Article
Cell Biology
Rui-Lin Zhu, Yuan Fang, Hong-Hua Yu, Dong Chen, Liu Yang, Kin-Sang Cho
Summary: Muller cells are considered dormant retinal progenitor cells in mammals, and ephrin-A2/A3 act as negative regulators of neural progenitor cells in the retina and brain. Ephrin-A2/A3 and their receptor EphA4 are expressed in retina, especially in Muller cells, with their expression levels increasing as the retina matures and correlating with reduced proliferative potential.
NEURAL REGENERATION RESEARCH
(2021)
Article
Hematology
Philippe Rousselot, Luigina Mollica, Joelle Guilhot, Agnes Guerci, Franck E. Nicolini, Gabriel Etienne, Laurence Legros, Aude Charbonnier, Valerie Coiteux, Caroline Dartigeas, Martine Escoffre-Barbe, Lydia Roy, Pascale Cony-Makhoul, Viviane Dubruille, Martine Gardembas, Francoise Huguet, Delphine Rea, Emilie Cayssials, Francois Guilhot, Anne Bergeron, Mathieu Molimard, Francois-Xavier Mahon, Jean-Michel Cayuela, Lambert Busque, Stephane Bouchet
Summary: Dasatinib, a second-generation BCR-ABL1 tyrosine kinase inhibitor, is approved for CML patients. This study evaluated therapeutic drug monitoring (TDM) to reduce dasatinib-associated pleural effusion (PlEff) incidence. Results showed that TDM during dasatinib treatment initiation significantly reduced the occurrence of PlEff in the long run without affecting molecular responses.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Review
Oncology
Peter W. Janes, Mary E. Vail, Matthias Ernst, Andrew M. Scott
Summary: Eph receptors and their ligands play critical roles in the tumor microenvironment, and inhibiting their functions can enhance the efficacy of immune-based therapies.
Article
Biochemistry & Molecular Biology
Seok Won Ham, Jung Yun Kim, Sunyoung Seo, Nayoung Hong, Min Ji Park, Yoonji Kim, Junseok Jang, Sehyeon Park, Silvee Jisoo Lee, Jun-Kyum Kim, Eun-Jung Kim, Sung-Ok Kim, Sung-Chan Kim, Jong-Whi Park, Hyunggee Kim
Summary: This study identified annexin A2 (ANXA2) as an essential modulator for stabilizing JICD1 and suppressing CSC properties in the treatment of GBM.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Anatomy & Morphology
Jeremiah P. C. Stinson, Cooper A. Brett, Julianne B. Carroll, Mark L. Gabriele
Summary: Guidance errors and unrefined neural map configurations may be linked to certain neurodevelopmental conditions, including autism spectrum disorders. The lateral cortex of the inferior colliculus (LCIC) integrates information from multiple levels and modalities, and Eph-ephrin signaling mechanisms may play a significant role in ordering behaviorally significant multisensory midbrain networks.
FRONTIERS IN NEUROANATOMY
(2021)
Article
Biochemistry & Molecular Biology
Andrej Porcnik, Metka Novak, Barbara Breznik, Bernarda Majc, Barbara Hrastar, Neja Samec, Alja Zottel, Ivana Jovcevska, Milos Vittori, Ana Rotter, Radovan Komel, Tamara Lah Turnsek
Summary: The study identifies TRIM28 as a biomarker for GB, showing significant inhibition of GB cell and GSC invasiveness and spread by anti-TRIM28 nanobody NB237, offering a new therapeutic opportunity.
