Genomic and DNA methylation-based analyses have transformed the classification of central nervous system (CNS) tumors by enabling robust molecular diagnosis and subclassification. However, these approaches primarily define tumor identity and do not directly capture the functional state of intracellular signaling networks. Proteomic and phosphoproteomic profiling provide complementary molecular layers by measuring protein abundance and site-specific phosphorylation. Recent methodological advances have made a comprehensive analysis of formalin-fixed, paraffin-embedded (FFPE) tissue increasingly feasible, raising the question of how functional proteomic information can complement established molecular diagnostics. Here, we applied an FFPE-compatible workflow for proteomic and phosphoproteomic profiling of ten comprehensively characterized glioblastomas, including five EGFR-amplified and five non-amplified tumors. Mass spectrometry generated robust proteomic and phosphoproteomic coverage across all cases. Global proteomic profiling revealed group-associated protein abundance and pathway differences, including increased EGFR abundance in EGFR-amplified tumors, while showing substantial intertumoral overlap. Protein-abundance-adjusted phosphoproteomic profiles similarly showed partial group-level separation with substantial intertumoral overlap. Differential analysis of protein-abundance-adjusted phosphoproteomic data identified 443 phosphosites based on predefined exploratory statistical criteria. Kinase-substrate enrichment further revealed coordinated EGFR- and SRC-family-associated signaling with marked variability across individual tumors. These findings demonstrate that routine FFPE tissue retains biologically coherent functional information at both the protein abundance and phosphosignaling levels that can be interpreted alongside genomic and epigenomic data. Phosphoproteomics therefore represents an orthogonal functional layer that may complement established molecular characterization of CNS tumors.

This letter comments on a recent review of theranostic lipid nanocarriers for pancreatic ductal adenocarcinoma, identifying three areas of concern in the evidence base. First, the 211-item reference list contains multiple duplicated citations listed under separate numbers with identical content (for example, refs. 6/8, 9/21, 55/89, 106/117, 132/143), a recurring pattern suggesting that the bibliography was not fully verified before submission. Second, Table 6 cites reference markers "[639]" and "[640]" for the NanoSMART and NBTXR3 trials, numbers that exceed the 211-entry reference list and appear to be residual artifacts from a source document with a different numbering scheme. Third, the review reports that NC-6004 (a micellar cisplatin formulation) has completed a phase III trial in combination with gemcitabine but omits the trial's outcome, despite the review's broader argument for the translational viability of lipid- and micelle-based nanocarriers and its extended discussion of nab-paclitaxel as a successful precedent. Reporting this outcome, favorable or not, alongside existing precedents, would allow readers to weigh the review's central claim against the complete record of late-stage clinical testing. While the review offers a valuable catalogue of nanocarrier platforms and regulatory precedents, these issues warrant correction before the citation base is treated as fully reliable.

Ataxia Telangiectasia Mutated (ATM), a central kinase in the DNA damage response, is recurrently altered across these disorders, including myelodysplastic neoplasms (MDS), acute myeloid leukemia (AML), and myeloproliferative neoplasms (MPN), yet its clinical significance remains underrecognized. We conducted a PROSPERO-registered systematic review (CRD420251142673) to evaluate the prognostic and biological impact of ATM alterations in MDS, AML, and MPN. Ten studies met inclusion criteria. In MDS, ATM alterations showed consistent downregulation, hypermethylation, and a predominance of oncogenic missense mutations, with methylation significantly enriched in cases progressing to AML. In AML, reduced ATM gene expression, often driven by miR-100 or miR-181a, was associated with increased blast proliferation, while the ATM genetic variant rs3092856 correlated with chemoresistance and inferior survival. Evidence in MPN/CML, although limited, suggests that ATM polymorphisms, such as rs228593, rs3092856 (C4138T), -5144A>T (rs228589), c.5753G>C, c.346A>G, c.4060C>A, and the germline variant L2307F, contribute to disease susceptibility and adverse prognostic stratification. Collectively, current evidence supports ATM alterations as clinically relevant biomarkers in myeloid malignancies, although their functional role in disease pathogenesis remains incompletely understood.. Rather than establishing ATM merely as a prognostic marker, future efforts should prioritize the characterization of ATM-related therapeutic vulnerabilities and integrate ATM status into treatment-oriented molecular panels to guide precision-based interventions in myeloid diseases.

