Article
Neurosciences
Fengjiao Liu, Jingyuan Shao, Haihong Yang, Guochao Yang, Qian Zhu, Yan Wu, Lingling Zhu, Haitao Wu
Summary: Our study found that Rack1 was significantly upregulated in the majority of human cerebellar MB tumors. Genetic ablation of Rack1 expression in SHH-MB tumor mice could significantly inhibit MB proliferation, reduce the tumor size, and prolong the survival of tumor rescue mice. Further studies showed that in rescue mice, while apoptosis and autophagy levels were unaffected, the expression of Gli1 and HDAC2 was significantly decreased suggesting the inactivation of the SHH signaling pathway.
CNS NEUROSCIENCE & THERAPEUTICS
(2021)
Article
Chemistry, Medicinal
Christopher Lawson, Thowaiba Babikr Ahmed Alta, Georgia Moschou, Vasiliki Skamnaki, Theodora G. A. Solovou, Caroline Topham, Joseph Hayes, Timothy J. Snape
Summary: Medulloblastoma is a highly aggressive and heterogeneous tumor that accounts for 15-20% of childhood brain tumors. In this study, potent in vitro anticancer activity against medulloblastoma cell lines was achieved using first-generation compounds, leading to the development of second-generation compounds with up to sixty times the activity, providing promising new leads for further research.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biology
Dario Cilleros-Rodriguez, Raquel Martin-Morales, Pablo Barbeito, Abhijit Deb Roy, Abdelhalim Loukil, Belen Sierra-Rodero, Gonzalo Herranz, Olatz Pampliega, Modesto Redrejo-Rodriguez, Sarah C. Goetz, Manuel Izquierdo, Takanari Inoue, Francesc R. Garcia-Gonzalo
Summary: Primary cilia are membrane protrusions responsible for sensory functions, and dysfunction of these cilia can lead to ciliopathies. INPP5E, a phosphoinositide phosphatase, is mutated in ciliopathies such as Joubert syndrome. This study uncovers the mechanism of INPP5E ciliary targeting and interactions, providing valuable insights into ciliary functions and related disorders.
Article
Cell Biology
Ping Shi, Jia Tian, Julianne C. Mallinger, Dahao Ling, Loic P. Deleyrolle, Jeremy C. Mcintyre, Tamara Caspary, Joshua J. Breunig, Matthew R. Sarkisian
Summary: This study found that increasing ARL13B expression in glioma cells can promote the accumulation of SMO and GLI2 in cilia, and this accumulation is resistant to SMO inhibitors. Furthermore, the increase in ARL13B also leads to changes in ciliary membrane characteristics and retrograde transport, which further promote SMO and GLI accumulation in glioma cells.
Article
Multidisciplinary Sciences
Shyam K. Akula, Jack H. Marciano, Youngshin Lim, David Exposito-Alonso, Norma K. Hylton, Grace H. Hwang, Jennifer E. Neil, Nicole Dominado, Rosie K. Bunton-Stasyshyn, Janet H. T. Song, Maya Talukdar, Aloisia Schmid, Lydia Teboul, Alisa Mo, Taehwan Shin, Benjamin Finander, Samantha G. Beck, Rebecca C. Yeh, Aoi Otani, Xuyu Qian, Ellen M. DeGennaro, Fowzan S. Alkuraya, Sateesh Maddirevula, Gregory D. Cascino, Caterina Giannini, Lindsay C. Undiagnosed Diseases Network, Lindsay C. Burrage, Jill A. Rosenfield, Shamika Ketkar, Gary D. Clark, Carlos Bacino, Richard A. Lewis, Rosalind A. Segal, J. Fernando Bazan, Kelly A. Smith, Jeffrey A. Golden, Ginam Cho, Christopher A. Walsh
