Article
Dentistry, Oral Surgery & Medicine
J. Nguyen, P. S. Saffari, A. S. Pollack, S. Vennam, X. Gong, R. B. West, J. R. Pollack
Summary: In this study, six new cell lines of ameloblastoma were established and their genomic characteristics were analyzed. The driver mutations in FGFR2, KRAS, NRAS, BRAF, PIK3CA, and SMO were identified. The new cell lines were used to investigate the oncogene dependency and drug sensitivity of ameloblastoma. It was found that ameloblastoma cells with KRAS or NRAS mutation were highly sensitive to MEK inhibition, promoting ameloblast differentiation. Additionally, AB cells with activating SMO-L412F mutation were insensitive to vismodegib but significantly reduced tumor cell viability when treated with a small-molecule SMO inhibitor, BMS-833923. This novel cell line resource enables preclinical studies and can accelerate the translation of new molecularly targeted therapies for the management of ameloblastoma and related odontogenic neoplasms.
JOURNAL OF DENTAL RESEARCH
(2022)
Review
Chemistry, Multidisciplinary
Min Huang, Mei-yu Geng, Jian Ding
Summary: Anticancer drug discovery has made unprecedented progress in recent decades, contributing to innovative treatment options for patients and the implementation of personalized medicine. This article pays tribute to cancer research at Shanghai Institute of Materia Medica, providing an overview of the conceptual revolution in anticancer therapy and summarizing recent progress in molecularly targeted therapeutics and exploration of new strategies in personalized medicine.
ACTA PHARMACOLOGICA SINICA
(2022)
Review
Cell Biology
Hong Dai, Razack Abdullah, Xiaoqiu Wu, Fangfei Li, Yuan Ma, Aiping Lu, Ge Zhang
Summary: Pancreatic cancer is a lethal cancer with limited effectiveness of current chemotherapy. Nucleic acid-based targeting therapies have shown promising progress in the treatment of pancreatic cancer, offering potential as a future treatment direction.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Chemistry, Medicinal
Wei Wang, Shipeng He, Guoqiang Dong, Chunquan Sheng
Summary: Targeted protein degradation (TPD) using proteolysis-targeting chimera (PROTAC) is a novel therapeutic modality in drug discovery, limited to protein targets with ligandable sites. The development of nucleic-acid-based modalities has expanded the scope of TPD, allowing for the degradation of nucleic acid targets. Ribonuclease-targeting chimera (RIBOTAC), a new type of chimeric RNA degrader, shows promising features in drug discovery.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Lisa Belfiore, Behnaz Aghaei, Andrew M. K. Law, Jeremy C. Dobrowolski, Lyndon J. Raftery, Angie D. Tjandra, Christine Yee, Alberto Piloni, Alexander Volkerling, Cameron J. Ferris, Martin Engel
Summary: 3D cell models are considered more accurate in predicting the efficacy of drug responses and are seen as more physiologically representative tools for in vitro modeling of in vivo tissues. In the future, 3D cell models will continue to play an important role in drug discovery applications.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Xintian Shao, Caicai Meng, Wenjing Song, Tao Zhang, Qixin Chen
Summary: Organelles play crucial roles in biological functions, and disorders in organelles or their interactions are associated with diseases. Cell imaging has become an essential tool for drug delivery, drug discovery, and pharmacological research. Advanced imaging techniques provide researchers with valuable information on organelle ultrastructure, protein interactions, and gene transcription activities, enabling the design and delivery of precision-targeted drugs. This review focuses on organelle-targeted drugs based on imaging technologies and the development of fluorescent molecules for medicinal purposes, and provides comprehensive analysis of subcellular-level elements of drug development.
ADVANCED DRUG DELIVERY REVIEWS
(2023)
Article
Engineering, Biomedical
Yixuan Lin, Yiqi Yang, Kai Yuan, Shengbing Yang, Shuhong Zhang, Hanjun Li, Tingting Tang
Summary: This study reports a three-dimensional bioprinted osteosarcoma model that incorporates osteosarcoma cells and a mimicked extracellular matrix. Compared to traditional models, this model shows significant differences in cell cycle, metabolism, and other cellular pathways, and is more sensitive to therapies targeting the autophagy pathway.
BIOACTIVE MATERIALS
(2022)
Article
Engineering, Biomedical
Farbod Amirghasemi, Emmanuela Adjei-Sowah, Barbara A. Pockaj, Mehdi Nikkhah
Summary: The burden of cancer is increasing, leading to a need for inexpensive preclinical platforms to accelerate drug discovery, particularly in female patients. Current methods often use costly animal models which do not accurately predict drug responses. 3D microscale platforms show potential for faster drug screening and personalized treatment approaches.
