Despite newly introduced treatment options, the 5-year survival rate for non-small cell lung cancer (NSCLC) remains below 20%, indicating a remaining need for new treatment strategies. Benzamil (BZ) has demonstrated inhibitory effects on brain tumors and osteosarcoma; however, its effects on NSCLC cells remain unknown. In this study, we investigated the potential anti-cancer effects of BZ in a panel of NSCLC cell lines. Compared to cells with EGFR L858R/T790M double mutations (H1975), BZ induced greater cytotoxicity in EGFR wild-type (A549, H1299, H292) and EGFR ex19del (PC9) cells. Mechanistically, BZ treatment was associated with inhibition of Akt, ERK1/2, and Stat3 signaling and increased mitochondrial damage. It was also associated with reduced Drp1 and Fis1 expression. Moreover, BZ induced release of cytochrome c, Smac/Diablo, and HtrA2/Omi from mitochondria. Additionally, BZ enhanced osimertinib-induced cytotoxicity in EGFR-mutant cells, and it suppressed H1975-derived cancer spheres. These findings support a proposed model in which BZ-induced mitochondrial damage is accompanied by the release of cytochrome c, Smac/Diablo, and HtrA2/Omi. These changes were accompanied by caspase activation and cell line-dependent alterations in XIAP expression, consistent with their potential contribution to apoptosis in NSCLC cells.

Transcatheter arterial embolisation is an established treatment for visceral pseudoaneurysms and pancreaticoduodenal arcade embolisation is generally well tolerated because of rich collateral flow. We report a man in his 70s with metastatic rectal cancer previously treated with bevacizumab who developed duodenal perforation and retroperitoneal abscess 15 days after embolisation of an inferior pancreaticoduodenal artery pseudoaneurysm using coils and adjunctive N-butyl cyanoacrylate-Lipiodol. He improved with broad-spectrum antibiotics, CT-guided drainage and conservative management, avoiding emergency surgery. The course is compatible with a multifactorial process in which procedure-related local ischaemic stress, altered collateral reserve, prior surgical alteration of regional vessels and impaired tissue repair after prior bevacizumab and recent fruquintinib exposure may have contributed. Pancreatic inflammation or leakage was not confirmed but remains a possible alternative or interacting mechanism. Causality cannot be established from a single case.

The gut microbiome has emerged as a key contributor to cancer biology. Prior studies have focused on individual cancers and often overlook comorbidities, obscuring whether reported associations are specific to a cancer type. Here, we present findings from a real-world mixed-cancer cohort (Mayo Clinic Cancer Microbiome), comprising 1,364 cancer patients and 287 healthy controls. By applying a framework to account for non-specific microbiome associations with cancer, comorbidities, and demographic and clinical variables, we identified 341 cancer-associated species across five cancer classes that represent the most plausible contributors to cancer pathogenesis. Within cancer classes, we found lower levels of fecal bile acids and C. scindens in early-onset breast cancer and elevated lactate and Veillonella parvula in early-onset colorectal cancer. Additionally, Anaerostipes hadrus encoding dihydropyrimidine dehydrogenase was protective against 5-fluorouracil-induced diarrhea. These findings demonstrate the strength of our cohort and provide a foundational resource for the discovery of cancer-specific microbiome signatures and predictive biomarkers.

Subperiosteal lesions encompass traumatic, infectious, benign neoplastic, and malignant processes arising between the periosteum and the underlying cortex. Because the periosteum is more loosely adherent in children and young adults, several entities are encountered more often in paediatric populations. Accurate diagnosis requires integration of imaging characteristics such as lesion location, composition and cortical response, and relevant clinical context. This imaging-focused review discusses subperiosteal haematoma, abscess, ganglion, osteoid osteoma, osteoblastoma, aneurysmal bone cyst, lipoma, haemangioma, chondroid lesions, Ewing sarcoma, osteosarcoma and metastases. We lead with a practical imaging diagnostic algorithm and use the accompanying tables as the core summary, with the subsequent discussion emphasising the principal imaging discriminators and differential diagnoses. Tissue diagnosis is discussed where imaging is indeterminate or an aggressive surface tumour is suspected.

