Article
Cell Biology
Alessandro Tancredi, Olga Gusyatiner, Pierre Bady, Michelle C. Buri, Remy Lomazzi, Davide Chiesi, Mahmoud Messerer, Monika E. Hegi
Summary: Bromodomain and extra-terminal tail (BET) proteins are potential epigenetic targets in cancer, including glioblastoma. BET inhibitors disrupt the histone code-gene transcription link. BET-induced differential gene expression in glioblastoma derived-spheres revealed 6 distinct response patterns. The O-6-methylguanine-DNA methyltransferase (MGMT) gene, a known resistance factor for glioblastoma treatment, showed consistent downregulation in response to BET inhibitors.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Cyntanna C. Hawkins, Amber B. Jones, Emily R. Gordon, Yuvika Harsh, Julia K. Ziebro, Christopher D. Willey, Corinne Griguer, David K. Crossman, Sara J. Cooper, Sasanka Ramanadham, Ninh Doan, Anita B. Hjelmeland
Summary: Sphingolipid metabolism is dysregulated in GBM, leading to cell evasion of apoptosis. This study found that the mRNA levels of acid ceramidase, a key enzyme in S1P production, were elevated in recurrent GBM. Inhibiting acid ceramidase decreased cell growth and increased apoptosis in TMZ-resistant GBM cells, suggesting the potential utility of targeting sphingolipid metabolism in recurrent GBM.
CELL DEATH DISCOVERY
(2023)
Article
Oncology
Martin Glas, Matthew T. Ballo, Ze'ev Bomzon, Noa Urman, Shay Levi, Gitit Lavy-Shahaf, Suriya Jeyapalan, Terence T. Sio, Paul M. DeRose, Martin Misch, Sophie Taillibert, Zvi Ram, Andreas F. Hottinger, Jacob Easaw, Chae-Yong Kim, Suyash Mohan, Roger Stupp
Summary: TTFields treatment affects the rate of distant progression in newly diagnosed GBM patients, with distant lesions appearing further from the primary lesion in the TTFields treatment arm. Distant progression correlates with improved clinical outcomes in TTFields patients.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2022)
Article
Oncology
Mario Caccese, Matteo Simonelli, Veronica Villani, Simona Rizzato, Tamara Ius, Francesco Pasqualetti, Marco Russo, Roberta Ruda, Rosina Amoroso, Luisa Bellu, Roberta Bertorelle, Francesco Cavallin, Angelo Dipasquale, Mariantonia Carosi, Stefano Pizzolitto, Daniela Cesselli, Pasquale Persico, Beatrice Casini, Matteo Fassan, Vittorina Zagonel, Giuseppe Lombardi
Summary: The study investigated the association between MGMT promoter methylation status and overall survival in glioblastoma patients, finding better survival when MGMT > 15% but a more complex, non-linear relationship between MGMT methylation and survival.
Article
Pharmacology & Pharmacy
Federico Cucchiara, Giacomo Luci, Noemi Giannini, Filippo Sean Giorgi, Paola Orlandi, Marta Banchi, Antonello Di Paolo, Francesco Pasqualetti, Romano Danesi, Guido Bocci
Summary: This study investigates the association between MGMT promoter methylation, LEV plasma concentration, and sex with the survival of GBM patients. The results show that methylated MGMT promoter is associated with longer PFS and OS, especially in female patients and those with lower LEV concentration. Female patients also have longer OS, and higher LEV concentration synergizes with MGMT promoter methylation to extend the OS. Higher plasma concentrations of LEV may promote better outcomes for chemoradiotherapy, especially in male patients.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Oncology
Mustafa Guven, Filiz Taspinar, Farika Nur Denizler-Ebiri, Javier S. Castresana, Mehmet Taspinar
Summary: Glioblastoma is a highly aggressive and deadly form of brain cancer. Current treatments have not yet achieved the desired outcomes, leading to the investigation of alternative therapies. This study aimed to determine the potential therapeutic effect of combining the chemotherapy drug temozolomide (TMZ) with the histone deacetylase inhibitor trichostatin A (TSA) for glioblastoma treatment.
