Article
Oncology
Gintvile Valinciute, Jonas Ecker, Florian Selt, Thomas Hielscher, Romain Sigaud, Johannes Ridinger, Venu Thatikonda, Charlotte Gatzweiler, Sarah Robinson, Julie Talbot, Flavia Bernardi, Daniel Picard, Mirjam Blattner-Johnson, Simone Schmid, David T. Jones, Cornelis M. van Tilburg, David Capper, Marcel Kool, Marc Remke, Ina Oehme, Stefan M. Pfister, Martine F. Roussel, Olivier Ayrault, Olaf Witt, Till Milde
Summary: The study shows that MYC-amplified medulloblastoma cells are sensitive to class I HDAC inhibitor treatment, but single drug treatment with HDAC inhibitor is not very effective. The addition of a second compound acting synergistically with HDAC inhibitor could enhance efficacy.
JOURNAL OF NEURO-ONCOLOGY
(2023)
Article
Oncology
Duygu Kuzuoglu-Ozturk, Ozlem Aksoy, Christin Schmidt, Robin Lea, Jon D. Larson, Ryan R. L. Phelps, Nicole Nasholm, Megan Holt, Adrian Contreras, Miller Huang, Shannon Wong-Michalak, Hao Shao, Robert Wechsler-Reya, Joanna J. Phillips, Jason E. Gestwicki, Davide Ruggero, William A. Weiss
Summary: Deregulation of N-myc is a major cause of malignant brain tumors in children. This study characterizes the translatome of medulloblastoma and reveals that N-myc drives selective translation of transcripts promoting protein homeostasis. These findings identify a hidden molecular program promoting medulloblastoma formation and suggest potential new therapies for clinical use.
Article
Biochemistry & Molecular Biology
Christophe Le Clorennec, Karen Lee, Yuchen Huo, Peter E. Zage
Summary: USP7 inhibition is a promising therapeutic strategy for high-risk and relapsed neuroblastoma (NB) in children. Inhibiting USP7 activates the p53 pathway, induces apoptosis in NB cells, and reduces N-myc protein levels. The combination of USP7 and MDM2 inhibition shows enhanced efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Marzena Swiderska-Syn, Julia Mir-Pedrol, Alexander Oles, Olga Schleuger, April D. Salvador, Sean M. Greiner, Cara Seward, Fan Yang, Benjamin R. Babcock, Chen Shen, Daniel T. Wynn, Avencia Sanchez-Mejias, Timothy R. Gershon, Vanesa Martin, Heather J. McCrea, Kathryn G. Lindsey, Carsten Krieg, Jezabel Rodriguez-Blanco
Summary: Single-cell transcriptomic analysis of medulloblastoma revealed that vismodegib treatment increased Sox2-expressing astrocyte-like cells. These Sox2(+) cells relied on Sonic Hedgehog (SHH) signaling, with MYC-dependent activation downstream of Smo. GLI inhibitors depleted resistant Sox2(+) cells, reduced their engraftment ability, and increased symptom-free survival.
Article
Multidisciplinary Sciences
Emma Martell, Helgi Kuzmychova, Esha Kaul, Harshal Senthil, Subir Roy Chowdhury, Ludivine Coudiere Morrison, Agnes Fresnoza, Jamie Zagozewski, Chitra Venugopal, Chris M. Anderson, Sheila K. Singh, Versha Banerji, Tamra E. Werbowetski-Ogilvie, Tanveer Sharif
Summary: The involvement of the mitochondrial pyruvate carrier-SOD2 signalling pathway in the regulation of MYC protein abundance in group 3 medulloblastoma is highlighted. MYC oncoprotein is elevated in group 3 medulloblastoma tumors, but the mechanisms behind its elevation remain unclear. Metabolic and mechanistic profiling reveals a role for mitochondrial metabolism in regulating MYC protein abundance.
