Olaparib, a poly (ADP-ribose) polymerase (PARP) Inhibitor, in Combination with Pembrolizumab and Carboplatin as First-Line Treatment of Recurrent or Metastatic Head and Neck Squamous-Cell Carcinoma (RM-HNSCC): A Single-Arm, Phase 2 Trial
The homologous recombination deficiency (HRD) phenotype is common in HNSCC and is due to mutation and promoter hypermethylation of DNA repair genes and PTEN. In pre-clinical models of HNSCC, HRD sensitizes tumors to PARP inhibition and to additive antitumor activity of PARP inhibition in combination with platinum agents. PARP inhibitors also activate the STING pathway and upregulate PD-L1 expression, resulting in synergistic antitumor activity when given with PD-1 inhibitors. Olaparib is a highly selective PARP inhibitor that has been safely combined with pembrolizumab and carboplatin. (Source: International Journal of Rad...
Source: International Journal of Radiation Oncology * Biology * Physics - March 14, 2024 Category: Radiology Authors: P. Oppelt, J. Ley, J. Liu, D. Adkins Tags: 161 Source Type: research
Apigenin Suppresses Innate Immune Responses and Ameliorates Lipopolysaccharide-Induced Inflammation via Inhibition of STING/IRF3 Pathway
Am J Chin Med. 2024 Mar 14:1-22. doi: 10.1142/S0192415X24500204. Online ahead of print.ABSTRACTThe stimulator of interferon genes (STING) signaling pathway is crucial for the pathogenesis of autoimmune and inflammatory disorders, including acute lung injury (ALI). Apigenin (4[Formula: see text],5,7-trihydroxyflavone) is a natural flavonoid widely found in fruits, vegetables, and Chinese medicinal herbs that exhibits a range of pharmacological effects, such as antibacterial and anti-inflammatory activities. However, the efficacy of apigenin in STING pathway-mediated diseases remains unclear. Accordingly, this study screened...
Source: The American Journal of Chinese Medicine - March 14, 2024 Category: Complementary Medicine Authors: Xu-Wei Zhou Juan Wang Wen-Fu Tan Source Type: research
Apigenin Suppresses Innate Immune Responses and Ameliorates Lipopolysaccharide-Induced Inflammation via Inhibition of STING/IRF3 Pathway
Am J Chin Med. 2024 Mar 14:1-22. doi: 10.1142/S0192415X24500204. Online ahead of print.ABSTRACTThe stimulator of interferon genes (STING) signaling pathway is crucial for the pathogenesis of autoimmune and inflammatory disorders, including acute lung injury (ALI). Apigenin (4[Formula: see text],5,7-trihydroxyflavone) is a natural flavonoid widely found in fruits, vegetables, and Chinese medicinal herbs that exhibits a range of pharmacological effects, such as antibacterial and anti-inflammatory activities. However, the efficacy of apigenin in STING pathway-mediated diseases remains unclear. Accordingly, this study screened...
Source: The American Journal of Chinese Medicine - March 14, 2024 Category: Complementary Medicine Authors: Xu-Wei Zhou Juan Wang Wen-Fu Tan Source Type: research
STING contributes to lipopolysaccharide-induced tubular cell inflammation and pyroptosis by activating endoplasmic reticulum stress in acute kidney injury
Cell Death & Disease, Published online: 14 March 2024; doi:10.1038/s41419-024-06600-1STING contributes to lipopolysaccharide-induced tubular cell inflammation and pyroptosis by activating endoplasmic reticulum stress in acute kidney injury (Source: Cell death and disease)
Source: Cell death and disease - March 14, 2024 Category: Internal Medicine Authors: Yun Cao Xinghua Chen Zijing Zhu Zilv Luo Yiqun Hao Xueyan Yang Jun Feng Zongwei Zhang Jijia Hu Yonghong Jian Jiefu Zhu Wei Liang Zhaowei Chen Source Type: research
Effect of Application of Autologous Conditioned Serum on Wound Healing in Diabetic Mice Through Inhibition of STING Pathway Activation
Biochem Genet. 2024 Mar 13. doi: 10.1007/s10528-024-10734-4. Online ahead of print.ABSTRACTSlow wound healing in diabetic patients is a common complication of diabetes. Autologous conditioned serum (ACS) therapy is an emerging and safe biological therapy, and may accelerate the wound healing in diabetes. To investigate the effect of ACS in promoting wound healing in diabetic mice and its possible mechanism. Twenty-four six-week-old male C57BL/6 J mice were selected and divided into 5 groups, including control group (Ctrl), diabetic wound group (DW), ACS treatment group (DW+ACS) and STING pathway validation group (DW+ACS+DM...
