• Immunohistochemical Evaluation of GATA3 Expression in Patch-Stage Mycosis Fungoides (MF) Compared With Benign Inflammatory Dermatoses (BID).
    5 days ago
    The histopathologic distinction between patch-stage mycosis fungoides (MF) and benign inflammatory dermatoses (BID) remains a persistent diagnostic challenge, often due to overlapping clinical and immunophenotypic features. GATA binding protein 3 (GATA3), a transcription factor critical in T-helper 2 cell differentiation, has emerged as a potential immunohistochemical marker in T-cell neoplasms. This study aimed to evaluate GATA3 expression in patch-stage MF compared with BID to assess its diagnostic value. Sixty formalin-fixed, paraffin-embedded skin biopsies were retrospectively analyzed, including 30 cases of patch-stage MF and 30 cases of BID (psoriasis, chronic dermatitis, and lichen planus). Immunohistochemical staining for GATA3 was performed, and lymphocytic nuclear staining was assessed in dermal and epidermal compartments. GATA3 expression > 50% in dermal lymphocytes was observed in 20% of MF cases and 6.7% of BID cases, yielding high specificity (93.3%) but low sensitivity (20%) for MF diagnosis. Epidermal GATA3 expression was uniformly low across both groups. No significant correlations were found between GATA3 expression and key histopathologic or immunophenotypic features of MF. Although elevated dermal GATA3 expression may support the diagnosis of MF in some cases, its substantial overlap with BID and low sensitivity limit its utility as a reliable standalone diagnostic marker for early-stage MF. GATA3 can be incorporated into broader immunohistochemical panels alongside more specific markers to improve diagnostic accuracy.
    Cancer
    Care/Management
  • Oral and dental complications and management in head and neck cancer patients: An umbrella review.
    5 days ago
    To synthesise evidence on oral and dental side-effects experienced by head and neck cancer (HNC) patients, assess the strength and quality of existing systematic reviews, evaluate the evidence for prevention and management interventions and identify key gaps to inform future research.

    Systematic reviews (with/without meta-analysis) published from 2015 onwards involving adults with HNC reporting oral/dental complications and/or interventions were included.

    MEDLINE (OVID), Embase, Cochrane Database of Systematic Reviews and Scopus were searched (19 June 2025). Two reviewers screened and extracted data independently.

    An umbrella review (PROSPERO CRD420251063188) was conducted following JBI/Cochrane guidance and reported in line with PRISMA 2020. Methodological quality was assessed using AMSTAR-2 and primary-study overlap quantified using corrected-covered-area (CCA). Owing to heterogeneity, findings were synthesised narratively by domain.

    A total of 131 systematic reviews were included, with most rated as low or critically low confidence. Oral mucositis was the most frequently reported complication, followed by xerostomia, dysphagia, trismus, dental caries, and dysgeusia; osteoradionecrosis was less common. Preventive and therapeutic interventions are widely studied but largely supported by low-quality evidence. Photobiomodulation was associated with reduced oral mucositis, while intensity-modulated radiotherapy was associated with reduced xerostomia and mandibular osteoradionecrosis. Overall, the evidence base is fragmented and of low confidence. Standardised outcome measures and high-quality prospective studies are needed to strengthen the evidence base and improve survivorship care.

