Glioblastoma is a devastating disease with a high mortality rate. Conventional therapies such as surgery, chemotherapy, and radiotherapy are used to treat it. However, the recurrence rate of glioblastoma is high, and the average lifespan, even with treatment, is 12-15 months. Therefore, more effective therapeutic modalities are needed to effectively treat glioblastoma. One novel approach is gene therapy using various types of therapeutic genes and delivery carriers such as virus, liposome, and polymeric carriers, each of which has pros and cons. Recently, cell-membrane nanovesicle (CMNV) systems have been developed to deliver genes into glioblastoma. CMNVs have some advantages over other types of delivery carriers. First, CMNVs are highly biocompatible and cause no remarkable toxicity to cells. Second, CMNVs can have a long circulation time in the blood due to their low interaction with blood components. Third, CMNVs are easy to modify with ligands to enable targeted delivery of therapeutic genes to glioblastoma. Fourth, CMNVs can form hybrid nanovesicles with lipids or polymers to provide additional functions. In this review, we describe the current progress in using CMNVs to deliver genes to glioblastoma and various delivery routes to glioblastoma. The strategies described here for preparing and applying CMNVs could facilitate successful gene therapy for glioblastoma.

Peripheral edema is a common but under-researched complication in advanced cancer, significantly impacting patients' quality of life. It can result from various causes beyond lymphatic dysfunction, necessitating a mechanism-based management approach.

This study aims to address knowledge gaps by characterizing the causes, treatments, and outcomes of peripheral edema in patients with advanced cancer.

A predefined protocol was registered on the Open Science Framework, using a five-step scoping review methodology. Eligible studies included adult patients with peripheral edema related to advanced cancer, its treatments, or comorbidities. Searches were conducted in MEDLINE, Embase, and the Cochrane Library from 2010 to June 30, 2023. Two independent reviewers screened titles, abstracts, and full texts; extracted data, and assessed the quality of observational studies using the Effective Public Health Practice Project's tool.

Of 426 publications, 31 studies met inclusion criteria: 10 observational studies (2,128 patients), 5 case series (79 patients), and 16 case reports (16 patients). Most studies involved patients with limited prognoses. The 10 observational studies had moderate (6/10) or weak (4/10) quality ratings. Among these studies, the reported causes included overhydration, malignant inferior vena cava obstruction, and multiple risk factors. Seven observational studies addressed treatments, often using mechanism-guided (and sometimes multimodal) strategies, encompassing stenting, parenteral fluid and medication management including diuretics, and decongestive physical therapy interventions.

Peripheral edema in patients with advanced cancer arises from diverse and often overlapping mechanisms, and the available limited evidence from this scoping review suggests that mechanism-based interventions can yield meaningful short-term improvements in symptom burden. Targeted management, such as hydration or medication management, decongestive therapy, or inferior vena cava stenting, produced measurable benefits. These findings underscore the need for standardized assessment and more prospective studies to strengthen the evidence base for individualized, mechanism-driven care for peripheral edema in the advanced cancer population.

The locus encoding Ras association domain family member 1 (RASSF1) encodes multiple transcripts with opposing roles in cancer, such as RASSF1A (tumor suppressor), RASSF1C (oncogene), and the lncRNA RASSF1-AS1 (function undefined). Although DNA methylation-mediated repression of RASSF1A expression has been extensively studied in different cancer types, the epigenetic regulation of RASSF1C and RASSF1-AS1 is unclear. We profiled gene expression and promoter DNA methylation of RASSF1A, RASSF1C, and RASSF1-AS1 across 11 tumor cell lines, quantified RASSF1A methylation in lung cancer tissues and plasma by quantitative methylation-specific PCR (qMSP), and integrated single-CpG methylation (pyrosequencing) with in silico transcription factor binding site (TFBS) prediction.

