• Integrating single-cell and bulk transcriptomes to reveal prognostic and immunological features of ecDNA-related genes in osteosarcoma.
    4 days ago
    The role of extrachromosomal DNA (ecDNA)-related genes in osteosarcoma remains largely unexplored. The aim of this study is to investigate the association between ecDNA-related genes and prognosis and tumor microenvironment (TME) in osteosarcoma.

    Differential gene expression analysis of GEO datasets was conducted to identify ecDNA-related genes in osteosarcoma. Based on bulk RNA-seq data, a novel ecDNA-related Gene Prognostic Score Model (EGPSM) was developed using an integrated framework of 101 machine learning algorithms, which was validated in training, testing, and external cohorts. The associations between risk scores, prognosis, and TME characteristics were comprehensively evaluated. Single-cell RNA sequencing (scRNA-seq) data were further analyzed to elucidate the relationship between EGPSM, pro-tumor behaviors, and immune modulation in osteosarcoma, as well as to identify key prognostic genes involved in tumor progression. Lastly, we conducted in vitro and in vivo assays to characterize the biological roles of MTDH and to elucidate its regulatory effects on CD8⁺ T cell function.

    A robust EGPSM was constructed, demonstrating superior predictive accuracy with a maximum C-index of 0.803. High-risk patients exhibited poorer survival, higher metastatic potential, and an "immune-cold" TME characterized by diminished CD8⁺ T/NK cell infiltration and impaired effector functions. Single-cell analysis confirmed the enrichment of malignant cells and depletion of T/NK populations with lower effector scores in the high-risk group. MTDH was identified as a key driver; functional assays showed it promotes proliferation and invasion while inhibiting apoptosis. Notably, MTDH knockdown potentiated CD8⁺ T-cell cytotoxicity by increasing the levels of granzyme B, IFN-γ, and perforin.

    The newly developed EGPSM represents an effective tool for prognostic assessment and therapeutic stratification in osteosarcoma. MTDH may serve as a promising prognostic biomarker and therapeutic target.
    Cancer
    Care/Management
    Policy
  • Contrast-enhanced MRI improves diagnostic accuracy in stage Tis-T1 rectal cancer: a head-to-head comparison with endorectal ultrasound.
    4 days ago
    To investigate whether the addition of contrast-enhanced sequences improves the diagnostic value of MRI in Tis-T1 rectal cancer and to compare its diagnostic performance with that of endorectal ultrasound (ERUS).

    Patients with pathologically confirmed Tis-T2 rectal cancer who underwent curative resection between January 2020 and December 2023 were enrolled. All patients underwent preoperative MRI (including contrast-enhanced sequencing) and ERUS. Tumor shape and the status of muscularis propria (SMP) were evaluated on T2-weighted images by a radiologist, whereas submucosal enhancing stripe (SES) was assessed on contrast-enhanced MRI. An MRI-based combined model was constructed by integrating tumor shape, SMP, and SES features. ERUS-based tumor staging was performed by an endoscopist. The diagnostic performance of SMP, SES, the combined model, and ERUS in identifying stage Tis-T1 lesions was evaluated. The area under the receiver operating characteristic curves (AUCs) was calculated, and statistical differences were assessed using the DeLong method.

    In total, 136 patients (mean age: 60 ± 10 years; 78 men) with 138 lesions (82 Tis-T1 and 56 T2 lesions) were enrolled. The AUC values for SMP, SES, the combined model, and ERUS were 0.762 (95% confidence interval [CI]: 0.682-0.830), 0.861 (95% CI: 0.792-0.914), 0.915 (95% CI: 0.856-0.956), and 0.806 (95% CI: 0.730-0.868), respectively. Adding contrast-enhanced MRI feature significantly improved the diagnostic performance over the common approach (combined model vs SMP: AUC difference = 0.154; p < 0.001), and the combined model was also better than ERUS (AUC difference = 0.109; p = 0.003).

    Incorporating contrast-enhanced MRI improves stage Tis-T1 rectal cancer diagnostic accuracy and outperforms ERUS.

