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3. Dynamic microscopic optical coherence tomography to visualize morphological and functional micro-anatomy of the airways

Author

Kohlfaerber, Tabea, Pieper, Mario, Münter, Michael, Holzhausen, Cornelia, Ahrens, Martin, Idel, Christian, Bruchhage, Karl Ludwig, Leichtle, Anke, König, Peter, Hüttmann, Gereon, and Schulz-Hildebrandt, Hinnerk

Subjects
Physics - Medical Physics, Physics - Optics
Abstract

Imaging airway tissue, optical coherence tomography (OCT) provides cross-sectional images of tissue structures, shows cilia movement and mucus secretion, but does not provide sufficient contrast to differentiate individual cells. By using fast sequences of microscopic resolution OCT (mOCT) images, OCT can picture small signal fluctuations (dynamic) OCT and overcomes the lack in contrast caused by speckle noise. In this way, OCT visualizes airway morphology on a cellular level and allows to track the dynamic behavior of immune cells, as well as mucus transport and secretion. Here, we demonstrate that mOCT, by using temporal tissue fluctuation as contrast (dynamic OCT), provides the possibility to study physiological and pathological tissue processes in vivo., Comment: 12 pages, 4 figures

Published
2022

4. DNA methylation-based classification of sinonasal tumors

Author

Jurmeister, Philipp, Glöß, Stefanie, Roller, Renée, Leitheiser, Maximilian, Schmid, Simone, Mochmann, Liliana H., Payá Capilla, Emma, Fritz, Rebecca, Dittmayer, Carsten, Friedrich, Corinna, Thieme, Anne, Keyl, Philipp, Jarosch, Armin, Schallenberg, Simon, Bläker, Hendrik, Hoffmann, Inga, Vollbrecht, Claudia, Lehmann, Annika, Hummel, Michael, Heim, Daniel, Haji, Mohamed, Harter, Patrick, Englert, Benjamin, Frank, Stephan, Hench, Jürgen, Paulus, Werner, Hasselblatt, Martin, Hartmann, Wolfgang, Dohmen, Hildegard, Keber, Ursula, Jank, Paul, Denkert, Carsten, Stadelmann, Christine, Bremmer, Felix, Richter, Annika, Wefers, Annika, Ribbat-Idel, Julika, Perner, Sven, Idel, Christian, Chiariotti, Lorenzo, Della Monica, Rosa, Marinelli, Alfredo, Schüller, Ulrich, Bockmayr, Michael, Liu, Jacklyn, Lund, Valerie J., Forster, Martin, Lechner, Matt, Lorenzo-Guerra, Sara L., Hermsen, Mario, Johann, Pascal D., Agaimy, Abbas, Seegerer, Philipp, Koch, Arend, Heppner, Frank, Pfister, Stefan M., Jones, David T. W., Sill, Martin, von Deimling, Andreas, Snuderl, Matija, Müller, Klaus-Robert, Forgó, Erna, Howitt, Brooke E., Mertins, Philipp, Klauschen, Frederick, and Capper, David

Published
2022
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8. Demographics and access to head and neck cancer care in rural areas compared to urban areas in Germany

Author

Vahl, Julius M., primary, Nagel, Gabriele, additional, Grages, Ayla, additional, Brand, Matthias, additional, von Witzleben, Adrian, additional, Sonntag, Michael, additional, Theodoraki, Marie‐Nicole, additional, Greve, Jens, additional, Aboukors, Tsima, additional, Denkinger, Michael, additional, Dallmeier, Dhayana, additional, Idel, Christian, additional, Hoffmann, Thomas K., additional, and Laban, Simon, additional

Published
2023
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12. BTK Isoforms p80 and p65 Are Expressed in Head and Neck Squamous Cell Carcinoma (HNSCC) and Involved in Tumor Progression

