Journal of the Egyptian National Cancer Institute最新文献

{"title":"Silver-loaded nanoemulsion of Nepeta glomerulosa extract enhances cytotoxicity and induces apoptosis in A549 and AGS cancer cells.","authors":"Sepideh Sahebi, Golaleh Mostafavi, Seyyedeh Mahdokht Maddah","doi":"10.1186/s43046-026-00373-8","DOIUrl":"10.1186/s43046-026-00373-8","url":null,"abstract":"<p><p>The global rise in cancer occurrence, together with the spread of multidrug resistance, highlights the critical demand for innovative treatment strategies. Nano-delivery approaches have emerged as promising solutions that enhance bioavailability and facilitate targeted drug delivery. This study evaluated the anticancer efficacy of Nepeta glomerulosa extract and its silver-loaded nanoemulsion (Ag-N.g.Ext. NEs) against human lung (A549) and gastric (AGS) cells.MethodsNepeta glomerulosa was collected from the Binaloud Mountains, and a hydroalcoholic extract was obtained by maceration. Ag-N.g.Ext. NEs were prepared via high-energy emulsification and characterized by FTIR, SEM, DLS, ZP, and XRD. Cytotoxicity and apoptosis were assessed using MTT assay, DAPI staining, and Real-time PCR of TP53 and BAX genes.ResultsAg-N.g.Ext. NEs were spherical (confirmed by SEM) with a PSA (DLS) size of 269.5 nm, a negative zeta potential of -23.1 mV, and a non-crystalline structure. The IC₅₀ of the extract for A549 and AGS was 500 and 250 µg/mL, while the Ag-N.g.Ext. NEs showed enhanced potency with an IC₅₀ of 125 µg/mL. Apoptosis and gene expression were significantly higher in Ag-N.g.Ext. NEs-treated cells (p ≤ 0.05). TP53 expression increased 3.317-fold in A549 and 8.027-fold in AGS; BAX increased 3.877-fold in A549 and 2.351-fold in AGS.ConclusionsNanoemulsion-based delivery significantly enhances the anticancer efficacy of the extract by promoting apoptosis, offering a promising strategy for plant-derived therapeutics.</p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"38 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bidirectional mendelian randomization identifies plasma proteins associated with cervical cancer risk.","authors":"Yan-Hong Zhao, Qing-Fen Ruan, Jing-Hua Ning, Xin Zhang, Run Qu, Jing Zou, Yi Liang, Cheng-Gui Zhang, Yu-Zhe Zhang","doi":"10.1186/s43046-026-00374-7","DOIUrl":"10.1186/s43046-026-00374-7","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer continues to pose a considerable challenge to global health, necessitating innovative approaches for improved diagnostics and personalized treatment strategies. Prior investigations have suggested that plasma proteins may play a role in the pathogenesis of cervical cancer; however, these studies do not confirm a causal relationship. To address this gap, conducted a large-scale Mendelian randomization (MR) study of the plasma proteome.</p><p><strong>Methods: </strong>We performed a two-sample bidirectional Mendelian randomization analysis involving 4,907 plasma proteins, utilizing publicly accessible genome-wide association study (GWAS) summary statistics, to examine the causal association between the plasma proteome and the risk of cervical cancer. Analytical methods included inverse variance weighting (IVW), weighted median, MR-Egger regression, and simple and weighted models. Additionally, we performed sensitivity analyses to evaluate heterogeneity and horizontal pleiotropy through Cochran's Q test, MR-Egger intercept, MR-PRESSO test, and leave-one-out analysis. We also applied false discovery rate (FDR) correction to the results of all IVW methods to identify the plasma proteins most strongly associated with cervical cancer. Finally, we enriched the most relevant plasma protein genes using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses and GeneMANIA to identify disease-related pathways.</p><p><strong>Results: </strong>According to the IVW method, seven plasma proteins are significantly associated with cervical cancer risk (P < 0.05). Specifically, six proteins demonstrated protective factors: DEFB135 (OR = 0.201, 95% CI = 0.082-0.492, P < 0.001), FGL2 (OR = 0.104, 95% CI = 0.032-0.338, P < 0.001), FTMT (OR = 0.612, 95% CI = 0.465-0.804, P < 0.001), PDIA4 (OR = 0.088, 95% CI = 0.026-0.295, P < 0.001), SPHK2 (OR = 0.102, 95% CI = 0.030-0.350, P < 0.001), and TMED2 (OR = 0.045, 95% CI = 0.008-0.246, P < 0.001). In contrast, RACGAP1 (OR = 1.755, 95% CI = 1.286-2.395, P < 0.001) was identified as a risk factor. Reverse MR analysis revealed no significant evidence of reverse causation (P > 0.05) between cervical cancer and these plasma proteins. Functional enrichment analysis identified several biologically relevant pathways potentially involved in cervical cancer pathogenesis, including the establishment of organelle localization, regulation of oxidoreductase activity, Ferroptosis, and Porphyrin metabolism.