Purpose To compare the diagnostic performance of superresolution US (SRUS) with that of US and contrast-enhanced US (CEUS) for detecting lymph node (LN) metastasis in rabbits. Materials and Methods US, CEUS, and SRUS were performed in 30 rabbits with 16 egg yolk-induced hyperplastic and 14 VX2 tumor-bearing metastatic LNs. Qualitative US, CEUS, and SRUS features and quantitative SRUS-based parameters of LN microvasculature were analyzed. Major qualitative features and quantitative parameters associated with metastatic LNs were identified, with histopathologic evaluation as reference. Spearman correlation between features and parameters was analyzed. Results Among qualitative features, chaotic microvasculature at SRUS achieved the highest area under the receiver operating characteristic curve of 0.92 (95% CI: 0.81, 1.00), outperforming cortical thickening at US (0.67 [95% CI: 0.51, 0.82]; P = .012), arterial phase enhancing pattern at CEUS (0.72 [95% CI: 0.57, 0.86]; P = .018), and SRUS vascular pattern (0.72 [95% CI: 0.55, 0.89]; P = .028). Among quantitative parameters, fractal dimension yielded the optimal area under the receiver operating characteristic curve of 0.92 (95% CI: 0.79, 1.00), outperforming vessel density (0.70 [95% CI: 0.48, 0.88]; P = .046), flow-weighted vessel density (0.70 [95% CI: 0.49, 0.88]; P = .046), and direction entropy (0.71 [95% CI: 0.51, 0.89]; P = .046). Chaotic microvasculature and fractal dimension were strongly correlated (ρ = 0.80; P < .001), and both correlated well with microvascular density (ρ = 0.82 and 0.65, respectively; both P < .001). Conclusion Chaotic microvasculature and fractal dimension assessed at SRUS showed improved diagnostic performance for detecting metastatic LNs in rabbits compared with US and CEUS and enabled noninvasive evaluation of microvascular tortuosity. Keywords: Ultrasound-Contrast, Ultrasound Supplemental material is available for this article. © The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license.

Cervical cancer remains an important public health problem. Prevention relies on vaccination against human papillomavirus (HPV) and Pap smears for early detection of precursor lesions. Both strategies should be implemented at appropriate intervals. However, the COVID-19 pandemic led to delays in preventive care, which may have negatively impacted cervical cancer (CC) indicators. Therefore, this study aims to assess the impact of the pandemic on the CC prevention program in Sao Paulo State, Brazil, using data from a public health database. An ecological study was conducted using quantitative data on HPV vaccination and Pap smears obtained from DATASUS between 2016 and 2021. Municipalities were grouped into clusters according to population size and their performance during 2020 and 2021 (increase or decrease in preventive services) and were compared according to socioeconomic variables. HPV vaccination rates increased in 2020, but this trend was not sustained in 2021. Regarding Pap smears, most municipalities experienced a decline in 2020, followed by an increase in 2021. Municipalities with the poorest socioeconomic indicators struggled to recover in 2021. The number of COVID-19 cases was not strongly associated with variations in preventive practices. CC prevention strategies were affected by the drop in HPV vaccination in 2021 and the postponement of routine screening during the most critical period of the pandemic, especially in the most vulnerable municipalities, which experienced a slower recovery. These findings suggest that the Brazilian healthcare system faced great challenges in both maintaining and restoring preventive care during a public health crisis.

