Pathology, research and practice最新文献_第6页

EZH2 regulatory roles in cancer immunity and immunotherapy EZH2在肿瘤免疫和免疫治疗中的调节作用

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-04-28 DOI: 10.1016/j.prp.2025.155992

Keywan Mortezaee

{"title":"EZH2 regulatory roles in cancer immunity and immunotherapy","authors":"Keywan Mortezaee","doi":"10.1016/j.prp.2025.155992","DOIUrl":"10.1016/j.prp.2025.155992","url":null,"abstract":"<div><div>Enhancer of zeste homolog 2 (EZH2) is a polycomb repressor complex 2 (PRC2) subunit that is responsible for silencing expression of target genes through generation of lysine 27 trimethylation on histone H3 (H3K27Me3). EZH2 is an oncogene aberrantly expressed in human cancers, and its overexpression favors immune escape and metastasis. Immune escape occurs via the impact of EZH2 on hampering antigen expression machinery, stabilizing FOXP3 in regulatory T cells (Tregs), inhibiting recruitment and activity of natural killer (NK) and CD8<sup>+</sup> T cells, and inducing recruitment and activity of myeloid-derived suppressor cells (MDSCs). Besides, EZH2 also promotes intra-tumoral recruitment of tumor-associated macrophages (TAMs). A point is that pharmacologic EZH2 inhibition (not knockdown) seemingly promotes polarization of macrophages toward pro-tumor M2 phenotype, which defines resistance mechanism. Besides, increased EZH2 expression after anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and a rise in the tumoral expression of programmed death-ligand 1 (PD-L1) after EZH2 inhibition account for secondary immunosuppression in tumor ecosystem after immunotherapy, indicating the applicability of using EZH2 targeted therapies as a combinatory approach with anti-programmed death-1 (PD-1) or anti-CTLA-4 therapy. Such combination reinvigorates anti-tumor immunity and presumably hampers T cell exhaustion and acting as a promising regimen for retarding cancer growth.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155992"},"PeriodicalIF":2.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886146","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 combined diagnostic value of 5-hmC and PRAME immunohistochemistry in melanocytic neoplasms 5-hmC与PRAME免疫组化在黑色素细胞肿瘤中的联合诊断价值

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-04-27 DOI: 10.1016/j.prp.2025.155993

Yanhong Yu , Niloufar Hosseini , David Dodington , Kimberly Wood , Danny Ghazarian , Zaid Saeed Kamil

{"title":"The combined diagnostic value of 5-hmC and PRAME immunohistochemistry in melanocytic neoplasms","authors":"Yanhong Yu , Niloufar Hosseini , David Dodington , Kimberly Wood , Danny Ghazarian , Zaid Saeed Kamil","doi":"10.1016/j.prp.2025.155993","DOIUrl":"10.1016/j.prp.2025.155993","url":null,"abstract":"<div><div>The diagnosis of melanocytic neoplasms, particularly those with borderline morphologic features, remains a challenging area in dermatopathology. 5-hydroxymethylcytosine (5-hmC) and PRAME (PReferentially expressed Antigen in MElanoma) are recent immunohistochemical markers which have been shown to be valuable in distinguishing benign from malignant melanocytic neoplasms. A retrospective cohort of 144 benign, borderline (Spitz nevi, atypical Spitz tumors and dysplastic nevi) and malignant melanocytic tumors at our institution were analyzed for 5-hmC and PRAME expression by immunohistochemistry. Compared to benign nevi, melanoma cases had higher PRAME expression (p < 0.0001) and lower 5-hmC (p < 0.0001) expression. In receiver operator curve analysis, 5-hmC and PRAME were good discriminators between benign and malignant neoplasms; the area under the curve (AUC) was 0.91 for 5-hmC (p < 0.0001) and 0.94 for PRAME (p < 0.001). Subgroup analysis showed that 5-hmC expression was significantly different between dysplastic nevi and melanoma. The combination of PRAME and 5-hmC significantly improved the predictive ability of these markers (AUC 0.97, p < 0.001). Having both PRAME expression of 4 + (> 75 % lesional cells positive) and 5-hmC of < 0.2 was highly specific for malignancy (98 %) with a sensitivity of 61 %. Utilizing 5-hmC and PRAME in conjunction improves their diagnostic value in distinguishing benign from malignant melanocytic neoplasms.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155993"},"PeriodicalIF":2.9,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905912","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 clinicopathological characteristics of co-mutations in exon 2 and 3 of the KRAS gene in patients with colorectal cancer 结直肠癌患者KRAS基因外显子2、3共突变的临床病理特征

