Pathology, research and practice最新文献

Discovering potential therapeutic targets in glioblastoma multiforme using a multi-omics approach

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-03-29 DOI: 10.1016/j.prp.2025.155942

Mohammad Umar Saeed , Arunabh Choudhury , Jaoud Ansari , Taj Mohammad , Afzal Hussain , Urooj Fatima , Mohamed F. Alajmi , Md. Imtaiyaz Hassan

Background

Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor associated with high fatality rates, poor prognosis, and limited treatment options. In this study, we utilized RNA-Seq gene count data from GBM patients, sourced from the Gene Expression Omnibus (GEO) database, to conduct an in-depth analysis of gene expression patterns.

Methods

Our investigation involved stratifying samples into two distinct sets, Group I and Group II, comparing normal, low-grade, and GBM tumor samples, respectively. Subsequently, we performed differential expression analysis and enrichment analysis to uncover significant gene signatures. To elucidate the protein-protein interactions associated with GBM, we used the STRING plugin within Cytoscape for comprehensive network visualization and analysis.

Results

By applying Maximal clique centrality (MCC) scores, we identified a set of 10 hub genes in each group. These hub genes were subjected to survival analysis, highlighting their prognostic relevance. In Group I, comprising BUB1, DLGAP5, BUB1B, CDK1, TOP2A, CDC20, KIF20A, ASPM, BIRC5, and CCNB2, these genes emerged as potential biomarkers associated with the transition to low-grade tumors. In Group II, genes such as LIF, LBP, CSF3, IL6, CCL2, SAA1, CCL20, MMP9, CXCL10, and MMP1 were found to be involved in the transformation to adult glioblastoma. Kaplan–Meier's overall survival analysis of these hub genes revealed that modifications, particularly the upregulation of these candidate genes, were associated with reduced survival in GBM patients.

Conclusions

The findings established the significance of genomic alterations and differential gene expression in GBM, presenting opportunities for prognostic and targeted therapeutic interventions. This study provides valuable insights into potential avenues for enhancing the clinical management of GBM.

{"title":"Discovering potential therapeutic targets in glioblastoma multiforme using a multi-omics approach","authors":"Mohammad Umar Saeed , Arunabh Choudhury , Jaoud Ansari , Taj Mohammad , Afzal Hussain , Urooj Fatima , Mohamed F. Alajmi , Md. Imtaiyaz Hassan","doi":"10.1016/j.prp.2025.155942","DOIUrl":"10.1016/j.prp.2025.155942","url":null,"abstract":"<div><h3>Background</h3><div>Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor associated with high fatality rates, poor prognosis, and limited treatment options. In this study, we utilized RNA-Seq gene count data from GBM patients, sourced from the Gene Expression Omnibus (GEO) database, to conduct an in-depth analysis of gene expression patterns.</div></div><div><h3>Methods</h3><div>Our investigation involved stratifying samples into two distinct sets, Group I and Group II, comparing normal, low-grade, and GBM tumor samples, respectively. Subsequently, we performed differential expression analysis and enrichment analysis to uncover significant gene signatures. To elucidate the protein-protein interactions associated with GBM, we used the STRING plugin within Cytoscape for comprehensive network visualization and analysis.</div></div><div><h3>Results</h3><div>By applying Maximal clique centrality (MCC) scores, we identified a set of 10 hub genes in each group. These hub genes were subjected to survival analysis, highlighting their prognostic relevance. In Group I, comprising <em>BUB1, DLGAP5, BUB1B, CDK1, TOP2A, CDC20, KIF20A, ASPM, BIRC5,</em> and <em>CCNB2</em>, these genes emerged as potential biomarkers associated with the transition to low-grade tumors. In Group II, genes such as <em>LIF, LBP, CSF3, IL6, CCL2, SAA1, CCL20, MMP9, CXCL10,</em> and <em>MMP1</em> were found to be involved in the transformation to adult glioblastoma. Kaplan–Meier's overall survival analysis of these hub genes revealed that modifications, particularly the upregulation of these candidate genes, were associated with reduced survival in GBM patients.</div></div><div><h3>Conclusions</h3><div>The findings established the significance of genomic alterations and differential gene expression in GBM, presenting opportunities for prognostic and targeted therapeutic interventions. This study provides valuable insights into potential avenues for enhancing the clinical management of GBM.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155942"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic potential of phytocompounds in rheumatoid arthritis: Molecular insights and clinical applications

