Conventional transarterial chemoembolization (cTACE) is a guideline-approved therapy for unresectable hepatocellular carcinoma (HCC). This study aimed to characterize systemic and local cytokine changes induced by cTACE, and to evaluate their correlation with treatment response, Lipiodol deposition, and overall survival (OS).

In this prospective single-center study, 46 patients with unresectable HCC underwent either cTACE followed by interstitial brachytherapy (iBT) after 24h (n = 23) or iBT alone (n = 23). Peripheral blood samples were obtained before treatment in both groups and 24h post-cTACE in the cTACE/iBT group. Additionally, tumor interstitial fluid (TIF) was isolated from tumor biopsies that were collected prior to iBT from untreated tumors (iBT group) or 24h post-cTACE (cTACE/iBT group). Serum and TIF cytokines were quantified using multiplex assays and correlated with radiologic response at 8-week MRI, Lipiodol patterns on CT 24h post-cTACE, and OS.

Post-cTACE, serum IFN-γ, MCP-1, TNF-α, MIP-1α, IL-17, IL-8, IL-4, and IL-5 significantly decreased, while IL-6 increased (p < 0.005). TIF analysis showed higher IL-17 in untreated tumors compared to post-cTACE (p = 0.038), but differences were modest. In the iBT group, responders had elevated TIF IL-8 (p = 0.0103) and VEGF-A (p = 0.0185) prior to treatment, whereas in the cTACE/iBT group, responders exhibited lower TIF bFGF post-cTACE than non-responders (p = 0.0449). Elevated baseline serum IL-6 (p = 0.052), IL-8 (p = 0.036), and IFN-γ (p = 0.0508) were associated with shorter OS, while higher TIF IFN-γ (p = 0.051) correlated with improved OS. Baseline serum IL-1β (p = 0.0266) and post-cTACE serum level of VEGF-A (p = 0.0318) were higher in patients with homogeneous Lipiodol deposition in tumors, which correlated with longer OS.

cTACE induces distinct systemic and local immune alterations that influence patient outcomes. Specifically, elevated serum IL-6 predicted poor survival, while homogeneous Lipiodol deposition marks favorable immune modulation and outcomes. Combining cytokine profiling with imaging biomarkers may enable improved, personalized treatment strategies in HCC.

Energy metabolism reprogramming of cancer cells with the abnormal glycolytic capacity represents a novel direction of tumor therapy. Nevertheless, there is a lack of evidence linking genetic variations in glycolysis-related genes to the risk and clinical progression of lung cancer (LC). This study is aimed at clarifying the genetic effect of glycolytic pathway-related genes on the occurrence and development of LC.

In this two-stage case-control study, we enrolled 300 LC patients and 600 healthy controls, as well as 1248 case-control pairs from several hospitals in Guangzhou, to evaluate the association between the genetic variations of glycolysis-related genes (GLUT1 rs1385129G>A, GLUT11 rs6003939A>C, GLUT12 rs1484180G>A and ENO2 rs11064467C>T) and the risk of LC. Follow-up data and the TCGA database were used to evaluate the relationship between GLUT1 rs1385129G>A and GLUT1 expression with the clinical progression of LC.

Only GLUT1 rs1385129G>A was found to be associated with increased risk of LC in this two-stage case-control study (p < 0.05). Further analysis of the expression levels of GLUT1 in GLUT1 rs1385129G>A genotypes showed that they were positively correlated with the number of A alleles (p < 0.01), and the GA genotype had a moderate effect on GLUT1 expression, whereas the AA genotype had a strong effect (GA vs. GG: Cohen's d = 0.768, 95% CI = 0.20-1.02; AA vs. GG: Cohen's d = 1.890, 95% CI = 0.93-3.57). The results were further verified by eQTL analysis based on the GTEx database. The GA and AA genotypes were associated with worse prognosis in LC compared with the GG genotype, as determined by Cox regression (GA + AA vs. GG: HR = 1.37, 95% CI = 1.20-1.57). Furthermore, the survival curve of LC plotted using the GEPIA website showed that the group with high expression of GLUT1 had an increased risk of poor prognosis compared with the low (Log-rank p < 0.01; HR = 1.40). The same result was obtained from the Kaplan-Meier Plotter database (Log-rank p < 0.01; HR = 1.34).

Altogether, GLUT1 rs1385129G>A may increase the risk of LC and contribute to a poor prognosis by upregulating GLUT1 expression.

