Pathology, research and practice最新文献

{"title":"Evaluation of the effect of bupivacaine on the heart tissue in rats with glycerol-induced acute kidney injury","authors":"Ahmet Turk ,&nbsp;Tuba Ozcan Metin ,&nbsp;Mehmet Duran","doi":"10.1016/j.prp.2025.156193","DOIUrl":"10.1016/j.prp.2025.156193","url":null,"abstract":"<div><h3>Aim</h3><div>This study aims to evaluate the effects of bupivacaine on acute kidney injury (AKI) through kidney function parameters and cardiac tissue damage via TRPM2, HSP70, TLR4, NF-κB, and TNF-α biomarkers.</div></div><div><h3>Material and method</h3><div>Male Wistar albino rats were divided into 4 groups, with seven rats in each group: Control group, AKI group (kidney damage induced by glycerol), AKI + L group (group treated with bupivacaine), and L group (group treated with bupivacaine alone). At the end of the experiment, kidney and heart tissues were collected for histological analysis, and serum samples were taken for biochemical analysis. In serum samples, urea nitrogen (BUN), creatinine (Cr), troponin t, Creatine Kinase, Creatine Kinase-MB, and total oxidant levels were measured. In histological analysis, changes in heart and kidney tissues were evaluated histopathologically and immunohistochemically through KIM-1, TNF-α, TRPM2, HSP70, NF-κB, and TLR4 parameters.</div></div><div><h3>Results</h3><div>In the AKI group, a significant increase in blood urea nitrogen (BUN) and creatinine (CR) levels was observed when compared to the control group (p &lt; 0.05). Notably, in the AKI + Local Anesthetic (L) group, these levels were found to be elevated compared to the AKI group. KIM-1 and TNF-α immunoreactivity in kidney tissue were both significantly elevated in the AKI group compared with the Control group, and further increased in the AKI + L group compared with the AKI group. In heart tissues, significant increases in the immunoreactivity levels of TLR4, NF-κB, TNF-α, HSP70, and TRPM2 were observed in the AKI + L group relative to the AKI group (p &lt; 0.05). Moreover, in the AKI + L group, the extent of histopathological damage was found to be more severe compared to the AKI group (p &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>This study demonstrates that bupivacaine exacerbates acute kidney injury and leads to significant histopathological changes in kidney function and heart tissue parameters. It was observed that bupivacaine might affect cardiac conduction, impairing heart functions, and lead to changes in molecular pathways such as KIM-1, TNF- α, TRPM2, HSP70, TLR4, and NF-κB. Furthermore, the increase of oxidant levels and biomarker levels suggest that bupivacaine may induce oxidative stress and inflammation, leading to damage in both kidney and heart tissues.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156193"},"PeriodicalIF":3.2,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004823","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":"Mechanisms of C5ORF13 in promoting epithelial-mesenchymal transition in hepatocellular carcinoma via eIF6 and the intervention of valproic acid","authors":"Yan Wang ,&nbsp;Lei Tao ,&nbsp;Qikun Lv ,&nbsp;Shuaiqi Wang ,&nbsp;Qinghua Jiang ,&nbsp;Yongpeng He","doi":"10.1016/j.prp.2025.156211","DOIUrl":"10.1016/j.prp.2025.156211","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the mechanism by which C5ORF13 promotes epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) through interaction with eukaryotic translation initiation factor 6 (eIF6) and its clinical significance, and to identify the potential use of valproic acid (VPA) as an eIF6 inhibitor in HCC.</div></div><div><h3>Methods</h3><div>The expression of C5ORF13 in HCC and its prognostic impact were analyzed using GEPIA, UALCAN, and The HUMAN PROTEIN ATLAS databases. Lentiviral transfection technology was used to knock down or overexpress C5ORF13 and eIF6. The effects on the biological behavior of HCC cells were assessed using CCK-8, scratch, Transwell assays, and animal models. The interaction between C5ORF13 and eIF6 was verified using co-immunoprecipitation and immunofluorescence co-localization techniques. Molecular docking, CETSA experiments, and Western Blot were utilized to investigate the mechanism of action of VPA (an eIF6 inhibitor) on eIF6.