Article
Chemistry, Medicinal
Jiakuo Liu, Chengjuan Chen, Dongmei Wang, Jie Zhang, Tiantai Zhang
Summary: Therapy based on Bruton's tyrosine kinase (BTK) inhibitors is a major treatment option for lymphoma patients, with the first generation showing remarkable progress but still facing issues like drug-resistance and serious side effects. New BTK inhibitors have been developed to address these challenges and their effects on immune-related diseases are being evaluated in clinical trials. Progress in the research and development of BTK inhibitors, focusing on structural characteristics and structure-activity relationships, has been summarized in this review.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Esmeralda Hemme, Danique Biskop, Marie A. C. Depuydt, Virginia Smit, Lucie Delfos, Mireia N. A. Bernabe Kleijn, Amanda C. Foks, Johan Kuiper, Ilze Bot
Summary: Atherosclerosis is characterized by the accumulation of lipids and immune cells in the arterial wall. Mast cells play a role in plaque growth and destabilization. The Fc epsilon RI-IgE pathway and BTK may be potential therapeutic targets in atherosclerosis.
VASCULAR PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Sona Krajcovicova, Radek Jorda, David Vanda, Miroslav Soural, Vladimir Krystof
Summary: An efficient synthetic approach for trisubstituted imidazo [4,5-c]pyridines as BTK inhibitors was reported, with high tolerance of C6 substitutions observed. Cellular experiments indicated selective BTK targeting, suggesting the inhibitors could be potential options after ibrutinib failure.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Max Von Suskil, Kazi Nasrin Sultana, Weam Othman Elbezanti, Omar S. Al-Odat, Robert Chitren, Amit K. Tiwari, Kishore B. Challagundla, Sandeep Kumar Srivastava, Subash C. Jonnalagadda, Tulin Budak-Alpdogan, Manoj K. Pandey
Summary: Multiple myeloma remains an incurable disease despite advancements in treatment, leading to aggressive relapses in patients. The cytosolic kinase BTK plays a crucial role in the survival of malignant clones and multiple myeloma stem cells, making it a promising therapeutic target. Inhibition of the BTK pathway may disrupt interactions between malignant clones and the bone marrow microenvironment in MM patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Inhye E. Ahn, Jennifer R. Brown
Summary: Targeting the B-cell receptor signaling pathway through BTK inhibition has shown significant efficacy in the treatment of CLL and B-cell lymphomas. Different selectivity of individual BTKis leads to differences in target-mediated and off-target adverse effects. Disease progression driven by histologic transformation or selective expansion of mutated CLL clones remains a major challenge, but new combination regimens and reversible BTKis hold promise for preventing and treating BTKi-resistant disease.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Dariusz Rozkiewicz, Justyna Magdalena Hermanowicz, Iwona Kwiatkowska, Anna Krupa, Dariusz Pawlak
Summary: There has been increasing interest in Bruton's tyrosine kinase (BTK) and its inhibitors in recent decades. BTK is a mediator of the B-cell receptor signaling pathway and has an impact on B-cell proliferation and differentiation. Studies have shown that BTK inhibitors, such as ibrutinib, have potential in treating various cancers and autoimmune diseases. This review article summarizes the latest findings on BTK and its inhibitors, focusing on their clinical applications in cancer and chronic inflammatory diseases.
Letter
Oncology
Brooke Benner, William E. Carson
Summary: BTK inhibitors have been found to protect against pulmonary injury in some COVID-19 patients, possibly by reducing levels of pro-inflammatory cytokines in circulation. Understanding the potential mechanism of action of BTK inhibition in SARS-CoV-2 is crucial for determining their protective effects against lung injury.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Biophysics
Manuel Eisentraut, Adal Sabri, Holger Kress
Summary: Antibody-opsonized bacteria interact with Fc receptors in macrophages and trigger signaling cascades that induce phagocytosis. The spreading distance of this initial stimulus created by the bacterium-cell contact in the cell is closely related to the spatial resolution limit of phagocytosis. This study used holographic optical tweezers to attach particles to macrophages and developed a model to explain the phagocytic uptake behavior.