IntroductionCell membrane-coated nanoparticles are emerging as promising biomimetic platforms for targeted cancer drug delivery, owing to their homotypic tumor-targeting ability and favorable biocompatibility. In this study, we fabricated a biomimetic DOX@Mem-HMnO₂ nanosystem based on hollow mesoporous manganese dioxide (HMnO₂) coated with A549 lung adenocarcinoma cell membrane (Mem) and loaded with doxorubicin (DOX), and evaluated its in vitro biological performance using the A549 cell model.MethodsMonodisperse silica nanoparticles were synthesized via a modified Stöber method as sacrificial templates to prepare hollow mesoporous HMnO₂. DOX was loaded into HMnO₂, and native A549 cell membrane was isolated by differential centrifugation and wrapped onto DOX-loaded HMnO₂. SEM and TEM characterized morphology and membrane coating; UV-Vis spectrophotometry confirmed DOX loading; particle size and zeta potential were measured, and colloidal stability was monitored over 72 h in deionized water and DMEM. CCK-8 and Transwell assays evaluated anti-proliferative and anti-migratory effects (≥3 independent replicates).ResultsDOX@Mem-HMnO₂ was successfully prepared as spherical, relatively monodisperse nanoparticles with an observable membrane-like outer layer and retained DOX characteristic absorbance. Zeta potential shifted from -42.1 ± 1.8 mV (bare HMnO₂) to -23.8 ± 1.5 mV after membrane coating and -30.2 ± 1.6 mV after DOX loading. The nanosystem remained stable without aggregation over 72 h. All DOX-containing groups inhibited A549 proliferation in a concentration-dependent manner; DOX@Mem-HMnO₂ produced significantly stronger anti-proliferative and anti-migratory effects than free DOX and DOX@HMnO₂ (P < 0.05), while empty carriers showed low intrinsic cytotoxicity. This study is limited to in vitro A549 experiments; direct evidence for homotypic targeting and in vivo performance is absent.ConclusionDOX@Mem-HMnO₂ can be readily synthesized with uniform morphology, favorable colloidal stability, and enhanced in vitro anti-proliferative and anti-migratory activity against A549 cells, providing a proof-of-concept basis for further biological validation.

Fatty acid binding protein 5 (FABP5) contributes to lipid metabolism and inflammation, but, its immunoregulatory role in hepatocellular carcinoma (HCC) is unclear. Considering the strong metabolic-immune interplay in HCC, elucidating how FABP5 shapes the tumor immune microenvironment may uncover new therapeutic targets.

TCGA, CCLE and single-cell RNA-seq datasets were employed to characterize FABP5 expression and clinical relevance. FABP5 knockdown was performed to assess effects on HCC cell proliferation. Immune infiltration, immune checkpoint profiles, TIDE scores and enrichment of immune-related pathways were analyzed. Differentially expressed genes underwent GO and KEGG pathway enrichment analyses. Protein-protein docking, molecular dynamics (MD) simulations and in vitro assays were conducted to explore the regulatory role of FABP5 in the NF-κB/PD-L1 axis. Drug screening, molecular docking and duplicate MD simulations were carried out to identify potential FABP5-targeting compounds.

FABP5 was significantly upregulated in HCC and predicted worse survival, serving as an independent prognostic factor. Single-cell analysis identified predominant FABP5 expression in fibroblasts and macrophages. FABP5 knockdown suppressed cell proliferation, colony formation, DNA synthesis and migration, accompanied by decreased expression of epithelial-mesenchymal transition (EMT) markers. FABP5-high tumors exhibited increased immune infiltration but raised immune checkpoint levels and higher TIDE scores, indicative of an immunosuppressive microenvironment. FABP5 correlated positively with NF-κB pathway genes and molecular docking predicted stable complexes between IκBα and P65. Experimental validation confirmed that FABP5 drives PD-L1 upregulation in an NF-κB-dependent manner. Drug screening identified CZS-241 as the most promising FABP5-binding candidate, and duplicate MD simulations demonstrated a stable FABP5-CZS-241 complex.

