Review
Oncology
Yujia Chen, Chao Zhao, Shenglun Li, Jun Wang, Hongwei Zhang
Summary: Diffuse intrinsic pontine glioma (DIPG) is a malignant primary glial tumor that mainly affects children and lacks effective treatment methods. Immunotherapy has shown promise in the treatment of DIPG, and this review summarizes the immune profile of DIPG and the results of clinical trials, aiming to clarify the development of novel immunotherapies for DIPG treatment.
Article
Biochemistry & Molecular Biology
Farshad Nassiri, Vikas Patil, Leeor S. Yefet, Olivia Singh, Jeff Liu, Rachel M. A. Dang, Takafumi N. Yamaguchi, Mariza Daras, Timothy F. Cloughesy, Howard Colman, Priya U. Kumthekar, Clark C. Chen, Robert Aiken, Morris D. Groves, Shirley S. Ong, Rohan Ramakrishna, Michael A. Vogelbaum, Simon Khagi, Thomas Kaley, Jason M. Melear, David M. Peereboom, Analiz Rodriguez, Maxim Yankelevich, Suresh G. Nair, Vinay K. Puduvalli, Kenneth Aldape, Andrew Gao, Alvaro Lopez-Janeiro, Carlos E. de Andrea, Marta M. Alonso, Paul Boutros, Joan Robbins, Warren P. Mason, Adam M. Sonabend, Roger Stupp, Juan Fueyo, Candelaria Gomez-Manzano, Frederick F. Lang, Gelareh Zadeh
Summary: Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, were evaluated in a multicenter phase 1/2 study for the treatment of recurrent glioblastoma. The combination of intratumoral DNX-2401 followed by intravenous pembrolizumab showed notable survival benefit with an objective response rate of 10.4% and overall survival at 12 months of 52.7%. Exploratory analyses suggested potential predictors of treatment response and resistance. Overall, this combination therapy demonstrated promising results in select patients with glioblastoma.
Article
Oncology
Michael Chastkofsky, Katarzyna C. Pituch, Hiroaki Katagi, Markella Zannikou, Liliana Ilut, Ting Xiao, Yu Han, Adam M. Sonabend, David T. Curiel, Erin R. Bonner, Javad Nazarian, Craig M. Horbinski, C. David James, Amanda M. Saratsis, Rintaro Hashizume, Maciej S. Lesniak, Irina Balyasnikova
Summary: The study demonstrates that oncolytic virus loaded MSCs can efficiently deliver to DIPG cells and release within brainstem xenografts in mice, leading to prolonged survival when combined with radiotherapy.
CLINICAL CANCER RESEARCH
(2021)
Article
Clinical Neurology
Changcun Pan, Mingxin Zhang, Xiong Xiao, Lu Kong, Yuliang Wu, Xiaobin Zhao, Tao Sun, Peng Zhang, Yibo Geng, Pengcheng Zuo, Yi Wang, Xiaoou Li, Guocan Gu, Tian Li, Zhen Wu, Junting Zhang, Liwei Zhang
Summary: In this study, a multimodal imaging-based radiological classification was established for pediatric DIPG, which was useful for selecting optimal treatment strategies. Four radiological DIPG types were identified and the effects of different treatment modalities were compared. CRS+RT showed a potential survival advantage compared to RT alone.
NEUROSURGICAL REVIEW
(2023)
Article
Oncology
Peng Zhang, Yunyun Duan, Guocan Gu, Liying Qu, Dan Xiao, Tianshu Xi, Changcun Pan, Ya'ou Liu, Liwei Zhang
Summary: This retrospective study investigated the clinical, radiological, and pathological features of 80 pediatric diffuse intrinsic pontine gliomas (DIPGs). The most common symptoms were cranial nerve palsy and limb weakness. Radiological results showed enhancement as a common feature. Surgery followed by comprehensive therapy improved overall survival, and H3K27 alteration was identified as an independent prognostic factor for DIPGs.
