Pathology, research and practice最新文献

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Targeting CDH11 with celecoxib and derivatives to suppress esophageal squamous cell carcinoma proliferation and invasion 塞来昔布及其衍生物靶向CDH11抑制食管鳞状细胞癌的增殖和侵袭
IF 2.9 4区 医学
Pathology, research and practice Pub Date : 2025-05-27 DOI: 10.1016/j.prp.2025.156042
Lin Xiao , Bingbing Yang , Yijuan Zhou , Jiarui Zhang , Xiaoyan Zhang , Wanjing Yang , Minjing Sun , Mengmeng Li , Xueyan Zhao , Fang Tian
{"title":"Targeting CDH11 with celecoxib and derivatives to suppress esophageal squamous cell carcinoma proliferation and invasion","authors":"Lin Xiao ,&nbsp;Bingbing Yang ,&nbsp;Yijuan Zhou ,&nbsp;Jiarui Zhang ,&nbsp;Xiaoyan Zhang ,&nbsp;Wanjing Yang ,&nbsp;Minjing Sun ,&nbsp;Mengmeng Li ,&nbsp;Xueyan Zhao ,&nbsp;Fang Tian","doi":"10.1016/j.prp.2025.156042","DOIUrl":"10.1016/j.prp.2025.156042","url":null,"abstract":"<div><h3>Background</h3><div>Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with limited therapeutic options. Cadherin-11 (CDH11) has been implicated in tumor progression, but its role in ESCC remains unclear.</div></div><div><h3>Methods</h3><div>CDH11 expression was analyzed in ESCC tissues and cell lines. Functional assays (proliferation, migration, invasion) and xenograft models were employed to assess CDH11’s role. Celecoxib and its derivative 2,5-dimethyl celecoxib (DMC) were evaluated as CDH11-targeted inhibitors.</div></div><div><h3>Results</h3><div>CDH11 was overexpressed in ESCC tissues and correlated with lymph node metastasis and poor prognosis. Knockdown of CDH11 suppressed ESCC proliferation and invasion (<em>P</em> &lt; 0.05), while overexpression exacerbated these phenotypes. Celecoxib and DMC directly bound CDH11 and inhibited ESCC growth in vitro and in vivo (IC<sub>50</sub>: 21.61–43.34 μM). Mechanistically, CDH11 knockdown attenuated JAK-STAT3 and AKT signaling.</div></div><div><h3>Conclusion</h3><div>CDH11 is a novel therapeutic target in ESCC, and its inhibition by celecoxib/DMC offers a promising strategy for ESCC treatment.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"272 ","pages":"Article 156042"},"PeriodicalIF":2.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144194966","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 paradoxical role of IFN-γ in cancer: Balancing immune activation and immune evasion IFN-γ在癌症中的矛盾作用:平衡免疫激活和免疫逃避
IF 2.9 4区 医学
Pathology, research and practice Pub Date : 2025-05-26 DOI: 10.1016/j.prp.2025.156046
Xiaojuan Liu
{"title":"The paradoxical role of IFN-γ in cancer: Balancing immune activation and immune evasion","authors":"Xiaojuan Liu","doi":"10.1016/j.prp.2025.156046","DOIUrl":"10.1016/j.prp.2025.156046","url":null,"abstract":"<div><div>Interferon-γ (IFN-γ) is recognized for its ability to inhibit cell growth, promote programmed cell death, and stimulate immune responses against tumor progression. However, cancerous cells exploit IFN-γ by producing factors that suppress anti-tumor immune responses. Exploring the diverse functions of IFN-γ can offer fresh perspectives for cancer research and the development of immune-based therapies. IFN-γ plays a multifaceted role in the immune system, which includes aiding in boosting the effectiveness of cancer immunotherapy, particularly immune checkpoint inhibitor therapy, by triggering the expression of checkpoint molecules like PD-L1 on tumor cells. Conversely, it can also diminish the effectiveness of immunotherapy by contributing to tumor resistance. Moreover, the level of IFN-γ present inside the microenvironment of the tumor appears to dictate whether IFN-γ acts as a pro-tumor or anti-tumor response. Therefore, enhanced comprehension of IFN-γ's multifaceted actions can revolutionize approaches to cancer biology and intervention strategies targeting the immune system. This review provides an overview of the regulatory roles of IFN-γ in cancer and immunology.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"272 ","pages":"Article 156046"},"PeriodicalIF":2.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205411","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
Nuclear receptors in cancer: Unveiling theranostic potentials and innovative therapeutic strategies 癌症中的核受体:揭示治疗潜力和创新治疗策略
IF 2.9 4区 医学
