Biomarker Research最新文献

{"title":"Advances in CAR-T therapy for central nervous system tumors.","authors":"Delian Zhou, Xiaojian Zhu, Yi Xiao","doi":"10.1186/s40364-024-00679-6","DOIUrl":"10.1186/s40364-024-00679-6","url":null,"abstract":"<p><p>The application of chimeric antigen receptor T-cell therapy in central nervous system tumors has significantly advanced; however, challenges pertaining to the blood-brain barrier, immunosuppressive microenvironment, and antigenic heterogeneity continue to be encountered, unlike its success in hematological malignancies such as acute lymphoblastic leukemia and diffuse large B-cell lymphomas. This review examined the research progress of chimeric antigen receptor T-cell therapy in gliomas, medulloblastomas, and lymphohematopoietic tumors of the central nervous system, focusing on chimeric antigen receptor T-cells targeting antigens such as EGFRvIII, HER2, B7H3, GD2, and CD19 in preclinical and clinical studies. It synthesized current research findings to offer valuable insights for future chimeric antigen receptor T-cell therapeutic strategies for central nervous system tumors and advance the development and application of this therapeutic modality in this domain.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The double-edged role and therapeutic potential of TREM2 in atherosclerosis.","authors":"Botao Zhu, Yuxuan Liu, Daoquan Peng","doi":"10.1186/s40364-024-00675-w","DOIUrl":"10.1186/s40364-024-00675-w","url":null,"abstract":"<p><p>Atherosclerosis is a chronic lipid-driven inflammatory disease characterized by infiltration of large numbers of macrophages. The progression of the disease is closely related to the status of macrophages in atherosclerotic plaques. Recent advances in plaque analysis have revealed a subpopulation of macrophages that express high levels of triggering receptor expressed on myeloid cells 2 (TREM2). Although TREM2 is known to play a critical role in inflammation, lipid metabolism, and tissue repair, its role in atherosclerosis is still not fully understood. Recent studies have shown that TREM2 promotes macrophage cholesterol uptake and efflux, enhances efferocytosis function, regulates inflammation and metabolism, and promotes cell survival, all of which are significant functions in atherosclerosis. In early plaques TREM2 promotes lipid uptake and increases lesion size. In advanced plaques TREM2 promotes macrophage survival and increases plaque stability. The dualistic nature of TREM2 in atherosclerosis, where it can exert both protective effect and a side effect of increased lesion size, presents a complex but crucial area of study. Understanding these dual roles could help in the development of new therapeutic strategies to modulate TREM2 activity and utilize its atheroprotective function while mitigating its deleterious effects. In this review, we discuss the roles and mechanisms of TREM2 during different stages of atherosclerotic plaques, as well as the potential applications of TREM2 in the diagnosis and treatment of atherosclerosis.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11533605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142577393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper homeostasis and copper-induced cell death in tumor immunity: implications for therapeutic strategies in cancer immunotherapy.","authors":"Suhang Zhang, Qibo Huang, Tuo Ji, Qilin Li, Chuanyu Hu","doi":"10.1186/s40364-024-00677-8","DOIUrl":"10.1186/s40364-024-00677-8","url":null,"abstract":"<p><p>Copper is an important trace element for maintaining key biological functions such as cellular respiration, nerve conduction, and antioxidant defense. Maintaining copper homeostasis is critical for human health, and its imbalance has been linked to various diseases, especially cancer. Cuproptosis, a novel mechanism of copper-induced cell death, provides new therapeutic opportunities for metal ion regulation to interact with cell fate. This review provides insights into the complex mechanisms of copper metabolism, the molecular basis of cuproptosis, and its association with cancer development. We assess the role of cuproptosis-related genes (CRGs) associated with tumorigenesis, their importance as prognostic indicators and therapeutic targets, and the impact of copper homeostasis on the tumor microenvironment (TME) and immune response. Ultimately, this review highlights the complex interplay between copper, cuproptosis, and cancer immunotherapy.