Pathology, research and practice最新文献

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Qiu’s Cervical Prescription inhibit the invasion and growth of cervical cancer through LncRNA ATB/miR-126 pathway Qiu’s Cervical方通过LncRNA ATB/miR-126通路抑制宫颈癌的侵袭和生长。
IF 2.9 4区 医学
Pathology, research and practice Pub Date : 2025-02-01 DOI: 10.1016/j.prp.2024.155784
Yingping Zhu , Yang Lv , Haili Yao , Zhilei Chen , Wenjuan Yang , Chuntao Tian , Weiyi Yang , Mingyang Li , Qingge Jia , Liangping Wang
{"title":"Qiu’s Cervical Prescription inhibit the invasion and growth of cervical cancer through LncRNA ATB/miR-126 pathway","authors":"Yingping Zhu ,&nbsp;Yang Lv ,&nbsp;Haili Yao ,&nbsp;Zhilei Chen ,&nbsp;Wenjuan Yang ,&nbsp;Chuntao Tian ,&nbsp;Weiyi Yang ,&nbsp;Mingyang Li ,&nbsp;Qingge Jia ,&nbsp;Liangping Wang","doi":"10.1016/j.prp.2024.155784","DOIUrl":"10.1016/j.prp.2024.155784","url":null,"abstract":"<div><h3>Background</h3><div>Cervical cancer (CC) is one of the most deadly cancers in women, its current treatments still result in poor outcomes and developing the novel targets and therapeutic strategies are urgently needed. Qiu’s Cervical Prescription (QCP) is one of the traditional Chinese medicines used in the treatment of cervical cancer in China. Although its curative effect is remarkable, the internal mechanism of its treatment is still poorly understood. Recent studies have shown that LncRNA ATB might be used as a new proliferation marker for cancer diagnosis and prognosis. This study aimed to investigate the possible mechanism of action of QCP in the treatment of cervical cancer.</div></div><div><h3>Methods</h3><div>The functional assays of migration and invasion in vitro using transwell assays and wound healing assays was performed to confirm the pro-carcinogenic effect of LncRNA ATB, and the changes of migration and invasion of HeLa cells were observed after treatment with QCP containing drug serum. The changes in tumor volume, general condition of transplanted tumor-bearing mice and expression of LncRNA ATB pathway-related proteins were detected by qPCR, Western blotting and HE staining after treatment with the QCP.</div></div><div><h3>Results</h3><div>We induced LncRNA ATB knockdown and overexpression in cervical cancer cell lines and detected the biological behavior changes <em>in vitro</em>. Furthermore, we established murine models using stable LncRNA ATB-shRNA HeLa cells or overexpression LncRNA ATB cells or normal Hela cells with QCP to evaluate how suppression of LncRNA ATB affects tumor growth.</div></div><div><h3>Conclusion</h3><div>We showed that potential mechanism of QCP in the treatment of cervical cancer may be through inhibition of the LncRNA ATB/miR-126/TGFβ1 signaling axis. In conclusion, QCP may be a promising approach for the treatment of CC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155784"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877824","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}
引用次数: 0
Mast cell proteases and metastasis 肥大细胞蛋白酶和转移。
IF 2.9 4区 医学
Pathology, research and practice Pub Date : 2025-02-01 DOI: 10.1016/j.prp.2024.155801
Domenico Ribatti
{"title":"Mast cell proteases and metastasis","authors":"Domenico Ribatti","doi":"10.1016/j.prp.2024.155801","DOIUrl":"10.1016/j.prp.2024.155801","url":null,"abstract":"<div><div>Mast cells exert multiple roles beyond their classical role in IgE-mediated allergic reactions. These cells secrete pro-inflammatory and anti-inflammatory agents and change from protective immune cells to pro-inflammatory cells, capable of influencing the progression of different pathological conditions, including tumors, in which they exert anti-tumorigenic and pro-tumorigenic roles. In this context, this article analyzes the potential role played by mast cell-derived proteases in tumor progression and more specifically in driving metastatic process and the potential therapeutic approaches that inhibiting the activation of these cells could help faith cancer spreading.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155801"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927717","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}