Natural killer (NK) cell neoplasms span indolent to highly aggressive entities, and flow cytometric immunophenotyping is central to their detection and classification. However, distinguishing reactive from neoplastic NK cell expansions can be challenging because NK cells lack somatically recombined antigen receptors, and reactive states may produce restricted phenotypes that mimic clonality. This best-practices manuscript outlines a practical, flow cytometry-based approach to NK cell analysis that integrates (i) robust lineage definition and gating, (ii) subset-aware interpretation of CD16/CD56 patterns, (iii) inference of clonality using killer cell immunoglobulin-like receptor (KIR; CD158) repertoire restriction and other NK cell receptors. We highlight key pitfalls-particularly the limited utility of KIR-based clonality inference in CD56^brightCD16^- NK cells and the potential for adaptive NK cell expansions to appear KIR-restricted-and propose an operational reflex algorithm triggered by NK cell expansion and/or defined immunophenotypic abnormalities in screening tubes. Case-based examples illustrate common scenarios, including NK-large granular lymphocytic leukemia, extranodal NK/T-cell lymphoma with circulating CD56^brightCD16^- cells, reactive adaptive NK cell expansions, and concurrent neoplastic and reactive NK clones. This framework supports standardized, reproducible NK cell assessment and improves specificity of flow-based clonality inference in routine clinical practice.

This study aimed to investigate the role and molecular mechanisms of origin recognition complex 1 (ORC1) in Cisplatin resistance and tumor stemness in non-small cell lung cancer (NSCLC), and to evaluate its potential as a target for reversing chemotherapy resistance. ORC1 expression and its clinical significance in NSCLC were analyzed using TCGA and GTEx databases. ORC1-knockdown NSCLC cell lines and Cisplatin-resistant A549 DDP cells were established. Colony formation, Transwell, tumor sphere formation, and flow cytometry assays were performed to assess proliferation, invasion, stemness, and drug resistance phenotypes. A subcutaneous xenograft model in nude mice was used to evaluate the in vivo antitumor efficacy of lentivirus-mediated ORC1 knockdown combined with Cisplatin. Protein expression levels of stemness markers (LGR5, NANOG, CD44), the resistance-associated protein P-gp, and EMT-related proteins were detected by Western blotting. ORC1 was significantly overexpressed in NSCLC tissues and resistant cells, and its expression positively correlated with poor prognosis and tumor stemness markers. ORC1 knockdown markedly inhibited proliferation, invasion, EMT, and sphere-forming capacity, and downregulated stemness-associated proteins. In A549 DDP cells, ORC1 knockdown reduced the Cisplatin IC₅₀, restored chemosensitivity, downregulated MDR1/P-gp, and enhanced Cisplatin-induced apoptosis. In vivo, ORC1 knockdown combined with Cisplatin significantly suppressed resistant tumor growth, reduced the proportion of CD133⁺CD44⁺ cancer stem cells, and promoted apoptosis. ORC1 mediated Cisplatin resistance in NSCLC by regulating tumor stemness and EMT. Targeted silencing of ORC1 effectively reversed resistance both in vitro and in vivo, representing a potential molecular target for overcoming Cisplatin resistance in NSCLC.

The present study aimed to characterize the expression pattern and biological function of sphingosine‑1‑phosphate phosphatase 1 (SGPP1) in esophageal squamous cell carcinoma (ESCC), investigate its potential molecular regulatory mechanisms, and evaluate its clinical value as a prognostic biomarker and therapeutic target. SGPP1 expression in ESCC cell lines was assessed by reverse transcription‑quantitative PCR and western blotting. Models of SGPP1 overexpression in KYSE150 cells and SGPP1 knockdown in ECA109 cells were established. 5‑Ethynyl‑2'‑deoxyuridine, Cell Counting Kit‑8, colony formation, terminal deoxynucleotidyl transferase dUTP nick‑end labeling, wound healing and Transwell assays were performed to systematically analyze the effects of SGPP1 on ESCC cell proliferation, apoptosis, migration and invasion. The Cancer Genome Atlas‑ESCC data were integrated with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, gene set enrichment analysis and UpSet plotting to identify key downstream pathways and candidate target genes. SGPP1 protein expression was evaluated by immunohistochemistry in tumor tissues from 68 patients with ESCC, and Cox regression analysis was used to assess its association with patient prognosis. The results demonstrated that SGPP1 expression varied markedly among ESCC cell lines, with low expression in KYSE150 cells and high expression in ECA109 cells. SGPP1 overexpression significantly inhibited ESCC cell proliferation, migration and invasion, and increased apoptosis‑associated DNA fragmentation, whereas SGPP1 knockdown produced the opposite effects. Mechanistically, the data suggested that SGPP1 modulates extracellular matrix remodeling and xenobiotic metabolism, potentially through negative regulation of UGT1A9 and UGT2B28 expression. Clinically, low SGPP1 expression was an independent risk factor for poor prognosis in patients with ESCC (HR=6.016, 95% CI: 3.143‑11.513, P<0.001), and the overall survival was significantly longer in the high‑expression group than in the low‑expression group (P<0.001). In conclusion, SGPP1 functions as a tumor suppressor gene in ESCC and may inhibit tumor progression by regulating UGT1A9/UGT2B28‑mediated metabolic pathways. SGPP1 may therefore serve as a prognostic biomarker and a potential therapeutic target in ESCC.

