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3. CD15 is a risk predictor and a novel target in clear cell renal cell carcinoma

Author

Stenzel, Philipp Joachim, primary, Schindeldecker, Mario, additional, Seidmann, Larissa, additional, Herpel, Esther, additional, Hohenfellner, Markus, additional, Hatiboglu, Gencay, additional, Foersch, Sebastian, additional, Porubsky, Stefan, additional, Macher-Goeppinger, Stephan, additional, Roth, Wilfried, additional, and Tagscherer, Katrin Elisabeth, additional

Published
2023
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6. Abstracts of the 52nd Workshop for Pediatric Research: Frankfurt, Germany. 27-28 October 2016

Author

van den Bruck, Rhea, Weil, Patrick P., Ziegenhals, Thomas, Schreiner, Philipp, Juranek, Stefan, Gödde, Daniel, Vogel, Silvia, Schuster, Frauke, Orth, Valerie, Dörner, Johannes, Pembaur, Daniel, Röper, Meike, Störkel, Stefan, Zirngibl, Hubert, Wirth, Stefan, Jenke, Andreas C. W., Postberg, Jan, Boy, Nikolas, Heringer, Jana, Haege, Gisela, Glahn, Esther M., Hoffmann, Georg F., Garbade, Sven F., Burgard, Peter, Kölker, Stefan, Chao, Cho-Ming, Yahya, Faady, Moiseenko, Alena, Shrestha, Amit, Ahmadvand, Negah, Quantius, Jennifer, Wilhelm, Jochen, El-Agha, Elie, Zimmer, Klaus-Peter, Bellusci, Saverio, Staufner, Christian, Kölker, Stefan, Prokisch, Holger, Hoffmann, Georg F., Seeliger, Stephan, Müller, Matthias, Hippe, Andreas, Steinkraus, Henrik, Wauer, Roland, Lachmann, Burkhard, Hofmann, Sigrun R., Hedrich, Christian M., Zierk, Jakob, Arzideh, Farhad, Haeckel, Rainer, Rascher, Wolfgang, Rauh, Manfred, Metzler, Markus, Thieme, Sebastian, Bandoła, Joanna, Richter, Cornelia, Ryser, Martin, Jamal, Arshad, Ashton, Michelle P., von Bonin, Malte, Kuhn, Matthias, Hedrich, Christian M., Bonifacio, Ezio, Berner, Reinhard, Brenner, Sebastian, Hammersen, Johanna, Has, Cristina, Naumann-Bartsch, Nora, Stachel, Daniel, Kiritsi, Dimitra, Söder, Stephan, Tardieu, Mathilde, Metzler, Markus, Bruckner-Tuderman, Leena, Schneider, Holm, Bohne, F., Langer, D., Cencic, R., Eggermann, T., Zechner, U., Pelletier, J., Zepp, F., Enklaar, T., Prawitt, D., Pech, Martin, Weckmann, Markus, Heinsen, Femke-Anouska, Franke, Andre, Happle, Christine, Dittrich, Anna-Maria, Hansen, Gesine, Fuchs, Oliver, von Mutius, Erika, Oliver, Brian G., Kopp, Matthias V., Paret, Claudia, Russo, Alexandra, Theruvath, Johanna, Keller, Bettina, El Malki, Khalifa, Lehmann, Nadine, Wingerter, Arthur, Neu, Marie A., Aslihan, Gerhold-Ay, Wagner, Wolfgang, Sommer, Clemens, Pietsch, Torsten, Seidmann, Larissa, Faber, Jörg, Schreiner, Felix, Ackermann, Merle, Michalik, Michael, Rother, Eva, Bilkei-Gorzo, Andras, Racz, Ildiko, Bindila, Laura, Lutz, Beat, Dötsch, Jörg, Zimmer, Andreas, Woelfle, Joachim, Fischer, Hendrik S., Ullrich, Tim L., Bührer, Christoph, Czernik, Christoph, Schmalisch, Gerd, Stein, Robert, Hofmann, Sigrun R., Hagenbuchner, Judith, Kiechl-Kohlendorfer, Ursula, Obexer, Petra, Ausserlechner, Michael J., Loges, Niki T., Frommer, Adrien Tobias, Wallmeier, Julia, Omran, Heymut, Öner-Sieben, Soner, Gimpfl, Martina, Rozman, Jan, Irmler, Martin, Beckers, Johannes, De Angelis, Martin Hrabe, Roscher, Adelbert, Wolf, Eckhard, Ensenauer, Regina, Nemes, Karolina, Frühwald, Michael, Hasselblatt, Martin, Siebert, Reiner, Kordes, Uwe, Kool, Marcel, Wang, Haicui, Hardy, Holly, Refai, Osama, Barwick, Katy E. S., Zimmerman, Holly H., Weis, Joachim, Baple, Emma L., Crosby, Andrew H., Cirak, Sebahattin, Hellmuth, C., Uhl, O., Standl, M., Heinrich, J., Thiering, E., Koletzko, B., Blümel, Lena, Kerl, Kornelius, Picard, Daniel, Frühwald, Michael C., Liebau, Max C., Reifenberger, Guido, Borkhardt, Arndt, Hasselblatt, Martin, Remke, Marc, Tews, D., Wabitsch, M., Fischer-Posovszky, P., Westhoff, Mike-Andrew, Nonnenmacher, Lisa, Langhans, Julia, Schneele, Lukas, Trenkler, Nancy, and Debatin, Klaus-Michael

