Article
Neurosciences
Yu Teranishi, Satoru Miyawaki, Masahiro Nakatochi, Atsushi Okano, Kenta Ohara, Hiroki Hongo, Daiichiro Ishigami, Yu Sakai, Daisuke Shimada, Shunsaku Takayanagi, Masako Ikemura, Daisuke Komura, Hiroto Katoh, Jun Mitsui, Shinichi Morishita, Tetsuo Ushiku, Shumpei Ishikawa, Hirofumi Nakatomi, Nobuhito Saito
Summary: This study investigated the characteristics of meningiomas in NF2 patients and found that these tumors showed less aggressive behavior but had a marked immune response compared to sporadic NF2-altered meningiomas, with a higher immune cell infiltration, particularly of macrophages.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Oncology
Katharina Wagener, Julia Beckhaus, Svenja Boekhoff, Carsten Friedrich, Hermann L. Mueller
Summary: This study aimed to explore the clinical and epidemiological characteristics of pediatric meningioma. The results showed that pediatric meningioma differs from adult meningioma in its clinical characteristics, and different WHO grades have an impact on event-free survival.
JOURNAL OF NEURO-ONCOLOGY
(2023)
Article
Clinical Neurology
Precious C. Oyem, Erion J. de Andrade, Pranay Soni, Roger Murayi, Derrick Obiri-Yeboah, Diana Lopez, Varun R. Kshettry, Pablo F. Recinos
Summary: The volumetric natural history of meningiomas in NF2 patients was described in this study. The majority of NF2-associated meningiomas do not show short-term growth, but a wide range of growth patterns can be observed. Younger age at first imaging and the presence of peritumoral brain edema (PTBE) are associated with tumor growth.
NEUROSURGICAL FOCUS
(2022)
Article
Clinical Neurology
Heather L. Thompson, Ann Blanton, Barbara Franklin, Vanessa L. Merker, Kevin H. Franck, D. Bradley Welling, REiNS Int Collaboration
Summary: The REiNS recommends the use of the "Self-Assessment of Communication" adult and adolescent forms for assessing patient-reported hearing function and hearing-related quality of life for NF2 clinical trials, further work is needed to demonstrate the utility of these measures in evaluating pharmacologic or behavioral interventions.
Review
Biochemistry & Molecular Biology
Ryota Tamura
Summary: Neurofibromatosis is a neurocutaneous syndrome characterized by tumors in the nervous system, with NF1, NF2, and SWN as its three main types. While NF1 and NF2 have known genetic mutations and targeted therapies, the molecular mechanisms of SWN remain unclear and require further research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Phanidhar Kukutla, Sherif G. Ahmed, Daniel M. DuBreuil, Ahmed Abdelnabi, Murat Cetinbas, Giulia Fulci, Berent Aldikacti, Anat Stemmer-Rachamimov, Scott R. Plotkin, Brian Wainger, Ruslan I. Sadreyev, Gary J. Brenner
Summary: Schwannomas can cause severe pain, and the upregulation of FGF7 in painful tumors may be associated with the development of pain. Behavioral support was found in a xenograft human NF2-schwannoma model, where over-expression of FGF7 induced pain behavior in nude mice.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Review
Genetics & Heredity
Tin-Suet Joan Lee, Meera Chopra, Raymond H. Kim, Patricia C. Parkin, Carolina Barnett-Tapia
Summary: This study provides updated estimates of the incidence and prevalence of NF1 and NF2, highlighting a potential underestimation of NF1 prevalence. More studies are needed to determine the prevalence of NF2, and these findings can help in healthcare planning and allocation.
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Article
Clinical Neurology
Heather L. Thompson, Ann Blanton, Barbara Franklin, Vanessa L. Merker, Kevin H. Franck, D. Bradley Welling
Summary: The study systematically evaluated published patient-reported outcome measures for hearing function and hearing-related quality of life, recommending specific measures for use in NF2 clinical trials. Measures were selected based on participant characteristics, item content, psychometric properties, and feasibility for use in clinical trials. Further research is needed to demonstrate the utility of these measures in evaluating interventions.
