Article
Chemistry, Medicinal
Juliana P. Vago, Natalia Valdrighi, Esmeralda N. Blaney-Davidson, Daniel L. A. H. Hornikx, Margot Neefjes, Maria E. Barba-Sarasua, Nathalie G. M. Thielen, Martijn H. J. van den Bosch, Peter M. van der Kraan, Marije I. Koenders, Flavio A. Amaral, Fons A. J. van de Loo
Summary: This study investigated the anti-inflammatory effects of Gas6, a TAM receptor ligand, in synovial fibroblasts from osteoarthritis (OA) patients. Gas6 was found to reduce the levels of inflammatory markers, and its effects depended on the activation of the Axl receptor and the induction of SOCS1/3.
Review
Biochemistry & Molecular Biology
Mai Tanaka, Dietmar W. Siemann
Summary: Dysregulated signaling pathways in cancer cells and the tumor microenvironment, including the Axl and Gas6 pathways, have led to the development of therapeutic agents targeting the Gas6/Axl pathway. Promising results have been observed in both preclinical and clinical settings, indicating potential clinical efficacy of targeting Gas6 and Axl.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Manuela Rizzi, Stelvio Tonello, Davide D'Onghia, Pier Paolo Sainaghi
Summary: Gas6 is a widely expressed protein involved in various biological processes. It serves as the main ligand for TAMs, and its activation plays a crucial role in modulating inflammatory responses and fibrotic evolution. This review focuses on Gas6/TAM axis activation in SARS-CoV-2 infection and highlights the potential therapeutic benefits of targeting Axl, a receptor member of TAMs, in COVID-19 management.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Masahiko Sugimoto, Mineo Kondo, Taro Yasuma, Corina N. D'Alessandro-Gabazza, Masaaki Toda, Hisanori Imai, Makoto Nakamura, Esteban C. Gabazza
Summary: This study evaluated the distribution of Protein S in diabetic retinopathy and diabetic macular edema, suggesting its involvement in the pathogenesis of these conditions. The higher expression of Protein S in eyes with DR and DME indicates its potential role in these complications of diabetes.
SCIENTIFIC REPORTS
(2021)
Review
Oncology
Xiaoqian Zhai, Dan Pu, Rulan Wang, Jiabi Zhang, Yiyun Lin, Yuqing Wang, Ni Zhai, Xuan Peng, Qinghua Zhou, Lu Li
Summary: Cancer is a disease that has a significant impact on human survival and quality of life. Gas6 has been found to play an important role in various malignancies, promoting tumor development and affecting overall survival. Gas6 interacts with the TAM receptors, especially Axl, affecting cell cycle progression and modulating the tumor microenvironment. This comprehensive review highlights the importance of the Gas6/AXL pathway in cancer progression and therapy resistance.
FRONTIERS IN ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Daria Zdzalik-Bielecka, Agata Poswiata, Kamila Kozik, Kamil Jastrzebski, Kay Oliver Schink, Marta Brewinska-Olchowik, Katarzyna Piwocka, Harald Stenmark, Marta Miaczynska
Summary: The study identified an interactome of AXL and its associations with proteins regulating actin dynamics. GAS6-mediated AXL activation triggered actin remodeling and macropinocytosis, promoting the survival of cancer cells under glutamine-deprived conditions. AXL activation by GAS6 drove invasion of cancer cells through actin-driven cytoskeletal rearrangements.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Oncology
Zhaowu Ma, Xiaoqiang Xiang, Shiya Li, Peng Xie, Quan Gong, Boon-Cher Goh, Lingzhi Wang
Summary: Rapid progress in molecular cancer biology and the discovery of new oncology drugs have opened new opportunities for cancer target discovery. HIF-1, a crucial signaling pathway related to tumorigenesis, regulates the activity of many transcription factors and downstream molecules that affect tumor growth and metastasis. Overexpression of HIF-1 alpha is strongly associated with poor prognosis in several solid cancers. Pharmacological targeting of the HIF-1 signaling pathway has been considered a new strategy for cancer therapy, but translation into clinically available treatments remains challenging.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Francesco Gavelli, Luca Molinari, Marco Baldrighi, Livia Salmi, Filippo Mearelli, Nicola Fiotti, Filippo Patrucco, Chiara Airoldi, Mattia Bellan, Pier Paolo Sainaghi, Salvatore Di Somma, Enrico Lupia, Efrem Colonetti, Maria Lorenza Muiesan, Gianni Biolo, Gian Carlo Avanzi, Luigi Mario Castello
Summary: This study found that measuring the concentration of sMer and Gas6 at the emergency department did not predict mortality, but these biomarkers were associated with acute kidney injury, thrombocytopenia, deranged prothrombin time-international normalized ratio, and sepsis-induced coagulopathy, suggesting a role in predicting sepsis-related organ damage.
