Pathology, research and practice最新文献

{"title":"Artificial intelligence challenge of discriminating cutaneous arteritis and polyarteritis nodosa based on hematoxylin-and-eosin images of skin biopsy specimens","authors":"Wataru Kashiwa ,&nbsp;Kenji Hirata ,&nbsp;Hiroki Endo ,&nbsp;Kohsuke Kudo ,&nbsp;Chietsugu Katoh ,&nbsp;Tamihiro Kawakami ,&nbsp;Hiroyuki Kanno ,&nbsp;Kei Takahashi ,&nbsp;Tatsuhiko Miyazaki ,&nbsp;Eiji Ikeda ,&nbsp;Toshiaki Oharaseki ,&nbsp;Yayoi Ogawa ,&nbsp;Mitsuho Onimaru ,&nbsp;Mie Kurata ,&nbsp;Daigo Nakazawa ,&nbsp;Eri Muso ,&nbsp;Yuka Nishibata ,&nbsp;Sakiko Masuda ,&nbsp;Utano Tomaru ,&nbsp;Yoshihiro Matsuno ,&nbsp;Akihiro Ishizu","doi":"10.1016/j.prp.2025.155915","DOIUrl":"10.1016/j.prp.2025.155915","url":null,"abstract":"<div><div>Diseases that develop necrotizing vasculitis of cutaneous muscular arteries include cutaneous arteritis (CA) and polyarteritis nodosa (PAN). It is difficult to distinguish them based on skin biopsy findings alone. This study demonstrated that artificial intelligence (AI) can discriminate them based on skin biopsy findings and revealed where AI focuses on the image. Ninety-three hematoxylin-and-eosin images of CA and 19 PAN images were used. Among them, 85 CA and 17 PAN images were used to train AI; thereafter, AI was challenged to classify the remaining images. The same test images were evaluated by 26 pathologists with different years of experience. AI accuracy was 75.2 %, whereas that of pathologists was 42.8 %. Gradient-weighted class activation mapping (Grad-CAM) indicated that AI focused on connective tissues around the affected vessels rather than the affected vessels. Twenty-two of the 26 pathologists were randomly divided into two groups of 11 each, one of which referred to Grad-CAM images and was challenged in the second-round test of images different from the first round. The accuracy significantly improved after referring to Grad-CAM images, whereas it was equivalent to the first round without referring to Grad-CAM images. In the survey after the second-round test, pathologists who referred to Grad-CAM images suggested that inflammation and fibrosis in the surrounding connective tissues in PAN might be abundant compared to CA. AI may be useful for histological differentiation between CA and PAN and can help pathologists improve the ability of discriminating CA and PAN based on histological findings of skin biopsy specimens.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155915"},"PeriodicalIF":2.9,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643103","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":"Role of H3F3A (H3G34W) antibody in the diagnosis of giant cell tumour of bone in the paediatric age group","authors":"Syeda Maria Ahmad Zaidi ,&nbsp;Muhammad Taha Nasim ,&nbsp;Javerya Hassan ,&nbsp;Nasir Ud Din","doi":"10.1016/j.prp.2025.155906","DOIUrl":"10.1016/j.prp.2025.155906","url":null,"abstract":"<div><div>Giant cell tumour of the bone (GCTB) occurring in paediatric patients is rare and may presents with atypical histology. Given that giant cell tumour mimics, such as osteosarcoma, are more prevalent in this demographic, diagnosing GCTB can often be challenging. This study aimed to investigate the efficacy of H3F3A immunohistochemistry (IHC) in the diagnosis of GCTB in the immature skeleton. This retrospective study included paediatric patients who were diagnosed with GCTB between 2009 and 2024. Histological features were re-evaluated and IHC staining was performed. Giant cell tumour mimics were included in the control group. 72 biopsy proven GCTB were reported in the paediatric patients during the study period. The age ranged from 12 to 18 years, with a median age of 16 ( ± 1.8) years. 