ANNALS OF BIOMEDICAL ENGINEERING
(2021)
Article
Biochemistry & Molecular Biology
Favio A. Krapacher, Diana Fernandez-Suarez, Annika Andersson, Alvaro Carrier-Ruiz, Carlos F. Ibanez
Summary: This study reports the synergistic effect of dopamine D1 receptor signaling and activin/ALK4/Smad3 pathway in enhancing the generation of Delta FosB mRNA and its nuclear translocation in medium spiny neurons. The RNA-binding protein PCBP1 regulates this process and its interaction with Smad3 plays a crucial role. Additionally, ALK4 is required in adult mice for behavioral sensitization to cocaine.
Review
Biochemistry & Molecular Biology
Guadalupe Tonantzin de Dios-Figueroa, Janette del Rocio Aguilera-Marquez, Tanya A. Camacho-Villegas, Pavel H. Lugo-Fabres
Summary: Three-dimensional cell culture models play a crucial role in virus research, helping to provide a rapid response to new viruses, establish reliable evaluations of pathophysiology, and contribute to the assessment of therapeutic drugs in pandemic situations.
Review
Pharmacology & Pharmacy
Maria Helena Macedo, Ana Baiao, Soraia Pinto, Andreia S. Barros, Helena Almeida, Andreia Almeida, Jose das Neves, Bruno Sarmento
Summary: 3D cell-based models are gaining attention for better replicating in vivo environments. Mucus can play a crucial role in drug absorption but is often overlooked, making it important to study mucus models.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Article
Chemistry, Analytical
Ming Zhang, Shengui He, Xiuyan Han, Jingnan Cui, Honglei Wang, Xiaokui Huo, Fei Yan, Lei Feng, Chao Wang, Xiaochi Ma
Summary: A near-infrared fluorescent probe was developed for the rapid and real-time monitoring of endogenous MtMET-AP1 activity in M. tuberculosis. Several potential inhibitors were discovered through high-throughput screening, which could inhibit the growth of M. tuberculosis and have low toxicities on intestinal bacteria strains and human cells.
ANALYTICAL CHEMISTRY
(2023)
Review
Agriculture, Dairy & Animal Science
Jacob van der Ende, Henk D. F. H. Schallig
Summary: This review examines the different animal models used in drug development for leishmaniasis and highlights the lack of thorough description of experimental procedures, ethical review, and consideration of alternative methods to animal studies. The study proposes a more standardized animal model and emphasizes the importance of reporting and ethical review. Overall, animal experiments for leishmaniasis drug development are poorly designed, lacking essential information and consideration of animal welfare.
Review
Pharmacology & Pharmacy
Chloe Whitehouse, Nicola Corbett, Janet Brownlees
Summary: The lack of robust in vitro models to represent complex cellular pathologies underlying neurodegeneration has created a translational gap and bottleneck in new therapeutics development. Recent progress in the development of 3D models of neurodegeneration is reviewed, discussing design benefits, validation techniques, and opportunities for implementation in drug discovery and development, as well as the need for standards.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Article
Biochemical Research Methods
Yu-Liang Wang, Fan Wang, Xing-Xing Shi, Chen-Yang Jia, Feng-Xu Wu, Ge-Fei Hao, Guang-Fu Yang
Summary: Effective drug discovery is crucial for treating diseases, but is hindered by high costs and long cycles. The introduction of the QSAR method has enhanced efficiency in drug discovery, while the Cloud 3D-QSAR server provides a comprehensive solution by integrating various functions to facilitate the development of good QSAR models.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Cell Biology
Karin Schelch, Lisa Vogel, Anja Schneller, Jelena Brankovic, Thomas Mohr, Rupert L. Mayer, Astrid Slany, Christopher Gerner, Michael Grusch
Summary: TGF beta and EGF can partly compensate for each other for stimulation of cell migration, but abrogation of TGF beta signaling may be more suitable to suppress cell invasion.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Dina Baier, Torsten Mueller, Thomas Mohr, Ursula Windberger
Summary: The study investigated the apparent Young's modulus and adhesion properties of different animal red blood cells, finding that the Young's modulus decreased with increasing temperature in all cell types, while adhesion increased with temperature in mammalian cells and correlated with reported membrane sialic acid concentrations.
Article
Oncology
Hans Peter Weitzenboeck, Anna Gschwendtner, Christoph Wiesner, Maren Depke, Frank Schmidt, Franz Trautinger, Markus Hengstschlaeger, Harald Hundsberger, Mario Mikula
Summary: The mechanisms of how NRF2 contributes to melanoma progression are not fully understood, but inhibition of NRF2 has been found to induce an EMT phenotype and increase cell survival after apoptosis induction. Cells lacking NRF2 show increased cell viability after specific treatment, and CD44 expression is crucial for survival upon a certain treatment.
