Article
Oncology
Man Xu, Ming Sun, Xiyuan Zhang, Rosa Nguyen, Haiyan Lei, Jack F. Shern, Carol J. Thiele, Zhihui Liu
Summary: This study reveals a core transcriptional regulatory network in noradrenergic neuroblastoma, involving transcription factors PHOX2B, HAND2, GATA3, and MYCN. MYCN can bind to enhancers as well as promoters when aberrantly upregulated. HAND2 regulates chromatin accessibility and assists MYCN in enhancer invasion. Targeting both MYCN and the core regulatory factors can effectively suppress tumor growth.
Article
Multidisciplinary Sciences
Zsuzsanna Nagy, Janith A. Seneviratne, Maxwell Kanikevich, William Chang, Chelsea Mayoh, Pooja Venkat, Yanhua Du, Cizhong Jiang, Alice Salib, Jessica Koach, Daniel R. Carter, Rituparna Mittra, Tao Liu, Michael W. Parker, Belamy B. Cheung, Glenn M. Marshall
Summary: The gain of 17q21-ter in neuroblastoma leads to overexpression of ALYREF, which forms a complex with MYCN and regulates MYCN stability via the deubiquitinating enzyme, USP3.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Johanna A. Seier, Julia Reinhardt, Kritika Saraf, Susanna S. Ng, Julian P. Layer, Dillon Corvino, Kristina Althoff, Frank A. Giordano, Alexander Schramm, Matthias Fischer, Michael Hoelzel
Summary: The study identified epigenetic drivers EHMT2 and EHMT1 as effectors of the MYCN-driven malignant phenotype and suppressors of IFN-gamma transcriptional responses in neuroblastoma cells. Inhibitors of EHMT enhanced T-cell recruitment into the tumor microenvironment through increased expression of Th1-type chemokines, which was further potentiated by co-inhibition of EZH2 in MYCN-amplified high-risk neuroblastomas.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Xiaosong Hu, Ruochen Liu, Jianbing Hou, Wen Peng, Sicheng Wan, Minghao Xu, Yongsen Li, Guanghui Zhang, Xuan Zhai, Ping Liang, Hongjuan Cui
Summary: This study reveals the critical oncogenic role of SMARCE1 gene in neuroblastoma, particularly in cases with MYCN amplification. SMARCE1 interacts with MYCN to mediate transcriptional activation of downstream target genes, promoting neuroblastoma proliferation and tumorigenicity. These findings provide a new potential therapeutic target for neuroblastoma with 17q21-ter gain and MYCN amplification.
Article
Oncology
Jirawan Panachan, Napat Rojsirikulchai, Nutkridta Pongsakul, Ladawan Khowawisetsut, Pongpak Pongphitcha, Teerapong Siriboonpiputtana, Takol Chareonsirisuthigul, Pitichai Phornsarayuth, Nisakorn Klinkulab, Natini Jinawath, Wararat Chiangjong, Usanarat Anurathapan, Kovit Pattanapanyasat, Suradej Hongeng, Somchai Chutipongtanate
Summary: This study aimed to establish a less invasive method to detect the MYCN status in pediatric neuroblastoma (NB) based on the content of MYCN mRNA in extracellular vesicles (EVs). The study successfully detected MYCN mRNA in microvesicles (MVs) of MYCN-amplified NB cells. The feasibility of the EV-based method was demonstrated using simulated samples and clinical specimens, showing promising results.