Article
Oncology
Jianfeng Li, Christopher A. Koczor, Kate M. Saville, Faisal Hayat, Alison Beiser, Steven McClellan, Marie E. Migaud, Robert W. Sobol
Summary: In this study, a novel approach to overcome glioblastoma resistance to temozolomide (TMZ) was discovered. By combining an NAD(+) precursor and a PARG inhibitor, the base excision repair (BER) pathway was strongly inhibited, leading to increased cytotoxicity of TMZ.
Article
Chemistry, Analytical
Nana Wang, Jiejun Wang, Pu Wang, Nan Ji, Shuhua Yue
Summary: Temozolomide (TMZ) is a first line chemotherapy drug for glioblastoma (GBM). However, GBMs without methylation of O-6-methylguanine-DNA methyltransferase (MGMT) show resistance to TMZ treatment. This study found that MGMT methylation affects lipid accumulation in GBM, and the amount and composition of lipid droplets (LDs) are significantly reduced in GBMs without MGMT methylation.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Jonas Feldheim, Almuth F. Kessler, Julia J. Feldheim, Ellina Schulz, David Wend, Lazaros Lazaridis, Christoph Kleinschnitz, Martin Glas, Ralf-Ingo Ernestus, Sebastian Brandner, Camelia M. Monoranu, Mario Loehr, Carsten Hagemann
Summary: Glioblastoma is a fatal tumor and chemotherapy with temozolomide (TMZ) is a crucial treatment. However, TMZ treatment may lead to changes in MGMT promoter methylation and affect the migration and proliferation behavior of tumor cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Qiong Wu, Anders E. Berglund, Robert J. Macaulay, Arnold B. Etame
Summary: This study provides evidence that the epigenetic reactivation of Tumor Suppressor Candidate 3 (TUSC3) can reprogram the sensitivity of glioblastoma stem cells (GSCs) to Temozolomide (TMZ), regardless of the promoter methylation status of the DNA repair gene O6-methylguanine DNA methyltransferase (MGMT). These findings offer a framework for further exploring TUSC3-mediated epigenetic reprogramming strategies to enhance TMZ sensitivity and outcomes in glioblastoma multiforme (GBM).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Moli Wu, Danyang Song, Hui Li, Nisar Ahmad, Hong Xu, Xiaobo Yang, Qian Wang, Xiaoxin Cheng, Sa Deng, Xiaohong Shu
Summary: Chemoresistance is a challenge in the treatment of glioblastoma (GBM), and the activity of O6-methylguanine-DNA methyltransferase (MGMT) and signal transducer and of transcription 3 (STAT3) have been linked to GBM resistance. Resveratrol (Res) inhibits tumor growth and improves chemosensitivity by targeting STAT3 signaling. This study found that Res effectively improved chemosensitivity of GBM cells to temozolomide (TMZ) and downregulated STAT3 activity, leading to inhibition of cell proliferation, migration, and induction of apoptosis. The combination therapy of Res and TMZ also reversed TMZ resistance and decreased MGMT and STAT3 levels. Therefore, Res may be an ideal candidate for combined chemotherapy with TMZ in GBM.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Denise Sighel, Michela Notarangelo, Shintaro Aibara, Angela Re, Gianluca Ricci, Marianna Guida, Alessia Soldano, Valentina Adami, Chiara Ambrosini, Francesca Broso, Emanuele Filiberto Rosatti, Sara Longhi, Mariachiara Buccarelli, Quintino G. D'Alessandris, Stefano Giannetti, Simone Pacioni, Lucia Ricci-Vitiani, Joanna Rorbach, Roberto Pallini, Sandrine Roulland, Alexey Amunts, Ines Mancini, Angelika Modelska, Alessandro Quattrone
Summary: This study suggests that targeting mitochondrial translation could be a potential therapeutic strategy to suppress GSC growth in GBM. The bacterial antibiotic quinupristin/dalfopristin (Q/D) was found to effectively inhibit GSC growth by binding to the large mitoribosomal subunit, inhibiting mitochondrial protein synthesis, and disrupting OXPHOS complexes.
