Pathology, research and practice最新文献

{"title":"Quantitative and spatial distribution characteristics of CD66b+ tumor-associated neutrophils in metaplastic and non-metaplastic triple-negative breast cancer treated with neoadjuvant therapy and their prognostic significance","authors":"Ting Xie ,&nbsp;Aoling Huang ,&nbsp;Bin Luo ,&nbsp;Honglin Yan ,&nbsp;Hongfeng Zhang ,&nbsp;Shuaijun Chen ,&nbsp;Zhongtao Chen ,&nbsp;Tian Jin ,&nbsp;Jingping Yuan","doi":"10.1016/j.prp.2025.156205","DOIUrl":"10.1016/j.prp.2025.156205","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aimed to compare the density and spatial distribution of tumor-associated neutrophils (TANs) in metaplastic breast cancer (MpBC) and non-metaplastic triple-negative breast cancer (TNBC) patients before neoadjuvant chemotherapy (NACT) to identify prognostic biomarkers and therapeutic implications.</div></div><div><h3>Methods</h3><div>We conducted a retrospective analysis of patients with MpBC and non-metaplastic TNBC both treated with NACT from three hospitals. CD66b+ TANs were quantified and spatially mapped using an artificial intelligence (AI) -based positive cell classifier. Clinicopathological characteristics were compared between the two groups. Statistical analyses were used to assess the prognostic value of TANs and their predictive value in NACT.</div></div><div><h3>Results</h3><div>Significant differences were observed between MpBC and non-metaplastic TNBC patients in age, tumor size, Ki-67 expression, residual cancer burden grade, pathologic complete remission (pCR) rate, disease-free survival (DFS), CD66b+ TAN density, and spatial distribution. No MpBC patients achieved pCR, whereas 30.8 % of non-metaplastic TNBC patients did. In MpBC, larger tumor size and stromal-predominant CD66b+ TAN distribution were associated with poorer prognosis. In non-metaplastic TNBC, tumor size &gt; 2 cm, androgen receptor positivity, and high CD66b+ TAN density correlated with lower pCR rates, while tumor size &gt; 2 cm, lymph node positivity, and elevated CD66b+ TAN density were linked to worse DFS.</div></div><div><h3>Conclusion</h3><div>CD66b+ TANs might serve as a potential prognostic biomarker in MpBC and non-metaplastic TNBC following NACT, and their density and spatial distribution also contributed insights into the prognosis of the patients.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156205"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933174","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}

{"title":"Multiscale identification of DNASE1L3 as a key target in MASLD progression to hepatocellular carcinoma","authors":"Lintao Xia ,&nbsp;Xiuli Yan ,&nbsp;Hui Zhang","doi":"10.1016/j.prp.2025.156192","DOIUrl":"10.1016/j.prp.2025.156192","url":null,"abstract":"<div><h3>Background</h3><div>The rising incidence of hepatocellular carcinoma (HCC) linked to metabolic dysfunction-associated steatotic liver disease (MASLD) underscores the need to identify key drivers of malignant transformation. This study aimed to discover critical genes governing MASLD-to-HCC progression for early intervention.</div></div><div><h3>Methods</h3><div>Bulk and single-cell transcriptomic data were analyzed using pseudotime algorithms (Mfuzz, Monocle3) to pinpoint progression-related genes. The scissor algorithm identified target cells, and diagnostic models were developed to validate MASLD-associated genes. Functional validation included siRNA knockdown and plasmid-driven overexpression of DNASE1L3 in MASLD and MASLD-HCC cell models. Protein and mRNA expression was assessed via Western blotting and RT<img>qPCR. Lipid accumulation (Oil Red O staining) and proliferation (CCK8 assays) were evaluated post-intervention.</div></div><div><h3>Results</h3><div>DNASE1L3 emerged as a pivotal gene, with marked downregulation in MASLD and HCC models. Overexpression suppressed HCC cell proliferation while enhancing lipid accumulation, whereas knockdown showed no significant effects.</div></div><div><h3>Conclusions</h3><div>DNASE1L3 is a potential therapeutic target in MASLD-driven HCC, regulating malignant progression through dual modulation of proliferation and lipid metabolism. These findings provide mechanistic insights for future interventions.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156192"},"PeriodicalIF":3.2,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144926254","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}