引用次数: 0
siRNA-based knockdown of lncRNAs: A new modality to target tumor progression 基于sirna的lncrna敲低:一种靶向肿瘤进展的新模式。
IF 2.9 4区 医学
Pathology, research and practice Pub Date : 2025-02-01 DOI: 10.1016/j.prp.2024.155746
Abdulrahman Qais Khaleel , Saade Abdalkareem Jasim , Soumya V. Menon , Mandeep Kaur , G.V. Sivaprasad , Safia Obaidur Rab , Ahmed Hjazi , Abhinav Kumar , Beneen Husseen , Yasser Fakri Mustafa
{"title":"siRNA-based knockdown of lncRNAs: A new modality to target tumor progression","authors":"Abdulrahman Qais Khaleel ,&nbsp;Saade Abdalkareem Jasim ,&nbsp;Soumya V. Menon ,&nbsp;Mandeep Kaur ,&nbsp;G.V. Sivaprasad ,&nbsp;Safia Obaidur Rab ,&nbsp;Ahmed Hjazi ,&nbsp;Abhinav Kumar ,&nbsp;Beneen Husseen ,&nbsp;Yasser Fakri Mustafa","doi":"10.1016/j.prp.2024.155746","DOIUrl":"10.1016/j.prp.2024.155746","url":null,"abstract":"<div><div>This study examines the potential of small interfering RNA (siRNA) as a therapeutic agent for cancer targeting long non-coding RNAs (lncRNAs). The article begins with an analysis of the structure and biogenesis of lncRNA. It explains the diverse functions of lncRNAs in cancer, establishing a foundation for assessing approaches to inhibit these molecules. The analysis focuses on the consequences of lncRNA suppression through siRNA on signaling pathways associated with cancer, connecting theoretical understanding to practical applications. An evaluation of ongoing clinical trials and applications contributes to the discourse by revealing the potential for siRNA-mediated interventions to be practiced. Furthermore, an evaluation of the advantages and disadvantages of this therapeutic approach offers a nuanced viewpoint. In conclusion, the paper synthesizes significant discoveries and outlines potential avenues for future research, contributing to the dialogue surrounding personalized cancer therapeutics and precision medicine. Future challenges in using siRNA to target lncRNAs in oncology include optimizing delivery systems for efficient tumor cell uptake, minimizing off-target effects, enhancing RNA stability for a longer therapeutic window, and overcoming barriers in the tumor microenvironment. Addressing these factors is essential for the practical application of siRNA-based cancer therapies.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155746"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807745","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}
引用次数: 0
Reduced GATA3 expression during breast cancer progression: A potential anchor for pulmonary metastatic deposition 乳腺癌进展过程中GATA3表达降低:肺转移沉积的潜在锚点。
IF 2.9 4区 医学
Pathology, research and practice Pub Date : 2025-02-01 DOI: 10.1016/j.prp.2025.155821
Shoujun Chen , Diana M. Oramas Mogrovejo , Xiao Huang, Gene P. Siegal, Shi Wei
{"title":"Reduced GATA3 expression during breast cancer progression: A potential anchor for pulmonary metastatic deposition","authors":"Shoujun Chen ,&nbsp;Diana M. Oramas Mogrovejo ,&nbsp;Xiao Huang,&nbsp;Gene P. Siegal,&nbsp;Shi Wei","doi":"10.1016/j.prp.2025.155821","DOIUrl":"10.1016/j.prp.2025.155821","url":null,"abstract":"<div><div>Estrogen receptor (ER) is a direct and reciprocal target gene for GATA3. Previous studies have shown that higher GATA3 expression in primary breast cancer (BC) is associated with a reduced probability of developing lung metastasis when compared to those with metastatic recurrence to other organs. Further, GATA3 downregulates several genes promoting BC lung metastasis and upregulates genes encoding known inhibitors of lung metastasis. In this study, we