BIOPHYSICAL JOURNAL
(2023)
Article
Immunology
Rachel H. Bonami, Christina E. Thurman, Sonam Verma, Camille S. Westlake, Lindsay E. Nyhoff, Bridgette B. Barron, Andrea Reboldi, Peggy L. Kendall
Summary: This study reveals that BTK is crucial for maintaining normal intestinal IgA development and the IgA coating of commensal bacteria. Deficiency in BTK leads to decreased IgA levels in the small intestines and a shift in the composition of IgA-coated microbes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Gareth S. D. Purvis, Haidee Aranda-Tavio, Keith M. Channon, David R. Greaves
Summary: This study identifies a new role of BTK in regulating myeloid cell recruitment through reducing the ability of monocytes/macrophages to undergo chemotaxis and reducing chemokine secretion. This finding has significant implications.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Erna-Zulaikha Dayang, Matthijs Luxen, Timara Kuiper, Rui Yan, Savithri Rangarajan, Matijs van Meurs, Jill Moser, Grietje Molema
Summary: Sepsis is a life-threatening condition with no pharmacological treatment available, where endothelial cells play a key role in inflammatory response. Kinases such as FAK1 and ALK are potential targets for inhibiting LPS-induced endothelial activation, with FAK1 inhibition showing promising results in attenuating inflammatory response. ALK inhibition, on the other hand, acts through a pathway independent of NF-kappa B signaling to attenuate LPS-induced inflammation.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Multidisciplinary Sciences
Simei Qiu, Yunfeng Liu, Quhuan Li
Summary: BTK kinase plays a crucial role in the treatment of B-cell malignancies. The T474M mutation leads to increased kinase activity by altering the protein structure, enhancing catalytic ability. This activation and resistance mechanism may offer new insights for drug development in B-cell malignancies.
ROYAL SOCIETY OPEN SCIENCE
(2021)
Review
Cell Biology
Stefan F. H. Neys, Rudi W. Hendriks, Odilia B. J. Corneth
Summary: BTK plays a crucial role in B cell development and BCR signaling. Recent studies suggest increased BTK expression in patients with autoimmune diseases, making it a potential target in inflammatory and systemic AID. Inhibition of BTK has shown efficacy in various diseases, with recent reports even indicating its effectiveness in reducing lung inflammation in COVID-19.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Shuo Geng, Yao Zhang, Ziyue Yi, Ran Lu, Liwu Li
Summary: TRAM mediates monocyte polarization through activating c-SRC, leading to changes in inflammatory and resolving mediators, suppressing atherosclerosis. TRAM-deficient monocytes can propagate the resolving phenotype and intravenous transfusion can effectively slow down the progression of atherosclerosis. Targeting TRAM may facilitate the generation of resolving monocytes for atherosclerosis treatment.
Article
Immunology
Yong Du, Ling Lei, Huihua Ding, Yanping Chen, Simanta Pathak, John Hicks, Phuongthy T. Tran, Minghua Wu, Betty Chang, Uwe Wirtz, Chandra Mohan
Summary: This study demonstrates that the inhibition of Bruton tyrosine kinase (Btk) has therapeutic and preventative effects in multiple models of end-organ inflammation, including lupus nephritis, anti-GBM nephritis, systemic sclerosis-like skin disease, and bleomycin-induced lung disease. BTK inhibitors effectively reduce renal damage and proteinuria in lupus nephritis, as well as skin thickness, fibrosis, collagen deposition, and inflammation in systemic sclerosis-like disease. Additionally, the inhibition of Btk results in decreased lung inflammatory cell infiltration. These findings have important implications for the management of systemic rheumatic diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
S. P. Parihar, M. Ozturk, M. J. Marakalala, D. T. Loots, R. Hurdayal, D. Beukes, M. Van Reenen, D. E. Zak, S. K. Mbandi, F. Darboe, A. Penn-Nicholson, W. A. Hanekom, M. Leitges, T. J. Scriba, R. Guler, F. Brombacher
MUCOSAL IMMUNOLOGY
(2018)
Article
Immunology
