Article
Chemistry, Medicinal
Yuqi Jiang, Jie Xu, Kairui Yue, Chao Huang, Mengting Qin, Dongyu Chi, Qixin Yu, Yue Zhu, Xiaohan Hou, Tongqiang Xu, Min Li, C. James Chou, Xiaoyang Li
Summary: The study focused on modifying HDAC inhibitors to deactivate the Michael reaction in order to improve their potency. Compound 11h showed significant improvements in both HDAC inhibitory activity and cell-based antitumor assay, demonstrating potential for clinical application and efficacy against AML.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Editorial Material
Oncology
Carlos Jimenez, Lucas Moreno, Miguel F. Segura
Summary: The low immunogenicity of neuroblastoma cells, represented by the low expression of major histocompatibility complex class I, poses a challenge to the development of immunotherapies. Cornel et al. demonstrated that epigenetic modulation of neuroblastoma cells using a histone deacetylase inhibitor can enhance the expression of major histocompatibility complex class I and other immune receptors, enabling their recognition by T- and natural killer cells. These discoveries leverage the aberrant epigenetic landscapes of neuroblastoma and provide a potential solution to overcome a major limitation in neuroblastoma immunotherapy.
MOLECULAR ONCOLOGY
(2023)
Article
Oncology
Weiyu Dai, Side Liu, Jieming Zhang, Miaomiao Pei, Yizhi Xiao, Jiaying Li, Linjie Hong, Jianjiao Lin, Jing Wang, Xiaosheng Wu, Guangnan Liu, Yaying Chen, Yusi Wang, Zhizhao Lin, Qiong Yang, Fachao Zhi, Guoxin Li, Weimei Tang, Aimin Li, Li Xiang, Jide Wang
Summary: miR-769-5p/miR-769-3p acts as a tumor suppressor in gastric cancer by targeting IGF1R and through the STAT3-IGF1R-HDAC3 complex. Treatment with the HDAC inhibitor SAHA triggers the expression of miR-769-5p/miR-769-3p, leading to inhibition of proliferation and induction of apoptosis in gastric cancer cells.
Review
Pharmacology & Pharmacy
Meran Keshawa Ediriweera
Summary: Histone acetylation is a crucial epigenetic event and continues to be an area of great interest in biochemical research. The balance between histone acetyltransferases (HATs) and histone deacetylases (HDACs) is disrupted in various human cancers. Histone deacetylase inhibitors (HDACi) have shown promising results in restoring dysregulated histone acetylation profiles and are considered as potential anti-cancer therapeutics. Recent studies have identified odd-chain fatty acids as novel HDACi, further expanding the understanding of fatty acids in cancer therapy.
DRUG DISCOVERY TODAY
(2023)
Review
Oncology
Md Sahab Uddin, Abdullah Al Mamun, Badrah S. Alghamdi, Devesh Tewari, Philippe Jeandet, Md Shahid Sarwar, Ghulam Md Ashraf
Summary: Research has shown that glioma progression is closely linked to different types of epigenetic phenomena, such as chromatin modifications, DNA methylation, chromatin remodeling, and aberrant microRNA. Targeting the genes and proteins that control these alterations can be an effective way to treat GBM. Treatment approaches include histone deacetylase inhibitors and DNA methyltransferase inhibitors.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Kristin C. Hicks, Paul L. Chariou, Yohei Ozawa, Christine M. Minnar, Karin M. Knudson, Thomas J. Meyer, Jing Bian, Margaret Cam, Jeffrey Schlom, Sofia R. Gameiro
Summary: Combining the histone deacetylase inhibitor, Entinostat, with the recombinant murine immune-cytokine NHS-rmIL12 can reprogram the tumor microenvironment and lead to tumor eradication. This combination therapy promotes the action of functional CD8(+) T cells and activated neutrophils, driving macrophage polarization and benefiting overall survival in multiple human tumor types.
NATURE COMMUNICATIONS
(2021)
Review
Pharmacology & Pharmacy
Ekta Shirbhate, Ravichandran Veerasamy, Sai H. S. Boddu, Amit K. Tiwari, Harish Rajak
Summary: One significant obstacle in cancer treatment is the decrease in drug efficacy and occurrence of adverse effects. Oncolytic viruses (OVs) have gained interest as a potential method to treat cancer due to their specificity for cancerous tissue and reduced likelihood of adverse effects. Clinical trials have shown that OVs have an acceptable safety profile and are effective in treating certain types of cancer, despite their limited availability. However, further advancements are needed to enhance tumor permeation and improve virus delivery in order to make oncolytic virotherapy more effective.
DRUG DISCOVERY TODAY
(2022)
Review
Oncology
Robert Jenke, Nina Ressing, Finn K. Hansen, Achim Aigner, Thomas Buch
Summary: Epigenetic changes can drive cancer malignancy, while histone deacetylase inhibitors (HDACis) hold promise as anticancer drugs due to their ability to target multiple pathways relevant to the disease.