Quinoline derivatives are a class of heterocycles featuring a fused benzene‑pyridine scaffold that have attracted notable interest in anticancer drug discovery owing to their favourable physicochemical properties, structural versatility and broad biological activities. Accumulating evidence indicates that quinoline‑based compounds exert antitumour effects through several targets and pathways, including via epigenetic regulation, interference with DNA topology, inhibition of signalling pathways, immune modulation, induction of autophagy and targeting of the cytoskeleton. Structure‑activity relationship (SAR) analyses demonstrate that the electronic effects and steric configurations of substituents on the quinoline ring critically determine potency, selectivity and metabolic stability. In particular, oxygenated, halogenated and strongly electron‑withdrawing groups, as well as nitrogen‑containing heterocyclic substituents, enhance hydrophobic interactions or hydrogen bonding with biological targets, thereby improving inhibitory efficacy. Consequently, the quinoline scaffold has emerged as a rated structural motif in anticancer lead compound discovery. Multidimensional optimisation strategies have been proposed to improve the pharmacokinetic profiles and clinical applicability of quinoline derivatives. Nanocarriers and smart stimuli‑responsive delivery systems markedly enhance solubility, circulation time and tumour targeting, whereas prodrug approaches employing enzyme‑sensitive, pH‑responsive or redox‑activated linkers enable selective activation at tumour sites. Combination therapies also exploit the multi‑pathway activity of quinoline derivatives, enhancing antitumour responses and delaying resistance when combined with immunotherapy, chemotherapy or radiotherapy. Furthermore, artificial intelligence and machine learning approaches have shown increasing utility in virtual screening, quantitative structure‑activity relationship modelling and multi‑objective optimisation, accelerating the identification of potent, low toxicity and synthetically accessible candidates. Overall, quinoline derivatives offer systemic advantages as multi‑target anticancer agents. The present review summarises recent advances in molecular mechanisms, SAR insights and drug design strategies, providing a comprehensive framework for advancing quinoline‑based agents towards next‑generation precision anticancer therapies.

Gastric cancer (GC) is one of the most common malignant tumors worldwide. Metabolic reprogramming and epigenetic dysregulation represent its key pathological characteristics. As a novel lactate‑mediated post‑translational modification, lactylation converts metabolic signals into epigenetic and protein functional regulation, and it is extensively and aberrantly activated in GC. Lactylation drives the malignant progression of GC by promoting cell proliferation, invasion, metastasis and stemness. In addition, lactylation suppresses antitumor immune cell functions, and mediates immune escape and therapeutic resistance. Clinically, global lactylation levels and specific lactylation sites can serve as independent prognostic biomarkers, and corresponding risk models enable prognostic stratification and prediction of immunotherapy response. Intervention strategies targeting lactate production, lactyltransferases and downstream effector axes have emerged as promising directions for GC treatment. The present review summarizes the regulatory mechanisms, biological functions and clinical translational value of lactylation in GC, aiming to provide novel insights for precision diagnostics and therapeutics.