BACKGROUND Methotrexate-induced encephalopathy is an uncommon but potentially serious neurotoxic complication of high-dose methotrexate therapy. Its clinical and radiological features can closely resemble acute ischemic stroke, leading to diagnostic confusion and unnecessary interventions. Early recognition is crucial to prevent mismanagement and ensure appropriate care. CASE REPORT We report a 16-year-old girl with high-grade osteosarcoma of the distal femur who developed sudden neurological symptoms, beginning with dysphasia and cognitive slowing, progressing within 1 hour to global aphasia and altered consciousness following high-dose methotrexate infusion. Laboratory findings were normal. Magnetic resonance imaging performed 2 hours after symptom onset revealed bilateral diffusion restriction in the centrum semiovale, without corresponding fluid-attenuated ınversion recovery (FLAIR) abnormalities, suggestive of acute ischemia. Intravenous thrombolysis with alteplase (0.9 mg/kg) was administered, but subsequent imaging showed shifting diffusion abnormalities without vascular occlusion, inconsistent with stroke. Methotrexate was withheld, and supportive care alone led to complete neurological recovery within 3 days. The patient resumed chemotherapy 1 week later and remained asymptomatic at 1-year follow-up. CONCLUSIONS Methotrexate-induced encephalopathy is an important stroke mimic in oncology patients. Diffusion restriction without FLAIR changes and a reversible clinical course help distinguish it from true ischemic stroke. Awareness of this condition is essential, as full recovery can occur with supportive care alone, without the need for specific therapeutic interventions.

The excellent biocompatibility and tunable optical properties of carbon dots make them highly promising for applications in photodynamic therapy (PDT). However, effectively enhancing their photodynamic performance remains a significant challenge. This work employed methylene blue and metformin as precursors along with three trace metal elements ion (Fe3+, Zn2+ and Cu2+) to synthesize carbon dots (CDs, FeCDs, ZnCDs and CuCDs) via a one-step hydrothermal method.

The menin-lysine methyltransferase 2A acute leukemia (KMT2A) protein-protein interaction has emerged as a clinically validated epigenetic target in acute leukemia, following the approval of the reversible menin inhibitor Revumenib for KMT2A-rearranged and nucleophosmin 1 (NPM1)-mutant disease. This success transformed a once "undruggable" interface into a tractable binding pocket, triggering the rapid expansion of medicinal-chemistry strategies aimed at achieving deeper and more durable transcriptional reprogramming. This review analyzes the full menin-inhibitor landscape from a medicinal-chemistry perspective, integrating reversible, covalent, and degrader-oriented modalities within a unified structure-activity framework. We highlight how scaffold architecture, pocket occupancy, electrophile placement toward Cys329, and polarity tuning control binding mode, residence time, metabolic stability, resistance susceptibility, and pharmacodynamic durability. Across all chemical classes, sustained target engagement-rather than equilibrium affinity alone-emerges as the dominant determinant of antileukemic efficacy. By integrating structure-activity relationship (SAR), resistance mechanisms, safety considerations, and translational scope across oncology and metabolic indications, this review provides a roadmap for the rational design of next-generation menin inhibitors and establishes menin as a model system for modern epigenetic drug discovery.

Marine organisms are considered as a reservoir of diverse metabolites with unique skeletons and multifaceted biological activities. Marine organisms, including Xenia, Cespitularia, and Heteroxenia, have been extensively studied in recent decades to explore their activities. Species of the genus Heteroxenia play a robust ecological role and afford a wide array of metabolites, including steroids, sesquiterpenoids, diterpenoids, and lipid derivatives with notable bioactivities as cytotoxic, antiviral, antimicrobial, and anti-inflammatory properties primarily based on in vitro studies. Fourteen compounds were isolated and their structures were elucidated based on NMR data and mass spectrometry. Most of these metabolites possess rare or uncommon structural frameworks such as gorgostane- and androstane-type steroids, and verticillane diterpenoids with an unusual C-6/C-12 skeleton, which are infrequently reported from marine sources. This review provides a comprehensive overview of Heteroxenia corals, highlighting their ecological role, metabolites isolated from Heteroxenia species, with emphasis on their 13C NMR spectroscopic features and reported bioactivities. This integrative approach provides a chemotaxonomic spectroscopic framework and identifies research gaps, that support future natural product discovery and pharmacological investigations of Heteroxenia species, while acknowledging that ecological function and general bioactivity do not necessarily predict direct therapeutic applicability and require further validation of selectivity and safety.