examined GATA3 expression in 34 consutive cases of paired primary BCs and their pulmonary metastases. Variable levels of GATA3 expression were seen in 94 % primary BCs (mean H-score 239), whereas a significantly reduced GATA3 expression was seen in the paired lung metastases (mean H-score 152; <em>P</em> &lt; 0.0001). However, this trend was not observed for ER (mean H-score 140 vs. 109; <em>P</em> = 0.1). These findings provide further evidence that GATA3 may inhibit pulmonary deposition or sondary growth of BC cells in the lung. The effect of GATA3 in metastatic tumor growth was independent of cell differentiation, and this process is likely mediated by a GATA3-regulated genetic program driven by metastasis-associated genes rather than ER. Further exploring the molecular pathways by which GATA3 regulates downstream targets is pivotal in understanding organ-specific BC dissemination.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155821"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009701","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}
引用次数: 0
Exosomal signaling in gynecologic cancer development: The role of cancer-associated fibroblasts 妇科癌症发展过程中的外泌体信号传导:癌症相关成纤维细胞的作用
IF 2.9 4区 医学
Pathology, research and practice Pub Date : 2025-02-01 DOI: 10.1016/j.prp.2024.155766
Mohamed J. Saadh , Omer Qutaiba B. Allela , Radhwan Abdul Kareem , Muktesh Chandra , H. Malathi , Deepak Nathiya , Ish Kapila , Hayder Naji Sameer , Atheer Khdyair Hamad , Zainab H. Athab , Mohaned Adil
{"title":"Exosomal signaling in gynecologic cancer development: The role of cancer-associated fibroblasts","authors":"Mohamed J. Saadh ,&nbsp;Omer Qutaiba B. Allela ,&nbsp;Radhwan Abdul Kareem ,&nbsp;Muktesh Chandra ,&nbsp;H. Malathi ,&nbsp;Deepak Nathiya ,&nbsp;Ish Kapila ,&nbsp;Hayder Naji Sameer ,&nbsp;Atheer Khdyair Hamad ,&nbsp;Zainab H. Athab ,&nbsp;Mohaned Adil","doi":"10.1016/j.prp.2024.155766","DOIUrl":"10.1016/j.prp.2024.155766","url":null,"abstract":"<div><div>Gynecologic cancer, a prevalent and debilitating disease affecting women worldwide, is characterized by the uncontrolled proliferation of cells in the reproductive organs. The complex etiology of gynecologic cancer encompasses multiple subtypes, including cervical, ovarian, uterine, vaginal, and vulvar cancers. Despite optimal treatment strategies, which typically involve cytoreductive surgery and platinum-based chemotherapy, gynecologic cancer frequently exhibits recalcitrant relapse and poor prognosis. Recent studies have underscored the significance of the tumor microenvironment in ovarian carcinogenesis, particularly with regards to the discovery of aberrant genomic, transcriptomic, and proteomic profiles. Within this context, cancer-associated fibroblasts (CAFs) emerge as a crucial component of the stromal cell population, playing a pivotal role in oncogenesis and cancer progression. CAF-derived exosomes, small extracellular vesicles capable of conveying biological information between cells, have been implicated in a range of tumor-related processes, including tumorigenesis, cell proliferation, metastasis, drug resistance, and immune responses. Furthermore, aberrant expression of CAF-derived exosomal noncoding RNAs and proteins has been found to strongly correlate with clinical and pathological characteristics of gynecologic cancer patients. Our review provides a novel perspective on the role of CAF-derived exosomes in gynecologic cancer, highlighting their potential as diagnostic biomarkers and therapeutic targets.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155766"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847134","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}
引用次数: 0
Novel ganglion cell marker B3GNT6: A step forward in Hirschsprung's disease diagnosis 新的神经节细胞标记物B3GNT6:巨结肠疾病诊断的新进展
IF 2.9 4区 医学