Article
Chemistry, Medicinal
Matthew J. J. Rybin, Mayra Juliana K. Laverde-Paz, Robert K. Suter, Maurizio G. Affer, Nagi G. Ayad, Yangbo Feng, Zane Zeier
Summary: The high rates of recurrence and treatment resistance in glioblastoma (GBM), the most common malignant adult brain cancer, suggest that monotherapies are not effective enough. Combination therapies are being pursued to address this issue, but the possibility of drug-drug interactions is a challenge. To overcome this, the development of single molecules with multiple targets provides a feasible alternative strategy. In this study, a novel dual inhibitor targeting both aurora kinases and lim kinases, called F114, was developed and found to inhibit GBM proliferation and invasion in vitro and ex vivo models.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Jong-Ho Cha, Li-Chuan Chan, Ying-Nai Wang, Yu-Yi Chu, Chie-Hong Wang, Heng-Huan Lee, Weiya Xia, Woei-Cherng Shyu, Shih-Ping Liu, Jun Yao, Chiung-Wen Chang, Fan-Ru Cheng, Jielin Liu, Seung-Oe Lim, Jennifer L. Hsu, Wen-Hao Yang, Gabriel N. Hortobagyi, Chunru Lin, Liuqing Yang, Dihua Yu, Long-Bin Jeng, Mien-Chie Hung
Summary: The expression of EphA10, a receptor tyrosine kinase, is associated with tumor progression and poor prognosis in several malignancies. This study demonstrates high expression levels of EphA10 in tumor regions and immune suppressive myeloid cells in the tumor microenvironment. The development of anti-EphA10 monoclonal antibodies and chimeric antigen receptor-T cell therapy targeting EphA10 shows potential as a promising strategy for patients with EphA10-positive tumors.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Julie Bolcaen, Shankari Nair, Cathryn H. S. Driver, Tebatso M. G. Boshomane, Thomas Ebenhan, Charlot Vandevoorde
Summary: Glioblastoma, a deadly brain tumor with high treatment resistance, has been explored with receptor tyrosine kinase inhibitors (RTKIs) to potentially improve prognosis and develop personalized targeted therapy. Approved RTKIs in clinics alongside radiopharmaceuticals in trials offer new avenues for theranostic applications in GB treatment.
Article
Pharmacology & Pharmacy
Enam Alhagh Charkhat Gorgich, Hamidreza Kasbiyan, Ronak Shabani, Mehdi Mehdizadeh, Fahimeh Hajiahmadi, Marziyeh Ajdary, Mahmood Barati, Fatemeh Moradi, Davoud Ahmadvand
Summary: This study developed smart chlorotoxin-functionalized liposomes for targeted delivery of sunitinib into glioblastoma cells. The liposomes showed high drug encapsulation efficiency, suitable stability, and inhibited cell viability and migration ability of glioblastoma cells.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2022)
Article
Oncology
Anne -Florence Blandin, Ross Giglio, Maya Srikanth Graham, Guadalupe Garcia, Seth Malinowski, Jared K. Woods, Shakti Ramkissoon, Lori Ramkissoon, Frank Dubois, Kathleen Schoolcraft, Jessica Tsai, Dayle Wang, Robert Jones, Jayne Vogelzang, Kristine Pelton, Sarah Becker, Fiona Watkinson, Claire Sinai, Elizabeth F. Cohen, Matthew A. Booker, Michael Y. Tolstorukov, Veerle Haemels, Liliana Goumnerova, Karen Wright, Mark Kieran, Katie Fehnel, David Reardon, Arnault Tauziede-Espariat, Rishi Lulla, Benjamin Carcamo, Stanley Chaleff, Alain Charest, Frederik De Smet, Azra H. Ligon, Adrian Dubuc, Melanie Pages, Pascale Varlet, Patrick Y. Wen, Brian M. Alexander, Susan Chi, Sanda Alexandrescu, Ralf Kittler, Robert Bachoo, Pratiti Bandopadhayay, Rameen Beroukhim, Keith L. Ligon
Summary: This study comprehensively analyzed ALK expression and genomic aberrations in 371 glioblastomas and validated the abnormalities in vitro and in vivo. The findings showed that ALK aberrations were present in 12% of gliomas across a wide age range and ALK fusions were more common in congenital/infant glioblastomas. ALK fusions promoted pathways related to tumor transformation and responded well to ALK inhibitors, supporting their use in clinical trials for glioblastomas in different age groups.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Bulent Polat, Gisela Wohlleben, Rebekka Kosmala, Dominik Lisowski, Frederick Mantel, Victor Lewitzki, Mario Lohr, Robert Blum, Petra Herud, Michael Flentje, Camelia-Maria Monoranu
Summary: CD133 and Nestin were found to be associated with survival in glioma patients, and may serve as candidate markers for further clinical investigation.
CANCER CELL INTERNATIONAL
(2022)
Article
Oncology
Qingsheng Xu, Kaiyuan Huang, Xiangqi Meng, Yuxiang Weng, Luyuan Zhang, Linghao Bu, Xiujue Zheng, Jinquan Cai, Renya Zhan, Qun Chen
Summary: The combination of anlotinib and temozolomide showed high efficacy and tolerability in treating recurrent GBM, with a good tumor response rate and disease control rate. This treatment regimen may contribute to an increase in progression-free survival and overall survival in patients with recurrent GBM.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Minling Gao, Yi Fu, Weiqiang Zhou, Gege Gui, Bachuchu Lal, Yunqing Li, Shuli Xia, Hongkai Ji, Charles G. Eberhart, John Laterra, Mingyao Ying
Summary: This study focuses on uncovering the key signaling pathways of EGFR/TAF, and identifies osimertinib as an effective inhibitor that can treat cancers like GBM effectively.