Immune checkpoint inhibitors (ICIs) targeted PD-1/PD-L1 axis generate immune-related adverse events such as myocarditis, limiting their clinical application. Herein, we tried to explore the potential mechanism of ICIs-induced myocarditis. We performed single-cell RNA sequencing of heart tissues and peripheral blood mononuclear cells (PBMC) collected from mice with or without a relative low dose of PD-1/PD-L1 inhibitor (BMS-1) treatment. Compared with PBS treatment, BMS-1 treatment increased T, B, NK cells, and neutrophils but decreased macrophages in the heart. Four T cell subclusters in the heart were identified, including Treg, LEF1+CD4+ T, CCL5+CD8+ T, and STMN1+CD8+ T cells. The BMS-1-heart exhibited increased CCL5+CD8+ T cells depicted by elevated Nkg7 and Ccl5 gene expression compared with the PBS-heart. The number of macrophages declined but revealed inflammatory activity in the BMS-1-heart. Interestingly, CCR5, a receptor for CCL5 expressed in both CCR2- resident and CCR2+ recruit macrophages in the heart, was upregulated by the BMS-1 treatment. In addition, fibroblasts, not endothelial cells, showed an inflammatory activation state. Last, we identified increased CCL5+CD8+ T cells in the BMS-1-PBMC. Immunofluorescence staining also confirmed significantly elevated CCL5+CD8+ T cells in the BMS-1-heart than that of PBS-heart. BMS-1 seems to recruit circulating CCL5+CD8+ T cells to the heart, which further interact with CCR5+ macrophages, resulting in fibroblast activation. The CCL5/CCR5 axis and circulating CCL5+CD8+ T cells may be potential therapeutic/diagnostic strategies for ICIs-induced myocarditis.

3-Mercaptopyruvate sulfurtransferase (3-MST), a key enzyme in sulfur metabolism, has recently gained attention as a potential anticancer target. However, reported 3-MST inhibitors remain limited, motivating the exploration of new scaffolds such as natural products. In this study, a library of 3744 natural products was virtually screened against human 3-MST using DiffDock (diffusion-model-based docking) followed by AutoDock Vina docking. Top-ranking candidates were further analyzed via molecular dynamics simulations and Molecular Mechanics Poisson-Boltzmann Surface Area binding free energy calculations. Methylophiopogonanone A (4), Daphnoretin (5), and L-asarinin (9) exhibited stable binding with favorable energetics, displaying binding free energies comparable to the reference ligand 7NC301. Binding mode analyses revealed that Methylophiopogonanone A primarily engaged in hydrophobic interactions, whereas Daphnoretin and L-asarinin formed extensive polar contacts, accompanied by higher desolvation penalties. In vitro cytotoxicity assays showed that Methylophiopogonanone A and L-asarinin reduced HCT116 cell viability by 40.3% and 26.3% at 25 µM, which is consistent with their inhibitory of 3-MST with IC50 = 5.83 ± 0.69 µM and IC50 = 19.11 ± 3.37 µM, respectively. These results suggested that the natural products identified in this study represent promising scaffolds for further optimization as potential 3-MST inhibitors. This work provides an AI-guided natural-product screening workflow for 3-MST and delivers prioritized inhibitor scaffolds for subsequent optimization and experimental validation.

Geraniol (GI), an acyclic monoterpene alcohol, exhibits diverse anti-cancer activities. However, its potential effects against gastric cancer remain poorly understood.

To assess the incidence of delayed chemotherapy-induced nausea and vomiting (CINV) and identify key risk factors among adult patients.

Identifying the mechanisms underlying resistance to immune checkpoint inhibitors (ICIs) has become a major focus in cancer immunotherapy. Our previous work identified F2RL1 expression, encoding the G protein-coupled receptor Protease-Activated Receptor-2 (PAR-2), as a negative biomarker of ICIs responsiveness. This study aims to evaluate the therapeutic potential of targeting PAR-2 to overcome resistance to ICIs.

Immune exclusion inhibits antitumor immunity and response to immunotherapy, but its mechanisms remain poorly defined. In triple-negative breast cancer (TNBC), an aggressive and generally immune-rich subtype, an immune-cold microenvironment predicts poor prognosis due to a limited response to chemotherapy and immune checkpoint inhibitors. This study aimed to identify mechanisms regulating immune infiltration in TNBC.