{"title":"Integrating network pharmacology and pharmacological evaluation for investigating the active ingredient of Chinese herbal formula Zhuhuang Granule in psoriasis","authors":"Jing Wang ,&nbsp;Meijunzi Luo ,&nbsp;Yujin Zhang,&nbsp;Yi Pan,&nbsp;Pan Huang,&nbsp;Rong Zhou,&nbsp;Yining Yan,&nbsp;Biying Wang,&nbsp;Maolin Jiang,&nbsp;Chongjun Ran,&nbsp;Haizhen Wang","doi":"10.1016/j.prp.2025.156201","DOIUrl":"10.1016/j.prp.2025.156201","url":null,"abstract":"<div><h3>Objective</h3><div>Psoriasis is a chronic, relapsing inflammatory skin disease associated with multiple factors, including genetics and environmental influences. The etiology and pathogenesis of this disease are not yet fully elucidated. Zhuhuang Granules (ZG) can improve psoriasis; however, their related molecular mechanism is not well defined. Therefore, this study aims to investigate the primary components and their molecular mechanisms for treating psoriasis through bioinformatics analysis and molecular biology experiments.</div></div><div><h3>Methods</h3><div>The differentially expressed genes (DEGs) in psoriatic lesion areas and normal skin in the GEO datasets GSE14905 and GSE13355 were analyzed. Pathway enrichment analysis of DEGs was performed using Metascape and via the ClusterProfiler package. Protein-protein interaction (PPI) network analysis of DEGs was used using the STRING database. Target genes for the main active ingredients of ZG were predicted using SymMap. Cytoscape was used to find the core target genes of the main components of ZG. In the in-vitro experiments, HaCaT cells, upon treatment with IL-22 and <em>Cortex Phellodendri</em> extracts (HB extracts), were used for the measurement of cell viability, the levels of inflammatory factors (IL-17A, IL-1β, and TNF-α), as well as the expression levels of CTNNBIP1 and the Wnt pathway-related proteins by CCK-8 assay, ELISA, and western blot. In the in vivo experiments, the effects of HB extracts and CTNNBIP1 knockdown on epidermal abnormal proliferation and inflammatory factor secretion in mice were examined using HE staining, IHC staining, ELISA, and western blot after induction of the mouse models of psoriasis with imiquimod (IMQ).</div></div><div><h3>Results</h3><div>The pathway enrichment results indicated a close correlation between DEGs of GSE14905 and GSE13355 and the pathological process of psoriasis. Cytoscape results revealed that <em>Cortex Phellodendri</em> was located in the core of ZG and targeted the most genes (n=20). CTNNBIP1 was selected for subsequent experiments, in combination with the group’s previous studies. The in vitro experiments suggested that HB extracts affected HaCaT cell proliferation and inflammatory factor secretion by promoting CTNNBIP1 expression. The in-vivo experiments demonstrated that HB extracts significantly alleviated the symptoms of psoriasis in mice, reduced ki-67 and IL-17A expression in skin tissues, and upregulated CTNNBIP1 expression. Besides, the knockdown of CTNNBIP1 in the skin partially reversed the effect of HB extracts.</div></div><div><h3>Conclusion</h3><div>This research underlines that HB extracts suppress the Wnt pathway activation and keratinocyte proliferation and inflammation through the upregulation of CTNNBIP1, ultimately improving psoriasis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156201"},"PeriodicalIF":3.2,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041102","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}