Article
Oncology
Cecile Alanio, Zev A. Blinder, Renee B. Chang, MacLean P. Nasrallah, Devora Delman, Joey H. Li, Oliver Y. Tang, Logan Y. Zhang, Jiasi Vicky Zhang, E. John Wherry, Donald M. O. Rourke, Gregory L. Beatty
Summary: The study found that T cells in the perivascular regions of recurrent GBM were enriched and activated, and their presence was associated with outcomes, indicating that these T cells may be potential therapeutic targets.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Oncology
Chewei Anderson Chang, Jayu Jen, Shaowen Jiang, Azin Sayad, Arvind Singh Mer, Kevin R. Brown, Allison M. L. Nixon, Avantika Dhabaria, Kwan Ho Tang, David Venet, Christos Sotiriou, Jiehui Deng, Kwok-Kin Wong, Sylvia Adams, Peter Meyn, Adriana Heguy, Jane A. Skok, Aristotelis Tsirigos, Beatrix Ueberheide, Jason Moffat, Abhyudai Singh, Benjamin Haibe-Kains, Alireza Khodadadi-Jamayran, Benjamin G. Neel
Summary: Resistance to targeted therapies in HER2-positive breast cancer is often attributed to the presence of drug-tolerant persisters (DTPs). This study reveals that HER2 TKI treatment leads to the emergence of DTPs with different transcriptomes, and these DTPs are originated from pre-DTP cells that cycle stochastically. The findings provide insights into the ontogeny of DTPs and potential vulnerabilities for therapeutic targeting.
Article
Clinical Neurology
Radwan Takroni, Nirmeen Zagzoog, Nimita Patel, Amanda Martyniuk, Sheila Singh, Forough Farrokhyar, Arunachala Trivedi, Mazen Alotaibi, Almunder Algird
Summary: This study retrospectively analyzed data from 172 patients with chronic subdural hematoma (CSDH) and compared the effect of two drainage systems on the recurrence rate of CSDH. The results showed no significant difference in the recurrence rate between the use of a pediatric size nasogastric tube and an external ventricular drainage catheter.
JOURNAL OF NEUROLOGICAL SURGERY PART A-CENTRAL EUROPEAN NEUROSURGERY
(2023)
Article
Oncology
Mathieu Seyfrid, William Thomas Maich, Vaseem Muhammad Shaikh, Nazanin Tatari, Deepak Upreti, Deween Piyasena, Minomi Subapanditha, Neil Savage, Dillon McKenna, Nicholas Mikolajewicz, Hong Han, Chirayu Chokshi, Laura Kuhlmann, Amanda Khoo, Sabra Khalid Salim, Blessing Archibong-Bassey, William Gwynne, Kevin Brown, Nadeem Murtaza, David Bakhshinyan, Parvez Vora, Chitra Venugopal, Jason Moffat, Thomas Kislinger, Sheila Singh
Summary: This study identifies CD70 as a potential therapeutic target for recurrent glioblastoma stem cells (CSCs). Targeting CD70 with CAR-T therapy significantly improves prognosis in animal models and the CD70/CD27 axis may provide a viable polytherapeutic avenue for targeting both glioblastoma and its tumor immune microenvironment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Engineering, Biomedical
Zongjie Wang, Sharif Ahmed, Mahmoud Labib, Hansen Wang, Xiyue Hu, Jiarun Wei, Yuxi Yao, Jason Moffat, Edward H. Sargent, Shana O. Kelley
Summary: A configurable microfluidic device efficiently recovers potent tumour-infiltrating lymphocytes (TILs) from solid tumours by leveraging specific expression levels of target cell-surface markers, potentially optimizing adoptive cell therapies.