49 (68.1 %) were females and 23 (31.9 %) were males (female to male ratio of 2.1:1). Tibia was most common site (23) involved followed by femur (12), fibula (8) and small bones of hand and feet (8). H3G34W was positive in 61 (84.7 %) of GCTB cases (p &lt; 0.01); and negative in all 33 GCTB mimics. H3G34V was positive in 3 of 11 H3G34W negative cases. All these 11 cases were negative for H3G34R and keratin AE1/AE3. Significant association of GCTB was found with gender (p = 0.02) and site of the tumour (p &lt; 0.01). HG34W was not associated with tumour site (p = 0.4533) or biopsy yield (p = 0.4533). A sensitivity of 84.74 %, specificity of 100 %, positive predictive value of 75 % and negative predictive value of 100 % was established. An ROC was constructed, with area under the curve of 0.924 (95 % CI 0.88–0.97). In conclusion H3G34W antibody is a valuable diagnostic tool for accurately diagnosing GCTB and distinguishing it from other giant cell mimics. Additionally, since a minimal tissue yield is adequate for determining the diagnosis, the need for larger biopsies is reduced.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155906"},"PeriodicalIF":2.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643036","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":"Clinicopathologic analysis and digital pathology evaluation of orchiectomy specimens in gender-affirmation surgery","authors":"Ivan De La Riva-Morales ,&nbsp;Alcino Gama ,&nbsp;Ruoji Zhou ,&nbsp;Bonnie Choy ,&nbsp;Bogdan Isaila ,&nbsp;Behtash G. Nezami ,&nbsp;Robert Brannigan ,&nbsp;Diana Bowen ,&nbsp;Ximing Yang","doi":"10.1016/j.prp.2025.155914","DOIUrl":"10.1016/j.prp.2025.155914","url":null,"abstract":"<div><div>Gender-affirmation therapies for transgender and gender diverse (TGD) individuals has been increasing in numbers in recent years. TGD patients usually undergo various forms of hormonal replacement therapy (HRT) followed by bilateral orchiectomy. We aimed to characterize the histological and biochemical alterations in these specimens. From 2018–2023, 63 TGD individuals undergone gender-affirming orchiectomy. Atrophic changes, decreased spermatogenesis, and reduced mean tubule diameter with basement membrane thickening, as well as maturation arrest and aspermatogenesis were identified. A subset of specimens (n = 81, 64.8 %) showed germ cell nucleomegaly with cytological atypia mimicking germ cell neoplasia in situ, and detailed digital pathology and immunohistochemical were performed to distinguish this finding from true neoplastic processes. To our knowledge, this is the largest single-center cohort of gender-affirming orchiectomy specimens.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155914"},"PeriodicalIF":2.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674484","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":"Ferroptosis in cancer: Mechanisms, therapeutic strategies, and clinical implications","authors":"Mina Pourhabib Mamaghani ,&nbsp;Seyedeh Nasibeh Mousavikia ,&nbsp;Hosein Azimian","doi":"10.1016/j.prp.2025.155907","DOIUrl":"10.1016/j.prp.2025.155907","url":null,"abstract":"<div><div>The resistance of cancer cells to existing treatments has become a major challenge for researchers despite advancements in cancer treatment. Studies have shown that this resistance is due to cancer cells evading apoptosis. Moreover, the most common form of cell death induced by chemotherapy and radiotherapy is apoptosis. One of the most essential mechanisms cancer cells escape apoptosis is the excessive expression of tumors' apoptosis inhibitors. Therefore, finding a non-apoptotic pathway that bypasses apoptosis could be a hopeful strategy for cancer treatment. Ferroptosis has been identified as a non-apoptotic and regulated cell death process characterized by the accumulation of lipid peroxides and iron-dependent reactive oxygen species (ROS). Although studies have shown that ferroptosis plays a role in the development of many diseases, including cancer, it also has the potential to decrease resistance to current treatments, such as chemotherapy. Additionally, research has shown that ferroptosis successfully kills cancer cells, such as breast, stem, and lung cancer cells. Therefore, ferroptosis can be identified as a beneficial therapeutic mechanism for cancer treatment. Although ferroptosis has been introduced as an effective treatment path for cancer, its role, along with its therapeutic inducers, in increasing the therapeutic effect has not been investigated.