{"title":"High-dose vitamin C improves BCG immunotherapy’s efficacy in a murine ectopic model of bladder cancer","authors":"Roham Deyhimfar ,&nbsp;Keykavos Gholami ,&nbsp;Iman Menbari Oskouie ,&nbsp;Leila Zareian Baghdadabad ,&nbsp;Parisa Zahmatkesh ,&nbsp;Mohammadreza Shoghi ,&nbsp;Gholamreza Mesbah ,&nbsp;Fateme Guitynavard ,&nbsp;Seyed Mohammad Kazem Aghamir","doi":"10.1016/j.prp.2025.156207","DOIUrl":"10.1016/j.prp.2025.156207","url":null,"abstract":"<div><div>Management of non-muscle-invasive bladder cancer (NMBIC) typically involves transurethral resection of bladder tumor (TURBT) followed by intravesical Bacillus Calmette-Guérin (BCG) immunotherapy. However, 30–50 % of patients may not respond to BCG or experience recurrence. High-dose vitamin C (VitC) has shown promise in improving the outcome of immunotherapies such as immune checkpoint blockade. However, evidence of its ability to augment BCG immunotherapy in bladder cancer remains lacking. Tumor-bearing male C57BL/6 mice were divided into four treatment groups receiving placebo, BCG, VitC, and BCG/VitC, respectively. After 22 days, tumors were collected and subjected to histopathological evaluation using H&amp;E staining. Expression of CD4, CD8, NK1.1, F4/80, CD80, CD163, and Ki67 in the tumor microenvironment was assessed by immunohistochemistry (IHC). mRNA levels of Th1 cytokines (<em>IL-2, IL-12, IFNG, TNFA</em>), Th2 cytokines (<em>IL-4, IL-5, IL-6, IL-10</em>), and <em>NOS2</em> were determined using qPCR. Serum levels of IL-12 and TNF-α were quantified using enzyme-linked immunosorbent assay (ELISA). The results demonstrated that VitC remarkably improves the efficiency of BCG immunotherapy. The combination of BCG and VitC resulted in greater inhibition of cell proliferation, reduced tumor sizes, and increased infiltration of inflammatory cells compared to BCG monotherapy, indicating a synergistic effect on the antitumor immune responses. Additionally, BCG/VitC treatment led to a predominance of M1 macrophages and a substantial increase in the infiltration of natural killer cells, as well as T-lymphocytes. Furthermore, mice receiving combination therapy exhibited the highest levels of intratumoral Th1 cytokines while decreasing Th2 cytokines. In conclusion, VitC appears to play a critical role in enhancing BCG-mediated immune responses against NMBIC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156207"},"PeriodicalIF":3.2,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933175","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}

{"title":"A case series of newly described rare mesenchymal tumors of the knee and the role of molecular testing in their histopathological diagnosis","authors":"Jan Balko ,&nbsp;William Golas ,&nbsp;Petr Skapa ,&nbsp;Jaromir Hacek ,&nbsp;Lenka Krskova ,&nbsp;Marcela Mrhalova,&nbsp;Josef Zamecnik","doi":"10.1016/j.prp.2025.156190","DOIUrl":"10.1016/j.prp.2025.156190","url":null,"abstract":"<div><h3>Aims</h3><div>In recent years, molecular methods have emerged as valuable tools for identifying novel characteristics and recognizing extremely rare entities, thereby enhancing our understanding of their occurrence. In this case series, we present four exceptionally rare mesenchymal lesions affecting the knee region. Each case posed unique challenges, highlighting the pivotal role of molecular testing in achieving accurate diagnoses.</div></div><div><h3>Methods</h3><div>For the diagnosis of each tumor, we utilized standard histopathological microscopic examination in combination with clinical data, supplemented by immunohistochemical analyses and molecular testing using fluorescence in situ hybridization and next-generation sequencing.</div></div><div><h3>Results</h3><div>Molecular examinations enabled the identification of four extremely rare tumors in the knee region: phosphaturic mesenchymal tumor, <em>EWSR1</em>::<em>SMAD3</em>-positive fibroblastic tumor, GLI1-amplified mesenchymal neoplasm, and hemangioblastoma of soft tissue. Notably, most of these lesions have not previously been reported in this anatomical location. In addition to their novel localization, we observed several notable features in their immunoprofile.</div></div><div><h3>Conclusion</h3><div>Our study demonstrates that without molecular analysis as an integral part of histopathological examination, the diagnosis of rare lesions is often impossible. At the same time, we emphasize that molecular genetic findings must always be interpreted in the context of corresponding morphology and immunohistochemistry. Identification of rare mesenchymal tumors contributes to expanding awareness of their possible occurrence in previously undocumented locations and reveals new features, including immunoprofiles with overlapping expression of markers previously considered highly specific to other entities (as seen with STAT6, brachyury, and TLE1 in our cohort).</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156190"},"PeriodicalIF":3.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144921369","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}

