Pathology, research and practice最新文献

{"title":"Translating preclinical insights into clinical strategies: Targeting cancer stem cells and stemness in prostate cancer","authors":"Najma Farahani ,&nbsp;Amin Maghsoodlou ,&nbsp;Mohammadarian Akbari ,&nbsp;Safa Tahmasebi ,&nbsp;Salman Daneshi ,&nbsp;Marzieh Ramezani Farani ,&nbsp;Ali Reza Yusefi ,&nbsp;Payman Rahimzadeh ,&nbsp;Afshin Taheriazam ,&nbsp;Maliheh Entezari ,&nbsp;Mehrdad Hashemi","doi":"10.1016/j.prp.2025.155934","DOIUrl":"10.1016/j.prp.2025.155934","url":null,"abstract":"<div><div>CSCs represent a unique group within the tumor microenvironment (TME) elevating the tumorigenesis. The cause of cancer recurrence can also be investigated in the function of CSCs possessing self-renewing capabilities and differentiation into various types of cells. Prostate cancer (PCa) is a malignant disease of the urogenital system characterized by aggressive behavior and heterogeneous nature due to the dysregulation of molecular pathways and the interactions among cells within the TME. The PCa can quickly become resistant to standard chemotherapy and other kinds of therapies such as radiotherapy along with ability to mediate immune evasion. The focus of biology has been on the molecular and cellular alterations in PCa. The CSCs have been recognized as potential biomarkers for predicting the outcome of prostate PCa. Furthermore, a positive correlation exists between CSCs and the metastatic growth and stemness of PCa. The existence of hypoxia enhances the stemness of PCa, and CSCs play a role in dormancy. Genomic and epigenetic elements, including non-coding RNAs, can influence CSCs and the advancement of PCa. Additionally, therapeutic agents and nanotechnology methods aimed at targeting CSCs have been developed to inhibit CSCs in PCa treatment<strong>.</strong></div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155934"},"PeriodicalIF":2.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143769205","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":"Automated assessment of skin histological tissue structures by artificial intelligence in cutaneous melanoma","authors":"Thamila Kerkour ,&nbsp;Loes Hollestein ,&nbsp;Alex Nigg ,&nbsp;Sjors A. Koppes ,&nbsp;Tamar Nijsten ,&nbsp;Yunlei Li ,&nbsp;Antien Mooyaart","doi":"10.1016/j.prp.2025.155923","DOIUrl":"10.1016/j.prp.2025.155923","url":null,"abstract":"<div><h3>Background</h3><div>Prognostic histopathological features such as mitosis in melanoma are excluded from the staging systems due to inter-observer variability and time constraints. While digital pathology offers artificial intelligence-driven solutions, existing melanoma algorithms often underperform or narrowly focus on specific features, limiting their clinical utility.</div></div><div><h3>Objective</h3><div>Develop and validate an automated artificial intelligence-driven segmentation framework to identify multiple histological tissue structures within cutaneous melanoma images.</div></div><div><h3>Methods</h3><div>Employing 157 melanoma whole slide images, U-Net and DeepLab3+ classifiers were independently trained Oncotopix ® platform using manual annotations, to detect specific histological features, termed application. All the applications are progressively executable. The performance of each application was measured when both operating independently and with sequential detection when applied to ten independent validation set images using accuracy and F1-score as metrics. The model was further validated by applying it to 442 whole-slide melanoma images, with dermatopathologists reviewing the segmentation outputs.</div></div><div><h3>Results</h3><div>Seven applications were developed for progressive automated detection: Whole tissue (1) and tumour microenvironment (TME) (2), Hair follicles &amp; sebaceous gland (3) within TME, ulceration (5), and melanoma cell area (6) based on DeepLab3+. Epidermis (4) and mitosis within the tumour area (7) based on U-Net. The applications demonstrated over 92 % accuracy and F1-score surpassing 80 %, except for the ulceration application (F1-score = 75 %). The pathologist examination indicated that 92 % of the 442 images had correct segmentations.</div></div><div><h3>Discussion and Conclusion</h3><div>The developed applications demonstrated high performance, enhancing the analysis of time-consuming histological features. The model facilitates the identification of histopathological features in large datasets allowing potential refinement of melanoma staging.