    Head and neck cancer patients experience a high burden of oral complications, yet dental management strategies are supported by limited high-quality evidence. This review highlights key areas of uncertainty and reinforces the need for multidisciplinary, evidence-based care, while identifying priorities for research to improve long-term oral health and quality of life.
    Cancer
    Care/Management
  • Lung cancer associated with cystic airspaces: Current concept, pathogenesis, imaging features, pathological basis, and management.
    5 days ago
    This narrative review summarizes the current concept, CT imaging features, pathologic basis, and the correlation between imaging and pathology in lung cancer associated with cystic airspaces (LCCAs). Lung cancer associated with cystic airspaces is a distinct subtype of lung cancer with unique imaging and pathological features. Lung cancer screening can identify patients with cystic lesions on imaging, but distinguishing benign from malignant lesions remains challenging. The pathologic types of LCCAs vary, and early diagnosis and accurate identification are of great clinical value for patient management and improved prognosis. Clinicians should pay more attention to LCCAs to promote early diagnosis, improve the timing of interventions, and achieve better survival benefits for patients.
    Cancer
    Chronic respiratory disease
    Care/Management
  • Prostate-specific Membrane Antigen-PET/CT in Nonprostatic Malignancies: Potential Applications in Theranostics.
    5 days ago
    68Gallium-prostate-specific membrane antigen (PSMA) PET/CT has evolved as a pivotal imaging modality for prostatic carcinoma. Prostate-specific membrane antigen (PSMA) is a zinc-dependent peptidase and a type II membrane protein that is expressed in prostate cancer and also tumor neovasculature of various nonprostatic malignancies. Recently, there have been many studies to demonstrate the expression of PSMA in vivo in nonprostatic malignancies like glioma, renal cell carcinoma, differentiated thyroid carcinoma, lung cancer, breast cancer, and salivary gland tumors, among others, and explore the diagnostic and therapeutic utility in these malignancies. While they have shown promising results with some even providing better imaging results than 18F-fluorodeoxyglucose PET/CT, it is important to evaluate the indications where PSMA PET/CT can be utilized efficiently. We must also be mindful of the benign conditions where PSMA uptake can be observed while we analyze the scans. In this review, we have described the clinical exploration of PSMA-based PET/CT in the imaging of various cancers and potential therapeutic applications.
    Cancer
    Care/Management
  • Natural Coumarins Galbanic Acid and Auraptene Improved the Efficacy of Alkeran on Human Osteosarcoma Cells by Targeting ABC Transporters.
    5 days ago
    Osteosarcoma is a severe bone malignancy, and current chemotherapeutic strategies often struggle to effectively halt disease progression. Galbanic acid (GBA) and auraptene (AUR) are natural sesquiterpene coumarins known for their diverse pharmacological activities. This study is the first to evaluate the ability of GBA and AUR to enhance Alkeran-induced toxicity in osteosarcoma cells. GBA and AUR were isolated from Ferula szowitsiana, and the viability and apoptosis of osteosarcoma cells were assessed following treatments with GBA, AUR, and Alkeran-alone and in combination. An efflux assay was conducted to determine the functional interactions of AUR and GBA with ABC transporters, and molecular docking and dynamics simulations were performed to explore their potential interactions. Single treatment of cells with each agent did not induce significant toxicity: however, combination treatments of GBA or AUR with Alkeran significantly (p < 0.0001) reduced cell viability. Synergistic interaction was strong for both coumarins and Alkeran, supported by flow cytometry detection of apoptosis and ABC transporter activity. Molecular docking and dynamics simulations demonstrated favorable and stable interactions of coumarins with ABC transporters. In conclusion, this study provides strong support that GBA and AUR enhanced Alkeran efficacy in osteosarcoma cells by targeting ABC transporters.
    Cancer
    Care/Management
  • Engineering High-fidelity Preclinical Mouse Model for Brain Metastasis using Interlock Pulsatile Injection Technique and Microsurgical Vascular Repair.
    5 days ago
    Brain metastasis remains a devastating clinical problem. A major challenge in brain metastasis research is the lack of high-quality models that accurately recapitulate the metastatic process, thereby enabling mechanistic insights into how cancer cells colonize in the brain. Traditional intracarotid artery injection models of brain metastasis often require permanent ligation of the common carotid artery (CCA), which alters cerebral hemodynamics and compromises the integrity of the blood-brain barrier (BBB). The protocol presents a refined method for establishing a high-fidelity mouse model of brain metastasis. The core innovation involves the Interlock Pulsatile Injection (IPI) technique for tumor cell delivery, followed by microsurgical arterial reconstruction at the puncture site to restore physiological blood flow in the CCA. Compared with the conventional CCA ligation model, the IPI-microsurgical repair approach significantly reduced perioperative mortality (2.86% vs. 25.71%) and increased the rate of brain metastasis establishment (94.12% vs. 65.38%). The IPI technique utilizes a tandem syringe configuration to minimize cell regurgitation during intracarotid injection. After tumor cell infusion, the CCA is meticulously repaired using microsurgical sutures under a stereomicroscope, thereby avoiding permanent occlusion. This preserves the native cerebral hemodynamics and the integrity of the BBB at the time of tumor cell entry, while significantly improving surgical success rates and reducing mortality. The metastatic intracranial lesions are validated by serial bioluminescence imaging and histopathology. The method provides a superior platform for studying the pathophysiology of brain metastasis and for preclinical therapeutic evaluation, thereby recapitulating the metastatic process.
    Cancer
    Care/Management
  • Interpretable miRNA-based prediction model for early detection of pancreatic cancer: Development and cross-platform validation.
    5 days ago
    Pancreatic cancer remains one of the most lethal malignancies, largely due to delayed diagnosis. Although microRNA (miRNA) biomarkers show promise, many previous studies lack cross-platform validation and model interpretability, limiting clinical applicability.

    We developed and externally validated an interpretable diagnostic model based on a 20-miRNA signature using publicly available datasets. A total of 801 samples were included, of which 767 were used for model training and validation. The training cohort comprised GSE59856 and GSE85589 (n = 216), and independent validation cohorts included TCGA-PAAD and GTEx pancreas (n = 585), with additional serum-based validation (GSE128508; n = 30). Feature selection and model development were conducted exclusively within the training cohort. A Random Forest classifier was applied, and model interpretability was assessed using SHAP analysis. Diagnostic performance was evaluated using cross-validation and independent external validation.