NATURE COMMUNICATIONS
(2023)
Review
Oncology
Bohan Wang, Yachong Liu, Zhibin Liao, Haofeng Wu, Bixiang Zhang, Lei Zhang
Summary: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death, and the accumulation of genetic and epigenetic changes plays a crucial role in its occurrence and development. Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, is suggested to be a key factor in mediating oncogenesis through epigenetic alteration. Recent studies have shown that EZH2 is extensively involved in the proliferation and metastasis of HCC cells. This review summarizes the functions of EZH2 in HCC progression, its role in tumor immunity, and the application of EZH2-related inhibitors in HCC therapy.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2023)
Article
Engineering, Biomedical
Virender Kumar, Qiyue Wang, Bharti Sethi, Feng Lin, Vinod Kumar, Donald W. Coulter, Yuxiang Dong, Ram Mahato
Summary: Chemoresistance and inadequate therapeutics transport across the blood brain barrier (BBB) remain the major barriers to treating medulloblastoma (MB). Hedgehog (Hh) signaling pathway inhibitors and BRD4/PI3K dual inhibitors show synergistic effects in inhibiting MB cell proliferation and reducing drug resistance. Targeted nanoparticles loaded with these inhibitors can increase drug concentration in the cerebellum and effectively reduce tumor burden without causing hepatic toxicity.
Review
Cell Biology
Zetao Ma, Lei Chen, Yushun Wang, Sheng Zhang, Jianrui Zheng, Yuhong Luo, Chao Wang, Hui Zeng, Lixiang Xue, Zhen Tan, Deli Wang
Summary: Degenerative musculoskeletal diseases, such as osteoporosis, osteoarthritis, degenerative spinal disease, and sarcopenia, have a significant impact on bone, cartilage, and muscle tissues, leading to functional impairment and pain. Enhancer of zeste homolog 2 (EZH2), an epigenetic regulator, plays a crucial role in the development of these diseases through the epigenetic regulation of gene expression. The pharmacological inhibition of EZH2 holds promise as a potential therapeutic approach for improving the treatment of degenerative musculoskeletal diseases.
AGEING RESEARCH REVIEWS
(2023)
Article
Oncology
Jiaqing Yi, BongWoo Kim, Xuanming Shi, Xiaoming Zhan, Q. Richard Lu, Zhenyu Xuan, Jiang Wu
Summary: This study reveals that PRC2 heterogeneity plays an oncogenic role in SHH medulloblastoma, promoting tumor growth. Deletion of PRC2 core subunit EED inhibits tumor growth, while mosaic deletion of EED enhances tumor growth. The presence of EED is essential for maintaining cerebellum granule neuron precursors.
Article
Immunology
Chen Li, Jiagui Song, Zhengyang Guo, Yueqing Gong, Tengrui Zhang, Jiaqi Huang, Rui Cheng, Xiaotong Yu, Yanfang Li, Li Chen, Xiaojuan Ma, Yan Sun, Yan Wang, Lixiang Xue
Summary: This study investigates the role of EZH2 inhibitors in modulating macrophage polarization in the tumor microenvironment of colorectal cancer. The two different EZH2 inhibitors, EPZ6438 and GSK126, were compared. The findings suggest that EZH2 inhibitors not only suppress CRC cell proliferation directly, but also regulate macrophage polarization to exert a tumor suppressive effect.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Zefeng Chen, Dexu Ren, Jinyu Lv, Yuxin Xu, Mengru Xie, Xingbei He, Wen Shi, Qilan Qian, Aixin Jing, Xinhui Ma, Jingting Qin, Yuanyuan Ding, Ting Geng, Jinming Ma, Wei Liu, Shunfang Liu, Jing Ji
Summary: RNF31, a component of the LUBAC complex, promotes carcinogenesis by enhancing cell proliferation, invasion and inhibiting apoptosis in various cancers. The specific molecular mechanism by which RNF31 exerts these effects is still unclear. Our study shows that RNF31 plays an important role in maintaining c-Myc protein levels in cancer cells by extending its half-life and reducing its ubiquitination.