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-03-29 DOI: 10.1016/j.prp.2025.155945

Md. Zamshed Alam Begh , Mehrukh Zehravi , Faruk Reza , Sherouk Hussein Sweilam , Thukani Sathanantham Shanmugarajan , Uppuluri Varuna Naga Venkata Arjun , Kadirivel Devi , Susithra Ethiraj , V. Santhosh Kumar , E. Thilagam , Ali Audah Fahaid Al Fahaid , Safia Obaidur Rab , Sharuk L. Khan , Talha Bin Emran

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic involvement, inflammation, and the destruction of synovial joints. RA can be categorized as anti-citrullinated protein antibodies-positive or negative based on genetic risk factors and autoantibodies. This review systematically sourced articles related to RA, phytocompounds, signaling pathways, and clinical insights from primary medical databases, including Scopus, PubMed, and Web of Science. This review explores the therapeutic potential of phytocompounds in treating RA by targeting key inflammation and immunological response signaling pathways. Phytocompounds such as curcumin, resveratrol, and flavonoids alter essential molecular pathways in RA pathophysiology, including nuclear factor kappa-light-chain-enhancer of activated B cells, mitogen-activated protein kinases, janus kinase-signal transducer and activator of transcription, and the inflammasome. These substances possess pro-resolving, anti-apoptotic, and antioxidant properties, which enhance their therapeutic efficacy. Alternative medicine, including dietary, herbal, and nutritional supplements, may help reduce RA symptoms. In vitro, in vivo, and clinical studies have demonstrated the effectiveness of these treatments. Phytocompounds have potential as a treatment for RA by altering signaling pathways, reducing oxidative stress, and protecting cartilage and bone. However, few clinical trials confirm its long-term safety, bioavailability, and effectiveness. Further clinical trials and translational research are needed to validate the effectiveness, safety, and pharmacokinetics of phytocompounds, while identifying novel plant-derived bioactive chemicals could improve patient outcomes.

{"title":"Therapeutic potential of phytocompounds in rheumatoid arthritis: Molecular insights and clinical applications","authors":"Md. Zamshed Alam Begh , Mehrukh Zehravi , Faruk Reza , Sherouk Hussein Sweilam , Thukani Sathanantham Shanmugarajan , Uppuluri Varuna Naga Venkata Arjun , Kadirivel Devi , Susithra Ethiraj , V. Santhosh Kumar , E. Thilagam , Ali Audah Fahaid Al Fahaid , Safia Obaidur Rab , Sharuk L. Khan , Talha Bin Emran","doi":"10.1016/j.prp.2025.155945","DOIUrl":"10.1016/j.prp.2025.155945","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic involvement, inflammation, and the destruction of synovial joints. RA can be categorized as anti-citrullinated protein antibodies-positive or negative based on genetic risk factors and autoantibodies. This review systematically sourced articles related to RA, phytocompounds, signaling pathways, and clinical insights from primary medical databases, including Scopus, PubMed, and Web of Science. This review explores the therapeutic potential of phytocompounds in treating RA by targeting key inflammation and immunological response signaling pathways. Phytocompounds such as curcumin, resveratrol, and flavonoids alter essential molecular pathways in RA pathophysiology, including nuclear factor kappa-light-chain-enhancer of activated B cells, mitogen-activated protein kinases, janus kinase-signal transducer and activator of transcription, and the inflammasome. These substances possess pro-resolving, anti-apoptotic, and antioxidant properties, which enhance their therapeutic efficacy. Alternative medicine, including dietary, herbal, and nutritional supplements, may help reduce RA symptoms. In vitro, in vivo, and clinical studies have demonstrated the effectiveness of these treatments. Phytocompounds have potential as a treatment for RA by altering signaling pathways, reducing oxidative stress, and protecting cartilage and bone. However, few clinical trials confirm its long-term safety, bioavailability, and effectiveness. Further clinical trials and translational research are needed to validate the effectiveness, safety, and pharmacokinetics of phytocompounds, while identifying novel plant-derived bioactive chemicals could improve patient outcomes.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155945"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tumor-derived extracellular vesicles: Hijacking T cell function through exhaustion

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-03-29 DOI: 10.1016/j.prp.2025.155948

