Pathology, research and practice最新文献

{"title":"Endoplasmic reticulum stress and the unfolded protein response in ischemic nephropathy: Pathogenic mechanisms and emerging therapeutic strategies","authors":"Janavie Patel,&nbsp;Siddhi Bagwe Parab,&nbsp;Gaurav M. Doshi","doi":"10.1016/j.prp.2026.156367","DOIUrl":"10.1016/j.prp.2026.156367","url":null,"abstract":"<div><div>One of the main causes of chronic kidney disease (CKD), ischemic nephropathy, is brought on by maladaptive cellular stress responses, specifically endoplasmic reticulum (ER) stress and unfolded protein response (UPR) signalling, in addition to vascular insufficiency. The primary goals of UPR activation via the Protein kinase R-like ER kinase (PERK), Inositol-requiring enzyme 1 (IRE1), and Activating Transcription Factor 6 (ATF6) pathways are to support renal tubular cell survival and restore proteostasis. Prolonged or severe ER stress, on the other hand, causes the UPR to shift toward pathogenic outcomes by triggering apoptotic (C/EBP homologous protein [CHOP], caspase-12), inflammatory (c-Jun N-terminal Kinase [JNK], nuclear factor kappa B [NF-κB]), and fibrotic (transforming growth factor-beta [TGF-β]/SMAD) cascades that lead to progressive renal dysfunction, tubular atrophy, and interstitial fibrosis. Furthermore, ER-mitochondria crosstalk connects acute ischemia injury to chronic fibrosis by exacerbating mitochondrial failure, oxidative stress, and cell death. Targeting therapy requires an understanding of the UPR's dual nature, which is beneficial during brief stress but harmful during prolonged ischemia. Promising approaches to maintain kidney function include interventions that alter particular UPR branches, improve autophagy, lower oxidative damage, and restore ER equilibrium. In addition to outlining the molecular bases of ER stress and UPR in ischemic nephropathy, this review suggests innovative therapeutic strategies meant to shift the equilibrium from maladaptive to adaptive stress responses, providing novel possibilities to slow or alter the course of CKD. This review aims to critically evaluate the molecular mechanisms of ER stress and the UPR in ischemic nephropathy, with a focus on identifying potential therapeutic strategies to preserve renal function and slow CKD progression.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156367"},"PeriodicalIF":3.2,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980041","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":"RNF6 activates JNK/c-JUN pathway in ovarian cancer by promoting K48-linked NME4 ubiquitination","authors":"Taoqiong Li,&nbsp;Fei Qian,&nbsp;Yumei Chen,&nbsp;Wei Li","doi":"10.1016/j.prp.2026.156366","DOIUrl":"10.1016/j.prp.2026.156366","url":null,"abstract":"<div><h3>Background</h3><div>RING finger protein 6 (RNF6), a member of the E3 ubiquitin ligase family, has been implicated in various cancers, yet its functional significance and regulatory mechanisms in ovarian cancer (OC) are poorly understood.</div></div><div><h3>Methods</h3><div>RNF6 expression levels were analyzed using TCGA data and confirmed by IHC, qRT-PCR, and western blotting in OC tissues or cell lines. Functional roles of RNF6 were evaluated through CCK-8, colony formation, wound healing, Transwell, and EMT marker assays. Protein interactions and ubiquitination patterns were investigated via Co-IP, CHX chase, and ubiquitination assays. Rescue experiments were conducted by co-modulating RNF6 and NME4 expression. In vivo tumorigenesis was assessed using a nude mouse xenograft model.</div></div><div><h3>Results</h3><div>RNF6 was markedly overexpressed in OC and associated with poor prognosis. Silencing RNF6 suppressed cell growth, invasive behavior, and EMT, while enhancing NME4 expression. Mechanistic analyses demonstrated that RNF6 directly binds to NME4 and facilitates its K48-linked polyubiquitination, leading to proteasomal degradation. Knockdown of NME4 reversed the tumor-suppressive effects of RNF6 depletion and reinstated JNK/c-JUN pathway activation. In vivo, RNF6 silencing significantly reduced tumor burden and impaired downstream signaling events.