CELLULAR SIGNALLING
(2023)
Article
Chemistry, Multidisciplinary
Qiangsheng Zhang, Xi Hu, Lu Li, Lidan Zhang, Guoquan Wan, Qiang Feng, Yongxia Zhu, Ningyu Wang, Zhihao Liu, Luoting Yu
Summary: SKLB-0335 displays high paralog-selectivity on EZH2 by targeting its unique Cys663, covalently binding to EZH2 at its S-adenosylmethionine (SAM) pocket and inhibiting H3K27Me3. This compound could serve as an effective chemical probe to further investigate the specific biological functions of EZH2.
CHEMICAL COMMUNICATIONS
(2021)
Review
Oncology
Liu Zhaoyun, Jia Yue, Guo Yixuan, Wang Hao, Fu Rong
Summary: In this paper, we reviewed the role of EZH2 in regulating bone marrow mesenchymal stem cell differentiation and immune cell function in the tumor microenvironment, summarized existing EZH2 inhibitors and main clinical trials, and proposed relevant ideas for potential clinical applications.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2022)
Article
Oncology
Matthew L. Fisher, Seamus Balinth, Yon Hwangbo, Caizhi Wu, Carlos Ballon, John E. Wilkinson, Gary L. Goldberg, Alea A. Mills
Summary: BRD4 plays a critical role in the regulation of cancer stem-like properties and is highly elevated in the aggressive subpopulation of cells in squamous cell carcinomas. Targeting BRD4 can effectively inhibit Delta Np63 alpha, reducing spheroid formation and inhibiting tumor growth.
Article
Oncology
Arthur R. Wolin, Melanie Y. Vincent, Taylor Hotz, Stephen C. Purdy, Sheera R. Rosenbaum, Connor J. Hughes, Jessica Y. Hsu, Michael U. J. Oliphant, Brock Armstrong, Veronica Wessells, Marileila Varella-Garcia, Matthew D. Galbraith, Angela Pierce, Dong Wang, Sujatha Venkataraman, Etienne Danis, Bethany Veo, Natalie Serkova, Joaquin M. Espinosa, Daniel L. Gustafson, Rajeev Vibhakar, Heide L. Ford
Summary: The study reveals that the highly expressed EYA2 gene in Group 3 Medulloblastoma (MB) is correlated with MYC gene and has a significant impact on MB growth and patient prognosis. Inhibition of EYA2 tyrosine phosphatase activity shows promising results in reducing MYC expression, providing a novel therapeutic avenue for this deadly disease.
Article
Clinical Neurology
Hiroyuki Yabata, Yufuko Saito, Takaaki Fukuoka, Akio Akagi, Yuichi Riku, Jun Sone, Hiroaki Miyahara, Manabu Doyu, Mari Yoshida, Yasushi Iwasaki
Summary: This article reports an autopsy case of multiple sclerosis (MS) with a long spinal cord lesion, which differs from the traditional anti-AQP4 antibody-negative neuromyelitis optica spectrum disorder (NMOSD), revealing the differences in the pathogenesis of these conditions.
Article
Clinical Neurology
Hiroaki Miyahara, Akio Akagi, Yuichi Riku, Jun Sone, Yasushi Otsuka, Motoko Sakai, Satoshi Kuru, Masato Hasegawa, Mari Yoshida, Akiyoshi Kakita, Yasushi Iwasaki
Summary: This study investigated the pathological features of subacute sclerotic panencephalitis (SSPE), a neurological disorder caused by the measles virus. The study found marked brain atrophy, demyelination, and fibrillary gliosis in the evaluated cases. Immunoreactivity against measles virus was observed in the untreated cases but not in the treated cases. Neurofibrillary tangles and phosphorylated tau were observed, independent of the distribution of the measles virus. The study suggests that tauopathy in SSPE is the result of diffuse brain inflammation triggered by measles, and antiviral therapies may not prevent tauopathy progression.
