Clinical and Experimental Medicine最新文献

{"title":"Donafenib activates the p53 signaling pathway in hepatocellular carcinoma, induces ferroptosis, and enhances cell apoptosis.","authors":"Jiaming Liang, Meifeng Chen, Guohong Yan, Pham Thi Thai Hoa, Shuxin Wei, Hailian Huang, Qichong Xie, Xiaoling Luo, Shutian Mo, Chuangye Han","doi":"10.1007/s10238-024-01550-6","DOIUrl":"10.1007/s10238-024-01550-6","url":null,"abstract":"<p><p>Donafenib is an improved version of sorafenib in which deuterium is substituted into the drug's chemical structure, enhancing its stability and antitumor activity. Donafenib exhibits enhanced antitumor activity and better tolerance than sorafenib in preclinical and clinical studies. However, the specific mechanism of its effect on hepatocellular carcinoma has not been reported. Iron deposition is a cell death pattern caused by disturbances in iron metabolism. Apoptosis is a form of programmed cell death. They may interact with each other during cell death. This study mainly explores the potential mechanism of donafenib activating the p53 signaling pathway, inducing iron deposition, and enhancing cell apoptosis in hepatocellular carcinoma. Hepa1-6 and Huh7 cells were treated with various concentrations of donafenib. Scratch healing and pore migration tests were conducted. Analyze apoptosis through flow cytometry and TUNEL fluorescence labeling. RNA sequencing was conducted on both untreated and donafenib-treated Huh7 cells. The key proteins involved in ferroptosis (SLC7A11, GPX4) and apoptosis (caspase3, caspase8, Bax, Bcl-2, p53) were then evaluated using immunoblotting and immunohistochemical staining. Reactive oxygen species (ROS) levels in the cancer cells were measured. Donafenib treatment resulted in a dose-dependent decrease in the proliferation, migration, and invasion capabilities of cancer cells. There was an increase in apoptosis rates and ROS accumulation, and a reduction in tumor volume. The key proteins involved in ferroptosis and apoptosis underwent significant changes. Donafenib activates the p53 signaling pathway, induce ferroptosis, and enhance apoptosis, suggesting its potential as an effective therapeutic agent for HCC.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"29"},"PeriodicalIF":3.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926674","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":"Primary tumor surgery in de novo metastatic breast cancer: Game-changer or misinterpretation?","authors":"Gianluca Franceschini","doi":"10.1007/s10238-024-01552-4","DOIUrl":"10.1007/s10238-024-01552-4","url":null,"abstract":"<p><p>The study titled \"Primary tumor surgery in patients with de novo metastatic breast cancer: a nationwide population-based retrospective cohort study in Belgium\" opens an important discussion about the potential role of surgery in the treatment of de novo MBC; although the results are promising, they should be interpreted with caution given the limitations of the study design. The question remains whether surgery is truly a game-changer for all patients or whether its benefits are more nuanced depending on individual patient factors and disease characteristics. As the oncology community continues to explore this question, a modern breast surgeon should emphasize the importance of further prospective trials and personalized treatment strategies that consider not only surgery but also the growing arsenal of available systemic therapies.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"26"},"PeriodicalIF":3.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920907","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":"Viral infections in celiac disease: what should be considered for better management.","authors":"Nastaran Asri, Shahnaz Mohammadi, Mahtab Jahdkaran, Mohammad Rostami-Nejad, Mostafa Rezaei-Tavirani, Seyed Reza Mohebbi","doi":"10.1007/s10238-024-01542-6","DOIUrl":"10.1007/s10238-024-01542-6","url":null,"abstract":"<p><p>Following a gluten-free diet (GFD) is known as the main effective therapy available for celiac disease (CD) patients, which in some cases is not enough to heal all patients presentations completely. Accordingly, emerging researchers have focused on finding novel therapeutic/preventive strategies for this disorder. Moreover, previous studies have shown that celiac patients, especially untreated subjects, are at increased risk of developing viral and bacterial infections, which can become a challenge for the clinician. Viruses, such as Rotavirus, Reovirus, Adenovirus, Enterovirus, Rhinovirus, Astrovirus, Hepatitis virus, COVID-19, Norovirus, and Herpesvirus, have been related to CD pathogenesis. Therefore, clinicians need to pay more attention to evaluate CD patients' viral infection history (especially nonresponders to the GFD), to look for effective preventive strategies and educate patients about important risk factors. In addition, there are still viruses whose role in CD pathogenesis has not been fully studied. In this review, current information on the association between CD and various viral infections was gathered to improve knowledge in this subject area and draw researchers'/clinicians' attention to unstudied/less studied viruses in CD pathogenesis, which might guide future prevention approaches.