Pathology, research and practice Pub Date : 2025-02-01 DOI: 10.1016/j.prp.2024.155780
Fatme Ghandour , Kesley D. Green , Ekta Jain , Prachi Bajpai , Chirag R. Patel , Upender Manne , Sameer Al Diffalha
{"title":"Novel ganglion cell marker B3GNT6: A step forward in Hirschsprung's disease diagnosis","authors":"Fatme Ghandour ,&nbsp;Kesley D. Green ,&nbsp;Ekta Jain ,&nbsp;Prachi Bajpai ,&nbsp;Chirag R. Patel ,&nbsp;Upender Manne ,&nbsp;Sameer Al Diffalha","doi":"10.1016/j.prp.2024.155780","DOIUrl":"10.1016/j.prp.2024.155780","url":null,"abstract":"<div><div>Hirschsprung's (HSCR) disease, also known as aganglionic megacolon, or congenital intestinal aganglionosis affects roughly 1 out of every 5000 newborns. It is a birth defect characterized by the partial or complete loss of ganglion cells in the myenteric and submucosal plexus of the distal intestine which leads to ineffective peristalsis, constipation, and obstruction. Clinical assessment and radiological observations might imply HSCR disease, but definitive diagnosis requires biopsy interpretation and confirmation of ganglion cell loss. The difficulty in identifying immature ganglion cells added to the variability in interpreting immunohistochemical markers of ganglion cells warrants the search for new markers. Our recent research identified Beta-1,3-N-acetylglucosaminyltransferase (B3GNT6) as a potential candidate, as it consistently stains the cytoplasm of ganglion cells. To evaluate its utility, we conducted a preliminary assessment of B3GNT6 expression in nineteen gastrointestinal tissue samples and observed cytoplasmic staining in ganglion cells across all samples. This consistent staining pattern suggests B3GNT6 could serve as a reliable marker for diagnosing Hirschsprung's disease. This article serves as a preliminary evaluation of B3GNT6 as a ganglion cell immunohistochemical marker, highlighting its potential significance while acknowledging the need for further validation in larger, more diverse cohorts.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155780"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896668","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}
引用次数: 0
The role of the circ_DOCK1-miR-1297-HOXA9 regulatory network in the development of oral squamous cell carcinoma circ_DOCK1-miR-1297-HOXA9调控网络在口腔鳞状细胞癌发展中的作用
IF 2.9 4区 医学
Pathology, research and practice Pub Date : 2025-02-01 DOI: 10.1016/j.prp.2024.155752
Bingxin Mei, Zhimei Zeng, Qinmin Xia, Ming Liu, Ying Zhang
{"title":"The role of the circ_DOCK1-miR-1297-HOXA9 regulatory network in the development of oral squamous cell carcinoma","authors":"Bingxin Mei,&nbsp;Zhimei Zeng,&nbsp;Qinmin Xia,&nbsp;Ming Liu,&nbsp;Ying Zhang","doi":"10.1016/j.prp.2024.155752","DOIUrl":"10.1016/j.prp.2024.155752","url":null,"abstract":"<div><h3>Objective</h3><div>Oral squamous cell carcinoma (OSCC) is a public health concern. The current study aimed to explore the role of circRNA Dedicator of Cytokinesis 1 (circ_DOCK1) and associated action mode in OSCC.</div></div><div><h3>Methods</h3><div>The expression of circ_DOCK1 and microRNA-1297 (miR-1297) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). EdU assay, colony formation assay, transwell assay and glycolysis stress test were applied for functional analyses. The expression level of Homeobox A9 (HOXA9) was detected by western blot. The interaction between miR-1297 and circ_DOCK1 or HOXA9 was verified by dual-luciferase reporter assay. Xenograft model was established to determine the role of circ_DOCK1 <em>in vivo</em>.