    Question Can adding contrast-enhanced MRI feature improve the diagnostic performance of MRI in identifying stage Tis-T1 rectal cancer compared to ERUS? Findings The MRI-based combined model incorporating contrast-enhanced and T2WI features achieved the best diagnostic performance (AUC value: 0.915), significantly superior to that of ERUS (p = 0.003). Clinical relevance Incorporating contrast-enhanced MRI offers a more reliable basis for personalized organ-sparing treatment planning and provides a foundation for future clinical practice guidelines.
    Cancer
    Care/Management
  • Establishing selection criteria for male New Zealand white rabbits in interventional radiology research using organ volumes and vessel diameters.
    4 days ago
    New Zealand White (NZW) rabbits are widely used in interventional radiology research due to their suitability for human-sized treatment and imaging equipment, offering high translational potential. This study aims to define selection criteria for rabbits by correlating body weight (BW) and age with abdominal organ and vessel dimensions measured on cross-sectional imaging.

    Computed tomography and magnetic resonance imaging scans of 80 male NZW rabbits were analyzed using 3D Slicer to measure abdominal organ volumes and vessel diameters. Additionally, an in-house nnU-Net was built for liver volumetry and validated against manual segmentations. Imaging-based measurements were confirmed by gross anatomy in five animals. Statistics included normality testing and Pearson correlation.

    BW ranged from 2.0 to 4.5 kg (median [IQR]: 3.5 [2.9-3.8]) and age from 10.0 to 24.9 weeks (17.7 [15.0-21.4]); age correlated strongly with BW (p < 0.001). Organ volumes (liver, both kidneys) correlated with BW and age (all p < 0.001), respectively. Additionally, several vessel diameters (left common and internal iliac arteries, inferior vena cava, right common carotid artery) significantly correlated with BW and age, while the celiac trunk (p = 0.010), common hepatic (p = 0.011), and right renal artery (p = 0.031) correlated with BW only. The liver segmentation model achieved a Dice Similarity Coefficient of 0.91.

    BW and age in NZW rabbits correlate with both organ volumes and large vessels relevant to interventional procedures, supporting the use of biometric data as selection criteria to improve standardization, reduce complications, and enhance preclinical research quality.

    Weight- and age-based selection of NZW rabbits improves anatomical suitability for image-guided interventions, enhancing technical success and reproducibility. It may reduce complications and dropouts, avoiding false attribution of adverse events to the technique rather than biometric unsuitability.

    Lack of standardized selection criteria in the VX2 rabbit model increases procedural risks and impairs reproducibility in interventional radiology research. Biometric data correlate with organ and vessel dimensions, enabling estimations of anatomical suitability for image-guided procedures in interventional radiological research. This study establishes anatomical reference data providing a quantitative basis to standardize and refine future VX2 rabbit research.
    Cancer
    Care/Management
  • Identification of a Novel Radiosensitivity-Related Signature and Validation of GPX8 in Regulating the Radiosensitivity of Glioma.
    4 days ago
    Radioresistance is fundamental to glioma progression and poor prognosis. Understanding its underlying mechanisms and identifying novel therapeutic targets through elucidating key molecules in glioma radiosensitivity pathways are therefore of significant clinical importance.

    Radiosensitivity-related genes were identified based on radiotherapy response, glioma stemness, and prognosis. A predictive signature was constructed using Lasso-Cox regression and validated via clinicopathological, functional enrichment, immune infiltration, and correlation analyses. GPX8 expression and prognostic significance were assessed by tissue microarray. In vitro functional and radiobiological assays, complemented by in vivo subcutaneous xenograft models using BALB/c nude mice (treated with or without radiotherapy), evaluated the role of GPX8 in regulating malignant progression and radiosensitivity in glioma.

    The radiosensitivity-related signature demonstrated significant potential in predicting glioma malignancy and prognosis, serving as an indicator of the mesenchymal subtype and contributing to the maintenance of an immunosuppressive microenvironment. GPX8 was overexpressed in high-grade gliomas and correlated with recurrence and poor survival. Knockdown of GPX8 suppressed the malignant biological behaviors of glioma cells. Radiation upregulated GPX8 expression while GPX8 knockdown significantly enhanced the cytotoxicity of radiation and induced apoptosis by promoting oxidative stress and DNA damage. Suppression of GPX8 effectively potentiated radiosensitivity in murine xenograft models and reduced intratumoral infiltration of tumor-associated macrophages.