Review
Biochemistry & Molecular Biology
Long Xu, Xiaoyu Yan, Jian Wang, Yuanxin Zhao, Qingqing Liu, Jiaying Fu, Xinyi Shi, Jing Su
Summary: This article provides an overview of ovarian cancer metastasis and the dysregulated expression of HDACs in ovarian cancer. It discusses the roles of HDACs in the regulation of ovarian cancer metastasis and highlights the importance of developing compounds that target HDACs in the future of ovarian cancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Wanlin Jiang, Megan E. Block, Chandra S. Boosani
Summary: This study investigates the role of TNF-alpha and IGF-1 in regulating the epigenetic mechanisms that promote VSMCs proliferation, and identifies a novel molecular mechanism involving DNMT1, HDAC10, and HDAC2. Results reveal the inter-dependence of epigenetic mediators in VSMCs proliferation.
Article
Immunology
Melanie A. Whitmore, Hong Li, Wentao Lyu, Sharmily Khanam, Guolong Zhang
Summary: The combination of HDACi and DNMTi/HMTi showed a strong synergy in inducing HDP gene expression, and also regulated the expression of tight junction proteins.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Chemistry, Medicinal
Xin-Hui Zhang, Qin-Ma, Hui-Pan Wu, Mussa Yussuf Khamis, Yi-Han Li, Li-Ying Ma, Hong-Min Liu
Summary: In this translation, the essential role of HDACs in maintaining homeostasis is discussed, with a focus on the unique characteristics and diverse functions of HDAC6. HDAC6 inhibitors have shown promising potential in treating various diseases with reduced toxicity. Progress has been made in defining the crystal structures of HDAC6 catalytic domains, which can inform the development of HDAC6 inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Christophe Le Clorennec, Divya Subramonian, Yuchen Huo, Peter E. Zage
Summary: UBE4B ubiquitin ligase is closely associated with neuroblastoma patient outcomes. It interacts with the E3 ubiquitin ligase ITCH/AIP4 and affects the ubiquitination and degradation of Ku70 and c-FLIPL. Additionally, UBE4B plays a role in apoptosis induced by histone deacetylase (HDAC) inhibition.
CELL DEATH & DISEASE
(2023)
Article
Chemistry, Medicinal
Kairui Yue, Simin Sun, Geng Jia, Mengting Qin, Xiaohan Hou, C. James Chou, Chao Huang, Xiaoyang Li
Summary: This study reports the development of a highly selective HDAC6 inhibitor with hydrazide as the zinc-binding group (ZBG), which exhibits superior pharmacokinetic properties compared to current hydroxamic acid inhibitors. Structure-activity relationship analysis reveals that the presence of an ethyl group substituent in the hydrazide-based ZBG and a cap group with increased rigidity and volume enhance the HDAC6 selectivity of the designed compounds. The representative inhibitor 35m demonstrates potent HDAC6 inhibitory activity and improved pharmacokinetic properties compared to hydroxamic acid-based HDAC6 inhibitors Tubastatin A and ACY1215. Furthermore, low-dose 35m effectively decreases LPS-induced IL-1 beta release by blocking the activation of NLRP3, indicating its potential as an orally active therapeutic agent for NLRP3-related diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Svetlana Demyanenko, Svetlana Sharifulina
Summary: HDAC and HAT play crucial roles in regulating cell functions through acetylating/deacetylating histones and non-histone proteins, impacting cell survival, death, and other processes. The effects of stroke on non-histone protein acetylation/deacetylation in brain cells are still poorly understood, but HDAC inhibitors have shown promise in protecting the brain from ischemic damage. The roles of different HDAC isoforms in brain cell survival and death after stroke remain controversial.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Annick Muehlethaler-Mottet, Julie Liberman, Kelly Ascencao, Marjorie Flahaut, Katia Balmas Bourloud, Pu Yan, Nicolas Jauquier, Nicole Gross, Jean-Marc Joseph
Article
Oncology
Marjorie Flahaut, Nicolas Jauquier, Nadja Chevalier, Katya Nardou, Katia Balmas Bourloud, Jean-Marc Joseph, David Barras, Christian Widmann, Nicole Gross, Raffaele Renella, Annick Muhlethaler-Mottet
Meeting Abstract
Oncology
Annick Muhlethaler-Mottet, Gisele Montavon, Marjorie Flahaut, Nicolas Jauquier, Jean-Marc Joseph, Olivier Delattre, Lukas Sommer, Isabelle Janoueix-Lerosey, Nicole Gross