</div></div><div><h3>Conclusion</h3><div>RNF6 contributed to OC malignancy by destabilizing NME4 and activating the JNK cascade. This newly identified RNF6/NME4/JNK axis provides potential targets for therapeutic intervention in OC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156366"},"PeriodicalIF":3.2,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078707","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":"OXPHOS inhibitor IACS010759 suppresses tumor growth by modulating autophagy in esophageal squamous cell carcinoma","authors":"Xiao Han ,&nbsp;Xueyuan Hu ,&nbsp;Guangzhao Zhu ,&nbsp;Yingchao Ma ,&nbsp;Kaige Li ,&nbsp;Hongtao Liu ,&nbsp;Tianli Fan ,&nbsp;Yue Xu ,&nbsp;Wenna Guo ,&nbsp;Yanting Zhang","doi":"10.1016/j.prp.2026.156363","DOIUrl":"10.1016/j.prp.2026.156363","url":null,"abstract":"<div><div>Esophageal squamous cell carcinoma (ESCC) is a prevalent and highly malignant digestive tract cancer with poor prognosis. Cancer cells generally exhibit increased glycolytic activity, and it was previously believed that oxidative phosphorylation (OXPHOS) is downregulated in all cancers. However, recent studies have shown increased OXPHOS activity in some tumors, even alongside active glycolysis. This has led to the exploration of targeting elevated OXPHOS as a therapeutic strategy. Despite this, the role of OXPHOS in ESCC tumorigenesis and progression remains unclear. In this study, we found that OXPHOS-related genes are highly expressed in ESCC cell lines and tissues, and this elevated expression correlates with clinical prognosis. The OXPHOS inhibitor IACS-010759 suppressed ESCC cell proliferation, clonogenicity, and migration, while disrupting mitochondrial morphology and function. Furthermore, IACS-010759 inhibited xenograft tumor growth in nude mice. Treatment with IACS-010759 also inhibited autophagy and activated the AKT/mTOR pathway in ESCC cells. The autophagy inducer rapamycin counteracted the inhibitory effects of IACS-010759, indicating that IACS-010759 inhibits ESCC autophagy via AKT/mTOR activation, thereby exerting anti-tumor effects. Interestingly, inhibiting OXPHOS increased glycolytic activity. Combining IACS-010759 with the glycolysis inhibitor 2-DG resulted in a significant synergistic anti-tumor effect in ESCC cells and xenografts. In conclusion, our findings suggest that the OXPHOS pathway may serve as a promising therapeutic target for ESCC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156363"},"PeriodicalIF":3.2,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023920","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":"Trilobatin ameliorates ulcerative colitis by reducing inflammation and enhancing intestinal barrier function via regulating HMGB1-mediated TLR4/NF-κB signaling pathway.","authors":"Tao Chen, Wei Wang","doi":"10.1016/j.prp.2026.156362","DOIUrl":"https://doi.org/10.1016/j.prp.2026.156362","url":null,"abstract":"<p><p>Ulcerative colitis (UC) stands as the predominant chronic inflammatory immune bowel disease. This research aimed to elucidate the mechanism of Trilobatin (TLB) in dextran sodium sulfate (DSS)-induced UC, utilizing DSS-induced mice and NCM460 cells as UC models. The findings of the study confirmed that TLB could ameliorate intestinal structural damage in DSS-treated mice. TLB treatment intensified ZO-1, Occludin, and Claudin-1 levels, as well as Bcl-2, and lessened the levels of Bax in DSS-treated mice. Moreover, TLB administration enhanced the activity of SOD and reduced the content of MDA, alongside decreased levels of IL-6, TNF-α, and IL-1β. In NCM460 cells, TLB promoted cell viability and suppressed apoptosis, oxidative stress, and inflammation triggered by DSS. Moreover, levels of tight junction proteins were elevated in DSS-triggered NCM460 cells following treatment with TLB. Further, TLB was found to suppress TLR4/NF-κB signaling in DSS-elicited NCM460 cells via regulating HMGB1. In conclusion, TLB exerted its protective function in DSS-induced colitis by inactivating HMGB1-mediated TLR4/NF-κB signaling, which might provide novel strategies for therapeutic intervention in UC.