markers’ Expression in Breast Cancer
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Szasz, A., Geszti, F., Zsákovics, I., Székely, B., Tokes, A.M., Rowan, A., Swanton, C., Krenács, T., and Kulka, J.
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- 2012
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32. 559 Galectin-1 expression in Hodgkin-lymphoma cells
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Mark, A., Hajdu, M., Nemes, K., Sticz, T., Krenács, T., Kopper, L., and Sebestyén, A.
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- 2010
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33. Characterization of Rare Chondrosarcoma Subtypes
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Meijer, D., Szuhai, K., Den Akker, B. E., Jong, D., Krenacs, T., Athanasou, N. A., Flanagan, A. M., Picci, P., Daugaard, S., Liegl-Atzwanger, B., Pancras C W Hogendoorn, Bovee, J. V., and EuroBoNet Consortium
34. The potential prognostic value of connexin 26 and 46 expression in neoadjuvant-treated breast cancer
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Teleki Ivett, Krenacs Tibor, Szasz Marcell A, Kulka Janina, Wichmann Barna, Leo Cornelia, Papassotiropoulos Barbel, Riemenschnitter Cosima, Moch Holger, and Varga Zsuzsanna
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Breast cancer ,Connexin ,Gap junction ,Preoperative chemotherapy ,Prognosis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Several classification systems are available to assess pathological response to neoadjuvant chemotherapy in breast cancer, but reliable biomarkers to predict the efficiency of primary systemic therapy (PST) are still missing. Deregulation of gap junction channel forming connexins (Cx) has been implicated in carcinogenesis and tumour progression through loss of cell cycle control. In this study we correlated Cx expression and cell proliferation with disease survival and pathological response to neoadjuvant chemotherapy in breast cancers using existing classification systems. Methods The expression of Cx26, Cx32, Cx43, Cx46 and Ki67 was evaluated in 96 breast cancer patients prior to and after neoadjuvant chemotherapy using duplicate cores in tissue microarrays (TMA). Cx plaques of Results In our cohort dominated by hormone receptor (ER/PR) positive and HER2 negative cases, only the CPS-EG classification showed prognostic relevance: cases with scores 1–2 had significantly better overall survival (p=0.015) than cases with scores 3–5. Pre-chemotherapy Cx43 expression correlated positively with hormone receptor status both before and after chemotherapy and had a negative correlation with HER2 expression pre-chemotherapy. There was a positive correlation between Cx32 and HER2 expression pre-chemotherapy and between Cx32 and Ki67 expression post-chemotherapy. A negative correlation was found between post-chemotherapy Cx46 and Ki67 expression. Decreased post-chemotherapy Cx26 expression (20%) pre- and post-chemotherapy correlated with significantly better survival in the intermediate prognostic subgroups of EWGBSP TR2b (ppre-chemo=0.006; Sataloff TB (ppre-chemo=0.005; ppost-chemo=0.029) and in Miller-Payne G3 (ppre-chemo=0.002; ppost-chemo=0.012) classifications. Pre-chemotherapy, Cx46 expression was the only marker that correlated with overall survival within these subgroups. Conclusion Our results suggest that Cx46 and Cx26 expression in breast cancer may improve the assessment of pathological response and refine intermediate prognostic subgroups of residual tumour classifications used after neoadjuvant chemotherapy.
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- 2013
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35. Validation of diagnostic accuracy using digital slides in routine histopathology
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Fónyad László, Krenács Tibor, Nagy Péter, Zalatnai Attila, Csomor Judit, Sápi Zoltán, Pápay Judit, Schönléber Júlia, Diczházi Csaba, and Molnár Béla
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Retrospective study ,Surgical pathology ,Diagnostic error ,Optical microscopy ,Whole slide imaging ,Pathology ,RB1-214 - Abstract
Abstract Background Robust hardware and software tools have been developed in digital microscopy during the past years for pathologists. Reports have been advocated the reliability of digital slides in routine diagnostics. We have designed a retrospective, comparative study to evaluate the scanning properties and digital slide based diagnostic accuracy. Methods 8 pathologists reevaluated 306 randomly selected cases from our archives. The slides were scanned with a 20× Plan-Apochromat objective, using a 3-chip Hitachi camera, resulting 0.465 μm/pixel resolution. Slide management was supported with dedicated Data Base and Viewer software tools. Pathologists used their office PCs for evaluation and reached the digital slides via intranet connection. The diagnostic coherency and uncertainty related to digital slides and scanning quality were analyzed. Results Good to excellent image quality of slides was recorded in 96%. In half of the critical 61 digital slides, poor image quality was related to section folds or floatings. In 88.2% of the studied cases the digital diagnoses were in full agreement with the consensus. Out of the overall 36 incoherent cases, 7 (2.3%) were graded relevant without any recorded uncertainty by the pathologist. Excluding the non-field specific cases from each pathologist's record this ratio was 1.76% of all cases. Conclusions Our results revealed that: 1) digital slide based histopathological diagnoses can be highly coherent with those using optical microscopy; 2) the competency of pathologists is a factor more important than the quality of digital slide; 3) poor digital slide quality do not endanger patient safety as these errors are recognizable by the pathologist and further actions for correction could be taken. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1913324336747310.