Pathology, research and practice Pub Date : 2025-05-26 DOI: 10.1016/j.prp.2025.156044
Tarik Aanniz , Saad Bakrim , Mohammed Amanullah , Abdelhakim Bouyahya
{"title":"Nuclear receptors in cancer: Unveiling theranostic potentials and innovative therapeutic strategies","authors":"Tarik Aanniz ,&nbsp;Saad Bakrim ,&nbsp;Mohammed Amanullah ,&nbsp;Abdelhakim Bouyahya","doi":"10.1016/j.prp.2025.156044","DOIUrl":"10.1016/j.prp.2025.156044","url":null,"abstract":"<div><div>Nuclear receptors (NRs) include a family of 48 transcription factors (TFs) that regulate gene expression implicated in biological processes such as cell proliferation, differentiation, metabolism, and immune response. Cancer development has been widely linked to the dysregulation of NRs and their signaling pathways, providing promising targets for therapeutic applications. Recent progress in OMIC approaches and high-throughput drug screening has facilitated the emergence of biomolecules, especially phytochemicals, as potential substitutes for synthetic anti-cancer drugs. This review aims to highlight the anticancer potency of diverse classes of biocompounds that target NRs, including phytocompounds, dietary components, venom constituents, microbial metabolites, as well as many small molecules generated from computer-aided drug design (CADD) approaches in the design of innovative and safe treatments. We examine critically the preclinical and clinical trials investigating these candidates for preventing and treating cancer, focusing on their modes of action, their proven efficacy, and their limitations. In addition, we underline significant molecular processes modulated by these natural compounds, highlighting their ability to surmount drug resistance and minimize the toxic effects of standard treatments. Overall, we believe this work has the potential to pave the way for new paradigms in identifying innovative therapeutic options for NR-mediated management of specific types of cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"272 ","pages":"Article 156044"},"PeriodicalIF":2.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178437","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
Innovative implications of botulinum toxin in head and neck cancer: Exploring novel opportunities and future prospects 肉毒杆菌毒素在头颈癌中的创新意义:探索新的机会和未来前景
IF 2.9 4区 医学
Pathology, research and practice Pub Date : 2025-05-26 DOI: 10.1016/j.prp.2025.156037
Mina Alimohammadi , Abbas Ali Imani Fooladi , Reza Mirnejad , Seyedeh Mana Alavioun , Amir Vaghari , Najma Farahani , Amirhosein Abbasi , Kiavash Hushmandi , Seyedeh Mahdieh Khoshnazar
{"title":"Innovative implications of botulinum toxin in head and neck cancer: Exploring novel opportunities and future prospects","authors":"Mina Alimohammadi ,&nbsp;Abbas Ali Imani Fooladi ,&nbsp;Reza Mirnejad ,&nbsp;Seyedeh Mana Alavioun ,&nbsp;Amir Vaghari ,&nbsp;Najma Farahani ,&nbsp;Amirhosein Abbasi ,&nbsp;Kiavash Hushmandi ,&nbsp;Seyedeh Mahdieh Khoshnazar","doi":"10.1016/j.prp.2025.156037","DOIUrl":"10.1016/j.prp.2025.156037","url":null,"abstract":"<div><div>Head and neck cancer (HNC) represents a significant global health challenge, with over 660,000 annual diagnoses and a mortality rate exceeding 49 %, making it the seventh most common cancer worldwide. Current standard treatments, including surgery, radiation, and chemotherapy, often result in significant side effects, underscoring the need for innovative and personalized therapeutic approaches. In recent years, botulinum toxin (BoNT) has emerged as a transformative adjunctive therapy in HNC management. Initially recognized for its neuromuscular blocking properties, BoNT has expanded its applications to alleviate complications such as sialorrhea, gustatory sweating, and neuropathic pain associated with HNC treatment. Beyond symptomatic relief, emerging evidence suggests that BoNT may influence tumor biology by modulating the tumor microenvironment, disrupting nerve-cancer interactions, and altering key molecular pathways to inhibit tumor growth and metastasis. This article explores BoNT's achievements and therapeutic potential in treating HNC, examining its molecular mechanisms, clinical efficacy, and implications for future research. By elucidating BoNT's role in symptom management and its potential as an anti-tumor agent, this review highlights a promising avenue for advancing personalized medicine and improving outcomes for HNC patients.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"272 ","pages":"Article 156037"},"PeriodicalIF":2.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168865","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