</p>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"280 ","pages":"156362"},"PeriodicalIF":3.2,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119472","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":"UBR5, a potential diagnostic and prognostic biomarker induces osteosarcoma progression","authors":"Mufan Li ,&nbsp;Jie Liang ,&nbsp;Xia Jiang ,&nbsp;Meiling Zheng ,&nbsp;Yao Liu ,&nbsp;Hua Jiang ,&nbsp;Hanan Long ,&nbsp;Vincent Kam Wai Wong ,&nbsp;Junjiang Fu","doi":"10.1016/j.prp.2026.156361","DOIUrl":"10.1016/j.prp.2026.156361","url":null,"abstract":"<div><h3>Background</h3><div>Ubiquitin protein ligase E3 component n-recognin 5 (<em>UBR5</em>) locates on chromosome 8q22, a region that commonly disrupted in a variety of cancers. Emerging evidence suggests UBR5 is involved in cancer progression, yet its oncogenic and prognostic roles, especially in osteosarcoma, remain poorly defined.</div></div><div><h3>Methods</h3><div>TCGA, GTEx, and GEO databases were integrated to analyze the expression level, and prognostic and diagnostic value of <em>UBR5</em> across cancers. <em>UBR5</em> genetic alterations and protein interactions were assessed using cBioPortal and GeneMANIA. UBR5 expression in osteosarcoma samples was validated by immunohistochemistry, Western blotting, and immunofluorescence staining. Functional assays, including gain- and loss-of-function experiments, CCK-8, colony formation, and transwell assays were used to evaluate the role of UBR5 in osteosarcoma cell lines. Additionally, the impact of Ubr5 knockdown on tumor growth was assessed in a mouse syngeneic transplant model.</div></div><div><h3>Results</h3><div>UBR5 expression was significantly elevated in osteosarcoma and various cancers, and its upregulation was strongly associated with poor prognosis. Furthermore, <em>UBR5</em> exhibited high diagnostic accuracy in distinguishing cancer from normal tissues. Genomic analysis revealed frequent <em>UBR5</em> alterations correlated with poor overall survival (OS). Protein interaction analysis showed UBR5’s association with chromatin assembly and histone modification. Knockdown of UBR5 inhibited proliferation, migration, invasion of osteosarcoma cell lines, while its overexpression promoted these malignant phenotypes <em>in vitro</em>. Moreover, knockdown of Ubr5 suppressed tumor growth <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>This study identifies UBR5 as a key driver of osteosarcoma progression and a promising diagnostic and prognostic biomarker across cancers, highlighting its potential as a biomarker and therapeutic target.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156361"},"PeriodicalIF":3.2,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980039","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":"Renal cell carcinoma with biphasic morphology: A cohort showing similar morphology but distinct clinicopathological and molecular features","authors":"Ye Liao ,&nbsp;Xin Wang ,&nbsp;Zhenhua Zhang ,&nbsp;Xinyi Shen ,&nbsp;Peng Su ,&nbsp;Daochen Chong ,&nbsp;Yanxia Jiang ,&nbsp;Yujun Li ,&nbsp;Wei Zhang ,&nbsp;Wenjuan Yu","doi":"10.1016/j.prp.2026.156360","DOIUrl":"10.1016/j.prp.2026.156360","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Biphasic morphology, characterized by small cells clustered around basement membrane material, is a distinctive feature of &lt;em&gt;TFEB&lt;/em&gt;-rearranged renal cell carcinoma (RCC). However, other RCC subtypes may exhibit similar histological characteristics. Clinicopathological data from 12 cases of RCC with biphasic morphology—including four cases of &lt;em&gt;TFEB&lt;/em&gt;-rearranged RCC, four cases of &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCC, and four cases of chromophobe RCC (ChRCC)—were collected. Most of the 12 patients survived without complications, except for one patient with ChRCC who died accidentally 25 months after surgery. Microscopically, all 12 tumors showed varying proportions of biphasic morphology, comprising clear or eosinophilic large cells arranged in nests, glandular, or papillary structures, and