Source: Biochemical Genetics - March 13, 2024 Category: Genetics & Stem Cells Authors: Hongxia Li Source Type: research
Chicken UFL1 Restricts Avian Influenza Virus Replication by Disrupting the Viral Polymerase Complex and Facilitating Type I IFN Production
In this study, we first identified chUFL1 as a negative regulator of AIV replication by enhancing innate immunity and disrupting the assembly of the viral polymerase complex. Mechanistically, chUFL1 interacted with chicken stimulator of IFN genes (chSTING) and contributed to chSTING dimerization and the formation of the STING-TBK1-IRF7 complex. We further demonstrated that chUFL1 promoted K63-linked polyubiquitination of chSTING at K308 to facilitate chSTING-mediated type I IFN production independent of UFMylation. Additionally, chUFL1 expression was upregulated in response to AIV infection. Importantly, chUFL1 also intera...
Source: Journal of Immunology - March 13, 2024 Category: Allergy & Immunology Authors: Weiqiang Li Yu Lin Xiyi Wang Huixing Yang Yangbao Ding Zuxian Chen Zhuoliang He Junsheng Zhang Luxiang Zhao Peirong Jiao Source Type: research
Effect of Application of Autologous Conditioned Serum on Wound Healing in Diabetic Mice Through Inhibition of STING Pathway Activation
Biochem Genet. 2024 Mar 13. doi: 10.1007/s10528-024-10734-4. Online ahead of print.ABSTRACTSlow wound healing in diabetic patients is a common complication of diabetes. Autologous conditioned serum (ACS) therapy is an emerging and safe biological therapy, and may accelerate the wound healing in diabetes. To investigate the effect of ACS in promoting wound healing in diabetic mice and its possible mechanism. Twenty-four six-week-old male C57BL/6 J mice were selected and divided into 5 groups, including control group (Ctrl), diabetic wound group (DW), ACS treatment group (DW+ACS) and STING pathway validation group (DW+ACS+DM...
Source: Biochemical Genetics - March 13, 2024 Category: Genetics & Stem Cells Authors: Hongxia Li Source Type: research
Chicken UFL1 Restricts Avian Influenza Virus Replication by Disrupting the Viral Polymerase Complex and Facilitating Type I IFN Production
In this study, we first identified chUFL1 as a negative regulator of AIV replication by enhancing innate immunity and disrupting the assembly of the viral polymerase complex. Mechanistically, chUFL1 interacted with chicken stimulator of IFN genes (chSTING) and contributed to chSTING dimerization and the formation of the STING-TBK1-IRF7 complex. We further demonstrated that chUFL1 promoted K63-linked polyubiquitination of chSTING at K308 to facilitate chSTING-mediated type I IFN production independent of UFMylation. Additionally, chUFL1 expression was upregulated in response to AIV infection. Importantly, chUFL1 also intera...
Source: Journal of Immunology - March 13, 2024 Category: Allergy & Immunology Authors: Weiqiang Li Yu Lin Xiyi Wang Huixing Yang Yangbao Ding Zuxian Chen Zhuoliang He Junsheng Zhang Luxiang Zhao Peirong Jiao Source Type: research
Pretreated MSCs with IronQ Transplantation Attenuate Microglia Neuroinflammation via the cGAS-STING Signaling Pathway
(Source: Journal of Inflammation Research)
Source: Journal of Inflammation Research - March 13, 2024 Category: Allergy & Immunology Tags: Journal of Inflammation Research Source Type: research
Neuronal STING activation in amyotrophic lateral sclerosis and frontotemporal dementia
AbstractThe stimulator of interferon genes (STING) pathway has been implicated in neurodegenerative diseases, including Parkinson ’s disease and amyotrophic lateral sclerosis (ALS). While prior studies have focused on STING within immune cells, little is known about STING within neurons. Here, we document neuronal activation of the STING pathway in human postmortem cortical and spinal motor neurons from individuals affected by familial or sporadic ALS. This process takes place selectively in the most vulnerable cortical and spinal motor neurons but not in neurons that are less affected by the disease. Concordant STING a...
