Article
Multidisciplinary Sciences
Gabriel K. Griffin, Jingyi Wu, Arvin Iracheta-Vellve, James C. Patti, Jeffrey Hsu, Thomas Davis, Deborah Dele-Oni, Peter P. Du, Aya G. Halawi, Jeffrey J. Ishizuka, Sarah Y. Kim, Susan Klaeger, Nelson H. Knudsen, Brian C. Miller, Tung H. Nguyen, Kira E. Olander, Malvina Papanastasiou, Suzanna Rachimi, Emily J. Robitschek, Emily M. Schneider, Mitchell D. Yeary, Margaret D. Zimmer, Jacob D. Jaffe, Steven A. Carr, John G. Doench, W. Nicholas Haining, Kathleen B. Yates, Robert T. Manguso, Bradley E. Bernstein
Summary: A CRISPR-Cas9 screen in mouse tumour models treated with immune checkpoint blockade identified SETDB1 as an epigenetic checkpoint protein that suppresses tumour-intrinsic immunogenicity. Loss of SETDB1 leads to derepression of immune-stimulating genes and triggers TE-specific cytotoxic T cell responses, suggesting it as a potential target for immunotherapy in cancer treatment.
Article
Oncology
Margarita E. Neganova, Sergey G. Klochkov, Yulia R. Aleksandrova, Gjumrakch Aliev
Summary: Epigenetic changes associated with histone modifications are important in the emergence and maintenance of various cancer types. Inhibitors of enzymes involved in these modifications are promising for anticancer drug development. This review explores the main features of common histone modifications and their role in malignant neoplasms, discussing strategies for inhibitor development and analyzing the use of multitarget drugs as the most promising strategy.
SEMINARS IN CANCER BIOLOGY
(2022)
Review
Chemistry, Medicinal
Dan Zhang, Jifa Zhang, Yuxi Wang, Guan Wang, Pan Tang, Yun Liu, Yiwen Zhang, Liang Ouyang
Summary: Parkinson's disease (PD) is a multifactorial disease caused by a complex interplay between genetic and epigenetic factors. Recent studies have revealed the epigenetic mechanisms involved in PD, such as DNA methylation, histone modifications, and microRNA (miRNA) regulation. Epigenetic regulators could be potential therapeutic targets in neurodegenerative disorders. This review summarizes the mechanisms of epigenetic regulation in PD and discusses the use of inhibitors and activators of these regulators, as well as the neuroprotective effects of small molecule epigenetic modulators. Additionally, the contribution of miRNAs to the underlying mechanisms of PD and miRNA-based therapies are also discussed.
MEDICINAL RESEARCH REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Ka-Wing Fong, Jonathan C. Zhao, Xiaodong Lu, Jung Kim, Andrea Piunti, Ali Shilatifard, Jindan Yu
Summary: PALI1 is a newly identified accessory protein that plays a role in advanced prostate cancer. It competes with JARID2 for binding to the PRC2 core subunit SUZ12 and interacts with the H3K9 methyltransferase G9A, forming a unique super-complex involved in dual H3K9/K27 methylation and gene repression. PALI1 and G9A promote prostate cancer cell proliferation and invasion, and drive tumor growth in xenograft models.
Review
Urology & Nephrology
Anbarasu Kumaraswamy, Katherine R. Welker Leng, Thomas C. Westbrook, Joel A. Yates, Shuang G. Zhao, Christopher P. Evans, Felix Y. Feng, Todd M. Morgan, Joshi J. Alumkal
Summary: This study systematically reviewed the role of epigenetic factors in prostate cancer from 2015 to 2020, highlighting key preclinical and translational data. Findings from both preclinical and clinical studies were reviewed and summarized, along with a discussion on 12 ongoing clinical studies with epigenetic targeted therapies.
Review
Plant Sciences
Jun-Li Wang, Dong-Wei Di, Pan Luo, Li Zhang, Xiao-Feng Li, Guang-Qin Guo, Lei Wu
Summary: This review focuses on the molecular mechanisms through which epigenetic modifications regulate auxin biosynthesis, demonstrating that complex signaling pathways affect gene expression and subsequently protein production.
