Aim: Validate the association RAD18 Arg302Gln (rs373572) and OGG1 Ser326Cys (rs1052133) - with Renal Cell Carcinoma (RCC) susceptibility and histopathological characterization.

Aim: To evaluate E-cadherin expression in various clinical and pathological prognostic scenarios to determine its significance in the development of molecular subtypes of invasive ductal breast cancer.

MammaPrint (MP), a 70-gene expression profile assay, informs treatment decisions in early-stage breast cancer by classifying patients into high or low risk of recurrence categories. However, racial disparities in breast cancer outcomes necessitate an evaluation of MP's prognostic utility across diverse populations. This study explores differences in MP scores and associated outcomes among women of various racial backgrounds.

As treatment options for advanced non-small cell lung cancer (NSCLC) evolve, biomarkers are needed to guide therapy selection while balancing efficacy and toxicity. Although tumor burden is a promising candidate, its prognostic role in guiding epidermal growth factor receptor (EGFR)-targeted kinase inhibitor (TKI) therapies remains understudied in real-world settings.

To identify demographic, ultrasonographic and cytological features that could improve the management of thyroid nodules with indeterminate cytology.

Meningeal carcinomatosis (MC) is a severe complication of systemic cancers. Although typical presentations involve meningeal irritation or cranial nerve deficits, its manifestation as rapidly progressive dementia (RPD) in the absence of classic signs is exceedingly rare. This complication poses a substantial diagnostic challenge, especially when the primary tumor remains occult.

Bladder cancer is prevalent worldwide; however, the detailed mechanisms underlying its initiation and progression remain incompletely understood. This study aimed to investigate the expression levels of long noncoding RNA activated by transforming growth factor-β (lncRNA-ATB) and microRNA-200c (miR-200c) in tumor tissues of patients with bladder cancer and to explore their association with clinicopathologic features.

Lung cancer treatment presents a major challenge globally. The advent of monoclonal antibodies (mAbs) has ushered in a new era in the treatment of non-small cell lung cancer (NSCLC). This study aimed to investigate the impact of the addition of mAbs to platinum-based doublet therapy on overall survival in NSCLC patients and the difference in median survival among patients treated with different treatment protocols. In this study, demographic, clinical, and therapeutic data from 359 NSCLC patients were recorded, and the histopathological and disease stages of the patients, along with the site of metastasis, were documented. The median survival rates, 1-, 3-, and 5-year survival rates, covariate hazard ratios, and independent predictors of overall survival were analyzed. Statistically significant differences were observed in the median survival of patients treated with different treatment protocols (p = 0.002). Comparing therapies, patients treated with carboplatin/paclitaxel+anti-PD-1/anti-PD-L1 mAb or cisplatin/vinorelbine+anti-PD-1/anti-PD-L1 mAb had highest median survival (median survival months ± SE) (49.4 months ± 9.15 and 34.9 months ± 8.61 respectively) with lowest hazard ratio (HR = 0.032; 95% confidence interval (CI) [0.003-0.310], p = 0.003 and HR = 0.048; 95% CI [0.005-0.465], p = 0.0083 respectively). Patients treated with triple therapy [platinum-based doublet chemotherapy combined with mAb drugs had significantly (p = 0.01) greater median survival (20.7 months ± 3.11; HR = 0.593; 95% CI [0.443-0.794], p = 0.00046) compared to patients treated with platinum-based doublet chemotherapy with concurrent radiation (13.6 months ± 3.8; HR = 0.742 95% CI, [0.531-1.035], p = 0.07884] or patients treated with platinum-based doublet chemotherapy (9.1 months ± 0.68; HR = 1) or single treatment (12.9 months ±3.81; HR = 0.927; 95% CI [0.629-1.365], p = 0.69970) and better 1-, 3-, and 5-year survival rates (95% CI) [66.20% (0.554-0.77), 26.40% (0.162-0.366), and16.25% (0.065-0.261) respectively] than patients treated with platinum-based doublet chemotherapy with concurrent radiation [54% (0.403-0.677), 22% (0.104-0.336), and 4% (0.001-0.079) respectively] or without concurrent radiation [39.10% (0.324-0.458), 12.80% (0.081-0.175) and 3.57% (0.012-0.381) respectively] or single treatment [51.50% (0.407-0.623), 12.12% (0.0193-0.223), and 10.12% (0.003-0.199) respectively]. The statistically significant predictors for overall survival were cancer metastasis (p = 0.0001), disease stage at diagnosis (p = 0.001), patient age (p = 0.017), and performance of lung resection surgery (p = 0.021). 64.1% of the patients had metastasis, and they had significantly lower median survival than patients without metastasis (p = 0.0001). Multi-organ metastasis was the most common type of metastasis (20.9%). In conclusion, the addition of mAbs such as anti-programmed cell death protein 1/programmed death-ligand 1 or epidermal growth factor receptor inhibitors or vascular endothelial growth factor inhibitors to platinum-doublet chemotherapy markedly improved the overall survival and survival rates of NSCLC patients.

