Review
Oncology
Colin Thorbinson, John-Paul Kilday
Summary: Brain tumors are the leading cause of childhood cancer deaths in developed countries, representing the most common solid tumor in this age group, accounting for approximately one-quarter of all pediatric cancers. Developments in neuro-imaging, neurosurgical techniques, adjuvant therapy, and supportive care have improved survival rates for certain tumors, allowing a focus on optimizing cure while minimizing long-term adverse effects. Recent advancements in the molecular characterization of common pediatric brain tumors have identified unique clinical and biological patient subgroups, but achieving a paradigm shift in translational therapy and subsequent survival for many tumors remains challenging, with recurrence presenting a significant clinical challenge. This review provides insight into key molecular developments and global cooperative trial results for the most common malignant pediatric brain tumors, highlighting potential future directions for management, including novel therapeutic options and unresolved critical challenges.
Review
Pediatrics
Weiya Mu, Hisham Dahmoush
Summary: This article discusses the classification, imaging characteristics, and clinical settings of ependymal tumors. The tumors are categorized based on histopathologic and molecular features and location, and accurate diagnosis and treatment rely on knowledge of the updated WHO classification and MRI imaging features.
FRONTIERS IN PEDIATRICS
(2023)
Article
Biochemistry & Molecular Biology
Joshua Branter, Maria Estevez-Cebrero, Mohammed Diksin, Michaela Griffin, Marcos Castellanos-Uribe, Sean May, Ruman Rahman, Richard Grundy, Surajit Basu, Stuart Smith
Summary: The lack of treatment options for high-grade brain tumors has led to the exploration of alternative therapeutic modalities, including electrical field therapy. This study demonstrates the effectiveness of electric fields, delivered via TTFields or Deep Brain Stimulation (DBS), in inhibiting the viability of brain tumor cell lines. The study also uncovers potential mechanisms of action, with both treatments affecting cell cycle progression and showing interactions with mitochondrial functioning and endoplasmic reticulum stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Andrew M. Donson, Kelsey C. Bertrand, Kent A. Riemondy, Dexiang Gao, Yonghua Zhuang, Bridget Sanford, Gregory A. Norris, Rebecca J. Chapman, Rui Fu, Nicholas Willard, Andrea M. Griesinger, Graziella Ribeiro de Sousa, Vladimir Amani, Enrique Grimaldo, Todd C. Hankinson, Ffyona Booker, Martin Sill, Richard G. Grundy, Kristian W. Pajtler, David W. Ellison, Nicholas K. Foreman, Timothy A. Ritzmann
Summary: The study focuses on the biology of recurrent PFA and reveals that chromosomal changes at recurrence are associated with poor prognosis. The genetic evolution of neoplastic cells leads to cellular heterogeneity in PFAs.
Review
Oncology
Raffaella De Pietro, Lucy Zaccaro, Francesco Marampon, Paolo Tini, Francesca De Felice, Giuseppe Minniti
Summary: There is currently no standard treatment for recurrent brain tumors, and managing them remains challenging. Advances in radiation therapy technology have allowed for more precise tumor localization and dose delivery, with techniques including IMRT, VMAT, SRS, and SRT. The use of reirradiation as a treatment option has been debated due to the controversial survival benefit and treatment-related toxicity. This article critically discusses the clinical status and technical challenges of reirradiation in patients with primary brain tumors and brain metastases, including radiation techniques, patient selection, optimal dose and fractionation, brain tolerance to reirradiation, and the risk of adverse radiation effects.
JOURNAL OF NEURO-ONCOLOGY
(2023)
Review
Oncology
Raffaella De Pietro, Lucy Zaccaro, Francesco Marampon, Paolo Tini, Francesca De Felice, Giuseppe Minniti
Summary: Despite the availability of various treatments for recurrent brain tumors, there are still challenges in managing this condition. Advances in imaging and radiation therapy technology have allowed for more precise tumor targeting and reduced damage to healthy brain tissue. Reirradiation has been suggested as a possible treatment option, but its benefits and potential side effects remain controversial.