Article
Clinical Neurology
Tetsuya Yamada, Shohei Tsuji, Shinsuke Nakamura, Yusuke Egashira, Masamitsu Shimazawa, Noriyuki Nakayama, Hirohito Yano, Toru Iwama, Hideaki Hara
Summary: Riluzole demonstrates significant growth-inhibitory effects on all GBM cell lines in a time- and dose-dependent manner. It synergistically enhances the antitumor effect of TMZ in MGMT-positive GBM cell lines, while suppressing MGMT expression and TMZ-induced MGMT upregulation. Combinatorial TMZ/riluzole treatment significantly suppresses tumor growth in an intracranial MGMT-positive GBM model, suggesting it as a promising therapeutic regimen for MGMT-positive GBMs.
JOURNAL OF NEUROSURGERY
(2021)
Article
Oncology
Kenichiro Asano, Toshio Fumoto, Masashi Matsuzaka, Seiko Hasegawa, Naoya Suzuki, Kenichi Akasaka, Kosuke Katayama, Akihisa Kamataki, Akira Kurose, Hiroki Ohkuma
Summary: This investigator-initiated study aimed to investigate the effectiveness of induction combination chemoradiotherapy and long-term maintenance therapy for glioblastoma. The 2-year overall survival tended to exceed historical controls, but further research may be needed as the lower limit of the 95% confidence interval was below 31.7%.
Article
Oncology
Marije E. Weidema, Ingrid M. E. Desar, Melissa H. S. Hillebrandt-Roeffen, Anke E. M. van Erp, Mikio Masuzawa, J. W. R. Meyer, J. W. R. Meyer, M. C. H. Hogenes, Uta E. Flucke, Winette T. A. van der Graaf, Yvonne M. H. Versleijen-Jonkers
Summary: Angiosarcoma (AS) is a rare vasoformative sarcoma with poor prognosis, especially when related to UV exposure. This study investigated the expression of PARP1 and SLFN11 in UV AS, and found that combination treatment of PARPi olaparib and TMZ showed synergistic effects in inducing apoptosis and DNA damage in UV AS cell lines, suggesting a potential novel treatment option for UV AS patients.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2021)
Article
Oncology
Wouter B. L. van den Bossche, Anne Kleijn, Charlotte E. Teunissen, Jane S. A. Voerman, Cristina Teodosio, David P. Noske, Jacques J. M. van Dongen, Clemens M. F. Dirven, Martine L. M. Lamfers
Article
Multidisciplinary Sciences
Ya Gao, Maurice de Wit, Eduard A. Struys, Herma C. Z. van der Linde, Gajja S. Salomons, Martine L. M. Lamfers, Rob Willemsen, Peter A. E. Sillevis Smite, Pim J. French
Meeting Abstract
Oncology
I. Ntafoulis, T. Kers, M. van der Kaaij, R. Balvers, J. Hayes, J. van Rij, R. Tching, A. Lindner, J. Prehn, A. Kremer, C. Dirven, S. Leenstra, M. Lamfers
Meeting Abstract
Oncology
I. Verploegh, A. Conidi, M. Lamfers, C. Dirven, S. Leenstra, D. Huylebroeck
Review
Biochemistry & Molecular Biology
Vera Kemp, Martine L. M. Lamfers, Gabri van der Pluijm, Bernadette G. van den Hoogen, Rob C. Hoeben
CYTOKINE & GROWTH FACTOR REVIEWS
(2020)
Review
Oncology
K. White, K. Connor, J. Clerkin, B. M. Murphy, M. Salvucci, A. C. O'Farrell, M. Rehm, D. O'Brien, J. H. M. Prehn, S. P. Niclou, M. L. M. Lamfers, M. Verreault, A. Idbaih, R. Verhaak, A. Golebiewska, A. T. Byrne
ANNALS OF ONCOLOGY
(2020)
Article
Oncology
Ivar Kommers, Linda Ackermans, Hilko Ardon, Wimar A. van den Brink, Wim Bouwknegt, Rutger K. Balvers, Niels van der Gaag, Lisette Bosscher, Alfred Kloet, Jan Koopmans, Mark ter Laan, Rishi Nandoe Tewarie, Pierre A. Robe, Olivier van der Veer, Michiel Wagemakers, Aeilko H. Zwinderman, Philip C. De Witt Hamer
Summary: In this study, the research team analyzed data from a national quality registry on glioblastoma surgeries, finding that patient characteristics were significant risk factors for complications and performance declines, but hospital characteristics did not have a clear impact. After risk-standardization, hospitals showed variations in complications and performance declines.