Source: Acta Neuropathologica - March 13, 2024 Category: Neurology Source Type: research
The activation of the adaptor protein STING depends on its interactions with the phospholipid PI4P
Sci Signal. 2024 Mar 12;17(827):eade3643. doi: 10.1126/scisignal.ade3643. Epub 2024 Mar 12.ABSTRACTActivation of the endoplasmic reticulum (ER)-resident adaptor protein STING, a component of a cytosolic DNA-sensing pathway, induces the transcription of genes encoding type I interferons (IFNs) and other proinflammatory factors. Because STING is activated at the Golgi apparatus, control of the localization and activation of STING is important in stimulating antiviral and antitumor immune responses. Through a genome-wide CRISPR interference screen, we found that STING activation required the Golgi-resident protein ACBD3, whic...
Source: Science Signaling - March 12, 2024 Category: Biomedical Science Authors: Rutger D Luteijn Sypke R van Terwisga Jill E Ver Eecke Liberty Onia Shivam A Zaver Joshua J Woodward Richard W Wubbolts David H Raulet Frank J M van Kuppeveld Source Type: research
DNA methylation landscapes in DIPG reveal methylome variability that can be modified pharmacologically
CONCLUSIONS: This study provides a resource for understanding the epigenetic instability that underlies DIPG heterogeneity. It suggests the application of epigenetic therapies to constrain the range of epigenetic states available to DIPG cells, as well as the use of decitabine in priming for immune-based therapies.PMID:38468866 | PMC:PMC10926944 | DOI:10.1093/noajnl/vdae023 (Source: Adv Data)
Source: Adv Data - March 12, 2024 Category: Epidemiology Authors: Ashley R Tetens Allison M Martin Antje Arnold Orlandi V Novak Adrian Idrizi Rakel Tryggvadottir Jordyn Craig-Schwartz Athanasia Liapodimitri Kayleigh Lunsford Michael I Barbato Charles G Eberhart Adam C Resnick Eric H Raabe Michael A Koldobskiy Source Type: research
Cytosolic DNA sensors in neurodegenerative diseases: from physiological defenders to pathological culprits
EMBO Mol Med. 2024 Mar 11. doi: 10.1038/s44321-024-00046-w. Online ahead of print.ABSTRACTCytosolic DNA sensors are a group of pattern recognition receptors (PRRs) that vary in structures, molecular mechanisms, and origins but share a common function to detect intracellular microbial DNA and trigger the innate immune response like type 1 interferon production and autophagy. Cytosolic DNA sensors have been proven as indispensable defenders against the invasion of many pathogens; however, growing evidence shows that self-DNA misplacement to cytoplasm also frequently occurs in non-infectious circumstances. Accumulation of cyt...
Source: Molecular Medicine - March 12, 2024 Category: Molecular Biology Authors: Jiatian Xie Jinping Cheng Ho Ko Yamei Tang Source Type: research
Tracing the STING exocytosis pathway during herpes viruses infection
mBio. 2024 Mar 12:e0037324. doi: 10.1128/mbio.00373-24. Online ahead of print.ABSTRACTThe STimulator of INterferon Genes (STING) constitutes a major DNA-sensing pathway that restricts HSV-1 infection in different models by activating type I interferon and pro-inflammatory responses. To counteract STING, HSV-1 has evolved numerous strategies including mechanisms to interfere with its oligomerization, post-translational modifications, and downstream signaling. Previously, we demonstrated that STING is packaged in extracellular vesicles (EVs) produced from HSV-1-infected cells. These EVs activated antiviral responses in uninf...
Source: Herpes - March 12, 2024 Category: Infectious Diseases Authors: Christos Dogrammatzis Rabina Saud Hope Waisner Sarah Lasnier Sreenath Muraleedharan Suma Brandon Grieshaber Maria Kalamvoki Source Type: research
The activation of the adaptor protein STING depends on its interactions with the phospholipid PI4P
Sci Signal. 2024 Mar 12;17(827):eade3643. doi: 10.1126/scisignal.ade3643. Epub 2024 Mar 12.ABSTRACTActivation of the endoplasmic reticulum (ER)-resident adaptor protein STING, a component of a cytosolic DNA-sensing pathway, induces the transcription of genes encoding type I interferons (IFNs) and other proinflammatory factors. Because STING is activated at the Golgi apparatus, control of the localization and activation of STING is important in stimulating antiviral and antitumor immune responses. Through a genome-wide CRISPR interference screen, we found that STING activation required the Golgi-resident protein ACBD3, whic...
Source: Science Signaling - March 12, 2024 Category: Biomedical Science Authors: Rutger D Luteijn Sypke R van Terwisga Jill E Ver Eecke Liberty Onia Shivam A Zaver Joshua J Woodward Richard W Wubbolts David H Raulet Frank J M van Kuppeveld Source Type: research