Summary: This study reveals the role of TMEM161B in regulating Sonic hedgehog signaling and cerebral cortical gyration during embryonic development. Mutations in TMEM161B are associated with multiple abnormalities including polymicrogyria. TMEM161B is involved in primary ciliary structure and its dysfunction may contribute to ciliary-related phenotypes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Neurosciences
Haritha Kunhiraman, Leon McSwain, Shubin W. Shahab, Timothy R. Gershon, Tobey J. MacDonald, Anna Marie Kenney
Summary: This study found that the Sonic Hedgehog (SHH) subtype of medulloblastoma (MB) has a unique tumor microenvironment compared to other subtypes. The SHH MB cells were found to produce elevated levels of IGFBP2, which is required for SHH MB cell proliferation, colony formation, and cell migration. These findings suggest that targeting the IGFBP2-STAT3 axis could be a novel therapeutic approach for SHH medulloblastoma.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Liam D. Hendrikse, Parthiv Haldipur, Olivier Saulnier, Jake Millman, Alexandria H. Sjoboen, Anders W. Erickson, Winnie Ong, Victor Gordon, Ludivine Coudiere-Morrison, Audrey L. Mercier, Mohammad Shokouhian, Raul A. Suarez, Michelle Ly, Stephanie Borlase, David S. Scott, Maria C. Vladoiu, Hamza Farooq, Olga Sirbu, Takuma Nakashima, Shohei Nambu, Yusuke Funakoshi, Alec Bahcheli, J. Javier Diaz-Mejia, Joseph Golser, Kathleen Bach, Tram Phuong-Bao, Patryk Skowron, Evan Y. Wang, Sachin A. Kumar, Polina Balin, Abhirami Visvanathan, John J. Y. Lee, Ramy Ayoub, Xin Chen, Xiaodi Chen, Karen L. Mungall, Betty Luu, Pierre Berube, Yu C. Wang, Stefan M. Pfister, Seung-Ki Kim, Olivier Delattre, Franck Bourdeaut, Francois Doz, Julien Masliah-Planchon, Wieslawa A. Grajkowska, James Loukides, Peter Dirks, Michelle Fevre-Montange, Anne Jouvet, Pim J. French, Johan M. Kros, Karel Zitterbart, Swneke D. Bailey, Charles G. Eberhart, Amulya A. N. Rao, Caterina Giannini, James M. Olson, Miklos Garami, Peter Hauser, Joanna J. Phillips, Young S. Ra, Carmen de Torres, Jaume Mora, Kay K. W. Li, Ho-Keung Ng, Wai S. Poon, Ian F. Pollack, Enrique Lopez-Aguilar, G. Yancey Gillespie, Timothy E. Van Meter, Tomoko Shofuda, Rajeev Vibhakar, Reid C. Thompson, Michael K. Cooper, Joshua B. Rubin, Toshihiro Kumabe, Shin Jung, Boleslaw Lach, Achille Lolascon, Veronica Ferrucci, Pasqualino de Antonellis, Massimo Zollo, Giuseppe Cinalli, Shenandoah Robinson, Duncan S. Stearns, Erwin G. Van Meir, Paola Porrati, Gaetano Finocchiaro, Maura Massimino, Carlos G. Carlotti, Claudia C. Faria, Martine F. Roussel, Frederick Boop, Jennifer A. Chan, Kimberly A. Aldinger, Ferechte Razavi, Evelina Silvestri, Roger E. McLendon, Eric M. Thompson, Marc Ansari, Maria L. Garre, Fernando Chico, Pilar Eguia, Mario Perezpena, A. Sorana Morrissy, Florence M. G. Cavalli, Xiaochong Wu, Craig Daniels, Jeremy N. Rich, Steven J. M. Jones, Richard A. Moore, Marco A. Marra, Xi Huang, Juri Reimand, Poul H. Sorensen, Robert J. Wechsler-Reya, William A. Weiss, Trevor J. Pugh, Livia Garzia, Claudia L. Kleinman, Lincoln D. Stein, Nada Jabado, David Malkin, Olivier Ayrault, Jeffrey A. Golden, David W. Ellison, Brad Doble, Vijay Ramaswamy, Tamra E. Werbowetski-Ogilvie, Hiromichi Suzuki, Kathleen J. Millen, Michael D. Taylor
Summary: Medulloblastoma (MB) is a pediatric embryonal neoplasm of the hindbrain with subtypes including Sonic hedgehog MB, WNT MB and G4 MB. Somatic mutations in G4 MB converge on the core binding factor alpha (CBFA) complex, and knocking down OTX2 can relieve differentiation blockage.
