Search Results (4,713)

This study aimed to develop machine learning models based on conventional MRI features to classify HER2 expression levels in invasive breast cancer and explore their association with disease-free survival (DFS). A total of 678 patients from two centers were included, with Center 1 divided into training and internal test sets and Center 2 serving as an external test set. Random Forest models were trained to distinguish HER2-positive vs. HER2-negative (Task 1) and HER2-low vs. HER2-zero tumors (Task 2) using BI-RADS–based MRI features. SHapley Additive exPlanations were applied to rank feature importance, assist feature selection, and enhance model interpretability. DFS was analyzed using Kaplan–Meier curves and log-rank tests. In Task 1, key features included tumor size, axillary lymph nodes, fibroglandular tissue, peritumoral edema, and multifocal, achieving AUCs of 0.75 and 0.73 in the internal and external test sets, respectively. In Task 2, tumor size, peritumoral edema, and multifocal yielded AUCs of 0.73 and 0.72, respectively. Higher task-specific model scores were associated with shorter DFS in Task 1 (p = 0.037) and longer DFS in Task 2 (p = 0.046). MRI-based machine learning models can noninvasively stratify HER2 expression levels, with potential for prognostic stratification and clinical application. Full article

Background: Cancer-associated fibroblasts (CAFs) are key mediators of metastatic progression in non-small cell lung cancer (NSCLC). Fibroblast activation protein (FAP) serves as the hallmark of CAF activation. However, the upstream regulation of FAP remains elusive, limiting stroma-targeted therapy development. Methods: ⁶⁸Ga-FAP inhibitor (FAPI)-04 PET/CT imaging was performed on 61 NSCLC patients to evaluate the clinical significance of FAP. CAFs and normal fibroblasts (NFs) were isolated from patient tissues. Bioinformatic analysis and qRT-PCR were employed to screen and validate miRNAs. Functional assays (CCK-8, collagen contraction, wound healing, transwell co-culture) were utilized to investigate the role of miR-624-5p in regulating fibroblast activation and the effects on the metastatic potential of NSCLC cells. The targeting relationship between miR-624-5p and FAP was validated using FISH, dual-luciferase assay, and Western blotting. Results: ⁶⁸Ga-FAPI-04 uptake was higher in advanced NSCLC (p < 0.001) and correlated with tumor size, lymph node metastases, and distant metastases (p < 0.05). Isolated primary CAFs significantly enhanced the migration and invasion of A549 and PC9 cells compared to NFs (p < 0.001). We identified miR-624-5p as a significantly downregulated miRNA in CAFs (p < 0.001). Functionally, miR-624-5p overexpression inhibited CAF proliferation and collagen contraction (p < 0.01) and reduced the proliferation, migration, and invasion capabilities of A549 and PC9 cells (p < 0.001). Mechanistically, miR-624-5p bound to FAP mRNA and negatively regulated FAP expression (p < 0.001), thus suppressing CAF activation and tumor metastasis. Conclusions: Our findings establish miR-624-5p as a novel upstream regulator that suppresses FAP expression, consequently inhibiting CAF activation and its pro-metastatic function. Targeting the miR-624-5p/FAP axis represents a promising therapeutic strategy for NSCLC metastasis. Full article