</div></div><div><h3>Results</h3><div>Circ_DOCK1 was highly expressed in OSCC tumor tissues and cell lines. Circ_DOCK1 knockdown suppressed colony formation, migration, invasion and glycolysis of OSCC cells. MiR-1297 was targeted by circ_DOCK1, and its inhibition reversed the anticancer effects of circ_DOCK1 knockdown. HOXA9 was a target of miR-1297, and its overexpression recovered miR-1297 reintroduction-evoked inhibition of colony formation, migration, invasion and glycolysis in OSCC cells. Furthermore, circ_DOCK1 knockdown repressed tumor growth <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>Circ_DOCK1 exerted its carcinogenic role in OSCC partially via the circ_DOCK1-miR-1297-HOXA9 regulatory network, which will broaden our insights to understand the pathogenesis of OSCC and provide promising biomarkers for the diagnosis and treatment of OSCC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155752"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896671","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}
引用次数: 0
Gastric duplication cysts with mixed hemangioma treated by endoscopic submucosal dissection: A case report and literature review 内镜下粘膜剥离术治疗胃重复囊肿合并混合性血管瘤1例并文献复习。
IF 2.9 4区 医学
Pathology, research and practice Pub Date : 2025-02-01 DOI: 10.1016/j.prp.2025.155819
Fu-guo Liu, Xue-Guo Sun, Wei-Hua Wang, Ti-Dong Shan
{"title":"Gastric duplication cysts with mixed hemangioma treated by endoscopic submucosal dissection: A case report and literature review","authors":"Fu-guo Liu,&nbsp;Xue-Guo Sun,&nbsp;Wei-Hua Wang,&nbsp;Ti-Dong Shan","doi":"10.1016/j.prp.2025.155819","DOIUrl":"10.1016/j.prp.2025.155819","url":null,"abstract":"<div><div>Gastric duplication cysts (GDCs) are rare cystic neoplasms that are often difficult to distinguish from other entities. Accurate diagnosis of cysts before resection is difficult even using the most advanced imaging techniques. We present a case of a gastric duplication cyst in a 17-year-old female, presenting with discomfort in the upper abdomen. Gastroscopy showed a submucosal mass about 40 mm in diameter on the side of the greater curvature of stomach. Computed tomography (CT) reveals a submucosal prominence in the body of stomach, which could indicate a foregut cyst or an ectopic structure. Endoscopic ultrasonography (EUS) showed a submucosal bulge of the corpus body of stomach, and may be lipomas. Patients undergo endoscopic submucosal dissection (ESD) to relieve symptoms and confirm the diagnosis of lesions. The procedure went smoothly and the solid cystic lesions were completely removed. Histopathological examination reveals gastric duplication with mixed hemangioma, and intrinsic fat liquefaction. After resection, the patient was successfully discharged from the hospital, and during the 6-month follow-up period, there are no symptoms or evidence of disease recurrence. This is a rare case of gastric duplication with mixed hemangioma. ESD can be used as an alternative treatment to provide a definitive diagnosis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155819"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009681","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}
引用次数: 0
Tumor infiltrating T-cells and loss of expression of SWI/SNF genes in varying stages of clear cell renal cell carcinoma 透明细胞肾细胞癌不同分期中肿瘤浸润t细胞及SWI/SNF基因表达缺失
IF 2.9 4区 医学
Pathology, research and practice Pub Date : 2025-02-01 DOI: 10.1016/j.prp.2024.155774
Alaa S. Hrizat , Ruihe Lin , Jaime Eberle-Singh , Raymond O'Neill , Yan Xia , Joseph R. Testa , Robert Uzzo , Peter A. McCue , Haifeng Yang , Li Li
{"title":"Tumor infiltrating T-cells and loss of expression of SWI/SNF genes in varying stages of clear cell renal cell carcinoma","authors":"Alaa S. Hrizat ,&nbsp;Ruihe Lin ,&nbsp;Jaime Eberle-Singh ,&nbsp;Raymond O'Neill ,&nbsp;Yan Xia ,&nbsp;Joseph R. Testa ,&nbsp;Robert Uzzo ,&nbsp;Peter A. McCue ,&nbsp;Haifeng Yang ,&nbsp;Li Li","doi":"10.1016/j.prp.2024.155774","DOIUrl":"10.1016/j.prp.2024.155774","url":null,"abstract":"<div><h3>Background</h3><div>Patients with clear cell renal cell carcinoma (ccRCC) metastases face poor prognoses, even with adjuvant therapies. Tumor-infiltrating T-cells and macrophages are critical in targeting tumor cells within the renal microenvironment. Beyond VHL mutations, loss-of-function mutations in SWI/SNF complex genes, including PBRM1, BAP1, ARID1A, SETD2, SMARCA4 (BRG1), and SMARCA2 (BRM), have been implicated in ccRCC progression.