RuiJuan Guo, Ping Wang

Extracellular vesicles (EVs) play a vital role in intercellular communication within the tumor microenvironment (TME). These vesicles, secreted by tumor cells, contain proteins, lipids, and nucleic acids that significantly influence immune responses, particularly impacting T-cell function. In cancer, T cell dysfunction and exhaustion—marked by reduced proliferation, diminished cytokine production, and impaired cytotoxic activity—are key barriers to effective immune responses. Tumor-derived extracellular vesicles (TEVs) contribute to this dysfunction by carrying immunosuppressive molecules, such as transforming growth factor-beta (TGF-β) and various microRNAs (miRNAs). These TEV-mediated mechanisms promote T cell exhaustion and foster a broader immunosuppressive environment, enabling tumor progression and immune evasion. Furthermore, TEVs have been implicated in resistance to cancer immunotherapies, including immune checkpoint inhibitors and T cell therapies. Understanding the molecular pathways and cargoes within TEVs that drive T cell dysfunction is crucial for developing novel therapeutic strategies aimed at reinvigorating exhausted T cells, enhancing anti-tumor immunity, and improving cancer treatment outcomes.

{"title":"Tumor-derived extracellular vesicles: Hijacking T cell function through exhaustion","authors":"RuiJuan Guo, Ping Wang","doi":"10.1016/j.prp.2025.155948","DOIUrl":"10.1016/j.prp.2025.155948","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) play a vital role in intercellular communication within the tumor microenvironment (TME). These vesicles, secreted by tumor cells, contain proteins, lipids, and nucleic acids that significantly influence immune responses, particularly impacting T-cell function. In cancer, T cell dysfunction and exhaustion—marked by reduced proliferation, diminished cytokine production, and impaired cytotoxic activity—are key barriers to effective immune responses. Tumor-derived extracellular vesicles (TEVs) contribute to this dysfunction by carrying immunosuppressive molecules, such as transforming growth factor-beta (TGF-β) and various microRNAs (miRNAs). These TEV-mediated mechanisms promote T cell exhaustion and foster a broader immunosuppressive environment, enabling tumor progression and immune evasion. Furthermore, TEVs have been implicated in resistance to cancer immunotherapies, including immune checkpoint inhibitors and T cell therapies. Understanding the molecular pathways and cargoes within TEVs that drive T cell dysfunction is crucial for developing novel therapeutic strategies aimed at reinvigorating exhausted T cells, enhancing anti-tumor immunity, and improving cancer treatment outcomes.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155948"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The heart of the matter: How gut microbiota-targeted interventions influence cardiovascular diseases

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-03-29 DOI: 10.1016/j.prp.2025.155931

Mohammad Abavisani , Pourya Tafti , Niloofar Khoshroo , Negar Ebadpour , Alireza Khoshrou , Prashant Kesharwani , Amirhossein Sahebkar

The human body is habitat to a wide spectrum of microbial populations known as microbiota, which play an important role in overall health. The considerable research has mostly focused on the gut microbiota due to its potential to impact numerous physiological functions and its correlation with a variety of disorders, such as cardiovascular diseases (CVDs). Imbalances in the gut microbiota, known as dysbiosis, have been linked to the development and progression of CVDs through various processes, including the generation of metabolites like trimethylamine-N-oxide and short-chain fatty acids. Studies have also looked at the idea of using therapeutic interventions, like changing your diet, taking probiotics or prebiotics, or even fecal microbiota transplantation (FMT), to change the gut microbiota's make-up and how it works in order to prevent or treat CVDs. Exploring the cause-and-effect connection between the gut microbiota and CVDs offers a hopeful path for creating innovative microbiome-centered strategies to prevent and cure CVDs. This review presents an in-depth review of the correlation between the gut microbiota and CVDs, as well as potential therapeutic approaches for manipulating the gut microbiota to enhance cardiovascular health.

