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2. A prognostic neural epigenetic signature in high-grade glioma

Author

Drexler, Richard, Khatri, Robin, Sauvigny, Thomas, Mohme, Malte, Maire, Cecile L., Ryba, Alice, Zghaibeh, Yahya, Dührsen, Lasse, Salviano-Silva, Amanda, Lamszus, Katrin, Westphal, Manfred, Gempt, Jens, Wefers, Annika K., Neumann, Julia E., Bode, Helena, Hausmann, Fabian, Huber, Tobias B., Bonn, Stefan, Jütten, Kerstin, Delev, Daniel, Weber, Katharina J., Harter, Patrick N., Onken, Julia, Vajkoczy, Peter, Capper, David, Wiestler, Benedikt, Weller, Michael, Snijder, Berend, Buck, Alicia, Weiss, Tobias, Göller, Pauline C., Sahm, Felix, Menstel, Joelle Aline, Zimmer, David Niklas, Keough, Michael B., Ni, Lijun, Monje, Michelle, Silverbush, Dana, Hovestadt, Volker, Suvà, Mario L., Krishna, Saritha, Hervey-Jumper, Shawn L., Schüller, Ulrich, Heiland, Dieter H., Hänzelmann, Sonja, and Ricklefs, Franz L.

Published
2024
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3. Temporal change of DNA methylation subclasses between matched newly diagnosed and recurrent glioblastoma

Author

Drexler, Richard, Khatri, Robin, Schüller, Ulrich, Eckhardt, Alicia, Ryba, Alice, Sauvigny, Thomas, Dührsen, Lasse, Mohme, Malte, Ricklefs, Tammo, Bode, Helena, Hausmann, Fabian, Huber, Tobias B., Bonn, Stefan, Voß, Hannah, Neumann, Julia E., Silverbush, Dana, Hovestadt, Volker, Suvà, Mario L., Lamszus, Katrin, Gempt, Jens, Westphal, Manfred, Heiland, Dieter H., Hänzelmann, Sonja, and Ricklefs, Franz L.

Published
2024
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7. 303 Long-Term Volumetric Analysis of Non-functioning Pituitary Microadenomas: An International, Multi-center Cohort Study

Author

Kilgallon, John, primary, Sarkar, Sauradeep, additional, Omara, Chady, additional, Sajed, Sulaiman, additional, Bakker, Leontine, additional, Biermasz, Nienke, additional, Van Furth, Wouter Ralph, additional, Verstegen, Marco, additional, Lobatto, Daniel, additional, Drexler, Richard, additional, Flitsch, Jörg, additional, Ricklefs, Franz Lennard, additional, Ryba, Alice, additional, Guaraldi, Federica, additional, Smith, Timothy R., additional, and Min, Le, additional

Published
2024
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8. Insights from a multicenter study on adult H3 K27M-mutated glioma: Surgical resection's limited influence on overall survival, ATRX as molecular prognosticator.

Author

Ryba, Alice, Özdemir, Zeynep, Nissimov, Nitzan, Hönikl, Lisa, Neidert, Nicolas, Jakobs, Martin, Kalasauskas, Darius, Krigers, Aleksandrs, Thomé, Claudius, Freyschlag, Christian F, Ringel, Florian, Unterberg, Andreas, Trong, Philip Dao, Beck, Jürgen, Heiland, Dieter Henrik, Meyer, Bernhard, Vajkoczy, Peter, Onken, Julia, Stummer, Walter, and Molina, Eric Suero

Published
2024
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9. CTNI-40. A MULTICENTER, RETROSPECTIVE ANALYSIS OF PROGNOSTIC FACTORS IN INTRACRANIAL H3 K27M-MUTANT DIFFUSE MIDLINE GLIOMA IN ADULTS

Author

Ryba, Alice, primary, Özdemir, Zeynep, additional, Nissimov, Nitzan, additional, Hönikl, Lisa, additional, Neidert, Nicolas Noel, additional, Jakobs, Martin, additional, Kalasauskas, Darius, additional, Krigers, Aleksandrs, additional, Freyschlag, Christian, additional, Ringel, Florian, additional, Trong, Philip Dao, additional, Heiland, Dieter Henrik, additional, Gempt, Jens, additional, Onken, Julia, additional, Molina, Eric Suero, additional, Westphal, Manfred, additional, Schüller, Ulrich, additional, and Mohme, Malte, additional

Published
2023
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10. IMMU-48. SOLUBLE CIRCULATING IMMUNE CHECKPOINT MOLECULES IN MALIGNANT BRAIN TUMORS