The incidence of hepatocellular carcinoma (HCC) is increasing each year, with challenges such as increasing drug resistance and a high post-treatment recurrence rate. Therefore, investigating the novel pathogenic mechanisms is warranted. In this study, we investigated novel molecular mechanisms that affect HCC progression. Immunofluorescence analysis, immunohistochemical staining, and immunoblotting were performed to assess elevated IGF-1R expression in HCC cells. The EdU incorporation and colony formation assays revealed that IGF-1R promotes HCC cell proliferation. Furthermore, wound healing and Transwell migration assays revealed that IGF-1R phosphorylation enhances the migration of HCC cells. In addition, JC-1 apoptosis assays revealed that IGF-1R inhibits HCC cell apoptosis. Immunoblotting was performed to assess the protein phosphorylation level of Akt/GSK-3β downstream of IGF1/IGF-1R to explore the molecular mechanism. IGF-1R expression was significantly increased in HCC cells, and ligand-induced phosphorylation promoted HCC cell proliferation and migration and inhibited apoptosis. Additional studies revealed that the activation of IGF-1R phosphorylation promotes epithelial-mesenchymal transition in HCC cells by increasing the phosphorylation levels of Akt and GSK-3β. Collectively, our study findings suggest that IGF-1/IGF-1R promotes HCC progression by activating the Akt/GSK-3β pathway.

M2-like macrophages play a critical role in breast cancer progression. Although JMJD3 is reported to play a significant role in M2-like macrophage polarization, its precise mechanism remains unclear. By using PMA, IL-4, and IL-13, we successfully induced THP-1 cells into M2-like macrophages, which subsequently promoted breast cancer cell proliferation and inhibited apoptosis, accompanied by increased JMJD3 expression. We demonstrated that JMJD3 enhances M2-like macrophage polarization: knockdown of JMJD3 decreased the M2-like macrophage gene expression, while overexpression of JMJD3 produced the opposite effects. Furthermore, JMJD3 promoted M2-like macrophage polarization through the STAT6/IRF4 axis. Knockdown of JMJD3 abrogated IL-4/IL-13 induced IRF4 expression, while overexpression of JMJD3 upregulated IRF4 expression. Inhibition of STAT6 downregulated the expression of JMJD3, IRF4, and M2-like macrophage marker genes. Additionally, inhibiting JMJD3 and STAT6 in macrophages increased cell apoptosis and decreased cell viability in breast cancer cells, while JMJD3 overexpression exhibited pro-tumor activity. In conclusion, our findings highlight the role of JMJD3 in regulating M2-like macrophage polarization and its impact on breast cancer development through the STAT6/IRF4 axis.