{"title":"The heart of the matter: How gut microbiota-targeted interventions influence cardiovascular diseases","authors":"Mohammad Abavisani , Pourya Tafti , Niloofar Khoshroo , Negar Ebadpour , Alireza Khoshrou , Prashant Kesharwani , Amirhossein Sahebkar","doi":"10.1016/j.prp.2025.155931","DOIUrl":"10.1016/j.prp.2025.155931","url":null,"abstract":"<div><div>The human body is habitat to a wide spectrum of microbial populations known as microbiota, which play an important role in overall health. The considerable research has mostly focused on the gut microbiota due to its potential to impact numerous physiological functions and its correlation with a variety of disorders, such as cardiovascular diseases (CVDs). Imbalances in the gut microbiota, known as dysbiosis, have been linked to the development and progression of CVDs through various processes, including the generation of metabolites like trimethylamine-N-oxide and short-chain fatty acids. Studies have also looked at the idea of using therapeutic interventions, like changing your diet, taking probiotics or prebiotics, or even fecal microbiota transplantation (FMT), to change the gut microbiota's make-up and how it works in order to prevent or treat CVDs. Exploring the cause-and-effect connection between the gut microbiota and CVDs offers a hopeful path for creating innovative microbiome-centered strategies to prevent and cure CVDs. This review presents an in-depth review of the correlation between the gut microbiota and CVDs, as well as potential therapeutic approaches for manipulating the gut microbiota to enhance cardiovascular health.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155931"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of endothelin and its receptors in cardiomyopathy: From molecular mechanisms to therapeutic insights

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-03-29 DOI: 10.1016/j.prp.2025.155932

Nandini Dubey , Aanchal Verma , Ahsas Goyal , Vishal Vishwakarma , Jagriti Bhatiya , Dharamvir Singh Arya , Harlokesh Narayan Yadav

Cardiomyopathy is an anatomical and pathologic condition that is related to the cardiac muscle or left ventricular failure. A diverse range of illnesses known as cardiomyopathies often result in progressive heart failure with high morbidity and death rates. Primary cardiomyopathies are hereditary, mixed, or adopted. Secondary cardiomyopathies are infiltrative, harmful, or pathogenic. The activation of many paracrine, autocrine, and neuroendocrine factors is closely linked to pathological left ventricular (LV) deformation. After the myocardial injury, in the context of higher LV wall pressure and haemodynamic disturbance, these variables are raised. New therapy techniques have been focused on these novel targets after recent studies revealed that endothelin, nitric oxide or cytokines may be implicated in the remodelling process. Vasoconstrictive peptide endothelin-1 (ET-1) is mostly generated in the endothelium and works by binding to the ETA- and ETB-endothelin receptors (ET-Rs). The expression of both ET-Rs is widespread in cardiac tissues. Heart failure, pulmonary arterial hypertension, hypertension, cardiomyopathy, and coronary artery disease are just a few of the cardiovascular disorders for which the endothelin system has been shown to play a crucial role over the years. The occurrence, pathogenesis, and natural history of endothelin antagonists in cardiomyopathies are currently not well understood, and specific aspects of their treatment responses have not received comprehensive attention. Therefore, in this study, we address the variable degrees of success that have been achieved in treating cardiomyopathy using endothelin-targeting treatments, such as endothelin receptor antagonists.

{"title":"The role of endothelin and its receptors in cardiomyopathy: From molecular mechanisms to therapeutic insights","authors":"Nandini Dubey , Aanchal Verma , Ahsas Goyal , Vishal Vishwakarma , Jagriti Bhatiya , Dharamvir Singh Arya , Harlokesh Narayan Yadav","doi":"10.1016/j.prp.2025.155932","DOIUrl":"10.1016/j.prp.2025.155932","url":null,"abstract":"<div><div>Cardiomyopathy is an anatomical and pathologic condition that is related to the cardiac muscle or left ventricular failure. A diverse range of illnesses known as cardiomyopathies often result in progressive heart failure with high morbidity and death rates. Primary cardiomyopathies are hereditary, mixed, or adopted. Secondary cardiomyopathies are infiltrative, harmful, or pathogenic. The activation of many paracrine, autocrine, and neuroendocrine factors is closely linked to pathological left ventricular (LV) deformation. After the myocardial injury, in the context of higher LV wall pressure and haemodynamic disturbance, these variables are raised. New therapy techniques have been focused on these novel targets after recent studies revealed that endothelin, nitric oxide or cytokines may be implicated in the remodelling process. Vasoconstrictive peptide endothelin-1 (ET-1) is mostly generated in the endothelium and works by binding to the ETA- and ETB-endothelin receptors (ET-Rs). The expression of both ET-Rs is widespread in cardiac tissues. Heart failure, pulmonary arterial hypertension, hypertension, cardiomyopathy, and coronary artery disease are just a few of the cardiovascular disorders for which the endothelin system has been shown to play a crucial role over the years. The occurrence, pathogenesis, and natural history of endothelin antagonists in cardiomyopathies are currently not well understood, and specific aspects of their treatment responses have not received comprehensive attention. Therefore, in this study, we address the variable degrees of success that have been achieved in treating cardiomyopathy using endothelin-targeting treatments, such as endothelin receptor antagonists.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155932"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recent developments in cuproptosis of glioblastoma