Author

Ryba, Alice, primary, Maire, Cecile, additional, Drexler, Richard, additional, Kolbe, Katharina, additional, Heinemann, Sarina, additional, Pantel, Klaus, additional, Gempt, Jens, additional, Westphal, Manfred, additional, Ricklefs, Franz L, additional, Wikman-Kocher, Harriet, additional, Riethdorf, Sabine, additional, Lamszus, Katrin, additional, and Mohme, Malte, additional

Published
2023
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11. CNSC-25. NEURAL SIGNATURE OF GBM EXHIBITS SYNAPTOGENIC AND OPC-LIKE FEATURES AND INDEPENDENTLY PREDICTS PATIENT SURVIVAL

Author

Drexler, Richard, primary, Khatri, Robin, additional, Sauvigny, Thomas, additional, Mohme, Malte, additional, Ryba, Alice, additional, Dührsen, Lasse, additional, Maire, Cecile, additional, Salviano-Silva, Amanda, additional, Lamszus, Katrin, additional, Westphal, Manfred, additional, Gempt, Jens, additional, Wefers, Annika, additional, Neumann, Julia, additional, Bode, Helena, additional, Hausmann, Fabian, additional, Huber, Tobias, additional, Bonn, Stefan, additional, Delev, Daniel, additional, Weber, Katharina, additional, Harter, Patrick, additional, Onken, Julia, additional, Vajkoczy, Peter, additional, Capper, David, additional, Wiestler, Benedikt, additional, Monje, Michelle, additional, Silverbush, Dana, additional, Hovestadt, Volker, additional, Suva, Mario, additional, Krishna, Saritha, additional, Hervey-Jumper, Shawn, additional, Schüller, Ulrich, additional, Heiland, Dieter Henrik, additional, Hänzelmann, Sonja, additional, and Ricklefs, Franz L, additional

Published
2023
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12. IMMU-01. IMMUNE PHENOTYPING OF BRAIN METASTASIS PATIENTS IDENTIFIES A DISTINCT DEPLETION AND EXHAUSTION PHENOTYPE OF THE CD4 T CELLS IN BLOOD AND BONE MARROW

Author

Reetz, Merle, primary, Ryba, Alice, additional, Heinemann, Sarina, additional, Kolbe, Katharina, additional, Stanik, Jessica, additional, Zapf, Svenja, additional, Gempt, Jens, additional, Westphal, Manfred, additional, Lamszus, Katrin, additional, Tolosa, Eva, additional, Maire, Cecile, additional, and Mohme, Malte, additional

Published
2023
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13. Epigenetic neural glioblastoma enhances synaptic integration and predicts therapeutic vulnerability

Author

Drexler, Richard, primary, Khatri, Robin, additional, Sauvigny, Thomas, additional, Mohme, Malte, additional, Maire, Cecile L., additional, Ryba, Alice, additional, Zghaibeh, Yahya, additional, Dührsen, Lasse, additional, Salviano-Silva, Amanda, additional, Lamszus, Katrin, additional, Westphal, Manfred, additional, Gempt, Jens, additional, Wefers, Annika K., additional, Neumann, Julia, additional, Bode, Helena, additional, Hausmann, Fabian, additional, Huber, Tobias B., additional, Bonn, Stefan, additional, Jütten, Kerstin, additional, Delev, Daniel, additional, Weber, Katharina J., additional, Harter, Patrick N., additional, Onken, Julia, additional, Vajkoczy, Peter, additional, Capper, David, additional, Wiestler, Benedikt, additional, Weller, Michael, additional, Snijder, Berend, additional, Buck, Alicia, additional, Weiss, Tobias, additional, Keough, Michael B., additional, Ni, Lijun, additional, Monje, Michelle, additional, Silverbush, Dana, additional, Hovestadt, Volker, additional, Suvà, Mario L., additional, Krishna, Saritha, additional, Hervey-Jumper, Shawn L., additional, Schüller, Ulrich, additional, Heiland, Dieter H., additional, Hänzelmann, Sonja, additional, and Ricklefs, Franz L., additional

Published
2023
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14. A Multicenter Study of Clinical Outcomes and Volumetric Trends in Microprolactinomas.

