Tertiary lymphoid structures (TLSs) are critical components of the tumor microenvironment in HCC. However, the role of TLS-related molecules in predicting HCC outcomes and guiding immunotherapy remains unexplored. This study aimed to develop TLS-related gene signature (TLSRS) to predict prognosis and immunotherapy response in patients with HCC​​​​​​.

TLS-related genes (TLSRGs) were identified through differential gene expression analysis combined with weighted correlation network analysis. TLSRGs were selected to take the intersection and LASSO regression to construct a TLSRS. Following validation of the associations between clinical prognosis and TLS-related gene features, analyses were further expanded to GSEA, HCC molecular classes, tumor microenvironment characteristics, immune-related molecular features and immunotherapy responsiveness. TLSRS was further explored using single-cell, spatial transcriptomics, immunohistochemistry, and multiplex immunofluorescence to determine their relationship with TLS.

TLSs are identified as a favorable prognostic factor in HCC. Three TLSRGs (ACKR1, CCR7, and IL7R), which were associated with both TLS presence and prognosis, were constructed with TLSRS. The TLSRS-high group, which was associated with inflammation-related HCC molecular subtypes, exhibited significantly improved clinical outcomes, along with enhanced immune cell infiltration, enriched immune response pathways, and a higher probability of response to immunotherapy. Results from single-cell, spatial transcriptomics, immunohistochemistry, and multiplex immunofluorescence revealed that ACKR1, CCR7, and IL7R shared similar expression patterns and spatial localization with TLS.

The TLSRS shows a correlation with both prognosis and immunotherapy response in patients with HCC, suggesting its potential value in advancing precision medicine for HCC.

Acute myeloid leukemia (AML) is a lethal and rapidly progressive hematologic malignancy with high rates of relapse and treatment refractoriness. Management of AML is complicated by biological heterogeneity in a disease that is broadly defined by the clonal expansion of myeloblasts that otherwise play an important role in healthy marrow tissues. While subtypes of AML are increasingly defined by druggable driver mutations including FLT3-ITD, IDH1, IDH2, and NPM1, conventional chemotherapy and reduced intensity induction regimens (e.g., azacitidine-venetoclax) remain therapeutic backbones. One area of active development for personalization of AML treatment is the assessment of measurable residual disease (MRD). MRD testing in AML is complicated by uncertainty regarding the physiologic compartment of persistent and relapsing myeloblasts, and by increasing recognition of myeloid driver mutations in some healthy bone marrow states, such as clonal hematopoiesis of indeterminate potential (CHIP). Even in large academic centers, MRD tools are not yet universally available. Standardized workflows for MRD implementation are only beginning to enter consensus and guideline documents. Current understanding of AML biology and state-of-the-art tools for MRD measurement are reviewed here in an effort to promote clinical and laboratory investigator collaboration for the development of reliable tools for improving outcomes in this deadly disease. Clinical trial number: not applicable.

Breast cancer (BCa) is the most frequently diagnosed malignancy in women worldwide, with approximately 70% of cases driven by oestrogen receptor alpha (ERα). Endocrine therapies aim to suppress ERα signalling activity and form the foundation of current therapeutic strategies. However, a substantial proportion of patients either fail to respond due to intrinsic resistance or acquire resistance over the course of the treatment. This resistance arises through a complex interplay of factors including crosstalk with other signalling pathways such as Notch. Notch signalling, essential for mammary gland development, is aberrantly activated in breast tumours, where it contributes to cancer stem cell maintenance, epithelial-mesenchymal transition, angiogenesis, and metastasis. Notch receptors exert context- and subtype-specific roles: Notch1 and 4 promote tumour aggressiveness, whereas Notch2 often exhibits tumour-suppressive roles. In ERα-positive BCa, ERα and Notch signalling cooperate to drive resistance, whereas in ERα-negative disease, Notch promotes stemness and angiogenesis. While anti-oestrogen therapies effectively inhibit tumour growth, they can paradoxically activate Notch signalling and promote therapeutic resistance. Co-targeting Notch alongside endocrine therapy has been proposed as a strategy to delay the onset of therapeutic resistance. However, clinical development of Notch inhibitors has been limited by toxicity associated with pan-Notch blockade. More selective approaches, such as paralogue-specific antibodies, transcription-complex disruption, rational drug combinations, and advanced delivery platforms, are under active development to overcome these limitations. This review outlines the ERα-Notch crosstalk in BCa and examines current and emerging strategies for targeting Notch to overcome endocrine resistance and improve clinical outcomes.