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
Pharmacology & Pharmacy
Huangyi Fang, Lingfei Wang, Lisheng Yu, Fang Shen, Zelin Yang, Yue Yang, Shize Li, Haipeng Dai, Feng Tan, Jian Lin, Hansong Sheng
Summary: This study investigated the inhibitory effect of metformin on medulloblastoma and the underlying mechanism involving the Sonic hedgehog (Shh) signaling pathway. The results showed that metformin effectively inhibited proliferation and metastasis of medulloblastoma cells, and this effect was associated with apoptosis, cell cycle arrest, and inhibition of the Shh pathway. In addition, metformin demonstrated anticancer effects in vivo using a murine model. These findings highlight the potential of metformin as a therapeutic strategy for medulloblastoma.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Cell Biology
Issei S. Shimada, Yoichi Kato
Summary: The primary cilium is a sensory compartment that protrudes from the cellular surface and has various signaling molecules that regulate stem cells.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Liangping Yuan, Hongying Zhang, Jingbo Liu, Anshu Malhotra, Abhinav Dey, Bing Yu, Kishore Kumar Jella, Leon F. McSwain, Matthew J. Schniederjan, Tobey J. MacDonald
Summary: This study highlights the critical role of STAT3 in Shh MB cells, its essential role in Smo-dependent Shh signaling and drug resistance, and its potential as a therapeutic target to overcome anti-Smo drug resistance in treating Shh MB. Additionally, STAT3 inhibitor treatment significantly prevents tumor formation and synergistic effects with Smo inhibitors in vitro suggest a promising approach for Shh MB treatment.
MOLECULAR ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Taishi Kanamaru, Annett Neuner, Bahtiyar Kurtulmus, Gislene Pereiral
Summary: Understanding the segmentation of primary cilia is important for controlling their length and signaling functions. Perturbations leading to cilia over-elongation have been shown to impact different segments of the cilia axonemes, influencing cilia behavior. Septins have been identified as novel repressors of distal segment (DS) growth.
Review
Cell Biology
Daniel Kopinke, Alessandra M. Norris, Saikat Mukhopadhyay
Summary: Primary cilia are crucial for intercellular communication and have a unique relationship with the Hedgehog signaling pathway, playing a key role in maintaining the basal repression and activation states of the pathway.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2021)
Article
Health Care Sciences & Services
Hongyan Liao, Jiagui Huang, Jie Liu, Yue Chen, Huimin Zhu, Xuemei Li, Jun Wen, Qin Xiang, Qin Yang
Summary: Activated microglia can worsen neurological function in the acute phase of stroke, making it important to explore methods or drugs that can inhibit their abnormal activation. Resveratrol has potential effects in regulating microglia activation and inflammation. Its mechanism of inhibiting microglial activation is not fully understood, but studies suggest that it may involve the activation of Smo receptor. This study found that resveratrol can partially inhibit microglial activation and improve functional outcome after stroke by triggering the translocation of Smo to primary cilia.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Review
Oncology
Minghao Li, Jiaxun Zhang, Haonan Zhou, Rong Xiang
Summary: Primary cilia, as microtubule-based structures, are closely related to the development of the central nervous system and play a crucial role in regulating the tumorigenesis of the central nervous system. The development of primary cilia can be regulated by several pathways, and primary cilia are also able to regulate a few signaling transduction pathways.