{"title":"Epigenetics in intestinal stem cells: Molecular mechanisms underpinning the guardians of homeostasis in health and aging-related senescence","authors":"Boning Liu ,&nbsp;Ying Wang ,&nbsp;Xiaoqian Chu ,&nbsp;Jida Wang ,&nbsp;Tianze Pan ,&nbsp;Lulu Xie ,&nbsp;Joseph K. Abankwah ,&nbsp;Yuhong Bian","doi":"10.1016/j.prp.2025.156187","DOIUrl":"10.1016/j.prp.2025.156187","url":null,"abstract":"<div><div>The intestine is a vital organ of the digestive system, with its function largely reliant on the continuous regeneration of mucosal epithelial cells by healthy intestinal stem cells (ISCs). However, as we age, the regenerative potential of ISCs declines, primarily due to deleterious aging processes, such as cellular senescence, which contribute to the development of various chronic gut diseases. A growing body of evidence indicates that both healthy ISCs, which maintain intestinal homeostasis, and aging-associated senescent ISCs are profoundly influenced by epigenetic mechanisms. At the molecular level, dynamic and often reversible epigenetic modifications including chromatin remodeling, histone modifications, DNA methylation, N6-methyladenosine (m⁶A) modifications, and non-coding RNAs (long non-coding RNAs, circular RNAs, and microRNAs) play a pivotal role in modulating ISCs gene expression and function. This review explores the role of epigenetics in regulating ISCs stemness, proliferation, differentiation, and plasticity to maintain epithelial homeostasis, as well as the impact of aging-associated epigenetic changes on these processes. A deeper understanding of these mechanisms may inform researchers on the development of translational approaches, therapeutic strategies, and effective interventions aimed at enhancing the regenerative capacity of gut ISCs and mitigating the onset of age-related gut disorders.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156187"},"PeriodicalIF":3.2,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044819","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}

{"title":"Should we subtype gastric intestinal metaplasia in gastric biopsies, a single institution’s experience","authors":"Haibo Wang ,&nbsp;Yu Liu ,&nbsp;Asra Froze ,&nbsp;Zengying Wu ,&nbsp;Jonathan D. Somma ,&nbsp;Zhiyan Fu","doi":"10.1016/j.prp.2025.156189","DOIUrl":"10.1016/j.prp.2025.156189","url":null,"abstract":"<div><div>Gastric intestinal metaplasia (GIM) is considered a risk factor for gastric dysplasia and adenocarcinoma. While surveillance endoscopies are often performed, particularly for incomplete GIM, the clinical value of histologic subtyping (complete, incomplete, or mixed) remains unclear. This study evaluated the progression risk of different GIM subtypes diagnosed through random gastric biopsies and their association with various clinical factors. Archived pathology data from 206 gastric biopsy cases were analyzed, including 52 negative controls, 56 complete GIM, 54 incomplete GIM, and 44 mixed GIM. Histologic slides were reviewed for subtype confirmation and other pathological changes; clinical data were extracted from medical records. Multiple linear regression was conducted for correlation analysis, and Analysis of Variance was used to compare group means. GIM was predominantly located in the antrum. Over a mean follow-up period of 52.2 months, none of the patients, including 12 under mapping surveillance, developed gastric neoplasia. Significant associations were found between <em>Helicobacter pylori</em> (<em>H. pylori</em>) and all types of GIM. <em>H. pylori</em> infection was also significantly associated with the extent of the GIM. Hypertension showed a trend toward significance in correlation with GIM, but no other associations were identified between GIM and demographic or clinical factors such as gender, age, smoking, diabetes mellitus, or hyperlipidemia. Our findings suggest that the routine subtyping GIM in pathology reports may not be necessary, given the lack of progression to any type of neoplasia within the follow-up period. However, the redemonstrated association between <em>H. pylori</em> and GIM emphasizes the importance of eradication therapy.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156189"},"PeriodicalIF":3.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916280","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}

