In colorectal cancer (CRC), cancer-associated fibroblasts (CAFs) and the fibrotic stroma generate form a dense stromal barrier that restricts the intratumoural exposure and spatial distribution of oxaliplatin. To enable local stromal remodelling of this pathological stromal compartment, we selected fibroblast activation protein (FAP) as a stromal target and co-assembled two amphiphilic conjugates, oncoFAP and retinoic acid (RA), into an FAP-directed RA nanoformulation termed LRA^FAP. LRA^FAP exhibited a uniform size distribution (107.1 ± 5.8 nm), remained stable for at least 7 d at 37 °C in PBS or serum-containing PBS, and showed accelerated esterase-responsive release. In a TGF-β-induced CAF-like model, LRA^FAP markedly suppressed the expression of CAF activation-associated markers, reducing Fap and Acta2 mRNA levels by approximately 70% and 60%, respectively. In vivo, LRA^FAP showed enhanced accumulation in CAF-enriched tumours and an increase in intratumoural oxaliplatin levels of approximately 2.5-fold relative to oxaliplatin alone. LRA^FAP also reduced collagen deposition and CAF activation markers, and enhanced the antitumour efficacy of oxaliplatin while maintaining good tolerability. Collectively, these findings indicate that LRA^FAP promotes local stromal remodelling and improves intratumoural oxaliplatin exposure, thereby enhancing the efficacy of oxaliplatin-based chemotherapy in CRC.

PurposeA lightweight deep learning network SMA-Net was proposed to intelligently segment the skeletal muscle of the third lumbar (L3) level in patients with cervical cancer radiotherapy, and the segmentation performance of the network was evaluated.Methods and MaterialsA total of 160 eligible patients with cervical cancer admitted to the oncology department of our hospital from September 2021 to June 2024 were randomly divided into training set (N = 112), validation set (N = 16) and test set (N = 32) according to 7 : 1 : 2. The lightweight Mamba architecture is introduced into the UNet network, and the SAB and CAB attention mechanisms are introduced on the skip connection. The attention mechanism is used to suppress the irrelevant information in the image and highlight the important local features. The trained network is geometrically evaluated on the test set for segmentation performance, comparison of manual segmentation and predicted skeletal muscle area (SMA). Compare the parameters and computations of SMA-Net with existing networks.ResultsThe dice similarity coefficient of SMA-Net network for skeletal muscle segmentation was 89.16%, the sensitivity SEN was 88.21%, the positive predictive value PPV was 90.13% and the 95% Hausdorff distance was 5.30mm. Manual segmentation is basically close to the predicted SMA. Our proposed network for cervical cancer patients predicted sarcopenia with 87.5% accuracy, 92.31% precision, 80% recall, 85.72% F1-Score, and 0.871 AUC. The calculation amount of SMA-UNet network is 1.50 GFLOPS, and the parameter amount is 1.24 M. The radiologist's scores show that minor and no revision accounted for 93.75% on manual revision of skeletal muscle.ConclusionThe lightweight SMA-Net proposed in this study can accurately segment L3 skeletal muscle and quickly calculate its area, which basically meets the clinical application and is convenient for clinical deployment. It is helpful for clinicians to quickly diagnose sarcopenia in patients with cervical cancer, save medical resources, reduce the workload of physicians, and improve diagnostic efficiency.

Breast cancer (BC) exhibits significant heterogeneity and complexity and is leading causes of mortality in women globally. Paclitaxel (PTX) is commonly utilized as the primary medication for BC. However, the resistance of BC to PTX poses a significant challenge in clinical treatment. This study aimed at to explore whether carboxy-terminal domain small phosphatase like 2 (CTDSPL2) affected PTX resistance in BC cells. PTX resistant BC cell lines, including MCF-7/PTX and MDA-MB-231/PTX, were developed by continuously increasing PTX concentration, and we found that CTDSPL2 was upregulated in BC cells with PTX resistance. Loss-of-function studies showed that CTDSPL2 knockdown caused a decrease in cytotoxicity and proliferative ability in PTX-resistant BC cells, as well as enhanced cell apoptotic rate and DNA damage. The results from nanoparticle tracking analysis (NTA) indicated that CTDSPL2 knockdown also suppressed the secretion of extracellular vesicles. In vivo tumorigenesis assays showed that CTDSPL2 downregulation inhibited tumorigenicity of nude mice injecting with PTX-resistant BC cells. Co-immunoprecipitation (Co-IP) assay demonstrated the binding between CTDSPL2 and SCY1-like pseudokinase 1 (SCYL1). The increased level of SCYL1 phosphorylation evoked by CTDSPL2 knockdown in PTX-resistant cancer cells was blocked after mutating the serine 754 site of SCYL1 to alanine. In conclusion, the present study identifies CTDSPL2 as a new factor in BC that plays an essential role in PTX-resistant BC cells through the regulation of SCYL1 phosphorylation.