Malignant lung tumors are the leading cause of cancer-related mortality worldwide, and therefore remodeling of the tumor microenvironment (TME) has become an important strategy to overcome anti-tumor therapy resistance in lung cancer. Flavonoid components isolated from Citri Reticulatae Pericarpium (CRP), such as nobiletin, hesperidin, and tangeretin, have been shown to modulate the lung cancer TME in a highly relevant manner. The present narrative review collected literature from the PubMed, Web of Science, Embase, CNKI, and Wanfang databases between 2016 and 2026, and hence discussed the molecular mechanisms by which CRP flavonoids reshape the lung cancer TME, namely their regulation of oxidative stress-inflammation homeostasis, correction of lipid metabolic reprogramming, induction of pyroptosis, and inhibition of epithelial-mesenchymal transition. Discussion of the role of EMT and tumor angiogenesis suppression were also presented. Then evidence regarding the modulation of emerging targets was introduced, namely ferroptosis and the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, which are both promising targets in lung cancer models. Translational prospects of CRP flavonoids were led to enhancing immune checkpoint inhibitor (ICI) efficacy and developing nano-delivery systems. The article first outlined the fundamental barriers, then gave a very systematic and critical review of the contradictory findings, context-dependent effects, and methodological limitations in the existing literature; and then pointed out the gaps in frontier research. Therefore, it provides an excellent theoretical foundation for the research and development of anti-lung cancer drugs from CRP flavonoids, while also objectively identifying the current knowledge gaps and clinical translation bottlenecks.

Fever of unknown origin (FUO) with lymphadenopathy poses a substantial diagnostic challenge, particularly in differentiating malignant lymphoma from benign lymph node disorders. Although PET/CT plays a crucial role in lesion detection, inflammatory and immune-mediated lymphadenopathies often exhibit metabolic patterns overlapping with lymphoma, leading to limited diagnostic specificity. Radiomics enables high-throughput extraction of quantitative imaging features that capture intratumoral heterogeneity beyond visual assessment, while blood-based biomarkers reflect systemic inflammatory and metabolic states. This study aimed to develop and validate a multimodal diagnostic model integrating PET/CT radiomics and clinical biomarkers to improve the discrimination of lymphoma from benign lymphadenopathy in patients with FUO.

This retrospective study included FUO who underwent PET/CT. Lymph nodes were selected if the short-axis diameter was ≥1 cm on CT or if metabolic activity exceeded the mediastinal blood pool. Clinical and laboratory data were collected, and radiomics features were extracted from 40%SUVmax-based VOIs using LIFEx. Patients were randomly divided into training and testing sets (7:3). A biomarker model, radiomics model, and combined model were constructed using logistic regression, with feature selection performed via the least absolute shrinkage and selection operator (LASSO) for radiomics. Model performance was evaluated using receiver operating characteristic (ROC) curves, and DeLong's test. A nomogram was developed for individualized prediction.

A total of 203 patients were enrolled (114 lymphoma, 89 benign). In the training cohort, under the curve (AUC)s for the biomarker, radiomics, and combined models were 0.924, 0.903, and 0.970, respectively, with the combined model showing significantly superior performance. In the testing cohort, the corresponding AUCs were 0.903, 0.912, and 0.958, again demonstrating the highest accuracy for the combined model. Key predictors in the final model included procalcitonin (PCT), serum amyloid A (SAA), and PET/CT radiomics features. A nomogram was generated to facilitate individualized risk estimation.

PET/CT radiomics provides strong discriminatory ability for differentiating lymphoma from benign lymphadenopathy in FUO. Incorporating multidimensional biomarkers such as PCT and SAA further enhances diagnostic performance.

Delayed platelet engraftment remains a major limitation of autologous stem cell transplantation (ASCT) for plasma-cell neoplasms. Romiplostim N01, a thrombopoietin receptor agonist, may enhance early megakaryocytic recovery, while the use of non-cryopreserved peripheral blood stem cells (PBSCs) eliminates dimethyl-sulfoxide-related toxicity and reduces procedural cost.

This retrospective study evaluated 15 patients receiving non-cryopreserved PBSCs and early Romiplostim N01 after ASCT and compared them with 21 historical controls who received cryopreserved PBSCs and recombinant human thrombopoietin. We tried to compare time to engraftment, transfusion burden, hospitalization duration and cost, safety, hematologic responses and survival outcomes.