Article
Oncology
Khoa Pham, Allison R. Hanaford, Brad A. Poore, Micah J. Maxwell, Heather Sweeney, Akhila Parthasarathy, Jesse Alt, Rana Rais, Barbara S. Slusher, Charles G. Eberhart, Eric H. Raabe
Summary: The oncogene MYC alters cellular metabolism and its amplification in medulloblastoma leads to distinct metabolic characteristics. Comprehensive metabolic profiling of MYC-amplified medulloblastoma revealed an increased reliance on targetable metabolic pathways. However, metabolism of MYC-amplified cell lines differed from in vivo tumor models, indicating the importance of in vivo metabolic analyses. Understanding the metabolic vulnerabilities of MYC-amplified medulloblastoma may inform the development of targeted therapies.
Review
Genetics & Heredity
Allison R. Hanaford, Yoon-Jae Cho, Hiroyuki Nakai
Summary: Mitochondrial diseases are rare disorders caused by gene mutations and result in defects in mitochondrial function. Effective treatments are currently lacking. Adeno-associated virus (AAV) gene replacement therapy has shown potential for treating mitochondrial diseases.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Genetics & Heredity
Chen Qian, Xiufu Wu, Tang Jianxun, Chen Zihao, Wenjie Shi, Jingfeng Tang, Ulf D. Kahlert, Renfei Du
Summary: The study developed online models to predict glioblastoma (GBM) survival using extracellular matrix (ECM) genes. It found that five ECM gene signatures were associated with prognosis, and patients with high ECM index had a worse prognosis. Additionally, the study predicted four small molecules that may reduce GBM development. The machine learning models were made available on a publicly accessible website.
FRONTIERS IN GENETICS
(2022)
Article
Oncology
Zhilin Chen, Ruifa Feng, Ulf Dietrich Kahlert, Zhitong Chen, Luz Angela Torres-dela Roche, Amr Soliman, Chen Miao, Rudy Leon De Wilde, Wenjie Shi
Summary: This research investigates the ceRNA network associated with CD8 T cell infiltration in breast cancer. Using expression profiles, differentially expressed RNAs were extracted and two ceRNA networks were constructed. The lncRNAs were used to develop machine learning models to predict CD8 T cell abundances and survival rates of breast cancer patients. The results provide insights into the ceRNA networks related to T cell infiltration and offer accurate models for T cell prediction.
FRONTIERS IN ONCOLOGY
(2022)
Review
Genetics & Heredity
Allison Hanaford, Simon C. Johnson
Summary: Genetic mitochondrial diseases pose a significant challenge to human health, and recent evidence suggests that the immune system plays a key role in the pathogenesis of at least some forms of these diseases.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Oncology
Ulf D. Kahlert, Wenjie Shi, Marco Strecker, Lorenz A. Scherpinski, Thomas Wartmann, Maximilian Doelling, Aristotelis Perrakis, Borna Relja, Miriam Mengoni, Andreas Braun, Roland S. Croner
Summary: This study demonstrates that COL10A1 expression is associated with metastasis and immunogenic properties in colorectal cancer, and its transcription may mediate tumor cell interaction with the stromal microenvironment.
FRONTIERS IN ONCOLOGY
(2022)
Review
Immunology
Elham Poonaki, Ulf Dietrich Kahlert, Sven G. Meuth, Ali Gorji
Summary: Zinc finger E-box binding homeobox 1 (ZEB1) is a critical regulator of epithelial-mesenchymal transition (EMT) and plays a key role in neuroinflammation. The ZEB1-neuroinflammation axis is crucial for the pathogenesis of various CNS disorders and may serve as a diagnostic, prognostic, and therapeutic target.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Oncology
Qiushi Yin, Qiuxi Yang, Wenjie Shi, Ulf D. Kahlert, Zhongyi Li, Shibu Lin, Qifeng Song, Weiqiang Fan, Li Wang, Yi Zhu, Xiaolong Huang
Summary: This study used a two-sample Mendelian randomization analysis to investigate the genetic association between inflammatory traits and liver cancer. The results showed no significant genetic association between extrahepatic immune-mediated diseases, circulating inflammatory biomarkers, cytokines, and liver cancer. These findings have important implications for liver cancer research.