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"25"},"PeriodicalIF":3.2,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11682017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892684","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":"Cancer vaccines: an update on recent achievements and prospects for cancer therapy.","authors":"Arezki Chekaoui, Mariangela Garofalo, Beata Gad, Monika Staniszewska, Jacopo Chiaro, Katarzyna Pancer, Aleksander Gryciuk, Vincenzo Cerullo, Stefano Salmaso, Paolo Caliceti, Aleksander Masny, Magdalena Wieczorek, Sari Pesonen, Lukasz Kuryk","doi":"10.1007/s10238-024-01541-7","DOIUrl":"10.1007/s10238-024-01541-7","url":null,"abstract":"<p><p>Decades of basic and translational research have led to a momentum shift in dissecting the relationship between immune cells and cancer. This culminated in the emergence of breakthrough immunotherapies that paved the way for oncologists to manage certain hard-to-treat cancers. The application of high-throughput techniques of genomics, transcriptomics, and proteomics was conclusive in making and expediting the manufacturing process of cancer vaccines. Using the latest research technologies has also enabled scientists to interpret complex and multiomics data of the tumour mutanome, thus identifying new tumour-specific antigens to design new generations of cancer vaccines with high specificity and long-term efficacy. Furthermore, combinatorial regimens of cancer vaccines with immune checkpoint inhibitors have offered new therapeutic approaches and demonstrated impressive efficacy in cancer patients over the last few years. In the present review, we summarize the current state of cancer vaccines, including their potential therapeutic effects and the limitations that hinder their effectiveness. We highlight the current efforts to mitigate these limitations and highlight ongoing clinical trials. Finally, a special focus will be given to the latest milestones expected to transform the landscape of cancer therapy and nurture hope among cancer patients.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"24"},"PeriodicalIF":3.2,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885038","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":"Non-invasive early-stage cancer detection: current methods and future perspectives.","authors":"Neelima Chacko, Rinat Ankri","doi":"10.1007/s10238-024-01513-x","DOIUrl":"10.1007/s10238-024-01513-x","url":null,"abstract":"<p><p>This review paper explores the realm of non-invasive methods for early cancer detection. Early identification is crucial for effective therapeutic intervention, and non-invasive techniques have emerged as promising tools to enhance diagnostic accuracy and improve patient outcomes. The paper thoroughly examines the advantages, limitations, and prospects of various non-invasive approaches, including blood tests, non-blood-based tests, and diverse imaging modalities. It discusses the biomarkers found in blood for early-stage cancer detection, specifying the types of cancer associated with each biomarker. The non-blood-based tests focus on components in saliva, urine, and breath for cancer detection, alongside current studies and future perspectives on various cancers. Optical imaging methods covered in this review include fluorescence imaging in the near-infrared (NIR) region, bioluminescence imaging, and Raman spectroscopy for early-stage cancer detection. The review also highlights the pros and cons of ultrasound imaging in early-stage cancer detection. Additionally, the clinical implications of using AI for cancer detection, both present and future, are explored. This paper provides valuable insights for researchers and clinicians working in the field of non-invasive early-stage cancer detection.