Search Results (5,505)

Background/Objectives: Lung cancer is characterized by a significant microstructural heterogenicity among different histological types. Artificial intelligence and digital pathology instruments can facilitate morphological analysis by introducing calculated metrics allowing for the distinguishment of different tissue patterns. Methods: We used computer vision models to calculate a number of morphometric features of tumor vascularization and proliferation. We used two frameworks to process whole-slide images: (1) LVI-PathNet framework for vascular detection, based on the SegFormer architecture; and (2) Mito-PathNet framework for mitotic figure detection, based on the RetinaNet detector and an ensemble classification model. The results were visualized in the segmented and gradient heatmaps. Results: SegFormer for vessel segmentation achieved the following quality metrics: IoU = 0.96, FBeta-score = 0.98, and AUC-ROC = 0.98. RetinaNet + CNN ensemble achieved the following quality metrics: specificity = 0.96 and sensitivity = 0.97. The analysis of the obtained parameters allowed us to identify trophic patterns of lung cancer according to the degree of aggressiveness, which can serve as potential targets for therapy, including proliferative-vascular, hypoxic, proliferative, vascular, and inactive. Conclusions: The analysis of the obtained parameters allowed us to identify distinct quantitative characteristics for each histological type of lung cancer. These patterns could potentially become markers for therapeutic choices, such as antiangiogenic and hypoxia-induced factor therapy. Full article

Nutrient deprivation causes dedifferentiation in solid tumors, driving an aggressive phenotype. We previously showed that glucose starvation-induced dedifferentiation is driven by epigenetic changes induced by a deficit of alpha-ketoglutarate (α-KG). Deficient activity of α-KG-dependent histone demethylases leads to unbalanced hypermethylation of histone 3 on lysine 27 (H3K27) by methyltransferase EZH2. H3K27 hypermethylation is a key mechanism of starvation-induced dedifferentiation. Here, we investigate a new aspect of this mechanism and show that epitranscriptomic changes are also induced by glucose restriction. Specifically, hypermethylation of select long non-coding RNAs leads to their upregulation under glucose deprivation as a consequence of reduced activity of the RNA demethylase FTO. We identified LINC00662 as an lncRNA required for EZH2 recruitment to target gene promoters induced by low glucose. These findings characterize the epigenetic response to glucose restriction beyond histone methylation, revealing that RNA methylation of lncRNAs such as LINC00662 represents a parallel mechanism converging on EZH2. Full article

Background/Objectives: Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular tumor of infancy, often complicated by Kasabach–Merritt phenomenon (KMP), a consumptive coagulopathy characterized by severe thrombocytopenia and hypofibrinogenemia. Airway involvement at birth is exceptionally rare and can be life-threatening. This study reports the clinical presentation and treatment course of a full-term male neonate with severe airway obstruction caused by KHE with KMP. Case Presentation: The patient had unremarkable prenatal imaging but presented at birth with severe respiratory distress requiring emergent intubation. Physical examination revealed firm violaceous swelling over the right cervicothoracic region. Laboratory tests showed profound thrombocytopenia (22,000/μL), hypofibrinogenemia (75 mg/dL), and coagulopathy. Imaging findings were consistent with KHE complicated by KMP. Due to bleeding risk, the biopsy was not performed. Initial treatment included platelet and plasma transfusions, intravenous immunoglobulin (IVIG), corticosteroids, and antithrombin III replacement. Vincristine was discontinued owing to gastrointestinal toxicity. Sirolimus therapy was initiated on day 14. Following sirolimus initiation, rapid platelet recovery was observed. At three months, marked tumor regression was documented. After mild recurrence, sirolimus was reintroduced, and the patient remained stable at 16-month follow-up. Conclusions: This case underscores the critical importance of prompt airway stabilization, early recognition of consumptive coagulopathy, and sirolimus-based therapy in managing neonatal KHE with airway involvement. Full article