Author

Betzler, A, Strobel, H, Abou Kors, T, Ezić, J, Lesakova, K, Pscheid, R, Azoitei, N, Sporleder, J, Staufenberg, A, Drees, R, Weissinger, S, Greve, J, Doescher, J, Theodoraki, M, Schuler, P, Laban, S, Kibe, T, Kishida, M, Kishida, S, Idel, C, Hoffmann, T, Lavitrano, M, Grassilli, E, Brunner, C, Betzler, Annika C, Strobel, Hannah, Abou Kors, Tsima, Ezić, Jasmin, Lesakova, Kristina, Pscheid, Ronja, Azoitei, Ninel, Sporleder, Johanna, Staufenberg, Anna-Rebekka, Drees, Robert, Weissinger, Stephanie E, Greve, Jens, Doescher, Johannes, Theodoraki, Marie-Nicole, Schuler, Patrick J, Laban, Simon, Kibe, Toshiro, Kishida, Michiko, Kishida, Shosei, Idel, Christian, Hoffmann, Thomas K, Lavitrano, Marialuisa, Grassilli, Emanuela, Brunner, Cornelia, Betzler, A, Strobel, H, Abou Kors, T, Ezić, J, Lesakova, K, Pscheid, R, Azoitei, N, Sporleder, J, Staufenberg, A, Drees, R, Weissinger, S, Greve, J, Doescher, J, Theodoraki, M, Schuler, P, Laban, S, Kibe, T, Kishida, M, Kishida, S, Idel, C, Hoffmann, T, Lavitrano, M, Grassilli, E, Brunner, C, Betzler, Annika C, Strobel, Hannah, Abou Kors, Tsima, Ezić, Jasmin, Lesakova, Kristina, Pscheid, Ronja, Azoitei, Ninel, Sporleder, Johanna, Staufenberg, Anna-Rebekka, Drees, Robert, Weissinger, Stephanie E, Greve, Jens, Doescher, Johannes, Theodoraki, Marie-Nicole, Schuler, Patrick J, Laban, Simon, Kibe, Toshiro, Kishida, Michiko, Kishida, Shosei, Idel, Christian, Hoffmann, Thomas K, Lavitrano, Marialuisa, Grassilli, Emanuela, and Brunner, Cornelia

Abstract

Here, we describe the expression of Bruton’s Tyrosine Kinase (BTK) in head and neck squamous cell carcinoma (HNSCC) cell lines as well as in primary HNSCC samples. BTK is a kinase initially thought to be expressed exclusively in cells of hematopoietic origin. Apart from the 77 kDa BTK isoform expressed in immune cells, particularly in B cells, we identified the 80 kDa and 65 kDa BTK isoforms in HNSCC, recently described as oncogenic. Importantly, we revealed that both isoforms are products of the same mRNA. By investigating the mechanism regulating oncogenic BTK-p80/p65 expression in HNSSC versus healthy or benign tissues, our data suggests that the epigenetic process of methylation might be responsible for the initiation of BTK-p80/p65 expression in HNSCC. Our findings demonstrate that chemical or genetic abrogation of BTK activity leads to inhibition of tumor progression in terms of proliferation and vascularization in vitro and in vivo. These observations were associated with cell cycle arrest and increased apoptosis and autophagy. Together, these data indicate BTK-p80 and BTK-p65 as novel HNSCC-associated oncogenes. Owing to the fact that abundant BTK expression is a characteristic feature of primary and metastatic HNSCC, targeting BTK activity appears as a promising therapeutic option for HNSCC patients.

Published
2023

14. Regional outcome disparities in German head and neck cancer patients: Shorter survival in Eastern Germany.

Author

Vahl, Julius M., Nagel, Gabriele, Abou Kors, Tsima, Brand, Matthias, von Witzleben, Adrian, Sonntag, Michael, Grages, Ayla, Theodoraki, Marie N., Greve, Jens, Denkinger, Michael, Dallmeier, Dhayana, Idel, Christian, Stilgenbauer, Stephan, Hoffmann, Thomas K., and Laban, Simon

Subjects
HEAD & neck cancer, REGIONAL disparities, OVERALL survival, CANCER patients, MULTIVARIATE analysis, SEX distribution
Abstract