</div><div>In this review, we aim to introduce ferroptosis, compare it with other cell deaths known so far, and explain its role in cancer treatment. We believe that ferroptosis can be widely used to overcome cancer cells.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155907"},"PeriodicalIF":2.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143636635","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":"Curcumin enhances anti-tumor immunity in anaplastic thyroid carcinoma by elevating CD8+ T cell function and downregulating the AKT/mTORC1/STAT3/PD-L1 axis","authors":"Jiaojiao Zheng ,&nbsp;Wei Liu ,&nbsp;Xiaolong Wang ,&nbsp;He Li ,&nbsp;Zhenglin Wang ,&nbsp;Zhilong Ai","doi":"10.1016/j.prp.2025.155898","DOIUrl":"10.1016/j.prp.2025.155898","url":null,"abstract":"<div><div>Curcumin, a compound isolated from turmeric, has been found to have promising anti-tumor effects in various cancers, including anaplastic thyroid carcinoma (ATC). However, the molecular mechanism of curcumin in ATC remains largely unclear. CD8 +T cells could eliminate rapidly proliferating malignant cells, whereas interaction between programmed death-1 (PD-1) and programmed cell death ligand 1 (PD-L1) could inhibit the activation and functions of CD8 + T cells. Thus, we aimed to explore whether curcumin could inhibit ATC progression via regulating CD8 + T cells and PD-L1 expression. The protein expression of PD-L1 in ATC cells was detected by western blot assay. Additionally, a syngeneic mouse model was used to assess the effect of curcumin or/and anti-PD-1 treatment on tumorigenesis <em>in vivo</em>. The effect of curcumin on CD8 +T cell function was investigated by flow cytometry <em>in vitro</em> and <em>in vivo</em>. The results indicated curcumin notably suppressed ATC cell proliferation, migration and invasion and induced cell apoptosis. Additionally, curcumin could reduce PD-L1 level in ATC cells through inactivating AKT/mTORC1/STAT3 signaling. Meanwhile, curcumin obviously elevated CD8 + T cell function by elevating the number of IFN-γ producing CD8 + T cells. Furthermore, curcumin or anti-PD-L1 treatment could enhance anti-tumor immunity by increasing infiltration of CD8 + T cells in tumor tissues <em>in vivo</em>. As expected, compared to the single treatment, combination curcumin and anti-PD-1 treatment further elevated CD8 + T cell function <em>in vivo</em>, thereby potentiating anti-tumor immunity in ATC. Collectively, curcumin could enhance anti-tumor immunity in ATC by elevating CD8 + T cell function and inactivating the AKT/mTORC1/STAT3/PD-L1 axis. Our findings demonstrated a novel mechanism of the anti-tumor effects of curcumin in ATC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155898"},"PeriodicalIF":2.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143636637","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":"FCGR1A(CD64) expression on monocyte subsets and FIL1Z(IL-37) serum level as biomarkers of rheumatoid arthritis activity: A case controlled study and in silico analysis","authors":"Entsar R. Mokhtar ,&nbsp;Doaa Aly Abd El-Fattah ,&nbsp;Neama R. Hussein ,&nbsp;Heba Elhakeem ,&nbsp;Lamia A. Gad ,&nbsp;Eman Fekry Mohamed ,&nbsp;Rehab Abd Elfattah Mohammed ,&nbsp;Sammar Ahmed Kasim ,&nbsp;Sara M. Elhadad ,&nbsp;Marwa Mohamed M. Ali Abd El Rahim ,&nbsp;Maha S. Mohamed ,&nbsp;Mohamed Sobhy