Article
Multidisciplinary Sciences
Julie Liberman, Herve Sartelet, Marjorie Flahaut, Annick Muehlethaler-Mottet, Aurelie Coulon, Carine Nyalendo, Gilles Vassal, Jean-Marc Joseph, Nicole Gross
Article
Cell Biology
A. Muehlethaler-Mottet, M. Flahaut, K. Balmas Bourloud, K. Nardou, A. Coulon, J. Liberman, M. Thome, N. Gross
CELL DEATH & DISEASE
(2011)
Article
Oncology
Gisele Montavon, Nicolas Jauquier, Aurelie Coulon, Michel Peuchmaur, Marjorie Flahaut, Katia Balmas Bourloud, Pu Yan, Olivier Delattre, Lukas Sommer, Jean-Marc Joseph, Isabelle Janoueix-Lerosey, Nicole Gross, Annick Muehlethaler-Mottet
Article
Oncology
Aurelie Coulon, Marjorie Flahaut, Annick Muehlethaler-Mottet, Roland Meier, Julie Liberman, Katia Balmas-Bourloud, Katya Nardou, Pu Yan, Stephane Tercier, Jean-Marc Joseph, Lukas Sommer, Nicole Gross
Article
Oncology
Lucie Vivancos Stalin, Marco Gualandi, Johannes Hubertus Schulte, Raffaele Renella, Olga Shakhova, Annick Muhlethaler-Mottet
FRONTIERS IN ONCOLOGY
(2019)
Article
Oncology
Angela Bellini, Ulrike Poetschger, Virginie Bernard, Eve Lapouble, Sylvain Baulande, Peter F. Ambros, Nathalie Auger, Klaus Beiske, Marie Bernkopf, David R. Betts, Jaydutt Bhalshankar, Nick Bown, Katleen de Preter, Nathalie Clement, Valerie Combaret, Jaime Font de Mora, Sally L. George, Irene Jimenez, Marta Jeison, Barbara Marques, Tommy Martinsson, Katia Mazzocco, Martina Morini, Annick Muehlethaler-Mottet, Rosa Noguera, Gaelle Pierron, Maria Rossing, Sabine Taschner-Mandl, Nadine Van Roy, Ales Vicha, Louis Chesler, Walentyna Balwierz, Victoria Castel, Martin Elliott, Per Kogner, Genevieve Laureys, Roberto Luksch, Josef Malis, Maja Popovic-Beck, Shifra Ash, Olivier Delattre, Dominique Valteau-Couanet, Deborah A. Tweddle, Ruth Ladenstein, Gudrun Schleiermacher
Summary: Genetic alterations of ALK (clonal mutations and amplifications) in high-risk neuroblastoma patients are independent predictors of poorer survival. These data provide a rationale for the integration of ALK inhibitors in upfront treatment of high-risk neuroblastoma with ALK alterations.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Biology
Maria-Vittoria Sepporta, Viviane Praz, Katia Balmas Bourloud, Jean-Marc Joseph, Nicolas Jauquier, Nicolo' Riggi, Katya Nardou-Auderset, Audrey Petit, Jean-Yves Scoazec, Herve Sartelet, Raffaele Renella, Annick Muhlethaler-Mottet
Summary: TWIST1 and TWIST2 have opposite effects in neuroblastoma, with TWIST1 associated with poor survival and metastasis, and TWIST2 correlating with good prognosis. Suppression of TWIST1 reduces tumor growth and metastasis, and affects multiple signaling and cell-cell interaction pathways.
COMMUNICATIONS BIOLOGY
(2022)
Article
Endocrinology & Metabolism
Annick Muhlethaler-Mottet, Silvia Uccella, Deborah Marchiori, Stefano La Rosa, Jean Daraspe, Katia Balmas Bourloud, Maja Beck Popovic, Philippe J. Eugster, Eric Grouzmann, Karim Abid
Summary: This study compared the biosynthesis, metabolism, and storage of catecholamines and metanephrines between patients with neuroblastoma (NB) and pheochromocytoma (PHEO). The results showed that NB patients had lower levels of catecholamines compared to PHEO patients, and their neurosecretory vesicles were also less abundant, leading to rapid conversion into metanephrines and diffusion into the blood, which explains the absence of systemic hypertension in most NB patients.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Meeting Abstract
Medicine, General & Internal
Chia-Lung Yang, Marco Gualandi, Nicolas Jauquier, Jean-Marc Joseph, Katia Balmas Bourloud, Annick Muhlethaler-Mottet, Olga Shakhova
SWISS MEDICAL WEEKLY
(2018)
Meeting Abstract
Medicine, General & Internal
M. Flahaut, A. Coulon, K. Nardou, A. Muhlethaler-Mottet, N. Gross
SWISS MEDICAL WEEKLY
(2011)
Meeting Abstract
Medicine, General & Internal
J. Liberman, M. Flahaut, A. Muhlethaler-Mottet, A. Coulon, J. M. Joseph, N. Gross
SWISS MEDICAL WEEKLY
(2011)
Meeting Abstract
Medicine, General & Internal
Annick Muhlethaler-Mottet, Marjorie Flahaut, Katia Balmas Bourloud, Katya Auderset Nardou, Aurelie Coulon, Julie Liberman, Margot Thome, Nicole Gross
SWISS MEDICAL WEEKLY
(2011)