Article
Chemistry, Multidisciplinary
Matthew J. Mosquera, Sungwoong Kim, Rohan Bareja, Zhou Fang, Shuangyi Cai, Heng Pan, Muhammad Asad, Maria Laura Martin, Michael Sigouros, Florencia M. Rowdo, Sarah Ackermann, Jared Capuano, Jacob Bernheim, Cynthia Cheung, Ashley Doane, Nicholas Brady, Richa Singh, David S. Rickman, Varun Prabhu, Joshua E. Allen, Loredana Puca, Ahmet F. Coskun, Mark A. Rubin, Himisha Beltran, Juan Miguel Mosquera, Olivier Elemento, Ankur Singh
Summary: This study defined the role of ECM signals in the development of CRPC-NEPC and identified potential therapeutic targets for neuroendocrine prostate cancer. In animal models, strong anti-tumor responses were observed with the use of a DRD2 inhibitor, and a combination of epigenetic inhibitors and DRD2 treatment was shown to overcome therapeutic resistance in CRPC-NEPC under drug-resistant ECM conditions.
ADVANCED MATERIALS
(2022)
Article
Oncology
Pengfei Su, Lin Jiang, Yingjing Zhang, Tian Yu, Weiming Kang, Yuqin Liu, Jianchun Yu
Summary: This study found that tumor-associated macrophages (TAMs) play an important role in chemoresistance in gastric cancer. Gastric cancer cells induce polarization of TAMs, leading to increased resistance to chemotherapy. Additionally, the protein CXCL5 produced by TAMs promotes chemoresistance by activating the PI3K/AKT/mTOR pathway. These findings have important implications for the treatment strategies of gastric cancer patients.
CANCER CELL INTERNATIONAL
(2022)
Article
Biochemistry & Molecular Biology
Yifat Koren Carmi, Hazem Khamaisi, Rina Adawi, Eden Noyman, Jacob Gopas, Jamal Mahajna
Summary: Ovarian cancer is the second most common gynecological malignancy with poor survival rates. Chemoresistance, a major obstacle in treating ovarian cancer, is influenced by tumor microenvironment and soluble factors. FDA-approved JAK inhibitors can partially restore platinum sensitivity in ovarian cancer cells in the tumor microenvironment. Crizotinib, in combination with platinum, can block the promotion of platinum resistance by HGF and restore platinum sensitivity in ovarian cancer cells. Additionally, 2HE2 can restore platinum sensitivity in ovarian cancer cells exposed to the tumor microenvironment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Mitali Das, Sujay Subbayya Ithychanda, Edward F. Plow
Summary: Plasminogen and its receptors, including histone 2B (H2B), play important roles in the responses of various cell types. This study investigated the involvement of H2B in plasminogen-induced endothelial cell migration. The results showed that H2B is present on viable endothelial cells and its antibody blockade inhibited plasminogen-dependent migration. Furthermore, H2B was found to interact with PAR1 and PAR2, suggesting a mechanism for linking plasminogen to wound healing and angiogenesis.
Article
Cell Biology
Kiyoko Uehara, Akira Uehara
Summary: PARs, including PAR1, PAR2, PAR3, and PAR4, play crucial roles in splenic sinus endothelial cells, contributing to endothelial barrier protection and firm adhesion to ring fibers.
CELL AND TISSUE RESEARCH
(2021)
Article
Medicine, Research & Experimental
Hongquan Qin, Jiali Chen, Katia Bouchekioua-Bouzaghou, Ya-Ming Meng, Jordi Bach Griera, Xue Jiang, Xiangzhan Kong, Minghui Wang, Qiuping Xu, Ping-Pui Wong
Summary: The study found that MAGEA regulates tumor-stromal crosstalk in PDAC, with high expression correlating with poor chemotherapeutic response and prognosis in multiple cancers. The mechanism includes inhibition of gemcitabine-induced cancer cell apoptosis and activation of GDF15 secretion to enhance gemcitabine resistance. Targeting MAGEA-mediated paracrine regulation of chemoresistance by immunotherapy could be a promising strategy for pancreatic cancer treatment.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Xin Zhuo, Yue Wu, Xiujuan Fu, Xiaoyu Liang, Yuxin Xiang, Jianbin Li, Canquan Mao, Yuhong Jiang
Summary: Inflammatory diseases are increasing globally, and COVID-19 also exhibits hyperinflammatory responses. Protease-activated receptors (PARs) are popular drug targets involved in regulating inflammatory responses in multiple systems. PARs activation has both anti-inflammatory and pro-inflammatory effects depending on the context of inflammation. Recent findings suggest that PARs also participate in COVID-19-related inflammatory cytokine release.