Background/Objectives: Fibroepithelial tumors (FETs) of the breast, including fibroadenomas (FAs) and phyllodes tumors (PTs), are among the most common breast masses encountered by breast radiologists and pathologists. Differentiating FAs from benign or borderline PTs can be challenging, especially on core biopsy specimens where sampling limitations obscure key histologic features. Although imaging techniques provide useful diagnostic context, their predictive accuracy for pathologic classification remains limited. Methods: We conducted a single-institution pilot study to assess whether tumor growth rate (TGR) derived from serial imaging could serve as a noninvasive correlate of histopathologic outcomes in FETs. Thirty-two patients with serial imaging and subsequent surgical excision (January 2020–May 2025) were analyzed. TGR, expressed as percentage volume increase per month, was calculated from diameter-based volumetrics. Results: The cohort included conventional FA (n = 10), cellular FA (n = 4), benign PT (n = 8), borderline PT (n = 6), and malignant PT (n = 4). Malignant PTs demonstrated significantly higher median TGRs (180.4%/month) and shorter imaging intervals (1.1 months) compared with other groups (p = 0.0357 and p = 0.005, respectively). These large effect-size differences suggest clinically meaningful growth dynamics. Conclusions: As a pilot, this study establishes foundational variance and effect-size estimates for powering a multicenter trial. If validated, TGR may provide an objective, noninvasive metric to enhance preoperative risk stratification and guide management of breast FETs. Full article

The incidence of peripheral lung squamous cell carcinoma (p-LUSC) has increased in recent years, but the clinical features of early-stage p-LUSC remain unclear. In the present study, we aim to elucidate the general clinical features of p-LUSC by comparing it with peripheral lung adenocarcinoma (p-LUAD). Patients with p-LUSC or p-LUAD who were at an early imaging stage and underwent complete lobectomy with systematic lymph node dissection were included. The clinical characteristics of p-LUSC were elucidated through comparative analysis with p-LUAD, and independent prognostic factors for recurrence-free survival were identified. A total of 103 patients with p-LUSC and 600 patients with p-LUAD were included. Compared with p-LUAD, all p-LUSC cases appeared as solid nodules (SDNs) on imaging, and p-LUSC was associated with the male sex, older age, smoking history, lobulation sign, interstitial pneumonia, and a shorter volume doubling time. In terms of malignant aggressiveness, p-LUSC demonstrated a significantly lower lymph node metastasis rate than SDNs of p-LUAD in the >2.0 to ≤3.0 cm group, while no statistically significant difference was observed between the two groups in the 0–2.0 cm group. As for prognosis, tumor size and lymph node metastasis were found as independent risk factors for tumor recurrence. Full article

Background: BCAR3 has been implicated in various cancers, yet its role in thyroid cancer (TC) remains unclear. This study aimed to investigate the methylation status, functional effects, and underlying mechanisms of BCAR3 in TC. Methods: BCAR3 methylation was analyzed using matrix-assisted laser desorption/ionization–time-of-flight (MALDI-TOF) mass spectrometry in 422 TC and 371 benign thyroid nodule samples. Expression levels were assessed via immunohistochemistry, qPCR, and Western blot. Functional assays including proliferation, migration, and invasion were performed after BCAR3 knockdown. Rescue experiments using a PI3K activator were conducted to examine pathway mechanisms. Results: BCAR3 was significantly hypomethylated in TC compared to benign tissues (p < 0.001), with CpG_6 most strongly associated with TC risk (odds ratio, OR = 1.73, p < 0.001). Notably, BCAR3 hypomethylation was more pronounced in cases with larger tumor size and advanced disease stage. Furthermore, BCAR3 methylation showed differential patterns across TC subtypes, with medullary thyroid carcinoma exhibiting the lowest methylation levels. BCAR3 expression was upregulated in TC tissues and cell lines (p < 0.05). Mechanistically, BCAR3 knockdown reduced phosphorylation of AKT/mTOR and altered expression of epithelial-to-mesenchymal transition (EMT) marker, characterized by an increase in E-cadherin and decreases in Vimentin and N-cadherin, and consequently suppressed proliferation, migration, and invasion (p < 0.05). Rescue experiments with a PI3K activator showed a trend towards restoration of these effects, although not to the level of the control groups. Conclusions: BCAR3 hypomethylation contributes to TC cells’ proliferation, migration, and invasion by promoting AKT/mTOR activation and EMT. These findings highlight the potential of BCAR3 methylation as both a biomarker and a therapeutic target in TC. Full article