Carlson Tsui, Nuria Martinez-Martin, Mauro Gaya, Paula Maldonado, Miriam Llorian, Nathalie M. Legrave, Merja Rossi, James I. MacRae, Angus J. Cameron, Peter J. Parker, Michael Leitges, Andreas Bruckbauer, Facundo D. Batista
Article
Neurosciences
Lesley A. Colgan, Mo Hu, Jaime A. Misler, Paula Parra-Bueno, Corey M. Moran, Michael Leitges, Ryohei Yasuda
NATURE NEUROSCIENCE
(2018)
Article
Cell Biology
Kerstin Siegmund, Nikolaus Thuille, Nina Posch, Friedrich Fresser, Michael Leitges, Gottfried Baier
CELL COMMUNICATION AND SIGNALING
(2019)
Article
Oncology
Ning Yin, Yi Liu, Andras Khoor, Xue Wang, E. Aubrey Thompson, Michael Leitges, Verline Justilien, Capella Weems, Nicole R. Murray, Alan P. Fields
Article
Biochemistry & Molecular Biology
Alexander E. Mayer, Mona C. Loeffler, Angel E. Loza Valdes, Werner Schmitz, Rabih El-Merahbi, Jonathan Trujillo Viera, Manuela Erk, Thianzhou Zhang, Ursula Braun, Mathias Heikenwalder, Michael Leitges, Almut Schulze, Grzegorz Sumara
Article
Cell Biology
Nikolaus Thuille, Kerstin Siegmund, Victoria Klepsch, Jacqueline Schoergenhuber, Sarah Danklmaier, Michael Leitges, Gottfried Baier
CELL COMMUNICATION AND SIGNALING
(2019)
Correction
Oncology
Ning Yin, Yi Liu, Andras Khoor, Xue Wang, E. Aubrey Thompson, Michael Leitges, Verline Justilien, Capella Weems, Nicole R. Murray, Alan P. Fields
Meeting Abstract
Endocrinology & Metabolism
Mini P. Sajan, Ursula Braun, Michael Leitges, Colin Park, David M. Diamond, Jin Wu, Barbara C. Hansen, Mildred Acevedo Duncan, Christopher A. Apostolatos, Andre H. Apostolatos, Mark Kindy, Robert V. Farese
METABOLISM-CLINICAL AND EXPERIMENTAL
(2020)
Article
Cell Biology
Eugene Park, Jingyu Chen, Andrew Moore, Maurizio Mangolini, Antonella Santoro, Joseph R. Boyd, Hilde Schjerven, Veronika Ecker, Maike Buchner, James C. Williamson, Paul J. Lehner, Luca Gasparoli, Owen Williams, Johannes Bloehdorn, Stephan Stilgenbauer, Michael Leitges, Alexander Egle, Marc Schmidt-Supprian, Seth Frietze, Ingo Ringshausen
SCIENCE TRANSLATIONAL MEDICINE
(2020)
Article
Multidisciplinary Sciences
Alicia K. Fleming Martinez, Heike R. Doppler, Ligia Bastea, Brandy Edenfield, Tushar Patel, Michael Leitges, Geou-Yarh Liou, Peter Storz
Summary: DCLK1(+) pancreatic cancer stem cells develop at a precancerous stage and may contribute to the lack of efficacy of pancreatic cancer therapy. Our study showed that EGFR signaling is not propagated to the nucleus in DCLK1(+) PanIN cells, and inhibition of EGFR led to a significant increase in DCLK1(+) PanIN cells. The activation of PKD1 by an increase in hydrogen peroxide is identified as a mechanism for the formation of DCLK1(+) cells, driving stemness and abundance in lesions.
Article
Multidisciplinary Sciences
Lijing Su, Muhammad Athamna, Ying Wang, Junmei Wang, Marina Freudenberg, Tao Yue, Jianhui Wang, Eva Marie Y. Moresco, Haoming He, Tsaffrir Zor, Bruce Beutler
Summary: Sulfatides can activate mouse immune responses via the TLR4-MD-2 complex, but exhibit antagonistic effects in human cells. Their activity is related to the presence of the sulfate group and the length of the fatty acid chain, and their structure mimics the activation mechanism of molecules like LPS in receptors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Kristin S. Inman, Yi Liu, Michele L. Scotti Buzhardt, Michael Leitges, Murli Krishna, Howard C. Crawford, Alan P. Fields, Nicole R. Murray
Summary: The protein kinase C iota (PKC iota) plays a promotive role in pancreatic cancer development, and inhibition of its expression prevents pancreatic cancer formation. It also affects the autophagy of pancreatic epithelial cells and the progression of pancreatic cancer.
Article
Cell & Tissue Engineering
Franziska von Heydebrand, Maximilian Fuchs, Meik Kunz, Simon Voelkl, Anita N. Kremer, Robert A. J. Oostendorp, Jochen Wilke, Michael Leitges, Alexander Egle, Andreas Mackensen, Gloria Lutzny-Geier
Summary: PKC beta plays a significant role in influencing glucose metabolism in CLL cells upon contact with BMSC, by stimulating glucose uptake to alleviate stress and apoptosis in CLL cells, and could potentially be targeted as a therapeutic strategy to overcome drug resistance mediated by the stromal microenvironment.