{"title":"TERT promoter mutations in meningiomas: associations with clinicopathological features and insights into spatial and temporal heterogeneity in a 165-case cohort","authors":"Ahmet Boduroğlu ,&nbsp;Mualla Özcan ,&nbsp;Güzide Ayşe Ocak","doi":"10.1016/j.prp.2025.156191","DOIUrl":"10.1016/j.prp.2025.156191","url":null,"abstract":"<div><h3>Background</h3><div>Although most meningiomas are benign, some behave aggressively despite low grade. We investigated the prognostic significance of <em>TERT</em> promoter (<em>TERT</em>p) mutations regarding clinicopathological features, heterogeneity, and outcomes.</div></div><div><h3>Methods</h3><div>A total of 165 meningiomas diagnosed between 2007 and 2019 were retrospectively re-evaluated according to the 2021 WHO CNS classification<em>. TERT</em>p mutations were assessed by real-time PCR targeting C228T and C250T. Spatial heterogeneity was examined by microdissecting rhabdoid and non-rhabdoid areas, and temporal heterogeneity by comparing initial and recurrent tumors. Associations between <em>TERT</em>p mutation status, clinicopathological parameters, and survival were analyzed.</div></div><div><h3>Results</h3><div><em>TERT</em>p mutations were detected in 6.7 % (n = 11). Mutation-positive tumors had higher mitotic counts (p = 0.007), but <em>TERT</em>p mutation status was not an independent predictor of recurrence or survival (p &gt; 0.05). Spatial heterogeneity was observed, with rhabdoid areas mutation-negative and non-rhabdoid areas mutation-positive. Temporal heterogeneity was observed in tumors initially negative but positive at relapse. Extent of resection, spinal location, and age were independent prognostic factors.</div></div><div><h3>Conclusion</h3><div><em>TERT</em>p mutation was associated with mitotic activity but did not independently predict outcome. However, the small number of mutation-positive cases (n = 11; three recurrences) and grade 3 tumors (n = 3), and absence of broader molecular profiling (e.g., <em>BAP1</em>, <em>NF2, CDKN2A/B</em>, methylation, CNVs) limit generalizability and statistical power, warranting cautious interpretation. Spatial heterogeneity underscores the need for representative sampling, while temporal heterogeneity suggests a potential role of <em>TERT</em>p mutations in tumor evolution. These findings highlight the potential importance of spatial and temporal heterogeneity of <em>TERT</em>p mutations in meningiomas, underscoring the need for integrated molecular profiling in future studies.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"274 ","pages":"Article 156191"},"PeriodicalIF":3.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908555","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}

{"title":"TMED10 expression in human cutaneous malignant melanoma","authors":"Tiziana Annese ,&nbsp;Daniela Coltrini ,&nbsp;Mirella Belleri ,&nbsp;Luca Mignani ,&nbsp;Marzia Corli ,&nbsp;Gerardo Cazzato ,&nbsp;Domenico Ribatti ,&nbsp;Marco Presta","doi":"10.1016/j.prp.2025.156188","DOIUrl":"10.1016/j.prp.2025.156188","url":null,"abstract":"<div><h3>Purpose</h3><div>TMED10 is involved in unconventional protein secretion and ER-Golgi trafficking. TMED10 may exert protumorigenic or oncosuppressive functions in different tumor types, but its role in human cutaneous melanoma has never been explored. Here, TMED10 expression has been investigated in human benign melanocytic tumors and cutaneous malignant melanoma (cMM).