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155923"},"PeriodicalIF":2.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eosinophilic solid and cystic renal cell carcinoma: A case with two novel TSC2 mutations","authors":"Junjie Li,&nbsp;Lei He,&nbsp;Jinsong Zhang,&nbsp;Zheng Wang,&nbsp;Dongge Liu,&nbsp;Chongqing Yang","doi":"10.1016/j.prp.2025.155926","DOIUrl":"10.1016/j.prp.2025.155926","url":null,"abstract":"<div><h3>Background</h3><div>Eosinophilic solid and cystic renal cell carcinoma (ESC RCC) is a recently identified subtype of renal tumors. Due to its rarity, pathologists currently have a limited understanding of its clinical and pathological characteristics, which increases the risk of misdiagnosis.</div></div><div><h3>Case report</h3><div>In this paper, we present a case of a 21-year-old male diagnosed with eosinophilic solid and cystic renal cell carcinoma that is more common in females. Histologically, the tumor appears solid-cystic at low magnification, featuring polygonal tumor cells with high-grade nuclei and abundant eosinophilic cytoplasm. Eosinophilic or basophilic globules are observable within the cytoplasm. Foamy histocytes are clustered among the tumor cells. The cysts are lined by tumor cells arranged in a hobnail pattern. Immunohistochemistry results indicate the expression of CK20, AMACR, Cathepsin K, PAX8 and MelanA, while CK7, CD117, CAIX, TFE3, and HMB45 are negative. There is no loss of SDHB and FH. Molecular analysis identified c2158A&gt;T and c.1258–2 A&gt;T mutations in the <em>TSC2</em> gene. The patient was followed up for two months without any disease progression.</div></div><div><h3>Conclusion</h3><div>By detailing the distinctive morphology, immunophenotype, and molecular traits of this ESC RCC case, we have outlined the histological, immunohistochemical, and molecular features of this new renal tumor type, and reviewed relevant literatures for a comprehensive understanding. Our findings expand current knowledge of ESC RCC and can assist in reducing misdiagnosis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155926"},"PeriodicalIF":2.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748173","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":"Identification of the crucial roles of BAXhigh NK cells in human derived mesenchymal stem cell therapy for chronic heart failure patients","authors":"Pengfei Zhang ,&nbsp;Yuanfeng Xin ,&nbsp;Hui Yuan ,&nbsp;Zhongmin Liu","doi":"10.1016/j.prp.2025.155924","DOIUrl":"10.1016/j.prp.2025.155924","url":null,"abstract":"<div><div>Mesenchymal stem cells (MSCs) have demonstrated significant potential in heart failure (HF) treatment, but the exact mechanisms are still not fully understood. This research utilized single-cell RNA sequencing to examine alterations in peripheral blood mononuclear cells from heart failure patients pre- and post-MSC therapy. Moreover, we utilized Mendelian randomization (MR) analysis to identify causal genes linked to HF. Specifically, through scRNA-seq, we observed a progressive increase in Natural Killer (NK) cells within peripheral blood mononuclear cells (PBMCs) following MSC treatment. Furthermore, MR analysis identified the differentially expressed gene (DEG) <em>BAX</em> as a potential target gene for HF. Notably, the expression of <em>BAX</em> was significantly downregulated after MSC treatment, suggesting its potential as a therapeutic response biomarker. Cell-cell communication analysis revealed that BAX^high NK cells displayed reduced cell-cell communication and increased apoptotic activity. Enrichment analysis indicated an association between BAX^high NK cells and the “coagulant” pathway. Taken together, our findings suggest that <em>BAX</em> may contribute to the pathogenesis of HF by promoting coagulation and apoptotic pathways. In contrast, MSCs appear to suppress <em>BAX</em> expression, thereby inhibiting these pathways. MSC treatment increases the proportion of NK cells and reduces BAX^high NK cells, ultimately improving NK cell function, and ameliorating HF.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155924"},"PeriodicalIF":2.