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- 2012
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36. Genome-wide analysis of Ollier disease: Is it all in the genes?
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Sciot Raf, Sangiorgi Luca, Verdegaal Suzan HM, Taminiau Antonie HM, Krenács Tibor, Oosting Jan, Pansuriya Twinkal C, Hogendoorn Pancras CW, Szuhai Karoly, and Bovée Judith VMG
- Subjects
Medicine - Abstract
Abstract Background Ollier disease is a rare, non-hereditary disorder which is characterized by the presence of multiple enchondromas (ECs), benign cartilaginous neoplasms arising within the medulla of the bone, with an asymmetric distribution. The risk of malignant transformation towards central chondrosarcoma (CS) is increased up to 35%. The aetiology of Ollier disease is unknown. Methods We undertook genome-wide copy number and loss of heterozygosity (LOH) analysis using Affymetrix SNP 6.0 array on 37 tumours of 28 Ollier patients in combination with expression array using Illumina BeadArray v3.0 for 7 ECs of 6 patients. Results Non-recurrent EC specific copy number alterations were found at FAM86D, PRKG1 and ANKS1B. LOH with copy number loss of chromosome 6 was found in two ECs from two unrelated Ollier patients. One of these patients also had LOH at chromosome 3. However, no common genomic alterations were found for all ECs. Using an integration approach of SNP and expression array we identified loss as well as down regulation of POU5F1 and gain as well as up regulation of NIPBL. None of these candidate regions were affected in more than two Ollier patients suggesting these changes to be random secondary events in EC development. An increased number of genetic alterations and LOH were found in Ollier CS which mainly involves chromosomes 9p, 6q, 5q and 3p. Conclusions We present the first genome-wide analysis of the largest international series of Ollier ECs and CS reported so far and demonstrate that copy number alterations and LOH are rare and non-recurrent in Ollier ECs while secondary CS are genetically unstable. One could predict that instead small deletions, point mutations or epigenetic mechanisms play a role in the origin of ECs of Ollier disease.
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- 2011
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37. Technical note on the validation of a semi-automated image analysis software application for estrogen and progesterone receptor detection in breast cancer
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Gurzó Péter, Czuni László, Császár Gergely, Jónás Viktor, Szabó Dániel, Krenács Tibor, Kiszler Gábor, Micsik Tamás, Krecsák László, Ficsor Levente, and Molnár Béla
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Pathology ,RB1-214 - Abstract
Abstract Background The immunohistochemical detection of estrogen (ER) and progesterone (PR) receptors in breast cancer is routinely used for prognostic and predictive testing. Whole slide digitalization supported by dedicated software tools allows quantization of the image objects (e.g. cell membrane, nuclei) and an unbiased analysis of immunostaining results. Validation studies of image analysis applications for the detection of ER and PR in breast cancer specimens provided strong concordance between the pathologist's manual assessment of slides and scoring performed using different software applications. Methods The effectiveness of two connected semi-automated image analysis software (NuclearQuant v. 1.13 application for Pannoramic™ Viewer v. 1.14) for determination of ER and PR status in formalin-fixed paraffin embedded breast cancer specimens immunostained with the automated Leica Bond Max system was studied. First the detection algorithm was calibrated to the scores provided an independent assessors (pathologist), using selected areas from 38 small digital slides (created from 16 cases) containing a mean number of 195 cells. Each cell was manually marked and scored according to the Allred-system combining frequency and intensity scores. The performance of the calibrated algorithm was tested on 16 cases (14 invasive ductal carcinoma, 2 invasive lobular carcinoma) against the pathologist's manual scoring of digital slides. Results The detection was calibrated to 87 percent object detection agreement and almost perfect Total Score agreement (Cohen's kappa 0.859, quadratic weighted kappa 0.986) from slight or moderate agreement at the start of the study, using the un-calibrated algorithm. The performance of the application was tested against the pathologist's manual scoring of digital slides on 53 regions of interest of 16 ER and PR slides covering all positivity ranges, and the quadratic weighted kappa provided almost perfect agreement (κ = 0.981) among the two scoring schemes. Conclusions NuclearQuant v. 1.13 application for Pannoramic™ Viewer v. 1.14 software application proved to be a reliable image analysis tool for pathologists testing ER and PR status in breast cancer.