Article
Pharmacology & Pharmacy
A. Barra, K. M. Freitas, D. G. Marconato, P. Faria-Pinto, M. T. P. Lopes, Andre Klein
Summary: The PAR4 plays a potential role in antiplatelet therapy and also mediates the inflammatory response triggered by LPS in macrophages, presenting a new approach in understanding innate immune mechanisms.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2021)
Article
Biophysics
Hui Peng, Jia-Hui Wang, Feng Guo, Fang-Fang Zhu, Zu-Jun Wen, Hai-Jun Zhong, De-Sheng Liang
Summary: In this study, a novel dual-targeting nanoparticle system for TAMs and tumor cells was developed for cancer chemotherapy. The system can be activated to promote tumor cells internalization and TAMs phagocytosis, leading to enhanced efficacy against tumor growth and TAMs depletion.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2021)
Article
Chemistry, Physical
Huamei He, Denghui Zhu, Aiqing Ma, Jian Ren, Ze Chen, Hui Ran, Zhaozhen Li, Ruiqing Qin, Ruijing Liang, Lanlan Liu, Lintao Cai
Summary: A promising strategy using photoresponsive cyanobacteria (Synechococcus 7942) is reported to remodel the solid tumor microenvironment (TME) and combat chemoresistance. The cyanobacteria is able to penetrate deep into the tumor and under laser irradiation, it generates oxygen and reactive oxidative species (ROS) to alleviate tumor hypoxia and increase drug sensitivity. This strategy achieves complete tumor ablation with no evident systemic toxicity in mice over a span of 90 days, providing a new insight to overcome chemotherapeutic resistance and eliminate tumors.
Article
Cardiac & Cardiovascular Systems
Christine Joseph, Eva Maria Berghausen, Arnica Behringer, Bernhard Rauch, Henrik Ten Freyhaus, Leoni Luisa Gnatzy-Feik, Maximilian Krause, Dickson W. L. Wong, Peter Boor, Stephan Baldus, Marius Vantler, Stephan Rosenkranz
Summary: This study characterizes the effects of thrombin and Factor Xa on PASMCs and their involvement in pulmonary vascular remodeling through PAR-1 and PAR-2. Inhibition of PAR-1 and PAR-2 significantly reduces vascular muscularization and improves right ventricular function in PAH. These findings suggest that PARs, rather than their activators, could be potential targets for PAH treatment.
CARDIOVASCULAR RESEARCH
(2022)
Article
Oncology
Fanfan Fan, Jian Gao, Yue Zhao, Jun Wang, Lu Meng, Jiaqiang Ma, Teng Li, Han Han, Jinglei Lai, Zhendong Gao, Xiongfei Li, Ran Guo, Zhiwei Cao, Yang Zhang, Xiaoming Zhang, Haiquan Chen
Summary: This study comprehensively characterized the mast cells in lung adenocarcinoma and found that they exhibit functional heterogeneity and different characteristics and functions in different types of lung adenocarcinoma. The interaction between mast cells and CCR2+ T cells is closely associated with the prognosis of lung adenocarcinoma.