Article
Clinical Neurology
Hiroaki Miyahara, Chisato Tamai, Masanori Inoue, Kazuhito Sekiguchi, Daisuke Tahara, Nao Tahara, Kazuhiro Takeda, Shusei Arafuka, Hideyuki Moriyoshi, Ryuichi Koizumi, Akio Akagi, Yuichi Riku, Jun Sone, Mari Yoshida, Kenji Ihara, Yasushi Iwasaki
Summary: The study found that the m. 3243A>G mutation is closely related to mitochondrial diseases, which can cause mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. The mutation leads to increased mitochondrial DNA heteroplasmy and decreased activity of oxidative phosphorylation complexes. High levels of mtDNA heteroplasmy and various cortical lesions were observed in the brain tissue. Swelling of smooth muscle cells and increased mitochondrial antibody immunoreactivity in vessels on the leptomeninges, as well as increased cytoplasmic size of epithelial cells in the choroid plexus, could serve as neuropathological hallmarks for the diagnosis of mitochondrial diseases.
Article
Multidisciplinary Sciences
Anna Schaufler, Ahmed Y. Sanin, I. Erol Sandalcioglu, Karl Hartmann, Roland S. Croner, Aristotelis Perrakis, Thomas Wartmann, Axel Boese, Ulf D. Kahlert, Igor Fischer
Summary: The current treatment for glioblastoma has limitations and can often result in recurrence. Standard MRI imaging surveillance may not accurately detect histological changes, leading to incorrect conclusions about treatment and interventions. To address these challenges, an implantable system using optical sensing of cancer cells is proposed to continuously monitor glioblastoma recurrence. The feasibility of the sensing principle has been demonstrated through experimental trials, and the system design has been further developed to include wireless energy transfer and power management circuitry.
SCIENTIFIC REPORTS
(2023)
Article
Clinical Neurology
Takashi Ando, Yuichi Riku, Akio Akagi, Hiroaki Miyahara, Takashi Uematsu, Ikuko Aiba, Jun Sone, Masahisa Katsuno, Mari Yoshida, Yasushi Iwasaki
Summary: Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder characterized by various combinations of autonomic dysfunction, cerebellar ataxia, parkinsonism, and pyramidal signs. This study found degeneration of the olivospinal tract in MSA patients, which was associated with younger age at disease onset, longer disease duration, and more severe olivopontocerebellar changes. The impaired neural connection between the inferior olivary nucleus and the spinal cord may develop in a descending manner in MSA.
Article
Chemistry, Analytical
Lennard M. Wurm, Bjoern Fischer, Volker Neuschmelting, David Reinecke, Igor Fischer, Roland S. Croner, Roland Goldbrunner, Michael C. Hacker, Jakub Dybas, Ulf D. Kahlert
Summary: Label-free identification of tumor cells using spectroscopic assays combined with machine learning algorithms can improve the rapid implementation of clinical care. The ability to distinguish different types of tumor cells and their phenotypes is important for accurate diagnosis and treatment.
Letter
Hematology
Lennart Lenk, Dorothee Winterberg, Fotini Vogiatzi, Anna Laqua, Lea Spory, Ahmad Mayar, Anna Dietterle, Gina Muench, Christian Vokuhl, Julia Richter, Andrew G. Polson, Thomas Schueler, Ulf D. Kahlert, Matthias Peipp, Thomas Valerius, Martin Schrappe, Gunnar Cario, Hassan Jumaa, Elias Hobeika, Monika Brueggemann, Ameera Alsadeq, Denis M. Schewe