B-cell lymphoma: Advances in pathogenesis, diagnosis, and targeted therapies b细胞淋巴瘤:发病机制、诊断和靶向治疗的进展
IF 2.9 4区 医学
Pathology, research and practice Pub Date : 2025-05-26 DOI: 10.1016/j.prp.2025.156036
Sneha Patil , Sudarshan Rajput , Shaktipal Patil , Amrapali Mhaiskar
{"title":"B-cell lymphoma: Advances in pathogenesis, diagnosis, and targeted therapies","authors":"Sneha Patil ,&nbsp;Sudarshan Rajput ,&nbsp;Shaktipal Patil ,&nbsp;Amrapali Mhaiskar","doi":"10.1016/j.prp.2025.156036","DOIUrl":"10.1016/j.prp.2025.156036","url":null,"abstract":"<div><div>B-cell lymphomas (BCL) represent a heterogeneous group of blood cancers originating from B-lymphocytes, characterized by diverse clinical manifestations and molecular characteristics. This review highlights recent progress in understanding their pathogenesis, diagnostic approach advancements, and therapeutic strategies developments. Key genetic alterations such as chromosomal translocations (e.g., t(14;18), MYC rearrangements), mutations in tumor suppressor genes like TP53, and disruptions in critical signaling pathways including B-cell receptor (BCR), NF-κB, PI3K/AKT, and JAK/STAT are central to disease development. Additionally, non-coding RNAs, especially microRNAs, play crucial regulatory roles in lymphomagenesis. Innovations in diagnostics, such as liquid biopsy technologies using cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA), have enhanced early detection, disease monitoring, and prognostication. Concurrently, molecular biomarkers and emerging classifiers improve risk assessment and guide treatment decisions. Treatment approaches have evolved beyond traditional chemotherapy and radiotherapy. Targeted therapies such as monoclonal antibodies, kinase inhibitors, bispecific antibodies, and CAR-T cell therapies have shown particular promise in relapsed or refractory cases. Stem cell transplantation remains a valuable option for select patients. Additionally, novel agents targeting epigenetic mechanisms and tumor angiogenesis are under active investigation. This review underscores both the significant advancements and ongoing challenges, such as therapy resistance and adverse effects. The integration of molecular diagnostics with precision-targeted and immune-based therapies is key to advancing personalized care. Future research should aim to characterize tumor heterogeneity better and optimize therapeutic strategies to improve outcomes for patients with B-cell lymphomas.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"271 ","pages":"Article 156036"},"PeriodicalIF":2.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144137957","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
Expression of TIM-3 in transitional cell carcinoma: A comparative study of tissue and serum levels TIM-3在移行细胞癌中的表达:组织和血清水平的比较研究
IF 2.9 4区 医学
Pathology, research and practice Pub Date : 2025-05-23 DOI: 10.1016/j.prp.2025.156031
Farrukh Siddique, Naveed Sharif, Abdul Salam, Saleha Saeed, Ayesha Qadir, Ayesha Siffat
{"title":"Expression of TIM-3 in transitional cell carcinoma: A comparative study of tissue and serum levels","authors":"Farrukh Siddique,&nbsp;Naveed Sharif,&nbsp;Abdul Salam,&nbsp;Saleha Saeed,&nbsp;Ayesha Qadir,&nbsp;Ayesha Siffat","doi":"10.1016/j.prp.2025.156031","DOIUrl":"10.1016/j.prp.2025.156031","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the expression of TIM-3 in tissue and serum specimens of patients diagnosed with transitional cell carcinoma (TCC), and to assess the correlation between local tissue expression and systemic serum levels.</div></div><div><h3>Material and method</h3><div>A cross-sectional study was conducted at Khyber Medical University, Peshawar, Pakistan. A total of 74 tissue samples (49 TCC cases, 25 controls) and 42 serum samples (35 TCC, 7 controls) were analyzed based on non-probability convenient sampling. Tissue TIM-3 expression was assessed using immunohistochemistry (IHC), while soluble TIM-3 (sTIM-3) concentrations in serum were measured by enzyme-linked immunosorbent assay ELISA.