Article
Biochemistry & Molecular Biology
Angelica Ferro, Dafni Graikioti, Emre Gezer, Constantinos M. M. Athanassopoulos, Muriel Cuendet
Summary: Although proteasome inhibitors have been used as the main treatment for multiple myeloma, patients often relapse and become resistant to drugs. Combining proteasome and histone deacetylase inhibitors has been found to be more effective, as it enhances anti-myeloma activity and improves patient outcomes. Hybrid molecules that combine the pharmacophores of entinostat and bortezomib have been synthesized and shown to have strong antiproliferative activity in multiple myeloma cells, including those resistant to bortezomib, as well as inhibiting histone deacetylase and proteasome activity.
Review
Chemistry, Medicinal
Angelica Ferro, Evangelia Pantazaka, Constantinos M. M. Athanassopoulos, Muriel Cuendet
Summary: Despite being an incurable disease, multiple myeloma (MM) can benefit from combined and targeted therapies, which have shown a decrease in drug resistance and an improvement in overall survival. Histone deacetylases (HDACs) play a crucial role in cancer treatment, including MM, and combining HDAC inhibitors with other regimens is of great interest. Recent advancements include the development of dual-inhibitor entities, which may reduce therapeutic doses and the risk of drug resistance.
MEDICINAL RESEARCH REVIEWS
(2023)
Article
Multidisciplinary Sciences
Mengmeng Dong, Jinna Zhang, Xiaoyan Han, Jingsong He, Gaofeng Zheng, Zhen Cai
Summary: This study retrospectively analyzed clinical data of 155 MM patients and found that baseline PN was age-related, leading to more severe BiPN during bortezomib induction therapy and worse PN outcome after induction therapy. MM patients with baseline PN also had worse PFS and OS.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Zhen Hua, Rongfang Wei, Mengjie Guo, Zigen Lin, Xichao Yu, Xinying Li, Chunyan Gu, Ye Yang
Summary: This study highlights the role of the YTHDF2/STAT5A/MAP2K2/p-ERK axis in the proliferation of multiple myeloma (MM), and targeting YTHDF2 may be a promising therapeutic strategy.
Review
Biochemistry & Molecular Biology
Francesca Alessandra Ambrosio, Giosue Costa, Maria Eugenia Gallo Cantafio, Roberta Torcasio, Francesco Trapasso, Stefano Alcaro, Giuseppe Viglietto, Nicola Amodio
Summary: Multiple myeloma (MM) is an aggressive and incurable disease, characterized by cycles of treatment, remission, and relapse. Proteasome inhibitors (PIs), such as Bortezomib, carfilzomib, and ixazomib, have become the gold standard for MM treatment, improving survival outcomes. Recent research has focused on natural compounds that can inhibit the proteasome, potentially leading to new anti-MM drugs.
Article
Pharmacology & Pharmacy
Gaojie Xu, Sheng Huang, Jian Peng, Xiaofang Gao, Minhui Li, Sisi Yu, Zuofeng Liu, Pengfan Qie, Yu Wang, Siqi Yu, Siyuan Liu, Hu Wen, Lijuan Su, Ping Li, Bin Guang, Renhan Dong, Jin Liu, Tai Yang
Summary: The study demonstrates the synergistic effect of lipid regulators with proteasome inhibitors in killing multiple myeloma cells. The novel derivative FCE shows significant synergy with ixazomib in vitro and in vivo. The abnormal lipid accumulation in multiple myeloma cells induced by proteasome inhibitors may be attributed to elevated SREBP1/2 expression induced by ATF4.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Liang Ren, Bei Xu, Jiadai Xu, Jing Li, Jifeng Jiang, Yuhong Ren, Peng Liu
Summary: A UBBRS risk score model was established by selecting UPPGs associated with overall survival of MM patients, which can predict the survival of MM patients and identify patients who would benefit more from PIs treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Rohitash Yadav, Uttam Kumar Nath, Ismail Celik, Shailendra Handu, Neeraj Jain, Puneet Dhamija
Summary: This study identifies risedronate and zoledronate as potential therapeutic molecules for targeting the PSM beta 5 gene in multiple myeloma. Molecular docking and simulation analysis demonstrate their high binding affinities and stable interactions with PSM beta 5. Furthermore, zoledronate shows enhanced anti-proliferative activity when combined with bortezomib in MM cell lines.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Aleksandra Mitric, Immacolata Castellano
Summary: GGT is an enzyme located on the outer membrane of the cells and plays a key role in regulating glutathione metabolism. It is upregulated in inflammatory conditions and various human tumors, and is involved in physiological disorders related to oxidative stress. This review focuses on the structure and function of human GGT, and discusses its potential as a target for drugs to alleviate oxidative stress-related diseases. The development of new GGT inhibitors and their potential clinical use is also discussed. GGT is considered a potential moonlighting protein due to its pleiotropic activities and evolved functions.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Review
Oncology
Philip Weir, David Donaldson, Mary Frances McMullin, Lisa Crawford
Summary: Multiple myeloma is a common blood cancer that affects plasma cells in bone marrow. Despite improvements in treatment options, drug resistance remains a challenge. This review discusses the metabolic changes in multiple myeloma and the development of resistance to proteasome inhibitors, and explores potential therapeutic interventions.
