Medical Oncology最新文献

{"title":"Transcriptomics analysis and experimental assay to screen prognostic genes of N6-methyladenosine RNA methylation related to cuproptosis in colorectal cancer.","authors":"Dongjie Sun, Zhu Liu, Meiyan Chen, Yang He, Xiangpeng Zeng, Dazhou Li, Wen Wang","doi":"10.1007/s12032-026-03441-0","DOIUrl":"https://doi.org/10.1007/s12032-026-03441-0","url":null,"abstract":"<p><p>Cuproptosis and N6-methyladenosine (m6A) RNA methylation have been identified as significant factors in cancer. Consequently, we seek to uncover m6A RNA methylation-related prognostic genes that are correlated with cuproptosis-related genes (CRGs) in colorectal cancer (CRC) and develop an effective prognostic model. Based on public datasets, differential expression analysis, correlation analysis, and machine learning were conducted to identify prognostic genes. Subsequently, a prognostic model was constructed and validated. Furthermore, independent predictive markers were found through the use of clinical characteristics and risk score, to establish a prognostic nomogram. Prognostic gene expression in CRC and normal samples was evaluated using reverse transcription-quantitative PCR (RT-qPCR). According to the prognostic genes, potential drugs for CRC were predicted using artificial intelligence drug design (AIDD) and computer-aided drug design (CADD). A prognostic model was developed utilizing 7 m6A RNA methylation-related prognostic genes that were significantly correlated with CRGs (MMP1, TIMP1, SNAI1, CDC25C, XRN2, COX5A, and FBXL5) in CRC. Survival analysis uncovered a notable contrast in survival outcomes between the high- and low-risk groups. The nomogram constructed based on age, stage, T stage, and risk scores demonstrated good predictive ability. RT-qPCR results showed that MMP1, TIMP1, SNAI1, and CDC25C were upregulated in CRC samples, while COX5A was downregulated, consistent with the bioinformatics analysis results. Furthermore, 186 candidate drugs targeting COX5A were identified, 153 of which showed better predicted binding affinity than the positive-control ligand 3,5‑diiodo‑L‑thyronine. Our analysis sets the groundwork for a more comprehensive comprehension of the fundamental molecular pathways involved in CRC.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 11","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228233","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}

{"title":"Antibody-drug conjugates and tumor immunity in breast cancer.","authors":"Shinichiro Kashiwagi","doi":"10.1007/s12032-026-03458-5","DOIUrl":"https://doi.org/10.1007/s12032-026-03458-5","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) combine antigen-directed delivery with cytotoxic or immunostimulatory payloads. Their antitumor activity can involve direct tumor-cell killing, but the extent to which conventional ADCs remodel human breast-cancer immunity remains incompletely defined. This review critically separates established cytotoxic mechanisms from immune-mediated effects and incorporates emerging STING agonist ADCs, neonatal Fc receptor (FcRn) trafficking, and quantitative antigen measurement. A focused narrative synthesis of mechanistic, translational, and clinical literature was performed, emphasizing primary studies of HER2-, TROP2-, and HER3-directed ADCs and tumor-targeted STING agonist conjugates. Peer-reviewed studies were prioritized; congress abstracts and non-peer-reviewed sources were used only when specifically requested or when no full report was available. Evidence was classified as preclinical, translational, or clinical, and causal claims were restricted accordingly. Conventional ADCs first produce antigen-dependent internalization, intracellular payload release, and direct cytotoxicity. Bystander killing can extend cytotoxic exposure beyond antigen-high cells. In selected preclinical systems, payload-induced stress or DNA damage can generate immunogenic-cell-death signals, engage cGAS-STING signaling, preserve Fcγ receptor-dependent effector functions, and support antigen presentation. These effects are platform- and context-dependent and are not uniformly demonstrated in patients. By contrast, STING agonist ADCs and immune-stimulating antibody conjugates are designed to deliver an innate agonist to antigen-bearing tumors and can activate STING in tumor and myeloid compartments in mouse models; their clinical value in breast cancer remains investigational. FcRn primarily rescues pinocytosed IgG in acidic endosomes and governs exposure and tissue disposition; wild-type IgG uptake at neutral pH is predominantly fluid-phase, whereas residual neutral-pH FcRn binding in engineered variants may increase uptake when FcRn is abundant. Current HER2 and TROP2 immunohistochemistry does not quantify accessible membrane antigen, internalization, or immune contribution with sufficient precision. Quantitative continuous scoring and membrane-localization metrics are promising but require prospective, breast-cancer-specific validation. ADC efficacy should not be interpreted as proof of immune activation. A rigorous framework must measure antigen abundance and localization, ADC delivery and trafficking, payload pharmacology, and serial immune changes, while separately evaluating target-independent toxicity. Mechanism-linked sampling and prospective validation are required before immune biomarkers, FcRn-related variables, or quantitative antigen metrics can guide routine ADC selection.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 11","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228240","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}