Article
Genetics & Heredity
Scott R. Plotkin, Ludwine Messiaen, Eric Legius, Patrice Pancza, Robert A. Avery, Jaishri O. Blakeley, Dusica Babovic-Vuksanovic, Rosalie Ferner, Michael J. Fisher, Jan M. Friedman, Marco Giovannini, David H. Gutmann, Clemens Oliver Hanemann, Michel Kalamarides, Hildegard Kehrer-Sawatzki, Bruce R. Korf, Victor-Felix Mautner, Mia MacCollin, Laura Papi, Katherine A. Rauen, Vincent Riccardi, Elizabeth Schorry, Miriam J. Smith, Anat Stemmer-Rachamimov, David A. Stevenson, Nicole J. Ullrich, David Viskochil, Katharina Wimmer, Kaleb Yohay, Susan M. Huson, Pierre Wolkenstein, D. Gareth Evans
Summary: The study aims to update the diagnostic criteria for neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) by incorporating recent advances in genetics, ophthalmology, neuropathology, and neuroimaging. The updated criteria include clinical features and genetic testing, emphasizing the phenotypic overlap between the two conditions.
GENETICS IN MEDICINE
(2022)
Article
Chemistry, Multidisciplinary
Marta Armentano, Luca Lucchino, Ludovico Alisi, Antonio Valerio Chicca, Valerio Di Martino, Emanuele Miraglia, Ludovico Iannetti, Anna Maria Comberiati, Sandra Giustini, Alessandro Lambiase, Antonietta Moramarco
Summary: Neurofibromatosis type 2 (NF2) is a genetically determined tumor-predisposing syndrome with ocular manifestations including cataracts, epiretinal membranes, retinal hamartomas, optic disk gliomas, and optic nerve sheath meningiomas. Other indirect signs such as optic disk edema, optical atrophy, motility disorders, pupil and lid dysfunction, and neurotrophic keratitis can also be observed.
APPLIED SCIENCES-BASEL
(2023)
Article
Clinical Neurology
Michael J. Fisher, David T. W. Jones, Yimei M. Li, Xiaofan Guo, Poonam S. Sonawane, Angela J. Waanders, Joanna J. Phillips, William A. Weiss, Adam C. Resnick, Sara Gosline, Jineta Banerjee, Justin Guinney, Astrid Gnekow, Daniela Kandels, Nicholas K. Foreman, Andrey Korshunov, Marina Ryzhova, Luca Massimi, Sri Gururangan, Mark W. Kieran, Zhihong Wang, Maryam Fouladi, Mariko Sato, Ingrid Ora, Stefan Holm, Stephen J. Markham, Pengbo Beck, Natalie Jaeger, Andrea Wittmann, Alexander C. Sommerkamp, Felix Sahm, Stefan M. Pfister, David H. Gutmann
Summary: Low-grade gliomas (LGGs) are the most common childhood brain tumor in the general population and in individuals with the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome. While most NF1-associated LGGs have bi-allelic NF1 inactivation as the main genetic abnormality, some tumors also harbor additional mutations, with FGFR1 mutation being the most common secondary alteration. This comprehensive characterization has important implications for the management of children with NF1-LGG, distinct from their sporadic counterparts.
ACTA NEUROPATHOLOGICA
(2021)
Article
Clinical Neurology
Cathal John Hannan, Charlotte Hammerbeck-Ward, Omar Nathan Pathmanaban, Miriam J. Smith, Scott A. A. Rutherford, Simon K. K. Lloyd, Simon Richard Mackenzie Freeman, Andrew J. Wallace, Andrew Thomas King, Dafydd Gareth Richard Evans
Summary: Patients presenting with unilateral vestibular schwannomas (UVS) and multiple meningiomas (MM) are more likely to be diagnosed with neurofibromatosis type 2 (NF2) compared to patients with UVS and multiple nonintradermal schwannomas (NIDS), but less likely to develop bilateral vestibular schwannomas. Some patients with MM without meeting NF2 criteria have pathogenic variants in SMARCE1 and mosaic NF2.