Mahmoud Rezk ,&nbsp;Doaa Fathy ,&nbsp;Nadia M. Hamdy ,&nbsp;Hekmat M. El Magdoub","doi":"10.1016/j.prp.2025.155910","DOIUrl":"10.1016/j.prp.2025.155910","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is one of the most common chronic autoimmune diseases. Chronic joint inflammation and bone destruction were shown to be caused by expanded monocytes in RA affected individuals. Interleukin-37 which known as FIL1Z(IL-37) is a well-known anti-inflammatory cytokine that plays a negative regulatory role of inflammation in RA. A total of 48 RA patients were divided equally into active RA group and stable RA group using the Disease Activity score (DAS)-28 score. Twenty-four age-and sex-matched healthy subjects were enrolled as controls. The expression level of Fc gamma receptor IA (FCGR1A(CD64)) on monocytes and their subsets in peripheral blood were assessed by flow cytometry (FC) and serum levels of FIL1Z(IL-37) were measured by ELISA. The mean fluorescence intensity (MFI) of FCGR1A(CD64) expressing classical and intermediate monocyte subsets and serum levels of FIL1Z(IL-37) were significantly elevated in RA patients compared to the control and positively correlated with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) and DAS-28 scores. The MFI of FCGR1A(CD64) expressing classical monocyte and serum levels of FIL1Z(IL-37) were significantly elevated in the active RA group compared to the stable RA group. The serum concentration of FIL1Z(IL-37) revealed very high specificity but limited sensitivity in discriminating between active and stable RA patients. Our results demonstrate a strong correlation between serum levels of FIL1Z(IL-37) and FCGR1A(CD64) expression on activated monocytes and their subsets in peripheral blood of RA patients. The results also depict that activated monocytes and their subsets may contribute to the elevated levels of FIL1Z(IL-37) during an active disease status to counter-act the inflammatory process.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155910"},"PeriodicalIF":2.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619806","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":"Advancements in bone malignancy research through next-generation sequencing focussed on osteosarcoma, chondrosarcoma, and Ewing sarcoma","authors":"Naveen Jeyaraman ,&nbsp;Madhan Jeyaraman ,&nbsp;Preethi Subramanian ,&nbsp;Swaminathan Ramasubramanian ,&nbsp;Sangeetha Balaji ,&nbsp;Sathish Muthu ,&nbsp;Ramya Lakshmi Rajendran ,&nbsp;Prakash Gangadaran","doi":"10.1016/j.prp.2025.155908","DOIUrl":"10.1016/j.prp.2025.155908","url":null,"abstract":"<div><div>Next-generation sequencing (NGS) technologies have revolutionized bone cancer research, enabling detailed insights into the genetic, transcriptional, and epigenetic layers of these malignancies. This overview discusses the pivotal role of NGS in enhancing the diagnosis, prognosis, and treatment of primary bone cancers such as osteosarcoma, chondrosarcoma, and Ewing sarcoma. By facilitating the identification of novel genetic mutations, gene fusions, and epigenetic alterations, NGS supports the development of personalized medicine approaches and targeted therapies, significantly impacting clinical outcomes. The utilization of various NGS platforms, including Illumina, SOLiD, and Ion Torrent, has provided comprehensive genomic profiles that inform targeted treatment strategies and enable early detection through liquid biopsies and circulating tumor DNA (ctDNA) analysis. Despite the profound clinical benefits, the integration of NGS into routine practice faces challenges such as technical limitations, complex data interpretation, and substantial infrastructure requirements. Future directions involve technological improvements, combinatorial omics approaches, and extensive validation through clinical trials to confirm the efficacy of NGS-guided interventions. These advancements promise to further enhance the precision and effectiveness of bone cancer management, offering hope for more tailored and effective therapeutic outcomes.