Ductal carcinoma in situ (DCIS) is a preinvasive form of breast cancer. Current treatment consists of surgery, radiation, and often systemic therapy exposing patients to unnecessary health risks. Vaccines targeting DCIS may be a way to intercept preinvasive lesions and prevent the development of invasive breast cancer.

We developed a Th1 selective multiantigen, polyepitope plasmid-DNA vaccine encoding segments of IGFBP-2, HER2, and IGF-IR, all antigens expressed in hormone receptor positive and negative DCIS. We then performed a Phase I study in participants with non-metastatic breast cancer with no evidence of disease. The primary objective was to assess the safety of 3 monthly intradermal doses (150, 300, or 600 µg) of the tri-antigen vaccine with granulocyte macrophage colony-stimulating factor as an adjuvant. 32 participants were enrolled, 10 per dose level. Toxicity evaluations occurred monthly with vaccination and at 1 and 6 months after the last vaccine. Blood was collected at baseline and at 1 and 6 months after the last immunization to assess cellular immune responses. Participants were followed annually for 5 years for long-term toxicity.

There was no significant difference in adverse events (AEs) across dose levels and all related AEs were grades 1 or 2. All doses were immunogenic; responders included 70% of participants at the 150 µg dose level, 67% at the 300 µg dose, and 40% at the 600 µg dose level. All participants at the 300 µg dose retained significant Th1-antigen-specific immune response at 6 months after end of immunizations. T-cells derived from vaccine immunologic responders exhibited gene expression profiles that indicated an increased metabolic fitness as compared with immunologic non-responders.

The tri-antigen vaccine appears safe and immunogenic. The intermediate dose (300 µg) was chosen as the Phase II dose due to the long-term persistence of immunity after vaccination. The vaccine will be studied in Phase II trials for the treatment of DCIS.

NCT02780401.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality worldwide. While immune checkpoint blockade has revolutionized the treatment of many cancers, responses in HCC remain limited. Robust functional platforms capable of predicting individual responses to immunotherapy are urgently needed. In this study, we developed a patient-derived organotypic tumor spheroid (PDOTS) model that preserves the heterogeneity and immune microenvironment of HCC, enabling rapid and reliable assessment of targeted and immunotherapeutic responses.

Tumor tissues from 30 HCC patients were processed using a "Five-Point Clock" sampling method and cultured within a three-dimensional microfluidic chip supplemented with IL-2 and CD3/28 activator to maintain tumor-infiltrating lymphocyte activity. The genomic, immune, and histopathological fidelity of PDOTS relative to parental tumors was evaluated. Drug responses were assessed ex vivo and validated in matched patient-derived xenograft (PDX) models. Transcriptomic profiling was subsequently performed to identify gene signatures associated with treatment sensitivity and to construct a transcriptomic predictive model.

The PDOTS retained ≥60% viability over 7 days and faithfully maintained the genomic, immune, and histopathological profiles of parental tumors. Functionally, PDOTS exhibited immune-dependent responses to PD-1 blockade and predicted treatment responses with 80% concordance in matched PDX models. Transcriptomic profiling revealed distinct metabolic and immune signatures in sensitive and resistant tumors, which were used to derive the "Organoid Killing Index (OKI)". The OKI gene-derived index, a composite index integrating the enrichment scores of gene signatures associated with the OKI, strongly correlated (R=0.829, p<0.001) and predicted clinical outcomes in an external patient cohort treated with atezolizumab plus bevacizumab.

These findings establish PDOTS as an immune-competent ex vivo platform for functional precision oncology and support the integration of functional testing with transcriptomic prediction to guide individualized immunotherapy in HCC.

A woman in her 30s presented with irregular vaginal bleeding and abdominal distension. Initial imaging suggested a uterine fibroid; however, intraoperative findings during planned laparotomy were atypical, prompting an excisional biopsy. The initial pathological diagnosis was endometrial stromal sarcoma, and staging imaging suggested liver metastases, prompting chemotherapy initiation. One month later, she developed urinary retention, oedema and dyspnoea. Imaging revealed a large pelvic mass causing bilateral hydronephrosis, extensive lymphadenopathy and tumour lysis syndrome, managed with stents and supportive care. Re-evaluation of the biopsy established the diagnosis of primary endometrial diffuse large B-cell lymphoma (DLBCL). Hepatitis B positivity delayed chemotherapy; interim dexamethasone provided relief. Intensive chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine and methotrexate/ifosfamide, etoposide and cytarabine resulted in a rapid response but was complicated by neutropenic sepsis, leading to death. This case highlights the diagnostic challenge of endometrial DLBCL, the critical importance of pathological re-evaluation and the need for careful toxicity monitoring during intensive chemotherapy.

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.

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.

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.

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.

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.

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.

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.