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)
Article
Biology
Mengxing Li, Suryavathi Viswanadhapalli, Bindu Santhamma, Uday P. Pratap, Yiliao Luo, Junhao Liu, Kristin A. Altwegg, Weiwei Tang, Zexuan Liu, Xiaonan Li, Behnam Ebrahimi, Hui Yan, Yi Zou, Swapna Konda, Gangadhara R. Sareddy, Zhenming Xu, Yidong Chen, Manjeet K. Rao, Andrew J. Brenner, Virginia G. Kaklamani, Rajeshwar R. Tekmal, Gulzar Ahmed, Ganesh Raj, Klaus J. Nickisch, Hareesh B. Nair, Ratna K. Vadlamudi
Summary: The study demonstrated that LIFR inhibitor EC359 could enhance the therapeutic efficacy of HDACi against TNBC, with RNA-seq studies showing that the combination therapy attenuated oncogenic/survival signaling pathways activated by HDACi. Importantly, the combination therapy showed potent inhibition of TNBC growth in vivo.
COMMUNICATIONS BIOLOGY
(2021)
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
Cell Biology
Richard A. Pepermans, Geetanjali Sharma, Eric R. Prossnitz
Summary: Estrogen plays crucial roles in various cancers, metabolism, and immune regulation. The G protein-coupled estrogen receptor (GPER) has been found to contribute to endocrine therapy resistance in breast cancer and has potential therapeutic value in targeting other diseases such as obesity and diabetes. Ongoing clinical trials are exploring the use of GPER-selective agonists like G-1 in combination with immune checkpoint inhibition for cancer treatment.
Review
Cell Biology
Iason Psilopatis, Kleio Vrettou, Florian Nima Fleckenstein, Stamatios Theocharis
Summary: Endometriosis is a chronic disorder that affects many women globally. Histone deacetylases (HDACs) play a role in gene transcription by regulating chromatin relaxation. This comprehensive review examines the impact of histone modifications and therapeutic targeting, specifically focusing on HDACs and their inhibitors in endometriosis. The five most studied HDAC enzymes, HDAC1, HDAC2, HDAC3, Sirtuin 1, and Sirtuin 3, have been found to influence the pathophysiology of endometriosis. Both established and novel HDACIs show promise as effective anti-endometriotic drugs. Overall, histone modifications and therapeutic targeting have a significant impact on endometriosis.
Review
Pharmacology & Pharmacy
Jeffrey B. Arterburn, Eric R. Prossnitz
Summary: The actions of estrogens and related estrogenic molecules are complex and multifaceted in both sexes. These molecules target pathways that produce and respond to estrogens, and multiple receptors are involved in the responses. In particular, the G protein-coupled estrogen receptor (GPER) plays important roles in physiological responses to estrogenic compounds and has therapeutic implications for various diseases.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
(2023)
Article
Environmental Sciences
Ignacio Babiloni-Chust, Reinaldo S. dos Santos, Regla M. Medina-Gali, Atenea A. Perez-Serna, Jose-Antonio Encinar, Juan Martinez-Pinna, Jan-Ake Gustafsson, Laura Marroqui, Angel Nadal
Summary: 17 beta-estradiol protects pancreatic beta-cells from apoptosis via estrogen receptors ER alpha, ER beta, and GPER. Conversely, the endocrine disruptor bisphenol-A (BPA) increases basal apoptosis in the same cell type through the same estrogen receptors. The molecular events that trigger these opposite actions have not been identified yet.
ENVIRONMENT INTERNATIONAL
(2022)
Article
Medicine, Research & Experimental
Carlotta Boscaro, Giovanni Eugenio Ramaschi, Lucia Trevisi, Andrea Cignarella, Chiara Bolego
Summary: miR-206 can interfere with GPER-mediated signaling and cell motility, and has the potential to act as pathway-selective antagonists in estrogen-dependent EOC.