Published
2017
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7. GD2 Expression in Medulloblastoma and Neuroblastoma for Personalized Immunotherapy: A Matter of Subtype

Author

Paret, Claudia, primary, Ustjanzew, Arsenij, additional, Ersali, Sara, additional, Seidmann, Larissa, additional, Jennemann, Richard, additional, Ziegler, Nicole, additional, Malki, Khalifa El, additional, Russo, Alexandra, additional, Wingerter, Arthur, additional, Ortmüller, Franziska, additional, Bornas, Angelina, additional, Wehling, Pia Charlotte, additional, Lepădatu, Adina, additional, Ottenhausen, Malte, additional, Roth, Wilfried, additional, Sommer, Clemens, additional, Fliss, Barbara, additional, Frauenknecht, Katrin B. M., additional, Sandhoff, Roger, additional, and Faber, Jörg, additional

Published
2022
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8. A single center experience in 90 cases with nonimmune hydrops fetalis: diagnostic categories ‒ mostly aneuploidy and still often idiopathic

Author

Sturm, Julia, primary, Milera, Heiko, additional, Essmann, Stephanie, additional, Fruth, Anja, additional, Jahn-Eimermacher, Antje, additional, Selig, Mareike, additional, Winter, Jennifer, additional, Seidmann, Larissa, additional, Kampmann, Christoph, additional, Kidszun, André, additional, Mildenberger, Eva, additional, and Whybra, Catharina, additional

Published
2022
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9. Identification of an Immunogenic Medulloblastoma-Specific Fusion Involving EPC2 and GULP1

Author

Paret, Claudia, primary, Lehmann, Nadine, additional, Bender, Hannah, additional, Sprang, Maximilian, additional, Sommer, Clemens J., additional, Cana, Denis, additional, Seidmann, Larissa, additional, Wingerter, Arthur, additional, Neu, Marie A., additional, El Malki, Khalifa, additional, Alt, Francesca, additional, Roth, Lea, additional, Marini, Federico, additional, Ottenhausen, Malte, additional, Glaser, Martin, additional, Knuf, Markus, additional, Russo, Alexandra, additional, and Faber, Joerg, additional

Published
2021
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10. A familial disorder of altered DNA-methylation

Author

Caliebe, Almuth, Richter, Julia, Ammerpohl, Ole, Kanber, Deniz, Beygo, Jasmin, Bens, Susanne, Haake, Andrea, Jüttner, Eva, Korn, Bernhard, Mackay, Deborah J G, Martin-Subero, José I, Nagel, Inga, Sebire, Neil J, Seidmann, Larissa, Vater, Inga, von Kaisenberg, Constantin Sylvius, Temple, I Karen, Horsthemke, Bernhard, Buiting, Karin, and Siebert, Reiner