FRONTIERS IN ONCOLOGY
(2021)
Editorial Material
Oncology
Anirban Das, Vijay Ramaswamy
Article
Oncology
Stephanie M. Ntoukas, Tatiana Ritchie, Susan Awrey, David C. Hodgson, Normand Laperriere, Ryan Yee, Vijay Ramaswamy, Barbara-Ann Millar, Nathan Becker, Derek S. Tsang
PRACTICAL RADIATION ONCOLOGY
(2020)
Review
Oncology
Chantel Cacciotti, Adam Fleming, Vijay Ramaswamy
JOURNAL OF PATHOLOGY
(2020)
Editorial Material
Oncology
Liana Nobre, Vijay Ramaswamy
Editorial Material
Oncology
Vijay Ramaswamy, Ute Bartels
Letter
Oncology
Ritu Lamichhane, Paromita Roy, Cynthia Hawkins, Lateef Zameer, Anisha Gehani, Rimpa B. Achari, Ben Ho, Annie Huang, Uri Tabori, Vijay Ramaswamy, Reghu K. Sukumaran, Anirban Das
PEDIATRIC BLOOD & CANCER
(2022)
Editorial Material
Oncology
Marc Remke, Vijay Ramaswamy
Summary: This article discusses the treatment of pediatric medulloblastoma and highlights the substantial long-term sequelae despite improved survival rates. It raises the question of how to safely de-escalate therapy without compromising its effectiveness.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Lucie Lafay-Cousin, Lorena Baroni, Vijay Ramaswamy, Eric Bouffet
Summary: Therapeutic strategies for young children with medulloblastoma are evolving, including high-dose chemotherapy with stem cell rescue and intraventricular chemotherapy. Studies on different molecular subgroups show excellent survival rates for sonic hedgehog medulloblastoma patients, while those with high-risk features may require innovative therapies.
PEDIATRIC BLOOD & CANCER
(2022)
Editorial Material
Oncology
Beth Frenkel, Elena Gerasimov, Allen Gustafson, Patti Gustafson, Ginny McLean, Aloysius Ochasi, Angela Waanders, Vijay Ramaswamy
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Hallie Coltin, Priscila Pequeno, Ning Liu, Derek S. Tsang, Sumit Gupta, Michael D. Taylor, Eric Bouffet, Paul C. Nathan, Vijay Ramaswamy
Summary: This study characterized the late effects of childhood medulloblastoma survivors using real-world health services data. The findings reveal significant long-term medical sequelae and increased mortality rates, emphasizing the need for a re-evaluation of current treatment approaches and prioritization of interventions targeting late effects.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Craig Erker, Martin Mynarek, Simon Bailey, Claire M. Mazewski, Lorena Baroni, Maura Massimino, Juliette Hukin, Dolly Aguilera, Andrea M. Cappellano, Vijay Ramaswamy, Alvaro Lassaletta, Sebastien Perreault, Cassie N. Kline, Revathi Rajagopal, George Michaiel, Michal Zapotocky, Vicente Santa-Maria Lopez, Andres Morales La Madrid, Chantel Cacciotti, Eric S. Sandler, Lindsey M. Hoffman, Darren Klawinski, Sara Khan, Ralph Salloum, Anna L. Hoppmann, Valerie Larouche, Kathleen Dorris, Helen Toledano, Stephen W. Gilheeney, Mohamed S. Abdelbaki, Beverly Wilson, Derek S. Tsang, Jeffrey Knipstein, Michal Yalon Oren, Shafqat Shah, Jeffrey C. Murray, Kevin F. Ginn, Zhihong J. Wang, Gudrun Fleischhack, Denise Obrecht, Svenja Tonn, Virginia L. Harrod, Kara Matheson, Bruce Crooks, Douglas R. Strother, Kenneth J. Cohen, Jordan R. Hansford, Sabine Mueller, Ashley Margol, Amar Gajjar, Girish Dhall, Jonathan L. Finlay, Paul A. Northcott, Stefan Rutkowski, Steven C. Clifford, Giles Robinson, Eric Bouffet, Lucie Lafay-Cousin