JOURNAL OF NEURO-ONCOLOGY
(2023)
Article
Pathology
Luke C. Olson, Joel A. Lefferts, Robert E. LeBlanc, Shaofeng Yan, Shabnam Momtahen, Aravindhan Sriharan, Konstantinos Linos
Summary: This study investigated melanocytic nevi in patients aged 40 to 74 years, identifying reproducible histomorphologic features and copy number gain of chromosome 15q. Despite cytologic variations, the histologic features showed limited variability and a characteristic pattern, without staining with BRAF V600E or NRAS Q61R immunohistochemistry. Further studies are needed to better understand the clinical and biological behavior of these lesions.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2021)
Article
Cell Biology
Ana Cristina Vargas, Nima M. Ardakani, Daniel D. Wong, Fiona M. Maclean, Joseph Kattampallil, Richard Boyle, Leonardo Santos, Anthony J. Gill
Summary: NTRK-rearranged sarcomas are a heterogeneous group of tumors with either relatively simple or complex karyotypes. Chromosomal copy number variations involve multiple chromosomes, with complex karyotypes associated with more aggressive clinical behavior. Gains at chromosome 6p and 1q were the most common recurrent genetic alterations.
Review
Neurosciences
Panagiotis Skouras, Mariam Markouli, Dimitrios Strepkos, Christina Piperi
Summary: Pediatric malignant brain tumors are the leading cause of cancer-related deaths in children. Despite improvements in patient management, the prognosis for these tumors remains poor. Recent advancements in molecular targets and mechanisms have opened up new possibilities for personalized therapy. Epigenetic drugs, such as DNA methyltransferase inhibitors and histone deacetylase inhibitors, are currently being tested in clinical trials and show promise in enhancing the efficacy of current treatment approaches.
CURRENT NEUROPHARMACOLOGY
(2023)
Review
Pediatrics
Edwin S. Kulubya, Matthew J. Kercher, H. Westley Phillips, Reuben Antony, Michael S. B. Edwards
Summary: Pediatric brain tumors are the most common solid malignancies in children. Advances in imaging, biopsy, surgical techniques, and molecular profiling have opened up opportunities for targeted therapies and immunotherapy in clinical trials for the most common types of pediatric brain tumors. This review discusses the latest efforts and challenges in targeted molecular therapy, immunotherapy, and newer modalities such as laser interstitial thermal therapy.
Article
Oncology
Nayan Lamba, Andrew Groves, Matthew Torre, Kee Kiat Yeo, J. Bryan Iorgulescu
Summary: This study evaluates the epidemiology of primary and metastatic pediatric brain tumors in the United States based on the WHO CNS 4th and 5th editions classifications. The results show the prevalence and characteristics of different types of tumors in pediatric patients, highlighting the differences in age distribution and racial/ethnic predisposition. The study provides important insights into the understanding of pediatric brain tumors.
JOURNAL OF NEURO-ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Tzu-Hsuan Chuang, Zih-Huei Wu, Chin-Sheng Kuan, Meng-Ju Lee, Chia-Lin Hsieh, Huai-Lin Wang, Hsing-Hua Lai, Yu-Jen Chang, Shee-Uan Chen
Summary: Ion S5 and Miseq NGS systems are widely used in clinical laboratories for PGT-A, with different library preparation steps and data processing algorithms. Both systems have shown comparable ability in detecting ploidy.
SCIENTIFIC REPORTS
(2021)
Review
Clinical Neurology
Heather L. Smith, Nitin Wadhwani, Craig Horbinski
Summary: This review discusses the significant changes in the World Health Organization classification scheme for central nervous system tumors in 2021, including the definition of tumor types and subtypes by key molecular features, the introduction of new supercategories, and the impact on diagnosis and treatment.
Article
Medical Laboratory Technology
Ann-Kristin Afflerbach, Christian Rohrandt, Bjorn Brandl, Marthe Soenksen, Jurgen Hench, Stephan Frank, Daniela Boernigen, Malik Alawi, Martin Mynarek, Beate Winkler, Franz Ricklefs, Michael Synowitz, Lasse Duehrsen, Stefan Rutkowski, Annika K. Wefers, Franz-Josef Mueller, Melanie Schoof, Ulrich Schueller
Summary: The research suggests that using cfDNA from cerebrospinal fluid for Nanopore sequencing could be a promising approach for initial brain tumor diagnosis and an important tool for disease monitoring.