</div></div><div><h3>Results</h3><div>TIM-3 expression was found to be significantly higher in TCC tissue samples compared to controls (p &lt; 0.001), and was associated with both higher tumor grade (p = 0.040) and stage (p = 0.008). Serum sTIM-3 concentrations were slightly elevated in TCC patients compared to healthy individuals, however, the difference was not statistically significant (p = 0.449). Also, no meaningful correlation was found between tissue TIM-3 expression and serum sTIM-3 levels (ρ = −0.119, p = 0.494).</div></div><div><h3>Conclusion</h3><div>Elevated TIM-3 expression in tumor tissue correlates with aggressive features of TCC, supporting its utility as a potential tissue-based biomarker. Serum sTIM-3, however, lacks diagnostic reliability and does not reflect tissue expression.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"271 ","pages":"Article 156031"},"PeriodicalIF":2.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123862","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
Understanding oncobiosis in ovarian cancer: Emerging concepts in tumor progression 了解卵巢癌的肿瘤共生:肿瘤进展中的新概念
IF 2.9 4区 医学
Pathology, research and practice Pub Date : 2025-05-23 DOI: 10.1016/j.prp.2025.156026
Preeti Sharma , Sumanta Das , Rituraj Rituraj , Bhagyashree Bhagyashree
{"title":"Understanding oncobiosis in ovarian cancer: Emerging concepts in tumor progression","authors":"Preeti Sharma ,&nbsp;Sumanta Das ,&nbsp;Rituraj Rituraj ,&nbsp;Bhagyashree Bhagyashree","doi":"10.1016/j.prp.2025.156026","DOIUrl":"10.1016/j.prp.2025.156026","url":null,"abstract":"<div><div>Ovarian cancer is a leading cause of gynecologic cancer mortality and has recently been linked to microbial dysbiosis or oncobiosis. Tumorigenesis is a highly complex process, and recent research has revealed numerous new mechanisms showing how tumors interact with their surrounding microenvironment. The inclusion of microbiome studies has significantly advanced this field revealing the important role microbes play, not only in maintaining normal physiological functions of the human body but also in influencing oncogenic pathways. This expanding knowledge is deepening our understanding of tumor pathophysiology and is helping to create new diagnostic, prognostic, therapeutic and preventive strategies for specific cancers. This review explores the role of the microbiome in ovarian carcinogenesis, focusing on its interaction with the tumor microenvironment (TME) and its influence on inflammation, immune regulation and metabolic signaling. This review studied dysbiosis in several anatomical compartments such as the gut, oral cavity, lower and upper genital tracts and ovarian tissues, in relation to ovarian oncobiosis. Emerging clinical implications of these studies include the use of microbial profiles as diagnostic or prognostic biomarkers. Therapeutic strategies such as fecal microbiota transplantation and probiotics are also discussed for their ability to restore microbial balance and enhance treatment efficacy. This review highlights the importance of continued research to explore causal relationships between the microbiome and tumorigenesis, positioning microbiome studies as promising tools in ovarian cancer management and improving patient care.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"271 ","pages":"Article 156026"},"PeriodicalIF":2.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144154490","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
Integrating multi-omics data with artificial intelligence to decipher the role of tumor-infiltrating lymphocytes in tumor immunotherapy 将多组学数据与人工智能相结合,解读肿瘤浸润淋巴细胞在肿瘤免疫治疗中的作用
IF 2.9 4区 医学
Pathology, research and practice Pub Date : 2025-05-23 DOI: 10.1016/j.prp.2025.156035
Ting Xie, Haochen Xue, Aoling Huang, Honglin Yan, Jingping Yuan