Glioblastoma (GBM) is a highly aggressive brain tumor characterized by invasive growth, intrinsic drug resistance, and the presence of the blood–brain barrier. All of these features make treatment extremely challenging and underscore the need for developing effective combination strategies and advanced drug delivery systems. This study aimed to develop a bovine serum albumin (BSA) nanoparticle (NP)-based delivery system to overcome the poor bioavailability and pharmacokinetic limitations of two potent anti-tumor agents, all-trans retinoic acid (ATRA) and curcumin (CURC), and to evaluate their antitumor activity in U87-MG GBM cells. Drug-free and ATRA/CURC-loaded BSA-NPs were synthesized using an optimized desolvation method and characterized in terms of particle size, polydispersity index, morphology, drug encapsulation efficiency, and release behavior. The cytotoxic, anti-migratory, and pro-apoptotic effects of the NPs on U87-MG GBM cells were assessed using real-time proliferation and migration assays and Annexin V/PI staining followed by flow cytometry. Collectively, the findings indicated that the co-delivery of ATRA and CURC using BSA-NPs showed enhanced antiproliferative, antimigratory, and pro-apoptotic effects. With its controlled release profile, high loading capacity, and favorable nanoscale dimensions, the ATRA-CURC-BSA–NP system represents a promising nanoplatform for GBM therapy that warrants further in vivo investigation. To the best of our knowledge, this is the first study demonstrating the inhibition of glioblastoma cell growth through the co-delivery of all-trans retinoic acid and curcumin using a bovine serum albumin-based nanoparticle system. Full article

Effective in situ pH sensing holds exciting prospects in environmental and biomedical applications, but still faces a great challenge. Until now, pH sensors with small size, high sensitivity, good stability and repeatability, great biosafety, wide detection range, and flexible structure have rarely been reported. Herein, we propose a novel dual-emission ratiometric fluorescent pH sensor by decorating ethyl cellulose (EC)-encapsulated CdSe/ZnS quantum dots (QDs) and oxazine 170 perchlorate (O170 dye) on the surface of the spider silk. When a 473 nm excitation light is coupled into the pH sensor, the evanescent wave transmitting along the surface of the spider silk will excite the CdSe/ZnS QDs and then the O170 dye based on the fluorescence resonance energy transfer (FRET) effect from the QDs; thus, the pH sensing of the surrounding liquid environment can be achieved in real time by collecting the photoluminescence (PL) spectra of the pH sensor and measuring the emission intensity ratio of the two fluorescent materials. The sensor has also demonstrated a high sensing sensitivity (0.775/pH unit) within a wide pH range of 1.92–12.11, as well as excellent reusability and reversibility, structure and time stability, biocompatibility, and biosafety. The proposed pH sensor has a potential application in an in situ monitor of water microenvironments, cellular metabolism, tumor microenvironments, etc. Full article

Background: Triple-negative breast cancer (TNBC) remains primarily treated with chemotherapy due to the lack of effective therapeutic targets, but this approach carries significant systemic toxicity and a high risk of drug resistance. Curcumin (Cur), despite its multifaceted antitumor activity, faces limitations in clinical application due to poor water solubility and weak targeting properties. This study aims to develop a folate/mitochondria dual-targeted curcumin–copper chelate liposome (Cu-Cur DTLPs) formulation that enables copper accumulation within tumor cells and induces copper-mediated cell death, thereby providing an effective and relatively low-toxicity therapeutic strategy for triple-negative breast cancer. Methods: Curcumin–copper chelates (Cu-Cur) were first synthesized and characterized using mass spectrometry, NMR, and infrared spectroscopy. Subsequently, dual-targeted liposomes (Cu-Cur DTLPs) were prepared via the thin-film dispersion method, with systematic evaluation of particle size, zeta potential, encapsulation efficiency, and in vitro release profiles. In vitro cytotoxicity was assessed against 4T-1 and MDA-MB-231 cells using the MTT assay. In a 4T-1 tumor-bearing BALB/c mouse model, comprehensive evaluation of targeting efficiency, antitumor efficacy, and mechanisms of action was conducted via in vivo imaging, tumor volume monitoring, immunohistochemistry (detecting FDX1 and DLAT proteins), and TUNEL staining. Results: Cu-Cur DTLPs with a uniform particle size of approximately 104.4 nm were successfully synthesized. In vitro and in vivo studies demonstrated that compared to free curcumin and conventional liposomes, Cu-Cur DTLPs significantly enhanced drug accumulation in tumor tissues and exhibited effective tumor growth inhibition. Mechanistic studies confirmed that this formulation specifically accumulates copper ions within tumor cells, upregulates FDX1, promotes DLAT oligomerization, and induces mitochondrial dysfunction, thereby driving copper death. TUNEL staining ruled out apoptosis as the primary mechanism. Safety evaluation revealed no significant toxicity in major organs. Conclusions: The Cu-Cur DTLPs developed in this study effectively induce copper-mediated death in TNBC through a dual-targeted delivery system, significantly enhancing antitumor activity with favorable safety profiles. This establishes a highly promising novel nanotherapeutic strategy for TNBC treatment. Full article