Oxaliplatin is widely used in the treatment of gastric and gastro-oesophageal junction cancer. However, oxaliplatin-induced nausea and vomiting often complicate treatment and negatively affect patients' quality of life. The current standard antiemetic regimen-dexamethasone (DEX) plus palonosetron-offers only limited efficacy, benefiting approximately 70% of patients, and is associated with steroid-related adverse effects, including insomnia and gastrointestinal bleeding. Consequently, there is a clear clinical need for effective DEX-free antiemetic regimens. This study aims to evaluate the efficacy and safety of megestrol acetate versus DEX in preventing oxaliplatin-induced nausea and vomiting in patients with gastric or gastro-oesophageal junction cancer.

Immunotherapy combined with chemotherapy is a standard treatment for advanced non-small cell lung cancer (NSCLC). However, the comparative efficacy and safety of cost-efficient modified PD-1 inhibitors remain incompletely characterized. This study aimed to determine the optimal choice for the 3 most commonly used modified PD-1 inhibitors-tislelizumab, sintilimab, and camrelizumab-combined with chemotherapy in locally advanced or metastatic NSCLC.

Photodynamic therapy (PDT) is an anti-cancer therapy that employs a photosensitizer (PS) and an optimal wavelength of light, causing a photochemical reaction that releases reactive oxygen species, thereby inducing cancer cell death via oxidative stress. Because light irradiation is limited to the tumor site, PDT has minimal adverse effects. The cancer cell selectivity of the PS is important for reducing damage to the normal mucosa caused by scattered light. Antibody-drug conjugates (ADC) are novel anti-cancer therapies that combine a monoclonal tumor-surface-receptor-targeting antibody with a drug bonded through chemical linkers. ADCs enable the targeted delivery of a variety of drugs to cancer cells while minimizing their delivery to healthy tissues. One such tumor surface receptor is the human epidermal growth factor receptor 2 (HER2), which is of interest in the treatment of many cancers, including gastrointestinal cancer. To improve tumor selectivity and minimize damage to the mucosa surrounding the tumor in PDT, we established a novel PS glucose-linked chlorin e6-conjugated trastuzumab (G-Ce6-trastuzumab) that is conjugated to existing PS glucose-linked chlorin e6 (G-Ce6) and evaluated its anti-cancer effect compared to G-Ce6. The effect of PDT was evaluated using HER2-high-expression cells NCI-N87 and HER2-low-expression cells MKN-45. G-Ce6-trastuzumab is internalized by the intracellular organelles in cancer cells. Evaluation of cell death using the WST-8 assay also demonstrated a significantly higher cytotoxic effect of G-Ce6-trastuzumab in HER2-high-expression cells compared with conventional PS G-Ce6. Thereby, G-Ce6-trastuzumab may be an excellent novel PS for PDT because of its strong selectivity for HER2-high-expression cells.

Hepatocellular carcinoma (HCC) has a very significant mortality rate and is one of the most common cancers worldwide. Jacaranda mimosifolia is reported to have potential antitumor activities against various human cancers. However, the effects of J. mimosifolia on HCC are yet elusive. This study aimed to investigate the anti-HCC potential of methanolic extract of J. mimosifolia leaves using in vitro and in vivo studies and a network pharmacology approach. The effect of J. mimosifolia extract was assessed on Huh-7.5 cells using MTT assay, wound healing assay, and DNA fragmentation assay. These experiments found that J. mimosifolia extract significantly suppressed Huh-7.5 cell proliferation, impaired cell migration, and induced cell apoptosis. The real-time PCR validated the upregulation of p53 and Bax, alongside the downregulation of AFP and GPC3 in Huh-7.5 cells after treatment with J. mimosifolia extract. In vivo experiments confirmed the hepatoprotective effects of J. mimosifolia extract in mice models with CCl4-induced hepatic injury. In addition, through network pharmacological analysis, J. mimosifolia was found to play a critical role against HCC via targeting multiple potential targets and pathways. Docking analysis identified apigenin and kaempferol with the lowest binding energy against PTGS2 and EGFR, respectively, while flavonol glycoside showed the lowest binding energy against MMP9. However, detailed research is needed to isolate the potential phytochemicals from J. mimosifolia against HCC.