Published
2014
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11. In vitro testing of a funnel-tip catheter model to decrease clot migration and to evaluate clot effects in mechanical thrombectomy

Author

Payne, Emily S., primary, Krost-Reuhl, Samantha, additional, Heimann, Axel, additional, Kempski, Oliver, additional, Keric, Naureen, additional, Masomi-Bornwasser, Julia, additional, Gerber, Tiemo, additional, Seidmann, Larissa, additional, Leithner, Doris, additional, Kloeckner, Roman, additional, Hahn, Felix, additional, Müller, Lukas, additional, Auer, Timo A., additional, Kirschner, Stefanie, additional, Brockmann, Marc A., additional, and Tanyildizi, Yasemin, additional

Published
2021
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12. Exploiting Gangliosides for the Therapy of Ewing’s Sarcoma and H3K27M-Mutant Diffuse Midline Glioma

Author

Wingerter, Arthur, primary, El Malki, Khalifa, additional, Sandhoff, Roger, additional, Seidmann, Larissa, additional, Wagner, Daniel-Christoph, additional, Lehmann, Nadine, additional, Vewinger, Nadine, additional, Frauenknecht, Katrin B. M., additional, Sommer, Clemens J., additional, Traub, Frank, additional, Kindler, Thomas, additional, Russo, Alexandra, additional, Otto, Henrike, additional, Lollert, André, additional, Staatz, Gundula, additional, Roth, Lea, additional, Paret, Claudia, additional, and Faber, Jörg, additional

Published
2021
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13. Tumor Lipids of Pediatric Papillary Renal Cell Carcinoma Stimulate Unconventional T Cells

Author

Lehmann, Nadine, primary, Paret, Claudia, additional, El Malki, Khalifa, additional, Russo, Alexandra, additional, Neu, Marie Astrid, additional, Wingerter, Arthur, additional, Seidmann, Larissa, additional, Foersch, Sebastian, additional, Ziegler, Nicole, additional, Roth, Lea, additional, Backes, Nora, additional, Sandhoff, Roger, additional, and Faber, Joerg, additional

Published
2020
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16. Function and mutual interaction of BiP-, PERK-, and IRE1 alpha-dependent signalling pathways in vascular tumours

Author

Anspach, Laura, Tsaryk, Roman, Seidmann, Larissa, Unger, Ronald E., Jayasinghe, Caren, Simiantonaki, Nektaria, Kirkpatrick, C. James, Proels, Felicitas, Anspach, Laura, Tsaryk, Roman, Seidmann, Larissa, Unger, Ronald E., Jayasinghe, Caren, Simiantonaki, Nektaria, Kirkpatrick, C. James, and Proels, Felicitas

Abstract

Spontaneously regressing infantile haemangiomas and aggressive angiosarcomas are vascular tumours with excessive angiogenesis. When analysing haemangiomas and angiosarcomas immunohistochemically with respect to their chaperone profiles we found that angiosarcomas have significantly elevated protein levels of binding immunoglobulin protein (BIP) and PERK with concomitant attenuated IRE1 alpha levels, whereas haemangioma tissue exhibits the same pattern as embryonal skin tissue. We show that BiP is essential for the maintenance of VEGFR2 protein, which is expressed in the endothelium of both tumour types. When studying the effects of BiP, the IRE1 alpha/Xbp1 -, and PERK/ATF4-signalling pathways on the migration and tube-forming potential of endothelial cells, we show that downregulation of BiP, as well as inhibition of the kinase activity of IRE1 alpha, inhibit in vitro angiogenesis. Downregulation of PERK (PKR-like kinase; PKR = protein kinase R) levels promotes Xbp1 splicing in endoplasmic reticulum (ER)-stressed cells, indicating that in angiosarcoma the elevated PERK levels might result in high levels of unspliced Xbp1, which have been reported to promote cell proliferation and increase tumour malignancy. The data presented in this study revealed that in addition to BiP or PERK, the kinase domains of IRE1 alpha and Xbp1 could be potential targets for the development of novel therapeutic approaches for treating angiosarcomas and to control tumour angiogenesis. (c) 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Published
2020

17. Multiphoton microscopy in the diagnostic assessment of pediatric solid tissue in comparison to conventional histopathology : results of the first international online interobserver trial