CLINICAL CHEMISTRY
(2023)
Review
Pediatrics
Cleiton Formentin, Andrei Fernandes Joaquim, Enrico Ghizoni
Summary: Pediatric posterior fossa tumors have a higher incidence rate compared to adult tumors. Molecular biomarkers play a crucial role in the diagnosis, prognosis, and treatment of these tumors. The current treatment strategy is mainly based on surgical resection, but molecular targeted therapies are also being explored.
EUROPEAN JOURNAL OF PEDIATRICS
(2023)
Article
Genetics & Heredity
Masashi Nishikawa, Marcello Scala, Muhammad Umair, Hidenori Ito, Ahmed Waqas, Pasquale Striano, Federico Zara, Gregory Costain, Valeria Capra, Koh-ichi Nagata
Summary: In this study, a novel RAC3 variant (p.F28S) was identified to play a critical role in brain development, leading to morphological and functional defects in cortical neurons, likely due to hyperactivation of PAK1.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Clinical Neurology
Jeffrey D. Calhoun, Miriam C. Aziz, Hannah C. Happ, Jonathan Gunti, Colleen Gleason, Najma Mohamed, Kristy Zeng, Meredith Hiller, Emily Bryant, Divakar S. Mithal, Irena Bellinski, Lisa Kinsley, Mona Grimmel, Eva M. C. Schwaibold, Constance Smith-Hicks, Anna Chassevent, Marcello Scala, Andrea Accogli, Annalaura Torella, Pasquale Striano, Valeria Capra, Lynne M. Bird, Issam Ben-Sahra, Nina Ekhilevich, Tova Hershkovitz, Karin Weiss, John Millichap, Elizabeth E. Gerard, Gemma L. Carvill
Summary: Biallelic pathogenic variants in SZT2 are associated with a neurodevelopmental disorder characterized by early-onset epilepsy, developmental delay, macrocephaly, and corpus callosum abnormalities. A novel assay was developed to identify SZT2 variants and reclassify variants of uncertain significance, leading to the identification of a recurrent loss-of-function variant and refinement of the phenotypic spectrum. This approach has wider applicability to other mTORopathies.
Article
Clinical Neurology
Thea Giacomini, Marcello Scala, Giulia Nobile, Mariasavina Severino, Domenico Tortora, Lino Nobili, Andrea Accogli, Annalaura Torella, Valeria Capra, Maria Margherita Mancardi, Vincenzo Nigro
Summary: This case expands the clinical spectrum of POLR2A-related syndrome, highlighting its phenotypic variability and supporting the relevance of epilepsy as a core feature of this emerging condition.
BRAIN & DEVELOPMENT
(2022)
Review
Developmental Biology
Ferruccio Romano, Mariateresa Falco, Gerarda Cappuccio, Nicola Brunetti-Pierri, Fortunato Lonardo, Annalaura Torella, Maria Cristina Digilio, Maria Lisa Dentici, Paolo Alfieri, Emanuele Agolini, Antonio Novelli, Livia Garavelli, Andrea Accogli, Pasquale Striano, Gioacchino Scarano, Vincenzo Nigro, Marcello Scala, Valeria Capra
Summary: In this study, five novel truncating variants in AHDC1 were identified in five XGS patients, expanding the genotype and phenotypic spectrum of this complex condition. The reported patients exhibited developmental delay, hypotonia, and distinctive facial dysmorphisms, along with uncommon clinical features such as congenital hypothyroidism and peculiar skeletal abnormalities.
BIRTH DEFECTS RESEARCH
(2022)
Letter
Clinical Neurology
Marcello Scala, Elisa De Grandis, Giulia Nobile, Michele Iacomino, Francesca Madia, Valeria Capra, Lino Nobili, Federico Zara, Pasquale Striano
Article
Clinical Neurology
Ana Filipa Geraldo, Cesar Augusto P. F. Alves, Aysha Luis, Domenico Tortora, Joana Guimaraes, Daisy Abreu, Sofia Reimao, Marco Pavanello, Patrizia de Marco, Marcello Scala, Valeria Capra, Rui Vaz, Andrea Rossi, Erin Simon Schwartz, Kshitij Mankad, Mariasavina Severino
Summary: This study investigates the neuroimaging findings and longitudinal evaluation of familial cerebral cavernous malformations (FCCM) in children. It reveals that the incidence and risk factors of symptomatic hemorrhage in children with FCCM are comparable to those in adults. Imaging features at the first brain MRI may help predict future symptomatic hemorrhage.
