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305 results on '"Kendziorra, E."'

301. Functional analyses and prognostic significance of SFRP1 expression in bladder cancer.

Author

Rogler A, Kendziorra E, Giedl J, Stoehr C, Taubert H, Goebell PJ, Wullich B, Stöckle M, Lehmann J, Petsch S, Hartmann A, and Stoehr R

Subjects
Adult, Aged, Aged, 80 and over, Cell Line, Cell Line, Tumor, Cell Movement genetics, Cell Proliferation genetics, Cell Survival genetics, DNA Methylation genetics, Female, Humans, Male, Middle Aged, Prognosis, Promoter Regions, Genetic genetics, Signal Transduction genetics, Urothelium pathology, Wnt Proteins genetics, Wnt Signaling Pathway genetics, Wound Healing genetics, Gene Expression Regulation, Neoplastic genetics, Intercellular Signaling Peptides and Proteins genetics, Membrane Proteins genetics, Urinary Bladder Neoplasms genetics, Urinary Bladder Neoplasms pathology
Abstract

Purpose: We previously showed that the Wnt-signaling antagonist SFRP1 (secreted frizzled-related protein 1) is a promising marker in bladder cancer. The aim of this study was to validate the prognostic role and analyze the functional significance of SFRP1., Methods: Four bladder cancer cell lines (RT112, RT4, J82 and BFTC905) and one urothelial cell line (UROtsa) were used for functional characterization of SFRP1 expression. Effects on viability, proliferation and wound healing were investigated, and canonical Wnt-pathway activity as well as Wnt-signaling target gene expression was analyzed. Additionally, tissue micro-arrays from two different bladder tumor cohorts were evaluated for SFRP1 expression, and associations with survival and histopathological parameters were analyzed., Results: The cell lines RT112, RT4, J82 and UROtsa showed SFRP1 expression. In BFTC905, SFRP1 expression was inhibited by promoter hypermethylation. Wnt-pathway activity was absent in all cell lines and independent from SFRP1 expression. RT112 and BFTC905 were used for further functional characterization. SFRP1 overexpression resulted in decreased viability and migration in BFTC905 cells. Knockdown of SFRP1 expression in RT112 cells resulted only in marginal effects. In bladder tumors, SFRP1 expression was associated with lower tumor grade, but not with progression in patients with papillary bladder cancer. SFRP1 expressing papillary bladder cancer tumors also demonstrated a tendency to longer overall survival., Conclusions: SFRP1 is reducing malignant potential of BFTC905 cells, but not by regulation of canonical Wnt-signaling pathway. Other pathways, like non-canonical Wnt or the MAPK pathway, could be activated via SFRP1-expression loss. In bladder tumors, SFRP1 has the potential to predict outcome for a subset of papillary bladder tumors.

Published
2015
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302. Silencing of the Wnt transcription factor TCF4 sensitizes colorectal cancer cells to (chemo-) radiotherapy.

Author

Kendziorra E, Ahlborn K, Spitzner M, Rave-Fränk M, Emons G, Gaedcke J, Kramer F, Wolff HA, Becker H, Beissbarth T, Ebner R, Ghadimi BM, Pukrop T, Ried T, and Grade M

Subjects
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors genetics, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors metabolism, Blotting, Western, Cell Line, Tumor, Colorectal Neoplasms drug therapy, Colorectal Neoplasms radiotherapy, Combined Modality Therapy, Genes, Reporter, Humans, Real-Time Polymerase Chain Reaction, Signal Transduction, Transcription Factor 4, Transcription Factors genetics, Transcription Factors metabolism, beta Catenin metabolism, Antineoplastic Agents therapeutic use, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors physiology, Colorectal Neoplasms genetics, Gene Silencing, Transcription Factors physiology
Abstract

A considerable percentage of rectal cancers are resistant to standard preoperative chemoradiotherapy. Because patients with a priori-resistant tumors do not benefit from multimodal treatment, understanding and overcoming this resistance remains of utmost clinical importance. We recently reported overexpression of the Wnt transcription factor TCF4, also known as TCF7L2, in rectal cancers that were resistant to 5-fluorouracil-based chemoradiotherapy. Because Wnt signaling has not been associated with treatment response, we aimed to investigate whether TCF4 mediates chemoradioresistance. RNA interference-mediated silencing of TCF4 was employed in three colorectal cancer (CRC) cell lines, and sensitivity to (chemo-) radiotherapy was assessed using a standard colony formation assay. Silencing of TCF4 caused a significant sensitization of CRC cells to clinically relevant doses of X-rays. This effect was restricted to tumor cells with high T cell factor (TCF) reporter activity, presumably in a β-catenin-independent manner. Radiosensitization was the consequence of (i) a transcriptional deregulation of Wnt/TCF4 target genes, (ii) a silencing-induced G(2)/M phase arrest, (iii) an impaired ability to adequately halt cell cycle progression after radiation and (iv) a compromised DNA double strand break repair as assessed by γH2AX staining. Taken together, our results indicate a novel mechanism through which the Wnt transcription factor TCF4 mediates chemoradioresistance. Moreover, they suggest that TCF4 is a promising molecular target to sensitize resistant tumor cells to (chemo-) radiotherapy.