{"title":"MG53 suppresses the progression of bladder cancer through E3 ubiquitin ligase-mediated degradation of AMPKα.","authors":"Xiangfei He, He Zhang, Yanping Zhang, Junwei Wu, Tianen Wang, Yunlong Liu, Ke Jin, Weixiang Tang, Qinghua Ye, Qingwei Wang","doi":"10.1007/s12032-026-03448-7","DOIUrl":"https://doi.org/10.1007/s12032-026-03448-7","url":null,"abstract":"<p><p>MG53/TRIM72 is a member of the tripartite motif family of E3 ubiquitin ligases that regulates metabolic homeostasis and tumor-associated signaling; however, its role in bladder cancer remains undefined. We investigated the expression, function, and molecular mechanism of MG53 in bladder cancer. MG53 expression was analyzed in bladder cancer tissues and cell lines. Functional assays including proliferation, invasion, glycolytic metabolism, intracellular reactive oxygen species (ROS) accumulation, and apoptosis were performed. The interaction between MG53 and AMPKα was examined using co-immunoprecipitation and ubiquitination assays. In vivo tumor growth was assessed in xenograft models. MG53 was significantly downregulated in bladder cancer tissues compared to adjacent normal tissues, and its expression was inversely correlated with AMPKα levels. Overexpression of MG53 suppressed cell proliferation, invasion, and glycolytic metabolism, and was also accompanied by increased intracellular ROS accumulation and a higher apoptotic rate, together with elevated cleaved caspase-3 and an increased Bax/Bcl-2 ratio, in bladder cancer cells. Mechanistically, MG53 promoted the ubiquitination and proteasomal degradation of AMPKα. In vivo experiments demonstrated that MG53 overexpression inhibited tumor growth in xenograft models. Our findings reveal that MG53 functions as a tumor suppressor in bladder cancer by promoting AMPKα degradation through its E3 ubiquitin ligase activity, thereby attenuating the Warburg effect; MG53 overexpression was also associated with intracellular ROS accumulation and apoptosis in bladder cancer cells. MG53 represents a candidate therapeutic target for bladder cancer treatment, whose translational value remains to be established in future preclinical and clinical studies.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 11","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228224","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}

{"title":"Primary cardiac angiosarcoma: From pathogenesis to therapeutic strategies.","authors":"Han Gao, Haoyi Zhang, Diandian Zhu, Yaru Zhang, Mengqi Guo, Mei Zhu, Yuan Wang, Ming Yang","doi":"10.1007/s12032-026-03467-4","DOIUrl":"https://doi.org/10.1007/s12032-026-03467-4","url":null,"abstract":"<p><p>Primary cardiac angiosarcoma (PCAS) is a rare yet highly aggressive malignancy arising from cardiac vascular endothelial cells. This tumor predominantly affects young to middle-aged males and carries a dismal prognosis, typically characterized by a median survival of less than one year. Owing to its nonspecific manifestations and rapid infiltrative growth, most patients present at an advanced or metastatic stage. Recent genomic and transcriptomic studies have revealed molecular drivers in PCAS, including recurrent mutations in POT1, KDR/VEGFR2, and PLCG1, loss of CDKN2A, and aberrant angiogenic cascade activation. In parallel, an immunosuppressive tumor microenvironment dominated by exhausted T cells and tumor-associated macrophages may collectively contribute to tumor progression and therapeutic resistance. Multimodal imaging, integrating echocardiography, cardiac magnetic resonance, computed tomography, and PET/CT, plays a central role in detection, tissue characterization, and systemic staging. Histopathology with immunohistochemistry remains the diagnostic gold standard. Current treatment strategies rely on multimodal approaches, including surgery, chemotherapy, and radiotherapy, with emerging targeted therapies and immunotherapies under active investigation. Despite recent advances, clinical outcomes remain poor, highlighting the urgent need for improved mechanistic understanding and more effective personalized therapeutic strategies.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 11","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228218","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}