- Published
- 2011
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38. An antiserum reacts with an evolutionary conserved region in the e subunit of the T-cell receptor-CD3 complex in phylogenetically distant species
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Kurucz, E., Glavits, R., Krenacs, L., and Krenacs, T.
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- 1993
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39. Elevated Serum Gastrin Is Associated with Melanoma Progression: Putative Role in Increased Migration and Invasion of Melanoma Cells.
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Varga AJ, Nemeth IB, Kemeny L, Varga J, Tiszlavicz L, Kumar D, Dodd S, Simpson AWM, Buknicz T, Beynon R, Simpson D, Krenacs T, Dockray GJ, and Varro A
- Subjects
- Humans, Gastrins pharmacology, Gastrins metabolism, Proteomics, Receptors, Cholecystokinin, Receptor, Cholecystokinin B genetics, Receptor, Cholecystokinin B metabolism, Melanoma metabolism, Skin Neoplasms
- Abstract
Micro-environmental factors, including stromal and immune cells, cytokines, and circulating hormones are well recognized to determine cancer progression. Melanoma cell growth was recently shown to be suppressed by cholecystokinin/gastrin (CCK) receptor antagonists, and our preliminary data suggested that melanoma patients with Helicobacter gastritis (which is associated with elevated serum gastrin) might have an increased risk of cancer progression. Therefore, in the present study, we examined how gastrin may act on melanoma cells. In 89 melanoma patients, we found a statistically significant association between circulating gastrin concentrations and melanoma thickness and metastasis, which are known risk factors of melanoma progression and prognosis. Immunocytochemistry using a validated antibody confirmed weak to moderate CCK2R expression in both primary malignant melanoma cells and the melanoma cell lines SK-MEL-2 and G361. Furthermore, among the 219 tumors in the Skin Cutaneous Melanoma TCGA Pan-Cancer dataset showing gastrin receptor (CCKBR) expression, significantly higher CCKBR mRNA levels were linked to stage III-IV than stage I-II melanomas. In both cell lines, gastrin increased intracellular calcium levels and stimulated cell migration and invasion through mechanisms inhibited by a CCK2 receptor antagonist. Proteomic studies identified increased MMP-2 and reduced TIMP-3 levels in response to gastrin that were likely to contribute to the increased migration of both cell lines. However, the effects of gastrin on tumor cell invasion were relatively weak in the presence of the extracellular matrix. Nevertheless, dermal fibroblasts/myofibroblasts, known also to express CCK2R, increased gastrin-induced cancer cell invasion. Our data suggest that in a subset of melanoma patients, an elevated serum gastrin concentration is a risk factor for melanoma tumor progression, and that gastrin may act on both melanoma and adjacent stromal cells through CCK2 receptors to promote mechanisms of tumor migration and invasion.
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- 2023
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40. Myelofibrosis progression grading based on type I and type III collagen and fibrillin 1 expression boosted by whole slide image analysis.
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Szekely T, Wichmann B, Maros ME, Csizmadia A, Bodor C, Timar B, and Krenacs T
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- Humans, Collagen Type III, Fibrillin-1, Collagen Type I, Silver, Collagen, Extracellular Matrix Proteins, Fibrosis, Transforming Growth Factor beta, Primary Myelofibrosis diagnosis
- Abstract
Aims: The progression of primary myelofibrosis is characterised 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, in this study we demonstrate that the expression of both types I and 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 fibrillin 1 immune signals offered the best inter-rater agreements and the highest statistical correlations with silver grading of the three markers, which was robustly confirmed by automated whole slide digital image analysis using a machine learning-based algorithm. The progressive up-regulation of fibrillin 1 during myelofibrosis may result from a negative feedback loop as fibrillin microfibrils sequester TGF-β, the major promoter of fibrosis. This can also reduce TGF-β-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., (© 2022 The Authors. Histopathology published by John Wiley & Sons Ltd.)
- Published
- 2023
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41. The Effect of Dietary Methyl-Donor Intake and Other Lifestyle Factors on Cancer Patients in Hungary.
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Kiss E, Hajdu A, Forika G, Dank M, Krenacs T, and Nemeth Z
- Abstract
Background: Nutrition is essential to life and can have an indisputable influence on health and prevention of disease development including cancer. Methyl-donors are macronutrients that are important in achieving a healthy balance of metabolic processes. Their deficiency can lead to several symptoms and diseases-even to severe SARS-CoV-2 infection. We aimed to explore the potential protective effect of methyl-donor intake in breast, colorectal and pancreatic cancer by patient follow up., Methods: A food frequency questionnaire and a diet diary were used to evaluate methyl-donor intake and blood samples were taken to evaluate Il-6 and IL-8 cytokine levels as well as MTHFR (C677T) polymorphism in breast, colorectal and pancreatic cancer patients., Results: We found that levels around the recommended daily intake of B6 and B9 were effective in supporting the overall survival of breast and colorectal, and a relatively higher level of pancreatic adenocarcinoma, patients. The total intake of methyl-donors significantly and negatively correlated with smoking in pancreatic cancer, while folate as well as betaine intake significantly and positively correlated with IL-8 in colorectal cancer patients., Conclusions: Our results suggest that the appropriate intake of methyl-donor can be an adjunct of conventional oncotherapy to improve quality of life. Whether methyl-donor intake supports cancer prevention and patient survival needs further confirmation in large patient cohorts.