NATURE BIOMEDICAL ENGINEERING
(2022)
Article
Biochemistry & Molecular Biology
Wayne Ngo, Jamie L. Y. Wu, Zachary P. Lin, Yuwei Zhang, Bram Bussin, Adrian Granda Farias, Abdullah M. Syed, Katherine Chan, Andrea Habsid, Jason Moffat, Warren C. W. Chan
Summary: Nanotechnology provides a platform for delivering medical agents to specific cells. This study identified the main interactions between nanoparticle-adsorbed proteins and cells, and found that the LDL receptor played a major role in the uptake of serum-coated gold nanoparticles. Understanding how serum proteins bind to cell receptors can help control the delivery of nanoparticles for therapeutic and diagnostic applications.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Immunology
Nazanin Tatari, Xiaoyu Zhang, Shawn C. Chafe, Dillon McKenna, Keith A. Lawson, Minomi Subapanditha, Muhammad Vaseem Shaikh, Mathieu Seyfrid, Neil Savage, Chitra Venugopal, Jason Moffat, Sheila K. Singh
Summary: The expression of CA9 was found to be high in BTICs of GBM and was associated with enhanced self-renewal and proliferation capacity of the stem cells. Researchers developed a novel therapeutic strategy targeting CA9-positive tumor cells and demonstrated its effectiveness in vitro and in vivo.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Clinical Neurology
Nazanin Tatari, Shahbaz Khan, Julie Livingstone, Kui Zhai, Dillon Mckenna, Vladimir Ignatchenko, Chirayu Chokshi, William D. Gwynne, Manoj Singh, Spencer Revill, Nicholas Mikolajewicz, Chenghao Zhu, Jennifer Chan, Cynthia Hawkins, Jian-Qiang Lu, John P. Provias, Kjetil Ask, Sorana Morrissy, Samuel Brown, Tobias Weiss, Michael Weller, Hong Han, Jeffrey N. Greenspoon, Jason Moffat, Chitra Venugopal, Paul C. Boutros, Sheila K. Singh, Thomas Kislinger
Summary: Glioblastoma (GBM) exhibits cellular and genetic heterogeneity, with a preferential transition from primary disease to recurrent disease towards a mesenchymal state. Immune regulatory/suppressive genes, particularly 2-5-oligoadenylate synthase 2 (OAS2), are identified as important drivers of recurrent GBM.
ACTA NEUROPATHOLOGICA
(2022)
Article
Cell Biology
Maleeha A. Qazi, Sabra K. Salim, Kevin R. Brown, Nicholas Mikolajewicz, Neil Savage, Hong Han, Minomi K. Subapanditha, David Bakhshinyan, Allison Nixon, Parvez Vora, Kimberly Desmond, Chirayu Chokshi, Mohini Singh, Amanda Khoo, Andrew Macklin, Shahbaz Khan, Nazanin Tatari, Neil Winegarden, Laura Richards, Trevor Pugh, Nicholas Bock, Alireza Mansouri, Chitra Venugopal, Thomas Kislinger, Sidhartha Goyal, Jason Moffat, Sheila K. Singh
Summary: Recurrence of solid tumors leads to advanced, treatment-resistant disease with distinct mutational and oncogenic landscape. By analyzing tumor stem cell populations, researchers identified different recurrence patterns and found clonal populations can acquire fitness advantage through therapy. Moreover, they discovered an immunomodulatory signature in the MRD state that has prognostic significance in solid cancers.
Article
Oncology
William D. Gwynne, Yujin Suk, Stefan Custers, Nicholas Mikolajewicz, Jeremy K. Chan, Zsolt Zador, Shawn C. Chafe, Kui Zhai, Laura Escudero, Cunjie Zhang, Olga Zaslaver, Chirayu Chokshi, Muhammad Vaseem Shaikh, David Bakhshinyan, Ian Burns, Iqra Chaudhry, Omri Nachmani, Daniel Mobilio, William T. Maich, Patricia Mero, Kevin R. Brown, Andrew T. Quaile, Chitra Venugopal, Jason Moffat, J. Rafael Montenegro-Burke, Sheila K. Singh
Summary: This research integrated data from genetic screening and metabolomic profiling to identify multiple cancer-selective metabolic vulnerabilities in MYC-driven medulloblastoma, providing potential therapeutic targets. The inhibition of DHODH, an enzyme involved in pyrimidine biosynthesis, leads to metabolic stress response, cell-cycle arrest, and apoptosis in tumor cells. A small-molecule DHODH inhibitor demonstrated strong therapeutic efficacy against patient-derived xenografts in vivo, offering a new treatment option for MYC-driven medulloblastoma.
Article
Clinical Neurology
Leonard H. H. Verhey, Arjuna Maharaj, Nikunj Patel, Branavan Manoranjan, Olufemi Ajani, Adam Fleming, Forough Farrokhyar, Sheila K. K. Singh, Blake Yarascavitch, Pediat Brain Tumor Study Grp
Summary: The purpose of this study was to determine whether intraoperative adjunctive EVD placement in patients with a posterior fossa tumor (PFT) led to improved surgical, radiographic, and clinical outcomes. The results showed that the routine use of EVD as an intraoperative adjunct in clinically stable pediatric patients with posterior fossa tumors and hydrocephalus may not be associated with improved radiological or clinical outcomes.