clustered small cells forming pseudorosette structures around basement membrane-like deposits. Large pale cells with clear to foamy cytoplasm were observed in the four ChRCC tumors. IHC revealed consistent nuclear and cytoplasmic expression of TFEB in all four cases of &lt;em&gt;TFEB&lt;/em&gt;-rearranged RCC and diffuse nuclear positivity of TFE3 in &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCC. Cathepsin K and GPNMB were expressed in most &lt;em&gt;TFEB&lt;/em&gt;- and &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCCs, whereas the melanocytic markers Melan A and HMB45 were expressed to varying degrees. Additionally, PD-L1 (22C3) was expressed with a high CPS of approximately 90 in two cases of &lt;em&gt;TFEB&lt;/em&gt;-rearranged RCC. CK7, CD117, and Ksp-cad were expressed in both large and small cells in the four cases of ChRCC. FISH identified TFEB rearrangement in all four cases of &lt;em&gt;TFEB&lt;/em&gt;-rearranged RCC and TFE3 rearrangement in all four cases of &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCC. RNA sequencing and whole-exome sequencing revealed &lt;em&gt;TFEB&lt;/em&gt;–&lt;em&gt;MALAT1&lt;/em&gt; fusion in all four cases of &lt;em&gt;TFEB&lt;/em&gt;-rearranged RCC. &lt;em&gt;TFE3&lt;/em&gt;–&lt;em&gt;SFPQ&lt;/em&gt; fusion was detected in two cases, and &lt;em&gt;TFE3&lt;/em&gt;–&lt;em&gt;MED15&lt;/em&gt; fusion in the other two &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCC cases. PD-L1 (22C3) expression was detected in three cases of &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCC, two &lt;em&gt;TFE3&lt;/em&gt;-&lt;em&gt;MED15&lt;/em&gt; fusion subtype showed a CPS of approximately 30 and 20, whereas one &lt;em&gt;TFE3&lt;/em&gt;-&lt;em&gt;SFPQ&lt;/em&gt; fusion subtype showed a CPS of approximately 5. Additionally, in the four ChRCC cases, multiple segments of chromosomes 1, 2, 6, 8, 9, 10, and 17 were either lost or amplified. The biphasic structure with small cell components in RCC is observed in &lt;em&gt;TFEB&lt;/em&gt;-rearranged RCC and in &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCC and ChRCC, which may be prone to misdiagnosis based solely on morphology. Patients with &lt;em&gt;TFEB&lt;/em&gt;- and &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCCs exhibiting small cell components tend to be younger and have more favorable prognoses. The &lt;em&gt;TFE3&lt;/em&gt;–&lt;em&gt;MED15&lt;/em&gt; gene fusion in RCC with a biphasic structure containing small cell components has been reported here for the first time. Genetic alterations in ChRCC with small cell components ","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156360"},"PeriodicalIF":3.2,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980040","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":"Performance of the VENTANA FOLR1 Assay for folate receptor alpha: Real-world evidence from 313 Chinese participants","authors":"Xiaoyan Chen ,&nbsp;Li Jiang ,&nbsp;Liangyan Ruan ,&nbsp;Teng Yu ,&nbsp;Weiwei Rui ,&nbsp;Yue Fan ,&nbsp;Huafeng Wang ,&nbsp;He Jiang ,&nbsp;Chaofu Wang","doi":"10.1016/j.prp.2026.156359","DOIUrl":"10.1016/j.prp.2026.156359","url":null,"abstract":"<div><div>Folate receptor-α is an ideal precision therapy target of ovarian cancer. The standardization of FRα assay and interpretative criteria is essential for ensuring diagnostic consistency and enhancing clinical efficacy in therapeutic applications. This study aims to analytically verify and evaluate the clinical performance of the VENTANA FOLR1 Assay. This real-world study of Chinese patients analyzed FRα expression using the VENTANA FOLR1 RxDx assay in 313 samples from diverse anatomical sites. Inter- and intra-observer agreement in FRα scoring was evaluated, and correlations between FRα positivity and clinicopathological parameters were examined. Three pathologists demonstrated excellent inter- and intra-observer agreement (&gt; 97 %) in FOLR1 interpretation. 