Summary: The purpose of this study was to assess salvage strategies and prognostic features of patients with infant and young childhood medulloblastoma (iMB) who relapse after craniospinal irradiation (CSI)-sparing therapy. The results showed that the 3-year postrelapse survival rate for patients treated with curative intent was 52.4%. Salvage radiotherapy and chemotherapy might be beneficial for a subset of patients. Therefore, CSI-sparing therapy can be effective in a substantial proportion of relapsed iMB patients.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Anna S. Kolodziejczak, Lea Guerrini-Rousseau, Julien Masliah Planchon, Jonas Ecker, Florian Selt, Martin Mynarek, Denise Obrecht, Martin Sill, Robert J. Autry, Eric Stutheit-Zhao, Steffen Hirsch, Elsa Amouyal, Christelle Dufour, Olivier Ayrault, Jacob Torrejon, Sebastian M. Waszak, Vijay Ramaswamy, Virve Pentikainen, Haci Ahmet Demir, Steven C. Clifford, Ed C. Schwalbe, Luca Massimi, Matija Snuderl, Kristyn Galbraith, Matthias A. Karajannis, Katherine Hill, Bryan K. Li, Mike Walsh, Christine L. White, Shelagh Redmond, Loizou Loizos, Marcus Jakob, Uwe R. Kordes, Irene Schmid, Julia Hauer, Claudia Blattmann, Maria Filippidou, Gianluca Piccolo, Wolfram Scheurlen, Ahmed Farrag, Kerstin Grund, Christian Sutter, Torsten Pietsch, Stephan Frank, Denis M. Schewe, David Malkin, Myriam Ben-Arush, Astrid Sehested, Tai-Tong Wong, Kuo-Sheng Wu, Yen-Lin Liu, Fernando Carceller, Sabine Mueller, Schuyler Stoller, Michael D. Taylor, Uri Tabori, Eric Bouffet, Marcel Kool, Felix Sahm, Andreas von Deimling, Andrey Korshunov, Katja von Hoff, Christian P. Kratz, Dominik Sturm, David T. W. Jones, Stefan Rutkowski, Cornelis M. van Tilburg, Olaf Witt, Gaelle Bougeard, Kristian W. Pajtler, Stefan M. Pfister, Franck Bourdeaut, Till Milde
Summary: This retrospective cohort study investigated medulloblastoma in Li-Fraumeni syndrome (LFS) patients and found poor prognosis. The results showed that patients who received radiotherapy and chemotherapy had better clinical outcomes, while chemotherapy intensity did not affect their prognosis.
Article
Cell Biology
Stephanie Borlase, Alexandria Decarlo, Ludivine Coudiere-Morrison, Lisa Liang, Christopher J. Porter, Vijay Ramaswamy, Tamra E. Werbowetski-Ogilvie
Summary: This study conducted preclinical testing of the MEK inhibitor trametinib on Sonic Hedgehog (SHH) medulloblastomas. The results showed that trametinib effectively reduced tumor properties, such as tumorsphere size, cell proliferation, viability, and migration. RNA-sequencing further confirmed these findings and revealed changes in gene expression related to cell cycle, stem cell pathways, and SHH signaling. The study also demonstrated that trametinib decreased tumor growth and increased survival in vivo. However, long-term MEK inhibition led to compensatory molecular changes in the IL6/JAK STAT3 and TNF & alpha;/NF & kappa;B signaling pathways. Overall, these findings suggest that trametinib could be a potential targeted therapy for SHH medulloblastomas with elevated MAPK pathway activity.
CELL DEATH DISCOVERY
(2023)
Article
Oncology
Adeoye Oyefiade, Iska Moxon-Emre, Kiran Beera, Eric Bouffet, Michael Taylor, Vijay Ramaswamy, Suzanne Laughlin, Jovanka Skocic, Donald J. Mabbott
Summary: The study found that there was greater segregation of WM networks after radiotherapy (RT), but no significant network differences were observed between patients treated with or without RT.
NEURO-ONCOLOGY ADVANCES
(2022)
Article
Oncology
Nisreen Amayiri, Maisa Swaidan, Ahmed Ibrahimi, Nader Hirmas, Awni Musharbash, Eric Bouffet, Maysa Al-Hussaini, Vijay Ramaswamy
Summary: The study found that in low- to middle-income countries, patients with SHH and group 4 medulloblastoma had survival rates comparable to high-income countries, highlighting the importance of compliance with treatment protocols and avoiding treatment delays for patient survival.
JCO GLOBAL ONCOLOGY
(2021)