Sinonasal adenocarcinomas are rare malignant tumors arising from the epithelial lining of the sinonasal tract. They are classified into intestinal-type (ITAC) and non-intestinal-type adenocarcinomas (non-ITAC), with different histopathological features, aetiologies, and prognostic outcomes. Occupational exposure, particularly to wood and leather dust, is strongly linked to ITAC. Diagnosis requires a combination of clinical evaluation, imaging, histology, and immunohistochemical profiling. Due to the complexity of the sinonasal anatomy and the aggressive behaviour of these tumors, an early and accurate diagnosis is fundamental. Treatment usually involves surgical resection, often followed by radiotherapy, while the role of chemotherapy remains limited. This review outlines the classification, etiopathogenesis diagnosis and management strategies for sinonasal adenocarcinomas, emphasizing the importance of multidisciplinary approaches for optimal outcomes. Full article

Hypoxia, oxidative stress, and impaired protein folding contribute to tumor progression and therapy resistance. Endoplasmic Reticulum Oxidoreductin 1 Alpha (ERO1α) is a key enzyme regulating redox homeostasis in the endoplasmic reticulum by reoxidizing protein disulfide isomerase, facilitating disulfide bond formation, and generating reactive oxygen species. Elevated ERO1α levels are associated with increased tumor aggressiveness, metastasis, and poor clinical outcomes. Despite growing evidence of its tumor-promoting functions, no clinically approved ERO1α inhibitors exist. This systematic review provides a comprehensive and integrative analysis of current research on ERO1α in breast cancer, emphasizing its roles in hypoxia response, angiogenesis, immune modulation, and ferroptosis resistance. We discuss mechanistic links, including VEGF-A maturation and PD-L1-mediated immune evasion, and highlight recent advances in small-molecule ERO1α inhibitors and preclinical therapeutic strategies. By consolidating molecular insights and translational considerations, this review underscores ERO1α as both a promising therapeutic target and potential prognostic marker, offering guidance for future drug development and targeted interventions in redox-dependent cancer pathways. Full article

Diffuse intrinsic pontine glioma (DIPG), or as it is newly redefined, diffuse midline glioma (DMG), remains one of the most horrific diagnoses in pediatric oncology. Aggressive and inaccessible to standard treatments, it is generally considered incurable. Focused ultrasound technology has developed over the last several decades as a noninvasive means to target various types of tumors in both adults and children. Recent advances, particularly in low-intensity focused ultrasound (LIFU), have opened new avenues for enhancing drug delivery and modulating the tumor microenvironment in these challenging tumors. This review provides a comprehensive overview of preclinical and clinical research developments in the use of LIFU for pediatric DMGs. We highlight key findings from animal models demonstrating improved blood–brain barrier (BBB) permeability, increased chemotherapeutic and nanoparticle delivery, and potential immunomodulatory effects of LIFU. Emerging clinical studies, including early-phase safety and feasibility trials, are also discussed, with attention to technical parameters, imaging guidance strategies, and biomarkers of response. The review concludes by addressing the challenges of translating LIFU into routine clinical practice, including device optimization for pediatric anatomy, regulatory hurdles, and the need for standardized treatment protocols. Collectively, these recent advances underscore the promise of LIFU as a minimally invasive, image-guided adjunct to current and future therapies for pediatric DMGs, warranting continued research and collaborative clinical efforts. Full article

Glioblastoma multiforme (GBM) is the most aggressive brain tumor with a high recurrence rate and mortality. A major obstacle to the effective treatment of GBM is the blood–brain barrier (BBB), which hinders the transfer of therapeutic cargo to the tumor lesion. Polysorbate-coated drug carriers are known to efficiently cross the BBB via apolipoprotein E (ApoE)-mediated transcytosis. In this study, we developed cancer-targeted nanocarriers using folic acid (FA)-conjugated polysorbate (Tween 80, T80) for safe and efficient chemo-sonodynamic combination therapy against GBM. T80-based nanocarriers effectively co-encapsulated doxorubicin (DOX, chemotherapeutic agent) and oxygen-deficient MnWOx nanoparticles (sonosensitizer). FA-conjugated T80 nanocarriers encapsulating DOX and MnWOx (FA-T-DOX@MnWOx) boosted the cellular uptake of DOX in human glioblastoma U87MG cells. The efficient ability of the T80-based drug carriers to cross the BBB was demonstrated using an in vitro transwell BBB model. In addition, sonosensitizer MnWOx nanoparticles in the T80-based carriers triggered GSH depletion, synergistically enhancing intracellular reactive oxygen species (ROS) generation in U87MG cells upon US irradiation. As a result, FA-T-DOX@MnWOx combined with US triggered significant apoptosis in U87MG cells. This study demonstrated that FA-conjugated, MnWOx-loaded, T80-based nanocarriers capable of crossing the BBB hold significant potential for treating GBM through a combined chemo-sonodynamic therapy. Full article