Introduction: Demographics are important prognostic factors in malignant diseases. A nationwide analysis concerning the prognostic impact of demographics in head and neck cancer (HNC) patients (HNCP) has not been performed previously. Methods: A retrospective analysis of data from the Center for Cancer Registry Data (ZfKD) and the Federal Statistical Office (Destatis) between 2002 and 2017 was performed. A total of 212′920 HNCP were included. Incidence, tumor stage, age development, sex distribution, age‐, residence‐, and diagnosis‐time‐specific survival were examined. Results: Mean age of HNCP increased more rapidly than in the general population (slope coefficient: 0.29 vs. 0.20; p < 0.0001). Higher age and male sex were associated with a worse prognosis. Whereas overall survival (OS) increased from the early to the later observation period for HNCP <70 years, no OS improvement for HNCP >70 years was found. Furthermore, an OS disadvantage was observed for East Germany compared to West Germany (median 47 vs. 60 months; p < 0.0001). This disparity was associated with a disproportionately high ratio of men in East Germany (men/women: 4.4 vs. 3.1; p < 0.0001) and a lower mean age (61 vs. 63 years; p < 0.0001). In addition to stage, age and sex, residence in East Germany were confirmed as an independent factor for OS in a multivariate analysis. Conclusion: Finally, three decades after the German reunion, a survival disadvantage for patients in East Germany still exists. This discrepancy may be a result of socioeconomic disparities. [ABSTRACT FROM AUTHOR]

Published
2023
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16. BTK Isoforms p80 and p65 Are Expressed in Head and Neck Squamous Cell Carcinoma (HNSCC) and Involved in Tumor Progression

Author

Betzler, Annika C., primary, Strobel, Hannah, additional, Abou Kors, Tsima, additional, Ezić, Jasmin, additional, Lesakova, Kristina, additional, Pscheid, Ronja, additional, Azoitei, Ninel, additional, Sporleder, Johanna, additional, Staufenberg, Anna-Rebekka, additional, Drees, Robert, additional, Weissinger, Stephanie E., additional, Greve, Jens, additional, Doescher, Johannes, additional, Theodoraki, Marie-Nicole, additional, Schuler, Patrick J., additional, Laban, Simon, additional, Kibe, Toshiro, additional, Kishida, Michiko, additional, Kishida, Shosei, additional, Idel, Christian, additional, Hoffmann, Thomas K., additional, Lavitrano, Marialuisa, additional, Grassilli, Emanuela, additional, and Brunner, Cornelia, additional

Published
2023
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18. A New Prognostic Instrument for Predicting the Probability of Completion of Cisplatin during Chemoradiation for Head and Neck Cancer.

Author

Rades, Dirk, Zwaan, Inga, Idel, Christian, Pries, Ralph, Bruchhage, Karl L., Hakim, Samer G., Yu, Nathan Y., and Soror, Tamer

Subjects
HEAD & neck cancer, HUMAN papillomavirus, CISPLATIN, KARNOFSKY Performance Status, CHEMORADIOTHERAPY, TUMOR classification
Abstract

Many head and neck cancer patients assigned to definitive or adjuvant chemoradiation treatment do not complete the concurrent cisplatin dose. We determined corresponding risk factors and developed a prognostic instrument to help identify these patients. Ten pre-treatment characteristics were retrospectively analyzed in 154 patients with head and neck cancer who were treated via chemoradiation with cisplatin. These pre-treatment characteristics included age, sex, Karnofsky performance score, tumor site, primary tumor stage, nodal stage, histologic grade, upfront surgery, human papilloma virus status, and history of smoking. The characteristics significantly associated with the completion of cisplatin-based treatment, the receipt of ≥80% cisplatin, or showing a strong trend of association after multivariate analyses were used for the prognostic instrument. For each characteristic, 0 points were assigned for worse outcomes, and 1 point was assigned for better outcomes. Patients' scores were calculated by adding these points. Age ≤ 60 years and a Karnofsky performance score of 90–100 were significantly associated with both endpoints after multivariate analysis, and male gender showed a trend for association with the receipt of ≥80% cisplatin. Patient scores were 0, 1, 2, and 3 points. The corresponding rates of completion of cisplatin-based treatment were 14%, 41%, 62%, and 72%, respectively (p = 0.004). The rates of receipt of ≥80% cisplatin were 29%, 54%, 72%, and 94%, respectively (p < 0.001). This new prognostic instrument helps to predict whether head and neck cancer patients scheduled for chemoradiation will receive cisplatin as planned. [ABSTRACT FROM AUTHOR]

Published
2023
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19. First Results of Concurrent Chemoradiation with Two Courses of 5 × 25 mg/m 2 Cisplatin for Locally Advanced Head and Neck Cancer.