- Published
- 2022
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42. Correlations Between the Expression of Stromal Cell Activation Related Biomarkers, L-NGFR, Phospho-ERK1-2 and CXCL12, and Primary Myelofibrosis Progression.
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Szekely T, Krenacs T, Maros ME, Bodor C, Daubner V, Csizmadia A, Vrabely B, and Timar B
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- Biomarkers metabolism, Chemokine CXCL12 metabolism, Endothelial Cells metabolism, Humans, Nerve Tissue Proteins metabolism, Receptors, Nerve Growth Factor metabolism, Stromal Cells metabolism, Mesenchymal Stem Cells metabolism, Primary Myelofibrosis metabolism
- Abstract
In myelofibrosis, pathologically enhanced extracellular matrix production due to aberrant cytokine signalling and clonal megakaryocyte functions result( s ) in impaired hemopoiesis. Disease progression is still determined by detecting reticulin and collagen fibrosis with Gomori's silver impregnation. Here, we tested whether the expression growth related biomarkers L-NGFR/CD271, phospho-ERK1-2 and CXCL12 can be linked to the functional activation of bone marrow stromal cells during primary myelofibrosis progression. Immunoscores for all tested biomarkers showed varying strength of positive statistical correlation with the silver impregnation based myelofibrosis grades. The intimate relationship between spindle shaped stromal cells positive for all three markers and aberrant megakaryocytes was likely to reflect their functional cooperation. L-NGFR reaction was restricted to bone marrow stromal cells and revealed the whole length of their processes. Also, L-NGFR positive cells showed the most intersections, the best statistical correlations with myelofibrosis grades and the strongest interrater agreements. CXCL12 reaction highlighted stromal cell bodies and a weak extracellular staining in line with its constitutive release. Phospho-ERK1-2 reaction showed a similar pattern to CXCL12 in stromal cells with an additional nuclear staining in agreement with its role as a transcription factor. Both p -ERK1-2 and CXCL12 were also expressed at a moderate level in sinus endothelial cells. Connexin 43 gap junction communication channels, known to be required for CXCL12 release to maintain stem cell niche, were also expressed progressively in the myelofibrotic stromal network as a support of compartmental functions. Our results suggest that, diverse growth related pathways are activated in the functionally coupled bone marrow stromal cells during myelofibrosis progression. L-NGFR expression can be a useful biological marker of stromal cell activation which deserves diagnostic consideration for complementing Gomori's silver impregnation., Competing Interests: The authors declare that this study received shared facilities from 3DHISTEC Ltd. AC has been both the employee of 3DHISTECH Ltd. and a PhD student at Semmelweis University under the Co-operative PhD Program funded by the Hungarian Ministry of Innovation. TK is Member of the Editorial Board regularly reviewing manuscripts for POR. TS is a PhD student at Semmelweis University which supports PhD students publications in POR. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Szekely, Krenacs, Maros, Bodor, Daubner, Csizmadia, Vrabely and Timar.)
- Published
- 2022
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43. Methyl Donors Reduce Cell Proliferation by Diminishing Erk-Signaling and NFkB Levels, While Increasing E-Cadherin Expression in Panc-1 Cell Line.