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-03-29 DOI: 10.1016/j.prp.2025.155939

Yajia Chen , Jingxian Zhang , Hongwu Xu

Glioblastoma (GBM) is the most malignant tumor within the central nervous system, attributed to its high-grade malignancy, propensity for recurrence, refractoriness to conventional therapeutic modalities, and the suboptimal efficacy of current targeted therapies. Hence, there is an urgent need to identify more efficacious molecular targets for the therapeutic intervention of GBM. The regulated cell death (RCD) has specific signaling factors and signaling pathways. Hence, targeting RCD is considered to be one of the effective targeted therapies for GBM. At present, cuproptosis is a novel form of RCD, characterized by a distinct molecular mechanism that differentiates it from apoptosis, pyroptosis, necroptosis, and ferroptosis. It is characterized by its principal mechanisms, which include copper dependency, the accumulation of acylated proteins, and the reduction of Fe-S cluster-containing proteins. These processes collectively induce proteotoxic stress, culminating in cell death. In previous studies, copper-ionized formulations have demonstrated cytotoxic effects on gliomas. Thus, the key factors of cuproptosis may be able to serve as a new target for GBM treatment. This review delves into several pivotal aspects, including the discovery of cuproptosis, the impact of copper homeostasis on tumorigenesis, the role of cuproptosis in GBM, and its potential as a therapeutic target in molecular targeted therapy for GBM. Hence, this article could reveal novel strategies for GBM treatment.

胶质母细胞瘤（GBM）是中枢神经系统中恶性程度最高的肿瘤，其特点是恶性程度高、易复发、对传统治疗方式耐受性差以及目前的靶向疗法疗效不佳。因此，亟需找到更有效的分子靶点来干预 GBM 的治疗。调节性细胞死亡（RCD）具有特定的信号因子和信号通路。因此，靶向 RCD 被认为是治疗 GBM 的有效靶向疗法之一。目前，杯状细胞凋亡（cuproptosis）是一种新型的调节性细胞死亡（RCD），其特点是具有不同于细胞凋亡、热凋亡、坏死和铁凋亡的分子机制。它的主要机制包括铜依赖性、酰化蛋白质的积累以及含 Fe-S 簇蛋白质的减少。这些过程共同诱发蛋白毒性应激，最终导致细胞死亡。在以往的研究中，铜离子化制剂对胶质瘤具有细胞毒性作用。因此，铜中毒的关键因素可能成为治疗脑胶质瘤的新靶点。这篇综述深入探讨了几个关键方面，包括铜氧化酶的发现、铜平衡对肿瘤发生的影响、铜氧化酶在 GBM 中的作用以及其作为 GBM 分子靶向治疗靶点的潜力。因此，这篇文章可以揭示治疗 GBM 的新策略。

{"title":"Recent developments in cuproptosis of glioblastoma","authors":"Yajia Chen , Jingxian Zhang , Hongwu Xu","doi":"10.1016/j.prp.2025.155939","DOIUrl":"10.1016/j.prp.2025.155939","url":null,"abstract":"<div><div>Glioblastoma (GBM) is the most malignant tumor within the central nervous system, attributed to its high-grade malignancy, propensity for recurrence, refractoriness to conventional therapeutic modalities, and the suboptimal efficacy of current targeted therapies. Hence, there is an urgent need to identify more efficacious molecular targets for the therapeutic intervention of GBM. The regulated cell death (RCD) has specific signaling factors and signaling pathways. Hence, targeting RCD is considered to be one of the effective targeted therapies for GBM. At present, cuproptosis is a novel form of RCD, characterized by a distinct molecular mechanism that differentiates it from apoptosis, pyroptosis, necroptosis, and ferroptosis. It is characterized by its principal mechanisms, which include copper dependency, the accumulation of acylated proteins, and the reduction of Fe-S cluster-containing proteins. These processes collectively induce proteotoxic stress, culminating in cell death. In previous studies, copper-ionized formulations have demonstrated cytotoxic effects on gliomas. Thus, the key factors of cuproptosis may be able to serve as a new target for GBM treatment. This review delves into several pivotal aspects, including the discovery of cuproptosis, the impact of copper homeostasis on tumorigenesis, the role of cuproptosis in GBM, and its potential as a therapeutic target in molecular targeted therapy for GBM. Hence, this article could reveal novel strategies for GBM treatment.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155939"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CAR T cells in lung cancer: Targeting tumor-associated antigens to revolutionize immunotherapy