Meeting Abstract
Hematology
Eugene Park, Jingyu Chen, Andrew Moore, Michael Leitges, Seth E. Frietze, Ingo Ringshausen
Article
Cell Biology
Ke Mi, Lizhong Zeng, Yang Chen, Jingya Ning, Siyuan Zhang, Peilin Zhao, Shuanying Yang
Summary: In this study, the researchers explored the role of DHX38 in NSCLC and its underlying molecular mechanism. They found that DHX38 was overexpressed in NSCLC and patients with high DHX38 expression had poor prognosis. DHX38 promoted cell proliferation, migration, and invasion in NSCLC and activated the MAPK pathway. The researchers also identified G3BP1 as a target protein that interacted with DHX38 and showed that DHX38 regulated the expression of G3BP1. Silencing G3BP1 reversed the effects of DHX38 overexpression on tumor cell proliferation, migration, and invasion and inhibited the MAPK pathway activation.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Tiina A. Jokela, Mark A. Dane, Rebecca L. Smith, Kaylyn L. Devlin, Sundus Shalabi, Jennifer C. Lopez, Masaru Miyano, Martha R. Stampfer, James E. Korkola, Joe W. Gray, Laura M. Heiser, Mark A. Labarge
Summary: Microenvironment signals have a significant impact on cell fate and tissue homeostasis. Understanding how different microenvironment factors regulate cellular phenotype has been challenging. In this study, a high-throughput microenvironment microarray was used to identify factors that support the proliferation and maintenance of primary human mammary luminal epithelial cells. Multiple factors that modulate luminal cell number were identified and their effects were confirmed using RNA sequencing and cell-based functional studies. Hepatocyte growth factor (HGF) was found to be robust to individual variation and played a role in expanding luminal cells. Our approach demonstrates the power of high-dimensional cell-based approaches in dissecting microenvironmental signals.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Chao He, Yongfeng Ding, Yan Yang, Gang Che, Fei Teng, Haohao Wang, Jing Zhang, Donghui Zhou, Yanyan Chen, Zhan Zhou, Haiyong Wang, Lisong Teng
Summary: This study categorized gastric cancer patients into three stemness subtypes, each demonstrating distinct prognoses, components of tumor microenvironment (TME) infiltration, and varying sensitivity or resistance to treatment. A stemness risk model was constructed to predict treatment response and prognosis.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Haile Zhao, Lijuan Feng, Rui Cheng, Man Wu, Xiaozhou Bai, Lifei Fan, Yaping Liu
Summary: miR-29c-3p is overexpressed in benign and malignant ovarian carcinoma and is associated with poor prognosis. Its overexpression modulates tumorigenesis in ovarian cancer cells, including epithelial-mesenchymal transition, proliferation, migration, and invasion, through the regulation of DNMT3A, TET1, and HBP1. miR-29c-3p may serve as a potential biomarker for clinical diagnosis or co-diagnosis of ovarian carcinoma.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Haiyan Zhao, Fangfang Bi, Mengyuan Li, Yuhan Diao, Chen Zhang
Summary: This study confirmed the tumor suppressor effect of RNF180 on ovarian cancer, elucidated the mechanism of the molecule network related to RNF180 and IPO4 in ovarian cancer, and identified a new therapeutic target for ovarian cancer.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Chu Chen, Guanhua Xu, Jiajia Chen, Chunshuai Wu, Jinlong Zhang, Jiawei Jiang, Hongxiang Hong, Zhiming Cui
Summary: This study investigated the role of transcription factor FoxO1 in facet joint osteoarthritis (FJOA) and found that FoxO1 deletion led to severe osteoarthritic changes. Transcriptome sequencing and bioinformatics analysis identified differentially expressed genes (DEGs) and potential key contributors to FJOA. Additionally, over-expression of certain genes and inhibition of others were shown to counteract the impairments caused by FoxO1 deletion in chondrocyte migration and extracellular matrix synthesis. These findings help unravel the molecular mechanisms underlying FJOA and open up promising therapeutic avenues for its treatment.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Wen Deng, Ru Chen, Situ Xiong, Jianqiang Nie, Hailang Yang, Ming Jiang, Bing Hu, Xiaoqiang Liu, Bin Fu