    The radiosensitivity-related signature serves as a significant predictor for assessing glioma malignancy and prognosis. GPX8 acts as a key regulator of malignant phenotypes and radiosensitivity in glioma, positioning it as a promising therapeutic target to counteract both malignant progression and radioresistance.
    Cancer
    Care/Management
    Policy
  • DeepDrugs: a mechanism-aware tri-linear attention framework for synergistic drug-combination prediction.
    4 days ago
    Accurate prediction of drug synergy is critical for the rational design of effective combination therapies against cancer. However, existing computational approaches usually characterize the effect of an individual drug on a cell line separately and then merge the effect representations of two drugs for synergy prediction, which seriously limits their abilities to capture how two drugs act together within a specific cellular environment. We introduce DeepDrugs, a mechanism-aware deep learning framework that employs a tri-linear attention network to directly characterize how two drugs jointly act within a specific cellular context to produce synergy. Extensive experiments demonstrate that DeepDrugs outperforms state-of-the-art approaches in predictive accuracy, robustness, and generalization. Systematic model interpretation analyses identify key pharmacophores that are consistent with experimental validations. Furthermore, DeepDrugs predicts multiple unseen drug combinations (e.g. the Docetaxel-Bortezomib pair in the MCF7 cell line) that align with empirical findings.
    Cancer
    Care/Management
  • Gleason Regrading After Prostatectomy-Results From the Irish Prostate Cancer Outcome Research (IPCOR) Situated in the International Context.
    4 days ago
    Accurate Gleason grading is crucial for prostate cancer (PCa) treatment decisions; incorrect assessment can lead to under- or overtreatment; discordance between biopsy and radical prostatectomy (RP) grades is a marker of this inaccuracy. Using the Irish Prostate Cancer Outcomes Research (IPCOR) cohort, we sought to quantify Gleason grade concordance, upgrading, and downgrading trends in PCa RP patients, assess the impact of pre-biopsy MRI on diagnostic accuracy, and compare Irish trends with international findings.

    A contextual literature review summarized international regrading rates. IPCOR enrolled 6816 men diagnosed with PCa. We included 1194 men who underwent both biopsy and RP within 180 days. Biopsy and RP Gleason Grade Groups (GG) were compared to estimate concordance, upgrading, and downgrading. Sub-analyses examined regrading by biopsy modality and pre-biopsy MRI.

    Overall concordance was 57.0%, similar international median of 52.9%. Concordance was lowest for GG1 (32.7%) and highest for GG2 (74.8%), while higher GGs showed frequent downgrading (GG4 46.8%; GG5 33.3%). Among men with TRUS biopsy, pre-biopsy MRI was associated with higher concordance (59.8% vs. 55.8%) and lower upgrading (19.3% vs. 29.4%), though differences were not statistically significant.

    Gleason regrading patterns in Ireland mirror global experience, with upgrading in lower and downgrading in higher GGs. Pre-biopsy MRI shows a favorable trend toward improved diagnostic accuracy, supporting its integration into clinical pathways.
    Cancer
    Care/Management
  • Use of sodium thiosulfate in prevention of aki in oncologic patient that underwent hipec (Hyperthermic Intraperitoneal Chemotherapy) with Cisplatin: a Case Report.
    4 days ago
    Ovarian cancer is among the most common cancers diagnosed in women. It is the eighth most common cause of cancer death, with five-year survival rates below 45%. It is fundamental to have weapons and strategies to treat this type of cancer. Cisplatin is a well-known anticancer molecule that works by damaging the DNA of cancer cells. It is used in a variety of tumors such as testicular, bladder, lung and mostly in ovarian cancer. We present a case report of a 72-year-old woman diagnosed with ovarian adenocarcinoma. She underwent surgery in another hospital, and the uterus, both ovaries and the left kidney were removed, as it was infiltrated by the cancer. HIPEC is a technique that permits delivery of the anticancer drug directly to its active site. It has been demonstrated that cytoreduction + HIPEC with cisplatin has a better outcome in terms of recurrence-free survival.
    Cancer
    Care/Management
  • Inflammatory myofibroblastic tumor in pediatric patients: a Bosnian cohort.
    4 days ago
    Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm of intermediate biological potential, characterized by spindle cell proliferation and significant inflammatory component. This study aimed to determine the clinicopathologic characteristics, the clinical outcomes of inflammatory myofibroblastic tumor cases in the low-volume pediatric surgery service in a developing country.