Author

Zwaan, Inga, Soror, Tamer, Idel, Christian, Pries, Ralph, Bruchhage, Karl L., Hakim, Samer G., Yu, Nathan Y., and Rades, Dirk

Subjects
HEAD & neck cancer, CHEMORADIOTHERAPY, SQUAMOUS cell carcinoma
Abstract

Many patients with squamous cell carcinoma of the head and neck (SCCHN) receive cisplatin-based chemoradiation. Cisplatin 100 mg/m2 every three weeks is toxic and alternative cisplatin regimens are desired. Two courses of 20 mg/m2/day 1–5 (cumulative 200 mg/m2) were shown to be similarly effective and better tolerated than 100 mg/m2 every three weeks. Previous studies suggested that cumulative doses >200 mg/m2 may further improve outcomes. In this study, 10 patients (group A) receiving two courses of 25 mg/m2/day 1–5 (cumulative 250 mg/m2) in 2022 were retrospectively matched and compared to 98 patients (group B) receiving two courses of 20 mg/m2/day 1–5 or 25 mg/m2/day 1–4 (cumulative 200 mg/m2). Follow-up was limited to 12 months to avoid bias. Group A achieved non-significantly better 12-month loco-regional control (100% vs. 83%, p = 0.27) and metastases-free survival (100% vs. 88%, p = 0.38), and similar overall survival (89% vs. 88%, p = 0.90). No significant differences were found regarding toxicities, completion of chemotherapy, and interruption of radiotherapy. Given the limitations of this study, chemoradiation with two courses of 25 mg/m2/day 1–5 appears an option for carefully selected patients as a personalized treatment approach. Longer follow-up and a larger sample size are needed to properly define its role. [ABSTRACT FROM AUTHOR]

Published
2023
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23. Dynamic microscopic optical coherence tomography to visualize the morphological and functional micro-anatomy of the airways

Author

Kohlfaerber, Tabea, primary, Pieper, Mario, additional, Münter, Michael, additional, Holzhausen, Cornelia, additional, Ahrens, Martin, additional, Idel, Christian, additional, Bruchhage, Karl-Ludwig, additional, Leichtle, Anke, additional, König, Peter, additional, Hüttmann, Gereon, additional, and Schulz-Hildebrandt, Hinnerk, additional

Published
2022
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26. Therapy-Related Transcriptional Subtypes in Matched Primary and Recurrent Head and Neck Cancer

Author

Weber, Peter, primary, Künstner, Axel, additional, Hess, Julia, additional, Unger, Kristian, additional, Marschner, Sebastian, additional, Idel, Christian, additional, Ribbat-Idel, Julika, additional, Baumeister, Philipp, additional, Gires, Olivier, additional, Walz, Christoph, additional, Rietzler, Sibylle, additional, Valeanu, Laura, additional, Herkommer, Timm, additional, Kreutzer, Lisa, additional, Klymenko, Olena, additional, Drexler, Guido, additional, Kirchner, Thomas, additional, Maihöfer, Cornelius, additional, Ganswindt, Ute, additional, Walch, Axel, additional, Sterr, Michael, additional, Lickert, Heiko, additional, Canis, Martin, additional, Rades, Dirk, additional, Perner, Sven, additional, Berriel Diaz, Mauricio, additional, Herzig, Stefan, additional, Lauber, Kirsten, additional, Wollenberg, Barbara, additional, Busch, Hauke, additional, Belka, Claus, additional, and Zitzelsberger, Horst, additional

Published
2022
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28. Spatial Distribution of Immune Cells in Head and Neck Squamous Cell Carcinomas

Author

Idel, Christian, primary, Ribbat-Idel, Julika, additional, Klapper, Luise, additional, Krupar, Rosemarie, additional, Bruchhage, Karl-Ludwig, additional, Dreyer, Eva, additional, Rades, Dirk, additional, Polasky, Christina, additional, Offermann, Anne, additional, Kirfel, Jutta, additional, Perner, Sven, additional, and Wollenberg, Barbara, additional

