This study investigates the impact of histamine H₂ receptor activation on glucocorticoid receptor (GR)-mediated transcriptional activity, as well as its effects on leukemic cell proliferation and chemotherapy resistance. We demonstrate that activation of the histamine H₂ receptor by its specific agonist, amthamine, enhances GR transcriptional activity induced by dexamethasone in both artificial promoter-driven luciferase reporter assays and endogenous GR-responsive genes. Mechanistically, histamine H₂ receptor signaling exerts a dual regulatory effect: an inhibitory influence mediated by cAMP and a stimulatory effect through inhibition of the PI3K-AKT-mTOR-S6K pathway and activation of the ERK pathway. Furthermore, while dexamethasone reduces leukemic cell proliferation at high doses, it increases it at lower concentrations, an effect that is abrogated by amthamine. Moreover, the combination of the glucocorticoid and the H₂ agonist reestablishes leukemic cell sensitivity to cytarabine, thereby restoring its cytotoxicity. Together, these findings offer insight into the molecular mechanisms and therapeutic potential of the interplay between histamine H₂ ligands and GR agonists, and may help guide dosage optimization and mitigate the well-known side effects of glucocorticoid therapy, with potential clinical implications for the treatment of acute myeloid leukemia.

Brain tumors, particularly glioblastoma multiforme (GBM), remain among the most lethal forms of cancer due to their aggressive nature and the formidable challenge posed by the blood-brain barrier (BBB), which restricts the delivery of therapeutic agents. Conventional treatment modalities, including surgery, radiotherapy, and chemotherapy, often fail to achieve effective and targeted therapy without inducing systemic toxicity or damaging healthy brain tissue. In recent years, mesoporous silica nanoparticles (MSNs)have emerged as a versatile platform for targeted brain tumor therapy because of their high surface area, tunable pore structure, biocompatibility, and ease of surface functionalization. This review critically examines advanced surface functionalization strategies, including chemical functionalization (amine, thiol, carboxyl groups), ligand conjugation (antibodies, aptamers, peptides), and polymeric coatings (PEG, chitosan, PLGA) that enhance BBB penetration, facilitate tumor-specific targeting, and enable stimuli-responsive drug release (different types of exogenous and endogenous). We also explore the interactions of these modifications with key signaling pathways (e.g., Wnt/β-catenin, PDGF-B, TGF-β) that regulate BBB integrity and glioma progression. Special emphasis is placed on how surface-engineered MSNs can improve site-specific drug delivery, increase therapeutic accumulation in brain tumor tissue, and minimize off-target toxicity. Despite the considerable promise demonstrated by these techniques in preclinical glioma models, obstacles such as scalable synthesis, regulatory compliance, and long-term biosafety must be addressed to facilitate clinical translation. This review focuses specifically on brain tumor targeting via functionalized MSNs and provides mechanistic insights while highlighting emerging strategies to advance MSNs as next-generation therapeutics for brain tumor treatment.

Endoscopic resection is an accepted treatment option for appropriately selected non-ampullary duodenal neuroendocrine tumors (DNETs) measuring 10 mm or less. However, multicenter data from routine practice settings remain limited, particularly regarding histologic outcomes, adverse events, and recurrence after endoscopic resection.

This retrospective multicenter cohort study included consecutive patients who underwent endoscopic resection for non-ampullary DNETs at six affiliated centers, including a cancer center, university hospitals, and community hospitals, between January 2012 and July 2024. Primary outcomes were histologically complete (R0) resection and procedure-related adverse events (bleeding and perforation). Secondary outcomes included en bloc resection and recurrence during follow-up. Technique-specific outcomes were summarized descriptively.

A total of 36 patients with 36 lesions were analyzed. Resection techniques were conventional endoscopic mucosal resection (CEMR, n = 4), EMR with a cap (EMR-C, n = 10), endoscopic submucosal resection with a ligation device (ESMR-L, n = 19), endoscopic muscularis resection with an over-the-scope clip (EMRO, n = 1), and endoscopic submucosal dissection (ESD, n = 2). En bloc resection was achieved in 35/36 lesions (97.2%) and R0 resection in 26/36 (72.2%). Adverse events occurred in 2/36 (5.6%; one bleeding and one perforation). During a median follow-up of 48 months (range < 1-156), no recurrence was documented. ESMR-L was the most frequently selected technique (19/36, 52.8%) and was performed at all six institutions. Among lesions treated with ESMR-L, en bloc resection was achieved in 19/19 lesions (100%), R0 resection in 15/19 lesions (78.9%), and no procedure-related adverse events were documented.