40.9 % of cases showed high FRα expression, with a significantly higher positivity rate in high-grade serous carcinoma among the Chinese cohort. Primary tumors exhibited higher FRα positivity than metastatic lesions (44.2 % vs 32.2 %, p = 0.04). Chemotherapy exposure did not significantly alter FRα positivity across ovarian, fallopian tube, and primary peritoneal cancers, remained comparable to that of the overall cohort (41.2 % vs 40.9 %). Excision/resection samples were identified as optimal for FRα assessment. Our findings demonstrate the high reliability of the VENTANA FOLR1 Assay in Chinese clinical settings. Additionally, we conducted a systematic investigation into the associations between FRα expression and clinicopathological characteristics, highlighting its capacity to reflect FRα heterogeneity, maintain stability in post-chemotherapy FRα expression across various tumor types, and achieve robust performance in excision/resection samples. These findings underscore the value of standardizing FRα testing to improve patient selection for FRα-targeted MIRV therapies in China.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156359"},"PeriodicalIF":3.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145928822","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":"Overcoming barriers in cancer therapy with oncolytic adenoviruses: Engineering strategies and clinical perspectives","authors":"Rohit Sharma ,&nbsp;Rahul Sharma ,&nbsp;Kamal Dua ,&nbsp;Gaurav Gupta ,&nbsp;Dinesh Kumar Chellappan ,&nbsp;Sachin Kumar Singh ,&nbsp;Thakur Gurjeet Singh ,&nbsp;Poonam Negi","doi":"10.1016/j.prp.2026.156351","DOIUrl":"10.1016/j.prp.2026.156351","url":null,"abstract":"<div><div>Oncolytic adenoviruses (OADVs) have emerged as promising therapeutics for cancer treatment, offering tumour-selective replication and potent antitumor effects. These genetically engineered viruses infect and lyse cancer cells while simultaneously activating antitumor immunity. OADV can be engineered with therapeutic genes and tumour-specific promoters, further enhancing their specificity and efficacy. Various researchers have explored the use of OADV in cancer treatment, integrating direct oncolysis with immune activation, hence revealing promising therapeutic effects in preclinical studies. This review provides comprehensive insights into the mechanism of OADV engineering with tumor-specific promoters and therapeutic payloads, emphasizing advances in vector design that enhance specificity and efficacy. Key evidence from preclinical and clinical studies across lungs, pancreatic, hepatic, breast, renal, and brain cancers is highlighted, demonstrating the translational impact of OADV therapy. The synergistic potential of OADVs in combination regimens, including chemotherapy, immunotherapy, and gene therapy, is critically appraised. The review further examines central hurdles such as antiviral immunity, tumor microenvironment complexity, and delivery challenges, discussing innovative strategies like genetic modulation and nanoparticle carriers to overcome these barriers. Through integrating direct oncolysis and immune modulation, OADVs offer a multifaceted approach for the treatment of resistant and heterogeneous malignancies. The future of OADV therapy requires continued refinement in vector engineering, personalized delivery systems, and multidisciplinary research, positioning OADVs as pivotal agents for enhancing patient outcomes and quality of life in cancer care.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156351"},"PeriodicalIF":3.2,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912594","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":"Prediction of high-grade lung adenocarcinomas in small biopsies: A triaging tool for patients with resectable tumors","authors":"Amber Louw,&nbsp;Jacqueline Bentel,&nbsp;Andrew Laycock","doi":"10.1016/j.prp.2026.156350","DOIUrl":"10.1016/j.prp.2026.156350","url":null,"abstract":"<div><h3>Background</h3><div>Following diagnosis of resectable non-small cell lung cancer (NSCLC), delays in surgery can lead to poorer outcomes, including interval progression of disease. In this study, we investigated the accuracy of a biopsy diagnosis of adenocarcinoma with high-grade features and its potential use to expedite surgery for patients with these poor prognosis tumors.