Published
2011
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303. Radio imaging of the very-high-energy gamma-ray emission region in the central engine of a radio galaxy.

Author

Acciari VA, Aliu E, Arlen T, Bautista M, Beilicke M, Benbow W, Bradbury SM, Buckley JH, Bugaev V, Butt Y, Byrum K, Cannon A, Celik O, Cesarini A, Chow YC, Ciupik L, Cogan P, Cui W, Dickherber R, Fegan SJ, Finley JP, Fortin P, Fortson L, Furniss A, Gall D, Gillanders GH, Grube J, Guenette R, Gyuk G, Hanna D, Holder J, Horan D, Hui CM, Humensky TB, Imran A, Kaaret P, Karlsson N, Kieda D, Kildea J, Konopelko A, Krawczynski H, Krennrich F, Lang MJ, LeBohec S, Maier G, McCann A, McCutcheon M, Millis J, Moriarty P, Ong RA, Otte AN, Pandel D, Perkins JS, Petry D, Pohl M, Quinn J, Ragan K, Reyes LC, Reynolds PT, Roache E, Roache E, Rose HJ, Schroedter M, Sembroski GH, Smith AW, Swordy SP, Theiling M, Toner JA, Varlotta A, Vincent S, Wakely SP, Ward JE, Weekes TC, Weinstein A, Williams DA, Wissel S, Wood M, Walker RC, Davies F, Hardee PE, Junor W, Ly C, Aharonian F, Akhperjanian AG, Anton G, Barres de Almeida U, Bazer-Bachi AR, Becherini Y, Behera B, Bernlöhr K, Bochow A, Boisson C, Bolmont J, Borrel V, Brucker J, Brun F, Brun P, Bühler R, Bulik T, Büsching I, Boutelier T, Chadwick PM, Charbonnier A, Chaves RC, Cheesebrough A, Chounet LM, Clapson AC, Coignet G, Dalton M, Daniel MK, Davids ID, Degrange B, Deil C, Dickinson HJ, Djannati-Ataï A, Domainko W, Drury LO, Dubois F, Dubus G, Dyks J, Dyrda M, Egberts K, Emmanoulopoulos D, Espigat P, Farnier C, Feinstein F, Fiasson A, Förster A, Fontaine G, Füssling M, Gabici S, Gallant YA, Gérard L, Gerbig D, Giebels B, Glicenstein JF, Glück B, Goret P, Göhring D, Hauser D, Hauser M, Heinz S, Heinzelmann G, Henri G, Hermann G, Hinton JA, Hoffmann A, Hofmann W, Holleran M, Hoppe S, Horns D, Jacholkowska A, de Jager OC, Jahn C, Jung I, Katarzyński K, Katz U, Kaufmann S, Kendziorra E, Kerschhaggl M, Khangulyan D, Khélifi B, Keogh D, Kluźniak W, Kneiske T, Komin N, Kosack K, Lamanna G, Lenain JP, Lohse T, Marandon V, Martin JM, Martineau-Huynh O, Marcowith A, Maurin D, McComb TJ, Medina MC, Moderski R, Moulin E, Naumann-Godo M, de Naurois M, Nedbal D, Nekrassov D, Nicholas B, Niemiec J, Nolan SJ, Ohm S, Olive JF, de Oña Wilhelmi E, Orford KJ, Ostrowski M, Panter M, Paz Arribas M, Pedaletti G, Pelletier G, Petrucci PO, Pita S, Pühlhofer G, Punch M, Quirrenbach A, Raubenheimer BC, Raue M, Rayner SM, Renaud M, Rieger F, Ripken J, Rob L, Rosier-Lees S, Rowell G, Rudak B, Rulten CB, Ruppel J, Sahakian V, Santangelo A, Schlickeiser R, Schöck FM, Schröder R, Schwanke U, Schwarzburg S, Schwemmer S, Shalchi A, Sikora M, Skilton JL, Sol H, Spangler D, Stawarz Ł, Steenkamp R, Stegmann C, Stinzing F, Superina G, Szostek A, Tam PH, Tavernet JP, Terrier R, Tibolla O, Tluczykont M, van Eldik C, Vasileiadis G, Venter C, Venter L, Vialle JP, Vincent P, Vivier M, Völk HJ, Volpe F, Wagner SJ, Ward M, Zdziarski AA, Zech A, Anderhub H, Antonelli LA, Antoranz P, Backes M, Baixeras C, Balestra S, Barrio JA, Bastieri D, Becerra González J, Becker JK, Bednarek W, Berger K, Bernardini E, Biland A, Bock RK, Bonnoli G, Bordas P, Borla Tridon D, Bosch-Ramon V, Bose D, Braun I, Bretz T, Britvitch I, Camara M, Carmona E, Commichau S, Contreras JL, Cortina J, Costado MT, Covino S, Curtef V, Dazzi F, De Angelis A, De Cea del Pozo E, Delgado Mendez C, De los Reyes R, De Lotto B, De Maria M, De Sabata F, Dominguez A, Dorner D, Doro M, Elsaesser D, Errando M, Ferenc D, Fernández E, Firpo R, Fonseca MV, Font L, Galante N, García López RJ, Garczarczyk M, Gaug M, Goebel F, Hadasch D, Hayashida M, Herrero A, Hildebrand D, Höhne-Mönch D, Hose J, Hsu CC, Jogler T, Kranich D, La Barbera A, Laille A, Leonardo E, Lindfors E, Lombardi S, Longo F, López M, Lorenz E, Majumdar P, Maneva G, Mankuzhiyil N, Mannheim K, Maraschi L, Mariotti M, Martínez M, Mazin D, Meucci M, Miranda JM, Mirzoyan R, Miyamoto H, Moldón J, Moles M, Moralejo A, Nieto D, Nilsson K, Ninkovic J, Oya I, Paoletti R, Paredes JM, Pasanen M, Pascoli D, Pauss F, Pegna RG, Perez-Torres MA, Persic M, Peruzzo L, Prada F, Prandini E, Puchades N, Reichardt I, Rhode W, Ribó M, Rico J, Rissi M, Robert A, Rügamer S, Saggion A, Saito TY, Salvati M, Sanchez-Conde M, Satalecka K, Scalzotto V, Scapin V, Schweizer T, Shayduk M, Shore SN, Sidro N, Sierpowska-Bartosik A, Sillanpää A, Sitarek J, Sobczynska D, Spanier F, Stamerra A, Stark LS, Takalo L, Tavecchio F, Temnikov P, Tescaro D, Teshima M, Torres DF, Turini N, Vankov H, Wagner RM, Zabalza V, Zandanel F, Zanin R, and Zapatero J