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancement in Multi-omics approaches for Uterine Sarcoma.","authors":"Wuyang Wang, Yu Hu, Fangfang Fu, Wu Ren, Tian Wang, Shixuan Wang, Yan Li","doi":"10.1186/s40364-024-00673-y","DOIUrl":"10.1186/s40364-024-00673-y","url":null,"abstract":"<p><p>Uterine sarcoma (US) is a rare malignant tumor that has various pathological types and high heterogeneity in the female reproductive system. Its subtle early symptoms, frequent recurrence, and resistance to radiation and chemotherapy make the prognosis for US patients very poor. Therefore, understanding the molecular mechanisms underlying tumorigenesis and progression is essential for an accurate diagnosis and targeted therapy to improve patient outcomes. Recent advancements in high-throughput molecular sequencing have allowed for a deeper understanding of diseases through multi-omics technologies. In this review, the latest progress and future potential of multi-omics technologies in US research is examined, and their roles in biomarker discovery and their application in the precise diagnosis and treatment of US are highlighted.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting NOX2 and glycolytic metabolism as a therapeutic strategy in acute myeloid leukaemia.","authors":"Carla Ijurko, Marta Romo-González, Rodrigo Prieto-Bermejo, María Díez-Campelo, María-Belén Vidriales, Sandra Muntión, Fermín Sánchez-Guijo, Jesús Sánchez-Yagüe, Ángel Hernández-Hernández","doi":"10.1186/s40364-024-00674-x","DOIUrl":"10.1186/s40364-024-00674-x","url":null,"abstract":"<p><p>Acute myeloid leukaemia (AML) is a highly heterogeneous malignancy, with a poor 5-year overall survival rate of approximately 30%. Consequently, the search for novel therapeutic strategies is ongoing, and the identification of new vulnerabilities could accelerate progress. Oxidative stress and metabolic rewiring are established hallmarks of cancer, and recent evidence suggests that NADPH oxidases may regulate metabolism, potentially linking these two processes. Increasing research highlights the importance of NOX2 in AML, particularly its role in metabolic regulation. In this study, we investigated the effects of simultaneously inhibiting NOX2 and glycolysis in AML cells. Dual inhibition of NOX2 and glycolysis-by targeting hexokinase or lactate dehydrogenase (LDH)-significantly reduced cell proliferation, markedly impaired clonogenic potential, and induced extensive cell death in a broad panel of AML cell lines. Importantly, these findings were further validated in primary bone marrow samples derived from AML patients, where combined inhibition triggered similar potent anti-leukemic effects. Furthermore, the combined inhibition of NOX2 and LDH enhanced the efficacy of cytarabine (AraC), suggesting this approach could boost the effectiveness of conventional therapies. In an in vivo AML model, targeting NOX2 and LDH in myeloid progenitor cells delayed the onset of leukaemia and extended survival. In conclusion, our findings propose a novel therapeutic strategy for AML through the dual targeting of NOX2 and glycolysis.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into the length and breadth of methodologies harnessed to study human telomeres.","authors":"Tiernan Coulter, Claire Hill, Amy Jayne McKnight","doi":"10.1186/s40364-024-00668-9","DOIUrl":"10.1186/s40364-024-00668-9","url":null,"abstract":"<p><p>Telomeres are protective structures at the end of eukaryotic chromosomes that are strongly implicated in ageing and ill health. They attrition upon every cellular reproductive cycle. Evidence suggests that short telomeres trigger DNA damage responses that lead to cellular senescence. Accurate methods for measuring telomeres are required to fully investigate the roles that shortening telomeres play in the biology of disease and human ageing. The last two decades have brought forth several techniques that are used for measuring telomeres. This editorial highlights strengths and limitations of traditional and emerging techniques, guiding researchers to choose the most