Author

Goedeke, Jan, Schreiber, Peter, Seidmann, Larissa, Li, Geling, Birkenstock, Jérôme, Simon, Frank, König, Jochem, and Muensterer, Oliver J

Subjects
pediatric, Cancer Management and Research, pediatric tissue, 610 Medical sciences, multiphoton microscopy, 610 Medizin, interobserver trial, solid tumors, conventional histopathology, Original Research
Abstract

Purpose: Clear resection margins are paramount for good outcome in children undergoing solid tumor resections. Multiphoton microscopy (MPM) can provide high-resolution, real-time, intraoperative microscopic images of tumor tissue. Objective: This prospective international multicenter study evaluates the diagnostic accuracy, feasibility, and interobserver congruence of MPM in diagnosing solid pediatric tissue and tumors for the first time. Material and methods: Representative fresh sections from six different neonatal solid tissues (liver, lung, kidney, adrenal gland, heart muscle, testicle) and two types of typical pediatric solid tumors (neuroblastoma, rhabdomyosarcoma) with adjacent nonneoplastic tissue were imaged with MPM and then presented online with corresponding H&E stained slides of the exact same tissue region. Both image sets of each tissue type were interpreted by 38 randomly selected international attending pediatric pathologists via an online evaluation software. Results: The quality of MPM was sufficient to make the diagnosis of all normal tissue types except cardiac muscle in >94% of assessors with high interobserver congruence and 95% sensitivity. Heart muscle was interpreted as skeletal muscle in 55% of cases. Based on MPM imaging, participating pathologists diagnosed the presented pediatric neoplasms with 100% specificity, although the sensitivity reached only about 50%. Conclusion: Even without prior training, pathologists are able to diagnose normal pediatric tissues with valuable accuracy using MPM. While current MPM imaging protocols are not yet sensitive enough to reliably rule out neuroblastoma or rhabdomyosarcoma, they seem to be specific and therefore useful to confirm a diagnosis intraoperatively. We are confident that improved algorithms, specific training, and more experience with the method will make MPM a valuable future alternative to frozen section analysis. Registration: The trial was registered at www.researchregistry.com, registration number 2967., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/gvwMDx3dyN0

Published
2019
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18. IGF1R is a potential new therapeutic target for HGNET-BCOR brain tumor patients

Author

Vewinger, Nadine, Huprich, Sabrina, Seidmann, Larissa, Russo, Alexandra, Alt, Francesca, Bender, Hannah, Sommer, Clemens, Samuel, David, Lehmann, Nadine, Backes, Nora, Roth, Lea, Harter, Patrick N., Filipski, Katharina, Faber, Jörg, and Paret, Claudia

Subjects
Male, HGNET-BCOR, Medizin, 610 Medizin, Antineoplastic Agents, Article, Receptor, IGF Type 1, lcsh:Chemistry, Insulin-Like Growth Factor II, IGF1R, Proto-Oncogene Proteins, 610 Medical sciences, vinblastine, Tumor Cells, Cultured, Humans, ceritinib, Molecular Targeted Therapy, Sulfones, lcsh:QH301-705.5, Brain Neoplasms, IGF2, Receptors, Somatomedin, DNA Methylation, Neoplasms, Neuroepithelial, body regions, Gene Expression Regulation, Neoplastic, Repressor Proteins, Pyrimidines, lcsh:Biology (General), lcsh:QD1-999, Female
Abstract