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-03-29 DOI: 10.1016/j.prp.2025.155947

Sattam Khulaif Alenezi

Tumor-targeted T cells engineered for targeting and killing tumor cells have revolutionized cancer treatment, specifically in hematologic malignancies, through chimeric antigen receptor (CAR) T cell therapy. However, the migration of this success to lung cancer is challenging due to the tumor microenvironment (TME), antigen heterogeneity, and limitations of T cell infiltration. This review aims to evaluate current strategies addressing these barriers, focusing on the optimization of tumor-associated antigen (TAA) targeting, such as epidermal growth factor receptor (EGFR), mucin-1 (MUC1), and mesothelin (MSLN), which are frequently overexpressed in lung cancer and offer promising targets for CAR T-cell therapy. In this review, we discuss recent progress in CAR T cell engineering, applying enhanced costimulatory molecules, cytokine-secreting CAR T cells, and engineered modifications to improve T cell resilience in immunosuppressive environments. Additionally, this review also evaluates combination therapies of immune checkpoint inhibitors and recently published clinical trials on lung cancer with CAR T cells. We offer insights into the way to optimize CAR T cell therapy for lung cancer by analyzing antigen selection, immune evasion, and the strategies to enhance T cell persistence and tumor infiltration.

{"title":"CAR T cells in lung cancer: Targeting tumor-associated antigens to revolutionize immunotherapy","authors":"Sattam Khulaif Alenezi","doi":"10.1016/j.prp.2025.155947","DOIUrl":"10.1016/j.prp.2025.155947","url":null,"abstract":"<div><div>Tumor-targeted T cells engineered for targeting and killing tumor cells have revolutionized cancer treatment, specifically in hematologic malignancies, through chimeric antigen receptor (CAR) T cell therapy. However, the migration of this success to lung cancer is challenging due to the tumor microenvironment (TME), antigen heterogeneity, and limitations of T cell infiltration. This review aims to evaluate current strategies addressing these barriers, focusing on the optimization of tumor-associated antigen (TAA) targeting, such as epidermal growth factor receptor (EGFR), mucin-1 (MUC1), and mesothelin (MSLN), which are frequently overexpressed in lung cancer and offer promising targets for CAR T-cell therapy. In this review, we discuss recent progress in CAR T cell engineering, applying enhanced costimulatory molecules, cytokine-secreting CAR T cells, and engineered modifications to improve T cell resilience in immunosuppressive environments. Additionally, this review also evaluates combination therapies of immune checkpoint inhibitors and recently published clinical trials on lung cancer with CAR T cells. We offer insights into the way to optimize CAR T cell therapy for lung cancer by analyzing antigen selection, immune evasion, and the strategies to enhance T cell persistence and tumor infiltration.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155947"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Toll-like receptors in kidney ischemia-reperfusion injury: Modulating macrophage responses for therapeutic insights

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-03-29 DOI: 10.1016/j.prp.2025.155940

H. Malathi , Gaurav Khandelwal , S. Gayathri , Samir Sahoo , Swati Sharma

Kidney ischemia-reperfusion (I/R) injury is an acute clinical condition associated with inflammation and tissue damage during and after ischemia and reperfusion periods. In I/R injury, macrophages contribute to injury, and a family of proteins called toll-like receptors seem to have an immune modulatory role. When activated, TLRs initiate a series of signaling pathways, including MyD88 and TRIF. These pathways regulate the activation of tissue macrophages into either ‘classically activated’ M1 or ‘alternatively activated’ M2 phenotypes. Indeed, the relative abundance of these macrophage phenotypes defines the tissue injury level, which consequently requires reparative processes. The initial effector pro-inflammatory M1 macrophages aggravate tissue injury. Conversely, tissue reparative and anti-inflammatory M2 macrophages promote tissue repair and resolution—increased TLR signalling results in increased inflammation, prolonged healing and even renal failure. New evidence indicates that the change of macrophage responses through pharmacological targeting of the TLR pathways that regulate inflammation and tissue repair may have therapeutic implications. Some experimental treatment methods, in which early phases have been elaborated through experimental animal models, are TLR antagonists, small molecule inhibitors and nanotechnology-based delivery systems for Antisense oligonucleotide. Nevertheless, because the pathways regulated by TLRs and the subsets of macrophages are so countless and entangled, more extensive study is needed to provide more targeted actions. These findings shed light on the role and regulation of TLRs in macrophages during kidney I/R injury and investigate potential treatments with the potential to enhance care in this highly damaging condition.