We aimed to analyze the correlation between radiomic features of pulmonary invasive mucinous adenocarcinoma (PIMA), abnormal expression of the FoxM1 and Sox9 genes, and pathological characteristics of the tumor.

Glioblastoma aggressively invades surrounding tissue by expressing matrix metalloproteinase-2 (MMP-2). Therefore, effective inhibition of MMP-2 is a desirable target for treatment. In some reports, the chlorotoxin (Ctx) polypeptide produced by the scorpion Leiurus quinquestriatus, interacts with human MMP-2 to inhibit tumor invasion without affecting surrounding tissue. We employed three molecular docking methodologies followed by molecular dynamics simulations to find consensus binding and calculate the binding energy of these peptide ligands to MMP-2. In addition to the Ctx itself, four C-terminal fragments were chosen to study their binding to MMP-2. The molecular docking platforms HPEPDOCK, HADDOCK, and AlphaFold2 created peptide - protein poses for each candidate binding to MMP-2. These poses underwent 500 ns molecular dynamics simulations. Peptide binding on MMP-2 and final binding energies were calculated using the Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) method. Configurational entropy and root-mean square deviation analyses showed stable peptide - protein complexes. Ctx and its peptide fragments frequently bound to regions on MMP-2 other than the catalytic site. All docking methods shared consensus on large negative binding energies, indicating favorable interaction between Ctx and its analogs with MMP-2. While Ctx and its fragments bind to MMP-2, there is no consensus on which region of MMP-2 they are bound to or which peptide binds strongest. Neither Ctx nor its fragments inhibited MMP-2 enzymatic activity, however, glioblastoma cellular migration was inhibited. Interactions with the non-catalytic regions of MMP-2 suggest allosteric binding to MMP-2. Inhibition of cellular migration without inhibition of MMP-2 activity warrants further study into the possible targets of Ctx expressed in glioblastoma.

Implementing a prognostic model in clinical practice requires assessing not just its accuracy but also how it may impact patient and healthcare outcomes. Evaluating these impacts requires clinical trials that are carefully designed to select, collect, and report key outcomes. However, there is currently no consensus on which outcomes are key to evaluating the impact of prognostication. Core Outcome Sets can standardise outcome selection, collection, and reporting, and thereby improve the comparability of studies. Our study aimed to develop a preliminary Core Outcome Set for evaluating the impact of prognostication on people living with advanced cancer.

Subsolid nodules (SSNs) refer to pulmonary nodules that exhibit ground-glass opacity on CT images. They may appear entirely as ground-glass attenuation (pure ground-glass nodules) or contain both ground-glass and solid components (part-solid nodules). Atypical pulmonary cysts (APCs) are air-filled lesions with features such as thick irregular walls, internal septa, or associated nodularity. Primary lung neoplasms that arise from SSNs or atypical cysts often have slow growth and may be misinterpreted as infectious or inflammatory processes due to atypical imaging features. With the increasing use of chest CT, particularly in lung cancer screening programs, the incidental detection of these lesions is more frequent, highlighting the need for standardized evaluation and management. The introduction of updated guidelines such as Lung CT Screening Data Reporting and Data System version 2022 reflects a shift toward a more structured approach to specifically address these lesion types. Optimal lesion assessment requires comparison with not only the most recent imaging findings but also with the oldest available prior studies. This is especially important in the evaluation of slow-growing lesions where subtle progression can be easily missed without a long-term baseline. Accurate identification and risk stratification are essential, as these lesions may represent early-stage pulmonary adenocarcinoma or, less commonly, other primary lung malignancies, although not all such lesions are neoplastic. Optimal management requires a multidisciplinary approach that integrates clinical history, imaging changes, comorbidities, and patient preferences. Radiologists play a crucial role in the early detection, monitoring, and personalized management of these potentially malignant lesions, ultimately enhancing patient outcomes. The authors focus on pulmonary adenocarcinomas that arise from or evolve into SSNs and APCs, with an emphasis on imaging characteristics, histopathologic correlations, guideline-based recommendations, and risk stratification. ©RSNA, 2026 Supplemental material is available for this article..