appropriate methodology for their research needs. These methods include Quantitative Polymerase Chain Reaction (qPCR), Omega qPCR (Ω-qPCR), Terminal Restriction Fragment analysis (TRF), Single Telomere Absolute-length Rapid (STAR) assays, Single TElomere Length Analysis (STELA), TElomere Shortest Length Assays (TESLA), Telomere Combing Assays (TCA), and Long-Read Telomere Sequencing. Challenges include replicating telomere measurement within and across cohorts, measuring the length of telomeres on individual chromosomes, and standardised reporting for publications. Areas of current and future focus have been highlighted, with recent methodical advancements, such as long-read sequencing, providing significant scope to study telomeres at an individual chromosome level.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering LAG-3: unveiling molecular mechanisms and clinical advancements.","authors":"Alejandra Martínez-Pérez, Rocío Granda-Díaz, Candelaria Aguilar-García, Christian Sordo-Bahamonde, Segundo Gonzalez","doi":"10.1186/s40364-024-00671-0","DOIUrl":"10.1186/s40364-024-00671-0","url":null,"abstract":"<p><p>Treatment based on immune checkpoint blockade has revolutionized cancer therapy. Despite the remarkable success achieved and the preclinical development of multiple checkpoint inhibitors targeting other checkpoints, only antibodies targeting the PD-1/PD-L1 axis and CTLA-4 have been approved for patient treatment, especially in solid tumors. Currently, with the approval of relatlimab, a LAG-3 blocking antibody, a third player, has been used in the fight against cancer. The endorsement of relatlimab marks a significant milestone in cancer immunotherapy, opening new avenues for combination therapies and enhancing treatment outcomes. However, the complex biology of LAG-3 may hinder its full development as a therapeutic alternative. In this review, we provide in-depth insight into the biology of LAG-3 and its current and future development in cancer treatment.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive atlas of mitochondrial distribution and dynamics during oocyte maturation in mouse models.","authors":"Xia Hao, Jian Zhao, Kenny A Rodriguez-Wallberg","doi":"10.1186/s40364-024-00672-z","DOIUrl":"https://doi.org/10.1186/s40364-024-00672-z","url":null,"abstract":"<p><strong>Background: </strong>Oocytes, the largest cells in mammals, harbor numerous mitochondria within their cytoplasm. These highly dynamic organelles are crucial for providing energy resources and serving as central regulators during oogenesis. Mitochondrial dynamics ensure proper energy distribution for various cellular processes involved in oocyte maturation. Previous studies have used alterations in mitochondrial distribution as a biomarker to assess the oocyte health. However, there are discrepancies between studies regarding mitochondrial distribution profiles in healthy oocytes. Consequently, a comprehensive mitochondrial distribution profile in oocytes during maturation has not been fully characterized. Additionally, there is a lack of objective, quantitative methods to evaluate alterations in mitochondrial distribution profiles in oocytes.</p><p><strong>Methods: </strong>This study aims to provide an in-depth overview of mitochondrial distribution profiles in mouse oocytes at different maturation stages: germinal vesicle (GV) stage, metaphase I (MI), and mature metaphase II (MII). Freshly collected mouse GV, MI and MII oocytes were stained with MitoTracker Red. Confocal microscopy was used to obtain images of mitochondrial distribution profiles in these oocytes. Using the Imaris software, we reconstructed three-dimensional (3D) surface renderings of each oocyte and quantitatively illustrated the mitochondrial distribution profiles.</p><p><strong>Results: </strong>At the GV stage, mitochondria in oocytes were evenly distributed throughout the ooplasm. As oocytes progressed to MI and MII stages, mitochondria aggregated and formed clusters, the mean size of mitochondrial clusters and the proportions of clustered mitochondria increased along with the maturation of oocytes.