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-04-24 DOI: 10.1016/j.prp.2025.155990

Huizhen Peng, Hongtian Yao, Xiaojun Jiang, Huijuan Zhu, Jun Li, Hui Tang

{"title":"The clinicopathological characteristics of co-mutations in exon 2 and 3 of the KRAS gene in patients with colorectal cancer","authors":"Huizhen Peng, Hongtian Yao, Xiaojun Jiang, Huijuan Zhu, Jun Li, Hui Tang","doi":"10.1016/j.prp.2025.155990","DOIUrl":"10.1016/j.prp.2025.155990","url":null,"abstract":"<div><div><em>KRAS,</em> one of the most frequently mutated oncogenes in colorectal cancer (CRC), with mutations in approximately 40 % of all CRC cases. <em>KRAS</em> mutations exhibit considerable diversity. Studies have shown that patients with mutations at codon 13 (G13) of the <em>KRAS</em> gene have a higher risk of mortality, while mutations at codon 12 (G12) of the <em>KRAS</em> gene are also associated with prognosis, though their impact on mortality risk is lower than that of codon 13 mutations. Therefore, identifying the specific <em>KRAS</em> mutation type is crucial for assessing patient prognosis and developing personalized treatment plans. <em>KRAS</em> mutations typically occur in a single exon, whereas co-mutations in exon 2 (G12/G13) and exon 3 (Q61) in a single tissue haven’t been reported yet. In this study, we reported a co-mutation in two exons (exon 2 and exon 3) of the <em>KRAS</em> gene in a 72-year-old male with CRC, adenocarcinoma located at 8 cm from the anus. NGS and ARMS-PCR revealed that two exons of <em>KRAS</em> were co-mutated in this patient-- Q61H in exon 3, with a mutation frequency of 21.09 % and G13D in exon 2, with a variance frequency of 6.06 %. A copy number increase (copy number: 5.65) in <em>MET</em> gene was also found in this patient simultaneously. The clinicopathological characteristics were analyzed, and the possible mechanisms were further discussed. However, due to the CRC patients with co-mutations in two exons of the <em>KRAS</em> are exceedingly rare, a cohort study with more patients’ clinical data is urged.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155990"},"PeriodicalIF":2.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873477","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

Defining molecular signatures of the solid/pseudopapillary and pseudoglandular patterns in so-called “solid-tubulocystic intrahepatic cholangiocarcinoma vs. NIPBL::NACC1 fusion hepatic carcinoma” 在所谓的“固体小管囊性肝内胆管癌与NIPBL::NACC1融合肝癌”中定义实性/假乳头状和假腺状模式的分子特征

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-04-23 DOI: 10.1016/j.prp.2025.155962

Prachi Bajpai , Fatme Ghandour , Ekta Jain , Raima Memon , Chirag R. Patel , Santhosh Kumar Karthikeyan , Sankarasubramanian Jagadesan , Babu Guda , Farrukh Afaq , Amr Elkholy , Sooryanarayana Varambally , Upender Manne , Sameer Al Diffalha