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
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
Biochemistry & Molecular Biology
Fujie Xu, Jipeng Ma, Xiaowu Wang, Xiaoya Wang, Weiyi Fang, Jingwei Sun, Zilin Li, Jincheng Liu
Summary: This article summarizes the function, tissue localization, ligands, and signaling pathways of GPER in different physiological and diseased conditions. It emphasizes the role of GPER in vascular pathology and physiology and presents evidence of GPER as a promising therapeutic target in hypertension, pulmonary hypertension, and atherosclerosis.
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
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
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)
Review
Pharmacology & Pharmacy
Hae Jin Kee, Inkyeom Kim, Myung Ho Jeong
Summary: This article provides an overview of the pathogenesis of hypertension, current anti-hypertensive drugs, and the need for novel drugs. It focuses on the role and regulatory mechanisms of HDACs in hypertension and discusses the progress in developing HDAC inhibitors as potential therapeutic targets.
BIOCHEMICAL PHARMACOLOGY
(2022)
Editorial Material
Oncology
Anja Irmisch, Ximena Bonilla, Stephane Chevrier, Kjong-Van Lehmann, Franziska Singer, Nora C. Toussaint, Cinzia Esposito, Julien Mena, Emanuele S. Milani, Ruben Casanova, Daniel J. Stekhoven, Rebekka Wegmann, Francis Jacob, Bettina Sobottka, Sandra Goetze, Jack Kuipers, Jacobo Sarabia del Castillo, Michael Prummer, Mustafa A. Tuncel, Ulrike Menzel, Andrea Jacobs, Stefanie Engler, Sujana Sivapatham, Anja L. Frei, Gabriele Gut, Joanna Ficek, Nicola Miglino, Rudolf Aebersold, Marina Bacac, Niko Beerenwinkel, Christian Beisel, Bernd Bodenmiller, Reinhard Dummer, Viola Heinzelmann-Schwarz, Viktor H. Koelzer, Markus G. Manz, Holger Moch, Lucas Pelkmans, Berend Snijder, Alexandre P. A. Theocharides, Markus Tolnay, Andreas Wicki, Bernd Wollscheid, Gunnar Ratsch, Mitchell P. Levesquel
Summary: The Tumor Profiler Study combines a prospective diagnostic approach with an exploratory strategy to assess the relevance of in-depth tumor profiling in supporting clinical decision-making and improving the biological understanding of the disease.
Review
Oncology
Jose Alejandro Perez-Fidalgo, Belen Ortega, Soraya Simon, Eleftherios Pierre Samartzis, Stergios Boussios
ANNALS OF TRANSLATIONAL MEDICINE
(2020)
Review
Oncology
Stergios Boussios, Elie Rassy, Eleftherios Samartzis, Michele Moschetta, Matin Sheriff, Jose Alejandro Perez-Fidalgo, Nicholas Pavlidis
Summary: Melanoma of unknown primary site (MUP) accounts for 3-4% of all melanomas and presents mostly in lymph nodes, subcutaneous sites, and visceral organs. MUP and stage-matched melanoma of known primary site (MKP) share similar prognostic factors, but treatment outcomes vary.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2021)
Article
Acoustics
Janna Pape, Anahita Bajka, Deivis Strutas, Tilo Burkhardt, Patrick Imesch, Daniel Fink, Eleftherios Pierre Samartzis, Michael Bajka
ULTRASCHALL IN DER MEDIZIN
(2023)
Review
Oncology
Stergios Boussios, Matin Sheriff, Elie Rassy, Michele Moschetta, Eleftherios P. Samartzis, Rachel Hallit, Agne Sadauskaite, Konstantinos H. Katsanos, Dimitrios K. Christodoulou, Nicholas Pavlidis
Summary: Immunotherapies hold great potential in cancer treatment, but severe adverse events limit their usage. Checkpoint inhibitors have shown promising clinical activity in hard to treat solid malignancies, but caution must be taken regarding potential risks and treatment strategies.