Renal oncocytic neoplasms present diagnostic challenges, both at imaging and pathologic evaluation. The World Health Organization classification of renal neoplasms defines a spectrum of oncocytic neoplasms, including emerging entities that help define previously uncharacterized or mischaracterized tumors. Low-grade oncocytic tumors and eosinophilic vacuolated tumors are distinguishable from other oncocytic neoplasms at pathologic evaluation and typically demonstrate indolent behavior. Nomenclature regarding hybrid neoplasms has been clarified in reference to hereditary cases associated with Birt-Hogg-Dubé syndrome. Preoperative diagnostic difficulties at imaging contribute to high rates of resected benign renal tumors, the majority being renal oncocytomas. The imaging appearances of oncocytic neoplasms are similar, and the inability to confidently diagnose them at imaging has led to increased resection rates. Preoperative renal mass biopsy may be preventative, but its utilization remains low, diagnoses can be equivocal, and establishing tumor aggressiveness may not always be reliable. Malignant renal oncocytic tumors, including chromophobe renal cell carcinoma, are generally considered the less aggressive subtypes of renal cell carcinoma. However, distinguishing them from the more aggressive clear cell subtype remains challenging, despite imaging frameworks designed to aid categorization. Active surveillance is a safe management option among biopsy-confirmed renal oncocytic neoplasms, but it remains uncertain which patients are suitable for this approach. Diagnostic imaging may assist in risk-stratifying oncocytic neoplasms, with mass enhancement, heterogeneity, and calcification potentially differentiating benign from malignant oncocytic neoplasms. Mass attenuation and heterogeneity may differentiate low-grade and high-grade cancers. Molecular imaging and other emerging techniques, such as MR fingerprinting, may play a role in the future. ©RSNA, 2026 Supplemental material is available for this article.

Pharmacological reversal of abnormal promoter DNA hypermethylation at tumor suppressor genes (TSGs) is a key therapeutic paradigm for cancer management. However, the clinical efficacy of currently approved nucleoside analog hypomethylating agents (HMAs) is limited by dose-dependent toxicity and high resistance rates. Nonnucleoside, DNA methyltransferase 1 (DNMT1)-selective inhibitors offer a promising alternative. To date, only limited chemotypes, exemplified by the dicyanopyridine derivative GSK3685032 (GSK5032), have demonstrated translatable DNMT1 inhibition, with resistance emerging upon prolonged exposure. To address these limitations, we employ structure-guided scaffold hopping and chemical optimization to develop a series of DNMT1 inhibitors (DNMT1i) featuring a bicyclic 7-azaindole scaffold. We identify DMI46, a potent enzymatic DNMT1i capable of reversing cancer-specific DNA methylation abnormalities and TSG silencing, leading to robust antileukemic effects and favorable tolerability. Cryoelectron microscopy (cryo-EM) studies reveal that the 7-azaindole inhibitor exhibits enhanced intercalation into hemi-methylated CpG dyads and increased minor-groove contacts within the DNMT1/hemimethylated DNA complex compared to GSK5032. These structural features enable sustained DNMT1 targeting and significant antiproliferative activity of DMI46 in GSK5032-resistant acute myeloid leukemia (AML) cells. We also demonstrate DMI46's capacity to overcome AML resistance to nucleoside-based HMAs both in vitro and in vivo. These findings introduce a distinct DNMT1i chemotype with enhanced on-target engagement and broad applicability against HMA-resistant AML.

