{"title":"Potential Roles of Serum Exosomal CD155 and its Impact on NK Cell Immunosuppression in Hepatocellular Carcinoma.","authors":"Wenzheng Han, Jinrong Lv, Mintuo Wang, Xiaoxin Wu, Dongdong Sun, Wenwen Chen, Yingying Wang, Wenjie Zhou, Yuxuan Yang, Jia Bao, Qingzhen Han, Xiaopeng Chen, Fei Guo, Gang Feng, Min Li, Qing Chen","doi":"10.4274/balkanmedj.galenos.2025.2025-1-129","DOIUrl":"https://doi.org/10.4274/balkanmedj.galenos.2025.2025-1-129","url":null,"abstract":"<p><strong>Background: </strong>Targeted therapies directed at tumor immune checkpoint, like programmed death-ligand (PD-L)1/programmed death (PD)-1, have shown remarkable progress. Nevertheless, treatment efficacy in hepatocellular carcinoma (HCC) is notably compromised due to the intricate immune microenvironment. Exploring alternative checkpoints beyond PD-L1/PD-1, including those not located on the cell surface, may improve our understanding of their roles in areas like diagnostic potential and immune tolerance in HCC.</p><p><strong>Aims: </strong>To explore the roles of serum exosomal CD155 (exo-CD155) in HCC.</p><p><strong>Study design: </strong>Experimental study.</p><p><strong>Methods: </strong>We separated and analyzed serum exosomes from HCC patients. We quantified the concentrations of serum soluble CD155 (sCD155) and serum exo-CD155, and examined their association with disease progression, hepatitis B surface antigen (HBsAg) presence, and the concentrations of α-fetoprotein fraction L3 (AFP-L3) or alpha-fetoprotein (AFP). Additionally, we assessed the diagnostic effect through the receiver operating characteristic (ROC) curve, and the immune suppressive effect on natural killer (NK) cells of exo-CD155.</p><p><strong>Results: </strong>This study reveal elevated exo-CD155 levels in all HCC patients, with a significant increase in early-stage patients, exhibiting normal AFP/AFP-L3 or HBsAg-positive status. Exo-CD155 is linked to the progression of HCC and shows significant diagnostic effectiveness for the disease. Furthermore, the incubation of NK-92MI with exosomes derived from HCC patients leads to a substantial reduction in immune function, which can be partially counteracted with an antibody that blocks T cell immune receptor immunoglobulin and ITIM domains, (TIGIT)-blocking antibody.</p><p><strong>Conclusion: </strong>These results disclose exo-CD155 shows promise for serving as a biomarker for HCC, especially in early-stage patients or those with normal AFP/AFP-L3 levels. Moreover, serum exosomes from HCC patients suppress NK cell immune functions through the TIGIT/CD155 pathway, contributing to immune tolerance in HCC.</p>","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":"42 3","pages":"242-253"},"PeriodicalIF":1.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968538","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}
Balkan Medical JournalPub Date : 2025-05-05Epub Date: 2025-01-15DOI: 10.4274/balkanmedj.galenos.2024.2024-10-105
Manahil Mubeen, Hafsa Ali, Syeda Sabika Zehra, Aman Khan
{"title":"Harnessing the Power of Vitexin as a Vitamin D Receptor Agonist in Colorectal Cancer: A New Frontier","authors":"Manahil Mubeen, Hafsa Ali, Syeda Sabika Zehra, Aman Khan","doi":"10.4274/balkanmedj.galenos.2024.2024-10-105","DOIUrl":"10.4274/balkanmedj.galenos.2024.2024-10-105","url":null,"abstract":"","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":"276-278"},"PeriodicalIF":1.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982526","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}
Balkan Medical JournalPub Date : 2025-04-22DOI: 10.4274/balkanmedj.galenos.2025.2025-1-133
Vedat Cicek, Ulas Bagci
{"title":"Enhancing Shared Decision-Making in Cardiology with Artificial Intelligence.","authors":"Vedat Cicek, Ulas Bagci","doi":"10.4274/balkanmedj.galenos.2025.2025-1-133","DOIUrl":"https://doi.org/10.4274/balkanmedj.galenos.2025.2025-1-133","url":null,"abstract":"","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955823","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}
Balkan Medical JournalPub Date : 2025-03-24DOI: 10.4274/balkanmedj.galenos.2025.2024-12-133
Damien Gruson, Tuğba Kemaloğlu Öz
{"title":"Trends in Healthcare and Laboratory Medicine: A Forward Look into 2025.","authors":"Damien Gruson, Tuğba Kemaloğlu Öz","doi":"10.4274/balkanmedj.galenos.2025.2024-12-133","DOIUrl":"https://doi.org/10.4274/balkanmedj.galenos.2025.2024-12-133","url":null,"abstract":"","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690997","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}
Balkan Medical JournalPub Date : 2025-03-03DOI: 10.4274/balkanmedj.galenos.2025.2024-12-47
Senem Noyan, Bala Gür Dedeoğlu
{"title":"Upregulation of miR-99b-5p Modulates ESR1 Expression as an Adaptive Mechanism to Circumvent Drug Response via Facilitating ER/HER2 Crosstalk.","authors":"Senem Noyan, Bala Gür Dedeoğlu","doi":"10.4274/balkanmedj.galenos.2025.2024-12-47","DOIUrl":"10.4274/balkanmedj.galenos.2025.2024-12-47","url":null,"abstract":"<p><strong>Background: </strong>Endocrine resistance remains a significant therapeutic challenge in estrogen receptor-positive (ER+) breast cancer, the most common subtype, contributing to increased morbidity and mortality. The interaction between ER and HER family receptors, particularly HER2 and epidermal growth factor receptor (EGFR), drives resistance to standard therapies such as tamoxifen and trastuzumab by activating key signaling pathways, including PI3K/AKT and RAS/MAPK. Dysregulated miRNAs, which are non-coding gene expression regulators, have been linked to therapy response.</p><p><strong>Aims: </strong>To investigate the role of miR-99b-5p in ER-HER2/EGFR crosstalk in BT-474 cells.