Published
2021
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29. Delta-Like Protein 3 Expression in Paired Chemonaive and Chemorelapsed Small Cell Lung Cancer Samples

Author

Kuempers, Christiane, primary, Jagomast, Tobias, additional, Krupar, Rosemarie, additional, Paulsen, Finn-Ole, additional, Heidel, Carsten, additional, Ribbat-Idel, Julika, additional, Idel, Christian, additional, Märkl, Bruno, additional, Anlauf, Martin, additional, Berezowska, Sabina, additional, Tiemann, Markus, additional, Bösmüller, Hans, additional, Fend, Falko, additional, Kalsdorf, Barbara, additional, Bohnet, Sabine, additional, Dreyer, Eva, additional, Sailer, Verena, additional, Kirfel, Jutta, additional, and Perner, Sven, additional

Published
2021
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30. Recurrent HNSCC Harbor an Immunosuppressive Tumor Immune Microenvironment Suggesting Successful Tumor Immune Evasion

Author

Watermann, Christian, Pasternack, Helen, Idel, Christian, Ribbat-Idel, Julika, Braegelmann, Johannes, Kuppler, Patrick, Offermann, Anne, Jonigk, Danny, Kuehnel, Mark, Schroeck, Andreas, Dreyer, Eva, Rosero, Christian, Nathansen, Jacqueline, Dubrovska, Anna, Tharun, Lars, Kirfel, Jutta, Wollenberg, Barbara, Perner, Sven, Krupar, Rosemarie, Watermann, Christian, Pasternack, Helen, Idel, Christian, Ribbat-Idel, Julika, Braegelmann, Johannes, Kuppler, Patrick, Offermann, Anne, Jonigk, Danny, Kuehnel, Mark, Schroeck, Andreas, Dreyer, Eva, Rosero, Christian, Nathansen, Jacqueline, Dubrovska, Anna, Tharun, Lars, Kirfel, Jutta, Wollenberg, Barbara, Perner, Sven, and Krupar, Rosemarie

Abstract

Purpose: Recurrent tumors (RT) of head and neck squamous cell carcinoma (HNSCC) occur in up to 60%, with poor therapeutic response and detrimental prognosis. We hypothesized that HNSCC RTs successfully evade antitumor immune response and aimed to reveal tumor immune microenvironment (TIME) changes of primary tumors (PT) and corresponding RTs. Experimental Design: Tumor-infiltrating leukocytes (TIL) of 300 PTs and 108 RTs from two large independent and clinically well-characterized HNSCC cohorts [discovery cohort (DC), validation cohort (VD)] were compared by IHC. mRNA expression analysis of 730 immune-related genes was performed for 18 PTs and RTs after adjuvant chemoradiotherapy (CRT). The effect of chemotherapy and radiation resistance was assessed with an in vitro spheroid/immunocyte coculture model. Results: TIME analysis revealed overall decrease of TILs with significant loss of CD8(+) T cells (DC P = 0.045/VC P < 0.0001) and B lymphocytes (DC P = 0.036/VC P < 0.0001) in RTs compared with PTs in both cohorts. Decrease predominantly occurred in RTs after CRT. Gene expression analysis confirmed loss of TILs (P = 0.0004) and B lymphocytes (P < 0.0001) and showed relative increase of neutrophils (P = 0.018), macrophages (P < 0.0001), dendritic cells (P = 0.0002), and mast cells (P = 0.0057) as well as lower overall expression of immune-related genes (P = 0.018) in RTs after CRT. Genes involved in B-lymphocyte functions and number of tertiary lymphoid structures showed the strongest decrease. SPP1 and MAPK1 were upregulated in vivo and in vitro, indicating their potential suitability as therapeutic targets in CRT resistance. Conclusions: HNSCC RTs have an immunosuppressive TIME, which is particularly apparent after adjuvant CRT and might substantially contribute to poor therapeutic response and prognosis.