Article
Biochemistry & Molecular Biology
Maria J. Ferreira, Tony A. Rodrigues, Ana G. Pedrosa, Ana R. Silva, Beatriz G. Vilarinho, Tania Francisco, Jorge E. Azevedo
Summary: This article summarizes and compares data on the peroxisome-glutathione topic in several organisms. The results indicate that the repertoire of glutathione-utilizing enzymes in peroxisomes varies widely among different organisms. Furthermore, the data suggest that the kinetic connectivity between the cytosolic and peroxisomal pools of glutathione may also differ among organisms. However, regardless of the differences, it is evident that glutathione is a crucial component of the antioxidative system in peroxisomes across all organisms.
Article
Biochemistry & Molecular Biology
Kristell Le Gal, Edward E. Schmidt, Volkan Sayin
Summary: Cellular redox homeostasis is crucial for balancing the reducing and oxidizing reactions within cells, regulating various biological responses and events. Despite the challenges in studying these biochemical reactions, recent advancements in technology have rapidly expanded the redox field, enhancing our understanding of its significance in biology. This short review aims to provide an overview of redox regulation in cellular signaling, development, and disease, as well as introduce some recent discoveries in these areas.
Article
Biochemistry & Molecular Biology
Roberta Ceci, Guglielmo Duranti, Stefano Giuliani, Marianna Nicoletta Rossi, Ivan Dimauro, Stefania Sabatini, Paolo Mariottini, Manuela Cervelli
Summary: A naturally occurring polyamine called spermidine (Spd) has been found to restore compromised viability and redox status of muscle cells, and reduce cell death. This study suggests that Spd treatment can protect skeletal muscle cells by restoring redox balance, promoting wound recovery, and improving the ability to withstand oxidative damage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Tina Paradzik, Cecilia Bandini, Elisabetta Mereu, Maria Labrador, Elisa Taiana, Nicola Amodio, Antonino Neri, Roberto Piva
Summary: Recent investigations are exploring novel combination strategies that could overcome drug resistance and broaden the applicability of proteasome inhibitors (PIs) to other hematological malignancies and solid tumors.
Review
Oncology
Jonas Schwestermann, Andrej Besse, Christoph Driessen, Lenka Besse
Summary: This review article summarizes the molecular mechanisms of resistance to proteasome inhibitors in the context of the bone marrow microenvironment in patients with multiple myeloma. It also discusses the interaction between the tumor microenvironment and malignant plasma cells and its impact on metabolic changes.
FRONTIERS IN ONCOLOGY
(2022)
Letter
Rheumatology
Antonello Villa, Daniela Belloni, Barbara Vergani, Simone Cenci, Giulio Cavalli, Riccardo Biavasco, Monica Rodolfo, Maria Giulia Cangi, Claudio Doglioni, Lorenzo Dagna, Elisabetta Ferrero, Marina Ferrarini
ANNALS OF THE RHEUMATIC DISEASES
(2019)
Article
Multidisciplinary Sciences
Satoshi Watanabe, Yuta Amagai, Sara Sannino, Tiziana Tempio, Tiziana Anelli, Manami Harayama, Shoji Masui, Ilaria Sorrentino, Momo Yamada, Roberto Sitia, Kenji Inaba
NATURE COMMUNICATIONS
(2019)
Article
Hematology
Oronza A. Botrugno, Silvia Bianchessi, Desiree Zambroni, Michela Frenquelli, Daniela Belloni, Lucia Bongiovanni, Stefania Girlanda, Simona Di Terlizzi, Marina Ferrarini, Elisabetta Ferrero, Maurilio Ponzoni, Magda Marcatti, Giovanni Tonon
Article
Biochemistry & Molecular Biology
Stefano Bestetti, Mauro Galli, Ilaria Sorrentino, Paolo Pinton, Alessandro Rimessi, Roberto Sitia, Iria Medrano-Fernandez
Editorial Material
Microbiology
Jean Armengaud, Agnes Delaunay-Moisan, Jean-Yves Thuret, Eelco van Anken, Diego Acosta-Alvear, Tomas Aragon, Carolina Arias, Marc Blondel, Ineke Braakman, Jean-Francois Collet, Rene Courcol, Antoine Danchin, Jean-Francois Deleuze, Jean-Philippe Lavigne, Sophie Lucas, Thomas Michiels, Edward R. B. Moore, Jonathon Nixon-Abell, Ramon Rossello-Mora, Zheng-Li Shi, Antonio G. Siccardi, Roberto Sitia, Daniel Tillett, Kenneth N. Timmis, Michel B. Toledano, Peter van der Sluijs, Elisa Vicenzi
ENVIRONMENTAL MICROBIOLOGY
(2020)
Review
Biochemistry & Molecular Biology
Roberto Sitia, Anna Rubartelli
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Cell Biology
Daria Sicari, Aristotelis Chatziioannou, Theodoros Koutsandreas, Roberto Sitia, Eric Chevet