Tumour mutation burden (TMB) is an emerging pan-cancer biomarker with predictive value for immune checkpoint inhibitor (ICI) outcomes, yet evidence is inconsistent due to methodological variability and cut-off thresholds. This systematic review and meta-analysis evaluated the impact of TMB on overall survival (OS) and progression-free survival (PFS) across solid tumours in ICI-treated cohorts and its predictive relevance in non-ICI-treated cohorts.

Following PRISMA 2020 guidelines, we searched PubMed, Scopus, ScienceDirect and Cochrane for studies published between 2010 and 2024 reporting hazard ratios (HRs) and 95% confidence intervals (CIs) for OS and PFS in high- versus low-TMB cohorts. High and low TMB were defined by study-specific cut-offs, and ultra-high TMB was defined as the top 20% of cohort-specific values. Study quality was assessed with the Newcastle-Ottawa Scale; heterogeneity with I²; publication bias with funnel plots/Egger's test; and robustness by leave-one-out analysis.

5278 patients across 28 studies were analysed. High TMB, defined by cohort-specific cut-offs, was significantly associated with improved OS and PFS, particularly in non-small cell lung cancer (OS: HR = 0.56), selected gastrointestinal cancers (OS: HR = 0.36), and advanced/recurrent tumours (OS: HR = 0.52). Benefits were greatest in ICI-treated patients, especially with combined anti-PD-L1/PD-1 and anti-CTLA-4 therapy (OS: HR = 0.47; PFS: HR = 0.50). Chemotherapy-treated cohorts also showed better outcomes, but less consistently (OS: HR = 0.60; PFS: HR = 0.55). Ultra-high TMB had better OS than the universal 10 mut/Mb cut-off (HR = 0.44 vs. 0.58). Non-beneficial associations were observed in glioma and penile squamous cell carcinoma, highlighting disease-specific variability. Sequencing platforms and cut-off definitions remained sources of heterogeneity.

TMB demonstrates prognostic relevance and predictive utility in a histology- and treatment-context-dependent manner, with the most consistent associations in selected ICI-treated tumours. Associations in non-ICI-treated cohorts were weaker and inconsistent, indicating putative predictive value. Standardising TMB assessment and refining relevant thresholds are essential for optimising its role in precision oncology.

PROSPERO Registration Number: CRD42024608809.

This review focuses on two core immunosuppressive mechanisms within the tumor immune microenvironment (TIME): the polarization of tumor-associated macrophages (TAMs) towards an M2 phenotype and the functional exhaustion of CD8⁺ T cells. We systematically elucidate the multi-dimensional strategies by which Traditional Chinese Medicine (TCM) remodels the TIME. The article first dissects the interplay between TAMs and CD8⁺ T cells and their pivotal role in tumor immune escape. It then comprehensively reviews how TCM formulations and active components, through their characteristic multi-target actions, coordinately reverse TAM polarization and T cell exhaustion by modulating key signaling pathways (e.g., STAT, PI3K/Akt), reprogramming cellular metabolism (e.g., glycolysis, oxidative phosphorylation), and reshaping cytokine networks. Particular emphasis is placed on metabolic reprogramming as an upstream "bridging" mechanism that concurrently regulates both processes. Finally, the review explores the synergistic potential of combining TCM with immune checkpoint inhibitors and analyzes current challenges, including compositional complexity, insufficient mechanistic depth, and a paucity of high-quality clinical evidence. This work aims to provide a theoretical foundation and forward-looking perspective for developing novel TCM-based strategies in cancer immunotherapy.

Sinonasal giant cell tumour (SnGCT) is very rarely reported. The aim of the study is to present a series of SnGCT treated with an endoscopic or combined approach and to carry out a review of the literature on this topic.

This case series encompassed the clinical data of all the SnGCT surgically treated with curative intent at two different referral centres, between 2001 and 2024. The information was extrapolated to report epidemiologic and clinical data, surgical approach and follow up. A comprehensive clinical review of the literature was also carried out.