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Kiss E, Forika G, Dank M, Krenacs T, and Nemeth Z
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- Apoptosis, Cadherins metabolism, Cell Line, Cell Line, Tumor, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p21 metabolism, Humans, NF-kappa B metabolism, Pancreatic Neoplasms, Adenocarcinoma, Pancreatic Neoplasms pathology
- Abstract
Pancreatic cancer is an aggressive malignancy with high metastatic potential. There are several lifestyle-related determinants in its etiology, including diet. Methyl donors are dietary micronutrients which play an important role in fueling vital metabolic pathways, and as bioactive food components provide methyl groups as substrates and cofactors. The imbalanced nutritional status of methyl donors has recently been linked to pathological conditions. Therefore, we hypothesized that dietary methyl donors may improve the physiology of cancer patients, including those with pancreatic cancer, and could be used for intervention therapy. In this study, methyl-donor treatment (L-methionine, choline chloride, folic acid and vitamin B12) of an aggressive pancreatic adenocarcinoma cell line (Panc-1) resulted in significantly increased p21
WAF1/Cip1 cyclin-dependent kinase inhibitor levels, along with apoptotic SubG1 fractions. At the same time, phospho-Erk1/2 levels and proliferation rate were significantly reduced. Though methyl-donor treatments also increased the pro-apoptotic protein Bak, Puma and Caspase-9, it failed to elevate cleaved Caspase-3 levels. In addition, the treatment significantly reduced the production of the pro-inflammatory cytokine IL-17a and the transcription factor NFkB. Similarly, a significant decrease in VEGF and SDF-1a levels were detected, which may indicate reduced metastatic potential. As expected, E-cadherin expression was inversely associated with these changes, showing elevated expression after methyl-donor treatment. In summary, we found that methyl donors may have the potential to reduce aggressive and proliferative phenotype of Panc-1 cells. This suggests a promising role of dietary methyl donors for complementing relevant cancer therapies, even in treatment-resistant pancreatic adenocarcinomas.- Published
- 2022
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44. Modulated Electro-Hyperthermia Supports the Effect of Gemcitabine Both in Sensitive and Resistant Pancreas Adenocarcinoma Cell Lines.
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Forika G, Kiss E, Petovari G, Danko T, Gellert AB, and Krenacs T
- Subjects
- Apoptosis drug effects, Carcinoma, Pancreatic Ductal metabolism, Carcinoma, Pancreatic Ductal pathology, Cell Adhesion drug effects, Cell Cycle Checkpoints drug effects, Cell Death drug effects, Cell Line, Tumor, Cell Survival drug effects, Combined Modality Therapy, Deoxycytidine pharmacology, Deoxycytidine therapeutic use, Heat-Shock Proteins metabolism, Humans, Neoplastic Stem Cells drug effects, Pancreatic Neoplasms metabolism, Pancreatic Neoplasms pathology, Gemcitabine, Carcinoma, Pancreatic Ductal therapy, Deoxycytidine analogs & derivatives, Drug Resistance, Neoplasm drug effects, Hyperthermia, Induced, Pancreatic Neoplasms therapy
- Abstract
The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is frequently associated to high treatment resistance. Gemcitabine (GEM) alone or in combination is the most used chemotherapy for unresecable PDACs. Here we studied whether modulated electro-hyperthermia (mEHT), a non-invasive complementary treatment, can support the effect of GEM on PDAC cells in vitro . The LD20 for the GEM-resistant Panc1 cells proved to be 200× higher than for the drug-sensitive Capan1. The mEHT alone caused significant apoptosis in Capan1 cultures as confirmed by the elevated SubG1 phase cell fraction and increased number of cleaved Caspase-3 positive cells 48 h after treatment, with an additive effect when GEM was used after hyperthermia. These were accompanied by reduced number of G1, S, and G2/M phase cells and elevated expression of the cyclin-dependent kinase inhibitor p21
waf1 protein. In GEM-resistant Panc1 cells, an initial apoptosis was detected by flow cytometry 24 h after mEHT ± GEM treatment, which however diminished by 48 h at persistent number of cleaved Caspase-3 positive tumor cells. Though GEM monotherapy reduced the number of tumor progenitor colonies in Capan1 cell line, an additive colony inhibitory effect of mEHT was observed after mEHT + GEM treatment. The heat shock induced Hsp27 and Hsp70 proteins, which are known to sensitize PDAC cells to GEM were upregulated in both Capan1 and Panc1 cells 24 h after mEHT treatment. The level of E-Cadherin, a cell adhesion molecule, increased in Capan1 cells after mEHT + GEM treatment. In conclusion, in GEM-sensitive PDAC cells mEHT treatment alone induced cell death and cell cycle inhibition and improved GEM efficiency in combination, which effects were milder and short-term up to 24 h in the GEM-resistant Panc1 cells. Our data further support the inclusion of hyperthermia, in particular of mEHT, into the traditional oncotherapy regimens of PDAC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Forika, Kiss, Petovari, Danko, Gellert and Krenacs.)- Published
- 2021
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45. Cell Cycle Regulatory Protein Expression in Multinucleated Giant Cells of Giant Cell Tumor of Bone: do They Proliferate?