We found that RASSF1A promoter hypermethylation was strongly and inversely associated with its mRNA levels. In contrast, RASSF1C promoter methylation did not correlate with expression. RASSF1-AS1 showed low promoter methylation accompanied by high expression. In clinical samples, RASSF1A methylation was detected in tissue biopsy (54% of cases) and plasma (42% of cases) from lung cancer patients, whereas no methylation was detected in 85% of control individuals, regardless of their smoking history. Finally, the analysis of DNA methylation at specific CpG sites combined with the prediction of TFBS in the evaluated promoter regions allowed the identification of binding domains overlapping differentially methylated regions. Notably, the RASSF1C promoter region exhibited a higher TFBS frequency containing CpG sites with low methylation levels, as determined by pyrosequencing.

These findings highlight isoform-specific epigenetic regulation at the RASSF1 locus and suggest that RASSF1A methylation may represent a promising minimally invasive marker in lung cancer.

Infective manifestations of hematological malignancies can be traced to a variety of pathogens, necessitating broad spectrum empiric antibiotic coverage, and prompt identification of pathogenic microbes to improve clinical outcomes. We present a case of Morganella morganii leading to pneumonia as the presenting illness in a previously undiagnosed, functionally neutropenic adult presenting with acute myeloid leukemia with monocytic differentiation. Our patient was a 64 year old man with no prior medical care who presented with complaints of progressive abdominal pain, productive cough and fevers. Chest radiography revealed no organized consolidations, and computed tomographic imaging of the chest showed bibasilar atelectasis and trace pleural effusions. Laboratory analysis revealed marked leukocytosis with predominant monocytosis, and circulating blasts, suggestive of acute myeloid leukemia with monocytic differentiation, later confirmed with bone marrow biopsy. The patient was initially started on guideline directed empiric therapy for respiratory infection, with sputum cultures later found to be growing Morganella morganii, necessitating a change in antimicrobial therapy, following which the patient showed clinical improvement. To our knowledge, this is the first reported case of Morganella morganii pneumonia presenting at the initial diagnostic encounter of de novo acute myelomonocytic leukemia. This report underscores the need for prompt microbiologic evaluation, broad empiric coverage with early de-escalation, and inclusion of M. morganii in the differential diagnosis of pneumonia in functionally neutropenic patients when standard pathogens are not identified. This case highlights the need to recognize atypical Gram-negative organisms as potential pathogens in these populations, even in the absence of characteristic radiographic findings.

Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon soft-tissue sarcomas, and primary retroperitoneal presentation in young adults is rare. Because imaging features may overlap with benign schwannoma, diagnosis and risk stratification rely on histopathology and proliferative indices.

A 27-year-old Arab male presented with a progressively enlarging abdominal mass associated with early satiety and heaviness. Abdominal ultrasonography and contrast-enhanced computed tomography (CT) demonstrated a well-circumscribed retroperitoneal mass measuring approximately 15 cm, located beneath the liver and posterior to the pancreatic head, closely related to the anterior surface of the right kidney and in proximity to the inferior vena cava, with heterogeneous predominantly hypoattenuating components and internal low-attenuation areas consistent with cystic/degenerative change. No lymphadenopathy or distant metastases were identified. The patient underwent exploratory laparotomy with complete excision; estimated blood loss was 250 mL and no transfusion or en bloc organ resection was required. Histopathology showed a spindle cell neoplasm with mild cytologic atypia and mitotic activity quantified as 6 mitoses per 10 high-power fields, without necrosis; margins were free of tumor. Immunohistochemistry demonstrated diffuse strong S100 positivity, negative Actin/CD117/CD34, and a Ki-67 index of 10-15%, supporting a low-grade MPNST. At 6 months postoperatively, the patient remained clinically well with no radiologic evidence of recurrence.

This case underscores that a large, well-circumscribed retroperitoneal peripheral nerve sheath tumor in a young adult may still be malignant. Pathology-driven risk stratification with quantified mitotic activity and Ki-67 is essential for accurate classification and for planning structured post-resection surveillance.

