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
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)
Review
Biochemistry & Molecular Biology
Jie Wang, Feng Yun, Jiahui Sui, Wenpeng Liang, Dingding Shen, Qi Zhang
Summary: Epilepsy, a common and severe chronic neurological disorder, has been the subject of extensive research on post-translational modification (PTM) mechanisms, particularly protein acetylation modifications. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate acetylation, with HATs transferring acetyl groups to lysine residues and HDACs removing acetyl groups. Epilepsy is associated with the regulation of gene expression through histone acetylation and deacetylation, as well as the acetylation modification of non-histone substrates. HDAC inhibitors (HDACi) have been developed as potential antiepileptic drugs. This review summarizes the changes in acetylation modification during epileptogenesis, the application of HDACi in epilepsy treatment, and the underlying mechanisms. Further understanding of acetylation regulation will provide insights into the pathological mechanism of epilepsy and novel therapeutic ideas.
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
Oncology
Fengyi Guo, Hongjing Wang
Summary: This review summarizes the classification and mechanisms of action of histone deacetylase and the clinical application of their inhibitors in ovarian cancer. Histone deacetylase inhibitors show promising potential as anti-cancer drugs, and combination therapy with other anticancer drugs for synergistic effects can improve efficacy.
FRONTIERS IN ONCOLOGY
(2022)
Article
Medicine, Research & Experimental
Georgiana Toma, Eliza Karapetian, Chiara Massa, Dagmar Quandt, Barbara Seliger
Summary: HDACi treatment increases intracellular protein acetylation level in CD8(+) T cells, but the protein expression profiles are similar between different age groups. CD8(+) T cells from old donors exhibit higher cytokine secretion and activation marker expression compared to those from young donors, which may have clinical relevance.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Virology
Shun Iida, Sohtaro Mine, Keiji Ueda, Tadaki Suzuki, Hideki Hasegawa, Harutaka Katano
Summary: The histone deacetylase inhibitor SBHA was found to efficiently induce KSHV reactivation and apoptosis in PEL cells, suggesting its potential as a tool for KSHV reactivation induction and a novel therapeutic strategy against PEL.
JOURNAL OF VIROLOGY
(2021)
Article
Plant Sciences
Yang Xu, Yameng Wang, Lulu Wang, Wenxing Liang, Qianqian Yang
Summary: Botrytis cinerea causes gray mold and leads to significant financial losses. Fungicide resistance of B. cinerea is a major concern in food safety and agricultural environmental protection. Sodium valproate (SV) has shown potential as a safe and effective antifungal agent by enhancing the acetylation of histone H3 and modifying gene expression to inhibit B. cinerea.
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)
Article
Cell Biology
Yang Shi, Zheng Xiang, Huiyu Yang, Suliman Khan, Ruizhe Li, Siran Zhou, Saif Ullah, Jiyu Zhang, Bingrong Liu
Summary: The study demonstrated the treatment response of esophageal squamous cell carcinoma (ESCC) to selective histone deacetylase inhibitor (HDACi) LMK-235 and identified TNS3 as a potential biomarker predicting treatment sensitivity. TNS3, highly expressed in ESCC, was found to be down-regulated in response to LMK-235 treatment and correlated with tumor malignancy and poor prognosis. Silencing TNS3 inhibited ESCC cell proliferation and sensitized the treatment response to LMK-235, providing insights into its oncogenic role in ESCC and clinical application for HDAC targeted therapy.
Article
Agronomy
Qin Lu, Yan Li, Jing Liao, Zhaohong Ni, Shunchao Xia, Maofa Yang, Haiyin Li, Jianjun Guo
Summary: This study investigated the role of histone H3 acetylation in diapause of the cotton bollworm and found that it is closely related to pupal diapause, suggesting its potential as a target for pest control.