In this multicenter real-world cohort, endoscopic resection for small non-ampullary DNETs achieved a high en bloc resection rate, an acceptable R0 resection rate, and a low frequency of adverse events, with no documented recurrence during the available follow-up. These findings support endoscopic resection as a reasonable treatment option for appropriately selected patients.

Cervical cancer remains a leading cause of cancer-related deaths among women worldwide. Targeting ferroptosis, a regulated form of cell death driven by lipid peroxidation, has emerged as a promising therapeutic strategy. This study aimed to elucidate the mechanisms by which cervical cancer cells acquire resistance to ferroptosis. AGRN expression and its prognostic significance were analyzed in cervical cancer using TCGA and GTEx data. In vitro, AGRN levels were measured in HeLa, CaSki, and Ect1/E6E7 cells via qRT-PCR. mRNA and protein expression levels of AGRN, beta-catenin, and ferroptosis-related markers were evaluated by qRT-PCR and western blot (WB). Cell viability, RSL3 sensitivity (IC50), and lipid ROS were assessed via CCK-8 assay and flow cytometry. In a xenograft model, RSL3's effect on tumor growth was examined. Immunohistochemistry (IHC) and molecular analyses (qRT-PCR, WB, and flow cytometry) were performed on tumor tissues to evaluate AGRN, beta-catenin, Ki-67, ferroptosis-related genes, and lipid ROS. It is found through research that, AGRN was significantly upregulated in cervical cancer tissues and cell lines. Its overexpression activated Wnt/beta-catenin signaling, resulting in elevated GPX4 and SLC7A11 levels and reduced CHAC1 and PTGS2 expression levels. These alterations decreased lipid ROS accumulation and enhanced resistance to RSL3-induced ferroptosis, an effect further confirmed in xenograft models. In short, In short, AGRN promotes ferroptosis resistance in cervical cancer by activating the Wnt/beta-catenin signaling pathway and upregulating GPX4 expression. Targeting the AGRN-Wnt/beta-catenin-GPX4 axis may represent a novel therapeutic approach for cervical cancer.

The objective of this study was to evaluate the safety and efficacy of ultrasound-guided single-session microwave ablation for benign thyroid nodules >4 cm by comparing outcomes with smaller nodules (<4 cm).

This retrospective single-center study (2016-2023) analyzed 1,107 patients with 1,463 pathologically confirmed benign thyroid nodules stratified by maximum diameter into four groups: ≤20, 20-40, 40-60, and ≥60 mm. Standardized follow-up was performed at 1, 3, 6, 12, and 24 months post-microwave ablation and then annually. Volume reduction ratio, maximum diameter reduction ratio, recurrence rate, and complications were assessed.

The cohort (127 males and 980 females) had a mean age of 45.8 ± 12.7 years and a mean maximum nodule diameter of 28.9 ± 14.6 mm. Complication rates significantly increased with nodule size (2.59, 5.55, 13.36, and 16.67%, respectively; P < 0.001). Technical efficacy exceeded 90% across all groups (P > 0.05). Volume reduction ratio improved significantly over time across all groups, with statistical differences at 1, 6, 12, and ≥24 months (all P < 0.001) but not at 3 months (P = 0.085). The ≤20 mm group achieved the highest volume reduction ratio at ≥24 months (96% ± 14%).

Ultrasound-guided single-session microwave ablation is safe and effective for large benign thyroid nodules, providing significant volume reduction with acceptable complication profiles while reducing treatment burden.

To investigate choroid plexus .   volume (CPV) alterations in patients with gliomas and glioneuronal and neuronal tumors (GNTs) and to evaluate their associations with tumor characteristics.

In this retrospective observational cohort study, 811 patients with histologically confirmed brain tumors (674 gliomas and 137 GNTs) and 744 controls were included. All participants underwent 3.0 T MRI with 3D T1-weighted imaging, and patient scans were acquired preoperatively. The choroid plexus was automatically segmented on 3D T1-weighted images using a 3D nnU-Net-based deep learning algorithm with expert quality control. CPV was normalized to total intracranial volume (CPV/TIV). Lateral ventricular volume (LVV) was quantified using FreeSurfer and included as a covariate. Group comparisons were performed using Mann-Whitney U and Kruskal-Wallis tests after case-control matching. Multivariable linear regression analyses were conducted to assess independent associations while adjusting for age, sex, and LVV, with additional sensitivity analyses incorporating scanner type.