FRONTIERS IN PLANT SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Qiong Wu, Anders E. Berglund, Arnold B. Etame
Summary: Glioblastoma is highly resistant to standard therapies and the durability of response to the best chemotherapy agent, Temozolomide, is often short-lived due to tumor resistance. The need for therapies that can provide synergy to chemoradiation is urgent, as adaptive resistance evolution in GBM is facilitated through treatment-induced epigenetic modifications. Understanding and targeting these epigenetic modifications associated with GBM resistance is a top priority.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Francisco Gimeno-Valiente, Gerardo Lopez-Rodas, Josefa Castillo, Luis Franco
Summary: This review focuses on the interconnections between epigenetics and alternative splicing in the development of cancer. It discusses the mechanisms involved in these interconnections and the potential diagnostic and therapeutic tools that can be derived from them. The reversible nature of epigenetic alterations and the possibility of correcting aberrant alternative splicing offer promising therapeutic possibilities for cancer treatment.
Article
Multidisciplinary Sciences
Haining Zhou, Chad B. Stein, Tiasha A. Shafiq, Gergana Shipkovenska, Marian Kalocsay, Joao A. Paulo, Jiuchun Zhang, Zhenhua Luo, Steven P. Gygi, Karen Adelman, Danesh Moazed
Summary: Polycomb repressive complexes (PRCs) and the RIX1 complex work together to silence Polycomb target genes in human cells, with the recruitment of the RIX1 complex to chromatin being essential for silencing.
Review
Genetics & Heredity
Vincenzo Cavalieri
Summary: The emergence of a nucleosome-based chromatin structure during the evolutionary transition from prokaryotes to eukaryotes plays a crucial role in adaptive responses to environmental influence through epigenetic mechanisms involving histones. The overwhelming number of post-translational modifications at multiple residues of histones and their implications in nucleosome dynamics and chromatin processes are discussed in this review.
Review
Plant Sciences
Qingshuai Chen, Jing Zhang, Gang Li
Summary: This article summarizes recent progress in uncovering the epigenetic mechanisms involved in sugar signal transduction, as well as the interactions between sugar signaling and light, temperature, and phytohormone signaling pathways.
TRENDS IN PLANT SCIENCE
(2022)
Article
Multidisciplinary Sciences
Michael Habig, Cecile Lorrain, Alice Feurtey, Jovan Komluski, Eva H. Stukenbrock
Summary: In this study, the authors demonstrated a causal effect of epigenetic modifications on mutation rates in fungal pathogens, as well as the impact of temperature stress and cytosine methylation on the rate and location of spontaneous mutations in the genome. Additionally, they found that histone modifications and transposable elements can significantly affect mutation rates.
NATURE COMMUNICATIONS
(2021)
Review
Cell Biology
Aidan J. Levinsky, Gregor McEdwards, Nasha Sethna, Mark A. Currie
Summary: H3K9 methyltransferases play crucial roles in genome stability, cell type-specific gene expression, and non-histone methylation. They are involved in histone modification and regulate the methylation of various non-histone targets, contributing to genome regulation and cellular functions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Haining Zhou, Wenzhi Feng, Juntao Yu, Tiasha A. Shafiq, Joao A. Paulo, Jiuchun Zhang, Zhenhua Luo, Steven P. Gygi, Danesh Moazed
Summary: The rixosome and PRC1 silencing complexes are associated with deSUMOylating and deubiquitinating enzymes, SENP3 and USP7, respectively. The enzymatic activities of SENP3 and USP7 are required for silencing of Polycomb target genes. SUMOylation and ubiquitination regulate the assembly and activities of the rixosome and Polycomb complexes.
Article
Biochemistry & Molecular Biology
George Hunt, Ann Boija, Mattias Mannervik
Summary: Maintenance of appropriate cell states involves epigenetic mechanisms, including Polycomb-group (PcG)-mediated transcriptional repression. This study reveals the association between the p300/CREB-binding protein (CBP) co-activator and PcG regions in Drosophila and mouse cells. CBP stabilizes Pol II at PcG-bound repressive sites and promotes Pol II pausing, which are necessary for R-loop formation and nucleosome depletion at Polycomb Response Elements (PREs), thereby supporting PcG-mediated silencing.