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155908"},"PeriodicalIF":2.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619680","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":"Loss of SWI/SNF complex expression (SMARCA4, SMARCA2, SMARCB1, ARID1A) is associated with dMMR in primary adenocarcinoma of jejunum and ileum: A clinicopathological and molecular analysis based on the Chinese population","authors":"Minying Deng ,&nbsp;Rongkui Luo ,&nbsp;Huimei Wang ,&nbsp;Ayizimugu Abuduwaili ,&nbsp;Dongxian Jiang ,&nbsp;Xinyi Zhang ,&nbsp;Lei Xu ,&nbsp;Xiaolei Zhang ,&nbsp;Zhiping Niu ,&nbsp;Jieakesu Su ,&nbsp;Chen Xu ,&nbsp;Yingyong Hou","doi":"10.1016/j.prp.2025.155891","DOIUrl":"10.1016/j.prp.2025.155891","url":null,"abstract":"<div><h3>Objective</h3><div>The SWI/SNF complex is an important chromatin remodeling complex that has been reported in various tumors. To date, there have been no reports on the subunits of this complex in primary small bowel adenocarcinoma (PSBA).</div></div><div><h3>Methods</h3><div>Hematoxylin &amp; Eosin (H&amp;E) staining slides were reviewed, and the expression of MMR protein, BRM (SMARCA2), BRG1 (SMARCA4), INI1 (SMARCB1), and ARID1A proteins was detected. Molecular genetic testing was performed utilizing the amplification-refractory mutation system (ARMS) and high-throughput sequencing technology.</div></div><div><h3>Results</h3><div>In this cohort of 58 cases, there was a trend toward a female predominance in ARID1A loss (<em>P</em> = 0.084), and BRM (SMARCA2) loss was associated with lymphatic invasion (<em>P</em> = 0.043). A significant positive correlation was observed between ARID1A loss and dMMR (<em>P</em> = 0.021), and BRG1 (SMARCA4) loss was more prevalent in poorly differentiated PSBA (<em>P</em> = 0.023). ARID1A loss was positively correlated with <em>PIK3CA</em> gene mutation (r = 0.551, <em>P</em> &lt; 0.001), and loss of MMR protein expression was also positively correlated with <em>PIK3CA</em> gene mutation (r = 0.354, <em>P</em> = 0.006). Additionally, BRM (SMARCA2) loss showed a significant positive correlation with <em>NRAS</em> gene mutation (r = 0.293, <em>P</em> = 0.025) and a significant negative correlation with <em>KRAS</em> gene mutation (r = -0.281, <em>P</em> = 0.033). Univariate analysis indicated a trend toward poor prognosis with BRM (SMARCA2) loss (<em>P</em> = 0.097).</div></div><div><h3>Conclusion</h3><div>This study represents the initial description of loss of the SWI/SNF complex expression in PSBA, which is rare and primarily originates in the jejunum and ileum. Further investigations are warranted to elucidate potential targets of <em>PIK3CA</em> inhibitors for dMMR PSBA and ARID1A loss of expression in PSBA.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155891"},"PeriodicalIF":2.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143636638","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":"MARCH8 ubiquitinates and degrades CEMIP to induce colorectal cancer cell ferroptosis through inactivating PI3K/AKT pathway","authors":"Lintao Liu ,&nbsp;Cheng Zhang ,&nbsp;Bo Yang ,&nbsp;Maonan Wang","doi":"10.1016/j.prp.2025.155909","DOIUrl":"10.1016/j.prp.2025.155909","url":null,"abstract":"<div><h3>Background</h3><div>Cell migration-inducing and hyaluronan-binding protein (CEMIP) is found to act as an oncogene in colorectal cancer (CRC) progression, but the underlying molecular mechanisms need to be further elucidated.