</div></div><div><h3>Results</h3><div>C5ORF13 was highly expressed in HCC and significantly correlated with cancer staging, tumor grading, lymph node metastasis, and poor patient prognosis. Knockdown of C5ORF13 significantly inhibited the proliferation, migration, invasion, and EMT process of HCC cells. C5ORF13 interacted with eIF6 in HCC cells, and C5ORF13 promoted EMT and HCC metastasis by regulating eIF6 protein expression. <em>In vivo</em> experiments further confirmed that knockdown of C5ORF13 or eIF6 significantly inhibited lung metastasis of HCC cells. Clinical sample analysis showed that the expression of C5ORF13 and eIF6 in HCC tissues was significantly higher than that in normal tissues, and the expression of both was positively correlated. Additionally, VPA reduced the protein stability of eIF6 by binding to it, inhibiting its expression, and subsequently suppressing the migration, invasion, and EMT process of HCC cells.</div></div><div><h3>Conclusion</h3><div>C5ORF13 drives the malignant progression of HCC by increasing eIF6 levels, including proliferation, invasion, migration, and the EMT process. VPA, as an eIF6 inhibitor, shows potential application value in the treatment of HCC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156211"},"PeriodicalIF":3.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020317","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":"Cancer-associated fibroblasts-derived exosome PIK3AP1 promotes the malignant progression and immune escape of prostate cancer cells","authors":"Tan Li ,&nbsp;Cheng Yi ,&nbsp;Zhendong Xiang,&nbsp;Xiangyun You,&nbsp;Junfeng Yu","doi":"10.1016/j.prp.2025.156209","DOIUrl":"10.1016/j.prp.2025.156209","url":null,"abstract":"<div><h3>Background</h3><div>Prostate cancer (PCa) is a common malignant cancer. Cancer-associated fibroblasts (CAFs) play an important role in occurrence and development of tumors. B-cell adapter protein (PIK3AP1) is related to cell growth, inhibits cell apoptosis and mediates tumor therapy. Thereby, this study aims to explore the role and mechanism of CAFs exosomes and PIK3AP1 in PCa.</div></div><div><h3>Methods</h3><div>Normal fibroblasts (NFs), CAFs, and exosomes were characterized by morphology observation and western blot. The proliferation, migration, invasion, and cell viability were examined by 5-Ethynyl-2’-deoxyuridine (EdU), transwell, and cell counting kit-8 (CCK8) assays, respectively. Proliferation and apoptosis of CD8⁺T cells were tested using flow cytometry. Gene expression was analyzed using qRT-PCR and western blot. Animal experiments were utilized to analyze the role of CAF-derived exosome PIK3AP1 <em>in vivo</em>.</div></div><div><h3>Results</h3><div>CAFs-derived exosomes promoted the PCa cell proliferation, migration, invasion, cell viability, and immune escape. PIK3AP1 was up-regulated in CAFs and PCa cells and related to tumor immune escape. PIK3AP1 facilitated the malignant behavior of PCa and the immune escape <em>in vivo</em> and <em>in vitro</em>. CAFs-derived exosome promoted PCa progression and immune escape via carrying PIK3AP1.</div></div><div><h3>Conclusions</h3><div>CAFs-derived exosomes promote the malignant behavior and immune escape of PCa cells by PIK3AP1.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156209"},"PeriodicalIF":3.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145027179","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":"YY1-VDR axis-mediated autophagy slows the progression of intervertebral disc degeneration","authors":"Piji Chen ,&nbsp;Jianfeng Huang ,&nbsp;Zhe Shen","doi":"10.1016/j.prp.2025.156185","DOIUrl":"10.1016/j.prp.2025.156185","url":null,"abstract":"<div><h3>Background</h3><div>Aging is accompanied by degeneration of the intervertebral discs (IVDD), which leads to a poor quality of life and a significant socioeconomic burden. The present study aimed to explore the effect of transcription factor Yin and Yang 1 (YY1) on IVDD and to elucidate the potential underlying mechanism.