ANNALS OF TRANSLATIONAL MEDICINE
(2021)
Article
Oncology
Ilaria Colombo, Sofia Genta, Federica Martorana, Monia Guidi, Milo Frattini, Eleftherios Pierre Samartzis, Simone Brandt, Sheila Gaggetta, Laura Moser, Mariarosa Pascale, Tatiana Terrot, Cristiana Sessa, Anastasios Stathis
Summary: This phase I study evaluated the safety, tolerability, pharmacokinetics, and preliminary activity of the PI3K/mTORC1/2 dual inhibitor gedatolisib combined with carboplatin and paclitaxel. The recommended phase II dose is gedatolisib 110 mg on days 1, 8, 15, and 22 alongside carboplatin and paclitaxel. The combination treatment showed tolerable profile and promising efficacy, particularly in clear cell ovarian cancer.
CLINICAL CANCER RESEARCH
(2021)
Meeting Abstract
Oncology
Hannah Woopen, Maren Keller, Ioana Braicu, Dario Zocholl, Joanna Baum, Petra Krabisch, Tamara Boxler, Pauline Wimberger, Catarina Madronal, Marta Gil-Martin, Vesna Bjelic-Radisic, Sinisha Trpchevski, Eleftherios Pierre Samartzis, Viola A. Heinzelmann-Schwarz, Patriciu Achimas-Cadariu, Paul Kubelac, Mehmet Ali Vardar, Marcin Andrzej Jedryka, Ignace Vergote, Jalid Sehouli
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Review
Immunology
Dimitrios Rafail Kalaitzopoulos, Ioannis G. Lempesis, Nicolas Samartzis, Georgios Kolovos, Ioannis Dedes, Angelos Daniilidis, Konstantinos Nirgianakis, Brigitte Leeners, Dimitrios G. Goulis, Eleftherios Pierre Samartzis
Summary: The study found that leptin concentrations were higher in peritoneal fluid and follicular fluid of women with endometriosis, but not significantly different in serum and plasma. This suggests a potential role of leptin in the pathophysiology of endometriosis.
JOURNAL OF REPRODUCTIVE IMMUNOLOGY
(2021)
Review
Public, Environmental & Occupational Health
Dimitrios Rafail Kalaitzopoulos, Nicolas Samartzis, Georgios N. Kolovos, Evangelia Mareti, Eleftherios Pierre Samartzis, Markus Eberhard, Kostantinos Dinas, Angelos Daniilidis
Summary: Various national and international guidelines recommend combined oral contraceptive pills and progestogens as therapies for endometriosis-associated pain. There is no clear consensus on surgical treatment for infertility. Discrepancies are also found in the recommendation of second- and third-line treatments.
Article
Oncology
Andre Fedier, Nadia Maggi, Alessandra Tozzi, Muriel Disler, Ricardo Coelho, Francis Jacob, Viola Heinzelmann-Schwarz
Summary: This study investigated the acquired resistance of ovarian cancer cells to olaparib and its cross-resistance to other chemotherapeutic drugs. The results showed that escalating concentrations of olaparib did not produce acquired resistance or cross-resistance to other drugs. The sensitivity of ovarian cancer cells to olaparib was correlated with their sensitivity to niraparib. Additionally, PARPi-sensitive cells also exhibited cross-sensitivity to non-platinum compounds and drugs not directly interacting with the DNA.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2022)
Article
Cell Biology
Cecile Cumin, Yen-Lin Huang, Charlotte Rossdam, Felix Ruoff, Susana Posada Cespedes, Ching-Yeu Liang, Flavio C. Lombardo, Ricardo Coelho, Natalie Rimmer, Martina Konantz, Monica Nunez Lopez, Shahidul Alam, Alexander Schmidt, Diego Calabrese, Andre Fedier, Tatjana Vlajnic, Mark von Itzstein, Markus Templin, Falk F. R. Buettner, Arun Everest-Dass, Viola Heinzelmann-Schwarz, Francis Jacob
Summary: The molecular repertoire promoting cancer cell plasticity remains partly unknown, but this study proposes that glyco-sphingolipids, specifically globo and ganglio series, play a role in promoting the transition between epithelial and mesenchymal cells. The study found elevated levels of globosides in tumor compartments compared to the ganglioside-rich stroma. It also discovered that the ganglioside-synthesizing enzyme ST8SIA1 was consistently elevated in mesenchymal-like samples, indicating a poor outcome.