FRONTIERS IN ONCOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Joji Ishida, Saira Alli, Andrew Bondoc, Brian Golbourn, Nesrin Sabha, Kristina Mikloska, Stacey Krumholtz, Dilakshan Srikanthan, Naohide Fujita, Amanda Luck, Colin Maslink, Christian Smith, Kullervo Hynynen, James Rutka
Summary: Diffuse intrinsic pontine glioma (DIPG) is a devastating tumor in children that cannot be surgically removed, and MRI-guided focused ultrasound (MRgFUS) shows promise in enhancing drug delivery for DIPG treatment.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Oncology
Michelle Monje, Tabitha Cooney, John Glod, Jie Huang, Cody J. Peer, Damien Faury, Patricia Baxter, Kim Kramer, Alicia Lenzen, Nathan J. Robison, Lindsay Kilburn, Anna Vinitsky, William D. Figg, Nada Jabado, Maryam Fouladi, Jason Fangusaro, Arzu Onar-Thomas, Ira J. Dunkel, Katherine E. Warren
Summary: This study aimed to determine the safety, tolerability, maximum tolerated dose, toxicity profile, and pharmacokinetics of panobinostat in children with DIPG. The study found that the maximum tolerated dose of panobinostat for children with progressive DIPG is 10 mg/m2/dose administered 3 times per week for 3 weeks on/1 week off, and for children with nonprogressive DIPG/DMG is 22 mg/m2/dose administered 3 times per week for 1 week on/1 week off.
Article
Chemistry, Multidisciplinary
Shaobo Shan, Junge Chen, Yu Sun, Yongchao Wang, Bozhang Xia, Hong Tan, Changcun Pan, Guocan Gu, Jie Zhong, Guangchao Qing, Yuxuan Zhang, Jinjin Wang, Yufei Wang, Yi Wang, Pengcheng Zuo, Cheng Xu, Fangzhou Li, Weisheng Guo, Lijun Xu, Meiwan Chen, Yubo Fan, Liwei Zhang, Xing-Jie Liang
Summary: This study developed a nano drug delivery system based on functionalized macrophage exosomes, which could efficiently deliver drugs and gene therapeutics for targeted therapy of DIPG tumor cells, resulting in prolonged survival of patients.
Review
Health Care Sciences & Services
Shahrukh Farrukh, Shagufta Habib, Amna Rafaqat, Zouina Sarfraz, Azza Sarfraz, Muzna Sarfraz, Karla Robles-Velasco, Miguel Felix, Ivan Cherrez-Ojeda
Summary: This research article summarizes recent clinical trial data and identifies the most promising therapies for diffuse intrinsic pontine glioma (DIPG) in the past five years. The study finds that re-irradiation may prolong survival in patients with progressive DIPG and highlights the importance of palliative radiotherapy as a prognostic choice.
Article
Medicine, Research & Experimental
Virginia Laspidea, Montserrat Puigdelloses, Sara Labiano, Lucia Marrodan, Marc Garcia-Moure, Marta Zalacain, Marisol Gonzalez-Huarriz, Naiara Martinez-Velez, Iker Ausejo-Mauleon, Daniel de la Nava, Guillermo Herrador-Canete, Javier Marco-Sanz, Elisabeth Guruceaga, Carlos E. de Andrea, Maria Villalba, Oren Becher, Massimo Squatrito, Veronica Matia, Jaime Gallego Perez-Larraya, Ana Patino-Garcia, Sumit Gupta, Candelaria Gomez-Manzano, Juan Fueyo, Marta M. Alonso
Summary: The study found that Delta-24-ACT treatment with oncolytic adenovirus can significantly improve the survival rate of mice with DIPG, leading to long-term survival and the development of immunological memory. In addition, this treatment method is safe and has no toxic side effects, and can modulate tumor-immune content.
Article
Biochemistry & Molecular Biology
David Roig-Carles, Holly Jackson, Katie F. Loveson, Alan Mackay, Rebecca L. Mather, Ella Waters, Massimiliano Manzo, Ilaria Alborelli, Jon Golding, Chris Jones, Helen L. Fillmore, Francesco Crea
Summary: The research found that H19 lncRNA is highly expressed in DIPG, and knocking down H19 can result in decreased proliferation and survival of DIPG cells. H19 functions as a buffer for let-7 microRNAs, leading to the up-regulation of oncogenic let-7 targets, making it a promising therapeutic candidate for DIPG.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Min Wang, Yi Zhang, Wei Shi, Renqing Zhu, Hao Li, Rui Zhao
Summary: This study compared the value of microsurgical biopsies and frameless robot-assisted stereotactic biopsies in the treatment of pediatric DIPGs. The results showed that frameless robot-assisted stereotactic biopsy is an effective and minimally invasive technique, which can reduce operation time, postoperative hospitalization time, and bleeding volume compared to microsurgical biopsies. It also decreases the need for perioperative blood transfusion and the occurrence of new neurological impairments.