(1) Background: The high-grade neuroepithelial tumor of the central nervous system with BCOR alteration (HGNET-BCOR) is a highly malignant tumor. Preclinical models and molecular targets are urgently required for this cancer. Previous data suggest a potential role of insulin-like growth factor (IGF) signaling in HGNET-BCOR. (2) Methods: The primary HGNET-BCOR cells PhKh1 were characterized by western blot, copy number variation, and methylation analysis and by electron microscopy. The expression of IGF2 and IGF1R was assessed by qRT-PCR. The effect of chemotherapeutics and IGF1R inhibitors on PhKh1 proliferation was tested. The phosphorylation of IGF1R and downstream molecules was assessed by western blot. (3) Results: Phkh1 cells showed a DNA methylation profile compatible with the DNA methylation class &ldquo, HGNET-BCOR&rdquo, and morphologic features of cellular cannibalism. IGF2 and IGF1R were highly expressed by three HGNET-BCOR tumor samples and PhKh1 cells. PhKh1 cells were particularly sensitive to vincristine, vinblastine, actinomycin D (IC50 &lt, 10 nM for all drugs), and ceritinib (IC50 = 310 nM). Ceritinib was able to abrogate the proliferation of PhKh1 cells and blocked the phosphorylation of IGF1R and AKT. (4) Conclusion: IGF1R is as an attractive target for the development of new therapy protocols for HGNET-BCOR patients, which may include ceritinib and vinblastine.

Published
2019
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19. Safety and Activity of the Combination of Ceritinib and Dasatinib in Osteosarcoma

Author

Beck, Olaf, primary, Paret, Claudia, additional, Russo, Alexandra, additional, Burhenne, Jürgen, additional, Fresnais, Margaux, additional, Steimel, Kevin, additional, Seidmann, Larissa, additional, Wagner, Daniel-Christoph, additional, Vewinger, Nadine, additional, Lehmann, Nadine, additional, Sprang, Maximilian, additional, Backes, Nora, additional, Roth, Lea, additional, Neu, Marie Astrid, additional, Wingerter, Arthur, additional, Henninger, Nicole, additional, El Malki, Khalifa, additional, Otto, Henrike, additional, Alt, Francesca, additional, Desuki, Alexander, additional, Kindler, Thomas, additional, and Faber, Joerg, additional

Published
2020
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20. Ceritinib-Induced Regression of an Insulin-Like Growth Factor-Driven Neuroepithelial Brain Tumor

Author

Russo, Alexandra, primary, Paret, Claudia, additional, Alt, Francesca, additional, Burhenne, Jürgen, additional, Fresnais, Margaux, additional, Wagner, Wolfgang, additional, Glaser, Martin, additional, Bender, Hannah, additional, Huprich, Sabrina, additional, Harter, Patrick N., additional, Filipski, Katharina, additional, Lehmann, Nadine, additional, Backes, Nora, additional, Roth, Lea, additional, Seidmann, Larissa, additional, Sommer, Clemens, additional, Brockmann, Marc A., additional, Pietsch, Torsten, additional, Neu, Marie A., additional, Wingerter, Arthur, additional, and Faber, Jörg, additional

Published
2019
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21. IGF1R Is a Potential New Therapeutic Target for HGNET-BCOR Brain Tumor Patients

Author

Vewinger, Nadine, primary, Huprich, Sabrina, additional, Seidmann, Larissa, additional, Russo, Alexandra, additional, Alt, Francesca, additional, Bender, Hannah, additional, Sommer, Clemens, additional, Samuel, David, additional, Lehmann, Nadine, additional, Backes, Nora, additional, Roth, Lea, additional, Harter, Patrick N., additional, Filipski, Katharina, additional, Faber, Jörg, additional, and Paret, Claudia, additional

Published
2019
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23. Ceritinib-induced regression of an insulin-like growth factor-driven neuroepithelial brain tumor

Author

Russo, Alexandra, Paret, Claudia, Alt, Francesca, Burhenne, Jürgen, Fresnais, Margaux, Wagner, Wolfgang, Glaser, Martin, Bender, Hannah, Huprich, Sabrina, Harter, Patrick Nikolaus, Filipski, Katharina Johanna, Lehmann, Nadine, Backes, Nora, Roth, Lea, Seidmann, Larissa, Sommer, Clemens, Brockmann, Marc Alexander, Pietsch, Torsten, Neu, Marie Astrid, Wingerter, Arthur, Faber, Jörg, Russo, Alexandra, Paret, Claudia, Alt, Francesca, Burhenne, Jürgen, Fresnais, Margaux, Wagner, Wolfgang, Glaser, Martin, Bender, Hannah, Huprich, Sabrina, Harter, Patrick Nikolaus, Filipski, Katharina Johanna, Lehmann, Nadine, Backes, Nora, Roth, Lea, Seidmann, Larissa, Sommer, Clemens, Brockmann, Marc Alexander, Pietsch, Torsten, Neu, Marie Astrid, Wingerter, Arthur, and Faber, Jörg