Article
Pharmacology & Pharmacy
Dina Baier, Beatrix Schoenhacker-Alte, Mate Rusz, Christine Pirker, Thomas Mohr, Theresa Mendrina, Dominik Kirchhofer, Samuel M. Meier-Menches, Katharina Hohenwallner, Martin Schaier, Evelyn Rampler, Gunda Koellensperger, Petra Heffeter, Bernhard Keppler, Walter Berger
Summary: Cellular energy metabolism is reprogrammed in cancer cells, leading to resistance against ruthenium-based chemotherapy drug BOLD-100 through enhanced glycolytic activity, increased lysosomal compartment, and defective downstream autophagy execution. Combining 2-deoxy-D-glucose with BOLD-100 reverses this resistance by inducing synergistic cell death and disrupting autophagy, suggesting glycolysis as a potential target to enhance BOLD-100 anticancer activity.
Article
Urology & Nephrology
Iris E. Ertl, Ursula Lemberger, Dafina Ilijazi, Melanie R. Hassler, Andreas Bruchbacher, Robert Brettner, Hannah Kronabitter, Michael Gutmann, Petra Vician, Gerhard Zeitler, Anna Koren, Charles-Hugues Lardeau, Thomas Mohr, Andrea Haitel, Eva Comperat, Andre Oszwald, Gabriel Wasinger, Thomas Clozel, Olivier Elemento, Stefan Kubicek, Walter Berger, Shahrokh F. Shariat
Summary: The study aimed to establish a model system for drug identification and repurposing to identify novel therapies for the treatment of bladder cancer. The results showed that clofarabine exhibited inhibitory effects on bladder cancer cells, suggesting potential clinical relevance.
Article
Anesthesiology
Nicolai Haase, Ronni Plovsing, Steffen Christensen, Lone M. Poulsen, Anne C. Brochner, Bodil S. Rasmussen, Marie Helleberg, Jens U. S. Jensen, Lars P. K. Andersen, Hanna Siegel, Michael Ibsen, Vibeke L. Jorgensen, Robert Winding, Susanne Iversen, Henrik P. Pedersen, Jacob Madsen, Christoffer Solling, Ricardo S. Garcia, Jens Michelsen, Thomas Mohr, George Michagin, Ulrick S. Espelund, Helle Bundgaard, Lynge Kirkegaard, Margit Smitt, David L. Buck, Niels-Erik Ribergaard, Helle S. Pedersen, Birgitte V. Christensen, Lone P. Nielsen, Esben Clapp, Trine B. Jonassen, Sarah Weihe, Kirstine la Cour, Frederik M. Nielsen, Emilie K. Madsen, Trine N. Haberlandt, Nick Meier, Anders Perner
Summary: After the first wave of COVID-19 in Denmark, a lower proportion of hospitalized patients with COVID-19 were admitted to ICU. Among ICU patients, use of organ support was lower and length of stay was reduced, but mortality rates remained relatively high.
ACTA ANAESTHESIOLOGICA SCANDINAVICA
(2022)
Article
Anesthesiology
Sarah Weihe, Camilla B. Mortensen, Nicolai Haase, Lars P. K. Andersen, Thomas Mohr, Hanna Siegel, Michael Ibsen, Vibeke R. L. Jorgensen, David L. Buck, Helle B. S. Pedersen, Henrik P. Pedersen, Susanne Iversen, Niels Ribergaard, Bodil S. Rasmussen, Robert Winding, Ulrick S. Espelund, Helle Bundgaard, Christoffer G. Solling, Steffen Christensen, Ricardo S. Garcia, Anne C. Brochner, Jens Michelsen, George Michagin, Lynge Kirkegaard, Anders Perner, Ole Mathiesen, Lone M. Poulsen
Summary: ICU admission due to COVID-19 may result in long-term cognitive and physical impairment, including cognitive and functional impairment and fatigue.
ACTA ANAESTHESIOLOGICA SCANDINAVICA
(2022)
Article
Anesthesiology
Lene Russell, Sarah Weihe, Emilie Kabel Madsen, Christine Lodberg Hvas, Jens Wolfgang Leistner, Jens Michelsen, Anne Craveiro Brochner, Anders Bastiansen, Frederik Molgaard Nielsen, Nick Meier, Anne Sofie Andreasen, Niels-Erik Ribergaard, Bodil Steen Rasmussen, Christoffer Grant Solling, David Levarett Buck, Helle Bundgaard, Helle Scharling Pedersen, Iben Strom Darfelt, Lone Musaeus Poulsen, Michael Ibsen, Ronni R. Plovsing, Sigurdur T. Sigurdsson, Susanne Iversen, Thomas Hildebrandt, Thomas Mohr, Ulrick Skipper Espelund, Vibeke Jorgensen, Nicolai Haase, Anders Perner
Summary: This study describes the occurrence of thromboembolic and bleeding events in ICU patients with COVID-19 in Denmark. Mechanical ventilation and increased D-dimer were associated with thrombosis, while mechanical ventilation, low platelet count, and presence of haematological malignancy were associated with bleeding. Thromboembolic events were not associated with mortality, whereas bleeding events were.
