Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare variant of hepatocellular carcinoma (HCC) that typically arises in non-cirrhotic livers and affects younger individuals compared with conventional HCC. Because patients usually have preserved hepatic function, surgical resection may be feasible even in the presence of large tumors. However, diagnostic uncertainty and concerns regarding extrahepatic disease may limit initial surgical decision-making.

We report the case of a 48-year-old male patient who presented with epigastric discomfort, weight loss, and a palpable abdominal mass. Contrast-enhanced imaging demonstrated a large hepatic lesion involving segments II, III, and IV, with additional pulmonary and adrenal findings initially raising concern for metastatic disease. The patient had previously been declined surgical treatment at another institution. Further multidisciplinary evaluation, imaging reassessment, and histological confirmation by percutaneous biopsy supported the diagnosis of FL-HCC without confirmed metastatic disease. An open anatomical left hepatectomy was performed. Histopathology confirmed FL-HCC with negative surgical margins and no lymph node metastases. Follow-up 36 months after surgery demonstrated no evidence of recurrence.

This case highlights the importance of comprehensive staging and multidisciplinary reassessment in patients with suspected FL-HCC. Even when surgery has initially been declined, careful evaluation may identify candidates for potentially curative hepatic resection. Long-term surveillance remains essential due to the risk of recurrence following resection. Additionally, this report illustrates that FL-HCC can occur outside the typical age range, emphasizing the need to consider this diagnosis in compatible clinical and radiologic contexts.

Breast cancer is a leading cause of mortality among women worldwide. Accurate survival prediction can improve clinical decision-making and support personalized treatment planning. This study aims to develop an interpretable and effective deep learning model for breast cancer survival prediction using multi-omics data.

This study proposes a novel deep learning model combining Bi-directional Long Short-Term Memory (BiLSTM) and Convolutional Neural Network (CNN) architectures, integrated with Minimum Redundancy Maximum Relevance (MRMR) feature selection. The model was evaluated on two large datasets: METABRIC (n=1980) and TCGA-BRCA (n=1080), using clinical, copy number alteration (CNA), and gene expression data. Performance was assessed through metrics such as AUC-ROC and accuracy.

The proposed model demonstrated superior performance compared to existing algorithms, achieving high AUC-ROC and accuracy values across all data modalities. The integration of BiLSTM and CNN architectures allowed the model to capture temporal and spatial patterns, improving prediction robustness. Notably, the model achieved an accuracy of 98% on the METABRIC dataset and 96% on the TCGA dataset.

The combination of BiLSTM, CNN, and MRMR offers an interpretable and accurate framework for breast cancer survival prediction using multi-omics data. This approach provides actionable insights for clinicians and highlights its potential for broader applications in oncology.

CXCR4 plays a pivotal role in liver fibrosis (LF) by mediating the activation of hepatic stellate cells (HSCs), which contribute to extracellular matrix (ECM) deposition and scar formation. The CXCR4/CXCL12 axis is essential in fibrogenesis, promoting HSCs activation, inflammation, and angiogenesis, which exacerbates fibrosis and creates an environment conducive to hepatocellular carcinoma (HCC) development. In HCC, CXCR4 signaling supports tumor cell proliferation, survival, and metastasis, linking chronic liver injury to cancer progression. Recent advancements in targeted drug delivery have facilitated the development of CXCR4-targeted therapies, improving treatment efficacy while minimizing systemic toxicity. This review examines the interactions between CXCR4 and its ligand CXCL12, the associated signaling pathways, and their role in LF and HCC. Furthermore, it explores CXCR4 as a therapeutic target, focusing on CXCR4 blockers, peptide inhibitors, and gene silencing/editing strategies. The review also highlights various CXCR4-targeted nano therapeutic strategies, such as liposomes, lipid NPs, microbubbles, polymeric NPs incorporating siRNA, miRNA, small molecules, peptides etc for the management of LF and HCC. Additionally, the review addresses the clinical progress of monoclonal antibodies, small molecules, and peptides targeting CXCR4 in both preclinical and clinical trials. Challenges and future directions of CXCR4-targeted nanotherapeutic are also discussed. In conclusion, this review emphasizes the therapeutic potential of CXCR4-targeted nanotherapeutic strategies for combating LF and HCC.

