Pub Date : 2023-12-21DOI: 10.46439/signaling.2.023
Sunil Palani, Keer Sun
{"title":"Commentary: Interferons in Influenza and Streptococcus Pneumoniae co-pathogenesis","authors":"Sunil Palani, Keer Sun","doi":"10.46439/signaling.2.023","DOIUrl":"https://doi.org/10.46439/signaling.2.023","url":null,"abstract":"","PeriodicalId":72543,"journal":{"name":"Cell signaling","volume":"57 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138950728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-21DOI: 10.46439/signaling.2.024
May-Lucie Meyer, Fred R. Hirsch
Targeting EGFR has a long history in the treatment of non-small cell lung cancer (NSCLC). It was around the 2000s that it was reported that EGFR protein expression increased with bronchial dysplasia in high-risk smokers and patients with lung cancer. However, EGFR inhibitors were not effective in unselected patients with advanced NSCLC. After the identification of sensitizing EGFR mutations, tyrosine kinase inhibitors became the cornerstone of treatment for patients with EGFR-mutated NSCLC. However, other drugs were developed to target EGFR in the EGFR-wild type population, such as monoclonal antibodies. Cetuximab is an anti-EGFR monoclonal antibody, and has been a focus over the past two decades. Though not approved in NSCLC due to marginal and inconsistent effects in phase 3 trials, research aimed to discover biomarkers to identify a subgroup of the population that might benefit. This includes a composite score that evaluates histology, immunohistochemistry, and gene copy amplification. This article reviews the history of the development and discontinuation of monoclonal antibodies in NSCLC and discusses the role of biomarkers in the treatment of advanced EGFR-wild type NSCLC.
{"title":"Biomarkers for monoclonal antibody targeting EGFR in NSCLC: Challenges, current status, and future perspectives","authors":"May-Lucie Meyer, Fred R. Hirsch","doi":"10.46439/signaling.2.024","DOIUrl":"https://doi.org/10.46439/signaling.2.024","url":null,"abstract":"Targeting EGFR has a long history in the treatment of non-small cell lung cancer (NSCLC). It was around the 2000s that it was reported that EGFR protein expression increased with bronchial dysplasia in high-risk smokers and patients with lung cancer. However, EGFR inhibitors were not effective in unselected patients with advanced NSCLC. After the identification of sensitizing EGFR mutations, tyrosine kinase inhibitors became the cornerstone of treatment for patients with EGFR-mutated NSCLC. However, other drugs were developed to target EGFR in the EGFR-wild type population, such as monoclonal antibodies. Cetuximab is an anti-EGFR monoclonal antibody, and has been a focus over the past two decades. Though not approved in NSCLC due to marginal and inconsistent effects in phase 3 trials, research aimed to discover biomarkers to identify a subgroup of the population that might benefit. This includes a composite score that evaluates histology, immunohistochemistry, and gene copy amplification. This article reviews the history of the development and discontinuation of monoclonal antibodies in NSCLC and discusses the role of biomarkers in the treatment of advanced EGFR-wild type NSCLC.","PeriodicalId":72543,"journal":{"name":"Cell signaling","volume":"135 49","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138953352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-21DOI: 10.46439/signaling.2.022
Yuyue Zuo, Yueqi Zhang, Lei Dai
Angiopoietin-like 4 (ANGPTL4) belongs to the angiopoietin-like protein family and mediates the inhibition of lipoprotein lipase activity. Emerging evidence suggests that ANGPTL4 has pleiotropic functions with anti- and pro-inflammatory properties. Here, we have reviewed the research progress on ANGPTL4 and systematically discussed the dual role of ANGPTL4 in inflammation and inflammatory diseases. Understanding the potential mechanisms of ANGPTL4 in inflammation will aid in drug discovery and treatment development.