Paraneoplastic neurological syndromes (PNSs) are a group of neurological disorders linked to malignancies. Their clinical trajectory, differential diagnoses, immune-mediated mechanisms, and outcomes remain inadequately understood. The review aims to improve our understanding of the main syndrome and its clinical progression by systematic review of studies involving patients with anti-Ri-antibody-associated paraneoplastic neurological syndrome (Ri-PNS).

The protocol adhered to the PRISMA guidelines and is registered with PROSPERO (ID: CRD420251152531).

Eighty-five cases with comprehensive clinical data were identified, with a median age of 61.0 ± 11.8 years, and the majority were female (78.6%). At the disease onset, ataxia was the most prevalent neurological symptom (70.6%). Ataxia rarely manifested as a state of isolation, and was frequently accompanied by other symptoms: tremor, dysarthria, spasticity, and dystonia. Twenty-six patients (30.6%) developed opsoclonus, and 22.4% developed myoclonus. The median interval from the onset of PNS to cancer diagnosis was 1.5 months (IQR, 0-7.0 months). Breast cancer was frequently observed in female patients (65.2%), whereas lung cancer was more common in male patients (38.9%). Of the patients with cancer, fifty-eight received oncological treatment. In addition, 62/85 patients (72.9%) underwent immunotherapy.

Ri-PNS is a multisystem neurological syndrome with significant involvement of the cerebellum and brainstem. The syndrome is frequently associated with tumors, and its appearance often signals the presence of a concurrent or occult tumor. Anti-tumor therapy and immunotherapy remain the two major management approaches in treatment. Considering that early intervention has the potential to enhance neurological function and improve the prognosis in patients with Ri-PNS, it could be given particular attention in clinical practice.

POLE2 exhibits oncogenic properties. This study aimed to clarify its effects and underlying mechanisms in renal cell carcinoma (RCC). Using bioinformatics analyses, we predicted the relationship between POLE2 and autophagy, epithelial-mesenchymal transformation (EMT), and the AKT/mTOR pathway. The expression pattern of POLE2 was further verified in the clinical cohort comprising 94 tumor samples from patients with RCC. Following, we constructed in vivo and in vitro models to further investigate the potential mechanisms of POLE2 using a series of molecular biology approaches. The results showed that GINS1 was the downstream target of POLE2, and its overexpression reversed the inhibitory effects of POLE2 knockdown on RCC proliferation, metastasis, and EMT, while restoring the autophagy suppression. Furthermore, POLE2/GINS1 inhibited AKT/mTOR-mediated autophagy, thereby promoting EMT and lung metastasis of RCC. These findings provide a more comprehensive perspective on the genetic function of POLE2 in RCC progression.

Herein, isatin was derivatized into tetra-imine derivative (8d) using active reactants and their anticancer potential against human breast cancer cell (MCF-7), are reported. However, the analytical techniques named FT-IR, ¹H and ^{1 3}C NMR, were utilized to confirming of the synthesized compounds. In vitro investigation, MTT assay was demonstrated a dose-dependent decrease in MCF-7 cell viability, with an IC₅₀ of 56 µM and 30% viability at 100 µM concentration as well. Morphological studies indicated apoptosis as the primary mechanism, evidenced by cell shrinkage, detachment, and reduced density. In silico analysis, the molecular docked complexes showed the strong binding affinity of 8d (-11.01 kcal/mol) to Human 3α-HSD3, with key interactions involving TYR24, ASN56, and TRP227. Molecular dynamics simulations (100 ns) confirmed complex stability, with minimal RMSD/RMSF variations and sustained hydrogen bonding. Radius of gyration and SASA analyses suggested increased protein compactness upon binding. MM-GBSA binding free energy was 11.29 ± 7.31 kcal/mol, dominated by van der Waals contributions. These results highlighted compound 8d as a promising scaffold for further development as a breast cancer therapeutic targeting Human 3α-HSD3.