JOURNAL OF NEURO-ONCOLOGY
(2021)
Article
Oncology
Angela Costagliola di Polidoro, Giorgia Zambito, Joost Haeck, Laura Mezzanotte, Martine Lamfers, Paolo Antonio Netti, Enza Torino
Summary: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with poor prognosis, and the use of functionalized nanoparticles offers potential for improving treatment outcomes and early diagnosis. In this study, angiopep-2 functionalized nanoparticles show promise in enhancing drug delivery and therapeutic effects for GBM.
Review
Oncology
Eftychia Stavrakaki, Clemens M. F. Dirven, Martine L. M. Lamfers
Summary: Oncolytic virotherapy offers a potential option for treating glioblastoma, with promising results in clinical trials. However, the low response rates to each oncolytic virus may be attributed to the large heterogeneity of tumors. Personalized utilization of oncolytic viruses against GBM based on specific tumor-related characteristics may improve response rates.
Article
Cell Biology
Viktorija Juric, Heiko Dussmann, Martine L. M. Lamfers, Jochen H. M. Prehn, Markus Rehm, Brona M. Murphy
Summary: This study highlights the potential of using transcriptional CDK inhibitors to prevent tumor recurrence, particularly in aggressive adult brain tumor GBM. The expression of GSC markers CD133 and CD44 is significantly upregulated in GBM patient tumors, and GSCs are more sensitive to transcriptional CDK inhibitors.
Article
Oncology
Fatih Incekara, Marion Smits, Linda Dirven, Eelke M. Bos, Rutger K. Balvers, Iain K. Haitsma, Joost W. Schouten, Arnaud J. P. E. Vincent
Summary: The study confirms that intraoperative B-mode ultrasound guided surgery leads to more frequent complete resection without harming patients, which helps to maximize the extent of glioblastoma resection.
FRONTIERS IN ONCOLOGY
(2021)
Review
Virology
Laura Hofman, Sean E. Lawler, Martine L. M. Lamfers
Summary: The role of macrophages in oncolytic virotherapy is multifaceted, with potential contributions to both anti-viral responses and anti-inflammatory, tumour-suppressive properties. Oncolytic viruses have been shown to induce a phenotypic shift in macrophages towards an anti-inflammatory state, mediating immune responses and inhibiting cancer immune evasion.
Review
Oncology
Federica Fabro, Martine L. M. Lamfers, Sieger Leenstra
Summary: Drug resistance is a major issue in brain tumor therapy, especially for glioblastoma (GBM). The development of different drug resistance mechanisms due to the heterogeneity of GBM leads to treatment failure. Therefore, it is crucial to gain a better understanding of these resistance mechanisms in order to improve clinical practice. Insights into therapy resistance can be achieved through the development of clinically relevant preclinical in vitro models.
Review
Oncology
Ioannis Ntafoulis, Stijn L. W. Koolen, Sieger Leenstra, Martine L. M. Lamfers
Summary: Treating glioblastoma is challenging due to the blood-brain barrier and disease heterogeneity. Drug repurposing offers a potential solution by identifying promising candidates for GBM treatment and accelerating drug development.
Article
Pharmacology & Pharmacy
Subramanian Venkatesan, Martine Lamfers, Sieger Leenstra, Arnold G. Vulto
GABI JOURNAL-GENERICS AND BIOSIMILARS INITIATIVE JOURNAL
(2017)