</div></div><div><h3>Methods</h3><div>Differentially expressed genes in nucleus pulposus (NP) tissues from patients with early or advanced IVDD were screened out using transcriptome sequencing. Mice were subjected to IVDD modeling, and NP cells were treated with H₂O₂ and lentivirus. The oxidative stress and autophagy were assessed in mice and H₂O₂-treated NP cells. Genes closely associated with YY1 expression were predicted, and ChIP and dual-luciferase experiments were conducted to authenticate their binding relationship. Autophagy agonist rapamycin rescue experiments were designed <em>in vitro</em>. Finally, the upstream mechanism for YY1 downregulation was examined.</div></div><div><h3>Results</h3><div>YYI expression was reduced in NP tissues of patients with advanced IVDD, and mice overexpressing YY1 showed significantly decreased oxidative stress and apoptosis, and increased levels of autophagy-related proteins. Overexpression of YY1 reduced the apoptosis and ROS levels, decreased the expression of apoptosis markers, and increased the autophagy in H₂O₂-treated NP cells. YY1 bound to the vitamin D3 receptor (VDR) promoter and stimulated the VDR transcription. Rapamycin-treated NP cells showed increased expression of LC3, decreased ROS levels, and apoptosis. YY1 methylation increased with worsening IVDD.</div></div><div><h3>Conclusions</h3><div>Activation of the VDR by YY1 improves oxidative stress and reduces NP cell apoptosis by promoting autophagy. This process may serve as a promising therapeutic target for managing IVDD.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156185"},"PeriodicalIF":3.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044821","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":"The Fritillaria alkaloid peiminine acts as a chemosensitizer to potentiate oxaliplatin efficacy against gastric cancer","authors":"Jing Zhang ,&nbsp;Lu Zhang ,&nbsp;Chenchen Wang ,&nbsp;Hui Liu ,&nbsp;Sitian Dai ,&nbsp;Lijuan Sun ,&nbsp;Xianchun Gao ,&nbsp;Liang Zhang ,&nbsp;Yunfei Wang ,&nbsp;Qiangqiang Yuan ,&nbsp;Zhongyang Zhang ,&nbsp;Sheng Zhao ,&nbsp;Wenjing Fan ,&nbsp;Xinyu Du ,&nbsp;Zhengyi Gu ,&nbsp;Yongzhan Nie","doi":"10.1016/j.prp.2025.156208","DOIUrl":"10.1016/j.prp.2025.156208","url":null,"abstract":"<div><h3>Background</h3><div><em>Fritillaria walujewii</em> Regel (Xinjiang Bei-Mu), an authentic (\"Dao-di\") medicinal herb documented in Chinese pharmacopoeias, is traditionally used to treat respiratory disorders. Its principal steroidal alkaloid, peiminine (PMI), demonstrates significant anticancer activity. Oxaliplatin (Oxa), a first-line chemotherapeutic cornerstone for gastric cancer (GC), is limited clinically by intrinsic chemoresistance. Natural product-derived monomers represent a promising strategy for developing chemosensitizers to overcome such resistance. However, the potential of PMI to counteract Oxa chemoresistance and its underlying mechanisms remain unexplored, warranting comprehensive investigation. To determine the chemosensitizing effects of PMI in combination with Oxa for GC treatment, specifically evaluating its capacity to reverse chemoresistance and enhance therapeutic efficacy.</div></div><div><h3>Materials and methods</h3><div>The effects of PMI combined with Oxa versus Oxa monotherapy on GC cells (HGC27, BGC823, MKN45) were assessed using CCK-8, colony formation, and flow cytometry apoptosis assays to evaluate cell proliferation and apoptosis. Subsequently, qPCR-based apoptosis pathway array and transcriptome sequencing (RNA-seq) were used to differentially expressed apoptosis-related genes and to uncover key signaling pathways mediating PMI-induced Oxa sensitization. The protein expression level of Bcl-2, Bax, PARP, cytochrome c (CYCS), Caspase-3/9, RAS and AKT was determined by Western blot. Finally, the efficacy of PMI+Oxa combination therapy was validated in vivo using both cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models.</div></div><div><h3>Results</h3><div>PMI (50 μM) synergized with Oxa (2.5 μM), significantly enhancing apoptosis and suppressing proliferation in GC cells. Mechanistically, the combination activated the mitochondrial apoptosis pathway by upregulating Bax and inducing the release of CYCS and the cleavage of caspase-9, caspase-3, and PARP. Concurrently, it suppressed the RAS/PI3K/AKT survival pathway by inhibiting Ras-GTP and phospho-AKT. In CDX models, PMI (2 mg/kg) + Oxa achieved a tumor growth inhibition (TGI) rate of &gt; 80.8 %, compared to 20.4 % for Oxa alone. Strikingly, in PDX models which preserve clinical tumor heterogeneity—the combination induced a TGI of &gt; 70 % without exacerbating systemic toxicity.