Published
2021

33. Performance of Different Diagnostic PD-L1 Clones in Head and Neck Squamous Cell Carcinoma

Author

Ribbat-Idel, Julika, primary, Dressler, Franz F., additional, Krupar, Rosemarie, additional, Watermann, Christian, additional, Paulsen, Finn-Ole, additional, Kuppler, Patrick, additional, Klapper, Luise, additional, Offermann, Anne, additional, Wollenberg, Barbara, additional, Rades, Dirk, additional, Laban, Simon, additional, Reischl, Markus, additional, Bruchhage, Karl-Ludwig, additional, Idel, Christian, additional, and Perner, Sven, additional

Published
2021
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34. Increased Abundances of CD16 + Non-Classical Monocytes Accompany with Elevated Monocytic PD-L1 and CD4 + T Cell Disturbances in Oropharyngeal Cancer.

Author

Idel, Christian, Polasky, Christina, Ribbat-Idel, Julika, Loyal, Kristin, Perner, Sven, Rades, Dirk, Bruchhage, Karl-Ludwig, and Pries, Ralph

Subjects
OROPHARYNGEAL cancer, T cells, PROGRAMMED death-ligand 1, MONOCYTES, PSYCHONEUROIMMUNOLOGY, PAPILLOMAVIRUSES, HEAD & neck cancer, CANCER cell differentiation
Abstract

Background: Patients with human papilloma virus (HPV)-related oropharyngeal cancer have a better prognosis than nonvirally associated patients, most likely because of better immune responses. Increased infiltration of T lymphocytes into the oropharyngeal tumor tissue has been observed, but the dynamics of circulating lymphocytes and monocytes are not fully understood. The aim of this study was to understand the population dynamics of circulating monocyte subsets in oropharyngeal cancer (OPC) patients with regard to the clinicopathological parameters and accompanying immunological consequences in view of the CD4/CD8 T cell subset composition, and the expression of checkpoint pathway proteins programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1). Materials and Methods: The abundance of circulating monocyte subsets and peripheral blood CD4/CD8 T cells of oropharyngeal cancer patients and their PD-L1 and PD-1 expression levels were analyzed by flow cytometry. Results: The studied oropharyngeal cancer patients revealed heterogeneous individual redistributions of CD14++CD16− (classical), CD14++CD16+ (intermediate), and CD14dim+CD16+ (nonclassical) monocyte subsets compared with healthy donors. These differences in monocyte subset alterations were independent in patients with TNM or HPV status but entailed further immunological consequences. Increased percentages of nonclassical monocytes significantly correlated with increased levels of monocytic PD-L1 expression. We observed significantly decreased levels of CD4+ effector T cells, which were accompanied by increased CD4+ effector memory T cells in OPC patients compared with healthy donors, each having a stronger effect in patients with decreased levels of classical monocytes. Conclusion: We conclude that oropharyngeal cancer, as a malignancy from a lymphoid-tissue-rich anatomical region, has a strong systemic impact on the differentiation and regulation of circulating innate and adaptive immune cells. Further comprehensive investigations are required for the possible future usability of the described immunological alterations as bioliquid parameters for prognosis or therapy response prediction. [ABSTRACT FROM AUTHOR]

Published
2022
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35. Increasing Mean Age of Head and Neck Cancer Patients at a German Tertiary Referral Center

Author

Vahl, Julius M., primary, Wigand, Marlene C., additional, Denkinger, Michael, additional, Dallmeier, Dhayana, additional, Steiger, Chiara, additional, Welke, Claudia, additional, Kuhn, Peter, additional, Idel, Christian, additional, Doescher, Johannes, additional, von Witzleben, Adrian, additional, Brand, Matthias, additional, Marienfeld, Ralf, additional, Möller, Peter, additional, Theodoraki, Marie-Nicole, additional, Greve, Jens, additional, Schuler, Patrick J., additional, Brunner, Cornelia, additional, Hoffmann, Thomas K., additional, and Laban, Simon, additional

Published
2021
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37. Immunologic “Cold” Squamous Cell Carcinomas of the Head and Neck Are Associated With an Unfavorable Prognosis

Author

Ribbat-Idel, Julika, primary, Perner, Sven, additional, Kuppler, Patrick, additional, Klapper, Luise, additional, Krupar, Rosemarie, additional, Watermann, Christian, additional, Paulsen, Finn-Ole, additional, Offermann, Anne, additional, Bruchhage, Karl-Ludwig, additional, Wollenberg, Barbara, additional, and Idel, Christian, additional