Article
Genetics & Heredity
S. Legoupil, D. Bessis, F. Picard, S. Mallet, J. Mazereeuw, A. Phan, D. Dupin-Deguine, M. Kalamarides, C. Chiaverini
Summary: Cutaneous manifestations are common and early in children with NF2 but rarely lead to diagnosis. Cafe au lait macules are the most frequent, but are often underdiagnosed. Multiple hypopigmented macules appear suggestive but inconsistent.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Review
Biochemistry & Molecular Biology
Suha Bachir, Sanjit Shah, Scott Shapiro, Abigail Koehler, Abdelkader Mahammedi, Ravi N. Samy, Mario Zuccarello, Elizabeth Schorry, Soma Sengupta
Summary: NF2 patients are highly likely to develop meningiomas and vestibular schwannomas, which can lead to significant morbidity. Mutations in the NF2 gene are closely associated with benign proliferative conditions, emphasizing the importance of early intervention and treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Sultan Abdulwadoud Alshoabi
Summary: This article presents a rare case of NF2 in a 36-year-old female who initially presented with right eye visual disturbances, followed by tinnitus and hearing impairment that eventually led to blindness. MRI revealed a right-side cerebellopontine angle vestibular schwannoma and multiple meningiomas around the brain, leading to the diagnosis of NF2. This case report highlights the importance of early brain imaging in visual disturbances in young adults and emphasizes the key role of medical imaging in diagnosing rare cases, while also describing the MRI features and diagnostic accuracy for tumors occurring in NF2 in detail.
PAKISTAN JOURNAL OF MEDICAL SCIENCES
(2023)
Article
Cell Biology
Luca Hegedues, Kata D. Szuecs, Matthias Kudla, Julian Heidenreich, Verena Jendrossek, Samuel Pena-Llopis, Tamas Garay, Andras Czirok, Clemens Aigner, Till Ploenes, Silvia Vega-Rubin-de-Celis, Balazs Hegedues
Summary: This study investigated the effect of Nintedanib on SRC kinase, one of its targets, in MPM cells. The results showed that Nintedanib did not inhibit SRC activation and even increased SRC phosphorylation in some MPM cell lines. However, combination treatment with the SRC inhibitor Dasatinib reversed this effect. The study also revealed that combination treatment promoted autophagy in MPM cells, which was independent of the AKT/mTOR and ERK pathways.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Martin Metzenmacher, Balazs Hegedues, Jan Forster, Alexander Schramm, Peter A. Horn, Christoph A. Klein, Nicola Bielefeld, Till Ploenes, Clemens Aigner, Jens T. Siveke, Martin Schuler, Smiths S. Lueong
Summary: This study evaluated the clinical utility of cfRNA for early detection and surveillance of NSCLC. The results showed that MORF4L2 cfRNA was more abundant in patients and its combination with tumor markers improved the predictive value. Furthermore, low baseline MORF4L2 levels were associated with better patient survival and progression-free survival. cfRNA transcripts better reflected tumor dynamics compared to tumor markers. These findings suggest the potential clinical application of cfRNA for detection and monitoring of NSCLC.
Article
Oncology
Ildiko Kovacs, Edina Bugyik, Katalin Dezso, Julia Tarnoki-Zach, Elod Mehes, Marton Gulyas, Andras Czirok, Elisabeth Lang, Michael Grusch, Karin Schelch, Balazs Hegedus, Ildiko Horvath, Nandor Barany, Zsolt Megyesfalvi, Anna Tisza, Zoltan Lohinai, Mir Alireza Hoda, Konrad Hoetzenecker, Francesco Pezzella, Sandor Paku, Viktoria Laszlo, Balazs Dome
Summary: This study investigates the microanatomical steps of malignant pleural mesothelioma (MPM) vascularization and the resistance mechanisms to anti-angiogenic drugs in MPM. The study reveals two distinct growth patterns of orthotopically implanted human MPM xenografts, invasive pattern and pushing/desmoplastic pattern.