</div></div><div><h3>Conclusions</h3><div>PMI is a novel dual-targeting chemosensitizer that overcomes Oxa resistance by simultaneously activating intrinsic apoptosis and inhibiting pro-survival signaling. Its demonstrated efficacy in clinically relevant PDX models highlights its significant translational potential for platinum-resistant GC therapy.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156208"},"PeriodicalIF":3.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987951","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":"Mitochondrial DNA release and cGAS-STING activation: Emerging insights into anti-tumor immunity.","authors":"Ghfren S Aloraini","doi":"10.1016/j.prp.2025.156158","DOIUrl":"10.1016/j.prp.2025.156158","url":null,"abstract":"<p><p>Mitochondrial DNA (mtDNA) leakage into the cytosol has emerged as a critical modulator of cancer immunity, bridging the gap between cellular stress and antitumor immune responses. Under genomic instability, metabolic stress, or therapy-induced damage, mtDNA escapes into the cytosol, where it activates the cGAS-STING pathway a central regulator of innate immunity. This pathway not only triggers type I interferon (IFN) responses but also influences dendritic cell maturation, T cell infiltration, and immunogenic cell death, shaping the tumor microenvironment (TME) toward immune activation or suppression. Recent studies reveal that mtDNA leakage is not merely a passive byproduct of mitochondrial dysfunction but is dynamically regulated by autophagy, mitochondrial outer membrane permeabilization (MOMP), and interactions with noncoding RNAs. Furthermore, tumors exploit mtDNA degradation mechanisms (e.g., TREX1 exonuclease) or STING silencing to evade immune detection, highlighting this axis as a therapeutic vulnerability. This review synthesizes current knowledge on mtDNA-driven cGAS-STING activation in cancer, its dual role in promoting inflammation versus immune escape, and the therapeutic potential of targeting mtDNA release or STING signaling to enhance immunotherapy. We also explore emerging strategies, such as mtDNA-stabilizing agents and STING agonists, in combination with checkpoint blockade. Deciphering the nuances of mtDNA sensing in different cancers may unlock novel biomarkers and precision immunotherapies for resistant malignancies.</p>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"273 ","pages":"156158"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799815","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":"CRC Management: Emerging Trends in Early Detection, Diagnosis, Biomarkers, Treatment, and Prevention","authors":"Aminah G. Alotaibi ,&nbsp;Bashayer A. Alfozan ,&nbsp;Sara S. Alotaibi ,&nbsp;Amal S. Al Mutairi ,&nbsp;Aisha Y. Al Humoudi ,&nbsp;Nora A. Al Jawini ,&nbsp;Adel H. Alshehri ,&nbsp;Hussah N. Albahlal ,&nbsp;Sahar S. Alghamdi","doi":"10.1016/j.prp.2025.156206","DOIUrl":"10.1016/j.prp.2025.156206","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is a significant global health concern, including in Saudi Arabia, where its incidence has increased in recent years. It contributes substantially to cancer-related morbidity and mortality, both regionally and worldwide. Recent advancements in genetic and epigenomic data, along with the use of biomarkers, have enhanced the potential for early diagnosis, effective treatment, and monitoring of CRC. Biomarkers are essential for precise medicine because they provide quantitative evidence of disease attributes and facilitate the formulation of treatment plans. By leveraging artificial intelligence (AI) and big data, advanced biomarker analysis has become more effective, further expanding the capabilities of precision medicine. However, the effects of novel biomarkers on mortality and treatment effectiveness remain inconclusive, largely because of insufficient data from large-scale clinical studies. The use of precision medicine in clinical practice presents several challenges, including regulatory hurdles, high implementation costs, and the complexity of integrating large-scale genomic data into routine health care systems. Considering these challenges, the use of biomarkers in precision medicine has demonstrated encouraging findings, enabling specific therapy and improving patient outcomes.