Review
Biochemistry & Molecular Biology
Soraya Epp, Shin Mei Chuah, Melinda Halasz
Summary: This review examines the intricate interplay between MYCN and known epigenetic mechanisms in neuroblastoma, and provides insights into emerging therapeutic strategies targeting these mechanisms to improve patient outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Jorg Otte, Cecilia Dyberg, Adena Pepich, John Inge Johnsen
Summary: Dysregulated expression of the transcription factor MYCN is frequently detected in nervous system tumors such as childhood neuroblastoma and is a strong predictor of poor prognosis. Increased MYCN expression is an early event in these cancers, leading to a peculiar dysregulation of cells that exhibit embryonal or cancer stem-like qualities.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kiyohiro Ando, Yusuke Suenaga, Takehiko Kamijo
Summary: Identifying the vulnerability of altered DNA repair machinery that displays synthetic lethality with MYCN amplification is a therapeutic rationale in unfavourable neuroblastoma. However, none of the inhibitors for DNA repair proteins are established as standard therapy in neuroblastoma. DNA-PK inhibitor (DNA-PKi) showed inhibitory effects on the proliferation of MYCN-driven neuroblastoma spheroids and cell lines. Among them, DNA ligase 4 (LIG4) was identified as a prognostic factor and its inhibition combined with DNA-PKi may overcome resistance to multimodal therapy in MYCN-amplified neuroblastoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Haoting Wu, Chenqing Wu, Hui Zheng, Lei Wang, Wenbin Guan, Shaofeng Duan, Dengbin Wang
Summary: A CT-based radiomics signature was constructed and showed great performance in predicting MYCN amplification in pediatric patients with neuroblastoma. The clinical radiomics nomogram, incorporating radiomics signature and clinical factors, outperformed the clinical model alone for predicting MNA.
EUROPEAN RADIOLOGY
(2021)
Article
Multidisciplinary Sciences
Hai-Feng Zhang, Alberto Delaidelli, Sumreen Javed, Busra Turgu, Taylor Morrison, Christopher S. Hughes, Xiaqiu Yang, Manideep Pachva, Michael M. Lizardo, Gurdeep Singh, Jennifer Hoffmann, Yue Zhou Huang, Khushbu Patel, Rawan Shraim, Sonia H. Y. Kung, Gregg B. Morin, Samuel Aparicio, Daniel Martinez, John M. Maris, Kristopher R. Bosse, Karla C. Williams, Poul H. Sorensen
Summary: This study reveals that GREB1 gene, located near MYCN locus, is frequently coexpressed with MYCN and promotes cell survival in high-risk neuroblastoma (NB). The research also identifies MYO1B gene as a crucial regulator of invasion and metastasis in MYCN amplified NB. Furthermore, MYO1B is found to regulate secretome reprogramming and the cytokine MIF mediates its pro-invasive and pro-metastatic activity.
Review
Oncology
Swapnil Parashram Bhavsar
Summary: Oncogenic drivers like MYCN in neuroblastoma subsets pose a significant challenge due to their strong correlation with high-risk metastatic disease and poor prognosis. However, the functional role of MYCN and its regulatory partners in neuroblastoma metastasis has only been partially elucidated. This minireview summarizes the recent progress in understanding their roles.
FRONTIERS IN ONCOLOGY
(2023)
Review
Oncology
Mohit Bansal, Anamika Gupta, Han-Fei Ding
Summary: Metabolic reprogramming plays a crucial role in high-risk neuroblastoma and offers potential therapeutic opportunities. This review summarizes the recent progress in understanding neuroblastoma metabolic reprogramming and highlights important areas for future research.
Article
Oncology
Zhiwei Dong, Kok Siong Yeo, Gonzalo Lopez, Cheng Zhang, Erin N. Dankert Eggum, Jo Lynne Rokita, Choong Yong Ung, Taylor M. Levee, Zuag Paj Her, Cassie J. Howe, Xiaonan Hou, Janine H. van Ree, Shuai Li, Shuning He, Ting Tao, Karen Fritchie, Jorge Torres-Mora, Julia S. Lehman, Alexander Meves, Gina L. Razidlo, Komal S. Rathi, S. John Weroha, A. Thomas Look, Jan M. van Deursen, Hu Li, Jennifer J. Westendorf, John M. Maris, Shizhen Zhu
Summary: Research has shown that GAS7 gene is preferentially deleted in high-risk MYCN-driven neuroblastoma, and its deficiency accelerates metastasis in neuroblastoma models. Loss of GAS7 affects cell-cell interaction and contact among tumor cells, identifying a novel mechanism underlying tumor metastasis in MYCN-driven neuroblastoma.