TRANSLATIONAL LUNG CANCER RESEARCH
(2022)
Article
Oncology
Ozlem Okumus, Khaled Mardanzai, Till Plones, Dirk Theegarten, Kaid Darwiche, Martin Schuler, Felix Nensa, Hubertus Hautzel, Ken Hermann, Martin Stuschke, Balazs Hegedus, Clemens Aigner
Summary: This study aimed to assess the association of preoperative PET parameters with nodal upstaging in lung adenocarcinoma and squamous cell carcinoma. The results showed that high preoperative PET-SUVmax values were associated with squamous cell carcinoma and larger tumors. However, SUVmax and metabolic PET parameters MTV and TLG were not significant predictors of nodal upstaging, except for tumor size and number of removed lymph nodes.
Article
Pharmacology & Pharmacy
Anna Tisza, Thomas Klikovits, Michal Benej, Szilvia Torok, Beata Szeitz, Zsuzsanna Valko, Mir Alireza Hoda, Balazs Hegedus, Maximilian Bonta, Winfried Nischkauer, Konrad Hoetzenecker, Andreas Limbeck, Karin Schelch, Viktoria Laszlo, Zsolt Megyesfalvi, Balazs Dome
Summary: This study examined platinum (Pt) levels in blood samples and surgically resected specimens from 25 pleural mesothelioma (PM) patients who had received neoadjuvant Pt-based chemotherapy. The results showed significant differences in Pt distribution between tumorous and non-tumorous areas of PM specimens. Serum Pt levels were found to correlate with tissue Pt levels, elapsed time from the last chemotherapy cycle, and overall survival.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Thomas Hager, Sabrina Borchert, Michael Wessolly, Alexander Mathilakathu, Elena Mairinger, Jens Kollmeier, Thomas Mairinger, Balazs Hegedus, Kristina Greimelmaier, Jeremias Wohlschlaeger, Ken Herrmann, Fabian Dominik Mairinger
Summary: Malignant pleural mesothelioma (MPM) is a deadly asbestos-related tumor with limited treatment options. This study examines the expression of two proteins, MSLN and CXCR4, in MPM tumor samples and their potential as targets for endo-radioligand therapy. The results show significant expression of these proteins in a majority of the samples, suggesting the possibility of using radioligand-based diagnostics and endo-radiotherapy for MPM patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Luca Hegedues, Oezlem Okumus, Fabian Mairinger, Till Ploenes, Sebastian Reuter, Martin Schuler, Anja Welt, Silvia Vega-Rubin-de-Celis, Dirk Theegarten, Agnes Bankfalvi, Clemens Aigner, Balazs Hegedues
Summary: The expression of TROP2 and sensitivity to SN38 in MPM cell lines support the biomarker-selected clinical exploration of sacituzumab govitecan in patients with MPM.
Article
Multidisciplinary Sciences
Christine Chiasson-MacKenzie, Jeremie Vitte, Ching-Hui Liu, Emily A. Wright, Elizabeth A. Flynn, Shannon L. Stott, Marco Giovannini, Andrea I. McClatchey
Summary: Schwannomas are common tumors that develop on cranial and spinal nerves and are associated with neurofibromatosis type 2 (NF2). Despite genetic uniformity, schwannomas exhibit clinical and therapeutic heterogeneity. The mechanism behind this heterogeneity in NF2-mutant schwannomas is unknown.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Berta Mosleh, Karin Schelch, Thomas Mohr, Thomas Klikovits, Christina Wagner, Lukas Ratzinger, Yawen Dong, Katharina Sinn, Alexander Ries, Walter Berger, Bettina Grasl-Kraupp, Konrad Hoetzenecker, Viktoria Laszlo, Balazs Dome, Balazs Hegedus, Marko Jakopovic, Mir Alireza Hoda, Michael Grusch
Summary: This study found that FGF18 expression is elevated in pleural mesothelioma (PM) tissue compared to normal mesothelium. However, despite high mRNA levels in PM cells, circulating FGF18 protein is significantly lower in PM patients and patients with pleural fibrosis than in healthy controls. The results suggest that FGF18 is not a prognostic biomarker in PM, and further investigation is needed to understand its role in tumor biology and the clinical significance of decreased plasma FGF18 in PM patients.