Philadelphia-negative myeloproliferative neoplasms are chronic blood neoplasms. Treatments control blood counts but disease can progress to myelofibrosis or acute myeloid leukaemia. We performed longitudinal whole-genome and targeted sequencing in 30 patients, integrating clonal dynamics with 7,986 blood counts and clinical histories. Distinct evolutionary patterns distinguished stable from progressive disease, with leukaemic transformation arising via TP53 loss, stepwise driver mutation acquisition within complex clones, or emergence of independent leukaemic clones. In contrast, stable disease showed long-term clonal equilibrium without new drivers. Phylogenetic analysis using 203 whole-genomes of haematopoietic colonies revealed age-appropriate polyclonal haematopoiesis in triple-negative essential thrombocythaemia and germline predisposition to thrombocytosis, supporting non-neoplastic origins. Therapy-associated mutagenesis was observed, including C>G mutations following azacitidine and characteristic T>A/T>G after hydroxycarbamide exposure in blood cells, although not in skin where UV damage predominated. These findings demonstrate progression is genomically encoded years in advance and support serial monitoring and further study of treatment-related mutagenesis.

Clonal mature plasmacytoid dendritic cell proliferations (MPDCP) are a recently recognized entity in the WHO fifth edition, but their pathologic spectrum remains poorly characterized. Cases with extensive MPDCP in the bone marrow (BM) are rare and can exhibit overlapping features with blastic plasmacytoid dendritic cell neoplasm (BPDCN). We compared clinicopathologic and genomic features of 11 patients with myeloid neoplasm-associated MPDCP to 5 patients with secondary BPDCN arising from clonally-related myeloid neoplasms. MPDCP exhibited variable degrees of BM involvement (5% to 50%) and architectural patterns, were uniformly positive for CD123, CD4, TCF4, and IRF8, variably positive for TCL1 (7/11), CD5 (7/11), and CD7 (2/11), and negative for SOX4, CD56, and TdT. MPDCP skin involvement was rare (1/11), with no CNS involvement. MPDCP heralded myeloid disease progression in a subset of patients, with increased blasts or progression to AML (4/11). In contrast, secondary BPDCN was uniformly positive for SOX4 and TCL1, with frequent CD56 (4/5) and subset/weak TdT (3/4). All BPDCN patients had characteristic skin lesions, and a subset with CNS involvement (2/5). The underlying myeloid neoplasms associated with MPDCP or BPDCN were enriched in TET2, SRSF2, ASXL1, RUNX1, and RAS pathway mutations. While karyotypic abnormalities were uncommon in MPDCP, all BPDCN showed chromosomal structural abnormalities and copy number variants, including deletions of 3p, 9p, and 12p. Our findings expand the histopathologic, immunophenotypic, and genetic characterization of MPDCP, and highlight pathologic features that distinguish it from BPDCN. Utilization of SOX4 immunohistochemistry, combined with careful clinical and molecular correlation, can aid in resolving these diagnostic challenges.

Non-small-cell lung cancer (NSCLC) is the predominant form of lung cancer and the leading cause of cancer-related mortality worldwide, largely due to its aggressive progression and resistance to current therapies. B7-H3 has emerged as a novel immunotherapeutic target worthy of investigation. Luteolin, a flavonoid polyphenolic compound abundantly present in vegetables and herbs, has demonstrated significant anti-tumor effects in various cancer types. However, its therapeutic mechanism of action in NSCLC remains poorly understood. This study aimed to examine the combined effects of luteolin and B7-H3-targeted immunotherapy in NSCLC. The results demonstrated that luteolin suppressed NSCLC cell proliferation in a dose-dependent manner and exhibited enhanced combined effects with B7-H3 inhibition, while also promoting apoptosis. This combination strategy produced significant inhibitory effects both in vitro and in vivo. A B7-H3-targeted bispecific killer cell engager (BiKE) was constructed, and antibody-dependent cell-mediated cytotoxicity (ADCC) was measured to evaluate its combined effect with luteolin. The B7-H3-targeted BiKE showed superior activity when combined with luteolin compared to either treatment of luteolin or BiKE alone. Our findings not only identify B7-H3 as a promising therapeutic target for NSCLC but also suggest luteolin as a potential anticancer adjuvant. The rationally designed combination strategy presented here may enhance existing treatment paradigms for NSCLC.