Article
Oncology
Xin Chen, Haoru Wang, Kaiping Huang, Huan Liu, Hao Ding, Li Zhang, Ting Zhang, Wenqing Yu, Ling He
Summary: This study aimed to develop and validate CT-based machine learning models for predicting MYCN amplification in pediatric abdominal neuroblastoma. By analyzing radiographic features and radiomics signature, accurate prediction of MYCN amplification was achieved, with Logistic, SVM, and Random Forest classifiers performing well, while the Bayes classifier showed lower predictive performance. Combining clinical and radiographic qualitative features can improve the predictive performance of MYCN amplification.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Yang Zhou, Hui Yan, Qiang Zhou, Penggao Wang, Fang Yang, Ziqiao Yuan, Qianming Du, Bo Zhai
Summary: The study found that CCNB1IP1 is upregulated in MYCN-amplified neuroblastoma and is associated with poor prognosis. CCNB1IP1 cooperates with MYCN to promote proliferation and tumorigenicity in neuroblastoma. This study also revealed a previously uncharacterized mechanism of CCNB1IP1-mediated MYCN protein stability, providing new prospects for precise treatment of MYCN-amplified neuroblastoma.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Immunology
Wolfgang Glienke, Anna Christina Dragon, Katharina Zimmermann, Alexandra Martyniszyn-Eiben, Mira Mertens, Hinrich Abken, Claudia Rossig, Bianca Altvater, Krasimira Aleksandrova, Lubomir Arseniev, Christina Kloth, Andriana Stamopoulou, Thomas Moritz, Holger N. Lode, Nikolai Siebert, Rainer Blasczyk, Lilia Goudeva, Axel Schambach, Ulrike Koehl, Britta Eiz-Vesper, Ruth Esser
Summary: This study demonstrates the feasibility of translating the manufacturing method of CAR T cells to produce TRUCKs, which secrete IL-18. Using the CliniMACS Prodigy (R) system and a lentiviral vector, IL-18-secreting TRUCKs targeting GD(2) tumor antigen were successfully generated. The engineered T cells obtained from two donors showed similar functionality to laboratory-scale TRUCKs and exhibited specific cytotoxicity towards GD(2)-expressing target cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Monika Scheer, Erika Hallmen, Christian Vokuhl, Joerg Fuchs, Per-Ulf Tunn, Marc Muenter, Beate Timmermann, Sebastian Bauer, Anton George Henssen, Bernarda Kazanowska, Felix Niggli, Ruth Ladenstein, Gustaf Ljungman, Angelika Eggert, Thomas Klingebiel, Ewa Koscielniak
Summary: This study evaluated the effects of neoadjuvant or adjuvant radiation therapy and surgery only on long-term outcomes in patients with synovial sarcoma. The results showed that the best local control was achieved when tumors were irradiated pre-operatively and underwent R0 or R1 resection thereafter.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Letter
Hematology
Michael Launspach, Dennis Temel, Emily Ohlendorf, Felix Zirngibl, Bianca Materne, Lena Oevermann, Hedwig E. Deubzer, Anton G. Henssen, Annette Kunkele, Patrick Hundsdorfer, Horst von Bernuth, Axel Pruss, Angelika Eggert, Arend von Stackelberg, Peter Lang, Johannes H. Schulte
Article
Medicine, Research & Experimental
Michela Carlet, Karin Schmelz, Jenny Vergalli, Tobias Herold, Daniela Senft, Vindi Jurinovic, Thomas Hoffmann, Jutta Proba, Nina Weichert, Christian Junghanss, Mareike Roth, Georg Eschenburg, Malwine Barz, Guenter Henze, Cornelia Eckert, Angelika Eggert, Johannes Zuber, Patrick Hundsdoerfer, Irmela Jeremias
Summary: In this study, researchers found that Smac mimetics (SM) could enhance the sensitivity of relapsed/refractory acute lymphoblastic leukemia (r/r ALL) cells to chemotherapy drugs. They also identified a crucial role of inhibitor of apoptosis proteins (IAP) in r/r ALL, suggesting that IAP could be a potential therapeutic target for r/r ALL.