</p><p><strong>Conclusion: </strong>These findings suggest that DEFB135, FGL2, FTMT, PDIA4, SPHK2, and TMED2 may protect against cervical cancer, while RACGAP1 may represent a potential risk factor. The identified tumor markers provide mechanistic insights into the molecular basis of cervical cancer and warrant further investigation in functional studies.</p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"38 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the functional landscape of long non-coding RNAs in hepatocellular carcinoma: molecular mechanisms, clinical implications, and therapeutic prospects.","authors":"Humera Naveed, Zain-Ul Abidien, Kaleem Maqsood, Iram Amin, Muhammad Shahid, Samia Afzal","doi":"10.1186/s43046-026-00380-9","DOIUrl":"10.1186/s43046-026-00380-9","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains the third leading cause of cancer-related mortality worldwide, with limited treatment efficacy and poor prognosis, particularly in advanced-stage disease. Despite progress in diagnostic imaging and systemic therapies, early detection and effective targeted interventions remain major clinical challenges. Long non-coding RNAs (lncRNAs), a class of regulatory RNA molecules exceeding 200 nucleotides in length, have emerged as essential regulators of oncogenic signaling, metabolism, and tumor microenvironment in HCC. This review provides a comprehensive overview of the molecular mechanisms, biological functions, and clinical relevance of key lncRNAs involved in HCC progression. We summarize the dual roles of lncRNAs as oncogenic drivers and tumor suppressors, with particular emphasis on oncogenic lncRNAs including CYTOR, UCA1, MALAT1, SPRY4-IT1, uc001ncr, AF085935, HULC, and HOTAIR. Their regulatory functions are discussed within major cancer-associated signaling networks, including the PI3K/AKT/mTOR, Wnt/β-catenin, TGF-β/NF-κB, and EMT-associated pathways. Furthermore, each lncRNA is discussed in the context of its expression pattern, endogenous RNA (ceRNA) interactions, molecular partners, and functional contributions to cellular proliferation, invasion, metastasis, angiogenesis, immune modulation, and therapeutic resistance. In addition, we explore the emerging potential of lncRNAs as minimally invasive diagnostic and prognostic biomarkers, owing to their stability and detectability in tissue and circulating biofluids. We also discuss recent advances in RNA- targeted therapeutic strategies, including RNA interference, siRNA-mediated silencing, antisense oligonucleotides, and CRISPR-based genome editing approaches. Collectively, this review highlights the importance of integrating lncRNA expression signatures into personalized HCC management and the promising role of lncRNA-based diagnostics and therapeutics in transforming the future landscape of liver cancer detection, prognosis, and treatment.</p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"38 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13315050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating toxicity in lung cancer immunotherapy: challenges and advances in Nano medicine drug delivery.","authors":"Rishab Jain, Ananda Kumar Chettupalli, Sarad Pawar Naik Bukke, Shikha Yadav, Vidya Sankarapandian, Ungo-Kore Hussain Yahaya","doi":"10.1186/s43046-026-00358-7","DOIUrl":"10.1186/s43046-026-00358-7","url":null,"abstract":"<p><p>Lung cancer is still among the most malignant cancers, with immunotherapy becoming a ground-breaking treatment option. The ICIs and other immunotherapeutic drugs usually cause severe immune-related adverse effects curtailing their therapeutic efficacy. Meeting this challenge, Nano medicine-based drug delivery systems have gained considerable interest as they hold the promise of increasing therapeutic benefits at the same time as reducing toxicity. This chapter discusses the complex balance between the effectiveness and toxicity of lung cancer immunotherapy, underlining the application of nanotechnology in maximizing drug delivery. Nano carriers like liposomes, polymeric nanoparticles, dendrites, and lipid-based systems have demonstrated the capacity to augment the bioavailability of pharmaceuticals, facilitating tumour-specific environments, and alleviating systemic side effects. Other options suggest that stimuli-responsive and ligand-functionalized Nano platforms can provide spatial control over the immune response by enhancing infiltration to the tumour site while reducing toxicity to healthy organs. On the battlegrounds of