{"title":"Defining molecular signatures of the solid/pseudopapillary and pseudoglandular patterns in so-called “solid-tubulocystic intrahepatic cholangiocarcinoma vs. NIPBL::NACC1 fusion hepatic carcinoma”","authors":"Prachi Bajpai , Fatme Ghandour , Ekta Jain , Raima Memon , Chirag R. Patel , Santhosh Kumar Karthikeyan , Sankarasubramanian Jagadesan , Babu Guda , Farrukh Afaq , Amr Elkholy , Sooryanarayana Varambally , Upender Manne , Sameer Al Diffalha","doi":"10.1016/j.prp.2025.155962","DOIUrl":"10.1016/j.prp.2025.155962","url":null,"abstract":"<div><div>Solid-tubulocystic variant of intrahepatic cholangiocarcinoma (ST-iCCA) is newly described entity characterized by two distinct histologic growth patterns: (1) solid sheets of tumor cells with focal necrosis giving pseudopapillary appearance and (2) tubular or pseudoglandular structures containing pink, colloid-like material. Tumor cells are inhibin-positive and harbor <em>NIPBL::NACC1</em> fusion gene. To date, only 28 cases of ST-iCCA have been documented. While prior molecular studies provided insights into ST-iCCA, genetic profiles of individual histologic components have not been explored. This study presents first transcriptomic analysis comparing the solid/pseudopapillary and pseudoglandular components of ST-iCCA. Two cases of histologically confirmed ST-iCCA were identified for RNA sequencing which was performed on solid/pseudopapillary component, pseudoglandular component, and normal tissue. Analysis revealed distinct gene expression profiles for each pattern. Solid/pseudopapillary component uniquely overexpressed <em>DMRTA1, NEXMIF, PRDM6, SORCS3,</em> and <em>NALF,</em> while pseudoglandular component exhibited unique overexpression of HRG<em>, ITIH3, TAT, APOA2, CP, ALDOB, CPS1, F2, KHG1, SERPINC1, HPX, C9, ADGRF1, MUC21, SAA2, SPRR2A, SAA1, FGL1, CFHR1,</em> and <em>LBP.</em> These findings establish unique gene signatures for these variants of ST-iCCA, providing potential biomarkers for differential diagnosis, prognosis and targeted therapy. The distinct genetic profiles may also uncover novel therapeutic targets to address the aggressive nature of ST-iCCA.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155962"},"PeriodicalIF":2.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143867798","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 critical role of GLP-1 signaling pathways in the pathology of Parkinson's disease and diabetes GLP-1信号通路在帕金森病和糖尿病病理中的关键作用

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-04-22 DOI: 10.1016/j.prp.2025.155985

Jinhao Chen , Xiang Dong , Yichen Lin , Cunming Lv

{"title":"The critical role of GLP-1 signaling pathways in the pathology of Parkinson's disease and diabetes","authors":"Jinhao Chen , Xiang Dong , Yichen Lin , Cunming Lv","doi":"10.1016/j.prp.2025.155985","DOIUrl":"10.1016/j.prp.2025.155985","url":null,"abstract":"<div><div>This review assesses the roles of GLP-1 and its receptor agonists (GLP-1RAs) in the treatment of diabetes and Parkinson’s disease, integrating current theories and research. GLP-1, a vital endogenous hormone, regulates insulin secretion, delays gastric emptying, and promotes satiety, showing significant potential for diabetes management. However, its brief lifespan and restricted blood-brain barrier penetration limit its clinical application. To overcome these constraints, researchers have developed GLP-1 receptor agonists that prolong its action and exhibit high efficacy in diabetes treatment. Recent studies further reveal GLP-1’s neuroprotective effects, notably its potential in managing neurodegenerative disorders such as Parkinson’s disease. GLP-1RAs mitigate neuroinflammation, reduce oxidative stress, and enhance neuroprotection, suggesting substantial potential for treating neurodegenerative diseases. Additionally, to enhance GLP-1RAs’ efficacy in the nervous system, researchers have introduced novel drug delivery approaches, including nanoparticle carriers and molecular modifications, to improve stability and targeting accuracy. In conclusion, this review comprehensively analyzes the mechanisms, clinical applications, and challenges of GLP-1 and its receptor agonists in managing diabetes and Parkinson’s disease, while identifying future research and clinical opportunities.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155985"},"PeriodicalIF":2.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143867794","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

Role of extracellular vesicles in the pathophysiology, diagnosis, and prognosis of gynecological cancers 细胞外囊泡在妇科癌症的病理生理、诊断和预后中的作用