EMBO MOLECULAR MEDICINE
(2023)
Article
Oncology
Jonas Ecker, Florian Selt, Dominik Sturm, Martin Sill, Andrey Korshunov, Steffen Hirsch, David Capper, Nicola Dikow, Christian Sutter, Carina Mueller, Romain Sigaud, Angelika Eggert, Thorsten Simon, Tim Niehues, Andreas von Deimling, Kristian W. Pajtler, Cornelis M. van Tilburg, David T. W. Jones, Felix Sahm, Stefan M. Pfister, Olaf Witt, Till Milde
Summary: The PTT 2.0 program aims to improve diagnostic accuracy and detect actionable alterations in relapsed pediatric oncology patients, even with limited tumor material. The study utilized molecular analyses such as DNA methylation array, targeted gene panel sequencing, RNA sequencing, and immunohistochemistry to provide relevant and robust information for diagnosis and treatment decisions.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Immunology
Sara Marie Ivasko, Kathleen Anders, Laura Grunewald, Michael Launspach, Anika Klaus, Silke Schwiebert, Peter Ruf, Horst Lindhofer, Holger N. N. Lode, Lena Andersch, Johannes H. H. Schulte, Angelika Eggert, Patrick Hundsdoerfer, Annette Kuenkele, Felix Zirngibl
Summary: Despite advances in treatment, relapse is still a concern for a significant number of high-risk neuroblastoma patients. Bispecific trifunctional antibodies (trAbs) have shown promising potential as a new immunotherapy for neuroblastoma. The SUREK trAb has been demonstrated to effectively kill neuroblastoma cells and enhance adaptive immune responses through binding to antigen-presenting cells. Combining trAb therapy with anti-PD-1 checkpoint blockade may further improve treatment outcomes.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Sascha Troschke-Meurer, Maxi Zumpe, Lena Meissner, Nikolai Siebert, Piotr Grabarczyk, Hannes Forkel, Claudia Maletzki, Sander Bekeschus, Holger N. N. Lode
Summary: We investigated the effects of combining chemotherapeutics with ch14.18/CHO (dinutuximab beta, DB) in high-risk neuroblastoma patients. The combined treatment showed a significantly stronger cytotoxic effect compared to chemotherapy alone, supporting further clinical evaluation of DB in frontline therapy.
Article
Public, Environmental & Occupational Health
Daniel Maier, Joerg Janne Vehreschild, Barbara Uhl, Sandra Meyer, Karin Berger-Thuermel, Melanie Boerries, Rickmer Braren, Viktor Gruenwald, Boris Hadaschik, Stefan Palm, Susanne Singer, Martin Stuschke, David Juarez, Pierre Delpy, Mohamed Lambarki, Michael Hummel, Caecilia Engels, Stefanie Andreas, Nicola Goekbuget, Kristina Ihrig, Susen Burock, Dietmar Keune, Angelika Eggert, Ulrich Keilholz, Hagen Schulz, Daniel Buettner, Steffen Loeck, Mechthild Krause, Mirko Esins, Frank Ressing, Martin Schuler, Christian Brandts, Daniel P. Brucker, Gabriele Husmann, Thomas Oellerich, Patrick Metzger, Frederik Voigt, Anna L. Illert, Matthias Theobald, Thomas Kindler, Ursula Sudhof, Achim Reckmann, Felix Schwinghammer, Daniel Nasseh, Wilko Weichert, Michael von Bergwelt-Baildon, Michael Bitzer, Nisar Malek, Oeznur Oener, Klaus Schulze-Osthoff, Stefan Bartels, Joerg Haier, Raimund Ammann, Anja Franziska Schmidt, Bernd Guenther, Melanie Janning, Bernd Kasper, Sonja Loges, Stephan Stilgenbauer, Peter Kuhn, Eugen Tausch, Silvana Runow, Alexander Kerscher, Michael Neumann, Martin Breu, Martin Lablans, Hubert Serve
Summary: The Clinical Communication Platform of the German Cancer Consortium is a potential catalyst for translational cancer research, providing comprehensive patient groups and improving understanding of the clinical course of various malignancies. It serves as a decision-making tool for clinical trial design and contributes to the evaluation of scientific findings in real-world conditions.