nanomedicine, inhibiting resistance mechanisms consolidated with immune checkpoint inhibitors and conventional chemotherapeutics has conferred better therapeutic responses upon the patient. Its stability, bio-distribution, and regulatory pathway concerns still challenge clinical translation. The chapter discusses recent advances in preclinical and clinical testing and describes the development of Nano medicine-based regulatory T-cell-directed immunotherapy for lung and lung-associated cancers. The problems concerning both toxicity and the application of nanotechnology for targeting therapy will open new avenues toward developing safer and more effective antitumor immunotherapeutic regimes for lung cancer.</p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"38 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13310874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiome and cancer immunotherapy: a bibliometric analysis.","authors":"Wenbin Tan","doi":"10.1186/s43046-026-00376-5","DOIUrl":"10.1186/s43046-026-00376-5","url":null,"abstract":"<p><strong>Objective: </strong>To systematically analyze the global research landscape, collaboration patterns, knowledge flow pathways, and frontier trends in the synergistic effects between the microbiome and cancer immunotherapy.</p><p><strong>Methods: </strong>A systematic bibliometric analysis of publications on the synergistic effects between the microbiome and cancer immunotherapy (2010-2026) was performed using the Web of Science Core Collection. After deduplication, 3,058 publications were analyzed with CiteSpace 6.3.1 (co-citation, keyword burst, timeline), VOSviewer 1.6.19 (co-authorship, co-occurrence networks), and bibliometrix R package 4.4.1 (dual-map overlay, knowledge flow).</p><p><strong>Results: </strong>Annual publications grew at an average rate of 23.0%, reaching 715 in 2025. China and the United States contributed 60.1% of global output, with MD Anderson Cancer Center, Shanghai Jiao Tong University, and Paris-Saclay University serving as core collaboration hubs. Three major academic lineages (fundamental mechanisms, clinical translation, tumor-specific research) and three knowledge flow pathways (mathematical modeling → molecular genetics; clinical medicine → molecular biology; ecology → molecular biology) were identified, shaping distinct research paradigms. Hotspots evolved from \"gut microbiota-ICIs\" toward \"oral microbiota,\" \"engineered bacteria,\" and \"precision prediction.\"</p><p><strong>Conclusion: </strong>The field has transitioned from mechanistic exploration to precision intervention, with multidisciplinary integration and clinical translation as future priorities. The identified knowledge flow pathways and academic lineages provide a framework for understanding the intellectual structure of this rapidly evolving domain.</p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"38 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13309577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148339005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue engineering driven regeneration in oral squamous cell carcinoma: from biomaterials to precision gene editing.","authors":"B Deva Darshinii, N Subhapradha, S Raghavi, K Anbarasu","doi":"10.1186/s43046-026-00378-3","DOIUrl":"10.1186/s43046-026-00378-3","url":null,"abstract":"<p><p>Oral cancer is a significant global health challenge, ranking as the sixth most prevalent cancer worldwide, with approximately 377,000 new cases diagnosed annually. The high morbidity and mortality rates are largely attributed to tobacco and alcohol use. While conventional treatments such as surgery, radiation, and chemotherapy have improved survival rates, they often lead to unfavourable aesthetic and functional outcomes. Tissue engineering offers a promising alternative, providing regenerative solutions aimed at restoring both oral function and appearance. By integrating biomaterials, biological systems, and engineering principles, tissue engineering enables the creation of functional tissue replacements. The current review examines different t pathways the potential applications of autologous tissue, oral cancer cell lines, CRISPR, gene-editing technologies, and epigenetic modifications for tissue regeneration. Advanced scaffold technologies that mimic the natural extracellular matrix, along with stem cell-based therapies and bioactive molecules, are employed to support tissue growth and differentiation. Mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs) show significant potential in regenerating hard and soft oral tissues, while also targeting cancer stem cells (CSCs) to prevent recurrence. Furthermore, innovative technologies like 3D bio printing, combined with vascularization strategies, hold promise for developing patient-specific tissue constructs for reconstructive procedures. In conclusion, tissue engineering offers transformative potential for oral cancer treatment, presenting regenerative therapies that can significantly enhance patient outcomes and quality of life.