Neoplasia of the cornea is overall rare, with corneal squamous-cell carcinoma (c-SCC) being most commonly reported in all species. C-SCC pathogenesis has been related to UV exposure in humans and horses, and to papillomavirus infection in humans. In dogs, brachycephalic conformation and chronic keratitis were associated with c-SCC. Corneal vascular tumors have also been exceptionally reported in humans, and rarely in animals. In dogs, they have been suggested to be UV-related. Except for equine c-SCCs, most studies on corneal neoplasms are case reports. The present study aimed to review the literature on epithelial and vascular corneal tumors in dogs, cats, and horses, adding new cases from our archives. Pubmed and Web of Science were searched (1980-2025) using the following keywords: cornea, neoplasia, carcinoma, hemangioma, hemangiosarcoma, dog, cat, and horse. Additionally, 94 new cases of corneal neoplasia were retrieved: 47 dogs (40 epithelial and seven vascular); 29 cats (14 epithelial and 15 vascular) and 18 horses. Signalment, clinical history, and histopathological characteristics were analyzed and compared with the literature. The combined results supported a strong association between brachycephalic dogs and c-SCC occurrence and highlighted the frequent coexistence in the feline species of symblepharon and corneal perforation, with corneal tumors.

Background and Clinical Significance: Polycythemia vera is a myeloproliferative neoplasm associated with a high thrombotic risk. Although this association is well recognized, acute coronary syndrome as the initial manifestation of polycythemia vera is rare. Case Presentation: We report the case of a previously healthy 57-year-old male with no conventional cardiovascular risk factors who presented with an anterior ST-elevation myocardial infarction. Coronary angiography revealed a subocclusive lesion in the left anterior descending artery, which was successfully treated with primary percutaneous coronary intervention. Initial laboratory testing showed markedly elevated hemoglobin (209 g/L) and hematocrit (64.9%), together with thrombocytosis (438 × 10⁹/L). In the absence of conventional risk factors, the combination of a single-vessel coronary lesion and marked hematologic abnormalities raised suspicion for polycythemia vera as a major contributor to coronary thrombosis. Subsequent work-up confirmed polycythemia vera based on the presence of a JAK2 V617F mutation and suppressed erythropoietin levels. The patient underwent therapeutic phlebotomy shortly after angioplasty and was subsequently started on hydroxyurea to maintain a hematocrit below 45%, together with dual antiplatelet therapy. Conclusions: This case highlights acute myocardial infarction as a rare initial presentation of polycythemia vera. It underscores the importance of considering polycythemia vera in patients presenting with acute coronary syndrome and unexplained erythrocytosis, while acknowledging that, in the absence of intracoronary imaging, a definitive causal link between PV and the coronary event cannot be established.

Background and Clinical Significance: Myolipoma is a rare benign tumor, typically found in the retroperitoneum and characterized by a combination of mature adipocytes and well-differentiated smooth muscle cells. Myoplipomas usually present a delay in diagnosis due to the painless and slow-growing clinical behavior; therefore, the lesion can reach a large dimension with challenging treatment. Case Presentation: We present the case of a retroperitoneal myolipoma infiltrating the left hip of an 11-year-old male. It was suspected based on magnetic resonance imaging. The patient has been successfully treated with surgical excision without complications. Histological examination revealed mature adipose tissue infiltrating smooth muscle cells. The muscle fibers appeared normal, while the dense connective tissue was infiltrated by clusters of mature lymphocytes. Conclusions: Although myolipoma is extremely rare in male children and has never been reported to infiltrate the hip, it should be considered in the differential diagnosis of fat-containing retroperitoneal masses.