Review
Microbiology
Daria Apostolo, Luciana L. Ferreira, Alice Di Tizio, Barbara Ruaro, Filippo Patrucco, Mattia Bellan
Summary: The tyrosine kinase receptors of the TAM family and their ligand Gas6 play a crucial role in innate immunity and inflammatory response. The Gas6/TAM system is involved in the recognition of apoptotic debris by immune cells, which has been exploited by viruses like COVID-19 for cell entry and infection. Understanding the mechanisms underlying COVID-related fibrosis, particularly in the lungs, is still limited, and this review aims to integrate the current knowledge of the Gas6/TAM axis with the pathophysiological mechanisms of COVID-19, focusing on the development of a fibrotic phenotype.
Article
Biochemistry & Molecular Biology
Daria Apostolo, Davide D'Onghia, Stelvio Tonello, Rosalba Minisini, Alessio Baricich, Carla Gramaglia, Filippo Patrucco, Patrizia Zeppegno, Antonio Acquaviva, Piero Emilio Balbo, Luigi Mario Castello, Giuseppe Cappellano, Annalisa Chiocchetti, Chiara Gerevini, Mara Giordano, Fatiha Laaguid, Marcello Manfredi, Davide Raineri, Cristina Rigamonti, Roberta Rolla, Valentina Romano, Marco Confalonieri, Paola Savoia, Elisa Zavattaro, Mario Pirisi, Barbara Ruaro, Pier Paolo Sainaghi, Mattia Bellan
Summary: Post-acute conditions are common after COVID-19, and the underlying mechanisms are not yet fully understood. This study suggests that Gas6 and its soluble receptors, sAxl and sMer, may be implicated in these conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Fan Yang, Zhigang Hu, Zhigang Guo
Summary: DNA damage repair is crucial for maintaining genomic stability and integrity, and FEN1 plays a critical role in this process. Abnormal expression or mutation of FEN1 is associated with various diseases, including cancers, making it a therapeutic target for cancer treatment. Small-molecule compounds targeting FEN1 have been developed and show promise in cancer therapy.
Review
Medicine, General & Internal
Jianjing Lin, Shicheng Jia, Weifei Zhang, Mengyuan Nian, Peng Liu, Li Yang, Jianwei Zuo, Wei Li, Hui Zeng, Xintao Zhang
Summary: Osteoarthritis is a degenerative disease characterized by joint pain, caused by factors such as fibrosis, chapping, ulcers, and loss of articular cartilage. Traditional treatments only delay its progression, while small molecule inhibitors targeting proteins show promising effects in managing osteoarthritis. This review examines small molecule inhibitors targeting various proteins and discusses disease-modifying osteoarthritis drugs based on them, providing valuable insights for the treatment of osteoarthritis.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Pharmacology & Pharmacy
Ava Safaroghli-Azar, Fatemeh Emadi, Jimma Lenjisa, Laychiluh Mekonnen, Shudong Wang
Summary: As the fifth pillar of cancer treatment, immunotherapy has revolutionized therapeutic strategies by focusing on the host's immune system. The discovery of immune-modulatory effects for kinase inhibitors has opened up new possibilities in this approach, as these small molecule inhibitors not only directly target essential proteins for tumor survival and proliferation, but also stimulate immune responses against malignant cells.
DRUG DISCOVERY TODAY
(2023)
Article
Biochemistry & Molecular Biology
Anirban Das, Yogesh M. Gangarde, Ranit Pariary, Anirban Bhunia, Ishu Saraogi
Summary: This article introduces a novel amphiphilic molecule called PAD-S, which acts as a chemical chaperone to completely inhibit the fibrillation of insulin and its biosimilars. PAD-S can bind to the key hydrophobic regions of insulin, preventing its self-assembly and protecting cells from insulin amyloid-induced cytotoxicity.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Review
Pharmacology & Pharmacy
Yinrong Wu, Zichao Yang, Kui Cheng, Huichang Bi, Jianjun Chen
Summary: Immunotherapy has revolutionized cancer treatment, with current therapies mostly based on antibodies. However, these therapies have limitations in terms of pharmacokinetics and immunogenicity. To overcome these limitations, researchers have focused on developing small molecule-based immunotherapy. This review provides an overview of the progress in small molecule-based immunomodulators for cancer therapy, including targeting PD-1/PD-L1, chemokine receptors, STING, TLR, etc. The importance of combining small molecule-based immunomodulators with therapeutic antibodies is also highlighted.