</div></div><div><h3>Methods</h3><div>This study utilized <em>in silico</em> analysis on various publicly available web platforms to investigate <em>TMED10</em> gene expression in normal skin and human melanoma at different Clark levels, and immunohistochemistry and digital morphometric analysis of TMED10 protein levels in 60 human samples of benign melanocytic tumors and cMMs at different Breslow T category.</div></div><div><h3>Results</h3><div><em>In silico</em> analysis revealed that <em>TMED10</em> is upregulated in cMM compared to normal skin. <em>TMED10</em> expression in cMM positively correlated with Clark level at diagnosis, and higher expression was associated with the BRAF^V600E mutation and poorer patient survival. <em>TMED10</em> co-expression with <em>TMED2</em>, <em>TMED8</em>, <em>HSP90AA1</em> and <em>HSP90B1</em>, along with Gene Ontology enrichment analysis, supported its role in ER-Golgi trafficking and unconventional protein secretion in human melanoma. Digital morphometric analysis of immunohistochemical investigation of 60 human specimens confirmed a significant increase in TMED10 protein levels with Breslow thickness-based T category in tumor cells and tumor-associated blood vessels. At variance, TMED10 immunoreactivity in infiltrating lymphocytes was reduced in T3 and T4 cMM.</div></div><div><h3>Conclusion</h3><div>These findings point to a pro-tumorigenic function of TMED10 in human cMM and pave the way to further studies aimed at identifying its contribution to tumor progression, neovascularization, and immune escape, and its potential as a therapeutic target in cMM.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156188"},"PeriodicalIF":3.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916262","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}

{"title":"Pracinostat inhibits the nefarious biological behavior of pancreatic cancer by targeting the miR-381–3p/MDM2 axis to activate the p53 signaling pathway","authors":"Dongyun Cun ,&nbsp;Feng Liu ,&nbsp;DaGuang Tian ,&nbsp;TieHan Li ,&nbsp;ZhaoHao Guo ,&nbsp;Peng Chen","doi":"10.1016/j.prp.2025.156186","DOIUrl":"10.1016/j.prp.2025.156186","url":null,"abstract":"<div><h3>Objective</h3><div>Pancreatic cancer is one of the most aggressive malignant tumors in humans, with poor prognosis. The acetylase tumor inhibitor (Pracinostat) has been shown to suppress the growth of various tumors. This study aimed to investigate the effects of Pracinostat on the pancreatic cancer cell line BxPC3 and to explore the underlying molecular mechanisms through both in vivo and in vitro experiments.</div></div><div><h3>Methods</h3><div>BxPC3 cells were treated with Pracinostat, and cell viability was assessed by CCK-8 assay; the differentially expressed miRNAs in cells before and after pracinostat treatment were screened by high-throughput sequencing, and miR-381–3p was selected as the target gene; the targeting relationship between miR-381–3p and MDM2 was verified by double luciferase reporter gene; the relationship between miR-381–3p, MDM2 and P53 signaling pathways was verified by immunoprecipitation, Western blot and other experiments. Pancreatic tumor models were established in BALB/c nude mice to study the role of pracinostat in vivo.</div></div><div><h3>Results</h3><div>Pracinostat upregulated the expression of miR-381–3p and p53, while downregulating MDM2 expression. It also inhibited the proliferation and migration of pancreatic cancer cells and promoted apoptosis. Treatment with a miR-381–3p inhibitor reversed the effects of Pracinostat. In addition, MDM2 was found to promote the ubiquitination and degradation of p53 via the ubiquitin-proteasome pathway. In vivo experiments confirmed that Pracinostat inhibited tumor growth in nude mice.</div></div><div><h3>Conclusion</h3><div>pracinostat activates the p53 signaling pathway by targeting the miR-381–3p/MDM2 axis, thereby inhibiting the proliferation of pancreatic cancer cells. These findings provide novel insights and potential therapeutic strategies for pancreatic cancer, and may also provide a reference for the treatment of other malignancies.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"274 ","pages":"Article 156186"},"PeriodicalIF":3.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144904099","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}