{"title":"Histologic and molecular transformation from non-small cell to small cell lung cancer: insights in the era of expanding treatment options.","authors":"Zeming Wang, Guoying Cai, Junquan Zhu, Juchao Wang","doi":"10.1007/s12032-026-03451-y","DOIUrl":"https://doi.org/10.1007/s12032-026-03451-y","url":null,"abstract":"<p><p>Lung cancer remains one of the leading causes of cancer-related mortality worldwide, with increasing attention being paid to the histologic transformation between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). This review provides a comprehensive overview of the current understanding of NSCLC-to-SCLC transformation, covering the classification of NSCLC subtypes, advances in targeted therapy for epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma, clinical manifestations of SCLC transformation, diagnostic technologies, therapeutic strategies, ongoing controversies, and future perspectives. By integrating extensive evidence from the literature, we systematically analyze the clinical findings, molecular mechanisms, diagnostic approaches, and treatment modalities related to this phenomenon. Our aim is to offer clinicians and researchers a thorough and insightful reference to facilitate further investigation into NSCLC-to-SCLC transformation and ultimately improve therapeutic outcomes and prognosis for patients with lung cancer.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 11","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228220","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}

{"title":"Bladder preservation is still feasible in the rare aggressive small cell carcinoma subtype.","authors":"Yahia Ismail, Amr Kamal, Hatem Aboulkassem, May Gamal Ashour, Ahmed Amin AbouGabal, Rasha M Allam, Mai Gad, Mohamed Elsayed Mostafa, Mohammad Taher","doi":"10.1007/s12032-026-03437-w","DOIUrl":"https://doi.org/10.1007/s12032-026-03437-w","url":null,"abstract":"<p><strong>Purpose: </strong>Primary urinary bladder small cell carcinoma (UBSCC) is a rare aggressive malignant neoplasm with no established treatment guidelines. Radical cystectomy (RC) alone is suboptimal in localized disease; therefore, chemotherapy and radiotherapy are required. We aimed to report our outcomes of UBSCC.</p><p><strong>Methods: </strong>UBSCC patients who presented to our institute between 2012 and 2021 were retrospectively evaluated for their clinicopathologic features, management modalities, event-free (EFS) and overall survival (OS).</p><p><strong>Results: </strong>Sixty patients included. Metastatic disease was present at diagnosis in 12 (20%). For localized disease patients, upfront RC was done in 9(19%); meanwhile, neoadjuvant chemotherapy was employed in the rest. In the latter group,18 patients (46%) achieved complete response (CR), and those proceeded to further concurrent chemoradiation as a bladder preservation management. Platinum-etoposide (PE) regimen was more frequently used than platinum-gemcitabine (PG) in the neoadjuvant/adjuvant and metastatic settings (57%). The latter combination was independent factor associated with less likelihood achievement of CR about 7 times that of PE (OR:7.27;95%CI:1.33-39.86;p = 0.02). The median EFS & OS were 42.4 & 52.7 months, respectively, with cumulative 5-year EFS & OS of 46.9 & 49.5%, respectively. On multivariate analysis, PG protocol was independent factor associated with worse EFS compared to PE, while initially metastatic disease was independent factor linked with poor OS compared to localized disease.</p><p><strong>Conclusions: </strong>Despite its hostile behavior, the high CR rate in our study confirms the remarkable sensitivity of localized UBSCC to chemotherapy especially PE. Bladder preservation is feasible in those achieved CR, and is associated with favorable outcomes. These findings, however, should be interpreted cautiously and warrant further prospective evaluation.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 11","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228311","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}