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156206"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004820","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":"E-cadherin, N-cadherin and ADAM12 in localized prostate cancer: A clinicopathological study.","authors":"Natalia Pérez-Barraza, Sebastián Concha, Pedro Acuña, Sebastián San Martín, Claudio Córdova, Juan Varas, Diego Toledo, Eva Madrid","doi":"10.1016/j.prp.2025.156160","DOIUrl":"10.1016/j.prp.2025.156160","url":null,"abstract":"<p><p>Prostate cancer (PC) is the most prevalent cancer and the second leading cause of death in males worldwide. One of the processes responsible for its mortality is the metastasizing capacity of malignant cells, which is associated with the epithelial-mesenchymal transition process (EMT). EMT is a physiological process during embryogenesis, with loss of cell adhesion molecules such as cadherins, and overexpression of molecules associated with invasive behaviour, such as matrix metalloproteinases (MMPs). We analyzed 321 tissue samples using immunohistochemistry. E-cadherin expression was significantly lower in PC than in BPH (107.1 ± 60.0 vs. 139.99 ± 36.65; p < 0.0001), while N-cadherin was expressed in all PC samples and only in 50 % of BPH, with significantly higher intensity in PC (65.04 ± 62.2 vs. 21.23 ± 35.8; p < 0.00001). ADAM12 expression was also significantly higher in PC (113.07 ± 63.26 vs. 37.54 ± 51.59; p < 0.00001). No significant associations were found between E-cadherin and PSA and Gleason score (p > 0.17). N-cadherin and ADAM12 showed statistically significant associations with PSA (p = 0.038 and p = 0.013, respectively) but not with other clinical variables. These findings support the involvement of EMT-related markers in PC and suggest their potential utility in biological characterization, although further studies are required to determine their prognostic value.</p>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"273 ","pages":"156160"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799814","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":"Assessment of anti-cancer activity of cyclovirobuxine D in nasopharyngeal carcinoma cells: Involvement of KIF23-mediated Akt/mTOR pathway","authors":"Gang Li ,&nbsp;Can Cui ,&nbsp;Zheng Li","doi":"10.1016/j.prp.2025.156204","DOIUrl":"10.1016/j.prp.2025.156204","url":null,"abstract":"<div><div>Cyclovirobuxine D (CVB-D) is a phytochemical ingredient that has potential antitumor effects in several types of cancer. However, its role and action mechanism in nasopharyngeal carcinoma (NPC) are still unclear. The present study found that CVB-D inhibited the viability of NPC cells, as well as induced NPC cell apoptosis. Kinesin family member 23 (KIF23) expression was inhibited by CVB-D treatment, and KIF23 knockdown exhibited viability-inhibitory and pro-apoptotic effects on NPC cells. Next, we demonstrated that overexpression of KIF23 prevented the inhibitory effect of CVB-D on cell viability, as well as its inductive effect on cell apoptosis. CVB-D treatment or KIF23 knockdown inhibited the Akt/mTOR pathway activation in NPC cells, with decreased expression levels of p-Akt and p-mTOR. Overexpression of KIF23 blocked the inhibitory effect of CVB-D on Akt/mTOR pathway activation. Additionally, Akt knockdown resisted KIF23-mediated antitumor effect of CVB-D. Our results indicated that CVB-D exerted viability-inhibitory and pro-apoptotic effects on NPC cells with the involvement of the KIF23/Akt/mTOR pathway. We provided experimental evidence for the antitumor potential and therapeutic implication of CVB-D in NPC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156204"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933173","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":"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}