Author

Hong, Christopher, Kilgallon, Jack, Sarkar, Sauradeep, Omara, Chady, Sajed, Sulaiman, Bakker, Leontine, Biermasz, Nienke, van Furth, Wouter, Verstegen, Marco, Lobatto, Daniel, Drexler, Richard, Flitsch, Jorg, Ricklefs, Franz, Ryba, Alice, Guaraldi, Federica, Min, Le, and Smith, Timothy

Subjects
TREATMENT effectiveness, TUMOR growth
Abstract

This article, titled "A Multicenter Study of Clinical Outcomes and Volumetric Trends in Microprolactinomas," explores the correlation between prolactin levels, tumor volumes, and clinical outcomes in patients with pituitary microadenomas. The study found that there was no significant correlation between prolactin levels and tumor volume at diagnosis. However, patients with higher tumor volumes tended to have higher prolactin levels. The article also discusses the different treatment options for microprolactinomas, including observation, medical therapy, and surgery. It concludes that tumors with higher prolactin levels may be more likely to undergo medical treatment, while tumors with lower levels may be suitable for surveillance as they tend to shrink over time. The article suggests that an elevated baseline PRL/volume ratio may indicate tumor growth that may require intervention. [Extracted from the article]

Published
2024
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15. Epigenetic neural glioblastoma enhances synaptic integration and predicts therapeutic vulnerability

Author

Drexler, Richard, Khatri, Robin, Sauvigny, Thomas, Mohme, Malte Eberhard, Maire, Cecile, Ryba, Alice, Zghaibeh, Yahya, Duhrsen, Lasse, Salviano-Silva, Amanda, Lamszus, Katrin, Westphal, Manfred, Gempt, Jens, Wefers, Annika K., Neumann, Julia, Bode, Helena, Hausmann, Fabian, Huber, Tobias, Bonn, Stefan, Jütten, Kerstin Maria, Delev, Daniel I., Weber, Katharina J., Harter, Patrick Nikolaus, Onken, Julia Sophie, Vajkoczy, Peter, Capper, David, Wiestler, Benedikt, Weller, Michael, Snijder, Berend, Buck, Alicia, Weiss, Tobias, Keough, Michael B., Ni, Lijun, Monje, Michelle, Silverbush, Dana, Hovestadt, Volker, Suva, Mario L., Krishna, Saritha, Hervey-Jumper, Shawn, Schüller, Ulrich, Heiland, Henrik Dieter, Hänzelmann, Sonja, Ricklefs, Franz Lennard, Drexler, Richard, Khatri, Robin, Sauvigny, Thomas, Mohme, Malte Eberhard, Maire, Cecile, Ryba, Alice, Zghaibeh, Yahya, Duhrsen, Lasse, Salviano-Silva, Amanda, Lamszus, Katrin, Westphal, Manfred, Gempt, Jens, Wefers, Annika K., Neumann, Julia, Bode, Helena, Hausmann, Fabian, Huber, Tobias, Bonn, Stefan, Jütten, Kerstin Maria, Delev, Daniel I., Weber, Katharina J., Harter, Patrick Nikolaus, Onken, Julia Sophie, Vajkoczy, Peter, Capper, David, Wiestler, Benedikt, Weller, Michael, Snijder, Berend, Buck, Alicia, Weiss, Tobias, Keough, Michael B., Ni, Lijun, Monje, Michelle, Silverbush, Dana, Hovestadt, Volker, Suva, Mario L., Krishna, Saritha, Hervey-Jumper, Shawn, Schüller, Ulrich, Heiland, Henrik Dieter, Hänzelmann, Sonja, and Ricklefs, Franz Lennard

Abstract

Neural-tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is nascent. We present an epigenetically defined neural signature of glioblastoma that independently affects patients survival. We use reference signatures of neural cells to deconvolve tumor DNA and classify samples into low- or high-neural tumors. High-neural glioblastomas exhibit hypomethylated CpG sites and upregulation of genes associated with synaptic integration. Single-cell transcriptomic analysis reveals high abundance of stem cell-like malignant cells classified as oligodendrocyte precursor and neural precursor cell-like in high-neural glioblastoma. High-neural glioblastoma cells engender neuron-to-glioma synapse formation in vitro and in vivo and show an unfavorable survival after xenografting. In patients, a high-neural signature associates with decreased survival as well as increased functional connectivity and can be detected via DNA analytes and brain-derived neurotrophic factor in plasma. Our study presents an epigenetically defined malignant neural signature in high-grade gliomas that is prognostically relevant.

Published
2023

16. IMMU-20. MODULATION OF THE PERIPHERAL T CELL BIOLOGY IN GLIOBLASTOMA

Author

Mohme, Malte, primary, Rünger, Alessandra, additional, Glau, Laura, additional, Ryba, Alice, additional, Fita, Krystian, additional, Saygi, Ceren, additional, Alawi, Malik, additional, Westphal, Manfred, additional, Tolosa, Eva, additional, Maire, Cecile, additional, and Lamszus, Katrin, additional

Published
2022
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25. Preoperative treatment with dopamine agonist therapy influences surgical outcome in prolactinoma: a retrospective single-center on 159 patients.