</div></div><div><h3>Methods</h3><div>The mRNA and protein levels of CEMIP and membrane-associated ring-CH-type finger 8 (MARCH8) were examined by qRT-PCR and western blot. Cell functions were detected by CCK8 assay, colony formation assay and transwell assay. The levels of ROS, Fe^2 +, GSH, and MDA were examined to evaluate cell ferroptosis. The interaction between MARCH8 and CEMIP was assessed by Co-IP assay and ubiquitination assay. The protein levels of ferroptosis-related markers (ACSL4, GPX4 and FTH1) and PI3K/AKT-related markers were tested using western bolt. The anti-tumor effect of MARCH8 was further confirmed by constructing xenograft tumor models.</div></div><div><h3>Results</h3><div>CEMIP expression was higher in CRC tissues and cells. CEMIP knockdown could suppress CRC cell proliferation, migration, invasion, and enhance ferroptosis. MARCH8 ubiquitinated CEMIP to decrease its expression, thus inhibiting CRC cell proliferation, metastasis and inducing ferroptosis. And CEMIP overexpression could abolish the anti-proliferation, anti-metastasis and pro-ferroptosis effect of MARCH8. Also, MARCH8 overexpression repressed the activity of PI3K/AKT pathway, and CEMIP upregulation partially reversed this effect. <em>In vivo</em> experiments suggested that MARCH8 reduced CRC tumorigenesis by inducing ferroptosis.</div></div><div><h3>Conclusion</h3><div>MARCH8 promoted CRC cell ferroptosis via inhibiting PI3K/AKT pathway by enhancing the ubiquitination and degradation of CEMIP.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155909"},"PeriodicalIF":2.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643102","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":"M2 macrophages-derived exosomal MDH1 drives lung adenocarcinoma progression via the Hippo/YAP signaling","authors":"Jie Zhang,&nbsp;Jinpeng Liu,&nbsp;Zhuixing Liu,&nbsp;Lihong Guo,&nbsp;Xueqin Liu","doi":"10.1016/j.prp.2025.155902","DOIUrl":"10.1016/j.prp.2025.155902","url":null,"abstract":"<div><h3>Background</h3><div>Exosomes are released by most cell types, including tumor-associated macrophages (TAMs), transfer diverse macromolecules and participate in intercellular communication in cancer. However, whether M2-polarized TAMs (M2-TAMs)-derived exosomes (M2-exos) transmit the oncogenic protein malate dehydrogenase 1 (MDH1) to reprogram lung adenocarcinoma (LUAD) cancer cells is unknown.</div></div><div><h3>Methods</h3><div>THP-1-differentiated macrophages were co-cultured with A549 cells to generate TAMs (M0-TAMs and M2-TAMs). Exosomes (M0-exos and M2-exos) were isolated from the co-culture supernatant and characterized. Xenograft studies were used to explore the effect of M2-exos-derived MDH1 on tumor growth. Expression analysis was performed by quantitative PCR, immunoblot and immunohistochemistry (IHC). Cell phenotype changes were detected by CCK-8, EdU, colony formation, wound-healing and transwell assays.</div></div><div><h3>Results</h3><div>Bioinformatics analyses confirmed that MDH1 was overexpressed in human LUAD and high MDH1 expression was associated with poor prognosis. MDH1 depletion resulted in the <em>in vitro</em> suppression of LUAD cell growth, migration and invasiveness. M2-exos contained and transferred MDH1 into LUAD cells to upregulate MDH1 level in these cells. M2-exos-derived MDH1 enhanced the growth of A549 xenograft tumors <em>in vivo</em> and activated the Hippo/YAP pathway <em>in vitro</em>. Furthermore, Yes-associated protein (YAP) depletion could abrogate M2-exos-induced enhancements in these malignant phenotypes of A549 and HCC827 LUAD cells.</div></div><div><h3>Conclusion</h3><div>These findings demonstrate that exosomal MDH1 derived from M2-TAMs enhance LUAD cell growth and metastasis by activating the Hippo/YAP signaling, uncovering a novel exosomal mechanism of crosstalk between tumor microenvironment and LUAD cells.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"269 ","pages":"Article 155902"},"PeriodicalIF":2.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628549","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}