Amino acid metabolism is central to the liver's multifaceted physiology, serving as the cornerstone for protein homeostasis, metabolic integration, and tissue repair and regeneration. In addition, the dysregulation of amino acid metabolism is intricately linked to the pathogenesis and progression of a wide spectrum of liver diseases, acting as a central pathological driver beyond a passive metabolic consequence. In metabolic dysfunction-associated steatotic liver disease (MASLD), characteristic alterations in circulating branched-chain amino acids (BCAAs) and glycine levels directly promote hepatic steatosis, oxidative stress, and inflammation. The progression to hepatocellular carcinoma (HCC) is fueled by a profound metabolic reprogramming that creates a dependency on amino acids like glutamine and aspartate for energy and biomass, while methionine and tryptophan metabolism foster an immunosuppressive microenvironment and epigenetic dysregulation to facilitate immune evasion and tumor growth. Furthermore, in liver fibrosis and cirrhosis, metabolic adaptations support disease progression, whereas in hepatic encephalopathy, the hallmark imbalance between BCAAs and aromatic amino acids, coupled with ammonia neurotoxicity, disrupts neurotransmitter balance. These disease-specific alterations not only provide robust biomarkers for diagnosis and prognosis but, more importantly, reveal critical therapeutic vulnerabilities. Consequently, targeting amino acid metabolism emerges as a promising strategic avenue, encompassing dietary interventions, targeted supplementation, and pharmacological inhibition for the development of novel therapeutics across the landscape of liver diseases. This review aims to systematically expound on these dual physiological and pathological roles, arguing that such disease-specific metabolic alterations not only provide biomarkers but, more importantly, unveil targetable vulnerabilities, thereby positioning amino acid metabolism as a strategic frontier for developing novel therapeutics across liver diseases.

To investigate the role and mechanism of DHCR24 in chemoresistance of ovarian cancer and to identify potential therapeutic targets for overcoming treatment resistance.

We integrated bioinformatic analysis of GEO datasets and clinical survival data from KMplot to identify chemoresistance-associated genes. DHCR24 expression and function were systematically evaluated using cisplatin-resistant cell lines (A2780/DDP, SKOV3/DDP), patient-derived primary cells, xenograft models, and clinical specimens through molecular biology techniques, immunohistochemistry, and functional assays. Mechanistic studies employed RNA interference, cholesterol modulation, lipid raft disruption with MβCD, cycloheximide chase assays, and STAT3 pathway inhibition.

DHCR24 was consistently upregulated in chemoresistant ovarian cancer models and significantly correlated with poor patient survival. Genetic or pharmacological inhibition of DHCR24 restored chemosensitivity in vitro and in vivo, while its overexpression induced cross-resistance to multiple chemotherapeutic agents. Mechanistically, DHCR24 enhanced cholesterol biosynthesis, which stabilized lipid raft microdomains to promote P-gp protein stability and facilitate STAT3 membrane recruitment and activation. Furthermore, activated STAT3 transcriptionally upregulated DHCR24 expression, establishing a positive feedback loop that perpetuates the chemoresistant phenotype.

DHCR24 drives chemoresistance through a cholesterol-dependent circuit that stabilizes drug efflux pumps and activates pro-survival signaling, identifying DHCR24 as a promising therapeutic target for overcoming chemotherapy resistance in ovarian cancer.