{"title":"Integrating multi-omics data with artificial intelligence to decipher the role of tumor-infiltrating lymphocytes in tumor immunotherapy","authors":"Ting Xie,&nbsp;Haochen Xue,&nbsp;Aoling Huang,&nbsp;Honglin Yan,&nbsp;Jingping Yuan","doi":"10.1016/j.prp.2025.156035","DOIUrl":"10.1016/j.prp.2025.156035","url":null,"abstract":"<div><div>Tumor-infiltrating lymphocytes (TILs) are capable of recognizing tumor antigens, impacting tumor prognosis, predicting the efficacy of neoadjuvant therapies, contributing to the development of new cell-based immunotherapies, studying the tumor immune microenvironment, and identifying novel biomarkers. Traditional methods for evaluating TILs primarily rely on histopathological examination using standard hematoxylin and eosin staining or immunohistochemical staining, with manual cell counting under a microscope. These methods are time-consuming and subject to significant observer variability and error. Recently, artificial intelligence (AI) has rapidly advanced in the field of medical imaging, particularly with deep learning algorithms based on convolutional neural networks. AI has shown promise as a powerful tool for the quantitative evaluation of tumor biomarkers. The advent of AI offers new opportunities for the automated and standardized assessment of TILs. This review provides an overview of the advancements in the application of AI for assessing TILs from multiple perspectives. It specifically focuses on AI-driven approaches for identifying TILs in tumor tissue images, automating TILs quantification, recognizing TILs subpopulations, and analyzing the spatial distribution patterns of TILs. The review aims to elucidate the prognostic value of TILs in various cancers, as well as their predictive capacity for responses to immunotherapy and neoadjuvant therapy. Furthermore, the review explores the integration of AI with other emerging technologies, such as single-cell sequencing, multiplex immunofluorescence, spatial transcriptomics, and multimodal approaches, to enhance the comprehensive study of TILs and further elucidate their clinical utility in tumor treatment and prognosis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"271 ","pages":"Article 156035"},"PeriodicalIF":2.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144137958","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
Developments in pancreatic cancer emerging therapies, diagnostic methods, and epidemiology 胰腺癌新疗法、诊断方法和流行病学的发展
IF 2.9 4区 医学
Pathology, research and practice Pub Date : 2025-05-22 DOI: 10.1016/j.prp.2025.156012
Mohd Haris Jamal , MD Nasiruddin Khan
{"title":"Developments in pancreatic cancer emerging therapies, diagnostic methods, and epidemiology","authors":"Mohd Haris Jamal ,&nbsp;MD Nasiruddin Khan","doi":"10.1016/j.prp.2025.156012","DOIUrl":"10.1016/j.prp.2025.156012","url":null,"abstract":"<div><div>Pancreatic cancer is still one of the deadliest malignancies, characterised by late-stage diagnosis, aggressive biology, and considerable resistance to conventional treatments. Despite improvements in understanding the molecular mechanisms and innovations in treatment, the overall survival remains abysmal: fewer than 9 % of patients survive beyond 5 years. By 2030, PC is predicted to become the second leading cause of cancer-related deaths in the U.S. owing to chemoresistance, rapid metastatic spread, and limited effective immunotherapeutic choices. This review highlights current progress in this field, including epidemiology, risk factors, diagnostic tools, and emerging biomarkers. Recent progress in genetic and molecular profiling has provided important information about pancreatic cancer. It has identified key mutations in genes like KRAS, TP53, CDKN2A, and SMAD4 that play a major role in driving the disease. Such revelations have provided the impetus to explore novel targeted therapies against these mutations. Furthermore, the advances in liquid biopsies incorporating circulating tumour cells, circulating tumour DNA, and exosomes hold substantial promise for early diagnosis, treatment response monitoring, and detection of minimal residual disease—any of which could radically transform PC management. While very limited options for the treatment of advanced-stage PC remain, the only potential curative treatment is surgery, yet only 10–15 % of patients are diagnosed with potentially resectable disease. Researchers are looking into new methods to help more patients qualify for surgery. This involves using chemotherapy and radiotherapy to reduce the size of the tumor before the operation. New chemotherapy