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-04-22 DOI: 10.1016/j.prp.2025.155987

Treena Rica D. Teh , Von Novi O. de Leon , Ourlad Alzeus G. Tantengco

{"title":"Role of extracellular vesicles in the pathophysiology, diagnosis, and prognosis of gynecological cancers","authors":"Treena Rica D. Teh , Von Novi O. de Leon , Ourlad Alzeus G. Tantengco","doi":"10.1016/j.prp.2025.155987","DOIUrl":"10.1016/j.prp.2025.155987","url":null,"abstract":"<div><div>Gynecological cancers account for one-sixth of disability-adjusted life years of women with malignancies. The burden of these diseases is more remarkable in low- and middle-income countries with limited access to human papillomavirus vaccines. Thus, early diagnosis and prompt treatment are vital in disease management. In connection, extracellular vesicles (EVs) are gaining traction in tumor biology. Biomolecular cargoes within EVs can be nucleic acids, proteins, or lipids that can reflect the biological state of the cell from which they are derived such as cancer cells, and consequently the influence of cancer cells to recipients including cancer and non-cancer cells. Combining this with the stability and detectability of EVs in biological samples, EVs present potential utility in the diagnosis and prognostic monitoring of gynecological malignancies. Therefore, this review discusses the role of extracellular vesicles in the pathophysiology of cervical, uterine, and ovarian cancers, and how these roles are exploited in the diagnosis and prognosis of patients with these malignancies through the presentation of evidence from in vitro, in vivo, and clinical studies.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155987"},"PeriodicalIF":2.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873476","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 application of direct immunofluorescence in the pathological diagnosis of oral mucosal diseases: Series of 116 cases 直接免疫荧光在口腔黏膜疾病病理诊断中的应用116例

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-04-22 DOI: 10.1016/j.prp.2025.155989

Yi Xu , Xiaotong He , Weiping Jie , Shidong Liu , Ji-an Hu , Yining Li

{"title":"The application of direct immunofluorescence in the pathological diagnosis of oral mucosal diseases: Series of 116 cases","authors":"Yi Xu , Xiaotong He , Weiping Jie , Shidong Liu , Ji-an Hu , Yining Li","doi":"10.1016/j.prp.2025.155989","DOIUrl":"10.1016/j.prp.2025.155989","url":null,"abstract":"<div><div>This study evaluated the diagnostic utility of direct immunofluorescence (DIF) in 116 oral mucosal bullous and atrophic lesions from Zhejiang University Stomatology Hospital (2022–2024). DIF and H&E analyses were performed on serial sections of the same biopsy specimens. Among the cases, 45 were diagnosed with pemphigus vulgaris, in which DIF revealed a reticular pattern of IgG (84.44 %) and C3 (73.33 %) deposition within the epithelial prickle cell layer. Benign mucous membrane pemphigoid was identified in 23 cases, characterized by linear deposits of IgG (56.52 %) and C3 (73.91 %) along the basement membrane zone (BMZ), with occasional expression of IgA (34.78 %) and IgM (17.39 %). In 14 cases of oral lichen planus, DIF demonstrated positive fibrinogen deposition in the BMZ (57.14 %), while IgA, IgG, IgM, and C3 were either weakly expressed or absent. 4 cases of chronic discoid lupus erythematosus exhibited granular deposits of IgG (100 %), sometimes accompanied by IgA, IgM, C3, and fibrinogen in the BMZ and perivascular. One case of linear IgA bullous dermatosis showed exclusive linear IgA deposition in the BMZ, with no detectable IgG, IgM, C3, or fibrinogen. DIF demonstrates significant clinical value in the diagnosis of atrophic and bullous lesions, particularly in pemphigus and lichen planus. The combination of IgG, C3 and fibrinogen may be economical and effective approach.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155989"},"PeriodicalIF":2.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878977","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

Epigenetic and post-translational modifications in ferroptosis regulation and hepatocellular carcinoma: New frontiers in therapeutic targeting 铁下垂调节和肝细胞癌的表观遗传和翻译后修饰：治疗靶向的新领域