</p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"38 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148302102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin enhances methylene blue-mediated photodynamic therapy in oral squamous cell carcinoma.","authors":"Mohamed A Osman, Marwa Sharaky, Hesham Abdel-Fattah, Ali M Safaan","doi":"10.1186/s43046-026-00359-6","DOIUrl":"10.1186/s43046-026-00359-6","url":null,"abstract":"<p><strong>Background: </strong>Head and neck squamous cell carcinoma (HNSCC) is the most common malignancy of the head and neck region with relatively low survival rate and response and high resistance to treatment. Tongue and floor of the mouth are the most commonly involved sites. New therapies for oral squamous cell carcinoma (OSCC) treatment are still required. An attractive option for the treatment of OSCC is the use of photodynamic therapy (PDT). Considering metformin's potential to reduce cancer risk and inhibit proliferation, therefore the present study aims to evaluate its ability to potentiate the methylene blue-mediated photodynamic effect against the growth of tongue cancer cells in vitro and the possible molecular mechanisms of action involved.</p><p><strong>Methods: </strong>Cytotoxic activity of metformin (MF) and/or Methylene blue (MB)+laser light (L) against the growth of HNO97 tongue cells was determined using the sulforhodamine (SRB) method. Several protein expressions were determined using ELISA kits include mechanistic target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and caspase 8.</p><p><strong>Results: </strong>Laser light at different energy per surface area induced inhibition in the surviving fraction of HNO97 cells, while in presence of MB (10 µg/ml for 4 h.), the surviving fractions showed more inhibition. Addition of MF (1000 µg/ml, for 24 h.) to MB + L induced significant 51 and 89% inhibition of cell survival at energy level of 45 and 337.5 J/cm², respectively. Addition of Metformin to MB-photodynamic therapy also increased the expression AMPK and decrease the expression of mTOR at the protein level. Moreover there were increase in Bax expression and decrease in Bcl2 expression with significant increase in caspase 8 expression at the protein level.</p><p><strong>Conclusion: </strong>Such combined treatment showed promising synergistic interaction via several molecular pathways, which is well tolerated and readily applicable strategy to improve the therapeutic outcome of PDT in cancer cell treatment.</p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"38 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic and nutritional impact of gastrectomy and perioperative treatment in gastric cancer: a prospective cohort study.","authors":"Tomasz Muszyński, Tomasz Jędrychowski, Adrianna Witalewska, Aldona Gawlewicz-Czepiel, Karina Polak, Michał Spieszny, Piotr Richter, Antoni Szczepanik, Kołodziejczyk Piotr","doi":"10.1186/s43046-026-00367-6","DOIUrl":"10.1186/s43046-026-00367-6","url":null,"abstract":"<p><strong>Background: </strong>Gastrectomy due to gastric cancer leads to metabolic alterations in body composition, significantly affecting nutritional status. This prospective study aimed to investigate the metabolic effects of gastrectomy and perioperative treatment on the nutritional status of gastric cancer patients.</p><p><strong>Methods: </strong>A total of 37 patients diagnosed with gastric cancer, treated with perioperative chemotherapy, without evidence of dissemination or metastasis, were included in the study. Demographic data, Body Mass Index, full blood count parameters, lipid profiles, vitamin B12, vitamin D, iron levels, albumin, prealbumin, total serum protein concentration, bioimpedance parameters, physical activity levels, quality of life, Prognostic Nutritional Index, neutrophil-to-lymphocyte ratio, and systemic immune-inflammation index were assessed preoperatively and at two follow-ups (6 and 12 months post-surgery) for each patient.</p><p><strong>Results: </strong>Significant changes were observed across the analyzed parameters, demonstrating the metabolic impact of gastrectomy and perioperative systemic treatment on the nutritional status of gastric cancer patients.