Article
Oncology
Morten N. Andersen, Niels F. Andersen, Kristina L. Lauridsen, Anders Etzerodt, Boe S. Sorensen, Niels Abildgaard, Trine Plesner, Marianne Hokland, Holger J. Moller
Summary: The activation of STAT3 in CD163(pos) TAMs in MM patients indicates that the CD163 scavenger receptor may be a useful target for delivering STAT3-inhibitory drugs to TAMs in the future.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Cell Biology
Martin Haschak, Samuel LoPresti, Elizabeth Stahl, Siddhartha Dash, Branimir Popovich, Bryan N. Brown
Summary: The study highlights the significant effect of both biomechanical and biochemical alterations in cardiac tissue on macrophage polarization and function, providing insights into the age-related shift towards pro-inflammatory macrophage populations associated with cardiovascular disease development.
Article
Biochemistry & Molecular Biology
Audrey Grossen, Kyle Smith, Nangorgo Coulibaly, Benjamin Arbuckle, Alexander Evans, Stefan Wilhelm, Kenneth Jones, Ian Dunn, Rheal Towner, Dee Wu, Young-Tae Kim, James Battiste
Summary: The invasive capabilities of glioblastoma (GBM) determine its aggressiveness, treatment resistance, and overall mortality. The tumor microenvironment influences the molecular behavior of cells, both epigenetically and genetically. This review outlines the advances made in understanding the physical forces involved in GBM and highlights the need for further research to target these forces and improve patient outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Critical Care Medicine
Michael C. McKelvey, Anthony A. Abladey, Donna M. Small, Declan F. Doherty, Richard Williams, Aaron Scott, C. Arnold Spek, Keren S. Borensztajn, Leslie Holsinger, Robert Booth, Cecilia M. O'Kane, Daniel F. McAuley, Clifford C. Taggart, Sinead Weldon
Summary: This study investigates the role of cathepsin S in acute respiratory distress syndrome (ARDS), a condition without specific pharmacological treatments. The results show that cathepsin S contributes to acute lung injury and could be a potential therapeutic target for ARDS. The study demonstrates that elevated cathepsin S activity and concentration are associated with acute lung inflammation, leading to neutrophil recruitment and protein leakage. Additionally, the study suggests that cathepsin S mediates its pathogenic effects partly through protease-activated receptor-1.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Article
Oncology
Lihui Guo, Bernadette Schurink, Eva Roos, Esther J. Nossent, Jan Willem Duitman, Alexander P. J. Vlaar, Paul van der Valk, Frederic M. Vaz, Syun-Ru Yeh, Zachary Geeraerts, Annemiek Dijkhuis, Lonneke van Vught, Marianna Bugiani, Rene Lutter
Summary: COVID-19 is associated with the accumulation of tryptophan degradation products in the lungs, heart, and brain. The expression of IDO-2, an isoform rarely expressed, is related to cell death and severe cellular stress in these organs. The early activation of the kynurenine/aryl-hydrocarbon receptor/IDO-2 axis may contribute to the pathology of severe COVID-19.
JOURNAL OF PATHOLOGY
(2022)
Review
Pharmacology & Pharmacy
Etienne J. Slapak, Mouad el Mandili, Maarten F. Bijlsma, C. Arnold Spek
Summary: Pancreatic cancer has a poor prognosis and limited response to chemotherapy. The use of mesoporous silica nanoparticles (MSNs) for targeted therapy in pancreatic cancer seems promising, although clinical translation is still lagging.
Article
Biochemistry & Molecular Biology
C. Arnold Spek, Hella L. Aberson, JanWillem Duitman
Summary: This study identifies C/EBP delta as an important transcription factor driving macrophage-induced gemcitabine resistance in pancreatic cancer cells.
Article
Respiratory System
Justin de Brabander, Erik Duijvelaar, Job R. Schippers, Patrick J. Smeele, Hessel Peters-Sengers, Jan Willem Duitman, Jurjan Aman, Harm Jan Bogaard, Tom van der Poll, Lieuwe D. J. Bos
Summary: The effect of imatinib on mortality in hospitalised COVID-19 patients is mediated through modulation of innate immune responses and reversal of endothelial dysfunction, and possibly moderated by biological subphenotypes.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Cell Biology
Leonie Hartl, Pien A. F. Maarschalkerweerd, Joe M. Butler, Xue D. Manz, Victor L. J. L. Thijssen, Maarten F. Bijlsma, JanWillem Duitman, C. Arnold Spek
Summary: Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive cancer with increasing incidence globally. Metastasis is the primary cause of cancer-related death in PDAC patients. The protein expression of the transcription factor CCAAT/Enhancer-Binding Protein Delta (C/EBP delta) negatively correlates with lymph node involvement. C/EBP delta plays a major role in regulating cell motility and inducing a more epithelial-like cellular phenotype.