{"title":"Curcumin in ovarian cancer: mechanistic insights and translational potential.","authors":"Mojtaba Esmaeli, Maryam Dehghanpour Dehabadi","doi":"10.1007/s12032-026-03454-9","DOIUrl":"10.1007/s12032-026-03454-9","url":null,"abstract":"<p><p>Ovarian cancer remains the most fatal gynecological malignancy, primarily due to delayed diagnosis, rapid progression, and resistance to standard chemotherapy. Curcumin, a natural polyphenol from Curcuma longa, has been investigated for its potential anticancer properties through the modulation of multiple molecular pathways. This systematic review examines the mechanistic and therapeutic roles of curcumin and its nanoformulations in preclinical models of ovarian cancer. Evaluation of 21 studies indicates that curcumin may influence key signaling pathways such as phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt)/ mechanistic target of rapamycin (mTOR), nuclear factor kappa β (NF-κβ), Janus kinase (JAK) /signal transducer and activator of transcription 3 (STAT3), and Wnt/β-catenin. Preliminary evidence also suggests that curcumin may modulate the tumor microenvironment through changes in tumor-associated macrophage polarization, although this finding is currently supported by limited evidence. These interactions are associated with increased apoptosis, reduced proliferation, inhibition of epithelial-to-mesenchymal transition (EMT), and enhanced sensitivity to chemotherapeutic agents like cisplatin and paclitaxel. Nanoformulations-such as micelles, dendrosomes, liposomes, and core-shell nanoparticles-have been shown to improve curcumin's bioavailability and therapeutic performance compared to its free form. While these preclinical findings suggest potential benefits, further clinical studies are necessary to confirm curcumin's role as a supportive treatment in ovarian cancer.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 11","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149708","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}

{"title":"The gut-pancreas axis: microbial dysbiosis as a pathogenic driver of diabetes and pancreatic cancer.","authors":"Yabin Li","doi":"10.1007/s12032-026-03421-4","DOIUrl":"10.1007/s12032-026-03421-4","url":null,"abstract":"<p><p>The gut microbiome dysbiosis is a potential contributing mediator for the gut and pancreas link. The gut microbiome contributes to the development of both diabetes and pancreatic cancer. There are approximately two distinct ways through which the gut microbiome leads to cell damage and then systemic inflammatory responses. The gut microbiome generates a unique set of metabolic products, activating diverse pathways and cytokines. The bottom line for this process leads to the generation of systemic inflammation. In type 2 diabetes, inflammatory signaling predominantly disrupts IRS-1/PI3K/AKT signaling, impairing insulin receptor pathways and glucose absorption, triggering β-cell malfunction and insulin resistance. Dysbiosis-associated inflammatory signaling in pancreatic cancer stimulates the growth of the tumour via activating oncogenic pathways, immune evasion, and epithelial-mesenchymal transition (EMT). The bacterial metabolites can cause. DNA mutations and affect the signaling pathways of cancer cells. In addition, this review offers an integrated microbiome-driven inflammatory-metabolic paradigm utilizing the gut-pancreas axis to associate pancreatic cancer and diabetes. A realistic and in-depth understanding of the above-described processes could result in the development of new techniques for the targeted modification of the gut microbiome for the prevention and management of such diseases.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 11","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137513","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}