Abstract

The insulin-like growth factor (IGF) pathway plays an important role in several brain tumor entities. However, the lack of inhibitors crossing the blood–brain barrier remains a significant obstacle for clinical translation. Here, we targeted the IGF pathway using ceritinib, an off-target inhibitor of the IGF1 receptor (IGF1R) and insulin receptor (INSR), in a pediatric patient with an unclassified brain tumor and a notch receptor 1 (NOTCH1) germline mutation. Pathway analysis of the tumor revealed activation of the sonic hedgehog (SHH), the wingless and integrated-1 (WNT), the IGF, and the Notch pathway. The proliferation of the patient tumor cells (225ZL) was inhibited by arsenic trioxide (ATO), which is an inhibitor of the SHH pathway, by linsitinib, which is an inhibitor of IGF1R and INSR, and by ceritinib. 225ZL expressed INSR but not IGF1R at the protein level, and ceritinib blocked the phosphorylation of INSR. Our first personalized treatment included ATO, but because of side effects, we switched to ceritinib. After 46 days, we achieved a concentration of 1.70 µM of ceritinib in the plasma, and after 58 days, MRI confirmed that there was a response to the treatment. Ceritinib accumulated in the tumor at a concentration of 2.72 µM. Our data suggest ceritinib as a promising drug for the treatment of IGF-driven brain tumors.

Published
2019

25. Personalized therapy: CNS HGNET-BCOR responsiveness to arsenic trioxide combined with radiotherapy

Author

Paret, Claudia, primary, Russo, Alexandra, additional, Otto, Henrike, additional, Mayer, Arnulf, additional, Zahnreich, Sebastian, additional, Wagner, Wolfgang, additional, Samuel, David, additional, Scharnhorst, David, additional, Solomon, David A., additional, Dhall, Girish, additional, Wong, Kenneth, additional, Bender, Hannah, additional, Alt, Francesca, additional, Wingerter, Arthur, additional, Neu, Marie A., additional, Beck, Olaf, additional, Prawitt, Dirk, additional, Eder, Stefan, additional, Henninger, Nicole, additional, El Malki, Khalifa, additional, Lehmann, Nadine, additional, Backes, Nora, additional, Roth, Lea, additional, Seidmann, Larissa, additional, Sommer, Clemens, additional, Brockmann, Marc A., additional, Staatz, Gundula, additional, Schmidberger, Heinz, additional, and Faber, Jörg, additional

Published
2017
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26. TRTH-08. HIGH GRADE NEUROEPITHELIAL TUMOR OF THE CENTRAL NERVOUS SYSTEM WITH BCOR ALTERATION IS SENSITIVE TO IGF1R INHIBITION

Author

Paret, Claudia, primary, Russo, Alexandra, additional, Lehmann, Nadine, additional, Backes, Nora, additional, Roth, Lea, additional, Malki, Khalifa El, additional, Wingerter, Arthur, additional, Neu, Marie A, additional, Seidmann, Larissa, additional, Gerhold-Ay, Aslihan, additional, Wagner, Wolfgang, additional, and Faber, Jörg, additional

Published
2017
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27. Activation of the basal cell carcinoma pathway in a patient with CNS HGNET-BCOR diagnosis: consequences for personalized targeted therapy

Author

Paret, Claudia, primary, Theruvath, Johanna, additional, Russo, Alexandra, additional, Kron, Bettina, additional, Malki, Khalifa El, additional, Lehmann, Nadine, additional, Wingerter, Arthur, additional, Neu, Marie A., additional, Gerhold-Ay, Aslihan, additional, Wagner, Wolfgang, additional, Sommer, Clemens, additional, Pietsch, Torsten, additional, Seidmann, Larissa, additional, and Faber, Jörg, additional

Published
2016
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29. Epigenetic dysregulation in the developing Down syndrome cortex