Among 4 patients included, 3 were treated with a pure endoscopic resection and remained disease-free at the last follow up, while one was managed with a combined approach, who is alive with disease. From the review we found only 32 cases of SnGCT reported, mostly treated with an open approach. Local recurrence was documented in 12.5% of cases, while distant metastasis in 3%.

SnGTC is a benign but locally aggressive neoplasm that can present as a lytic lesion. The clinical behaviour of GCT is unpredictable, and it tends to recur locally and may even metastasise. In the nose and paranasal sinuses it is an exceedingly rare entity, but should be considered in the differential diagnosis with a large variety of histologies. Surgery is the treatment of choice for resectable lesions.

Radiotherapy is a fundamental component of rectal cancer treatment, yet patient responses remain highly heterogeneous due to the lack of reliable biomarkers supported by genomic variation evidence. Integrating multi-cohort transcriptomic data with machine-learning approaches enables systematic identification of genes with both predictive and therapeutic relevance. This study aimed to develop a robust model for predicting radiotherapy response and to functionally characterize CES1 as a key regulator of radiosensitivity and a potential therapeutic target.

Three independent GEO cohorts were standardized and integrated, followed by a comprehensive machine-learning pipeline incorporating LASSO, Elastic Net, Random Forest, XGBoost, and information gain. A consensus-ranked five-gene model was constructed using nested cross-validation. CES1, identified as the top-ranked contributor to model performance, was selected for biological validation. To connect transcriptomic findings with genetic variation, copy number alteration (GISTIC2) and somatic mutation analyses were performed in TCGA-READ. Functional assays-including quantitative PCR, CCK-8 viability assays, colony formation, wound-healing migration assays, Annexin V/PI flow cytometry, and rescue by CES1 overexpression-were performed in HT-29 and SW480 cells to evaluate its mechanistic role in radiotherapy response.

The machine-learning model demonstrated high discriminative accuracy across datasets and consistently highlighted CES1 as a dominant contributor to radiosensitivity prediction. CES1 expression increased after clinical chemoradiotherapy and showed dose-dependent induction following irradiation in vitro. CES1 knockdown significantly reduced radiation-induced apoptosis, enhanced clonogenic survival, and promoted migratory capacity, collectively indicating a radioresistant and more aggressive phenotype. Restoration of CES1 expression in CES1-silenced cells reversed radioresistance and re-established irradiation sensitivity. Genomic analysis in TCGA-READ further demonstrated that CES1 expression was positively associated with copy number status, whereas coding-sequence mutations in CES1 were infrequent, suggesting dysregulation primarily through copy-number and transcriptional mechanisms.

This integrative computational and experimental study identifies CES1 as a predictive biomarker and copy number-linked regulator of radiosensitivity in rectal cancer. Modulation of CES1 directly alters cellular responses to irradiation, supporting its role as a mechanistically interpretable biomarker for response stratification. These findings align with the emerging concept that integrating genetic variation profiling with functional validation can accelerate variant-to-biomarker translation in precision oncology.

Chemotherapeutic resistance remains a major contributor to tumor recurrence and unfavorable clinical outcomes in colorectal cancer (CRC). Although cholesterol metabolic reprogramming has been implicated in tumorigenesis, metastasis, and drug resistance across multiple malignancies, its specific role in CRC chemoresistance requires systematic investigation. We analyzed RNA-seq data from GEO dataset GSE196900 to identify differentially expressed genes (|Log2FC| ≥ 1.5, adjusted p < 0.05). Functional enrichment analysis (GO/KEGG), protein-protein interaction (PPI) network construction, and gene set enrichment analysis (GSEA) were performed. Experimental validation using 5-fluorouracil (5-FU)-resistant CRC cell lines (HCT8/HCT15) included cholesterol/25-hydroxycholesterol (25-HC) treatments, assessed through CCK-8 proliferation assays, wound healing migration tests, quantitative real-time PCR (qRT-PCR), Western blotting, and cholesterol metabolite quantification. Integrative bioinformatics and experimental evidence revealed that 5-FU-resistant CRC cells demonstrate significant upregulation of cholesterol metabolism regulators, including lectin-type oxidized LDL Receptor 1 (LOX1), cholesterol 25-hydroxylase (CH25H), and Cytochrome P450 Family 7 Subfamily B Member 1 (CYP7B1). These cells exhibited impaired cholesterol efflux capacity and consequent intracellular cholesterol accumulation. Exogenous supplementation with cholesterol or 25-HC promoted proliferation, migration, and chemoresistance in both parental and resistant cells. Conversely, CH25H knockdown in resistant cells significantly attenuated malignant phenotypes and restored drug sensitivity. Our findings establish cholesterol metabolic dysregulation as a novel mechanistic contributor to 5-FU resistance in CRC, mediated through the LOX1-CH25H-CYP7B1 regulatory axis. These results propose that therapeutic targeting of cholesterol homeostasis may overcome chemoresistance and improve clinical management of refractory CRC patients.