JOURNAL OF CELL BIOLOGY
(2020)
Letter
Medicine, General & Internal
Giulio Cavalli, Giacomo De Luca, Claudio Doglioni, Elisabetta Ferrero, Marina Ferrarini, Lorenzo Dagna
ANNALS OF INTERNAL MEDICINE
(2021)
Article
Cell Biology
Elisabetta Vergani, Matteo Dugo, Mara Cossa, Simona Frigerio, Lorenza Di Guardo, Gianfrancesco Gallino, Ilaria Mattavelli, Barbara Vergani, Luca Lalli, Elena Tamborini, Barbara Valeri, Chiara Gargiuli, Eriomina Shahaj, Marina Ferrarini, Elisabetta Ferrero, Macarena Gomez Lira, Veronica Huber, Michele Del Vecchio, Marialuisa Sensi, Biagio Eugenio Leone, Mario Santinami, Licia Rivoltini, Monica Rodolfo, Viviana Vallacchi
CELL COMMUNICATION AND SIGNALING
(2020)
Correction
Cell Biology
Daria Sicari, Aristotelis Chatziioannou, Theodoros Koutsandreas, Roberto Sitia, Eric Chevet
JOURNAL OF CELL BIOLOGY
(2020)
Article
Hematology
Raffaella Molteni, Riccardo Biavasco, Davide Stefanoni, Travis Nemkov, Jorge Dominguez-Andres, Rob J. Arts, Ivan Merelli, Davide Mazza, Samuel Zambrano, Maddalena Panigada, Eleonora Cantoni, Isak W. Tengesdal, Philippe Maksud, Francesco Piras, Daniela Cesana, Laura Cassina, Gianfranco Distefano, Alessia Loffreda, Daniela Gnani, Giacomo De Luca, Alessandro Tomelleri, Corrado Campochiaro, Leo A. B. Joosten, Charles A. Dinarello, Anna Kajaste-Rudnitski, Julien Haroche, Simone Cardaci, Simone Cenci, Lorenzo Dagna, Claudio Doglioni, Marina Ferrarini, Elisabetta Ferrero, Alessandra Boletta, Angelo D'Alessandro, Eugenio Montini, Mihai G. Netea, Giulio Cavalli
Summary: This study revealed the deleterious potential of inappropriate activation of trained immunity in the pathogenesis of human inflammatory myeloid neoplasms, and highlighted the opportunity for inhibition of trained immunity in conditions characterized by maladaptive myeloid-driven inflammation. Effective therapeutic strategies in patients with Erdheim-Chester disease combat the maladaptive trained immunity phenotype, and pharmacologic inhibition of immunometabolic changes underlying trained immunity effectively dampens cytokine production by myeloid cells.
Article
Biochemistry & Molecular Biology
Chiara Giannone, Maria Rita Chelazzi, Andrea Orsi, Tiziana Anelli, Tuan Nguyen, Johannes Buchner, Roberto Sitia
Summary: Antibodies of the IgM class are secreted as planar polymers, with the formation of non-native intra-subunit disulfide bonds playing a key role in the biogenesis of secretory IgM. This unusual assembly pathway is ensured by the engagement of protein disulfide isomerase ERp44, which promotes polymerization and formation of disulfide linkages. This allows secretory polymers to form without disrupting the function of membrane IgM.
Article
Biochemistry & Molecular Biology
Ilaria Sorrentino, Mauro Galli, Iria Medrano-Fernandez, Roberto Sitia
Summary: Some AQPs can transport H2O2 across membranes, allowing redox signals to proceed in and between cells. In this study, it is found that silencing Ero1 alpha leads to an increase in luminal H2O2 levels, but downregulation of AQP11 prevents this increase, indicating that H2O2 enters the ER from external sources. The downregulation of Ero1 alpha activates superoxide production by complex III, and AQP11 channels H2O2 from mitochondria to the ER. Additionally, the number of ER-mitochondria contact sites increases, irrespective of AQP11 expression.
Review
Immunology
Virginia Guzzeloni, Lorenzo Veschini, Federica Pedica, Elisabetta Ferrero, Marina Ferrarini
Summary: Therapeutic monoclonal antibodies have revolutionized clinical outcomes in oncology, but identifying the right patients for treatment remains a challenge. To address this, the development of 3D models that accurately reproduce tumor microenvironment interactions is urgently needed. These models have the potential to bridge the gap between traditional 2D cultures and animal models, contributing to personalized medicine.
Article
Biochemical Research Methods
Daniela Belloni, Marina Ferrarini, Elisabetta Ferrero, Virginia Guzzeloni, Federica Barbaglio, Paolo Ghia, Cristina Scielzo
Summary: This protocol describes the generation of 3D culture surrogates of chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) bone marrow microenvironments. It involves the use of culturing scaffolds populated with BM stromal cells and tumor cells in the RCCSTM bioreactor. This 3D culture system efficiently recapitulates tumor-stroma crosstalk and allows drug testing.