Copyright: © 2026 Aleid et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Copyright: © 2026 Adeyika et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Aberrant DNA methylation changes lead to abnormal gene expression that contributes to the development and progression of prostate cancer (PCa). Inquiry of genome-wide DNA methylation dataset, we identified the homeodomain pancreatic and duodenal homeobox 1 (PDX1) gene as differentially hypermethylated in PCa compared to normal prostate tissues. Immunohistochemical analysis of matched PCa and normal prostate tissues using tissue microarray showed a significant 2.33-fold (p = 0.0001) higher PDX1 protein expression in the PCa compared to the normal prostate tissues. In PCa cell lines (PC-3 and LNCaP) engineered to stably overexpress or knockdown PDX1, the ectopic PDX1 expression significantly enhanced cell proliferation and migration, whereas PDX1 knockdown suppressed these phenotypic processes. Quantitative RT-PCR and Western blot analysis demonstrated that PDX1 overexpression was associated with increased expression of key metabolic regulators; INSR, IGF1R, CXCR4, CDH2, TWIST1, and SNAI1, whereas there is decreased expression of ESR2, and TNFα. Conversely, PDX1 knockdown led to the opposite effect in expression profiles of these metabolites. Notably, these effects were more pronounced under high-glucose conditions compared to low-glucose environments. Overall, our findings suggest that PDX1 plays a tumor-promoting role in human PCa cells by influencing expression of metabolites in insulin, inflammatory, and epithelial-mesenchymal transition (EMT) signaling pathways. Given its potential role in metabolic regulation, full insights into the function of PDX1 in PCa could contribute to improved treatment and prevention strategies, particularly for men with PCa and comorbidities such as obesity and diabetes.

Copyright: © 2026 Ahmed and Núñez-Ríos. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Burgeoning technological and clinical advances have significantly reshaped glioma classification. To assess the evolution of these changes, we analyzed bibliometric data from Web of Science to explore patterns in the socio-clinical domains of glioma classification research. Using network analysis, we built a direct citation network linking articles to authors, focusing on citations. Main Path Analysis provided an overview of research evolution, Key Route Analysis identified influential papers, and K-core analysis revealed densely connected articles. The network comprised 46,204 nodes and 231,432 arcs, highlighting DNA methylation profiling’s role in advancing molecular biomarker-based classification models. KRA emphasized advanced imaging and molecular techniques as key drivers, while K-core analysis identified articles cited at least 19 times. The findings indicate that the subset of articles focusing on glioma classification that incorporate social factors is relatively scarce in the analyzed data, in contrast to the prominence of epigenetic and imaging factors in the literature. Unlike previous studies that focused primarily on metrics such as the h-index, our approach identifies the limited but notable mention of social factors in glioma classification research, thereby highlighting a thematic gap. Through quantitative network analysis complemented by narrative interpretation, we uncovered patterns and substructures that offer deep insights into the evolving research landscape.

Copyright: © 2026 Makovec et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Prostate gland cells can be transcriptionally and morphologically characterized as basal and luminal. About 30–40% of advanced prostate cancers (PC) harbor basal-like transcription programs. In castration-resistant PC (CRPC), studies indicate that basal and stem cell-like (SCL) tumors are major resistance mechanisms to androgen receptor (AR)-targeted therapies. SCL tumors have reduced AR activity and increased stem-cell activity that promotes tumor formation, which contributes to poor clinical outcomes. We determined that CREB5 is a key regulator of basal and SCL transcriptional programs and tumor-forming phenotypes in PC. Through in silico modeling of PC transcriptomes and several pre-defined PC signaling programs, CREB5 expression was best associated with basal-like gene signatures and SCL-associated genes in primary PC and CRPCs (n = 493 and 208). This included associations with FOSL1 and other AP-1 transcription factors. We further found that CREB5 interacted with AP-1 proteins and bound to the regulatory elements of AP-1 genes, suggesting a mechanistic role in regulating the activity of AP-1 genes. In AR-positive cells, CREB5 overexpression promoted cell colony growth with tumorigenic properties and increased tumor size in vivo. These findings implicate CREB5 as a driver of the transcriptional programs underlying AR-independent basal and SCL CRPC subtypes, and this activity is detectable in primary PC.