Author

El Hajj, Nady, primary, Dittrich, Marcus, additional, Böck, Julia, additional, Kraus, Theo F. J., additional, Nanda, Indrajit, additional, Müller, Tobias, additional, Seidmann, Larissa, additional, Tralau, Tim, additional, Galetzka, Danuta, additional, Schneider, Eberhard, additional, and Haaf, Thomas, additional

Published
2016
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30. PNR-35CNS HGNET-BCOR - MOLECULAR CHARACTERIZATION AND IDENTIFICATION OF POSSIBLE THERAPEUTIC TARGETS OF A NEW BRAIN TUMOR ENTITY

Author

Paret, Claudia, primary, Theruvath, Johanna, additional, Russo, Alexandra, additional, Kron, Bettina, additional, ElMalki, Khalifa, additional, Lehmann, Nadine, additional, Neu, Marie, additional, Gerhold-Ay, Aslihan, additional, Wagner, Wolfgang, additional, Sommer, Clemens, additional, Seidmann, Larissa, additional, and Faber, Jörg, additional

Published
2016
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31. Next-generation sequencing reveals germline mutations in an infant with synchronous occurrence of nephro- and neuroblastoma

Author

Theruvath, Johanna, primary, Russo, Alexandra, additional, Kron, Bettina, additional, Paret, Claudia, additional, Wingerter, Arthur, additional, El Malki, Khalifa, additional, Neu, Marie A., additional, Alt, Francesca, additional, Staatz, Gundula, additional, Stein, Raimund, additional, Seidmann, Larissa, additional, Prawitt, Dirk, additional, and Faber, Jörg, additional

Published
2016
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35. RELATION OF THE PATTERN OF P16INK4A EXPRESSION TO THE GRADE OF CERVICAL INTRAEPITHELIA NEOPLASIA.

Author

Babkina, Natalia, Seidmann, Larissa, Korotkikh, Irina, Coerdt, Wiltrud, and Gerein, Valentin

Subjects
*PAPILLOMAVIRUSES, *IMMUNOHISTOCHEMISTRY, *STAINS & staining (Microscopy), *METAPLASIA, CERVIX uteri tumors
Abstract

Background: The purpose of our study was to determine whether the picture of immunohistochemical expression of p161NK4a is related to the grade of cervical intraepithelial neoplasia (CIN) and HPV status. Materials and Methods: 44 women with histologically confirmed CIN (mean age 31.1 ± 6.1): 18 patients with CIN 1, 14 with CIN 2, 12 with CIN 3 and 12 women with benign cervical lesions such as hyperkeratosis and glandular papillary metaplasia (mean age 32.4 ± 6.0) were accepted for a present study. Of 44 patients with CIN, 28 were treated with LEEP, 16 were followed with regular Pap smears and colposcopic exams. Thirty-two biopsy specimens: two with benign glandular papillary metaplasia, 13 with CIN 1, 10 with CIN 2 and 7 with CIN 3 were stained using p161NK4a mouse monoclonal antibodies (Abcam plc., Cambridge, UK) according to the instructions of the manufacturer. The staining pattern was diffuse full-thickness, diffuse basal, focal or negative. Results: lmmunohistochemical staining fur p161NK4a was focal in 3 CIN 1 (23%), 3 CIN 2 (30%) and 1 CIN 3 (14.3%). The staining pattern was diffuse basal in 4 CIN 2 (40%); diffuse full-thickness in 3 CIN 2(30%) and 6 CIN 3 185.7%). Both cases with benign metaplasia were negative for p161NK4a expression. Diffuse basal staining for p161N K4a was associated with CIN 2 (p<0.01): diffuse full-thickness staining was associated with CIN 3 (p<0.001). All samples positive for p161NK4a had histological signs of HPV infection. Conclusions: The pattern of immunohistochemical staining for p161NK4a is related to the grade of CIN and evolves from focal to diffuse full-thickness staining with CIN progression. [ABSTRACT FROM AUTHOR]

Published
2008

36. HPV INFECTION IN MOTHERS OF CHILDREN WITH RECURRENT RESPIRATORY PAPILLOMATOSIS.

Author

Babkina, Natalia, Soldatski, Iouri, Seidmann, Larissa, Borovkova, Ekaterina, Pfister, Herbert, and Gerein, Valentin