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"17"},"PeriodicalIF":3.2,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871504","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":"FUS and METTL3 collaborate to regulate RNA maturation, preventing unfolded protein response and promoting gastric cancer progression.","authors":"Dongtao Liu, Bo Ding, Gang Liu, Zhijuan Yang","doi":"10.1007/s10238-024-01525-7","DOIUrl":"10.1007/s10238-024-01525-7","url":null,"abstract":"<p><p>FUS-mediated alternative splicing and METTL3-regulated RNA methylation play crucial roles in RNA processing. The purpose of this study was to investigate the interactive roles of FUS and METTL3 in gastric cancer (GC) progression. RNA sequencing data were obtained from the TCGA-STAD dataset. Differentially expressed genes (DEGs) were analyzed across groups stratified by the medians of FUS, METTL3, and NEAT1, respectively. Endoplasmic reticulum (ER) stress markers PERK, IRE1, pIRE1, Bip, and CHOP, as well as related apoptosis stress markers PARP, cleaved-PARP, (Cleaved) Caspase 7, and (Cleaved) Caspase 3, were assessed through western blotting. Alternative splicing and N6-methyladenosine (m(6)A) methylation of specific genes were detected with MeRIP-PCR. Finally, in vivo experiments were conducted using nude mice bearing sh-FUS-transfected HGC27 xenograft tumors. FUS and METTL3 expression levels were elevated in GC tissues. A significant overlap of DEGs was observed between the FUS- and METTL3-stratified groups. These overlapping DEGs were predominantly enriched in mRNA processing and protein processing in the ER. ER stress and apoptosis were induced by sh-FUS or sh-METTL3, which was further enhanced by ER stress inducer tunicamycin in both MKN45 and HGC27 cells. Similarly, DEGs for NEAT1 high- and low-expressed groups were enriched in protein processing in the ER and spliceosome. To a lesser extent, ER stress was also induced by sh-NEAT1 and enhanced by tunicamycin in HGC27 cells. Furthermore, sh-FUS or sh-METTL3 influenced alternative splicing and methylation of specific mRNAs, including FUS, NEAT1, PCNA, MCM2, and BIRC5. Tumor progression was inhibited by sh-FUS in mice, and ER stress and apoptosis were induced, which were further enhanced by tunicamycin. FUS and METTL3 collaborate to facilitate RNA maturation. Inhibiting FUS or METTL3 promoted ER stress and apoptosis and inhibited progression in GC.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"15"},"PeriodicalIF":3.2,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871472","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":"Impact of hyperkalaemia on renin-angiotensin-aldosterone (RAAS) inhibitor reduction or withdrawal following hospitalisation.","authors":"Hugh Logan Ellis, Mohammad Al-Agil, Philip A Kelly, James Teo, Claire Sharpe, Martin B Whyte","doi":"10.1007/s10238-024-01531-9","DOIUrl":"10.1007/s10238-024-01531-9","url":null,"abstract":"<p><strong>Background: </strong>Inhibitors of the renin-angiotensin-aldosterone system (RAAS), such as ACE inhibitors (ACEi), angiotensin-II receptor blockers and mineralocorticoid receptor antagonists, reduce morbidity and mortality in hypertension, congestive heart failure and chronic kidney disease. However, their use can lead to hyperkalaemia. We examined the proportions of RAAS inhibitor (RAASi) reduction or withdrawal, across GFR strata, following hospitalisation and the effect on patient mortality.</p><p><strong>Methods: </strong>This was a retrospective cohort study of adult patients hospitalised from 1 January2017 to 31 December2020. Biochemistry data, clinical notes and medicines use were extracted using the CogStack platform, from electronic health records. Patients were identified by creatinine measurement during hospitalisation. Hyperkalaemia was defined as potassium > 5.0 mmol/L, with severity categorisation. RAASi discontinuation defined as ≥ 48 h without administration. Mortality risk associated with RAASi cessation was assessed using Cox proportional hazards models.</p><p><strong>Results: </strong>Among 129,172 patients with potassium measurements, 49,011 were hospitalised. Hyperkalaemia prevalence was 8.57% in the emergency department and 16.79% among hospitalised patients. Higher hyperkalaemia levels correlated with increased CKD and heart failure. RAASi use was more common in hyperkalaemic patients, with higher discontinuation rates during hospitalisation (36% with potassium 5-5.5 mmol/L; 61% with potassium > 6.5 mmol/L). By discharge, 32% of patients had RAASi stopped, and 2% doses reduced. Discontinuation of RAASi was associated with 37% worse survival probability.</p><p><strong>Conclusion: </strong>RAASi cessation was greater with hyperkalaemia and associated with increased mortality in hospitalised patients. Reinstitution of RAASi after hospital discharge, or alternative management of hyperkalaemia if maintained on RAASi therapy, may improve clinical outcomes.