EUROPEAN JOURNAL OF EPIDEMIOLOGY
(2023)
Article
Oncology
Tim Flaadt, Ruth L. Ladenstein, Martin Ebinger, Holger N. Lode, Helga Bjoerk Arnardottir, Ulrike Poetschger, Wolfgang Schwinger, Roland Meisel, Friedhelm R. Schuster, Michaela Doering, Peter F. Ambros, Manon Queudeville, Joerg Fuchs, Steven W. Warmann, Juergen Schaefer, Christian Seitz, Patrick Schlegel, Ines B. Brecht, Ursula Holzer, Tobias Feuchtinger, Thorsten Simon, Johannes H. Schulte, Angelika Eggert, Heiko-Manuel Teltschik, Toni Illhardt, Rupert Handgretinger, Peter Lang
Summary: This study investigates the use of haploidentical stem cell transplantation and the anti-GD2 antibody dinutuximab beta (DB) in treating patients with relapsed high-risk neuroblastoma (rHR-NB). The results show that DB therapy is feasible and improves the chances of cure in rHR-NB patients.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Genetics & Heredity
Rocio Chamorro Gonzalez, Thomas Conrad, Maja C. Stoeber, Robin Xu, Madalina Giurgiu, Elias Rodriguez-Fos, Katharina Kasack, Lotte Brueckner, Eric van Leen, Konstantin Helmsauer, Heathcliff Dorado Garcia, Maria E. Stefanova, King L. Hung, Yi Bei, Karin Schmelz, Marco Lodrini, Stefan Mundlos, Howard Y. Chang, Hedwig E. Deubzer, Sascha Sauer, Angelika Eggert, Johannes H. Schulte, Roland F. Schwarz, Kerstin Haase, Richard P. Koche, Anton G. Henssen
Summary: This study presents a method called scEC&T-seq that allows parallel sequencing of circular DNA and full-length mRNA from individual cancer cells. The research reveals intercellular differences in ecDNA content, structural heterogeneity, and transcriptional impact. The findings suggest that oncogene-containing ecDNAs are clonally present in cancer cells and drive intercellular oncogene expression differences, while other small circular DNAs are exclusive to individual cells.
Article
Immunology
Julia Scheiermann, Annette Kuenkele, Arend von Stackelberg, Angelika Eggert, Peter Lang, Felix Zirngibl, Luise Martin, Johannes Hubertus Schulte, Horst von Bernuth
Summary: Chronic granulomatous disease is a congenital immunodeficiency disorder caused by a disruption in the function of the NADPH oxidase complex. It leads to impaired respiratory burst and inadequate killing of bacteria and fungi. Allogeneic HSCT is the only available curative therapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Niklas Abele, Soenke Langner, Ute Felbor, Holger Lode, Norbert Hosten
Summary: This study analyzed the quantified diffusion weighed imaging in MRI for neuroblastoma. It found that there is a significant increase in the apparent diffusion coefficient for regressive diseases and a decrease for progressive diseases. This change can be observed within the first 120 days of therapy. Neuroblastoma is a common malignant tumor in children, and MRI with contrast-enhanced and diffusion-weighted imaging is used for staging and therapy monitoring. The study evaluated the early change in the ADC values under therapy and its correlation with the form of therapy and prognosis.
Article
Health Care Sciences & Services
Tabea Troschke, Aleksandra Wieczorek, Konrad Kulinski, Tomasz Ociepa, Karolina Zielezinska, Holger N. Lode, Tomasz Urasinski
Summary: This article presents the development, implementation, and management of a German-Polish telemedicine network in pediatric oncology and hematology in the Euroregion Pomerania. It discusses the achievements and challenges of joint medical case reviews and cross-border education activities. The article also includes a progress report, evaluation results of participants and teachers, and knowledge growth measurement.
Article
Medicine, General & Internal
Tim Flaadt, Martin Ebinger, Malin Schreiber, Ruth L. Ladenstein, Thorsten Simon, Holger N. Lode, Barbara Hero, Martin U. Schuhmann, Jurgen Schaefer, Frank Paulsen, Beate Timmermann, Angelika Eggert, Peter Lang
Summary: Haploidentical stem cell transplantation (haplo-SCT) followed by dinutuximab beta+/- subcutaneous interleukin-2 (scIL-2) is a promising treatment option with good tolerability for patients with high-risk neuroblastoma (HRNB) and central nervous system (CNS) relapse.
JOURNAL OF CLINICAL MEDICINE
(2023)