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Maros ME, Balla P, Micsik T, Sapi Z, Szendroi M, Wenz H, Groden C, Forsyth RG, Picci P, and Krenacs T
- Subjects
- Adolescent, Adult, Aged, Bone Neoplasms metabolism, Female, Follow-Up Studies, Giant Cell Tumor of Bone metabolism, Humans, Male, Middle Aged, Prognosis, Retrospective Studies, Tumor Cells, Cultured, Young Adult, Biomarkers, Tumor metabolism, Bone Neoplasms pathology, Cell Cycle, Cell Cycle Proteins metabolism, Cell Proliferation, Giant Cell Tumor of Bone pathology
- Abstract
Cells of the monocyte macrophage lineage form multinucleated giant cells (GCs) by fusion, which may express some cell cycle markers. By using a comprehensive marker set, here we looked for potential replication activities in GCs, and investigated whether these have diagnostic or clinical relevance in giant cell tumor of bone (GCTB). GC rich regions of 10 primary and 10 first recurrence GCTB cases were tested using immunohistochemistry in tissue microarrays. The nuclear positivity rate of the general proliferation marker, replication licensing, G1/S-phase, S/G2/M-phase, mitosis promoter, and cyclin dependent kinase (CDK) inhibitor reactions was analyzed in GCs. Concerning Ki67, moderate SP6 reaction was seen in many GC nuclei, while B56 and Mib1 positivity was rare, but the latter could be linked to more aggressive ( p = 0.012) phenotype. Regular MCM6 reaction, as opposed to uncommon MCM2, suggested an initial DNA unwinding. Early replication course in GCs was also supported by widely detecting CDK4 and cyclin E, for the first time, and confirming cyclin D1 upregulation. However, post-G1-phase markers CDK2, cyclin A, geminin, topoisomerase-2a, aurora kinase A, and phospho-histone H3 were rare or missing. These were likely silenced by upregulated CDK inhibitors p15
INK4b , p16INK4a , p27KIP1 , p53 through its effector p21WAF1 and possibly cyclin G1, consistent with the prevention of DNA replication. In conclusion, the upregulation of known and several novel cell cycle progression markers detected here clearly verify early replication activities in GCs, which are controlled by cell cycle arresting CDK inhibitors at G1 phase, and support the functional maturation of GCs in GCTB., Competing Interests: MM reports non-related funding from the German Ministry for Education and Research (MI-I 01ZZ1801E) and non-related consultancy for Siemens Healthineers and SmartReporting GmbH. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Maros, Balla, Micsik, Sapi, Szendroi, Wenz, Groden, Forsyth, Picci and Krenacs.)- Published
- 2021
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46. Methyl-Donors Can Induce Apoptosis and Attenuate Both the Akt and the Erk1/2 Mediated Proliferation Pathways in Breast and Lung Cancer Cell Lines.
- Author
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Kiss E, Forika G, Mohacsi R, Nemeth Z, Krenacs T, and Dank M
- Subjects
- Apoptosis drug effects, Breast pathology, Breast Neoplasms metabolism, Cell Line, Tumor metabolism, Cell Proliferation drug effects, Cell Survival drug effects, Choline pharmacology, Folic Acid pharmacology, Humans, Lung pathology, Lung Neoplasms metabolism, MAP Kinase Signaling System drug effects, Methionine pharmacology, Methylation drug effects, Proto-Oncogene Proteins c-akt drug effects, Signal Transduction drug effects, Vitamin B 12 pharmacology, Apoptosis physiology, MAP Kinase Signaling System physiology, Proto-Oncogene Proteins c-akt metabolism
- Abstract
Dietary methyl-donors play important roles in physiological processes catalyzed by B vitamins as coenzymes, and are used for complementary support in oncotherapy. Our hypothesis was that methyl-donors can not only assist in tolerating cancer treatment but may also directly interfere with tumor growth and proliferation. Therefore, we investigated the proposed cancer inhibitory effects of methyl-donors (in a mixture of L-methionine, choline chloride, folic acid, and vitamin B12) on MCF7 and T47D breast cancer as well as A549 and H1650 lung cancer cell lines. Indeed, methyl-donor treatment significantly reduced the proliferation in all cell lines, possibly through the downregulation of MAPK/ERK and AKT signaling. These were accompanied by the upregulation of the pro-apoptotic Bak and Bax, both in MCF7 and H1650 cells, at reduced anti-apoptotic Mcl-1 and Bcl-2 levels in MCF7 and H1650 cells, respectively. The treatment-induced downregulation of p-p53(Thr55) was likely to contribute to protecting the nuclear localization and apoptosis inducing functions of p53. The presented features are known to improve the sensitivity of cancer therapy. Therefore, these data support the hypothesis, i.e., that methyl-donors may promote apoptotic signaling by protecting p53 functions through downregulating both the MAPK/ERK and the AKT pathways both in breast and lung adenocarcinoma cell lines. Our results can emphasize the importance and benefits of the appropriate dietary supports in cancer treatments. However, further studies are required to confirm these effects without any adverse outcome in clinical settings.
- Published
- 2021
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47. Proteomic identification of Placental Protein 1 (PP1), PP8, and PP22 and characterization of their placental expression in healthy pregnancies and in preeclampsia.