Compared with supratentorial tumors and controls, infratentorial tumors showed significantly larger CPV (both P < 0.001). Tumor grade was not independently associated with CPV after adjustment among patients. Pediatric-type diffuse high-grade gliomas and GNTs exhibited larger CPV than adult-type diffuse gliomas (P < 0.01). In exploratory molecular analyses of adult-type diffuse gliomas, + 7/ - 10 status was associated with lower CPV (β = -0.127, P = 0.009).

CPV alterations in brain tumors are primarily associated with tumor location and histological classification rather than tumor grade. An exploratory association between +7/ - 10 status and lower CPV was also observed, although this finding requires further validation.

In Ethiopia, according to the GLOBOCAN 2022 report, there were 1,494 cases of esophageal cancer and 1,422 deaths attributed to the disease. The incidence and mortality of esophageal cancer are projected to increase to 3,210 and 3,057 cases by 2040, respectively. Approximately 68.3% of the cases were reported from the Arsi and Bale Zones, which also had the highest disease burden and mortality. Thus, undertaking a thorough study to identify hotspot areas for local preventative and control actions is important.

To assess the spatial clustering of esophageal cancer in Central Oromia, Ethiopia.

A cross-sectional study design was employed to investigate the spatial clustering of esophageal cancer patients. Data were collected from records of 367 patients who visited four hospitals (namely, Tikur Anbessa Specialized Hospital, Adama Hospital Medical College, Asella Teaching and Referral Hospital, and Meda Walabu University General Hospital) between April 3, 2019, and August 25, 2025. The kebele, woreda, and zone of each patient were collected from the records and linked to Ethiopian shapfiles obtained from the Ethiopian Space Science and Geospatial Institute (SSGI). The spatial inequality of esophageal cancer was measured using the Gini coefficient; while spatial autocorrelation was assessed using Moran's I. The risks within clusters were quantified using relative risk (RR) with its 95% confidence interval, as well as log-likelihood ratio (LLR) and p-values.

The annual incidence of esophageal cancer in the study area was 2.60 cases per 100,000 populations [95% CI: 2.34, 2.88]. The Gini coefficient revealed spatial inequality in the distribution of cases at both the district (G = 0.33; 95% CI: 0.24, 0.40) and kebele levels (G = 0.38; 95% CI: 0.33, 0.43). The Moran's I showd significant positive spatial autocorrelation at the kebele level (I = 0.17, p-value = 0.037). The risk of developing esophageal cancer was high in Robe district [RR = 1.93; 95% CI: 1.43, 2.61; LLR = 6.82; p-value = 0.022], Robe 01 kebele [RR = 7.8; 95% CI: 4.57, 13.31; LLR = 16.35; p-value = 0.000024], and Kula 01 kebele [RR = 9.96; 95% CI: 4.45, 22.32; LLR = 8.35; p-value = 0.034]. In contrast, 17 districts [RR = 0.55; 95% CI: 0.41, 0.73; LLR = 9.31; p-value = 0.0051] and 52 kebeles [RR = 0.55; 95% CI: 0.41, 0.73; LLR = 0.87; p-value = 0.014] were identified as low-risk areas.

Esophageal cancer showed uneven spatial distribution and significant autocorrelation in the study area. The presence of both high- and low-risk areas indicated significant geographic disparities. Robe district had nearly twice the risk, Robe 01 kebele had more than seven times the risk, and Kula 01 kebele had nearly ten times the risk of developing esophageal cancer compared to other districts and kebeles, respectively. Allocating diagnostic resources to health facilities serving high-risk districts and kebeles, promoting community health education on modifiable risk factors, and investigating individual-level risk factors are required to explain the observed clustering patterns.

This study investigated the impact of advanced molecular imaging, race, socioeconomic status, and metabolic dysregulation on the outcome of salvage radiotherapy (sRT) for prostate cancer recurrence in a clinical trial setting.

The authors randomized post-prostatectomy men with detectable prostate-specific antigen to sRT guided by conventional imaging (arm A) or ¹⁸F-fluciclovine-positron emission tomography/computed tomography (arm B) and followed them up for up to 48 months to determine failure-free survival (FFS). The authors computed socioeconomic status (SES) and allostatic load (AL) scores to quantify socioeconomic status and level of metabolic dysregulation. They stratified patients by race as African American men (AAM) versus men of other races (MOR) and compared FFS between them using the z-test.