PEST MANAGEMENT SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Jakub Ptacek, Ivan Snajdr, Jiri Schimer, Zsofia Kutil, Jana Mikesova, Petra Baranova, Barbora Havlinova, Werner Tueckmantel, Pavel Majer, Alan Kozikowski, Cyril Barinka
Summary: This article compares hydroxamate-based HDAC6-selective inhibitors commonly used in the treatment of neurological and psychiatric disorders with a novel HDAC6 inhibitor containing the difluoromethyl-1,3,4-oxadiazole function (compound 7). In vitro screening revealed HDAC10 as a primary off-target for hydroxamate-based HDAC6 inhibitors, while compound 7 showed exquisite selectivity over all other HDAC isoforms. Cell-based assays showed lower potency for all compounds when using tubulin acetylation as a surrogate readout. Additionally, the limited selectivity of some HDAC6 inhibitors was shown to be linked to cytotoxicity in RPMI-8226 cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Hye Sun Shin, Yuri Lee, Mi Hee Shin, Soo Ick Cho, Christos C. Zouboulis, Min Kyoung Kim, Dong Hun Lee, Jin Ho Chung
Summary: Proper regulation of histone acetylation is crucial for sebocyte lipogenesis, with inhibitors of p300 histone acetyltransferase leading to decreased expression of key lipogenic genes and decreased lipid droplet formation. In contrast, inhibition of histone deacetylase promotes lipogenesis by increasing the expression of these genes. These findings suggest a potential therapeutic strategy for skin diseases related to excess sebum production.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Flore Nardella, Ludovic Halby, Irina Dobrescu, Johanna Viluma, Corentin Bon, Aurelie Claes, Veronique Cadet-Daniel, Ambre Tafit, Camille Roesch, Elie Hammam, Diane Erdmann, Melissa Mairet-Khedim, Roger Peronet, Salah Mecheri, Benoit Witkowski, Artur Scherf, Paola B. Arimondo
Summary: The newly developed derivatives combining pan-histone deacetylase inhibitor with DNA methyltransferase inhibitor show superior activity in treating malaria and potent inhibition against human HDAC6. These compounds are fully active against multidrug-resistant Plasmodium and offer a cost-effective alternative to current failing antimalarial therapy.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
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.
Article
Oncology
Su Yeon Han, Aram Ko, Haruhisa Kitano, Chel Hun Choi, Min-Sik Lee, Jinho Seo, Junya Fukuoka, Soo-Youl Kim, Stephen M. Hewitt, Joon-Yong Chung, Jaewhan Song
Article
Cell Biology
Joon-Yong Chung, Joon Seon Song, Kris Ylaya, John D. Sears, Lauren Choi, Hanbyoul Cho, Avi Z. Rosenberg, Stephen M. Hewitt
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
(2018)
Article
Oncology
Paola A. Rojas, Maria May, Gonzalo R. Sequeira, Andres Elia, Michelle Alvarez, Paula Martinez, Pedro Gonzalez, Stephen Hewitt, Xiaping He, Charles M. Perou, Alfredo Molinolo, Luz Gibbons, Martin C. Abba, Hugo Gass, Claudia Lanari
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2017)
Article
Transplantation
Laura H. Mariani, Sebastian Martini, Laura Barisoni, Pietro A. Canetta, Jonathan P. Troost, Jeffrey B. Hodgin, Matthew Palmer, Avi Z. Rosenberg, Kevin V. Lemley, Hui-Ping Chien, Jarcy Zee, Abigail Smith, Gerald B. Appel, Howard Trachtman, Stephen M. Hewitt, Matthias Kretzler, Serena M. Bagnasco
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2018)
Review
Oncology
Maria Vittoria Dieci, Nina Radosevic-Robin, Susan Fineberg, Gert van den Eynden, Nils Ternes, Frederique Penault-Llorca, Giancarlo Pruneri, Timothy M. D'Alfonso, Sandra Demaria, Carlos Castaneda, Joselyn Sanchez, Sunil Badve, Stefan Michiels, Veerle Bossuyt, Federico Rojo, Baljit Singh, Torsten Nielsen, Giuseppe Viale, Seong-Rim Kim, Stephen Hewitt, Stephan Wienert, Sybille Loibl, David Rimm, Fraser Symmans, Carsten Denkert, Sylvia Adams, Sherene Loi, Roberto Salgado
SEMINARS IN CANCER BIOLOGY
(2018)
Editorial Material
Oncology
Stephen M. Hewitt
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2020)
Article
Pathology
Jeong Won Kim, Joon-Yong Chung, Kris Ylaya, Yoonho Park, Sun-Young Jun, Seung-Mo Hong, Stephen M. Hewitt
Summary: The study revealed that high expression of SOX2 in patients with small intestinal adenocarcinomas is associated with shorter overall survival and has the potential to predict clinical outcomes.