Background/Objectives: Hepatocellular carcinoma remains a major cause of death from cancer globally. While ¹⁸F-FDG PET/CT is commonly used for tumor imaging, its sensitivity is limited, especially due to high liver background uptake. Recently, ⁶⁸Ga-FAPI PET/CT, which targets fibroblast activation protein in tumor stroma, has emerged as a promising diagnostic tool. In this study, we aimed to assess the diagnostic performance of ⁶⁸Ga-FAPI-04 PET/CT in HCC patients with and without liver cirrhosis and to explore the relationship between PET metrics, tumor size, and PIVKA-II serum marker. Methods: In this prospective single-center study, 59 patients with confirmed HCC (37 with cirrhosis, 22 without) underwent ⁶⁸Ga-FAPI-04 PET/CT. The standard dose (1.5–2.0 MBq/kg) was administered intravenously, and imaging was carried out 60 min post-injection. Semi-quantitative parameters including SUVmax, SUVmean, and tumor-to-background ratio were calculated. Diagnostic performance was assessed using histopathology and multimodal imaging. Statistical analyses included the Mann–Whitney U test and Spearman correlation. Results: The overall sensitivity for HCC detection was 89.8%, with a specificity of 60% and accuracy of 87%. Sensitivity and specificity showed a tendency to be lower in cirrhotic compared with non-cirrhotic patients, with a notably higher background liver uptake in cirrhosis (SUVmax 3.60 vs. 1.3, p < 0.001), resulting in lower TBR values (3.7 vs. 7.0, p < 0.001). A strong correlation between SUVmax and tumor size was seen in non-cirrhotic HCC, while a moderate association between SUVmax and PIVKA-II levels was observed in cirrhotic patients. Conclusions:⁶⁸Ga-FAPI-04 PET/CT demonstrates high sensitivity for HCC detection and may serve as a complementary imaging modality, particularly when interpreted through conventional cross-sectional imaging. Image interpretation in cirrhotic livers may be challenging due to increased background uptake and reduced TBR. Associations between PET-derived parameters, tumor size, and serum PIVKA-II levels should be considered hypothesis-generating and require validation in larger, multicenter studies with clinical outcome data. Full article