    The study included data from all IMTcases diagnosed and operated from 2010 to 2024 &nbsp;at the Clinic of Pediatric Surgery, Clinical Center University of Sarajevo.

    Three pediatric patients (two females, one male) diagnosed with IMT were analyzed for demographic, clinical, histopathological, immunohistochemical, and outcome parameters. All tumors were located in the abdominal or abdominopelvic region, with a median patient age of 4 years. Clinical manifestations included non-specific gastrointestinal symptoms (n=2) and systemic signs such as fever (n=2), weight loss and weakness (n=1). Complete surgical resection was conducted in all patients, and all experienced complete remission without recurrence. Histopathological analysis revealed consistent presence of spindle cells within a prominent inflammatory milieu, rich in plasma cells and lymphocytes. Immunohistochemically, all tumors were positive for vimentin, ALK, and SMA, while ALK-FISH analysis (performed in one case) was negative. No significant nuclear atypia or mitotic activity was observed.

    Our study showed the constant of its heterogeneous morphology, and significance of IMTs immunophenotype, particularly in older children, where the inflammatory component is more pronounced. ALK gene alterations are commonly associated with IMT, as well as with other types of pediatric neoplasms, however, favorable outcomes in our cohort study, raise question regarding further need to clarify the prognostic significance of molecular findings and their potential therapeutic implications.
    Cancer
    Care/Management
  • The use of the HPV vaccine in a group of primarily unvaccinated HPV-positive patients.
    4 days ago
    Human papillomavirus (HPV) infection remains the most prevalent sexually transmitted viral infection worldwide and a major etiologic factor for cervical and other anogenital cancers. HPV-related precancerous lesions continue to represent a substantial clinical and epidemiological burden.

    We aim to assess the effects of nine-valent HPV vaccination on viral clearance, genotype distribution, and lesion regression among HPV-positive women who were unvaccinated in childhood.

    We enrolled 461 women between January 2020 and August 2025 to the study who presented with abnormal cytology, positive hrHPV tests, or abnormal colposcopic findings. Participants underwent LBC, HPV genotyping, colposcopy, and biopsy or LEEP when indicated. The vaccinated cohort (n = 351) received the Gardasil®9 series (0-2-6 months), while 110 women served as unvaccinated controls. Statistical analyses were performed using R software (v4.4.2) with a significance threshold of α = 0.05.

    Following vaccination, HPV positivity for any genotype was significantly lower in the vaccinated group than in the control group (29.3% vs 56.4%, p < .001). Clearance of Gardasil-specific genotypes occurred in 83.5% of vaccinated women compared with 63.6% in the controls. Complete remission was higher in the vaccinated group (70.7% vs 43.6% in the control group). Persistence of identical HPV genotypes was markedly reduced after vaccination (8.5% vs 27.3%).

    Nine-valent HPV vaccination significantly enhanced viral clearance and reduced persistence and recurrence of high-grade squamous intraepithelial lesions (HSIL) among previously unvaccinated HPV-positive women. These findings support extending vaccination recommendations to adult HPV-positive patients as an adjunctive strategy to surgical and cytologic management.
    Cancer
    Care/Management
    Advocacy
  • Infra-slow body-surface potentials show a group-level association with thyroid cancer.
    4 days ago
    Thyroid cancer is a common malignancy with broad systemic endocrine and metabolic effects (Hammond et al., 2024). Regarding diagnostics, if infra-slow body-surface potential (BSP) features reflect a systemic state, then this type of cancer is a reasonable clinical test case. Prior electrodermal work has focused on faster transients above 0.5 Hz (Boucsein, 2012; Posada-Quintero and Chon, 2020), and task-state skin potential abnormalities have been shown to distinguish mood disorders from healthy controls (Lyu et al., 2024). We concentrated on an infra-slow band from 0.025 to 0.2 Hz, called Band 1 herein. We evaluated whether infra-slow features carry reproducible group-level information when artifacts are explicitly controlled, with one pre-specified primary endpoint. "Separable" here means a group-level statistical difference, not individual-level diagnosis. In a cohort of 321 cancer patients, Band 1 energy showed a clear group-level association with thyroid cancer, which persisted after automated quality control (QC) and under stricter artifact-removal settings.
    Cancer
    Mental Health
    Care/Management