Microcephalin-1 (MCPH1) is a tumour suppressor protein that regulates homologous recombination repair (HRR) and is down-regulated in several tumour types. Given that HRR-defective cancer cells can be killed via synthetic lethal approaches, MCPH1 thus represents an attractive target in cancer therapy. Functionally, cells lacking MCPH1 have reported defects in the recruitment and retention of BRCA2 and RAD51 to DNA double strand breaks (DSBs) during HRR, though the magnitude of this defect in human cells is not entirely clear. Multiple studies have demonstrated that HRR-defective cells, particularly those lacking BRCA1 and BRCA2, can be specifically killed by inhibitors of the base excision repair enzyme, poly(ADP-ribose) polymerase-1 (PARP-1). Mechanistically, PARP-1 inhibition can cause (i) elevated DNA single strand breaks (SSBs) and (ii) 'PARP-1 trapping' on damaged DNA, both of which can lead to the formation of DSBs during DNA replication, which would normally be repaired by HRR. Given the functional link between MCPH1 and BRCA2, this study aimed to compare HRR-deficiency in cells lacking either protein and correlate this with PARP-1 inhibitor sensitivity. Our data shows that MCPH1-deficient cells are defective in HRR but still retain ~50% activity and this results in little to no sensitivity to two clinically-relevant PARP-1 inhibitors. In contrast, BRCA2-deficient cells showed a far greater defect in HRR and consistent sensitivity to both PARP-1 inhibitors, which was not enhanced by co-depletion of MCPH1. These data suggest that the magnitude of HRR defect in cancer cells influences PARP-1 inhibitor sensitivity and BRCA2 retains significant functionality in the absence of MCPH1.

Fruquintinib, a targeted therapeutic agent approved in 2018 for the treatment of metastatic colorectal cancer, is gradually being applied in an expanding range of clinical settings. Given the complexities associated with real-world dosing, a comprehensive evaluation of its safety profile is essential for optimizing clinical decision-making. We conducted a retrospective pharmacovigilance study utilizing a spontaneous reporting system. Reports related to Fruquintinib were extracted through a standardized data cleaning process and cross-validated using 3 complementary signal detection algorithms: proportional reporting ratio, Bayesian confidence propagation neural network, and reporting odds ratio (ROR). This approach was employed to systematically assess the drug's safety and identify potential adverse event signals. A total of 92 statistically significant safety signals were identified from 1188 independent cases included in the analysis, corresponding to 1836 adverse event reports. The signal distribution exhibited organ system specificity, with gastrointestinal reactions being the most prevalent category. These reactions primarily manifested as typical drug-related toxicities, including diarrhea and nausea. Other notable complications included neurological, respiratory, dermatological, renal, and cardiovascular events. Important aes not mentioned in the instructions, such as bone marrow suppression (ROR = 11.17), peripheral neuropathy (ROR = 4.24) and dehydration (ROR = 3.98), were also discovered. This study systematically characterizes the post-marketing safety profile of Fruquintinib through a multi-algorithm synergistic analysis, confirming that its safety profile aligns with the clinically expected outcomes based on its mechanism of action. Future research should focus on analyzing drug interaction mechanisms and exploring biomarkers to develop a precise risk-benefit assessment model.

Leuprolide and Goserelin, both gonadotropin-releasing hormone (GnRH) agonists, are commonly used for ovarian function suppression and the management of hormone-dependent cancers. However, systematic comparisons of their adverse event (AE) profiles based on real-world pharmacovigilance data remains limited. This study aimed to compare the safety signals associated with Leuprolide and Goserelin using the the U.S. Food and Drug Administration AE Reporting System (FAERS), thereby providing insights into their distinct AE patterns. Food and Drug Administration Adverse Event Reporting System reports from the first quarter of 2004 to the third quarter of 2024 were extracted and standardized. Disproportionality signal detection was performed using the reporting odds ratio, proportional reporting ratio, chi-square (χ2) test, and Bayesian confidence propagation neural network. Significant signals were defined as reporting odds ratio lower 95% CI >1, proportional reporting ratio ≥2 with χ2 ≥4, or Bayesian confidence propagation neural network information component (IC)-2SD >0. Key signals were compared between Leuprolide- and Goserelin-related reports. A total of 12,418,989 AE reports were identified, including 64,324 Leuprolide-related and 4253 Goserelin-related cases. Both drugs showed strong signals for "prostatic specific antigen increased" (Leuprolide: χ2 = 84,009.65, IC-2SD = 5.42; Goserelin: χ2 = 820.31, IC-2SD = 3.38), "blood testosterone increased" (Leuprolide: χ2 = 22,845.52, IC-2SD = 5.56; Goserelin: χ2 = 290.23, IC-2SD = 2.28), and "prostatic specific antigen abnormal" (Leuprolide: χ2 = 51,615.98, IC-2SD = 6.46; Goserelin: χ2 = 422.43, IC-2SD = 2.16). Additional strong signals, such as "prostate cancer metastatic" and "hot flush," were consistently detected in both groups. Notably, the distribution of AEs differed between drugs, suggesting drug-specific safety patterns. Leuprolide demonstrated strong associations with AEs in "Reproductive system and breast disorders," "Neoplastic benign and malignant conditions," and procedure-related categories, whereas Goserelin was more strongly linked to "Endocrine disorders." These findings highlight distinct pharmacovigilance profiles between the 2 drugs and provide clinically relevant evidence to support individualized risk monitoring in hormone-dependent cancer therapies.