Published
2021
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38. Recurrent HNSCC Harbor an Immunosuppressive Tumor Immune Microenvironment Suggesting Successful Tumor Immune Evasion

Author

Watermann, Christian, primary, Pasternack, Helen, additional, Idel, Christian, additional, Ribbat-Idel, Julika, additional, Brägelmann, Johannes, additional, Kuppler, Patrick, additional, Offermann, Anne, additional, Jonigk, Danny, additional, Kühnel, Mark Philipp, additional, Schröck, Andreas, additional, Dreyer, Eva, additional, Rosero, Christian, additional, Nathansen, Jacqueline, additional, Dubrovska, Anna, additional, Tharun, Lars, additional, Kirfel, Jutta, additional, Wollenberg, Barbara, additional, Perner, Sven, additional, and Krupar, Rosemarie, additional

Published
2021
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39. Tumour ischaemia by interferon- resembles physiological blood vessel regression

Author

Kammertoens, Thomas, Friese, Christian, Arina, Ainhoa, Idel, Christian, Briesemeister, Dana, Rothe, Michael, Ivanov, Andranik, Szymborska, Anna, Patone, Giannino, Kunz, Severine, Sommermeyer, Daniel, Engels, Boris, Leisegang, Matthias, Textor, Ana, Joerg Fehling, Hans, Fruttiger, Marcus, Lohoff, Michael, Herrmann, Andreas, Yu, Hua, Weichselbaum, Ralph, Uckert, Wolfgang, Hbner, Norbert, Gerhardt, Holger, Beule, Dieter, Schreiber, Hans, and Blankenstein, Thomas

Subjects
Tumors -- Physiological aspects, Interferon -- Physiological aspects, Ischemia -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Thomas Kammertoens [1, 2]; Christian Friese [1, 2]; Ainhoa Arina [3]; Christian Idel [4]; Dana Briesemeister [1, 2]; Michael Rothe [1, 2]; Andranik Ivanov [5, 6]; Anna Szymborska [2]; [...]

Published
2017
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40. CDK19 as a Potential HPV-Independent Biomarker for Recurrent Disease in HNSCC

Author

Paulsen, Finn-Ole, Idel, Christian, Ribbat-Idel, Julika, Kuppler, Patrick, Klapper, Luise, Rades, Dirk, Bruchhage, Karl-Ludwig, Wollenberg, Barbara, Braegelmann, Johannes, Perner, Sven, Offermann, Anne, Paulsen, Finn-Ole, Idel, Christian, Ribbat-Idel, Julika, Kuppler, Patrick, Klapper, Luise, Rades, Dirk, Bruchhage, Karl-Ludwig, Wollenberg, Barbara, Braegelmann, Johannes, Perner, Sven, and Offermann, Anne

Abstract

The Mediator complex is a central integrator of transcription and a hub for the regulation of gene expression. Cyclin dependent kinase (CDK) 19 and its paralog CDK8 are part of its kinase domain and contribute to cancer progression in different cancer entities. STAT1 is an important immune modulator and a downstream substrate of CDK8/CDK19 mediated phosphorylation. So far, little is known about CDK19's role in head and neck squamous cell carcinoma (HNSCC) progression, its link to STAT1 activity, and related immune modulation. Immunohistochemistry for CDK19, activated pSTAT1, and PD-L1, known to be affected by STAT1, was conducted on samples of 130 primary tumors, 71 local recurrences, 32 lymph node metastases, and 25 distant metastases of HNSCC. Compared to primary tumors, CDK19 is overexpressed in local recurrences and distant metastases as well as in primary tumors that developed local recurrence after initial therapy. Patients with high-CDK19-expressing primary tumors have a significantly shorter disease-free survival. CDK19 expression correlates with pSTAT1 expression in primary tumors associated with recurrent disease, local recurrent tumors, lymph node metastases, and distant metastases. pSTAT1 expression correlates with PD-L1 expression in recurrent tumors. Our findings identify CDK19 as a potential biomarker in HNSCC to predict recurrent disease and support recent developments to target CDK19 and its paralog CDK8 in advanced cancer.