Article
Oncology
Safa Majeed, Mansi K. Aparnathi, Kevin C. J. Nixon, Vidhyasagar Venkatasubramanian, Fariha Rahman, Lifang Song, Jessica Weiss, Ranya Barayan, Vijithan Sugumar, Samir H. Barghout, Joel D. Pearson, Rod Bremner, Aaron D. Schimmer, Ming S. Tsao, Geoffrey Liu, Benjamin H. Lok
Summary: TAK-243 exhibits efficacy in preclinical models of small cell lung cancer (SCLC), with associations to various gene sets. TAK-243 synergizes with cisplatin/etoposide chemotherapy (C/E) and PARP inhibitor olaparib. TAK-243 is a potential therapeutic strategy to improve SCLC patient outcomes.
CLINICAL CANCER RESEARCH
(2022)
Editorial Material
Endocrinology & Metabolism
Sylvia L. Asa, Lori A. Erickson, Ozgur Mete
ENDOCRINE PATHOLOGY
(2022)
Review
Pathology
Claudio Luchini, Liron Pantanowitz, Volkan Adsay, Sylvia L. Asa, Pietro Antonini, Ilaria Girolami, Nicola Veronese, Alessia Nottegar, Sara Cingarlini, Luca Landoni, Lodewijk A. Brosens, Anna V. Verschuur, Paola Mattiolo, Antonio Pea, Andrea Mafficini, Michele Milella, Muhammad K. Niazi, Metin N. Gurcan, Albino Eccher, Ian A. Cree, Aldo Scarpa
Summary: Ki-67 assessment plays a key role in the diagnosis of neuroendocrine neoplasms (NENs) from all anatomic locations. Digital pathology combined with machine learning has shown to be highly accurate and reproducible for evaluating Ki-67 in NENs. In this systematic review, the advantages of digital image analysis (DIA) in assessing Ki-67 in pancreatic NENs (PanNENs) were highlighted, including improved standardization and reliability, as well as increased speed and practicality compared to manual counting. However, limitations such as higher costs and operator qualification issues need to be addressed. A comparative meta-analysis showed a high concordance between DIA and manual counting. These findings support the widespread adoption of validated DIA methods for Ki-67 assessment in PanNENs.
Editorial Material
Endocrinology & Metabolism
Sylvia L. Asa, Ozgur Mete
ENDOCRINE PATHOLOGY
(2022)
Article
Pathology
Luvy D. Mendez, Nicholas S. Wolsefer, Sylvia L. Asa, Jay Wasman, Jennifer M. Yoest, Ivan J. Stojanov
Summary: This study evaluated the usefulness of immunohistochemistry (IHC) using the BRAF VE1 mutant-specific antibody as a diagnostic adjunct in mandibular ameloblastoma. The study found that the BRAF(V600E) mutation is more frequent in mandibular ameloblastoma and less frequent in maxillary ameloblastoma. BRAF VE1 IHC is a highly accurate tool for the diagnosis of mandibular ameloblastoma.
Editorial Material
Endocrinology & Metabolism
Ozgur Mete, Sylvia L. Asa
Article
Pathology
Sylvia L. Asa, Ozgur Mete, Ulrich Schueller, Biswarathan Ramani, Kanish Mirchia, Arie Perry
Summary: The tumor formerly known as cauda equina paraganglioma was recently renamed as cauda equina neuroendocrine tumor (CENET) based on distinct biological and genetic properties. All tumors tested were positive for INSM1, synaptophysin, chromogranin A, SSTR2, and CD56 as well as at least 1 keratin (AE1/AE3, CAM5.2).