Abstract

The accretion of matter onto a massive black hole is believed to feed the relativistic plasma jets found in many active galactic nuclei (AGN). Although some AGN accelerate particles to energies exceeding 10(12) electron volts and are bright sources of very-high-energy (VHE) gamma-ray emission, it is not yet known where the VHE emission originates. Here we report on radio and VHE observations of the radio galaxy Messier 87, revealing a period of extremely strong VHE gamma-ray flares accompanied by a strong increase of the radio flux from its nucleus. These results imply that charged particles are accelerated to very high energies in the immediate vicinity of the black hole.

Published
2009
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304. Fast variability of tera-electron volt gamma rays from the radio galaxy M87.

Author

Aharonian F, Akhperjanian AG, Bazer-Bachi AR, Beilicke M, Benbow W, Berge D, Bernlöhr K, Boisson C, Bolz O, Borrel V, Braun I, Brown AM, Bühler R, Büsching I, Carrigan S, Chadwick PM, Chounet LM, Coignet G, Cornils R, Costamante L, Degrange B, Dickinson HJ, Djannati-Ataï A, Drury LO, Dubus G, Egberts K, Emmanoulopoulos D, Espigat P, Feinstein F, Ferrero E, Fiasson A, Fontaine G, Funk S, Funk S, Füssling M, Gallant YA, Giebels B, Glicenstein JF, Goret P, Hadjichristidis C, Hauser D, Hauser M, Heinzelmann G, Henri G, Hermann G, Hinton JA, Hoffmann A, Hofmann W, Holleran M, Hoppe S, Horns D, Jacholkowska A, de Jager OC, Kendziorra E, Kerschhaggl M, Khélifi B, Komin N, Konopelko A, Kosack K, Lamanna G, Latham IJ, Le Gallou R, Lemière A, Lemoine-Goumard M, Lenain JP, Lohse T, Martin JM, Martineau-Huynh O, Marcowith A, Masterson C, Maurin G, McComb TJ, Moulin E, de Naurois M, Nedbal D, Nolan SJ, Noutsos A, Orford KJ, Osborne JL, Ouchrif M, Panter M, Pelletier G, Pita S, Pühlhofer G, Punch M, Ranchon S, Raubenheimer BC, Raue M, Rayner SM, Reimer A, Ripken J, Rob L, Rolland L, Rosier-Lees S, Rowell G, Sahakian V, Santangelo A, Saugé L, Schlenker S, Schlickeiser R, Schröder R, Schwanke U, Schwarzburg S, Schwemmer S, Shalchi A, Sol H, Spangler D, Spanier F, Steenkamp R, Stegmann C, Superina G, Tam PH, Tavernet JP, Terrier R, Tluczykont M, van Eldik C, Vasileiadis G, Venter C, Vialle JP, Vincent P, Völk HJ, Wagner SJ, and Ward M

Abstract

The detection of fast variations of the tera-electron volt (TeV) (10(12) eV) gamma-ray flux, on time scales of days, from the nearby radio galaxy M87 is reported. These variations are about 10 times as fast as those observed in any other wave band and imply a very compact emission region with a dimension similar to the Schwarzschild radius of the central black hole. We thus can exclude several other sites and processes of the gamma-ray production. The observations confirm that TeV gamma rays are emitted by extragalactic sources other than blazars, where jets are not relativistically beamed toward the observer.

Published
2006
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