ACTA ANAESTHESIOLOGICA SCANDINAVICA
(2023)
Article
Oncology
Stefan Moritsch, Bernadette Moedl, Irene Scharf, Lukas Janker, Daniela Zwolanek, Gerald Timelthaler, Emilio Casanova, Maria Sibilia, Thomas Mohr, Lukas Kenner, Dietmar Herndler-Brandstetter, Christopher Gerner, Mathias Mueller, Birgit Strobl, Robert Eferl
Summary: This study investigates the role of Janus kinase Tyk2 in solid tumors and suggests its tumor-suppressive functions in immune cells and epithelial cancer cells. It also reveals the different immune editing patterns and regulation of immune checkpoint genes in Tyk2-deficient tumors, highlighting the importance of Tyk2 in colorectal cancer progression and immune surveillance.
Article
Cell Biology
Iris E. Ertl, Robert Brettner, Hannah Kronabitter, Thomas Mohr, Sophia Derdak, Markus Jeitler, Martin Bilban, Nathalie Garstka, Shahrokh F. Shariat
Summary: Previous studies have shown that chromatin-remodelling SWI/SNF complexes are involved in prostate cancer development, with both tumor suppressor and oncogenic activities. Our study on SMARCD family members revealed their role in regulating hormone-dependent genes and their involvement in castration-resistance. We also found that SMARCD proteins play a role in cellular processes like cellular morphology and cytokinesis. Overall, our findings highlight the important and paradoxical role of SMARCD proteins in prostate carcinogenesis.
Article
Cell Biology
Katrin Colleselli, Marie Ebeyer-Masotta, Benjamin Neuditschko, Anna Stierschneider, Christopher Pollhammer, Mia Potocnjak, Harald Hundsberger, Franz Herzog, Christoph Wiesner
Summary: The interaction between monocytes and endothelial cells plays a key role in inflammation, including chemoattraction, adhesion, and transendothelial migration. Toll-like receptor 2 (TLR2) is critical for sensing pathogens and initiating an immune response. In this study, we found that TLR2 promotes monocyte adhesion to endothelial cells, disrupts the endothelial barrier, and affects actin polymerization. Our findings also revealed the association of TLR2 with specific integrins and identified novel proteins affected by TLR2.
Article
Cell Biology
Anna Stierschneider, Benjamin Neuditschko, Katrin Colleselli, Harald Hundsberger, Franz Herzog, Christoph Wiesner
Summary: Optogenetic cell lines based on light-oxygen-voltage-sensing (LOV) domains (opto-TLR4-LOV LECs and opto-TLR4-LOV HUVECs) allow fast, precise, and reversible activation of TLR4 signaling pathways, providing a better simulation of inflammatory responses than LPS. Light-induced TLR4 activation can promote the expression of inflammatory proteins and significantly impact cell function and cell migration. This technology enables specific studies of TLR4.
Review
Biochemistry & Molecular Biology
Katrin Colleselli, Anna Stierschneider, Christoph Wiesner
Summary: While inflammation is crucial for human survival in response to infection and injury, prolonged inflammation can be fatal. Toll-like receptors (TLRs) are important in initiating inflammatory processes, and TLR2, in particular, has been extensively studied and known to recognize a wide range of pathogens through heterodimerization. However, many unanswered questions still remain about the mechanisms of TLR2 in both health and disease. This review provides an up-to-date overview of TLR2, including its homo- and heterodimers, and discusses its pro- and anti-inflammatory properties and recent findings in infectious and neurodegenerative diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Alexander Ries, Astrid Slany, Christine Pirker, Johanna C. C. Mader, Doris Mejri, Thomas Mohr, Karin Schelch, Daniela Flehberger, Nadine Maach, Muhammad Hashim, Mir Alireza Hoda, Balazs Dome, Georg Krupitza, Walter Berger, Christopher Gerner, Klaus Holzmann, Michael Grusch
Summary: In this study, novel hTERT-transduced mesothelial cell and Meso-CAF models were generated and characterized, and their impact on PM cell growth was investigated.