CHILDS NERVOUS SYSTEM
(2023)
Correction
Multidisciplinary Sciences
Michelle M. Kameda-Smith, Helen Zhu, En-Ching Luo, Yujin Suk, Agata Xella, Brian Yee, Chirayu Chokshi, Sansi Xing, Frederick Tan, Raymond G. Fox, Ashley A. Adile, David Bakhshinyan, Kevin Brown, William D. Gwynne, Minomi Subapanditha, Petar Miletic, Daniel Picard, Ian Burns, Jason Moffat, Kamil Paruch, Adam Fleming, Kristin Hope, John P. Provias, Marc Remke, Yu Lu, Tannishtha Reya, Chitra Venugopal, Jueri Reimand, Robert J. Wechsler-Reya, Gene W. Yeo, Sheila K. Singh
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Michelle M. M. Kameda-Smith, Helen Zhu, En-Ching Luo, Yujin Suk, Agata Xella, Brian Yee, Chirayu Chokshi, Sansi Xing, Frederick Tan, Raymond G. G. Fox, Ashley A. A. Adile, David Bakhshinyan, Kevin Brown, William D. D. Gwynne, Minomi Subapanditha, Petar Miletic, Daniel Picard, Ian Burns, Jason Moffat, Kamil Paruch, Adam Fleming, Kristin Hope, John P. P. Provias, Marc Remke, Yu Lu, Tannishtha Reya, Chitra Venugopal, Juri Reimand, Robert J. J. Wechsler-Reya, Gene W. W. Yeo, Sheila K. K. Singh
Summary: The RNA-binding protein Musashi-1 (MSI1) has been found to play an essential role in Group 3 (G3) medulloblastoma (MB), and its inhibition can effectively suppress tumor initiation and prolong survival in G3 MB mouse models and patient-derived xenografts. By identifying MSI1 binding targets in normal neural and G3 MB stem cells and cross-referencing them with large-scale screens at different levels, multiple MYC-associated pathways have been discovered to be selectively targeted by MSI1 in G3 MB, providing valuable resources for context-specific therapeutic strategies.
NATURE COMMUNICATIONS
(2022)
Article
Clinical Neurology
Ieta Shams, Branavan Manoranjan, Rebecca Voth, Malavan Ragulojan, Olufemi Ajani, Blake Yarascavitch, Sheila K. Singh, Adam J. Fleming
Summary: This study retrospectively analyzed 40 cases of progressive juvenile pilocytic astrocytoma (JPA) treated at a single center over an 18-year period (1998-2016). The findings showed that the treatment of progressive JPA is variable and may require numerous surgeries and adjuvant therapies.
JOURNAL OF NEUROSURGICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Blessing Iquo Bassey- Archibong, Chirayu Rajendra Chokshi, Nikoo Aghaei, Agata Monika Kieliszek, Nazanin Tatari, Dillon McKenna, Mohini Singh, Minomi Kalpana Subapanditha, Arun Parmar, Daniel Mobilio, Neil Savage, Fred Lam, Tomas Tokar, John Provias, Yu Lu, Shawn Christopher Chafe, Charles Swanton, Robert Edward Hynds, Chitra Venugopal, Sheila Kumari Singh
Summary: Brain metastases (BM) are the most common brain neoplasm in adults, but current therapies have limited efficacy. This study analyzed the transcriptional profile of brain metastasis initiating cells (BMICs) at two distinct stages of the metastatic cascade. The researchers found that premetastatic BMICs exhibited increased expression of HLA-G, which plays a role in promoting brain metastatic lesions. Understanding the molecular landscape of premetastatic BMICs could lead to the development of more effective therapies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Christoph Bock, Paul Datlinger, Florence Chardon, Matthew A. Coelho, Matthew B. Dong, Keith A. Lawson, Tian Lu, Laetitia Maroc, Thomas M. Norman, Bicna Song, Geoff Stanley, Sidi Chen, Mathew Garnett, Wei Li, Jason Moffat, Lei S. Qi, Rebecca S. Shapiro, Jay Shendure, Jonathan S. Weissman, Xiaowei Zhuang
Summary: CRISPR screens are a powerful tool for unbiased investigation of gene functions in various applications and species. By introducing genetically encoded perturbations into cell pools, these screens allow the evaluation of gene effects under biological challenges. High-content read-outs and dedicated software tools enhance the analysis and reproducibility of the results, making it a flexible and reliable method for biological discovery and drug development.
NATURE REVIEWS METHODS PRIMERS
(2022)