Platelet engraftment occurred significantly earlier in the Romiplostim N01 cohort (median 11 vs. 13 days; P = 0.008), and complete platelet recovery by day +30 was higher (100% vs. 66.7%; P = 0.027). Neutrophil recovery, transfusion requirements, and hospitalization duration were comparable between groups. Total hospitalization cost was markedly lower with Romiplostim N01 (77, 609 ± 21, 624 vs. 106, 188 ± 14, 910 CNY; P < 0.001). The two patient groups also demonstrated comparable safety profiles, treatment responses, and survival outcomes.

Romiplostim N01 safely accelerates thrombopoietic recovery and substantially reduces cost when combined with non-cryopreserved PBSCs. This strategy represents a practical and economically favorable supportive-care model for ASCT.

Mucosal melanomas arise from melanocytes in mucosal tissues, and it's usually detected at a late stage owing to its anatomic location. Advances in immunotherapies have proved to be promising therapeutic approaches for advanced mucosal melanoma patients, however, clinical studies have shown mucosal melanoma patients are less responsive to ICIs than cutaneous melanoma. Effective therapy is still lacking.

To investigate the efficacy and safety of SHR-1210 (an anti-programmed cell death-1 antibody) in combination with Apatinib (a vascular endothelial growth factor receptor 2 inhibitor) as late-line treatment in patients with advanced mucosal melanoma (Ethics approval number 2019184;ClinicalTrials.gov ID: NCT03986515).

Patients with confirmed metastatic mucosal melanoma according to AJCC 8.0. In this single-arm, single-center, phase II nonrandomized clinical trial, patients with advanced mucosal melanoma who have received several line treatments were enrolled between 2019.06 and 2022.12. The data cutoff date was June 11th, 2025. Patients received 200mg SHR-1210 intravenously every 3 weeks, and oral Apatinib 250 mg daily until unacceptable toxic effects or disease progression.

A total of 13 patients were enrolled and received treatment. The disease control rate (DCR) reached 100% (SD = 13). The objective response rate (ORR) was 0%. The estimated median overall survival (OS) was 29.9 months (95% CI 15.26-44.54),. The estimated median progression-free survival (PFS) was 5.17 months (95% CI 3.27-10.27),. The most common grade 1-2 was hand and foot induration with desquamation and pain, and one case of grade 4 abnormal liver function and grade 3 hypertension. No treatment-related deaths occurred.

This suggests that this combination therapy model may be a promising disease control for mucosal melanomas. However, the sample size is relatively small and needs to be increased for further research.

https://clinicaltrials.gov/study/NCT03986515, identifier NCT03986515.

Urological malignancies, including prostate, bladder, and renal cancers, remain a major clinical challenge because of tumor heterogeneity, disease progression, and therapeutic resistance. In this context, RNA methylation has emerged as an important post-transcriptional regulatory layer in cancer biology. Importantly, the biological consequences of RNA methylation are not dictated by chemical modifications alone, but by coordinated networks of regulatory proteins that install, remove, and interpret these marks, thereby shaping RNA fate and gene expression programs. Among currently studied RNA modifications, N⁶-methyladenosine (m⁶A) provides the most mature mechanistic framework, whereas non-m⁶A regulators remain comparatively less well characterized. In this review, we systematically summarize the regulatory logic underlying RNA methylation-mediated control in urological cancers, with particular emphasis on how distinct classes of regulatory proteins influence RNA stability, translation, metabolism, and other post-transcriptional processes. We further integrate current evidence across multiple RNA methylation types, including m⁶A, 5-methylcytosine (m⁵C), N¹-methyladenosine (m¹A), and N⁷-methylguanosine (m⁷G), while highlighting the relative immaturity of non-m⁶A evidence in these malignancies. We also provide an overview of current m⁶A detection technologies and discuss their methodological strengths, limitations, and appropriate research applications. Beyond mechanistic insights, we discuss the emerging clinical relevance of RNA methylation regulators in urological malignancies, particularly in relation to diagnostic-related evidence, prognostic stratification, immune-related relevance, and treatment-associated adaptation. In addition, we summarize current therapeutic efforts targeting RNA methylation pathways, including small-molecule inhibitors and related translational strategies, while emphasizing their present limitations. Overall, current evidence supports RNA methylation as a biologically important and increasingly translationally relevant framework in urological cancers, but not yet as a clinically mature one.