treatments like FOLFIRINOX (which includes 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) have improved results for some patients, but they can still cause significant side effects. Immunotherapy, though revolutionary in other cancers, has had limited success in PC due to the tumour's immunosuppressive microenvironment. Researchers are looking into using immune checkpoint inhibitors together with chemotherapy, radiation, and drugs that target the surrounding tissue to improve the body's immune response. There is also considerable excitement surrounding personalised approaches with adoptive cell therapies such as CAR-T cells and TILs, which are trialled with early evidence of potential efficacy. Attempts are also being made to address the dense desmoplastic stroma of the tumour that characterises PC. Drugs that can fight resistance or new medicines that might affect the tumor environment, stop changes in surrounding tissues, and improve how drugs are delivered have shown some potential in laboratory tests so far. Nanoparticle-based drug delivery systems are also being developed to improve the bioavailability and targeted delivery of chemotherapy.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"271 ","pages":"Article 156012"},"PeriodicalIF":2.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124151","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
ETV4 promotes the growth, metastasis, glycolysis, and oxaliplatin resistance of colorectal cancer by transcription activation-mediated SLC38A5 upregulation ETV4通过转录激活介导的SLC38A5上调,促进结直肠癌的生长、转移、糖酵解和奥沙利铂耐药
IF 2.9 4区 医学
Pathology, research and practice Pub Date : 2025-05-21 DOI: 10.1016/j.prp.2025.156033
Yujun Huang , Jinyong He , Nan Chen , Xiuting Du , Junhui Peng
{"title":"ETV4 promotes the growth, metastasis, glycolysis, and oxaliplatin resistance of colorectal cancer by transcription activation-mediated SLC38A5 upregulation","authors":"Yujun Huang ,&nbsp;Jinyong He ,&nbsp;Nan Chen ,&nbsp;Xiuting Du ,&nbsp;Junhui Peng","doi":"10.1016/j.prp.2025.156033","DOIUrl":"10.1016/j.prp.2025.156033","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer (CRC) is one of the most common malignancies worldwide with a poor prognosis. Previous studies have indicated that solute carrier family 38 member 5 (SLC38A5), an amino acid transporter, plays an important role in some solid tumors. However, the role and mechanism of SLC38A5 in the progression of CRC are poorly defined.</div></div><div><h3>Methods</h3><div>In this research, TIMER, UALCAN, and GEPIA databases were applied to analyze the expression of SLC38A5 in CRC. SLC38A5 and E26 transformation-specific variant 4 (ETV4) mRNA levels were determined using real-time quantitative polymerase chain reaction (RT-qPCR) assay. SLC38A5, ETV4, HK-2, and LDHA protein levels were measured using western blot. Cell proliferation, migration, invasion, and Oxaliplatin (L-OHP) resistance were examined using Cell Counting Kit-8 (CCK-8) assay and Transwell assay. Glucose consumption, lactate production, and ATP levels were assessed using relevant kits. Binding between ETV4 and SLC38A5 promoter was predicted by JASPAR and validated using Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. The biological role of ETV4 on CRC tumor growth was examined by the xenograft tumor model <em>in vivo.</em></div></div><div><h3>Results</h3><div>ETV4 and SLC38A5 were highly expressed in CRC tissues and cells. Moreover, SLC38A5 deficiency could hinder CRC cell proliferation, migration, invasion, glycolysis, and improved L-OHP sensitivity <em>in vitro</em>. Mechanistically, ETV4 was a transcription factor of SLC38A5 and activated the transcriptional activity of SLC38A5 via binding to its promoter region. ETV4 silencing knockdown repressed tumor growth <em>in vivo.</em></div></div><div><h3>Conclusion</h3><div>SLC38A5 transcriptionally mediated by ETV4 expedites CRC cell growth, metastasis, glycolysis, L-OHP resistance, which provides a promising therapeutic target for CRC treatment.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"271 ","pages":"Article 156033"},"PeriodicalIF":2.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144137889","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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