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2023)
Article
Endocrinology & Metabolism
Sylvia L. Asa, Amr Mohamed
ENDOCRINE PATHOLOGY
(2023)
Review
Oncology
Amr Mohamed, Sulin Wu, Mohamed Hamid, Amit Mahipal, Sakti Cjakrabarti, David Bajor, J. Eva Selfridge, Sylvia L. L. Asa
Summary: Appendiceal neuroendocrine neoplasms (ANENs) are usually found incidentally during appendectomy. They are rare, accounting for a small percentage of intestinal neoplasms. The management of ANENs varies based on histological differentiation and tumor grade.
Article
Endocrinology & Metabolism
Sylvia L. Asa, Lori A. Erickson, Guido Rindi
Summary: Endocrine pathology encompasses a wide range of disorders originating from different parts of the body. Understanding this field requires knowledge of the structure and function of the endocrine system, including the signaling pathways involved in hormone synthesis and secretion. Molecular genetics has provided insights into both sporadic and hereditary diseases common in endocrine pathology.
ENDOCRINE PATHOLOGY
(2023)
Article
Endocrinology & Metabolism
Sylvia L. Asa, Ozgur Mete, Nicole D. Riddle, Arie Perry
Summary: This study identified a rare type of pituitary neuroendocrine tumors (PitNETs) that express both PIT1 and SF1 transcription factors. These tumors exhibit variable clinical and morphological features, commonly presenting as large tumors with growth hormone excess and occasionally coexisting with other types of PitNETs.
ENDOCRINE PATHOLOGY
(2023)
Review
Endocrinology & Metabolism
Sylvia L. Asa, Silvia Uccella, Arthur Tischler
Summary: The assessment of cell differentiation in endocrine neoplasms involves the identification of cell structure, specific transcription factors, hormones, and enzymes. Differentiation status serves as prognostic and predictive factors for endocrine neoplasms. Hormones can act as biomarkers for clinical surveillance and loss of differentiated hormone production can indicate dedifferentiation and aggressiveness of the tumor. Differentiated endocrine cells express targets for therapy, providing opportunities for targeted treatment.
ENDOCRINE PATHOLOGY
(2023)
Article
Endocrinology & Metabolism
Arthur S. Tischler, Virginia A. LiVolsi, Sylvia L. Asa
Summary: The pathology of neoplasia not only focuses on the tumor itself but also provides information about the non-tumorous tissue surrounding the lesion, which can reveal pathogenetic mechanisms and confirm the effects of medical therapies. This article reviews clinically relevant features in endocrine neoplasms and emphasizes the importance of assessing and reporting these features to enhance clinical management.
ENDOCRINE PATHOLOGY
(2023)
Article
Immunology
Ioannis D. Dimitriou, David Meiri, Yulia Jitkova, Alisha R. Elford, Marianne Koritzinsky, Aaron D. Schimmer, Pamela S. Ohashi, Nahum Sonenberg, Robert Rottapel
Summary: In this study, the researchers found that 4E-BP1/2 proteins play a critical role in the proliferation of mouse CD8(+) T cells and the development of antiviral effector function. They also discovered that the translation of genes related to mitochondrial biogenesis is impaired in T cells derived from 4E-BP1/2-deficient mice.
JOURNAL OF IMMUNOLOGY
(2022)
Correction
Biochemistry & Molecular Biology
Qi Zhang, Bridget Riley-Gillis, Lina Han, Yannan Jia, Alessia Lodi, Haijiao Zhang, Saravanan Ganesan, Rongqing Pan, Sergej N. Konoplev, Shannon R. Sweeney, Jeremy A. Ryan, Yulia Jitkova, Kenneth Dunner, Shaun E. Grosskurth, Priyanka Vijay, Sujana Ghosh, Charles Lu, Wencai Ma, Stephen Kurtz, Vivian R. Ruvolo, Helen Ma, Connie C. Weng, Cassandra L. Ramage, Natalia Baran, Ce Shi, Tianyu Cai, Richard Eric Davis, Venkata L. Battula, Yingchang Mi, Jing Wang, Courtney D. DiNardo, Michael Andreeff, Jeffery W. Tyner, Aaron Schimmer, Anthony Letai, Rose Ann Padua, Carlos E. Bueso-Ramos, Stefano Tiziani, Joel Leverson, Relja Popovic, Marina Konopleva
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