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748171","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":"Crystal-storing histiocytosis of multiple myeloma with a novel multi-exon deletion of WRN: A case report and mini review of literature","authors":"Tian Wei ,&nbsp;Minhua Zhong ,&nbsp;Jinfu Li ,&nbsp;Jiande Han ,&nbsp;Xiaohong Chen ,&nbsp;Zhuo Wang","doi":"10.1016/j.prp.2025.155921","DOIUrl":"10.1016/j.prp.2025.155921","url":null,"abstract":"<div><div>Crystal-storing histiocytosis (CSH) is a rare condition composed of nonneoplastic histiocytes, which showed the abnormal intra-lysosomal accumulation of immunoglobulin (Ig) as crystals. At the same time, CSH is often associated with lymphoplasmacytic neoplasms. Previous research suggested that crystal deposition was caused by a change in protein activity. However, the reasons for Ig structural alterations are unknown. Only 8 examples of skin lesions associated with a human condition called CSH in the skin have been documented. Now we described a skin condition in the patient caused by CSH. More specifically, we first demonstrated a novel multi-exon deletion of WRN, including exon10-intron13, in this patient. Chr8:g.30941261_30947513del was displayed. It is a novel gross deletion mutation of WRN. WRN protein is a member of the RecQ subfamily of DNA helicase proteins. It is crucial for maintaining the stability of the genome and participating in DNA metabolism. 83 different WRN mutations, the majority of which were point mutations, were identified in earlier research. It is the first report of the novel WRN mutation in our patient. WRN loss of function due to point mutations may result in Werner syndrome, an autosomal recessive disorder. There was no evidence of Werner syndrome in our patient. Our case is a rare CSH in the skin associated with multiple myeloma. Diagnosis of this disorder is challenging. The somatic mutation of WRN was found in the histiocytic lesions of our patient’s skin. It would suggest that the WRN gene might be one of the reasons for the accumulation of crystals in the histiocytes. There may be a potential connection between WRN mutation and CSH pathogenesis. It would help us to comprehend why some patients with lymphoplasmacytic neoplasm have CSH.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155921"},"PeriodicalIF":2.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725818","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":"FBLN2 inhibits gastric cancer proliferation and metastasis via the TGFβ/TGIF2 pathway","authors":"Ming Zhou ,&nbsp;Xiaozhe Mao ,&nbsp;Kanger Shen ,&nbsp;Qin Zhan ,&nbsp;Haoxiang Ni ,&nbsp;Chun Liu ,&nbsp;Ziyi Huang ,&nbsp;Rui Li","doi":"10.1016/j.prp.2025.155899","DOIUrl":"10.1016/j.prp.2025.155899","url":null,"abstract":"<div><div>Gastric cancer (GC) ranks among the most common gastrointestinal tumours and is a significant contributor to cancer mortality globally. The proliferation, metastasis, occurrence and development of GC have obvious malignant tendencies. This study is based on our previous studies. Previously, we reported that Fibulin-2 (FBLN2) can inhibit the distant metastasis of GC by promoting lost-nest apoptosis. Despite its clinical importance, the biological function of FBLN2 in GC remains inadequately understood. This study investigated the underlying molecular mechanisms of FBLN2 in the pathogenesis and progression of GC, as well as its impact on the biological behaviour of GC cells. <em>In vivo</em> and <em>in vitro</em> experiments, we demonstrated that FBLN2 overexpression resulted in a reduction in GC cell proliferation and metastasis, whereas its knockdown led to enhancement of GC proliferation and metastasis. Moreover, we used RNA-seq technology to conduct KEGG enrichment analysis of differential genes in wild-type GC cells and FBLN2 knockout GC cells and successfully confirmed that FBLN2 plays a corresponding biological role through the TGFβ/TGIF2 axis. In addition, in terms of the clinical data, we revealed a correlation between FBLN2 and TGIF2 and patient prognosis. In summary, our study revealed that FBLN2 suppressed GC proliferation, migration and invasion by downregulating the TGFβ/TGIF2 axis, suggesting that FBLN2 is a promising target for GC treatment.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155899"},"PeriodicalIF":2.9,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748143","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":"RCC-Ma loss predicts poor survival and metastatic risk in clear cell renal cell carcinoma","authors":"PJ Stenzel ,&nbsp;KE Tagscherer ,&nbsp;C. Justenhoven ,&nbsp;PJ Wild ,&nbsp;A. Haferkamp ,&nbsp;S. Macher-Goeppinger ,&nbsp;W. Roth ,&nbsp;S. Frees ,&nbsp;S. Porubsky","doi":"10.1016/j.prp.2025.155919","DOIUrl":"10.1016/j.prp.2025.155919","url":null,"abstract":"<div><h3>Background</h3><div>With the increasing number of renal cell carcinoma subtypes and implications for prognosis and therapy, correct classification of renal masses remains a challenging issue. Clear cell renal cell carcinoma (ccRCC) is a tumor with an immunoprofile that often does not follow paradigmatic rules. Thus, the aim of this study was to analyze the heterogeneity of immunohistochemical staining patterns in ccRCC regarding patient prognosis.