ACTA PHARMACEUTICA SINICA B
(2022)
Meeting Abstract
Oncology
Nitu Bansal, Stanley Kimani, Kamlendra Singh, Thomas Comollo, Sushi Kumar, Vladyslav Kholodovych, Youyi Peng, William Welsh, Bertino Joseph, Raymond B. Birge
Review
Oncology
Viralkumar Davra, Stanley G. Kimani, David Calianese, Raymond B. Birge
Article
Oncology
Canan Kasikara, Sushil Kumar, Stanley Kimani, Wen-I Tsou, Ke Geng, Viralkumar Davra, Ganapathy Sriram, Connor Devoe, Khanh-Quynh N. Nguyen, Anita Antes, Allen Krantz, Grzegorz Rymarczyk, Andrzej Wilczynski, Cyril Empig, Bruce Freimark, Michael Gray, Kyle Schlunegger, Jeff Hutchins, Sergei V. Kotenko, Raymond B. Birge
MOLECULAR CANCER RESEARCH
(2017)
Article
Immunology
Ke Geng, Sushil Kumar, Stanley G. Kimani, Vladyslav Kholodovych, Canan Kasikara, Kensaku Mizuno, Oleta Sandiford, Pranela Rameshwar, Sergei V. Kotenko, Raymond B. Birge
FRONTIERS IN IMMUNOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Nootan Pandey, Chaturbhuj A. Mishra, Dinesh Manvar, Alok K. Upadhyay, Tanaji T. Talele, Thomas W. Comollo, Neerja Kaushik-Basu, Virendra N. Pandey
Meeting Abstract
Oncology
Shelly Hsieh, Khanh Q. Nguyen, Stanley Kimani, Raymond B. Birge
Meeting Abstract
Oncology
William J. Welsh, Vladyslav Kholodovych, Raymond Birge, Tom Comollo, Stanley Kimani, Kamal Singh
Article
Biochemistry & Molecular Biology
Khanh-Quynh N. Nguyen, Wen-I Tsou, Daniel A. Calarese, Stanley G. Kimani, Sukhwinder Singh, Shelly Hsieh, Yongzhang Liu, Bin Lu, Yi Wu, Scott J. Garforth, Steve C. Almo, Sergei V. Kotenko, Raymond B. Birge
JOURNAL OF BIOLOGICAL CHEMISTRY
(2014)
Article
Chemistry, Organic
Stanley Kimani, Goutam Ghosh, Ashwini Ghogare, Benjamin Rudshteyn, Dorota Bartusik, Tayyaba Hasan, Alexander Greer
JOURNAL OF ORGANIC CHEMISTRY
(2012)
Article
Biochemistry & Molecular Biology
Stanley G. Kimani, James B. Phillips, James I. Bruce, Alexander J. MacRobert, Jon P. Golding
PHOTOCHEMISTRY AND PHOTOBIOLOGY
(2012)
Article
Immunology
Stanley Gititu Kimani, Ke Geng, Canan Kasikara, Sushil Kumar, Ganapathy Sriram, Yi Wu, Raymond B. Birge
FRONTIERS IN IMMUNOLOGY
(2014)
Article
Biochemistry & Molecular Biology
Thomas W. Comollo, Xinle Zou, Chuangeng Zhang, Divya Kesters, Thomas Hof, Kevin J. Sampson, Robert S. Kass
Summary: Congenital long QT syndrome (LQTS) is a common cardiac channelopathy treated with beta blockers. However, the effectiveness of this treatment has been questioned for LQT3 patients. This study found that the beta blocker propranolol selectively inhibits the ion channel current expressed by specific mutations, suggesting its protective effect in LQT3 treatment is due in part to its modulation of the ion channel current.
Article
Biochemistry & Molecular Biology
Ashutosh K. Pandey, Updesh Dixit, Vlad Kholodovych, Thomas W. Comollo, Virendra N. Pandey