Background: Glioblastoma (GBM) is a highly aggressive tumor characterized by elevated plasticity and poor differentiation. Platelet-derived preparations such as Concentrated Growth Factors (CGF) are rich in bioactive molecules, but their effects on tumor biology remain underexplored. Methods: U87MG glioblastoma cells were cultured with a conditioned medium obtained from CGF over 14 days (CGF-CM). We analyzed cell viability, morphology, DNA integrity, migration, proliferation, and expression of astrocytic markers. Results: CGF-CM treatment induced early enhancement of cell viability, followed by decreased proliferation and reduced migration at later time points. Morphological analyses revealed astrocyte-like features. The expression of glial fibrillary acidic protein (GFAP), an astrocytic marker, and its α/δ isoform ratio increased over time, while GBM -GBM-associated markers, such as AQP-4 and S100B, were downregulated. Conclusions: Our findings demonstrate that CGF-CM modulates the phenotypic plasticity of U87MG cells and promotes differentiation toward an astroglial-like profile. These results provide a basis for future studies on the modulation of GBM aggressiveness using bioactive autologous derivatives. Full article

Background: The purpose of this study was to investigate the value of machine learning models for preoperative non-invasive prediction of International Society of Urological Pathology (ISUP) grading in clear cell renal cell carcinoma (ccRCC) based on CT urography (CTU)-related peritumoral area (PAT) radiomics features. Methods: We retrospectively analysed 328 ccRCC patients from our institution, along with an external validation cohort of 175 patients from The Cancer Genome Atlas. A total of 1218 radiomics features were extracted from contrast-enhanced CT images, with LASSO regression used to select the most predictive features. We employed four machine learning models, namely, Logistic Regression (LR), Multilayer Perceptron (MLP), Support Vector Machine (SVM), and Extreme Gradient Boosting (XGBoost), for training and evaluation using Receiver Operating Characteristic (ROC) analysis. The model performance was assessed in training, internal validation, and external validation sets. Results: The XGBoost model demonstrated consistently superior discriminative ability across all datasets, achieving AUCs of 0.95 (95% CI: 0.92–0.98) in the training set, 0.93 (95% CI: 0.89–0.96) in the internal validation set, and 0.92 (95% CI: 0.87–0.95) in the external validation set. The model significantly outperformed LR, MLP, and SVM (p < 0.001) and demonstrated prognostic value (Log-rank p = 0.018). Transcriptomic analysis of model-stratified groups revealed distinct biological signatures, with high-grade predictions showing significant enrichment in metabolic pathways (DPEP3/THRSP) and immune-related processes (lymphocyte-mediated immunity, MHC complex activity). These findings suggest that peritumoral imaging characteristics provide valuable biological insights into tumor aggressiveness. Conclusions: The machine learning models based on PAT radiomics features of CTU demonstrated significant value in the non-invasive preoperative prediction of ISUP grading for ccRCC, and the XGBoost modeling had the best predictive ability. This non-invasive approach may enhance preoperative risk stratification and guide clinical decision-making, reducing reliance on invasive biopsy procedures. Full article