</div></div><div><h3>Design</h3><div>A tissue microarray of 160 ccRCC cases was analyzed via immunohistochemistry (IHC) for SWI/SNF protein expression and CD4 + /CD8 + T-cell infiltration. Clinical and pathologic features were obtained through electronic medical records. Statistical analyses included one-way ANOVA, two-way ANOVA, Pearson’s chi-square and t-tests.</div></div><div><h3>Results</h3><div>Loss of SWI/SNF protein expression was observed in PBRM1 (31 %), ARID1A (51 %), SETD2 (14 %), BRG1 (15 %), BRM (38 %), and BAP1 (40 %). T-cell counts varied significantly with stage: CD4 + counts peaked at Stage 3, while CD8 + counts increased through Stage 4 (p &lt; 0.001). Loss of PBRM1 was more frequent in advanced stages (29.4 %, p &lt; 0.001), while BRM and BRG1 losses were more common in earlier stages (p &lt; 0.001, p = 0.006). ARID1A and BRM losses correlated with reduced CD8 + counts (p = 0.016, p = 0.032) and stage-specific CD4 + variations (p &lt; 0.001, p = 0.042).</div></div><div><h3>Conclusion</h3><div>Loss of PBRM1, SMARCA2/BRM, and SMARCA4/BRG1 expression is significantly associated with ccRCC progression, with PBRM1 loss prevalent in advanced stages and SMARCA2/BRM and SMARCA4/BRG1 in earlier stages. ARID1A and SMARCA2/BRM losses correlate with reduced CD8 + counts and stage-specific CD4 + infiltration, highlighting their potential as biomarkers for disease progression and immunotherapeutic response<strong>.</strong></div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155774"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855041","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}
引用次数: 0
Decoding poly (RC)-binding protein 1 (PCBP1), the underrated guard at the foothill of ferroptosis 解码聚(RC)结合蛋白1 (PCBP1),在铁下垂的山脚下被低估的守卫。
IF 2.9 4区 医学
Pathology, research and practice Pub Date : 2025-02-01 DOI: 10.1016/j.prp.2024.155771
Arulkumaran Rithvik, Sakshi Wadhavane, Mahaboobkhan Rasool
{"title":"Decoding poly (RC)-binding protein 1 (PCBP1), the underrated guard at the foothill of ferroptosis","authors":"Arulkumaran Rithvik,&nbsp;Sakshi Wadhavane,&nbsp;Mahaboobkhan Rasool","doi":"10.1016/j.prp.2024.155771","DOIUrl":"10.1016/j.prp.2024.155771","url":null,"abstract":"<div><div>PCBP1 is a multifunctional adaptor protein, whose function as an iron chaperone and epigenetic regulator of several chemical messengers involved in ferroptosis has garnered much attention. Herein, this review, several attempts have been made to simplify our understanding of the complex roles of PCBP1. The review begins by elucidating the relevance of PCBP1 in key events governing ferroptosis. We expeditiously shed light on some of the important mechanisms that have critical implications for the ferroptosis landscape. For instance, senescence, EMT, hypoxia, and regulation of the cell cycle and immune checkpoints, among others, have been demonstrated to influence ferroptosis sensitivity to varying degrees. Thus, this review entails a conscious attempt to carefully examine the relevance of PCBP1 in such potential mechanisms. Furthermore, we investigated the therapeutic relevance of PCBP1 in tumor biology and autoimmunity, while underscoring the contrasting perspective of ferroptosis targeting across the disease spectrum. Finally, we debate the different strategies that can be exploited to target PCBP1 in promoting or inhibiting ferroptosis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155771"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865043","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}
引用次数: 0
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