Article
Biochemistry & Molecular Biology
Leonie Hartl, Joris J. T. H. Roelofs, Frederike Dijk, Maarten F. Bijlsma, JanWillem Duitman, C. Arnold Spek
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a serious disease with limited treatment options. The low expression of CCAAT/Enhancer-Binding Protein Delta (C/EBP delta) in PDAC is associated with poor patient survival and lymph node involvement. However, C/EBP beta and C/EBP gamma can partly compensate for the loss of C/EBP delta and improve patient outcomes. C/EBP beta also serves as a new predictor for reduced lymph node involvement.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Mark P. G. Dings, Amber P. van der Zalm, Sanne Bootsma, Tatum F. J. van Maanen, Cynthia Waasdorp, Tom van den Ende, Dajia Liu, Peter Bailey, Jan Koster, Danny A. Zwijnenburg, C. Arnold Spek, Jan P. G. Klomp, Arthur Oubrie, Gerrit K. J. Hooijer, Sybren L. Meijer, Mark I. van Berge Henegouwen, Maarten C. Hulshof, Jacques Bergman, Cesar Oyarce, Jan Paul Medema, Hanneke W. M. van Laarhoven, Maarten F. Bijlsma
Summary: This study reveals a metabolic rewiring in esophageal adenocarcinoma cells following neoadjuvant chemoradiotherapy, leading to acquired resistance. Oxidative phosphorylation is identified as the most upregulated biological program, and EsRRA is identified as the transcription factor responsible for this reprogramming. Pharmacological inhibition of EsRRA successfully resensitizes the cancer cells to radiation.
CELL REPORTS MEDICINE
(2022)
Letter
Critical Care Medicine
C. Arnold Spek, Jan Willem Duitman
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Review
Oncology
Leonie Hartl, JanWillem Duitman, Maarten F. Bijlsma, C. Arnold Spek
Summary: CCAAT/Enhancer-Binding Protein delta (C/EBP8) is a transcription factor involved in differentiation and inflammation. Its aberrant expression has been associated with different cancers. While initially thought to act as a tumor suppressor, it is now widely accepted that C/EBP8 contributes to tumor-promoting effects, such as inflammation, hypoxia adaptation, and blood vessel recruitment. This review summarizes the research on C/EBP8 in cancer and seeks to explain conflicting results.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Etienne J. Slapak, Mouad el Mandili, Marieke S. Ten Brink, Alexander Kros, Maarten F. Bijlsma, C. Arnold Spek
Summary: Pancreatic adenocarcinoma (PDAC) is difficult to treat with chemotherapy and has a poor survival rate. Targeted drug delivery approaches using mesoporous silica nanoparticles (MSNs) have shown promise in killing PDAC cells in vitro. However, when tested in clinically relevant models, off-target toxicity was observed. Optimized ADAM9-responsive MSNs (OPT-MSNs) were developed to minimize off-target cytotoxicity while still efficiently killing PDAC cells. In a preclinical PDAC xenograft model, paclitaxel-loaded OPT-MSNs reduced organ damage and leukopenia but did not exhibit antitumor activity. This study highlights the challenges in translating MSN-based tumor-targeting strategies into effective clinical treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Respiratory System
Wanhai Qin, C. Arnold Spek, Brendon P. Scicluna, Tom van der Poll, JanWillem Duitman
Summary: This study found that deficiency of DNA methyltransferase DNMT3B promotes macrophage polarization during pulmonary fibrosis and enhances fibrosis development. The results suggest that myeloid DNMT3B plays a crucial role in inhibiting fibrotic macrophage polarization and protecting against bleomycin-induced pulmonary fibrosis.
RESPIRATORY RESEARCH
(2022)