Cancer immunity is commonly interpreted through tumor-centric and immune-intrinsic frameworks centered on antigenicity, immune checkpoint signaling, stromal architecture, and local immunosuppression within the tumor microenvironment. Although these models explain major determinants of immune surveillance and therapeutic response, they do not fully account for the marked heterogeneity in antitumor immunity observed across tumor types and among patients with apparently similar immunological features. Emerging evidence indicates that immune competence is also shaped by host-level regulatory systems, particularly neural and neuroendocrine pathways. Here, we propose the hallmarks of neuro-immune reprogramming in cancer as a conceptual framework to organize recurrent and analytically distinguishable modes through which neural circuits interact with tumor-, stromal-, and immune-intrinsic processes to influence antitumor immunity across its initiation, tissue access, metabolic sustainability, temporal coordination, and persistence. These hallmarks include neural calibration of innate immune set points, neurogenic control of antigen presentation and immune priming, neural gating of immune cell trafficking and tissue access, neuroendocrine constraint of immune metabolic fitness, circadian-neural orchestration of immune timing, neural imprinting of durable immunosuppressive bias, and neuro-immune-tumor circuit reinforcement. Importantly, the evidentiary maturity supporting these hallmarks is not uniform: some are supported by direct cancer-relevant mechanistic studies, whereas others currently remain best understood as cross-disciplinary inferences or testable conceptual extensions. Together, this framework positions neuro-immune regulation as an under integrated systems-level determinant of immune heterogeneity, therapeutic responsiveness, and resistance in cancer, and provides a foundation for mechanistic investigation, biomarker development, and neural-informed immunotherapeutic strategies.

Primary breast leiomyosarcoma is a rare mesenchymal malignancy, thought to arise from smooth muscle elements of the nipple-areolar complex, vascular structures, or stromal tissue. Owing to its low incidence, current knowledge is largely derived from isolated case reports and small case series. Patients typically present with a painless, gradually enlarging breast mass, while imaging findings are often non-specific, posing diagnostic challenges. Definitive diagnosis relies on histopathological evaluation supplemented by immunohistochemistry (IHC) to differentiate it from other spindle cell neoplasms of the breast. Treatment strategies are extrapolated from the management of soft-tissue sarcomas at other sites, with wide local excision and negative surgical margins forming the mainstay of therapy. The role of adjuvant radiotherapy and chemotherapy remains unclear due to limited evidence and a lack of consensus guidelines. Given its rarity, reporting such cases is essential to enhance understanding of its clinical behavior, optimize management approaches, and inform future therapeutic recommendations. A patient in her 30s, status post a simple mastectomy two years ago (histopathological diagnosis: borderline malignant phyllodes tumor), presented with a rapidly growing right chest wall swelling. Ultrasound of the swelling showed an oval, well-circumscribed, heterogeneous lesion measuring 3.9 cm × 2.8 cm, with solid and cystic components in the right chest wall. Fine-needle aspiration showed clusters of spindle cells with nuclear atypia. Wide local excision demonstrated a high-grade spindle cell tumor, confirmed by histopathology and IHC (smooth muscle actin positive, Ki-67 >10%) as leiomyosarcoma. On follow-up, no evidence of residual disease or distant metastasis was identified. This case highlights the challenges in diagnosing rare breast sarcomas, the potential for recurrence or transformation of phyllodes tumors, and the reliance on complete surgical excision followed by adjuvant radiotherapy for optimal local disease control.

Intradermal delivery of the Toll-like receptor (TLR)-9 agonist agatolimod/CPG7909, prior to sentinel lymph node (SLN) biopsy was previously shown to induce locoregional and systemic immunity, reduce tumor-involved SLN rates, and improve recurrence-free survival in patients with early-stage melanoma. Remarkably, men exhibited superior dendritic cell (DC) maturation. Here, we report on further sex-based differences in the immune response after intradermal administration of CPG7909, which included higher CD80/CD83 expression levels in conventional (c) DC subsets in men's as compared to women's SLN, as well as higher ex-vivo release levels of IL-1β, TNF, and IL-6 (all contributors to cDC activation) and Th1/Th2 cytokines. In an effort to identify a more effective DC-activating therapy for women, we compared the in-vitro effects of CPG7909 with those of the TLR7/8 agonist resiquimod/R848 on SLN single cells from female patients. R848 induced superior cDC subset activation and TNF, IL-6, IL-10, IL-12, IFNγ, and CXCL10 release. Correlation analyses suggested that IFNα, TNF, and IL-6 were key for CPG7909-induced LNR-cDC activation, whereas R848's effect appeared more cytokine-independent. We conclude that combining locally delivered CPG7909 and R848 in early-stage melanoma will ensure full-range DC subset activation and robust pro-inflammatory T-cell responses in melanoma SLN, independent of sex.