{"title":"Toll-like receptors in kidney ischemia-reperfusion injury: Modulating macrophage responses for therapeutic insights","authors":"H. Malathi , Gaurav Khandelwal , S. Gayathri , Samir Sahoo , Swati Sharma","doi":"10.1016/j.prp.2025.155940","DOIUrl":"10.1016/j.prp.2025.155940","url":null,"abstract":"<div><div>Kidney ischemia-reperfusion (I/R) injury is an acute clinical condition associated with inflammation and tissue damage during and after ischemia and reperfusion periods. In I/R injury, macrophages contribute to injury, and a family of proteins called toll-like receptors seem to have an immune modulatory role. When activated, TLRs initiate a series of signaling pathways, including MyD88 and TRIF. These pathways regulate the activation of tissue macrophages into either ‘classically activated’ M1 or ‘alternatively activated’ M2 phenotypes. Indeed, the relative abundance of these macrophage phenotypes defines the tissue injury level, which consequently requires reparative processes. The initial effector pro-inflammatory M1 macrophages aggravate tissue injury. Conversely, tissue reparative and anti-inflammatory M2 macrophages promote tissue repair and resolution—increased TLR signalling results in increased inflammation, prolonged healing and even renal failure. New evidence indicates that the change of macrophage responses through pharmacological targeting of the TLR pathways that regulate inflammation and tissue repair may have therapeutic implications. Some experimental treatment methods, in which early phases have been elaborated through experimental animal models, are TLR antagonists, small molecule inhibitors and nanotechnology-based delivery systems for Antisense oligonucleotide. Nevertheless, because the pathways regulated by TLRs and the subsets of macrophages are so countless and entangled, more extensive study is needed to provide more targeted actions. These findings shed light on the role and regulation of TLRs in macrophages during kidney I/R injury and investigate potential treatments with the potential to enhance care in this highly damaging condition.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155940"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multiomics evaluation and machine learning optimize molecular classification, prediction of prognosis and immunotherapy response for ovarian cancer

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-03-29 DOI: 10.1016/j.prp.2025.155925

Fang Ren , Xiaoao Pang , Ning Liu, Liancheng Zhu

Background

Ovarian cancer (OC), owing to its substantial heterogeneity and high invasiveness, has historically been devoid of precise, individualized treatment options. This study aimed to establish integrated consensus subtypes of OC using different multiomics integration methodologies.

Methods

We integrated five distinct multiomics datasets from multicentric cohorts to identify high-resolution molecular subgroups using a combination of 10 and 101 clustering and machine learning algorithms, respectively, to develop a robust consensus multiomics-related machine learning signature (CMMS).

Results

Two cancer subtypes with prognostic significance were identified using multiomics clustering analysis. 10 essential genes were identified in the CMMS. Patients in the high CMMS group exhibited a poorer prognosis, with a “cold tumor” phenotype and an immunosuppressive state with reduced immune cell infiltration. In contrast, patients in the low CMMS group exhibited a more favorable prognosis, with immune activation and a “hot tumor" phenotype characterized by increased tumor mutation burden, tumor neoantigen burden, PD-L1 expression, and enriched M1 macrophages. Eight independent immunotherapy datasets were validated to further corroborate our findings regarding patients in the low CMMS group who responded better to immunotherapy.

Conclusions

CMMS detection has significant utility in the prognosis of patients at an early stage and identification of potential candidates for immunotherapy.