Background: Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy where endogenous steroid excess may foster immune evasion. However, whether this hormonal axis directly modulates the antigen presentation machinery remains unclear. Methods: We applied an immunoinformatics approach to the TCGA-ACC cohort (n = 79) to investigate relationships among steroid phenotype, HLA expression, tumor microenvironment (TME), and patient outcome. Key findings were assessed in an independent validation cohort (ENSAT-ACC, n = 44) using C1A/C1B molecular subtypes corresponding to the steroid phenotypes. Results: Stratification by steroid phenotype revealed two distinct immunological profiles. The high steroid production (HSP) phenotype was associated with suppressed HLA expression and a lymphocyte-depleted “cold” TME. In contrast, the low steroid production (LSP) phenotype displayed elevated HLA expression, enriched T-cell infiltration, and upregulation of immune checkpoints (e.g., PDCD1, CTLA4), consistent with an inflamed but exhausted TME. The core signature of HLA downregulation in the HSP-like phenotype (C1A) and the significant survival advantage of the LSP-like phenotype (C1B) were confirmed in the validation cohort, demonstrating biological robustness despite platform and sample size differences. Conclusions: These findings identify the steroid phenotype as a critical regulator of immune escape in ACC. Our results support incorporating this stratification as a biomarker for patient selection, identifying LSP tumors as the subgroup most likely to benefit from immune checkpoint blockade due to their “hot” yet exhausted microenvironment. Full article

Background/Objectives: Stereotactic body radiation therapy (SBRT) is widely used for small lung tumors, but the physics of electron transport in low-density lungs remains incompletely understood. This study quantifies the effect of lung density on dosimetry for small lesions. Methods: To study the dosimetric parameters a pseudo patient option was chosen. A lung SBRT patient with a central lesion was modeled in the Eclipse treatment planning system using the AAA algorithm. Three target sizes (1.0, 1.5, and 2.0 cm) were planned with lung densities overridden from 0.1 to 1.0 g/cm³. Standard SBRT constraints were applied, and dosimetry indices (CI, HI, GI), maximum dose, and MU/Gy were recorded to see the pattern. Results: Dose–volume histograms (DVHs) showed marked dependence on both lesion size and lung density. Lower densities produced higher maximum doses (up to 135% at 0.1 g/cm³), steeper DVH tails, and significantly increased MU/Gy. Conformity was achievable in all cases, but at the cost of degraded homogeneity and gradient indices. At higher density (1.0 g/cm³), maximum dose values fell to 108–110% which is typical in non-lung cases. Conclusions: SBRT planning in low-density lungs requires substantially higher MU and results in greater dose spillage despite acceptable conformity. These findings highlight the importance of considering density effects when comparing clinical outcomes across institutions and selecting optimal plans, where minimizing MU/Gy may reduce unnecessary dose burden. Full article

Accurate brain tumor segmentation in both adult and pediatric populations remains a challenge due to substantial differences in brain anatomy, tumor distribution, and subregion size. This study proposes a unified segmentation framework based on nnU-Net, integrating encoder-level self-supervised pretraining with a lightweight, boundary-aware decoder. The encoder is initialized using a large-scale 3D masked autoencoder pretrained on brain MRI, while the decoder is trained with a hybrid loss function that combines region-overlap and boundary-sensitive terms. A harmonized training and evaluation protocol is applied to both the BraTS-GLI (adult) and BraTS-PED (pediatric) cohorts, enabling fair cross-cohort comparison against baseline and advanced nnU-Net variants. The proposed method improves mean Dice scores from 0.76 to 0.90 for adults and from 0.64 to 0.78 for pediatric cases, while reducing HD95 from 4.42 to 2.24 mm and from 9.03 to 6.23 mm, respectively. These results demonstrate that combining encoder-level pretraining with decoder-side boundary supervision significantly enhances segmentation accuracy across age groups without adding inference-time computational overhead. Full article