Subjects
*PAPILLOMAVIRUSES, *MOTHERS, *PEDIATRIC respiratory diseases, *GYNECOLOGY, *DNA
Abstract

HPV infection and associated lesions in mothers of patients with recurrent respiratory papillomatosis (RRP) and to investigate the relation between mother's gynecological history and the local status of her child with RRP. Materials and Methods: Twenty-five mothers of patients with RRP in a German group (mean age 38.9 ± 11.7) and 23 mothers in a Russian group (mean age 29.3 ± 7.2) were accepted for a present study and followed for the mean of 16.7 ± 0.3 and 0.86 ± 0.2 years, respectively. The work-up included a speculum exam, Pap smears, cervical biopsy and HPV typing. Children of these mothers had juvenile or adult-onset RRP; they underwent surgery and treatment with interferon α Results: Three of 23 German (13%) and nine of 23 Russian mothers (39%) had condyloma accuminatum. Three of 23 German (13%) and 14 of 20 Russian mothers (70%) had HPV signs in Pap smears. HPV DNA was detected in 5 of 14 German (35.7%) and 10 of 23 Russian mothers (43.5%). Six of 21 German (28.6%) and three of 20 Russian (15%) mothers had CIN 1 Seven German mothers (28%) had a hysterectomy. Five mothers with a hysterectomy had children with an aggressive course of juvenile-onset RRP and in three of these children squamous cell carcinoma of the lung developed 29.7 ± 6.9 years a After the onset of RRP. Conclusions: HPV DNA, cytological and histological indicators were found in the genital tract of mothers of patients with RRP. Prevalence of cytological HPV indicators and condyloma accuminatum was higher in Russian mothers; prevalence of cervical dysplasia and hysterectomy was higher in German mothers who had a longer period of observation. An adverse outcome of the disease in the child was associated with adverse gynecological history of the mother. [ABSTRACT FROM AUTHOR]

Published
2008

37. Sex-specific windows for high mRNA expression of DNA methyltransferases 1 and 3A and methyl-CpG-binding domain proteins 2 and 4 in human fetal gonads.

Author

Galetzka D, Weis E, Tralau T, Seidmann L, and Haaf T

Subjects
DNA (Cytosine-5-)-Methyltransferase 1, DNA Methyltransferase 3A, Embryonic Development, Female, Fetal Development, Gene Expression Regulation, Developmental, Gene Expression Regulation, Enzymologic, Gestational Age, Humans, Male, Pregnancy, Reverse Transcriptase Polymerase Chain Reaction, DNA (Cytosine-5-)-Methyltransferases genetics, DNA-Binding Proteins genetics, Ovary embryology, Ovary enzymology, RNA, Messenger genetics, Testis embryology, Testis enzymology, Transcription Factors genetics
Abstract

DNA methyltransferases (DNMTs) and 5-methyl-CpG-binding domain proteins (MBDs) are involved in the acquisition of parent-specific epigenetic modifications in human male and female germ cells. Reverse Northern blot analyses demonstrated sex-specific differences in mRNA expression for the maintenance DNMT1 and the de novo DNMT3A in developing testis and ovary. In fetal testis DNMT1 and DNMT3A expression peaked in mitotically arrested spermatogonia around 21 weeks gestation. In fetal ovary transcriptional upregulation of DNMT1 and DNMT3A occurred during a very brief period at 16 weeks gestation, when the oocytes proceeded through meiotic prophase. Fetal gonads showed several fold higher DNMT3A expression levels than fetal brain and adult tissues. The most abundant DNMT3A isoform in fetal testis and ovary was DNMT3A2, whereas in all other analyzed tissues DNMT3A1 predominated. The catalytically inactive DNMT3A3 isoform was also present at relatively high levels in developing gonads and may perform a regulatory function(s). In both male and female fetal gonads expression of genes for MBD2 and MBD4, which may be implicated in chromatin remodeling of methylated genomic DNA sequences, was tightly linked to DNMT expression. We propose that the sex-specific time windows for concomitant upregulation of DNMT1, DNMT3A, MBD2, and MBD4 are associated with prenatal remethylation of the human male and female germ line.

Published
2007
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