- Author
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Szabo S, Karaszi K, Romero R, Toth E, Szilagyi A, Gelencser Z, Xu Y, Balogh A, Szalai G, Hupuczi P, Hargitai B, Krenacs T, Hunyadi-Gulyas E, Darula Z, Kekesi KA, Tarca AL, Erez O, Juhasz G, Kovalszky I, Papp Z, and Than NG
- Subjects
- Adult, Chromatography, Liquid, Female, Humans, Mass Spectrometry, Pregnancy, Proteomics, Placenta metabolism, Pre-Eclampsia metabolism, Pregnancy Proteins metabolism
- Abstract
Introduction: Placental Protein 1 (PP1), PP8, and PP22 were isolated from the placenta. Herein, we aimed to identify PP1, PP8, and PP22 proteins and their placental and trophoblastic expression patterns to reveal potential involvement in pregnancy complications., Methods: We analyzed PP1, PP8, and PP22 proteins with LC-MS. We compared the placental behaviors of PP1, PP8, and PP22 to the predominantly placenta-expressed PP5/TFPI-2. Placenta-specificity scores were generated from microarray data. Trophoblasts were isolated from healthy placentas and differentiated; total RNA was isolated and subjected to microarray analysis. We assigned the placentas to the following groups: preterm controls, early-onset preeclampsia, early-onset preeclampsia with HELLP syndrome, term controls, and late-onset preeclampsia. After histopathologic examination, placentas were used for tissue microarray construction, immunostaining with anti-PP1, anti-PP5, anti-PP8, or anti-PP22 antibodies, and immunoscoring., Results: PP1, PP8, and PP22 were identified as 'nicotinate-nucleotide pyrophosphorylase', 'serpin B6', and 'protein disulfide-isomerase', respectively. Genes encoding PP1, PP8, and PP22 are not predominantly placenta-expressed, in contrast with PP5. PP1, PP8, and PP22 mRNA expression levels did not increase during trophoblast differentiation, in contrast with PP5. PP1, PP8, and PP22 immunostaining were detected primarily in trophoblasts, while PP5 expression was restricted to the syncytiotrophoblast. The PP1 immunoscore was higher in late-onset preeclampsia, while the PP5 immunoscore was higher in early-onset preeclampsia., Discussion: PP1, PP8, and PP22 are expressed primarily in trophoblasts but do not have trophoblast-specific regulation or functions. The distinct dysregulation of PP1 and PP5 expression in either late-onset or early-onset preeclampsia reflects different pathophysiological pathways in these preeclampsia subsets., (Copyright © 2020. Published by Elsevier Ltd.)
- Published
- 2020
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48. Modulated Electro-Hyperthermia-Induced Tumor Damage Mechanisms Revealed in Cancer Models.
- Author
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Krenacs T, Meggyeshazi N, Forika G, Kiss E, Hamar P, Szekely T, and Vancsik T
- Subjects
- Cell Hypoxia, Combined Modality Therapy, DNA Damage, Glycolysis, Humans, Electric Stimulation Therapy methods, Hyperthermia, Induced methods, Neoplasms therapy
- Abstract
The benefits of high-fever range hyperthermia have been utilized in medicine from the Ancient Greek culture to the present day. Amplitude-modulated electro-hyperthermia, induced by a 13.56 MHz radiofrequency current (mEHT, or Oncothermia), has been an emerging means of delivering loco-regional clinical hyperthermia as a complementary of radiation-, chemo-, and molecular targeted oncotherapy. This unique treatment exploits the metabolic shift in cancer, resulting in elevated oxidative glycolysis (Warburg effect), ion concentration, and electric conductivity. These promote the enrichment of electric fields and induce heat (controlled at 42 °C), as well as ion fluxes and disequilibrium through tumor cell membrane channels. By now, accumulating preclinical studies using in vitro and in vivo models of different cancer types have revealed details of the mechanism and molecular background of the oncoreductive effects of mEHT monotherapy. These include the induction of DNA double-strand breaks, irreversible heath and cell stress, and programmed cells death; the upregulation of molecular chaperones and damage (DAMP) signaling, which may contribute to a secondary immunogenic tumor cell death. In combination therapies, mEHT proved to be a good chemosensitizer through increasing drug uptake and tumor reductive effects, as well as a good radiosensitizer by downregulating hypoxia-related target genes. Recently, immune stimulation or intratumoral antigen-presenting dendritic cell injection have been able to extend the impact of local mEHT into a systemic "abscopal" effect. The complex network of pathways emerging from the published mEHT experiments has not been overviewed and arranged yet into a framework to reveal links between the pieces of the "puzzle". In this paper, we review the mEHT-related damage mechanisms published in tumor models, which may allow some geno-/phenotype treatment efficiency correlations to be exploited both in further research and for more rational clinical treatment planning when mEHT is involved in combination therapies.