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-04-22 DOI: 10.1016/j.prp.2025.155991

Soheil Bolandi , Samaneh Dodge , Zahra Zahed , Anvar Soleimani , Khaterehsadat Monirvaghefi , Mahshid Ghodsifar , Moein Ghasemi , Nahal Aghajamal avval , Seyedeh Sahar Mojtaba Zadeh , Seyed Mohammad Ali Fazayel , Reza Morovatshoar , Vahid Barfi , Qumars Behfar , Sima Dehghani

{"title":"Epigenetic and post-translational modifications in ferroptosis regulation and hepatocellular carcinoma: New frontiers in therapeutic targeting","authors":"Soheil Bolandi , Samaneh Dodge , Zahra Zahed , Anvar Soleimani , Khaterehsadat Monirvaghefi , Mahshid Ghodsifar , Moein Ghasemi , Nahal Aghajamal avval , Seyedeh Sahar Mojtaba Zadeh , Seyed Mohammad Ali Fazayel , Reza Morovatshoar , Vahid Barfi , Qumars Behfar , Sima Dehghani","doi":"10.1016/j.prp.2025.155991","DOIUrl":"10.1016/j.prp.2025.155991","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC), the predominant kind of liver cancer, continues to be a significant contributor to cancer-related deaths globally, influenced by intricate molecular processes and strong resistance to existing chemotherapy. Iron-dependent lipid peroxidation induces ferroptosis, a controlled form of cell death that plays a crucial role in inhibiting tumor growth and treatment resistance in HCC. Recent research has shown that epigenetic modifications, such as DNA methylation, histone modifications, regulation by non-coding RNAs (ncRNAs), and post-translational modification (PTM) like ubiquitination, phosphorylation, acetylation, and methylation, play a crucial role in fine-tuning ferroptosis. These alterations alter the structure of chromatin, gene expression, and protein function, thereby affecting cancer cells' fate. This review emphasizes the complex functions of epigenetic and post-translational alterations in controlling ferroptosis, providing valuable insights into their potential as therapeutic targets in HCC. The unraveling of these pathways offers a significant opportunity for novel therapies targeted at surmounting drug resistance and enhancing patient outcomes in liver cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155991"},"PeriodicalIF":2.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886144","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 advances in the delivery of microRNAs via exosomes derived from MSCs, and their role in regulation of ferroptosis 通过MSCs衍生的外泌体传递microrna的最新进展及其在铁凋亡调节中的作用

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-04-21 DOI: 10.1016/j.prp.2025.155984

Mohamed J. Saadh , Hanan Hassan Ahmed , Gaurav Sanghvi , Mohd Zaki Bin Awang Isa , Priyanka Singh , Kiranjeet Kaur , M.Ravi Kumar , Beneen Husseen

{"title":"Recent advances in the delivery of microRNAs via exosomes derived from MSCs, and their role in regulation of ferroptosis","authors":"Mohamed J. Saadh , Hanan Hassan Ahmed , Gaurav Sanghvi , Mohd Zaki Bin Awang Isa , Priyanka Singh , Kiranjeet Kaur , M.Ravi Kumar , Beneen Husseen","doi":"10.1016/j.prp.2025.155984","DOIUrl":"10.1016/j.prp.2025.155984","url":null,"abstract":"<div><div>Mesenchymal stem cell (MSC) therapy, with its unique properties, has garnered interest in cancer treatment. Exosomes (EXOs)-derived from MSC retain the paracrine components of MSCs and demonstrate increased stability, minimal immunogenicity, and low risk of unintended tumorigenesis. Enhanced endocytosis methods make them versatile delivery vehicles for therapeutic cargo. MSC-EXOs can either promote or inhibit carcinogenesis, mediated by paracrine factors and various RNA molecules, particularly microRNAs (miRNAs). The prospect of using MSC-EXOs as a delivery tool for antitumor miRNAs in solid tumor therapy is promising. Exosomes' intrinsic tumor-targeting abilities and low immunogenicity make them ideal for delivering miRNAs, which have shown potential as cancer therapeutics. miRNAs within MSC-EXOs molecules can stimulate tumor growth or induce non-apoptotic cell death pathways, such as ferroptosis, depending on context. Ferroptosis is a kind of controlled cell death that is associated with the pathophysiology of several illnesses and includes iron metabolism. There is growing evidence that miRNAs carried by exosomes derived from MSCs may control ferroptosis in tumor cells by altering key genes related to antioxidant defense, lipid peroxidation, and iron metabolism. Understanding their complex mechanisms in the tumor microenvironment and optimizing their cargo are critical steps toward harnessing their full therapeutic potential. This review provides a comprehensive overview of MSC-EXOs and their role in cancer treatment. We also discuss the potential of MSC-EXOs as delivery vehicles for miRNAs to enhance therapeutic efficacy, as well as the role of exosomal miRNAs in the induction of ferroptosis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155984"},"PeriodicalIF":2.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892240","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