JOURNAL OF NEURO-ONCOLOGY
(2022)
Article
Neurosciences
Guisheng Zhao, Patrick Newbury, Yukitomo Ishi, Eugene Chekalin, Billy Zeng, Benjamin S. Glicksberg, Anita Wen, Shreya Paithankar, Takahiro Sasaki, Amreena Suri, Javad Nazarian, Michael E. Pacold, Daniel J. Brat, Theodore Nicolaides, Bin Chen, Rintaro Hashizume
Summary: This study used a computational pipeline and cell experiments to identify potential drugs for treating diffuse intrinsic pontine glioma (DIPG). Two drugs, Triptolide and mycophenolate mofetil (MMF), were found to have the ability to reverse DIPG gene signatures and inhibit tumor growth in both in vitro and in vivo models. This novel approach allows for drug repurposing and reduces the cost and time required for drug discovery.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Neurosciences
Xiaolei Lian, Dina Kats, Samuel Rasmussen, Leah R. Martin, Anju Karki, Charles Keller, Noah E. Berlow
Summary: DIPG, a rare pediatric brain tumor, is highly lethal with current treatments showing limited success. IL13R alpha 2 has been identified as a potential therapeutic target, with anti-IL13R alpha 2 antibody-drug conjugates showing strong pharmacological response in DIPG cell models.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Maria Grazia Perrone, Antonio Ruggiero, Antonella Centonze, Antonio Carrieri, Savina Ferorelli, Antonio Scilimati
Summary: DIPG is a dangerous tumor that mainly affects children, with a low survival rate. Current treatments primarily involve radiotherapy, but new drugs like ONC201 may offer potential for further research.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Dentistry, Oral Surgery & Medicine
Nancy Lyn Wilson Westmark, Herve Sroussi, Ibon Tamayo, Alessandro Villa
Article
Oncology
Lide Alana, Caroline E. Nunes-Xavier, Laura Zaldumbide, Idoia Martin-Guerrero, Lorena Mosteiro, Piedad Alba-Pavon, Olatz Villate, Susana Garcia-Obregon, Hermenegildo Gonzalez-Garcia, Raquel Herraiz, Itziar Astigarraga, Rafael Pulido, Miguel Garcia-Ariza
Summary: In this study, we analyzed the histology, molecular characteristics, and functional properties of 88 pediatric medulloblastoma tumor samples. We identified a subset of patients with WNT activation, characterized by CTNNB1 mutations and nuclear beta-catenin staining. We also discovered a novel CTNNB1 mutation resulting in the deletion of beta-catenin Ser37 residue. Functional analysis showed that the Delta S37 beta-catenin variant exhibited higher protein expression levels and increased TCF/LEF transcriptional activity in cells.
Article
Medicine, Research & Experimental
Virginia Laspidea, Montserrat Puigdelloses, Sara Labiano, Lucia Marrodan, Marc Garcia-Moure, Marta Zalacain, Marisol Gonzalez-Huarriz, Naiara Martinez-Velez, Iker Ausejo-Mauleon, Daniel de la Nava, Guillermo Herrador-Canete, Javier Marco-Sanz, Elisabeth Guruceaga, Carlos E. de Andrea, Maria Villalba, Oren Becher, Massimo Squatrito, Veronica Matia, Jaime Gallego Perez-Larraya, Ana Patino-Garcia, Sumit Gupta, Candelaria Gomez-Manzano, Juan Fueyo, Marta M. Alonso
Summary: The study found that Delta-24-ACT treatment with oncolytic adenovirus can significantly improve the survival rate of mice with DIPG, leading to long-term survival and the development of immunological memory. In addition, this treatment method is safe and has no toxic side effects, and can modulate tumor-immune content.