Background and Clinical Significance: Hepatic sarcoidosis is a benign lesion of unknown etiology. The gold standard for diagnosing hepatic sarcoidosis is histopathological examination. The symptoms and imaging findings of patients with hepatic sarcoidosis are often atypical, leading to misdiagnosis as hepatocellular carcinoma (HCC). Ultrasound resolution microscopy (URM) can overcome the diffraction limit, enabling fine visualization and quantitative analysis of the microvascular networks. This study aimed to provide new evidence for the differential diagnosis of these two diseases by comparing the URM parameters of hepatic sarcoidosis initially misdiagnosed as HCC with those of HCC. Case Presentation: A 67-year-old woman was admitted to the hospital due to upper abdominal pain for two weeks. Ultrasonography revealed a liver mass. The lesion was located in segment IV of the left hepatic lobe, was approximately 18 × 10 mm in size, and appeared hypoechoic. Contrast-enhanced ultrasound and enhanced magnetic resonance imaging both showed a “fast-in, fast-out” pattern, strongly suggesting HCC. The tumor markers were within the normal range. The patient underwent a laparoscopic left hepatic lobectomy. The histopathological diagnosis of the resected specimen was “hepatic sarcoidosis”. URM examination was performed during the preoperative diagnostic process. Subsequently, the URM parameters of the patient’s lesion were analyzed and compared with those of HCC. The results showed differences in multiple URM parameters, including microvascular flow velocity, diameter, microvascular density ratio, and vascular distribution, between this case of hepatic sarcoidosis and HCC. Conclusions: URM can quantitatively and multidimensionally evaluate the microvasculature of liver lesions, providing new reference data for the diagnosis and differential diagnosis of hepatic sarcoidosis. Full article

Background/Objectives: Premalignant laryngeal lesions carry a variable risk of malignant transformation to squamous cell carcinoma. Identifying reliable biomarkers that predict malignant transformation could improve patient management and surveillance strategies. The objective of this work is to perform a systematic review of the literature on biomarkers that predict malignant transformation of premalignant laryngeal lesions. Methods: We conducted a systematic review following PRISMA 2020 guidelines. The PubMed, Scopus and Embase databases, and Google Scholar were searched for studies published between January 2011 and November 2025. Studies investigating biomarkers that predict malignant transformation of histopathologically confirmed premalignant laryngeal lesions were included. Risk of bias was assessed using the ROBINS-I tool. Results: From 166 initially identified records, 11 studies met the inclusion criteria, including 730 patients. These studies investigated diverse biomarker categories such as protein markers (cortactin, FAK, NANOG, SOX2, CSPG4), immune markers (tumor-infiltrating lymphocytes, immune gene signatures), microRNAs (miR-183-5p, miR-155-5p, miR-106b-3p), and genetic markers (chromosomal instability, PIK3CA amplification and mutations, FGFR3 mutations). Five studies provided adequate follow-up data on transformation outcomes. Most studies showed a moderate to serious risk of bias primarily due to limited confounder control and incomplete reporting. Conclusions: While several promising biomarker candidates have been identified, the evidence base remains limited due to small sample sizes, heterogeneous methodologies, and inadequate follow-up data. Cortactin/FAK protein expression and immune signatures are the most promising but require validation in larger, well-designed prospective cohorts. Full article

Oral squamous cell carcinoma (OSCC) is an aggressive disease with a glycoproteomically unmapped progression and a low five-year survival rate. Thus, the aim of this pilot study was to explore the N-glycosylation pattern differences in malignant, adjacent mucosal and healthy tissues in the context of OSCC. Oral mucosal soft tissue samples was obtained by incisional biopsy from five patients with OSCC, both from the malignant and the opposite healthy gingival sides, and from seven age-sex-matched healthy controls. The collected tissues were homogenized, followed by N-glycan profiling of the endoglycosidase-released and fluorophore-labeled carbohydrates using capillary electrophoresis with ultra-sensitive laser-induced fluorescent detection (CE-LIF). Six out of the twenty-two identified N-glycan structures, including glycogens, showed significant (p < 0.05) differences between the malignant tissue samples of the OSCC patients and the healthy controls. Comparing the healthy and the positive control oral mucosal samples, differences in four N-glycan structures were revealed, while only one alteration was observed between the N-glycan profiles of the malignant tumor and positive control samples. However, the results are presented descriptively, reflecting the limited sample size of the pilot study, it shows the potential of high-resolution CE-LIF-based glyocoanalytical protocol to be highly efficient and sensitive for glycobiomarker-based molecular diagnostics of oral malignant lesions. Full article