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"16"},"PeriodicalIF":3.2,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871474","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":"CYB561 a potential prognostic biomarker for liver hepatocellular carcinoma.","authors":"Yanchun Zhao, Jingfang Du, Jian Zhuo, Quanai Zhang, Luxian Dai, Yubao Tang, Yao Wang, Ankang Sheng, Hanyu Yao, Weiguang Liu","doi":"10.1007/s10238-024-01522-w","DOIUrl":"10.1007/s10238-024-01522-w","url":null,"abstract":"<p><p>Liver hepatocellular carcinoma (LIHC) is a malignancy characterized by a high rate of recurrence, metastasis, and poor prognosis. Cytochrome b561 (CYB561) has been previously reported to be associated with tumor progression, but it has not been revealed in LIHC. The aim of this study was to investigate the prognostic value and potential function of CYB561 in LICH. The expression level, clinical correlation, prognosis, and biological function of CYB561 in LIHC were analyzed using The Cancer Genome Atlas（TCGA), Gene Expression Omnibus (GEO), TIMER2, Kaplan-Meier Plotter, and GEPIA2 databases. The expression of CYB561 in LIHC tissue samples was analyzed by immunohistochemical staining. The effect of CYB561 on the proliferation and migration of LIHC cells was investigated by using CYB561 knockdown in vitro. GSE149614 dataset was used to analyze the expression distribution of CYB561 in LIHC on a single-cell dimension. This study showed that CYB561 mRNA and protein were highly expressed in LIHC. High expression of CYB561 suggests poor prognosis in LICH patients and is an independent risk factor for LIHC. Wound-healing experiment, transwell experiment, and clonal formation experiment confirmed that CYB561 knockdown could inhibit the proliferation and migration of LIHC cells. Functional enrichment analysis showed that CYB561 was related to biological processes such as cell adhesion and immune response. KEGG enrichment analysis showed that CYB561 interacts with tumor-related signaling pathways. Single-cell analysis showed that CYB561 was mainly expressed in hepatocytes. Cells with high CYB561 expression had a higher degree of malignancy. Our study found that abnormal expression of CYB561 in LIHC suggested poor prognosis of LIHC and was related to tumor migration and proliferation. CYB561 is a potential prognostic predictor or therapeutic biomarker.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"23"},"PeriodicalIF":3.2,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871194","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":"The long-term survival outcome of sporadic bilateral renal cell carcinoma and optimization of surgical treatment: a large-scale population-based cohort study.","authors":"Ruiyi Deng, Jianhui Qiu, Jiaheng Shang, Chaojian Yu, Peidong Tian, Zihou Zhao, Lin Cai, Jingcheng Zhou, Kan Gong","doi":"10.1007/s10238-024-01535-5","DOIUrl":"10.1007/s10238-024-01535-5","url":null,"abstract":"<p><p>Sporadic bilateral renal cell carcinoma (BRCC) is a rare situation of RCC. The treatment for BRCC is controversial and there is a lack of authoritative guidelines about the management of BRCC. Patients diagnosed with sporadic BRCC between 2004 and 2020 were identified from Surveillance, Epidemiology, and End Results (SEER) database. The primary outcome was overall survival (OS). Kaplan-Meier survival analysis, Cox regression analysis, and competing risk regression models were used to compare survival outcomes and identify prognostic factors. A total of 20,523 patients (16,534 unilateral RCC [URCC] patients and 3989 BRCC patients) were included. The prognosis of BRCC patients is between metastatic and non-metastatic URCC patients. 3677 patients were diagnosed with localized BRCC (2180 synchronous BRCC patients and 1497 metachronous BRCC patients). Compared with metachronous BRCC, synchronous BRCC patients had relatively poor OS. However, the CSS was similar. Partial nephrectomy (PN) leads to the best OS and provides equivalent oncological outcomes to radical nephrectomy. Local tumor destruction (LTD) could also achieve an acceptable cancer-control effect. Then we developed treatment flowchart for localized BRCC patients. Additionally, we identified the prognostic factors, and analyzed the association between factors using the multivariable Cox regression method. PN should be the initial treatment for sporadic localized BRCC patients if feasible. LTD could be considered as an effective treatment alternative. This study could provide evidence for the optimization of individualized treatment for sporadic BRCC patients.Trial registration: The trial was registered on the ClinicalTrials.gov (NCT06369519).</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"20"},"PeriodicalIF":3.2,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871507","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":"CRISPR screening and cell line IC50 data reveal novel key genes for trametinib resistance.","authors":"Hengrui Liu, Panpan Wang","doi":"10.1007/s10238-024-01538-2","DOIUrl":"10.1007/s10238-024-01538-2","url":null,"abstract":"","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"21"},"PeriodicalIF":3.2,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870829","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}