Article
Clinical Neurology
Seojin Lee, Ivan Martinez-Valbuena, Carlos E. de Andrea, Maria Villalba-Esparza, Suganthini Ilaalagan, Blas Couto, Naomi P. Visanji, Anthony E. Lang, Gabor G. Kovacs
Summary: This study provides the first cell type-specific evaluation of iron homeostasis and oxygen homeostasis in relation to tau pathology in patients with progressive supranuclear palsy (PSP). Astrocytes were identified as the major cell type accumulating iron in the early affected regions of PSP, highly associated with tau pathology. Dysregulated expression of iron and oxygen homeostasis genes associated with brain aging was also found, as well as dysregulated expression of rare neurodegeneration with brain iron accumulation (NBIA) genes associated with tau pathology, distinguishing PSP from the healthy aging brain.
ANNALS OF NEUROLOGY
(2023)
Letter
Dermatology
Javier Antonanzas, Elena Querol-Cisneros, Gorka Alkorta-Aranburu, Ana Patino-Garcia, Agustin Espana
INTERNATIONAL JOURNAL OF DERMATOLOGY
(2023)
Article
Biochemical Research Methods
Manuela Gonzalez-Aparicio, Maria Bunuales, Inaki Ortiz de Landazuri, Jesus Prieto, Ruben Hernandez-Alcoceba
Summary: This study improves the performance of packaging cells and increases the production efficiency of high-capacity adenoviral vectors (HC-AdV) by using a dimerizable Cre system. It also reduces the time and cost of HC-AdV production, contributing to the standardization of HC-AdV production.
BIOTECHNOLOGY JOURNAL
(2023)
Article
Orthopedics
M. San-Julian, J. Gomez-Alvarez, M. a. Idoate, J. D. Aquerreta, B. Vazquez-Garcia, J. M. Lamo-Espinosa
Summary: Canadell's technique involves pre-resection Type I epiphysiolysis with continuous distraction using an external fixator, aiming to achieve safe margin resection, avoid joint reconstruction, and preserve growth capacity, playing a significant role in the treatment of paediatric bone sarcomas.
BONE & JOINT JOURNAL
(2023)
Article
Medicine, Research & Experimental
Amy R. Cross, Carlos E. de Andrea, Maria Villalba-Esparza, Manuel F. Landecho, Lucia Cerundolo, Praveen Weeratunga, Rachel E. Etherington, Laura Denney, Graham Ogg, Ling -Pei Ho, Ian S. D. Roberts, Joanna Hester, Paul Klenerman, Ignacio Melero, Stephen N. Sansom, Fadi Issa
Summary: This study used spatial transcriptomics to explore the interactions between different immune and stromal cell populations in COVID-19-affected lung tissue. Through gene expression analysis of well-preserved lung samples from 3 patients, a common immune-cell signaling circuit involving cytotoxic lymphocytes and pro-inflammatory macrophages was identified in areas of severe lung damage. The expression of IFNG by cytotoxic lymphocytes was associated with the induction of chemokines, while TNF superfamily members (BAFF and TRAIL) were consistently upregulated in severely damaged areas. Validation of these findings in additional COVID-19 patient cohorts supports the potential use of this immune-mediated tissue pathology model for future therapeutic strategies.
Article
Biochemistry & Molecular Biology
Luis Mejias Sosa, Alvaro Lopez-Janeiro, Alicia Cordoba Iturriagagoitia, Pablo Sala, Belen P. Solans, Laura Hato, Susana Inoges, Ascension Lopez-Diaz de Cerio, Francisco Guillen-Grima, Jaime Espinos, Susana De la Cruz, Maria Dolores Lozano, Miguel A. Idoate, Marta Santisteban
Summary: This study found that the addition of dendritic cell vaccines (DCV) to neoadjuvant chemotherapy (NAC) led to a slight increase in the proportion of CD8 cells in triple-negative breast cancer (TNBC) samples, but the increase was not statistically significant. However, a higher CD8 cell proportion was associated with pathological complete response in the vaccinated group. Overall, stimulating the antitumor immune system using DCV and NAC may be beneficial for TNBC patients.