FABP5 drives immunosuppression in HCC by inducing PD-L1 via the NF-κB pathway. CZS-241 is identified as a promising FABP5-targeting compound with therapeutic potential for HCC.

The therapeutic goal in multiple myeloma (MM) is changing from long-term disease control to a potential cure. While anti-CD38-containing quadruplets have improved outcomes, relapses continue to occur in many patients. In recent years, advancements in immunotherapy have fundamentally changed this paradigm. Bispecific antibodies (BsAbs) and chimeric antigen receptor T-cells (CAR T-cells) have deepened responses and achieved sustained MRD negativity in an unprecedented way, raising the possibility of curing MM in a subset of patients. Recently, the International Myeloma Society (IMS) reached a consensus and discussed a framework to define cure. This review examines how novel immunotherapies are redefining frontline strategies in newly diagnosed MM (NDMM) and attempts to summarize how BsAbs, CAR T-cells, and cereblon E3 ligase modulators (CELMoDs) can be integrated into induction, consolidation, and maintenance phases. It also discusses the evolving role of autologous stem cell transplant (ASCT) in the immunotherapy era and MRD-guided treatment and discontinuation strategies. Together, this review attempts to provide a roadmap to fulfill the criteria for cure.

Multiple myeloma is a plasma cell malignancy associated with heterogeneous clinical outcomes. The majority of patients are diagnosed during their seventh decade and often present with age-related comorbidities and organ dysfunction. Myeloma therapeutic landscape is rapidly evolving with the introduction of immune-based therapies, including monoclonal and bispecific antibodies and chimeric antigen receptor (CAR) T-cell therapies targeting CD38, BCMA, and GPRC5D. These novel therapies have led to deeper and more durable responses and have raised the possibility of functional or definitive cure. However, older and frail patients continue to experience poorer outcomes, higher toxicity rates, and substantial treatment attrition, representing a major unmet clinical challenge. In this review, we discuss current approaches to the assessment and management of frailty in patients with multiple myeloma, with a focus on optimizing frontline therapy and treatment at relapse in the era of the possible achievement of a cure. We highlight emerging data on cellular therapies in this population and the importance of individualized, goal-directed treatment strategies aimed at balancing efficacy, tolerability, and quality of life.

B-cell maturation antigen (BCMA) targeted chimeric antigen receptor T-cell (CAR-T) cell therapy has proven highly efficacious for relapsed multiple myeloma, inducing deep and durable remissions. Recent reporting has bolstered significant enthusiasm, describing upwards of one-third of patients in continued remission, 5 years following BCMA CAR-T without receiving any subsequent therapy, suggesting the possibility that this treatment may offer the hope of a cure. There are many well-characterized side effects from CAR-T, and mitigation strategies have been established to make this therapy safe. However, as the use of CAR-T cells has become more widespread, several novel and unanticipated side effects have emerged. These novel toxicities of CAR-T can be delayed, occurring within the first 3 to 6 months, and can be life-threatening or life-altering. Thus, early detection and timely management are essential. This comprehensive review will cover the diagnosis and management of common and emerging toxicities associated with CAR T-cell therapy for multiple myeloma.

Bispecific antibodies (BsAbs) bind simultaneously to an antigen on the surface of multiple myeloma (MM) cells and to CD3 on the surface of T cells. This engagement leads to T-cell activation and degranulation, releasing perforin and granzymes, followed by the killing of the MM cell. Off-the-shelf available BsAbs targeting BCMA, GPRC5D, and FcRH5 have pronounced antitumor activity in heavily pretreated MM with cytokine-release syndrome, neutropenia, and infections as the most common side effects. To further improve clinical outcomes, BsAb-based combinations are being evaluated in earlier treatment lines, including newly diagnosed MM. Notably, the MajesTEC-3 trial established the combination of teclistamab and daratumumab as a new standard-of-care for relapsed/refractory MM as early as first relapse. The most common mechanism underlying acquired resistance to BsAbs is loss of antigen expression; therefore, dual-targeting strategies (combination of BsAbs targeting different tumor antigens or trispecific antibodies) are being intensively investigated to enhance the depth and duration of response.