</p><p><strong>Study design: </strong>Experimental study.</p><p><strong>Methods: </strong>The expression profile and prognostic significance of miR- 99b-5p in breast cancer were analyzed using The Cancer Genome Atlas (TCGA) database. BT-474 cells were transfected with miR-99b-5p mimics and inhibitors, followed by treatment with tamoxifen and trastuzumab to assess their impact on cell proliferation and ER-HER2/EGFR crosstalk. Western blotting was performed to quantify EGFR, HER2, and ESR1 protein levels. Real-time proliferation analysis evaluated changes in cell growth following miRNA transfection and drug treatment.</p><p><strong>Results: </strong>The study revealed that miR-99b-5p is significantly overexpressed in tumors compared to normal tissues and is associated with poor patient survival and enhanced ER signaling. Transfection with miR-99b-5p mimics increased ESR1 expression and cell proliferation, even in the presence of tamoxifen or trastuzumab, indicating that miR-99b-5p contributes to therapy resistance through receptor crosstalk. Conversely, miR-99b-5p inhibition significantly restored drug sensitivity, reducing proliferation and enhancing the effectiveness of tamoxifen and trastuzumab.</p><p><strong>Conclusion: </strong>These findings establish miR-99b-5p as a key regulator of endocrine and HER2-targeted therapy resistance. Targeting miR-99b-5p could represent a potential therapeutic strategy to improve treatment outcomes in ER+/HER2+ breast cancer. Further research is needed to clarify the underlying molecular mechanisms and validate the therapeutic potential of miR-99b-5p inhibition in clinical applications.</p>","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":"42 2","pages":"150-156"},"PeriodicalIF":1.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539996","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}
Balkan Medical JournalPub Date : 2025-03-03DOI: 10.4274/balkanmedj.galenos.2025.2024-10-40
Mestan Emek
{"title":"The Importance of Age Standardisation in Comparing Regional Inequalities.","authors":"Mestan Emek","doi":"10.4274/balkanmedj.galenos.2025.2024-10-40","DOIUrl":"10.4274/balkanmedj.galenos.2025.2024-10-40","url":null,"abstract":"","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":"42 2","pages":"180"},"PeriodicalIF":1.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539946","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}
Balkan Medical JournalPub Date : 2025-03-03DOI: 10.4274/balkanmedj.galenos.2025.2025-1-91
Salih Keskin, Gül Ergör
{"title":"Excess Mortality in Türkiye during 2020-2022: Regional and Time-Based Analysis.","authors":"Salih Keskin, Gül Ergör","doi":"10.4274/balkanmedj.galenos.2025.2025-1-91","DOIUrl":"10.4274/balkanmedj.galenos.2025.2025-1-91","url":null,"abstract":"<p><strong>Background: </strong>The coronavirus disease-2019 (COVID-19) pandemic significantly impacted global mortality, albeit Türkiye has been largely excluded from mortality studies owing to delayed data release and a lack of nationwide analyses.</p><p><strong>Aims: </strong>To identify the excess mortality rates in Türkiye between 2020 and 2022, analyze the temporal trends and regional differences, and determine factors associated with excess deaths at the regional level.</p><p><strong>Study design: </strong>A cross-sectional ecological analysis.</p><p><strong>Methods: </strong>We analyzed all-cause mortality data from the Turkish Statistical Institute from January 2015 to December 2022. The projected deaths during 2020-2022 were derived from Quasi-Poisson Regression models applied to the 2015-2019 provincial mortality data, adjusting for seasonal trends, population offsets, and overdispersion. The results were aggregated to national and socioeconomic levels for comparative analyses. Excess deaths were calculated as the difference between observed and projected deaths. P-scores and excess mortality per 100,000 inhabitants were utilized as standardized metrics. Socioeconomic disparities were examined using the Socioeconomic Development Ranking of Provinces and Regions (SEGE-2017). We assessed the associations between excess mortality and vaccination coverage, elderly population ratio, intensive care unit beds per 100,000 population, and population per family physician.</p><p><strong>Results: </strong>Türkiye experienced 247,640 excess deaths [95% confidence interval (CI): 176,405-315,204] from 2020 to 2022. Excess mortality peaked in 2021 with 121,426 excess deaths (27.2% P-score, 143.5 per 100,000 population). Lower vaccination coverage [estimate: -0.51, 95% CI: (-0.81, -0.20), <i>p</i> = 0.001] and higher population per family physician [estimate: 0.01, 95% CI: (0.00, 0.02), <i>p</i> = 0.005] were significantly associated with higher excess mortality. A higher elderly population ratio was positively associated with excess deaths [estimate: 1.41, 95% CI: (0.50, 2.32), <i>p</i> = 0.003]. Socioeconomically less developed regions (SEGE 5 and SEGE 6) exhibited higher P-scores (21.3% and 20.2%, respectively), indicating greater relative increases in mortality when compared with the relatively more developed regions.</p><p><strong>Conclusion: </strong>Excess mortality in Türkiye during the COVID-19 pandemic was substantial, particularly in 2021, and was influenced by regional socioeconomic disparities, vaccination coverage, and healthcare access. These findings underscore the importance of addressing sociodemographic factors and strengthening primary healthcare services in pandemic responses.</p>","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":"42 2","pages":"130-137"},"PeriodicalIF":1.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539890","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}