Pancreatic sclerosing epithelioid mesenchymal neoplasms (SEMN) are extremely rare mesenchymal tumors, with only approximately 10 cases reported globally to date, resulting in limited understanding of their clinical, imaging, and pathological characteristics. We present a 55-year-old female admitted to our hospital following the incidental detection of a pancreatic mass during a routine health check-up. The patient had no specific clinical symptoms or relevant medical history. Preoperative multimodal imaging-including computed tomography (CT), dynamic contrast-enhanced MRI (dynamic contrast MRI), and positron emission tomography (PET)/CT-revealed a 1.6 × 1.4 cm solid lesion at the pancreatic body-neck junction, with a novel, previously unreported radiological feature: main pancreatic duct (MPD) interruption and distal dilation. Combined with postoperative histopathological findings of direct tumor infiltration into the MPD wall and disruption of ductal epithelium, this confirmed true ductal invasion rather than mechanical compression. Due to overlapping imaging manifestations with common pancreatic tumors, initial differential diagnosis strongly favored pancreatic neuroendocrine tumor (pNET). A preoperative attempt at duodenoscopic pancreatic duct stenting was performed to restore ductal patency and facilitate organ-sparing resection; however, the procedure failed, presumably due to tumor infiltration of the MPD. Intraoperative frozen section analysis was unable to definitively characterize the lesion, prompting laparoscopic spleen-preserving distal pancreatectomy (SPDP) to ensure complete resection and rule out malignancy. Postoperative histopathology demonstrated nests of epithelioid and spindle cells embedded within a dense sclerotic stroma, and immunohistochemical staining (Vimentin+, CK8/18+, CD99+; Syn-, CgA-, INSM1-) confirmed the diagnosis of SEMN. The patient had an uneventful postoperative recovery, with no evidence of recurrence or metastasis at the one-year follow-up. This case expands the clinical and imaging spectrum of SEMN by documenting its occurrence in middle-aged females and identifying MPD obstruction as a novel radiological phenotype. It further highlights the diagnostic pitfalls of SEMN due to imaging overlap with prevalent pancreatic tumors, and provides valuable insights for preoperative differential diagnosis and individualized surgical management-particularly the necessity of adapting resection strategies when minimally invasive ductal interventions fail to enable organ-sparing procedures. Collectively, our findings underscore the importance of integrating preoperative imaging, interventional outcomes, intraoperative observations, and postoperative immunohistochemical results to avoid misdiagnosis of this rare entity.

Rectal tumors extending to the dentate line (RTDL) represent a distinct subtype of rectal neoplasms due to the unique anatomical features of the dentate line, for which endoscopic submucosal dissection (ESD) has proven to be an effective therapeutic approach. Furthermore, when tumors invade diverticula, the likelihood of perforation during ESD markedly escalates. Reports detailing the simultaneous management of these three high-risk factors-large tumor size, involvement of the dentate line, and association with a diverticulum-are scarce. Thus, this paper outlines the diagnostic and therapeutic process for a patient who underwent successful endoscopic resection of a huge rectal tumor with these combined challenging features by ESD.

A 70-year-old male patient was admitted with a history of "altered bowel habits" persisting for 2 years. Subsequent examinations, including a colonoscopy, led to the diagnosis of a lesion with high-grade intraepithelial neoplasia and focal intramucosal carcinoma. The lesion, measuring approximately 7 cm × 8 cm, extended to the dentate line and was accompanied by a diverticulum. Following a multidisciplinary consultation, the patient underwent radical resection through endoscopic submucosal dissection (ESD). The procedure successfully managed the affected diverticulum without complications. Postoperative histological analysis of the en bloc specimen confirmed a conventional serrated adenoma with high-grade intraepithelial neoplasia and focal intramucosal carcinoma (pTis). The resection margins were negative (R0 resection), and there was no lymphovascular invasion. At 1-year postoperative follow-up, no tumor recurrence or distant metastasis was observed, and anal function was preserved.

This case demonstrates the feasibility and curative effect of ESD for large intramucosal rectal carcinoma involving the dentate line and associated with a diverticulum. However, larger cohort studies and long-term follow-up are required to validate the generalizable safety and efficacy of this approach.