Background: Visceral pleural invasion (VPI) has traditionally been regarded as a negative prognostic indicator in non-small-cell lung cancer (NSCLC). However, with the increasing adoption of sublobar resection for small-sized NSCLC, the clinical significance of VPI is being fundamentally reassessed. Specifically, it remains uncertain whether VPI is indicative of tumor size or represents distinct metastatic behavior. Methods: We conducted a retrospective comprehensive multicenter study involving 2464 patients with pathologically confirmed NSCLC ≤ 3 cm who underwent complete resection at three Japanese institutions. The prevalence, metastatic patterns, and prognostic impact of VPI were systematically evaluated, with particular focus on histological growth patterns. Results: VPI was identified in 370 patients (15%). Notably, VPI-positive tumors demonstrated a doubled incidence of lymph node metastasis (31% vs. 15%, p < 0.001) and a distinct metastatic profile characterized by preferential hilar spread (#12, 16.9%) and an increased risk of skip N2 metastasis (4.0% vs. 2.0%). Five-year recurrence-free survival was significantly reduced in the VPI group (33.7% vs. 50.6%, respectively). Conversely, adenocarcinomas with lepidic characteristics demonstrated a minimal risk of VPI or nodal metastasis, with incidences of 2% and 1%, respectively. This finding highlights the heterogeneity in the biological aggressiveness of small-sized NSCLC. Conclusions: Our findings suggest that VPI is not merely a histopathological descriptor but also acts as a clinically significant indicator of aggressive metastatic behavior, potentially enhancing surgical and staging approaches beyond just considering tumor size. With the increasing adoption of sublobar resection for small-sized NSCLC, recognizing that VPI appears to be associated with predominant hilar involvement and an elevated risk of skip N2 metastasis may help refine decisions on the extent of lung and lymph node resection. Full article

Metastatic breast cancer (MBC) remains one of the most aggressive and fatal malignancies in women, primarily due to tumor heterogeneity, multidrug resistance, and the limitations of conventional therapeutic approaches. Aim: This review aims to evaluate recent advances in nanomaterial-based photothermal therapy (PTT) platforms and their potential in the treatment of metastatic breast cancer. Method: A comprehensive analysis of current literature was conducted to examine how various nanomaterials are engineered for targeted PTT, with particular emphasis on their mechanisms of action, synergistic applications with chemotherapy, immunotherapy, and photodynamic therapy, as well as their capacity to overcome challenges associated with targeting metastatic niches. Results: The findings indicate that nanotechnology-enabled PTT provides spatiotemporal precision, efficient tumor ablation, and reduced systemic toxicity, while significantly enhancing therapeutic outcomes when integrated into multimodal treatment strategies. Recent preclinical studies and early clinical trials further underscore advancements in imaging guidance, thermal efficiency, and site-specific drug delivery; however, issues related to biocompatibility, safety, and large-scale clinical translation remain unresolved. Conclusions: Nanomaterial-assisted PTT holds substantial promise for improving therapeutic efficacy against metastatic breast cancer. Future research should prioritize optimizing imaging resolution, minimizing adverse effects, and addressing translational challenges to accelerate clinical integration and ultimately enhance health outcomes for women. Full article

Background and Objectives: Undifferentiated pleomorphic sarcoma (UPS) is a rare but aggressive soft tissue tumor. Achieving a tumor-free surgical margin is believed to be crucial for reducing local recurrence; however, the effect of margin thickness on recurrence and survival remains a matter of controversy. This study aimed to assess the association between histopathological margin status and outcomes, including local recurrence, disease-free survival (DFS), and overall survival (OS), in patients with UPS. Materials and Methods: We retrospectively analyzed 69 patients with histologically confirmed UPS, identified from a tertiary university hospital tumor database between January 2010 and December 2023. Patients were grouped by histopathological margin status as follows: >1 mm, ≤1 mm, or positive. Recurrence and survival outcomes were analyzed using Kaplan–Meier estimates, Cox regression, and multivariate logistic regression. Patients who underwent reoperation were also evaluated separately. Results: Minimum follow-up was 24 months (mean: 52.2 months). Local recurrence occurred in 21 patients, 20 of whom underwent reoperation. Positive margins were significantly associated with higher recurrence risk compared to the >1 mm group (OR: 17.6; 95% CI: 2.88–107.61; p = 0.0019). Although recurrence odds were lower in the ≤1 mm group than in the positive group, this was not statistically significant compared to the >1 mm group (OR: 0.52; 95% CI: 0.076–3.50; p = 0.498). In reoperated patients, surgical margin status was significantly associated with local recurrence (p = 0.0044), and overall survival tended to be longer in those with margins > 1 mm (67.3 ± 47.7 months) or ≤1 mm (50 ± 28.2 months) compared to positive margins (23.3 ± 17.3 months). A moderate negative correlation was observed between age and DFS (p < 0.001, r = –0.495). Conclusions: This study highlights the prognostic value of surgical margin status in patients undergoing reoperation for local recurrence. In this unique subgroup, margin status was significantly associated with recurrence risk, and patients with negative margins had improved overall survival compared to those with positive margins. Full article