Lymphoma is a heterogeneous malignancy originating from the lymphatic and hematopoietic systems. Traditional diagnostic and therapeutic approaches face significant limitations due to the complexity, dissemination, and drug resistance associated with lymphoma. Thus, novel approaches are required for precise management and treatment. Recently, advances in nanotechnology have provided new possibilities for lymphoma therapy, particularly through interdisciplinary research combining materials science and biomedicine, thus offering promising strategies for precision treatment. This review systematically summarizes recent advancements in nanomedicine for lymphoma management. First, it introduces mechanisms of nanotechnological interventions, emphasizing lymphoma's pathological features. Next, cutting-edge diagnostic applications, including extracellular vesicle detection, high-sensitivity nucleic acid biomarker sensing, and multimodal imaging, are highlighted. Additionally, emerging therapeutic strategies such as integrated nanoplatforms combining diagnostics, treatment, and real-time monitoring are discussed. Examples include optimized mRNA vaccine delivery, enhanced chimeric antigen receptor (CAR) T-cell therapy, bispecific nanoparticle systems, and combination gene/chemotherapy approaches. Finally, this review outlines the challenges associated with clinical translation and suggests future directions for intelligent adaptive nanomedicine, emphasizing its potential to significantly advance lymphoma diagnosis and therapeutic paradigms.

Breast cancer is the most common malignancy among women worldwide, with high incidence and mortality rates. Tumor-associated macrophages (TAMs) are key mediators in the immunosuppressive tumor microenvironment (TME), contributing to poor prognosis and reducing immunotherapy efficacy. This review examines the dual roles of TAMs in breast cancer progression. TAMs are known to promote tumor development through angiogenesis, immune evasion, and metastasis, while M1-polarized TAMs conversely enhance antitumor immunity. Herein, the nanoparticle-based strategies targeting TAMs presented in preclinical research are explored, including reprogramming M2 to M1 macrophages, delivering MYC inhibitors, depleting TAMs, and inhibiting TAM recruitment. Integration with immune checkpoint inhibitors is also discussed. Challenges in translating these nanoparticle approaches from preclinical models to clinical practice are further addressed, with an emphasis placed on human-relevant models, optimized production processes, and personalized therapeutic approaches.

Myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) are clonal myeloid neoplasms shaped by genetic lesions and immune dysregulation, both of which contribute to disease progression and poor outcomes. Existing prognostic systems, such as IPSS-R and IPSS-M, do not incorporate immune alterations. We assessed the biological and clinical relevance of an immune dysfunction signature (IDS) across multi-center MDS and CMML cohorts. IDS scores, derived from bulk transcriptomic data, were significantly associated with inferior leukemia-free and overall survival. In multivariable analyses, IDS retained independent prognostic value alongside IPSS-R, IPSS-M, and bi-allelic TP53 inactivation. Incorporation of IDS into existing models improved prognostic discrimination and time-dependent predictive accuracy. Longitudinal analyses revealed that rising IDS scores paralleled disease progression and acute transformation, whereas declining scores were observed in remission. Biologically, IDS-high cases demonstrated reduced cytotoxic T-cell activity, expansion of regulatory T cells, enrichment of primitive progenitor signals, and increased expression of checkpoint pathway genes. These findings were validated across multiple independent MDS cohorts and consistently reproduced in CMML, where IDS also stratified risk and tracked disease evolution. Finally, integration with drug response signatures from the BeatAMLv2 cohort suggested potential therapeutic vulnerability of IDS-high cases to multikinase and NF-κB pathway inhibitors. These results establish IDS as a robust and dynamic biomarker in MDS and CMML, with applications in refined risk stratification, longitudinal disease monitoring, and guiding personalized therapeutic strategies targeting immune dysfunction. Trial Registration: #201709072RINC, #202109078RINB, #202207050RINB.