Expression of functionally glycosylated PSGL-1 in ALK-positive anaplastic large cell lymphoma 功能糖基化PSGL-1在alk阳性间变性大细胞淋巴瘤中的表达

IF 2.9 4区医学

Pathology, research and practice Pub Date : 2025-04-21 DOI: 10.1016/j.prp.2025.155988

Natsumi Yonemoto , Mana Fukushima , Hitomi Hoshino , Yusuke Fukiage , Akifumi Muramoto , Yasuharu Kaizaki , Yasuni Nakanuma , Yukinori Inadome , Takuya Komeno , Haruo Ohtani , Motohiro Kobayashi

{"title":"Expression of functionally glycosylated PSGL-1 in ALK-positive anaplastic large cell lymphoma","authors":"Natsumi Yonemoto , Mana Fukushima , Hitomi Hoshino , Yusuke Fukiage , Akifumi Muramoto , Yasuharu Kaizaki , Yasuni Nakanuma , Yukinori Inadome , Takuya Komeno , Haruo Ohtani , Motohiro Kobayashi","doi":"10.1016/j.prp.2025.155988","DOIUrl":"10.1016/j.prp.2025.155988","url":null,"abstract":"<div><div>Anaplastic lymphoma kinase (ALK)-positive (ALK+) anaplastic large cell lymphoma (ALCL) is defined as a CD30-positive mature T-cell lymphoma characterized by proliferation of large anaplastic cells and aberrant ALK protein expression. These cells often infiltrate lymphatic sinuses, proliferate and exhibit intercellular cohesiveness and accumulate around blood vessels. However, molecular mechanisms underlying such vascular-related histogenesis remain to be elucidated. Since PSGL-1 is more highly expressed in ALK+ ALCL than in other T-cell lymphomas and sLe<sup>x</sup> glycan expression has been reported in ALK+ ALCL, the interaction between PSGL-1, which is functionally glycosylated with sLe<sup>x</sup>, and P-selectin, which is expressed on endothelial cells, may contribute to such vascular-related histogenesis. To analyze glycans on PSGL-1 expressed in ALK+ ALCL in the context of P-selectin binding function, we first performed immunohistochemical analysis of 12 cases of ALK+ ALCL to identify those that express both PSGL-1 and sLe<sup>x</sup> glycans and found that a substantial portion of both molecules co-localizes in those cases. We then conducted western blot analysis, together with glycosyltransferase gene expression analysis, of ALK+ ALCL cells and observed that PSGL-1 is decorated with sLe<sup>x</sup> glycans, especially those displayed on core 2 <em>O</em>-glycans. Finally, we carried out a P-selectin•IgM chimera binding assay to show that ALK+ ALCL cells bind to P-selectin. These results indicate that the PSGL-1 glycoform expressed on ALK+ ALCL cells is functional and that interaction of functionally glycosylated PSGL-1 with P-selectin may be partially responsible for the vascular-related histogenesis characteristics of ALK+ ALCL.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155988"},"PeriodicalIF":2.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855747","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