Letter
Gastroenterology & Hepatology
Miguel A. Idoate-Gastearena, Jesus Machuca-Aguado, Inmaculada Trigo-Sanchez, Pablo Gargallo-Tatay, Enrique Rodriguez-Zarco, Carmen Garcia De Sola, Juan Jose Rios-Martin
JOURNAL OF DIGESTIVE DISEASES
(2023)
Article
Pediatrics
Idoya Serrano-Pejenaute, Anabel Carmona-Nunez, Ainhoa Zorrilla-Sarriegui, Garazi Martin-Irazabal, Julio Lopez-Bayon, Jesus Sanchez-Echaniz, Itziar Astigarraga
Summary: This study aims to describe the context of death and end-of-life decision-making in pediatric patients. The results show that in our setting, death of children usually occurs in relation to complex underlying pathology and after the decision of withdrawing or withholding life-sustaining treatment. In this context, palliative care and advance care planning acquire greater importance.
JOURNAL OF PAEDIATRICS AND CHILD HEALTH
(2023)
Article
Clinical Neurology
Jaime Gallego Perez-Larraya, Marc Garcia-Moure, Marta M. Alonso
Summary: Diffuse intrinsic pontine glioma (DIPG) is the deadliest brain tumor in children and current treatments offer little benefit. A study conducted a phase 1 clinical trial using an oncolytic adenovirus, Delta-24-RGD, injected directly into the tumor. The treatment showed a good safety profile and promising efficacy results, highlighting the potential of oncolytic viruses for treating devastating tumors like DIPG.
REVUE NEUROLOGIQUE
(2023)
Article
Multidisciplinary Sciences
Piedad Alba-Pavon, Lide Alana, Miriam Gutierrez-Jimeno, Susana Garcia-Obregon, Teresa Imizcoz, Elena Panizo, Paula Gonzalez-Urdiales, Aizpea Echebarria-Barona, Ricardo Lopez Almaraz, Laura Zaldumbide, Itziar Astigarraga, Ana Patino-Garcia, Olatz Villate
Summary: Genetic predisposition plays a significant role in pediatric cancer, but the relationship between individual genetic mutations and childhood cancer is still being investigated. Sarcomas are often associated with cancer predisposition syndromes, but this is frequently overlooked due to the rarity and heterogeneity of sarcomas and limited search for genetic syndromes. This study identified potential pathogenic germline variants in several genes associated with cancer predisposition syndromes in pediatric sarcoma patients through tumor profiling and sequencing analysis. The results indicate that somatic testing can help identify individuals at risk of underlying cancer predisposition syndromes.
SCIENTIFIC REPORTS
(2023)
Article
Medicine, Research & Experimental
Saja Fadila, Bertrand Beucher, Iria Gonzalez Dopeso-Reyes, Anat Mavashov, Marina Brusel, Karen Anderson, Caroline Ismeurt, Ethan M. Goldberg, Ana Ricobaraza, Ruben Hernandez-Alcoceba, Eric J. Kremer, Moran Rubinstein
Summary: DS, a severe childhood epileptic encephalopathy caused by SCN1A mutations, has limited pharmaceutical treatment options. Delivery of a modified SCN1A gene into the brain improved DS comorbidities and showed potential as a therapeutic approach for infants and adolescents with DS-associated comorbidities.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Jesus Machuca-Aguado, Antonio Felix Conde-Martin, Alejandro Alvarez-Munoz, Enrique Rodriguez-Zarco, Alfredo Polo-Velasco, Antonio Rueda-Ramos, Rosa Rendon-Garcia, Juan Jose Rios-Martin, Miguel A. Idoate, Apostolos Zaravinos
Summary: This study utilized a machine learning system to classify and quantify tumor-infiltrating lymphocytes in high-grade serous ovarian carcinoma (HGSOC) patients, and correlated the results with patient survival. The results showed that intense colonization of tumor cords by TILs was associated with a better prognosis. Furthermore, the concentration of intraepithelial TILs was found to be an independent prognostic factor for overall survival and progression-free survival. Additionally, a synergistic effect was observed between complete surgical cytoreduction and high levels of intraepithelial TILs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)