Article
Chemistry, Multidisciplinary
Dan Wu, Gonzalo Duran-Sampedro, Sheila Fitzgerald, Massimiliano Garre, Donal F. O'Shea
Summary: Sequential azide/diyne cycloadditions were used for efficient macrocyclization of a bis-azido aza-dipyrrin. Macrocyclic aza-dipyrrin could be obtained in just 30 minutes at room temperature in water, with measurable changes in fluorescence intensity and lifetimes during the reaction. Live cell microscopy demonstrated the suitability of aza-dipyrrins for confocal and STED super-resolution imaging, and a bioorthogonal response to macrocyclization was observed in cellular compartments. These findings will encourage further exploration of the sensing and imaging applications of aza-dipyrrins.
CHEMICAL COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Niamh Curtin, Massimiliano Garre, Dan Wu, Donal F. F. O'Shea
Summary: BF2-azadipyrromethenes are versatile fluorophores used for cellular and in vivo imaging in the near-infrared and far-red regions. However, their usage with super-resolution imaging techniques like STED nanoscopy has not been explored. In this study, a series of structurally related BF2-azadipyrromethenes were evaluated for their suitability in STED imaging. The study demonstrated successful live cell STED imaging using far-red emitting BF2-azadipyrromethenes, achieving resolution below the diffraction limit.
Article
Clinical Neurology
Gelsomina Aruta, Pietro Fiaschi, Marco Ceraudo, Gianluca Piatelli, Valeria Capra, Andrea Bianconi, Andrea Rossi, Francesca Secci, Marco Pavanello
Summary: This article examines the association between multisutural craniosynostosis with Chiari malformation (CM), venous hypertension, and hydrocephalus, and proposes a simple and effective therapeutic flow-chart for managing these rare pathologies.
PEDIATRIC NEUROSURGERY
(2023)
Article
Developmental Biology
Ferruccio Romano, Francesca Madia, Patrizia De Marco, Marzia Ognibene, Sara Guerrisi, Marcello Scala, Michele Iacomino, Simona Baldassari, Nadia Vercellino, Francesca Manunza, Ramona Tallone, Marco Pavanello, Gianluca Piatelli, Alberto Garaventa, Federico Zara, Valeria Capra
Summary: Segmental overgrowth syndromes are a group of clinical entities characterized by excessive tissue or organ proliferation in association with vascular abnormalities, ranging from limited involvement to complex cases. Somatic mutations in genes of the mTOR pathway are responsible for these syndromes, and not all cells carry the same causative mutation.
BIRTH DEFECTS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Simona Amenta, Giuseppe Marangi, Daniela Orteschi, Silvia Frangella, Fiorella Gurrieri, Elisa Paccagnella, Marcello Scala, Ferruccio Romano, Valeria Capra, Vincenzo Nigro, Marcella Zollino
Summary: Loss-of-function variants in CHAMP1 cause intellectual disability, autism, and distinctive facial characteristics, possibly through haploinsufficiency or a dominant negative effect. In addition, a deletion and a missense variant in CHAMP1 are associated with borderline neurodevelopmental impairment and refractory seizures, respectively. This study suggests that loss-of-function variants in CHAMP1 lead to a severe phenotype, while haploinsufficiency may result in milder impairment and missense variants are associated with severe epileptic encephalopathy.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Gianluca D'Onofrio, Marcello Scala, Mariasavina Severino, Roberta Roberti, Ferruccio Romano, Patrizia De Marco, Michele Iacomino, Simona Baldassari, Paolo Uva, Marco Pavanello, Stefano Gustincich, Pasquale Striano, Federico Zara, Valeria Capra
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Rute Luisa Cabrita Pinto, Silvia Viaggi, Edoardo Canale, Marina Martinez Popple, Valeria Capra, Giuseppina Conteduca, Barbara Testa, Domenico Coviello, Angela Elvira Covone
Summary: This article describes a pediatric patient from Italy with Joubert Syndrome who carries a novel missense and deletion variant in the CC2D2A gene, identified through whole exome sequencing.