</div></div><div><h3>Methods</h3><div>Hematoxylin and eosin (H&amp;E) stained slides from lung biopsies of 144 patients who proceeded to resection were reviewed. The histologic subtype, presence and percentage of architectural patterns in tumor biopsies were recorded. Results were compared to the diagnosis and grading of the excision specimens.</div></div><div><h3>Results</h3><div>High-grade architectural features, including solid, micropapillary, complex glandular or cribriform histology were identified in 29 of 89 biopsies from adenocarcinomas. Following resection, 22 of these tumors were diagnosed as high-grade, while 55 of 62 biopsies with low/intermediate-grade histologies were found to be low/intermediate-grade on resection. Use of biopsy specimens to predict final grade was associated with a positive predictive value of 75.9 % and a negative predictive value of 91.7 %. Overall, the sensitivity was 81.5 % and specificity was 88.7 %.</div></div><div><h3>Conclusions</h3><div>Identification of high-grade histologic patterns in lung adenocarcinoma biopsies is strongly indicative of high-grade tumors. In combination with imaging and clinical information, provisional diagnosis of high-grade adenocarcinomas can help to prioritize surgery for patients with these poor prognosis tumors.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156350"},"PeriodicalIF":3.2,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912602","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":"Glutamine metabolites promote the progression of cervical cancer by inducing M2 macrophage polarization","authors":"Tingting Liu ,&nbsp;Lanyue Zhang ,&nbsp;Yang Li,&nbsp;Wenxin Liao,&nbsp;Juexiao Deng,&nbsp;Hua Liang,&nbsp;Fujin Shen","doi":"10.1016/j.prp.2025.156348","DOIUrl":"10.1016/j.prp.2025.156348","url":null,"abstract":"<div><h3>Background</h3><div>Tumour-associated macrophages (TAMs) within the tumour microenvironment play crucial roles in tumour initiation, invasion, and metastasis. While glutamine synthetase (GS) is expressed predominantly in the tumour stroma, particularly in TAMs, the role of glutamine metabolism in regulating TAM polarization and function in cervical cancer (CC) remains poorly understood. This study aims to clarify this role and its implications for cancer progression.</div></div><div><h3>Methods</h3><div>CD68 and GS expression in cervical tissues was detected using immunofluorescence staining. The effects of glutamine metabolism on TAM polarization were investigated via RT<img>qPCR, flow cytometry, Western blotting and NAA treatment analyses. CCK8, colony formation, and Transwell assays were conducted to determine the effects of MSO-treated macrophages on tumour cell proliferation, migration, and invasion.</div></div><div><h3>Results</h3><div>We observed a significant increase in GS expression in TAMs within cervical cancer (CC) tissues, particularly in M2-like TAMs. Glutamine synthesized by TAMs with high GS expression was found to increase the proliferation, migration, and invasion of CC cells. Inhibition of GS in TAMs notably reduced their tumour-promoting effects. Additionally, the byproducts of glutamine metabolism in CC cells contributed to the polarization of TAMs towards the M2 phenotype. This polarization was completely abrogated when SNAT1, a key glutamine transporter, was inhibited in CC cells.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrate that glutamine synthesized by TAMs with high GS expression promotes tumour progression in CC. Furthermore, glutamine byproducts produced by CC cells induce TAM polarization towards the M2 phenotype, suggesting crucial metabolic crosstalk between tumour cells and macrophages that supports tumour progression. These results highlight the potential of targeting glutamine metabolism to modulate TAM function and inhibit tumour growth.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156348"},"PeriodicalIF":3.2,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884322","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}