</p><p><strong>Conclusions: </strong>Our findings reveal that mitochondria in mouse oocytes are highly dynamic, undergoing significant reorganizations during oocyte maturation. We for the first time provided comprehensive mitochondrial distribution profiles in mouse oocytes at the GV, MI and MII stages. These mitochondrial distribution profiles were further quantitatively evaluated. Our methods provide an objective and standardized approach for evaluating alterations in mitochondrial dynamics, which can be used as biomarkers to monitor oocyte conditions during maturation.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRD4 inhibitor reduces exhaustion and blocks terminal differentiation in CAR-T cells by modulating BATF and EGR1.","authors":"Songnan Sui, Mengjun Zhong, Shuxin Zhong, Xueting Peng, Lipeng Mao, Cunte Chen, Chengwu Zeng, Oscar Junhong Luo, Yangqiu Li","doi":"10.1186/s40364-024-00667-w","DOIUrl":"https://doi.org/10.1186/s40364-024-00667-w","url":null,"abstract":"<p><strong>Background: </strong>Exhaustion is a key factor that influences the efficacy of chimeric antigen receptor T (CAR-T) cells. Our previous study demonstrated that a bromodomain protein 4 (BRD4) inhibitor can revise the phenotype and function of exhausted T cells from leukemia patients. This study aims to elucidate the mechanism by which a BRD4 inhibitor reduces CAR-T cell exhaustion using single-cell RNA sequencing (scRNA-Seq).</p><p><strong>Methods: </strong>Exhausted CD123-specific CAR-T cells were prepared by co-culture with CD123 antigen-positive MV411 cells. After elimination of MV411 cells and upregulation of inhibitory receptors on the surface, exhausted CAR-T cells were treated with a BRD4 inhibitor (JQ1) for 72 h. The CAR-T cells were subsequently isolated, and scRNA-Seq was conducted to characterize phenotypic and functional changes in JQ1-treated cells.</p><p><strong>Results: </strong>Both the proportion of exhausted CD8⁺ CAR-T cells and the exhausted score of CAR-T cells decreased in JQ1-treated compared with control-treated cells. Moreover, JQ1 treatment led to a higher proportion of naïve, memory, and progenitor exhausted CD8⁺ CAR-T cells as opposed to terminal exhausted CD8⁺ CAR-T cells accompanied by enhanced proliferation, differentiation, and activation capacities. Additionally, with JQ1 treatment, BATF activity and expression in naïve, memory, and progenitor exhausted CD8⁺ CAR-T cells decreased, whereas EGR1 activity and expression increased. Interestingly, AML patients with higher EGR1 and EGR1 target gene ssGSEA scores, coupled with lower BATF and BATF target gene ssGSEA scores, had the best prognosis.</p><p><strong>Conclusions: </strong>Our study reveals that a BRD4 inhibitor can reduce CAR-T cell exhaustion and block exhausted T cell terminal differentiation by downregulating BATF activity and expression together with upregulating EGR1 activity and expression, presenting an approach for improving the effectiveness of CAR-T cell therapy.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The detection, biological function, and liquid biopsy application of extracellular vesicle-associated DNA.","authors":"Shan Guo, Xin Wang, Danni Shan, Yu Xiao, Lingao Ju, Yi Zhang, Gang Wang, Kaiyu Qian","doi":"10.1186/s40364-024-00661-2","DOIUrl":"https://doi.org/10.1186/s40364-024-00661-2","url":null,"abstract":"<p><p>Cell-derived extracellular vesicles (EVs), which carry diverse biomolecules such as nucleic acids, proteins, metabolites, and lipids reflecting their cell of origin, are released under both physiological and pathological conditions. EVs have been demonstrated to mediate cell-to-cell communication and serve as biomarkers. EV-associated DNA (EV-DNA) comprises genomic and mitochondrial DNA (i.e., gDNA and mtDNA) fragments. Some studies have revealed that EV-DNA can represent the full nuclear genome and mitochondrial genome of parental cells. Furthermore, DNA fragments loaded into EVs are stable and can be transferred to recipient cells to regulate their biological functions. In this review, we summarized and discussed EV-DNA research advances with an emphasis on EV-DNA detection at the population-EV and single-EV levels, gene transfer-associated biological functions, and clinical applications as biomarkers for disease liquid biopsy. We hope that this review will provide potential directions or guidance for future EV-DNA investigations.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}