</div></div><div><h3>Methods</h3><div>The study cohort consisted of 727 ccRCC patients with surgical treatment between 1995 and 2006 and with comprehensive clinicopathological information and follow-up data. Only 1.6 % of patients received modern targeted therapy after surgery. The patients were stratified analogue to the Leibovich Risk Score (LRS). A tissue microarray was immunohistochemically stained for vimentin, CAIX, CD10, RCC-Ma, AMACR, CK7 and CD117. The expression in the tumor tissue was semiquantitatively scored and tested for association with clinicopathological tumor features and patient survival.</div></div><div><h3>Results</h3><div>Loss of RCC-Ma was an independent prognostic biomarker for disease specific survival (p = 0.01) and associated with a higher risk of developing metastasis in the intermediate risk group of the LRS as well as aggressive tumor features, such as higher tumor grade and stage, metastasis and necrosis. The other analyzed immunohistochemical biomarkers had no impact on patient prognosis.</div></div><div><h3>Conclusion</h3><div>As a predictor of poor survival and metastatic risk, RCC-Ma is likely to be a valuable contributor to the risk stratification in ccRCC patients. Moreover, this study cohort provides a valuable resource for investigations on the natural, therapy-naive clinical course of the disease and can serve as a reference for other study collectives, including patients treated with up-to-date targeted therapies.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155919"},"PeriodicalIF":2.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"INHBA, transcriptionally activated by SPI1, facilitates gastric cancer progression by inducing macrophage recruitment and M2 polarization via activating the TGF-β signaling to increase CCL2","authors":"Fan Zhang ,&nbsp;Congya Zhou ,&nbsp;Xifang Wang ,&nbsp;Ying Liu ,&nbsp;Yinyin Hou ,&nbsp;Lu Niu","doi":"10.1016/j.prp.2025.155920","DOIUrl":"10.1016/j.prp.2025.155920","url":null,"abstract":"<div><div>Tumor-associated macrophages (TAMs) are associated with the occurrence, development, and poor prognosis of human cancers. Inhibin beta A subunit (INHBA) is found to be aberrantly upregulated in gastric cancer (GC). However, whether INHBA is involved in macrophage recruitment and M2 polarization is unclear. Herein, INHBA expression was increased in GC tumor tissues and cells. INHBA expression was positively correlated with macrophage infiltration and M2 macrophage markers. Knockdown of INHBA in GC cells suppressed macrophage recruitment and M2 polarization by downregulaitng CCL2 expression and secretion. Mechanistic assays showed that SPI1 could bind to INHBA and transcriptionally activate its expression. SPI1 promoted macrophage recruitment and M2 polarization by upregulating INHBA expression. Moreover, SPI1 induced CCL2 expression by regulating INHBA in GC cells. INHBA upregulated CCL2 expression by activating the TGF-β signaling. Furthermore, SPI1-induced macrophages facilitated cell proliferation, migration, and invasion by increasing INHBA expression. INHBA-induced macrophages promoted cell proliferation, migration, and invasion by inducing CCL2 expression. Additionally, knockdown of INHBA inhibited tumor growth <em>in vivo</em>. In conclusion, SPI1 induces the macrophage recruitment and M2 polarization by transcriptionally regulating INHBA to activating the TGF-β signaling, thereby upregulating CCL2 expression and then contributing to GC cell malignant progression. Targeting SPI1/INHBA/CCL2 axis might be a promising therapeutic strategy for GC and potentially used for cancer immunotherapy.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155920"},"PeriodicalIF":2.