Article
Medicine, Research & Experimental
Ilseon Hwang, Jeong Won Kim, Kris Ylaya, Eun Joo Chung, Haruhisa Kitano, Candice Perry, Jun Hanaoka, Junya Fukuoka, Joon-Yong Chung, Stephen M. Hewitt
JOURNAL OF TRANSLATIONAL MEDICINE
(2020)
Article
Multidisciplinary Sciences
Saumya Tiwari, Andre Kajdacsy-Balla, Joshua Whiteley, Georgina Cheng, Stephen M. Hewitt, Rohit Bhargava
Summary: This study introduces a measurement framework based on high-definition infrared imaging that uses the intrinsic chemical contrast of tissue to label unique components of tumors and their microenvironments, predicting overall survival in colon cancer patients. The results reveal the association between tumor spatial organization and disease progression.
Article
Medicine, Research & Experimental
Candace C. Liu, Marc Bosse, Alex Kong, Adam Kagel, Robert Kinders, Stephen M. Hewitt, Sushama Varma, Matt van de Rijn, Stanislaw H. Nowak, Sean C. Bendall, Michael Angelo
Summary: The study validated the use of MIBI-TOF for imaging proteins in human tissue and compared it to traditional immunohistochemistry methods. The results showed that MIBI-TOF can generate consistent and quantitative annotations of clinically relevant cell states and provide a scalable benchmark for multiplexed immunohistochemistry approaches.
LABORATORY INVESTIGATION
(2022)
Article
Medicine, Research & Experimental
Sandeep K. Singhal, Jung S. Byun, Tingfen Yan, Ryan Yancey, Ambar Caban, Sara Gil Hernandez, Sediqua Bufford, Stephen M. Hewitt, Joy Winfield, Jaya Pradhan, Vesco Mustkov, Jasmine A. McDonald, Eliseo J. Perez-Stable, Anna Maria Napoles, Nasreen Vohra, Adriana De Siervi, Clayton Yates, Melissa B. Davis, Mei Yang, Yien Che Tsai, Allan M. Weissman, Kevin Gardner
Summary: Women of African ancestry have higher rates of breast cancer mortality, and differences in tumor biology may play a role in these disparities. The protein gp78, found in patient breast cancer cells, is associated with poor survival outcomes in both ER+ and ER- tumors. Breast cancers with high levels of gp78 are enriched in gene expression pathways related to cell cycle, metabolism, signaling, and stress response. Gp78 protein is an independent predictor of poor outcomes in women of African ancestry, and gene expression signatures stratified by gp78 expression are strong predictors of recurrence and treatment response.
Article
Oncology
Sherry X. Yang, Stephen M. Hewitt, John Yu
Summary: The role of lymph node involvement and tumor size in metastatic disease, including breast cancer, is examined in this study. The findings suggest that nodal involvement and T stage are independent risk factors for mortality in patients with de novo metastatic breast cancer. The study also highlights the significance of positive lymph node count, tumor size, and chest wall involvement in breast cancer-specific mortality. These findings have important implications for the management and treatment of metastatic breast cancer patients.
NPJ PRECISION ONCOLOGY
(2022)
Article
Cell Biology
Kyungeun Kim, Kris Ylaya, Candice Perry, Mi-Yeon Lee, Jeong Won Kim, Joon-Yong Chung, Stephen M. Hewitt
Summary: Water is a crucial factor for protein and RNA degradation in stored tissue sections, and storage conditions can affect the expression of certain key proteins and RNA integrity in breast tissue.
BIOPRESERVATION AND BIOBANKING
(2023)
Article
Multidisciplinary Sciences
Lichun Ma, Sophia Heinrich, Limin Wang, Friederike L. Keggenhoff, Subreen Khatib, Marshonna Forgues, Michael Kelly, Stephen M. Hewitt, Areeba Saif, Jonathan M. Hernandez, Donna Mabry, Roman Kloeckner, Tim F. Greten, Jittiporn Chaisaingmongkol, Mathuros Ruchirawat, Jens U. Marquardt, Xin Wei Wang
Summary: Intratumor heterogeneity arises from the evolution of tumor cells and their interactions with the tumor microenvironment. This study uses single-cell RNA sequencing to analyze liver cancer patients, identifying cellular dynamics and communication networks between malignant cells and tumor-associated immune cells. The findings validate the stable molecular networks of malignant ecosystems and potentially open up new therapeutic opportunities.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Nathan Simon, Antonella Antignani, Stephen M. Hewitt, Massimo Gadina, Christine Alewine, David FitzGerald