{"title":"A propionate metabolism-related gene signature predicts prognosis and immunological features in colorectal cancer.","authors":"Shanmin Yuan, Sha Li, Cong Chen","doi":"10.1007/s12032-026-03431-2","DOIUrl":"10.1007/s12032-026-03431-2","url":null,"abstract":"<p><p>Propionate metabolism has emerged as a key metabolic axis shaping colorectal cancer (CRC) biology and the tumor microenvironment; however, propionate metabolism-related molecular stratification and its prognostic and therapeutic implications remain insufficiently characterized. Transcriptomic profiles of The Cancer Genome Atlas colon adenocarcinoma (TCGA-COAD) and rectum adenocarcinoma (TCGA-READ) were integrated to construct a CRC training cohort, and GSE38832 served as an external validation set. Propionate metabolism-related genes (PMRGs) were curated from GeneCards and intersected with differentially expressed genes to define differentially expressed PMRGs (DEPMRGs). Prognostic DEPMRGs were screened by univariate Cox regression and used for consensus clustering to identify propionate metabolism-related subtypes, followed by functional enrichment and immune landscape profiling (ESTIMATE, single-sample Gene Set Enrichment Analysis, and CIBERSORT). After adjustment for clinicopathological characteristics, Cox proportional hazards modeling was performed to verify whether the signature retained independent prognostic relevance. To facilitate individualized risk estimation, a nomogram was constructed from the significant variables, and its reliability and potential value in clinical decision-making were further evaluated through calibration analysis and decision curve analysis. Immunotherapy relevance was explored using Immunophenoscore and Tumor Immune Dysfunction and Exclusion, and anti-PD-L1 response was assessed in the IMvigor210 cohort. To characterize molecular differences across risk subgroups, the mutational landscape and tumor mutational burden were profiled with the maftools package, whereas potential therapeutic susceptibility was inferred from pRRophetic prediction and CellMiner-based drug response analyses. Application of consensus clustering to prognostic PMRG-related genes revealed two molecular classes in CRC, which were distinguished by different prognostic patterns and immune microenvironmental characteristics. A four-gene prognostic signature was then established, enabling classification of patients into low- and high-risk subsets with clearly separated survival curves in the training cohort; this predictive pattern was further reproduced in GSE38832. Comprehensive immune characterization demonstrated that the two risk groups differed substantially in immune-cell infiltration, checkpoint-gene expression, and immunotherapy-associated signatures, with the low-risk group showing a more favorable predicted response in the IMvigor210 cohort. Propionate metabolism-associated subtyping and a four-gene prognostic signature enable robust risk stratification in CRC and link metabolic programs to immune contexture and therapeutic vulnerability, providing a potential framework for prognosis assessment and individualized treatment.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 11","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137264","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}

{"title":"Nano-Diosmin mitigates EAC-induced renal injury through Nrf2-mediated antioxidant activation and NF-κB-dependent apoptotic suppression.","authors":"Ahmad Najem Alshammari, Mohammed Saleh Alfawaz, Fatma Oraby, Ahmed M Mohamed, Ekramy M Elmorsy, Suzan S A Mohamed, Marwa M F Atta, Ali Ali El-Raghi","doi":"10.1007/s12032-026-03387-3","DOIUrl":"10.1007/s12032-026-03387-3","url":null,"abstract":"<p><p>The present study provides the first evidence of the anticancer-associated renoprotective efficacy of diosmin (DI) delivered via chitosan nanoparticles (DI-CHNPs) in mice bearing Ehrlich ascites carcinoma (EAC). Sixty female Swiss albino mice were divided into six groups: controls, DI, DI-CHNPs, EAC, EAC+DI, and EAC+DI-CHNPs. Treatments involved DI or DI-CHNPs (100 mg/kg/day) for 20 days with or without tumor induction. DI-CHNPs significantly reduced tumor burden, as evidenced by lower body weight gain, abdominal circumference, tumor volume, and viable tumor cell count, and these effects were superior to free DI. DI-CHNPs also prolonged survival and improved renal function markers (urea, creatinine, electrolytes), indicating that attenuation of tumor progression was accompanied by reduced secondary renal injury. Antioxidant defenses in kidney tissues were strengthened through increased superoxide dismutase, catalase, glutathione peroxidase activities, and reduced glutathione levels, alongside reduced malondialdehyde. DI-CHNPs activated the Nrf2/HO-1/NQO1 pathway while down-regulated the inflammatory pathways controlling genes (Tgfb 1, Nfkb 1, Il6) and pro-apoptotic markers (Bax, Caspase-3), with increased Bcl-2 expression. Histopathological and ultrastructural analyses confirmed superior renal protection compared with DI. Molecular docking provided in silico supportive evidence for DI interaction with Nrf2, NF-κB, caspase-3, and TGF-β-related molecular targets involved in oxidative stress, inflammation, and apoptosis. Overall, the findings suggest that nanoparticle formulation enhanced the therapeutic performance of DI, likely through improved stability and sustained-release properties, resulting in superior antitumor efficacy and attenuation of tumor-associated renal injury.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 11","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137432","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}