{"title":"Multiomics evaluation and machine learning optimize molecular classification, prediction of prognosis and immunotherapy response for ovarian cancer","authors":"Fang Ren , Xiaoao Pang , Ning Liu, Liancheng Zhu","doi":"10.1016/j.prp.2025.155925","DOIUrl":"10.1016/j.prp.2025.155925","url":null,"abstract":"<div><h3>Background</h3><div>Ovarian cancer (OC), owing to its substantial heterogeneity and high invasiveness, has historically been devoid of precise, individualized treatment options. This study aimed to establish integrated consensus subtypes of OC using different multiomics integration methodologies.</div></div><div><h3>Methods</h3><div>We integrated five distinct multiomics datasets from multicentric cohorts to identify high-resolution molecular subgroups using a combination of 10 and 101 clustering and machine learning algorithms, respectively, to develop a robust consensus multiomics-related machine learning signature (CMMS).</div></div><div><h3>Results</h3><div>Two cancer subtypes with prognostic significance were identified using multiomics clustering analysis. 10 essential genes were identified in the CMMS. Patients in the high CMMS group exhibited a poorer prognosis, with a “cold tumor” phenotype and an immunosuppressive state with reduced immune cell infiltration. In contrast, patients in the low CMMS group exhibited a more favorable prognosis, with immune activation and a “hot tumor\" phenotype characterized by increased tumor mutation burden, tumor neoantigen burden, PD-L1 expression, and enriched M1 macrophages. Eight independent immunotherapy datasets were validated to further corroborate our findings regarding patients in the low CMMS group who responded better to immunotherapy.</div></div><div><h3>Conclusions</h3><div>CMMS detection has significant utility in the prognosis of patients at an early stage and identification of potential candidates for immunotherapy.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155925"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel variation in the LMX1B gene with nail-patella syndrome

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2025-03-29 DOI: 10.1016/j.prp.2025.155936

Lu Zhang , Jilong Xiong , Hiu-Ming Li , Xia Li , Xuewen Yu , Yingying Liang , Huili Sun , ShuDong Yang , Mumin Shao

Nail-patella syndrome (NPS; OMIM #161200) is an autosomal dominant disorder characterized by developmental defects in dorsal limb structures, kidneys, and eyes. The incidence of NPS is attributed to variations in the LMX1B gene. In this report, we present a novel LMX1B variation identified in a Chinese family affected by NPS. The proband, a 15-year-old male, exhibited a history of proteinuria and microscopic hematuria accompanied by renal dysfunction, nail dysplasia, bilateral patellar dysplasia, bilateral shoulder and elbow joint dysplasia and iliac horns. Histological examination revealed mild glomerular lesions. Under electron microscopy, irregular thickening of the glomerular basement membrane was observed, characterized by an appearance resembling occasional electron lucent areas ("moth-eaten" appearance) and the presence of disorganized collagen fiber bundles. Pathological findings were consistent with NPS. Genetic analysis identified a novel heterozygous variant, c.791 A>C, p.(Gln264Pro), in the patient, his father and younger brother. This new variant has been annotated as potentially pathogenic according to the recommendation of the American Society for Medical Genetics and Genomics. This represents the first report of a novel variation in the LMX1B gene. These findings expand the spectrum of variations associated with LMX1B in NPS.

{"title":"A novel variation in the LMX1B gene with nail-patella syndrome","authors":"Lu Zhang , Jilong Xiong , Hiu-Ming Li , Xia Li , Xuewen Yu , Yingying Liang , Huili Sun , ShuDong Yang , Mumin Shao","doi":"10.1016/j.prp.2025.155936","DOIUrl":"10.1016/j.prp.2025.155936","url":null,"abstract":"<div><div>Nail-patella syndrome (NPS; OMIM #161200) is an autosomal dominant disorder characterized by developmental defects in dorsal limb structures, kidneys, and eyes. The incidence of NPS is attributed to variations in the <em>LMX1B</em> gene. In this report, we present a novel <em>LMX1B</em> variation identified in a Chinese family affected by NPS. The proband, a 15-year-old male, exhibited a history of proteinuria and microscopic hematuria accompanied by renal dysfunction, nail dysplasia, bilateral patellar dysplasia, bilateral shoulder and elbow joint dysplasia and iliac horns. Histological examination revealed mild glomerular lesions. Under electron microscopy, irregular thickening of the glomerular basement membrane was observed, characterized by an appearance resembling occasional electron lucent areas (\"moth-eaten\" appearance) and the presence of disorganized collagen fiber bundles. Pathological findings were consistent with NPS. Genetic analysis identified a novel heterozygous variant, c.791 A>C, p.(Gln264Pro), in the patient, his father and younger brother. This new variant has been annotated as potentially pathogenic according to the recommendation of the American Society for Medical Genetics and Genomics. This represents the first report of a novel variation in the <em>LMX1B</em> gene. These findings expand the spectrum of variations associated with <em>LMX1B</em> in NPS.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155936"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0