{"title":"Friend or foe? The elusive role of ANGPTL4 in inflammation","authors":"Yuyue Zuo, Yueqi Zhang, Lei Dai","doi":"10.46439/signaling.2.022","DOIUrl":"https://doi.org/10.46439/signaling.2.022","url":null,"abstract":"Angiopoietin-like 4 (ANGPTL4) belongs to the angiopoietin-like protein family and mediates the inhibition of lipoprotein lipase activity. Emerging evidence suggests that ANGPTL4 has pleiotropic functions with anti- and pro-inflammatory properties. Here, we have reviewed the research progress on ANGPTL4 and systematically discussed the dual role of ANGPTL4 in inflammation and inflammatory diseases. Understanding the potential mechanisms of ANGPTL4 in inflammation will aid in drug discovery and treatment development.","PeriodicalId":72543,"journal":{"name":"Cell signaling","volume":"54 27","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138949525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-28DOI: 10.46439/signaling.1.020
Suridh Adhikari, A. Azhdarinia, M. Kolonin
Progression to metastases remains the overriding cause of cancer-associated mortality. Metastatic cancer is not amenable to surgery and its treatment is further complicated by the development of therapy resistance often observed at advanced cancer stages. Early detection of metastases is therefore critical but has been limited by the lack of probes that can effectively localize them. Similar challenges persist with therapeutics specifically targeting metastasized cancer cells. Thus, agents that specifically target disseminating tumor cells at an early stage could produce new theranostic applications and be transformative for the survival of patients with advanced cancers. Recent studies have described new approaches for early detection and targeted eradication of metastatic cancer. Here we summarize the results from preclinical validation of the experimental probes reported to date.
{"title":"Probes for cancer metastasis imaging and therapeutic targeting","authors":"Suridh Adhikari, A. Azhdarinia, M. Kolonin","doi":"10.46439/signaling.1.020","DOIUrl":"https://doi.org/10.46439/signaling.1.020","url":null,"abstract":"Progression to metastases remains the overriding cause of cancer-associated mortality. Metastatic cancer is not amenable to surgery and its treatment is further complicated by the development of therapy resistance often observed at advanced cancer stages. Early detection of metastases is therefore critical but has been limited by the lack of probes that can effectively localize them. Similar challenges persist with therapeutics specifically targeting metastasized cancer cells. Thus, agents that specifically target disseminating tumor cells at an early stage could produce new theranostic applications and be transformative for the survival of patients with advanced cancers. Recent studies have described new approaches for early detection and targeted eradication of metastatic cancer. Here we summarize the results from preclinical validation of the experimental probes reported to date.","PeriodicalId":72543,"journal":{"name":"Cell signaling","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139225021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-27DOI: 10.46439/signaling.1.019
Andrea Frustaci, R. Verardo, C. Chimenti
{"title":"Pathogenic contribute of unaffected cardiac cells in female Fabry cardiomyopathy","authors":"Andrea Frustaci, R. Verardo, C. Chimenti","doi":"10.46439/signaling.1.019","DOIUrl":"https://doi.org/10.46439/signaling.1.019","url":null,"abstract":"","PeriodicalId":72543,"journal":{"name":"Cell signaling","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139233306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-24DOI: 10.46439/signaling.1.017
Wen Su, Rong Cao, Qijun Wan, Hui-Yao Lan
Recent studies have shed light on the pivotal roles of estrogen in various pathophysiological processes related to kidney diseases. However, the precise mechanisms governing the estrogen actions remain enigmatic. The downstream impacts of estrogen primarily hinge on estrogen receptors (ERs), namely ERα (NR3A1) and ERβ (NR3A2). Building upon our previous finding that ERβ participates in subcutaneous adipose tissue browning in female mice, our recent study found that ERβ functions to protect kidney from progressive renal fibrosis by inactivating transforming growth factor-β (TGF-β)/Smad3 signaling. In the normal kidney, ERβ is highly expressed by proximal tubular epithelial cells but it is lost when kidney becomes fibrotic. In contrast, activation of ERβ inhibits kidney fibrosis. Mechanistically, we uncovered that ERβ can bind to Smad3, thereby transcriptionally downregulating Smad3 and inhibiting TGF-β1/Smad3-mediated renal fibrosis. Thus, ERβ is protective in renal fibrosis and may have therapeutic potential for chronic kidney disease.