Article
Biochemical Research Methods
Anne Bertolini, Michael Prummer, Mustafa Anil Tuncel, Ulrike Menzel, Maria Lourdes Rosano-Gonzalez, Jack Kuipers, Daniel Johannes Stekhoven, Niko Beerenwinkel, Franziska Singer
Summary: Single-cell RNA sequencing (scRNA-seq) is a powerful technique for understanding tissue composition and disease mechanisms at the single-cell level. However, analyzing and interpreting the large amounts of data generated by scRNA-seq is challenging. In this study, we developed a workflow called scAmpi (Single Cell Analysis mRNA pipeline) that processes and analyzes scRNA-seq data from raw sequencing to provide clinically relevant information. The workflow removes low quality cells, identifies cell types, and visualizes gene expression and functional pathways in single cells. Additionally, scAmpi can link gene expression to potential drug candidates for disease treatment.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Cell Biology
Ricardo Coelho, Alessandra Tozzi, Muriel Disler, Flavio Lombardo, Andre Fedier, Monica Nunez Lopez, Florian Freuler, Francis Jacob, Viola Heinzelmann-Schwarz
Summary: PARP inhibitors have shown outstanding benefits in the treatment of epithelial ovarian cancer, especially in patients with BRCA1/2 mutations or defects in the homologous recombination repair system. This study identified ATM, MUS81, NBN, BRCA2, and RAD51B as predictive markers for olaparib response and highlighted CDK12 as a potential therapeutic target in EOC.
CELL DEATH & DISEASE
(2022)
Article
Nanoscience & Nanotechnology
Fabienne D. Schwab, Manuel C. Scheidmann, Lauren L. Ozimski, Andre Kling, Lucas Armbrecht, Till Ryser, Ilona Krol, Karin Strittmatter, Bich Doan Nguyen-Straeuli, Francis Jacob, Andre Fedier, Viola Heinzelmann-Schwarz, Andreas Wicki, Petra S. Dittrich, Nicola Aceto
Summary: In this study, we introduce a novel microfluidic device called MyCTC chip, which enables the isolation, culture, and drug susceptibility testing of cancer cells from liquid biopsies. The chip uses a label-free, antigen-agnostic enrichment method to capture cancer cells, followed by cultivation and drug screening. We demonstrate the chip's effectiveness in spike-in experiments with breast circulating tumor cells, as well as in processing blood from breast cancer patients and ascites fluid from patients with ovarian, tubal, and endometrial cancer. The MyCTC chip has the potential to identify personalized drug response patterns in patients with advanced metastatic disease and limited treatment options.
MICROSYSTEMS & NANOENGINEERING
(2022)
Article
Medicine, Research & Experimental
Bettina Sobottka, Marta Nowak, Anja Laura Frei, Martina Haberecker, Samuel Merki, Mitchell P. Levesque, Reinhard Dummer, Holger Moch, Viktor Hendrik Koelzer
Summary: CD8+ tumor-infiltrating T cells play a crucial role in predicting responses to immune checkpoint inhibitors in immune-oncology. A computational diagnostic algorithm was established to quantitatively measure the spatial densities of these cells in tumor compartments, leading to the successful classification into immune diagnostic categories. This approach allows for efficient immune phenotyping of metastatic lesions, even in the absence of material from the invasive margin, providing valuable insights for immunotherapy strategies in metastatic melanoma.
LABORATORY INVESTIGATION
(2021)