    The model achieved a cross-validation AUC of 0.87 (95% CI 0.82-0.92), with sensitivity of 84.7% and specificity of 83.1% in the training cohort. External validation across independent RNA-seq and qRT-PCR datasets demonstrated AUC values ranging from 0.78 to 0.83. Performance remained broadly consistent across sample types and platforms. SHAP analysis identified miR-6875-5p, miR-196a-5p, and miR-1246 among the principal contributors to classification. Functional enrichment analysis suggested involvement in canonical cancer-related pathways.

    We developed and externally validated an interpretable 20-miRNA signature for pancreatic cancer diagnosis with consistent performance across independent cohorts. Although based on retrospective datasets, the structured validation strategy and explainable modeling framework provide a transparent foundation for future prospective evaluation.
    Cancer
    Care/Management
    Policy
  • Automated counting of prostate cell types with image processing and machine learning.
    5 days ago
    Traditional cell counting in clinical and research settings often relies on hemocytometry, a manual technique that is labor-intensive and prone to human error. These limitations in precision and throughput can hinder the development of effective diagnostic and therapeutic strategies, particularly in the context of prostate cancer. Recent advances in machine learning have shown considerable promise in enhancing the accuracy and efficiency of cell enumeration. In this study, we present a novel software system for the automated counting of prostate cancer cells, integrating image processing with deep learning methodologies. Unique to our approach, the system robustly utilizes images acquired from conventional mobile phone cameras, offering a highly accessible and scalable solution. It applies a convolutional neural network (CNN) in conjunction with a selective search algorithm to accurately identify regions of interest (ROIs), followed by robust image analysis algorithms for precise cell detection and quantification. This two-stage pipeline addresses the inherent variability and extraneous content in mobile-captured images, which is a significant advancement over methods reliant on controlled microscopic environments. Experimental evaluations demonstrate that the proposed method achieves superior accuracy compared to conventional manual counting approaches. This automated framework offers a practical, scalable solution that may significantly improve the reliability and efficiency of cell counting in both research and clinical diagnostics.
    Cancer
    Care/Management
  • Population Pharmacokinetics and Exposure-Response Analysis of Ziftomenib in Relapsed or Refractory Acute Myeloid Leukemia Patients With NPM1 Mutation.
    5 days ago
    Ziftomenib, a potent, highly selective, oral menin inhibitor, has demonstrated significant clinical benefit and deep responses in relapsed and/or refractory (R/R) nucleophosmin 1-mutated (NPM1-m) acute myeloid leukemia (AML) patients. Here we present data from analyses conducted to characterize ziftomenib pharmacokinetics (PK) in healthy volunteers and R/R AML patients and exposure-response (ER) relationships in R/R NPM1-m AML patients. A sequential two-stage modeling approach was employed to develop the popPK model for ziftomenib and its metabolites. A 2-compartment model with first-order elimination and first-order absorption with a lag time adequately described the PK data for ziftomenib with good precision. Thorough covariate analysis showed that the mutational status (NPM1-m vs. KMT2A-r) of patients, body weight, sex, race, age, mild or moderate renal or hepatic impairment, and P-gp inhibition did not impact ziftomenib PK. ER analyses were conducted using logistic regression models in a total of six combinations of efficacy endpoints and 12 safety endpoints. No steady-state exposure parameters of ziftomenib were statistically related to any of the efficacy or safety endpoints in R/R NPM1-m AML patients. In fact, flat ER profiles were observed between all ziftomenib exposure parameters and efficacy or safety endpoints over a wide range of ziftomenib exposure. The modeling results demonstrated a wide therapeutic margin for ziftomenib in adult R/R NPM1-m AML patients and supported a dose of 600 mg once daily in this patient population. Additionally, ER analyses demonstrated that antifungal azoles had no clinically meaningful impact on efficacy or safety profiles and thus could be co-administered with ziftomenib.
    Cancer
    Care/Management
  • Lower Limb Nonvisualization Caused by Macroarterial Thrombosis After Cervical Cancer TP Chemotherapy in Whole-body Bone Scintigraphy.
    5 days ago
    A 68-year-old woman with cervical cancer and pulmonary metastases presented with limb paresthesia and pain one week after chemotherapy. Whole-body bone scintigraphy performed to evaluate for bone metastases revealed rib metastases, along with poor visualization of the right distal lower extremity, raising suspicion for possible arterial flow obstruction in the right lower limb. Further imaging confirmed extensive thrombosis in the right common iliac artery and its distal branches. This case suggests that decreased uptake in the skeletal structures and surrounding soft tissues on whole-body bone scintigraphy may indicate a risk of arterial thrombosis.
    Cancer
    Cardiovascular diseases
    Care/Management