</p><p><strong>Conclusions: </strong>The study provides a comprehensive evaluation of the long-term nutritional status of gastric cancer patients post-gastrectomy, offering valuable insights into postoperative metabolic and dietary adaptations. Obtained results underscore the dynamic physiological adaptations following gastric resection, emphasizing the importance of nutritional and metabolic monitoring for long-term recovery. Targeted rehabilitation strategies and micronutrient supplementation are crucial in reducing postoperative complications and improving patient outcomes.</p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"38 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Programmed cell death protein 1 (PD-1) / programmed cell death ligand 1 (PD-L1) in multiple myeloma.","authors":"Shimaa El-Garf, Reham Hammad, Eman Kandeel, Ahmed Rabea, Mona Alrayes","doi":"10.1186/s43046-026-00379-2","DOIUrl":"10.1186/s43046-026-00379-2","url":null,"abstract":"<p><strong>Background: </strong>The bone marrow microenvironment in multiple myeloma (MM) is characterized by complex immune dysregulation involving multiple inhibitory pathways. Among these, the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis contributes to T-cell dysfunction; However, its isolated role within this multifactorial network remains incompletely defined.</p><p><strong>Methods: </strong>This prospective observational study performed a cross-sectional immunophenotypic analysis of 39 newly diagnosed MM (NDMM) patients. PD-1 expression on T cells and PD-L1 expression on bone marrow (BM) plasma cells (PCs) were assessed using flow cytometry. Associations with clinical and laboratory parameters were analyzed using correlation analysis.</p><p><strong>Results: </strong>PD-L1 mean fluorescence intensity (MFI) on PCs showed a positive correlation with BM T-cell percentage (r = 0.350, p = 0.029). PD-1 MFI on T cells correlated with total leukocytic count (TLC) (r = 0.326, p = 0.043). In International Staging System (ISS) stage III patients, PD-L1 expression on PC correlated with T cells% (r = 0.501, p = 0.018) and TLC (r = 0.427, p = 0.047), while PD-1 expression showed a strong positive correlation with TLC (r = 0.676, p = 0.001) and a negative correlation with age (r = - 0.492, p = 0.020). No significant association was observed with treatment response.</p><p><strong>Conclusion: </strong>These findings provide an exploratory description of PD-1/PD-L1 expression patterns within the BM microenvironment in MM. Only in advanced cases according to ISS, PD-L1 expression on PC was linked to BM T cells frequency. PD-1/PD-L1 expression patterns were not linked to treatment response.</p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"38 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune checkpoint crosstalk between LAG-3 and CD39/CD73 in glioblastoma: dual-pathway regulation of metabolic exhaustion and therapeutic reversal strategies.","authors":"Arpita Mukherjee","doi":"10.1186/s43046-026-00361-y","DOIUrl":"10.1186/s43046-026-00361-y","url":null,"abstract":"<p><p>Glioblastoma (GBM) represents an immunologically \"cold\" and metabolically suppressive tumor characterized by profound T-cell exhaustion, hypoxia-induced adenosinergic signaling, and resistance to checkpoint blockade. Converging evidence identifies lymphocyte-activation gene 3 (LAG-3) and the CD39/CD73 ectonucleotidase cascade as cooperative regulators of immune dysfunction within the GBM microenvironment. LAG-3 attenuates TCR/CD3 signaling and disrupts mitochondrial oxidative phosphorylation, diminishing effector T-cell persistence. Concurrently, CD39/CD73-mediated ATP hydrolysis elevates adenosine levels, activating A₂A receptors that inhibit glycolysis, suppress IFN-γ, and promote Treg and M2 macrophage polarization. Spatial and single-cell omics reveal co-localization of LAG-3⁺ exhausted T cells with CD73⁺ stromal and myeloid niches, suggesting a reciprocal immunometabolic feedback loop reinforcing exhaustion. This review elucidates the molecular crosstalk between LAG-3 signaling and the adenosine pathway, emphasizing key metabolic regulators including AMPK, mTOR, and HIF-1α. It further evaluates therapeutic strategies combining LAG-3 or PD-1 blockade with adenosine receptor antagonists or CD73 inhibitors to restore T-cell bioenergetics and antitumor activity. By integrating mechanistic immunometabolism with translational insights, this review establishes a dual-pathway framework of checkpoint synergy underlying resistance in GBM and proposes rational combination immunotherapies to reverse metabolic and immune exhaustion.</p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"38 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}