Summary: This study demonstrates that circFSCN1 is upregulated in bladder cancer and associated with cancer-specific survival. CircFSCN1 promotes tumor progression and epithelial-mesenchymal transition in bladder cancer through enhancing MDM2-mediated silencing of p53 by sponging miR-145-5p.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Jun Wu, Weibin Hu, Wenhui Yang, Yihao Long, Kaizhao Chen, Fugui Li, Xiaodong Ma, Xun Li
Summary: Cholesterol biosynthesis and metabolism play critical roles in tumor development and microenvironmental conditions. Squalene Epoxidase (SQLE), the second rate-limiting enzyme in cholesterol synthesis, is found to be uniquely expressed in various cancers, and its expression level is closely associated with tumor mutation burden and microsatellite instability. SQLE expression is negatively correlated with immune cell infiltration. Inhibition of SQLE alters the immune response in the tumor microenvironment. Furthermore, protein metabolism and translation are identified as main binding factors with SQLE.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Zhihong Zhang, Mingyue Li, Yi Tai, Yue Xing, Hongxiang Zuo, Xuejun Jin, Juan Ma
Summary: ZNF70 plays an important role in colitis-associated colorectal cancer (CAC) by regulating macrophages IL-1 beta secretion to promote HCT116 proliferation. It may serve as a promising target for treating CAC.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Zenghong Wu, Gangping Li, Weijun Wang, Kun Zhang, Mengke Fan, Yu Jin, Rong Lin
Summary: This study comprehensively explored the role of immune checkpoints and tumor microenvironment in gastric cancer patients based on genomic data. It constructed an ICIs signature and ICI score to evaluate patient prognosis and heterogeneity.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Yantong Wan, Jieshu Zhou, Panpan Zhang, Xuemei Lin, Hao Li
Summary: This study found that Rac1 plays a role in astrocyte activation and attenuates chronic inflammatory pain by blocking the phosphorylation of NLRP3 inflammasome and NF-kappa B.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Zhen Wang, Diankun She, Lei Liu, Xianming Hua, Hao Zhu, Lingfeng Yu, Han Wang, Yan Zhu, Gentao Fan, Yicun Wang, Meng Xu, Guangxin Zhou
Summary: Circular RNAs (circRNAs) are non-coding RNAs that play a role in the regulation of various cancers, including osteosarcoma (OS). This study identified circSATB2 as a highly expressed circRNA in OS tissues and cell lines, and demonstrated its involvement in promoting OS proliferation and migration. Mechanistically, circSATB2 was found to regulate the progression of OS by sponging miR-661 and FUS to regulate ZNFX1 mRNA. These findings suggest that circSATB2 could serve as a prognostic marker and therapeutic target for osteosarcoma.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Kenichi Ogata, Masafumi Moriyama, Tatsuya Kawado, Hiroki Yoshioka, Aiko Yano, Mayu Matsumura-Kawashima, Seiji Nakamura, Shintaro Kawano
Summary: This study found that extracellular vesicles released by induced pluripotent stem cells can reduce inflammatory cell infiltration, increase saliva volume, and decrease the production of antibodies associated with Sjogren's syndrome in a mouse model. The let-7 family in these vesicles may suppress the expression of TLR4 and NF-kappa B, which leads to the inhibition of pro-inflammatory cytokine production through the MAPK pathway.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Mikayla R. Erdelsky, Sarah A. Groves, Charmi Shah, Samantha B. Delios, M. Bibiana Umana, Donald H. Maurice
Summary: Recent evidence suggests that cAMP signaling within the primary cilium plays a crucial role in promoting adipogenic differentiation of 3T3-L1 preadipocytes. In this study, the researchers identified the specific cAMP phosphodiesterases expressed by these cells and found that inhibition of PDE4 promotes FFAR4-mediated adipogenesis. This work could potentially lead to the discovery of more targeted therapeutic approaches for controlling adipogenesis and differentiation of other stem cells.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Chun-Hui Liu, Jun-Jie Zhang, Qian-Jin Zhang, Yang Dong, Zhen-Duo Shi, Si-Hao Hong, Hou-Guang He, Wei Wu, Cong-Hui Han, Lin Hao
Summary: Bladder cancer, the most common malignant tumor in the urinary system, is associated with significantly up-regulated expression of P3H4, which is regulated by METTL3 and plays a crucial role in the proliferation, metastasis, and EMT progression of bladder cancer. Targeting this METTL3-P3H4 pathway may serve as a potential therapeutic strategy for bladder cancer.
CELLULAR SIGNALLING
(2024)