{"title":"Commentary: Role of estrogen receptor β in kidney disease","authors":"Wen Su, Rong Cao, Qijun Wan, Hui-Yao Lan","doi":"10.46439/signaling.1.017","DOIUrl":"https://doi.org/10.46439/signaling.1.017","url":null,"abstract":"Recent studies have shed light on the pivotal roles of estrogen in various pathophysiological processes related to kidney diseases. However, the precise mechanisms governing the estrogen actions remain enigmatic. The downstream impacts of estrogen primarily hinge on estrogen receptors (ERs), namely ERα (NR3A1) and ERβ (NR3A2). Building upon our previous finding that ERβ participates in subcutaneous adipose tissue browning in female mice, our recent study found that ERβ functions to protect kidney from progressive renal fibrosis by inactivating transforming growth factor-β (TGF-β)/Smad3 signaling. In the normal kidney, ERβ is highly expressed by proximal tubular epithelial cells but it is lost when kidney becomes fibrotic. In contrast, activation of ERβ inhibits kidney fibrosis. Mechanistically, we uncovered that ERβ can bind to Smad3, thereby transcriptionally downregulating Smad3 and inhibiting TGF-β1/Smad3-mediated renal fibrosis. Thus, ERβ is protective in renal fibrosis and may have therapeutic potential for chronic kidney disease.","PeriodicalId":72543,"journal":{"name":"Cell signaling","volume":"26 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139241934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-17DOI: 10.46439/signaling.1.015
Wenyu Li, Liuqing Wang, Youjun Wang, Lian He
Optogenetic-based genetically encoded Ca2+ actuators (GECA) have been developed to enable remote control of Ca2+ entry into cells. However, current blue light-dependent tools either lack high calcium selectivity or exhibit crosstalk with other targets, raising concerns about potential side effects. In this commentary, we present our successful design of a single-component optogenetic Ca2+ ion channel (LOCa) that selectively elevates cytoplasmic Ca2+ concentration with high spatial and temporal resolution. Furthermore, LOCa has demonstrated promising applications in regulating Ca2+-dependent cellular physiological responses and investigating diseases through animal models.
{"title":"Development of an authentic light-activated calcium channel","authors":"Wenyu Li, Liuqing Wang, Youjun Wang, Lian He","doi":"10.46439/signaling.1.015","DOIUrl":"https://doi.org/10.46439/signaling.1.015","url":null,"abstract":"Optogenetic-based genetically encoded Ca2+ actuators (GECA) have been developed to enable remote control of Ca2+ entry into cells. However, current blue light-dependent tools either lack high calcium selectivity or exhibit crosstalk with other targets, raising concerns about potential side effects. In this commentary, we present our successful design of a single-component optogenetic Ca2+ ion channel (LOCa) that selectively elevates cytoplasmic Ca2+ concentration with high spatial and temporal resolution. Furthermore, LOCa has demonstrated promising applications in regulating Ca2+-dependent cellular physiological responses and investigating diseases through animal models.","PeriodicalId":72543,"journal":{"name":"Cell signaling","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139317889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-03DOI: 10.46439/signaling.1.014
Li Tan, Juan Ren
The prognosis of brain metastases in non-small cell lung cancer (NSCLC) is poor, and patients with EGFR mutations are more likely to have brain metastases. The epidermal growth factor receptor (EGFR) gene status has changed the direction of treatment for NSCLC patients with brain metastases. The development of EGFR tyrosine kinase inhibitors (EGFR-TKI) has prolonged the survival time of NSCLC patients with brain metastases. The treatment of patients with NSCLC brain metastases should be individualized according to the clinical symptoms, tumor stage, and different gene mutation status. As cancer is heterogeneous at the molecular level, related biomarker studies looking for individualized characteristics are recommended.
{"title":"The value of EGFR in individualized treatment for brain metastases in non-small cell lung cancer","authors":"Li Tan, Juan Ren","doi":"10.46439/signaling.1.014","DOIUrl":"https://doi.org/10.46439/signaling.1.014","url":null,"abstract":"The prognosis of brain metastases in non-small cell lung cancer (NSCLC) is poor, and patients with EGFR mutations are more likely to have brain metastases. The epidermal growth factor receptor (EGFR) gene status has changed the direction of treatment for NSCLC patients with brain metastases. The development of EGFR tyrosine kinase inhibitors (EGFR-TKI) has prolonged the survival time of NSCLC patients with brain metastases. The treatment of patients with NSCLC brain metastases should be individualized according to the clinical symptoms, tumor stage, and different gene mutation status. As cancer is heterogeneous at the molecular level, related biomarker studies looking for individualized characteristics are recommended.","PeriodicalId":72543,"journal":{"name":"Cell signaling","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135738759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-03DOI: 10.46439/signaling.1.012
Chenghua Luo, Dengyu Ji, Wen Wang
{"title":"A vicious cycle happened in the progress of hyperhomocysteinemia, the same may exist in the development of cancer","authors":"Chenghua Luo, Dengyu Ji, Wen Wang","doi":"10.46439/signaling.1.012","DOIUrl":"https://doi.org/10.46439/signaling.1.012","url":null,"abstract":"","PeriodicalId":72543,"journal":{"name":"Cell signaling","volume":"78 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135695983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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