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683948","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":"Mechanistic role of stromal cancer-associated fibroblasts in tumorigenesis and brain metastasis: Highlighting drug resistance and targeted therapy","authors":"Md Rashedunnabi Akanda ,&nbsp;Umme Lubaba ,&nbsp;Md Khalesur Rahman ,&nbsp;Anowarul Islam ,&nbsp;Momota Akter ,&nbsp;Md Sadikul Islam ,&nbsp;Md Nazim Uddin ,&nbsp;Byung-Yong Park","doi":"10.1016/j.prp.2025.155918","DOIUrl":"10.1016/j.prp.2025.155918","url":null,"abstract":"<div><div>Brain metastases remain a major clinical challenge due to their high resistance to conventional and targeted therapies. Cancer-associated fibroblasts are the most common cellular component of the brain metastases tumor microenvironment. They significantly impact the tumor microenvironment because they promote cancer cell invasion, enhance metastasis, boost immune evasion, and contribute to drug resistance. We searched the PubMed and Google Scholar databases and included 99 studies to summarize the present review. Based on the searched articles, the present review emphasizes that biomarkers including PDGFR-β, α-SMA, and collagen I can identify metastatic brain cancer-associated fibroblasts, which lead to a poor prognosis and recurrence. In addition, cancer-associated fibroblasts can cause resistance to therapy by modifying the extracellular matrix (e.g., collagen I, fibronectin), secreting growth factors (e.g., TGF-β, HGF, IL-6), causing immunological evasion (e.g., Tregs, MDSCs), secreting exosomes (e.g., miRNAs), metabolic reprogramming, stemness induction, and plasticity. We also describe the molecular mechanisms by which cancer-associated fibroblasts confer drug resistance in brain metastases, such as extracellular matrix restoration, immunological evasion, metabolic reprogramming, etc. We also cover prospective therapeutic options for overcoming medication resistance, such as cancer-associated fibroblasts depletion, paracrine signaling blockage, metabolic inhibitors, and cancer-associated fibroblasts-targeted immunotherapies. Targeting cancer-associated fibroblasts in addition to existing medications may improve cancer treatment efficacy and survival rates for individuals with brain metastases. However, more research is required to better understand their role in metastatic brain tumors.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155918"},"PeriodicalIF":2.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143684047","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":"Chemo-sensitive and chemo-resistant ovarian cancer cells show differences in cellular processes leading to pyroptotic cell death","authors":"Caglar Berkel,&nbsp;Aysun Keskin,&nbsp;Ercan Cacan","doi":"10.1016/j.prp.2025.155911","DOIUrl":"10.1016/j.prp.2025.155911","url":null,"abstract":"<div><div>Tumor immunology in ovarian cancer is not completely understood. Chemoresistance limits the success of available treatment options for patients with ovarian cancer. Pyroptosis, pro-inflammatory programmed cell death characterized by membrane pore formation by gasdermin proteins, is important for both immunogenicity and drug resistance. Here, we showed that estrogen increases GSDMC and GSDMD mRNA levels in chemo-sensitive ovarian cancer cells; but, not in chemo-resistant ovarian cancer cells <em>in vitro</em>. GSDMC or GSDMD overexpression increases cell viability in chemo-sensitive ovarian cancer cells; but, not in chemo-resistant ovarian cancer cells. Silencing of GSDMD in chemo-sensitive ovarian cancer cells and silencing of GSDMC in chemo-resistant ovarian cancer cells limit the effect of nigericin, a pyroptosis inducer, on cell viability. Inhibition of caspase-1, −4, −6 or −8 blocks nigericin-induced cell death (pyroptosis) in chemo-sensitive ovarian cancer cells; however, only the inhibition of caspase-1 blocks nigericin-induced cell death in chemo-resistant ovarian cancer cells, showing that caspases participating in pyroptosis might differ between ovarian cancer cells based on their chemo-sensitivity profiles. Treatment with disulfiram, a GSDMD pore formation inhibitor, decreases cell viability in both cell lines. Lastly, we found that in chemo-resistant ovarian cancer cell line, disulfiram and nigericin combination treatment decreases cell viability even more compared to only disulfiram or only nigericin treatment. Combined, our study points that ovarian cancer cells with different chemosensitivity profiles might have certain differences in pyroptotic cell death.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155911"},"PeriodicalIF":2.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670078","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}