Brain tumors are among the most aggressive and hard-to-treat cancers, characterized by poor prognosis and high resistance to conventional therapies. In this study, we explore the potential dual role of Cefamezin (cefazolin)-a widely used antibiotic in treating a broad range of infections in two high-grade cancer cell models: glioblastoma (LN-18) and neuroblastoma (SH-SY5Y). By investigating the impact of cefazolin on cancer cell viability and its interaction with chemotherapeutic agents, we aim to uncover how antibiotics, typically used to combat infections, might influence cancer treatment outcomes. In this study, the metabolic activity of SH-SY5Y and LN-18 cells under irinotecan, cefazolin, and combined treatment conditions was assessed using the MTT assay. In addition, cell cycle phase distribution and cell death-associated changes were evaluated by flow cytometry. Irinotecan induced significant cytotoxicity in both cell lines and increased the proportion of Sub G0/G1 cells while causing arrest in the S and G2/M phases. Co-treatment with cefazolin attenuated the inhibitory effects of irinotecan on cell viability and partially attenuated irinotecan-induced changes in cell cycle distribution. In SH-SY5Y cells, irinotecan-induced cytotoxicity and cell cycle disruption were reduced in the presence of cefazolin. In LN-18 cells, cefazolin partially attenuated the effects of irinotecan on cell viability, while necrosis rates were not significantly altered. These findings suggest that cefazolin may antagonize the cytotoxic effects of irinotecan in vitro. This study highlights the potential for antibiotic-chemotherapy interactions and underscores the need for further validation in in vivo and clinically relevant models.

Conventional radiotherapy target delineation for glioblastoma (GBM) includes an isotropic expansion from gross tumor visible on anatomic MRI to an empirically defined clinical target volume (CTV) for coverage of microscopic infiltrative disease. GBM spreads preferentially along white matter tracts, but this information has not previously been systematically incorporated into radiotherapy planning. We investigated using white matter tractography from diffusion-weighted MRI (dwMRI) to inform target delineation.

Thirteen patients with GBM underwent 55-directional dwMRI at the time of post-operative radiation planning MRI. Whole-brain tractography was performed, and streamlines passing within 5 mm of gross disease were used to generate maps representing white matter path length from gross disease. Clinical target volumes were generated using tractography (CTV_tract) and conventional isotropic expansion (CTV_isotropic). MRI at time of GBM recurrence was registered to the radiation planning MRI, and coverage of the recurrence volume was compared between CTV_tract and CTV_isotropic.

CTV_tract demonstrated non-isotropic expansion of the primary tumor along regional white matter tracts while respecting natural anatomic boundaries. CTV_tract volumes using a 2 cm path-length were a median of 67 cc smaller (-19%) than the paired 2 cm CTV_isotropic volumes (p = 0.003). 10/13 recurrence volumes were included in CTV_isotropic, while 12/13 recurrence volumes were included in CTV_tract.

Tractography can be used to define CTV that may provide superior coverage of areas at risk of recurrence while simultaneously reducing target volume.

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.