Article
Oncology
Tobias Sikosek, Rastislav Horos, Franziska Trudzinski, Julia Jehn, Maurice Frank, Timothy Rajakumar, Laura V. Klotz, Nathaniel Mercaldo, Mustafa Kahraman, Marco Heuvelman, Yasser Taha, Jennifer Gerwing, Jasmin Skottke, Alberto Daniel-Moreno, Marta Sanchez-Delgado, Sophie Bender, Christina Rudolf, Franziska Hinkfoth, Kaja Tikk, Judith Schenz, Markus A. Weigand, Peter Feindt, Christian Schumann, Petros Christopoulos, Hauke Winter, Michael Kreuter, Marc A. Schneider, Thomas Muley, Stephan Walterspacher, Martin Schuler, Kaid Darwiche, Christian Taube, Balazs Hegedus, Klaus F. Rabe, Kimberly Rieger-Christ, Francine L. Jacobsen, Clemens Aigner, Martin Reck, Alexander A. Bankier, Amita Sharma, Bruno R. Steinkraus
Summary: Lung cancer is the deadliest cancer and its survival is influenced by tumor stage. Low-dose computed tomography screening can reduce mortality but has low adherence in the US and limited implementation in Europe. Therefore, additional screening tests, such as blood tests, are needed for early detection in primary care settings.
JOURNAL OF THORACIC ONCOLOGY
(2023)
Article
Oncology
Till Milde, Jason Fangusaro, Michael J. Fisher, Cynthia Hawkins, Fausto J. Rodriguez, Uri Tabori, Olaf Witt, Yuan Zhu, David H. Gutmann
Summary: Pediatric low-grade gliomas (pLGGs) are common brain tumors in young children, which often result in chronic tumor- and therapy-related morbidities. The growth of pLGGs is influenced by genetic alterations and nonneoplastic cells in the microenvironment. Preclinical models are necessary to identify potential drugs for clinical evaluation and improve treatment for children with pLGGs.
Editorial Material
Medicine, Research & Experimental
David H. Gutmann
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Review
Oncology
Yunshuo Tang, David H. Gutmann
Summary: Optic pathway glioma (OPG) occurs in a significant number of individuals with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome. While often benign and slow growing, some patients with NF1-OPGs experience symptoms such as vision loss and precocious puberty. Studies using genetically engineered Nf1-OPG mouse models have provided valuable insights into the molecular and cellular pathways of optic gliomagenesis and identified potential new treatments. Research focusing on determining the factors underlying optic glioma development and tumor-induced optic nerve injury will contribute to personalized risk assessment and improved treatment for children with NF1-OPG.
CANCER MANAGEMENT AND RESEARCH
(2023)
Meeting Abstract
Oncology
Amita Sharma, Tobias Sikosek, Rastislav Horos, Timothy Rajakumar, Kaja Tikk, Christian Schumann, Stephan Walterspacher, Petros Christopoulos, Martin H. Schuler, Kaid Darwiche, Christian Taube, Balazs Hegedus, Klaus Rabe, Kimberly M. Rieger-Christ, Francine Jacobnson, Clemens Aigner, Alexander A. Bankier, Martin Reck, Bruno Steinkraus
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Nicole M. Brossier, Jennifer M. Strahle, Samuel J. Cler, Michael Wallendorf, David H. Gutmann
NEURO-ONCOLOGY ADVANCES
(2022)