Article
Oncology
Marzia Ognibene, Marcello Scala, Michele Iacomino, Irene Schiavetti, Francesca Madia, Monica Traverso, Sara Guerrisi, Marco Di Duca, Francesco Caroli, Simona Baldassari, Barbara Tappino, Ferruccio Romano, Paolo Uva, Diego Vozzi, Cristina Chelleri, Gianluca Piatelli, Maria Cristina Diana, Federico Zara, Valeria Capra, Marco Pavanello, Patrizia De Marco
Summary: In this study, rare variants of the RNF213 gene were investigated as potential genetic modifiers of Moyamoya syndrome (MMS) phenotype in a pediatric cohort of patients. Next-generation sequencing revealed that RNF213 does not modify the risk of Moyamoya occurrence in MMS patients. Instead, the loss of neurofibromin 1, encoded by the NF1 gene, is likely responsible for the excessive proliferation of vascular smooth muscle cells leading to arterial stenosis. Further studies are needed to confirm these findings and identify other genetic factors in MMS pathogenesis.
Article
Chemistry, Multidisciplinary
Cathal Caulfield, Dan Wu, Massimiliano Garre, Donal F. O'Shea
Summary: Three bis(anilino)-substituted NIR-AZA fluorophores were designed, synthesized, and tested for live-cell microscopy imaging in the 800-850 nm spectral range. The synthetic route allowed for the introduction of tailored peripheral substituents to guide sub-cellular localization and imaging. Successful imaging of lipid droplets, plasma membrane, and cytosolic vacuoles was achieved, and the photophysical and ICT properties of each fluorophore were examined.
Review
Oncology
Xinru Zhou, Yin Jia, Chuanbin Mao, Shanrong Liu
Summary: Small extracellular vesicles (sEVs), such as exosomes, have emerged as crucial targets for liquid biopsy and promising drug delivery vehicles in tumor progression. They can serve as biomarkers for tumor diagnosis and as drug carriers for cancer treatment.
Article
Oncology
Ruochan Chen, Ju Zhu, Xiao Zhong, Jie Li, Rui Kang, Daolin Tang
Summary: The interplay between autophagy and apoptosis plays a crucial role in tumorigenesis and cancer therapy, with HMGB1 serving as a key regulator in these processes.
Article
Oncology
Zongfu Pan, Xixuan Lu, Tong Xu, Jinming Chen, Lisha Bao, Ying Li, Yingying Gong, Yulu Che, Xiaozhou Zou, Zhuo Tan, Ping Huang, Minghua Ge
Summary: This study uncovered the emerging role of HN1 in promoting dedifferentiation of anaplastic thyroid cancer (ATC) cells. HN1 negatively regulated the thyroid differentiation markers and had an inhibitory effect on the transcriptional activation of CTCF, thereby influencing the chromatin accessibility of thyroid differentiation genes.
Article
Oncology
Yi Qin, Shengjun Xiong, Jun Ren, Gautam Sethi
Summary: Autophagy plays an important regulatory role in glioblastoma, and its dysregulation can lead to drug resistance and radioresistance. It also affects stem cell characteristics, overall growth, and metastasis. Therefore, autophagy is a promising target for glioblastoma therapy.
Article
Oncology
Katsuya Nagaoka, Xuewei Bai, Dan Liu, Kevin Cao, Joud Mulla, Chengcheng Ji, Hongze Chen, Muhammad Azhar Nisar, Amalia Bay, William Mueller, Grace Hildebrand, Jin-Song Gao, Shaolei Lu, Hiroko Setoyama, Yasuhito Tanaka, Jack R. Wands, Chiung-Kuei Huang
Summary: This study found that serum 2-OG levels in cholangiocarcinoma patients are associated with the effectiveness of chemotherapy. Patients with progressive disease showed significantly higher levels of serum 2-OG compared to stable disease and partial response patients. The study also revealed that overexpression of ASPH mimics the effects of 2-OG, and knockdown of ASPH improves chemotherapy. Targeting ASPH enhances the effects of chemotherapy by modulating ATM and ATR, two key regulators of DDRs.