Eighty-one (AAM = 29, MOR = 52) and 76 (AAM = 26, MOR = 50) men completed per-protocol sRT in arms A and B, respectively. Across study arms, AAM showed a higher FFS rate than MOR (72.8% [95% CI, 53.8%-85.0%] vs. 58.7% [95% CI, 46.6%-68.9%]; p = .002). In arm A, FFS rate was better for AAM than MOR, (64.0% [95% CI, 34.4%-82.9%] vs. 45.3% [95% CI, 28.8%-60.4%]; p = .008). In arm B, FFS improved for both groups but less so for AAM, (81.5% [95% CI, 57.2%-92.7%] vs. 73.0% [95% CI, 56.3%-84.1%]; p = .131). The authors found lower SES scores and higher AL scores for AAM in both study arms than MOR.

Despite lower socioeconomic status and higher burden of metabolic dysregulation, in a clinical trial setting that controls for disparities in health care access, AAM have a more favorable sRT outcome than MOR.

Entrectinib is effective for ROS1-positive non-small cell lung cancer (NSCLC), but its postmarketing safety profile remains incompletely characterized outside clinical trials. We conducted a dual-database pharmacovigilance study to characterize real-world reporting patterns, identify cross-database replicated adverse event signals, explore age- and sex-related reporting heterogeneity, and evaluate time-to-onset patterns.

Reports were retrieved from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS; 2020Q1-2025Q4; 520 patients; 1,573 preferred-term [PT] events) and the Japanese Adverse Drug Event Report database (JADER; 2020Q1-2025Q3; 254 patients; 393 PT events). Molecular fusion status was not available for verification. Four disproportionality methods were applied, with reporting odds ratio (ROR) as the primary signal criterion.

At the system organ class level, shared positive signals involved nervous system disorders (FAERS/JADER ROR: 4.48/4.76), cardiac disorders (3.20/5.43), and renal and urinary disorders (2.04/3.92). At the PT level, 23 signals were detected in both databases, whereas 58 PTs were unique to FAERS and 8 to JADER. Representative shared PT signals included dizziness (12.94/14.33), taste disorder (38.03/13.28), renal impairment (6.89/8.18), blood creatinine increased (8.31/24.99), cardiac failure (7.57/8.90), cognitive disorder (18.04/78.29), ataxia (51.73/351.45), syncope (8.87/89.45), myocarditis (3.47/5.91), electrocardiogram QT prolonged (4.01/5.35), and hyperuricaemia (7.36/59.63). Subgroup analyses suggested exploratory age- and sex-related reporting heterogeneity, including relatively more renal and mobility-related reports in older patients and female predominance for ataxia in FAERS. In the FAERS-based time-to-onset analysis, 203 of 520 reports (39.0%) had valid onset data. The median time to onset was 13 days, 70.94% of evaluable reports had onset dates within 30 days, and Weibull analysis suggested an early-failure pattern.

Entrectinib-associated reports in NSCLC showed reproducible neurologic, cardiac, renal, and laboratory-related disproportional reporting signals across FAERS and JADER. These findings may help prioritize early safety monitoring but should be interpreted as hypothesis-generating signals rather than evidence of incidence or causality.

There is an increasing demand for pharmacists in Japan's health care system, particularly in cancer chemotherapy. Task shifting/sharing has enabled clinical pharmacists to take a more active role; however, only a few hospitals have adopted this method, suggesting that institutional factors influence its implementation. Therefore, this study aimed to explore the process of implementing task shifting/sharing from physicians to pharmacists and identify the factors of promoting task shifting/sharing in cancer chemotherapy in Japan.

We conducted semi-structured focus group interviews with hospital pharmacists in management and nonmanagement positions, between February 2023 and May 2024. All interviews were recorded, transcribed, and independently coded by two researchers. A modified grounded theory approach was used, and data collection continued until theoretical saturation was reached.

Data saturation was reached after 10 group interviews and two additional interviews were conducted to ensure the comprehensiveness of the data. Five categories were identified: "Barriers," "Cultural change," "Workflow redesign," "Improving professional knowledge and clinical skills," and "Success of interprofessional collaborative practices." Revisions to medical fees and government notifications facilitated task shifting/sharing; however, most hospitals encountered significant barriers. Three key factors-"Cultural change," "Workflow redesign," and "Improving professional knowledge and clinical skills"-were essential in overcoming challenges and promoting implementation.

This study highlighted the process of promoting task shifting/sharing in cancer chemotherapy. Most participants perceived that this initiative improved patient outcomes and safety and reduced the workloads of health care professionals. To further promote this initiative, it is crucial to evaluate and publish evidence of its effectiveness. Moreover, sustained support from government bodies and professional organizations is vital for broader implementation.