Relapsed acute lymphoblastic leukemia (ALL), particularly with central nervous system (CNS) involvement, remains a major cause of treatment failure and is inadequately controlled by existing antibody-drug conjugates (ADCs) with tubulin inhibitors. To address this limitation, we developed IL-7Rα-targeted monoclonal antibodies and identified clone 577 as the lead candidate. Using this antibody, we generated ADCs conjugated with either monomethyl auristatin E (MMAE) or the highly potent DNA-damaging payload-PNU-159682 (PNU). In head-to-head comparisons, 577-PNU showed >50-fold greater potency than 577-MMAE in vitro and induced complete tumor regression in xenografts at a 20-fold lower dose. Additionally, 577-PNU provided durable systemic disease control and markedly reduced leukemic infiltration in the brain and spinal cord in both preventive and established murine CNS disease models, offering direct evidence of effective CNS penetration. Safety assessments demonstrated stable body weight, normal hematology and serum biochemistry, and no treatment-related pathologies. Collectively, these findings provide the first preclinical evidence that IL-7Rα-directed ADCs armed with DNA-targeting payload PNU-159682 can achieve durable elimination of systemic and CNS leukemia at tolerable doses, demonstrating both clinical feasibility and CNS disease control, and establishing a compelling rationale for their translational and clinical development in relapsed and refractory ALL.

Spiradenomas are rare adnexal neoplasms that clinically mimic other cutaneous entities, such as epidermoid cysts and basal cell carcinomas. Although ultrasound diagnosis of common cutaneous tumors has significantly evolved over the last decades, the sonographic presentations of spiradenomas have been scarcely described. This study includes a case report and systematic review of previously reported sonographic characteristics of spiradenomas. A comprehensive search of the Pubmed/MEDLINE database identified studies with histological confirmation and ultrasound characterization of spiradenomas. Eight articles, comprising seven case reports and one case series with eight cases, were included. Data on clinical, demographic and sonographic features were extracted and analyzed. On B-mode ultrasound, spiradenomas appeared as well-defined, multilobulated, heterogeneous, hypoechoic masses located within the dermis and/or hypodermis, with posterior acoustic enhancement. Color Doppler imaging showed increased intralesional vascularization without anarchic pattern. The identified features helped differentiate spiradenomas from similar conditions, potentially reducing misdiagnoses, and optimizing management.

Plant sterols are naturally occurring tetracyclic triterpenes that serve as essential structural components of plant cell membranes. Structurally similar to cholesterol, these bioactive compounds have gained considerable attention for their diverse therapeutic properties, particularly their anticancer potential. Among them, stigmasterol, campesterol, and β-sitosterol are the most abundant and well-studied phytosterols known for their multifaceted roles in tumor suppression and apoptosis induction. They modulate several oncogenic signaling pathways, including PI3K/AKT/mTOR, JAK/STAT, NF-κB, and Wnt/β-catenin, thereby inhibiting cancer progression. Their anticancer activities involve mechanisms such as cell cycle arrest, activation of mitochondria-mediated apoptosis, inhibition of angiogenesis, and suppression of metastasis. Specifically, stigmasterol promotes apoptosis by upregulating Bax and p53, downregulating Bcl-2, and inhibiting angiogenic and JAK/STAT signaling. Campesterol induces cancer cell death through mitochondrial dysfunction, oxidative stress, and endoplasmic reticulum stress, enhancing the efficacy of chemotherapeutic agents. β-sitosterol inhibits proliferation, triggers cell cycle arrest, regulates apoptotic proteins, and suppresses metastasis while overcoming drug resistance. Despite extensive individual studies, a comprehensive review summarizing their collective anticancer mechanisms is lacking. This work bridges that gap by systematically analyzing literature from the past 10 years across major databases, including Google Scholar, ScienceDirect, Scopus, Wiley Online Library, and Web of Science. Evidence from preclinical, clinical, and pharmacological studies was critically evaluated to highlight the therapeutic potential of these sterols in tumor suppression and apoptosis, providing a consolidated foundation for future drug discovery and development. The unique contribution of this review lies in proposing a comparative mechanistic framework for stigmasterol, campesterol, and β-sitosterol, integrating their multi-targeted actions across key oncogenic signaling pathways to highlight their collective potential in anticancer therapy.

Hairy cell leukemia variant (HCL-v) is a rare B-cell malignancy with limited treatment options in relapsed or refractory settings. We describe the first reported case of chemo-refractory HCL-v successfully treated with zanubrutinib monotherapy. An 84-year-old man, previously refractory to rituximab and bendamustine, achieved early hematologic improvement and reduction in spleen size after starting zanubrutinib, with a sustained clinical and laboratory response at 17 months. A clinical study with ibrutinib has shown durable disease control in classic and variant HCL, supporting BTK inhibition as a therapeutic strategy. This case suggests zanubrutinib as a promising chemo-free option for frail HCL-v patients.