Author

Ryba A, Gonzalez Lopez D, Rotermund R, and Flitsch J

Subjects
Humans, Male, Retrospective Studies, Female, Adult, Middle Aged, Treatment Outcome, Young Adult, Preoperative Care methods, Aged, Adolescent, Prolactin blood, Prolactinoma drug therapy, Prolactinoma surgery, Dopamine Agonists therapeutic use, Pituitary Neoplasms surgery, Pituitary Neoplasms drug therapy, Pituitary Neoplasms pathology
Abstract

Introduction: Prolactinoma account to the most common pituitary adenomas and current therapy regime constitutes of dopamine agonist therapy (DA) and surgery in selected cases [17]. Due to tumor fibrosis induced by previous DA therapy, surgical removal can be challenging though. Therefore, this study investigates how preoperative DA usage influences perioperative treatment and surgical outcome in prolactinoma and aims to ascertain whether a specific subgroup of prolactinoma patients could derive greater benefit from exclusive surgical intervention., Methods: We retrospectively analyzed n = 159 surgically treated and histologically confirmed prolactinomas in the sella region from 2013-2022 in our institution. Clinical, radiological and surgical features were analyzed. Univariate and multivariate analyses were performed., Results: Out of total of 159 prolactinoma patients, 83.6% received previous treatment with DA followed by surgery, while only 16.4% received exclusive surgery. Both groups presented similar initial tumor volumes (1.9cm 3 vs. 1.5cm 3 , p = 0.59) and equal preoperative prolactin levels (PRL) (199.7 µg/l vs. 191.0 µg/l, p = 0.44). Surgical procedures took significantly longer when patients received prior DA treatment (79 min. vs. 70 min., p = 0.0479). Six months after surgery, pretreated patients revealed significantly higher PRL compared to non-treated (107 g/l vs. 8.64 µg/, p = 0.0009). Additionally, untreated microprolactinoma presented a remission of 100%, whereas pretreated exhibited a remission rate of 88.75%., Conclusion: The current study demonstrates that prior DA treatment is associated with significantly longer surgeries, higher recurrence rates and lower rates of normalization of PRL levels after surgery, particularly in microprolactinomas and support the latest recommendations of the Pituitary Society's Consensus Statement 2023, which favors the option of surgery alone as first-line therapy for microprolactinomas., (© 2024. The Author(s).)

Published
2024
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26. Epigenetic neural glioblastoma enhances synaptic integration and predicts therapeutic vulnerability.

Author

Drexler R, Khatri R, Sauvigny T, Mohme M, Maire CL, Ryba A, Zghaibeh Y, Dührsen L, Salviano-Silva A, Lamszus K, Westphal M, Gempt J, Wefers AK, Neumann J, Bode H, Hausmann F, Huber TB, Bonn S, Jütten K, Delev D, Weber KJ, Harter PN, Onken J, Vajkoczy P, Capper D, Wiestler B, Weller M, Snijder B, Buck A, Weiss T, Keough MB, Ni L, Monje M, Silverbush D, Hovestadt V, Suvà ML, Krishna S, Hervey-Jumper SL, Schüller U, Heiland DH, Hänzelmann S, and Ricklefs FL

Abstract

Neural-tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is nascent. We present an epigenetically defined neural signature of glioblastoma that independently affects patients' survival. We use reference signatures of neural cells to deconvolve tumor DNA and classify samples into low- or high-neural tumors. High-neural glioblastomas exhibit hypomethylated CpG sites and upregulation of genes associated with synaptic integration. Single-cell transcriptomic analysis reveals high abundance of stem cell-like malignant cells classified as oligodendrocyte precursor and neural precursor cell-like in high-neural glioblastoma. High-neural glioblastoma cells engender neuron-to-glioma synapse formation in vitro and in vivo and show an unfavorable survival after xenografting. In patients, a high-neural signature associates with decreased survival as well as increased functional connectivity and can be detected via DNA analytes and brain-derived neurotrophic factor in plasma. Our study presents an epigenetically defined malignant neural signature in high-grade gliomas that is prognostically relevant., Competing Interests: Competing Interests M.L.S. is equity holder, scientific co-founder and advisory board member of Immunitas Therapeutics. M.M. holds equity in MapLight Therapeutics.

Published
2023
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