- Published
- 2020
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49. Modulated Electro-Hyperthermia Resolves Radioresistance of Panc1 Pancreas Adenocarcinoma and Promotes DNA Damage and Apoptosis In Vitro.
- Author
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Forika G, Balogh A, Vancsik T, Zalatnai A, Petovari G, Benyo Z, and Krenacs T
- Subjects
- Apoptosis, Carcinoma, Pancreatic Ductal metabolism, Carcinoma, Pancreatic Ductal pathology, Cell Cycle Checkpoints, Cell Line, Tumor, Cell Proliferation, Combined Modality Therapy, Cyclin-Dependent Kinase Inhibitor p21 metabolism, DNA Damage, Humans, Neoplastic Stem Cells pathology, Pancreatic Neoplasms metabolism, Pancreatic Neoplasms pathology, Proto-Oncogene Proteins c-akt metabolism, Radiation Tolerance, Radiofrequency Therapy, Carcinoma, Pancreatic Ductal therapy, Hyperthermia, Induced methods, Pancreatic Neoplasms therapy
- Abstract
The poor outcome of pancreas ductal adenocarcinomas (PDAC) is frequently linked to therapy resistance. Modulated electro-hyperthermia (mEHT) generated by 13.56 MHz capacitive radiofrequency can induce direct tumor damage and promote chemo- and radiotherapy. Here, we tested the effect of mEHT either alone or in combination with radiotherapy using an in vivo model of Panc1, a KRAS and TP53 mutant, radioresistant PDAC cell line. A single mEHT shot of 60 min induced ~50% loss of viable cells and morphological signs of apoptosis including chromatin condensation, nuclear shrinkage and apoptotic bodies. Most mEHT treatment related effects exceeded those of radiotherapy, and these were further amplified after combining the two modalities. Treatment related apoptosis was confirmed by a significantly elevated number of annexin V single-positive and cleaved/activated caspase-3 positive tumor cells, as well as sub-G1-phase tumor cell fractions. mEHT and mEHT+radioterapy caused the moderate accumulation of γH2AX positive nuclear foci, indicating DNA double-strand breaks and upregulation of the cyclin dependent kinase inhibitor p21
waf1 besides the downregulation of Akt signaling. A clonogenic assay revealed that both mono- and combined treatments affected the tumor progenitor/stem cell populations too. In conclusion, mEHT treatment can contribute to tumor growth inhibition and apoptosis induction and resolve radioresistance of Panc1 PDAC cells.- Published
- 2020
- Full Text
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50. Dysregulation of Placental Functions and Immune Pathways in Complete Hydatidiform Moles.
- Author
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King JR, Wilson ML, Hetey S, Kiraly P, Matsuo K, Castaneda AV, Toth E, Krenacs T, Hupuczi P, Mhawech-Fauceglia P, Balogh A, Szilagyi A, Matko J, Papp Z, Roman LD, Cortessis VK, and Than NG
- Subjects
- Choriocarcinoma, Cytokines, DNA Methylation, Down-Regulation, Female, Gene Expression, Gestational Trophoblastic Disease, Humans, Immunohistochemistry, Pregnancy Trimester, First, Systems Biology, Up-Regulation, Hydatidiform Mole genetics, Hydatidiform Mole immunology, Placenta metabolism, Pregnancy immunology
- Abstract
Gene expression studies of molar pregnancy have been limited to a small number of candidate loci. We analyzed high-dimensional RNA and protein data to characterize molecular features of complete hydatidiform moles (CHMs) and corresponding pathologic pathways. CHMs and first trimester placentas were collected, histopathologically examined, then flash-frozen or paraffin-embedded. Frozen CHMs and control placentas were subjected to RNA-Seq, with resulting data and published placental RNA-Seq data subjected to bioinformatics analyses. Paraffin-embedded tissues from CHMs and control placentas were used for tissue microarray (TMA) construction, immunohistochemistry, and immunoscoring for galectin-14. Of the 14,022 protein-coding genes expressed in all samples, 3,729 were differentially expressed (DE) in CHMs, of which 72% were up-regulated. DE genes were enriched in placenta-specific genes (OR = 1.88, p = 0.0001), of which 79% were down-regulated, imprinted genes (OR = 2.38, p = 1.54 × 10
-6 ), and immune genes (OR = 1.82, p = 7.34 × 10-18 ), of which 73% were up-regulated. DNA methylation-related enzymes and histone demethylases were dysregulated. "Cytokine-cytokine receptor interaction" was the most impacted of 38 dysregulated pathways, among which 17 were immune-related pathways. TMA-based immunoscoring validated the lower expression of galectin-14 in CHM. In conclusion, placental functions were down-regulated, imprinted gene expression was altered, and immune pathways were activated, indicating complex dysregulation of placental developmental and immune processes in CHMs.- Published
- 2019
- Full Text
- View/download PDF
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