Published
2020

41. NR2F6 as a Prognostic Biomarker in HNSCC

Author

Klapper, Luise, primary, Ribbat-Idel, Julika, additional, Kuppler, Patrick, additional, Paulsen, Finn-Ole, additional, Bruchhage, Karl-Ludwig, additional, Rades, Dirk, additional, Offermann, Anne, additional, Kirfel, Jutta, additional, Wollenberg, Barbara, additional, Idel, Christian, additional, and Perner, Sven, additional

Published
2020
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43. Cooperation of genes in HPV16 E6/E7-dependent cervicovaginal carcinogenesis trackable by endoscopy and independent of exogenous estrogens or carcinogens

Author

Böttinger, Paula, primary, Schreiber, Karin, additional, Hyjek, Elizabeth, additional, Krausz, Thomas, additional, Spiotto, Michael T, additional, Steiner, Madeline, additional, Idel, Christian, additional, Booras, Heather, additional, Beck-Engeser, Gabriele, additional, Riederer, Jessie, additional, Willimsky, Gerald, additional, Wolf, Steven P, additional, Karrison, Theodore, additional, Jensen, Elizabeth, additional, Weichselbaum, Ralph R, additional, Nakamura, Yusuke, additional, Yew, Poh Yin, additional, Lambert, Paul F, additional, Kurita, Takeshi, additional, Kiyotani, Kazuma, additional, Leisegang, Matthias, additional, and Schreiber, Hans, additional

Published
2020
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44. EVI1 as a Marker for Lymph Node Metastasis in HNSCC

Author

Idel, Christian, primary, Ribbat-Idel, Julika, additional, Kuppler, Patrick, additional, Krupar, Rosemarie, additional, Offermann, Anne, additional, Vogel, Wenzel, additional, Rades, Dirk, additional, Kirfel, Jutta, additional, Wollenberg, Barbara, additional, and Perner, Sven, additional

Published
2020
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48. Immunometabolic Determinants of Chemoradiotherapy Response and Survival in Head and Neck Squamous Cell Carcinoma

Author

Krupar, Rosemarie, primary, Hautmann, Matthias G., additional, Pathak, Ravi R., additional, Varier, Indu, additional, McLaren, Cassandra, additional, Gaag, Doris, additional, Hellerbrand, Claus, additional, Evert, Matthias, additional, Laban, Simon, additional, Idel, Christian, additional, Sandulache, Vlad, additional, Perner, Sven, additional, Bosserhoff, Anja K., additional, and Sikora, Andrew G., additional

Published
2018
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49. Tumour ischaemia by interferon-γ resembles physiological blood vessel regression

Author

Kammertoens, Thomas, primary, Friese, Christian, additional, Arina, Ainhoa, additional, Idel, Christian, additional, Briesemeister, Dana, additional, Rothe, Michael, additional, Ivanov, Andranik, additional, Szymborska, Anna, additional, Patone, Giannino, additional, Kunz, Severine, additional, Sommermeyer, Daniel, additional, Engels, Boris, additional, Leisegang, Matthias, additional, Textor, Ana, additional, Fehling, Hans Joerg, additional, Fruttiger, Marcus, additional, Lohoff, Michael, additional, Herrmann, Andreas, additional, Yu, Hua, additional, Weichselbaum, Ralph, additional, Uckert, Wolfgang, additional, Hübner, Norbert, additional, Gerhardt, Holger, additional, Beule, Dieter, additional, Schreiber, Hans, additional, and Blankenstein, Thomas, additional

Published
2017
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50. Eradication of Large Solid Tumors by Gene Therapy with a T-Cell Receptor Targeting a Single Cancer-Specific Point Mutation

Author

Leisegang, Matthias, primary, Engels, Boris, additional, Schreiber, Karin, additional, Yew, Poh Yin, additional, Kiyotani, Kazuma, additional, Idel, Christian, additional, Arina, Ainhoa, additional, Duraiswamy, Jaikumar, additional, Weichselbaum, Ralph R., additional, Uckert, Wolfgang, additional, Nakamura, Yusuke, additional, and Schreiber, Hans, additional

Published
2016
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