The clinical use of nivolumab has significantly improved the prognosis for survival in patients with a wide range of advanced malignancies. Given the increased incidence of tumors, there is a need to gain insight into the true extent of adverse events (AEs) associated with the nivolumab drug in the middle-aged and elderly population. This pharmacovigilance study was based on an analysis of reports from the US Food and Drug Administration's adverse event reporting system for the period January 1, 2014 to December 31, 2024, and compared AEs of the drug nivolumab in the middle-aged and elderly populations using proportional reporting ratio, reporting odds ratio, BCPN, and multi-item gamma Poisson shrinker methods. The analyses showed the presence of AEs in a variety of systems, mainly involving several systems such as endocrine disorders, nervous system disorders, skin and subcutaneous tissue disorders. The immune-related AEs listed in the package insert were validated by us and their clinical significance warrants careful consideration to further guide clinical dosing, adjust therapeutic decision-making, and develop age-adapted dosing algorithms for population pharmacokinetic development in order to minimize potential risks to patients. With the exception of reports of an unspecified nature, a greater proportion of the sample was male (65.7%) than female (32.5%), indicating significant variations. The highest percentage of reports was observed in patients aged between 65 and 85 years and in patients with a body mass index ranging from 50 to 100 kg/m2. The primary indication was non-small cell lung cancer. The top 3 AE signals reported with nivolumab were malignant neoplasm progression, death, and pyrexia, with the majority of AE cases occurring within the first month following nivolumab initiation.

Thalidomide represents one of the most instructive case studies in modern medicinal chemistry, embodying both a historic pharmaceutical tragedy and a remarkable example of drug repurposing and molecular reinvention. Initially introduced as a sedative and antiemetic, its catastrophic teratogenic effects reshaped global drug regulatory frameworks. Decades later, renewed investigation uncovered potent immunomodulatory, anti-inflammatory and antiangiogenic activities, leading to its controlled clinical use in erythema nodosum leprosum, multiple myeloma and related disorders. Central to this renaissance was the identification of cereblon as a key molecular target, transforming thalidomide and its analogs into versatile chemical tools for targeted protein degradation. This review provides a comprehensive overview of thalidomide from a synthetic and medicinal chemistry perspective, covering classical and modern synthetic strategies, access to analogs, stereochemical considerations and asymmetric approaches. Particular emphasis is placed on thalidomide-derived cereblon binders in PROTACs and molecular glue technologies. Beyond protein degradation, the diverse biological activities of thalidomide are discussed, including modulation of cytokines, angiogenesis, and immune signaling pathways. Collectively, thalidomide exemplifies how mechanistic insight, synthetic innovation and careful risk-benefit evaluation can transform a once-discarded molecule into a cornerstone of contemporary drug design.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the immunohistochemical images shown in Fig. 1A on p. 1377, the 'DNMT3A' and 'DNMT3B' images for the 'BN' row of data contained an overlapping section, such that date which were intended to show the results from differently performed experiments had apparently been derived from the same original source. In addition, upon performing an independent analysis of the data in this paper in the Editorial Office, it came to light that the same data had been included for the Petri dish images in Fig. 3B on p. 1382 for the DMSO experiments with the T24 and EJ cell lines, albeit the EJ image had been rotated through 90°. The authors were contacted by the Editorial Office to offer an explanation for this apparent duplication of data within these figures; however, up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [Oncology Reports 35: 1375‑1384, 2016; DOI: 10.3892/or.2015.4492].