Cholangiocarcinoma (CC) is a rare and aggressive malignancy that arises from the epithelial cells (cholangiocytes) of the biliary tree. Biliary tract cancers (BTC) include both CC and gall bladder cancer. Surgical resection is considered the only curative treatment. Recently, however, a fundamental shift in the understanding of the molecular profiles of these tumors has led to a molecular-targeted approach with improved survival rates in some patients with these tumors. In patients with local or limited regional disease, neoadjuvant therapies offer a way to downstage tumors, assess tumor biology, potentially achieve R0 resection, and potentially prevent both locoregional and distant recurrence by treating occult micrometastatic disease. Because BTC are rare and surgery is the standard of care for patients with non-metastatic disease, there is very little data evaluating neoadjuvant strategies in resectable disease. Immunotherapies and molecularly targeted agents originally developed for advanced disease in the adjuvant or palliative settings are now being considered for neoadjuvant use. This review aims to summarize the data and provide a rationale for the role of neoadjuvant treatment in patients with resectable BTC. While there is no high-level evidence, studies show that neoadjuvant therapy that incorporates targeted treatments and immunotherapies under multidisciplinary oversight benefits select patients and is a valuable tool in the treatment of BTC. We favor molecular testing to guide neoadjuvant therapy for patients with BTC, when feasible, to prevent unnecessary operations and minimize the risk of recurrence or metastasis. Full article

Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive subtype of kidney cancer. This study aimed to construct a prognostic model for ccRCC based on glycosyltransferase genes, which play important roles in cell processes like proliferation, apoptosis. Glycosyltransferase genes were collected from four public databases and analyzed using RNA-seq data with clinical information from three ccRCC datasets. Prognostic models were constructed using eight machine learning algorithms, generating a total of 117 combinatorial algorithm models, and the StepCox[forward]+Ridge model with the highest predictive accuracy (C-index = 0.753) which selected and named the Glycosyltransferases Risk Score (GTRS) model. The GTRS effectively stratified patients into high- and low-risk groups with significantly different overall survival and maintained robust performance across TCGA, CPTAC, and E-MTAB1980 cohorts (AUC > 0.75). High-risk patients exhibited higher tumor mutational burden, immunosuppressive microenvironment, and poorer response to immunotherapy. TYMP and GCNT4 were experimentally validated as key genes, functioning as oncogenic and tumor-suppressive factors. In conclusion, GTRS serves as a reliable prognostic tool for ccRCC and provides mechanistic insights into glycosylation-related tumor progression. Full article

Thymic carcinoma (TC) is a rare, aggressive cancer that originates from thymus’s epithelial cells. It distinguishes itself from other thymic epithelial tumors with its unique pathological structure, clinical behavior, and immune characteristics. Immune checkpoint inhibitors (ICIs) targeting the Programmed cell death protein 1/Programmed cell death protein ligand 1 (PD-1/PD-L1) pathway have shown promise in advanced TC, potentially benefiting from frequent PD-L1 overexpression and abundant CD8⁺ tumor-infiltrating lymphocytes (TILs), despite typically low tumor mutational burden (TMB). While ICI monotherapy can achieve disease control in some patients, its overall efficacy is limited and it is associated with a distinct profile of immune-related adverse events (irAEs) which occur less often than in thymomas. The predictive value of biomarkers—particularly PD-L1 expression—remains uncertain, underscoring the importance of consistent assessment criteria. In this review, we summarize evidence on ICI monotherapy as well as combination approaches that incorporate anti-angiogenic agents, chemotherapy, or dual checkpoint blockade. Emerging therapeutic targets—such as CD70, TIM-3, and B7-H4—are also considered in the context of their potential clinical relevance. Finally, we discuss future directions aimed at improving efficacy, extending response durability, and reducing treatment-related toxicity through biomarker-based patient selection and tailored therapeutic strategies. Full article