Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality globally. Previous studies have reported that oral cancer overexpression 1 (ORAOV1) is overexpressed in HCC and correlated with poor prognosis, yet its molecular mechanisms remain incompletely understood. In this study, ORAOV1 overexpression was confirmed in HCC tissues via tissue microarray analysis and functionally linked to tumor cell proliferation through a positive correlation with Ki-67 expression in the human HCC cell line MHCC-97L. Bioinformatics analyses using The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) HCC datasets further supported these findings. Multiple mechanisms appear to drive ORAOV1 upregulation, including promoter hypomethylation, amplification of the 11q13 region, and a putative ceRNA network involving AC005332.1, AC012615.1, and hsa-miR-100-5p. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses implicated ORAOV1 in various cellular processes, such as abnormal membrane channel function, extracellular matrix-receptor interactions, IL-17 signaling, and peroxisome proliferator-activated receptor (PPAR) signaling. Co-expression analysis identified significant associations between ORAOV1 and the oncogenes TPCN2 and CCND1. Additionally, ORAOV1 expression correlated with enhanced infiltration of immunosuppressive cells, including regulatory T cells, myeloid-derived suppressor cells, and cancer-associated fibroblasts, as well as upregulation of immune checkpoint markers (PD-1, PD-L1, and CTLA-4). These results indicate that ORAOV1 may modulate the immunosuppressive tumor microenvironment and contribute to resistance against immunotherapy, highlighting its potential as a therapeutic target in HCC.

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by increased erythrocytes and commonly associated with JAK2 mutations. Primary hyperparathyroidism (PHPT), which is often caused by a parathyroid adenoma, is a common cause of hypercalcemia. Although unrelated, a potential association between PV and PHPT has been described in the literature. We report the case of a 41 year-old male presenting with concurrent PV and PHPT due to a parathyroid adenoma. Following parathyroidectomy, the patient's hemoglobin and hematocrit levels normalized without further treatment, suggesting remission of PV. This case report and literature review highlight a possible relationship between the calcium-parathyroid hormone axis and hematopoiesis, providing insight into potential shared pathophysiological mechanisms.

Given the crucial roles of GSK-3β in epithelial-mesenchymal transition (EMT), we assume that it may also be involved in tumor stemness, immune evasion, and drug resistance in triple-negative breast cancer (TNBC). This study was designed to analyze the expression and clinical significance of GSK-3β and investigate its association with tumor stemness-related and immune-related genes.

GSK-3β expression and clinical data of TNBC patients were obtained from TCGA. Survival analysis, differential gene expression, and gene set enrichment analysis (GSEA) were performed to explore associations between GSK-3β and tumor stemness, immune response, and clinical outcomes in TNBC. Immune cell infiltration was assessed using xCell, and key GSK-3β-related proteins were validated via parallel reaction monitoring-based proteomics.

GSK-3β expression was significantly upregulated in TNBC and was associated with poorer overall survival. In TNBC, 24 GSK-3β-associated genes linked to tumor stemness and immune response were identified, all of which were downregulated in the high GSK-3β expression group. Proteomic analysis further validated differential expression of key proteins, including upregulation of SERPINB2, KIT, and NOTCH1 and downregulation of DNMT1, MAPK1, and EP300 in GSK-3β-overexpressing cells.

GSK-3β overexpression was associated with poor prognosis and was found to influence tumor stemness, immune modulation, and key signaling pathways that drive tumor progression and therapeutic resistance.

This study aims to investigate computed tomography (CT) radiomic features and dosimetric-clinical biomarkers to predict vocal cord dysfunction (VCD) in nonlaryngeal head and neck cancer (HNC) patients treated with chemoradiation therapy (CRT), using machine learning (ML) models.

Sixty-five HNC patients who underwent CRT were recruited to assess radiation-induced VCD 6 months posttreatment. For each patient, CT radiomic features of the laryngeal region, clinical, and dose-volume histogram (DVH) metrics were collected to develop ML models. Nine classifiers were trained using selected features obtained from three feature selection algorithms: least absolute shrinkage and selection operator (LASSO), extra trees, and elastic net. The models were built using imaging features alone (radiomics model) and in combination with clinical and dosimetric features (combined model). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC-ROC).

Of the 65 patients, 31 developed VCD. Among radiomics models, the AdaBoost and random forest (RF) classifiers performed best, with AUCs of 0.74 and 0.84, respectively. For the combined models, nine classifiers achieved an AUC greater than 0.95 using LASSO and elastic net algorithms. In contrast, only one classifier surpassed an AUC of 0.95 when using the extra trees algorithm.

Our findings demonstrate that pretreatment CT radiomic features are predictive biomarkers for radiation-induced toxicities, including VCD. Furthermore, combining radiomic features with clinical and dosimetric data can improve the predictive modeling of radiotherapy outcomes.

SG001 is a humanized, IgG4 monoclonal antibody against human PD-1. This phase 1b study aimed to evaluate efficacy and safety of SG001 in advanced solid tumors.

Patients with previously treated solid tumors that are PD-L1-positive, and/or dMMR/MSI-H, and/or Epstein-Barr virus positive were enrolled in Cohort A, while patients with PD-L1-unselected malignant mesothelioma and PD-L1-unselected non-small cell lung cancer (NSCLC) were enrolled in Cohorts C and E, respectively. All patients in Cohorts A, C, and E received SG001 at a dose of 240mg every two weeks for 2 years or until disease progression, intolerable toxicities, or withdrawal of consent. The primary endpoint was the investigator-assessed overall response rate (ORR).

A total of 87 patients were enrolled: 33 in Cohort A, 24 in Cohort C, and 30 in Cohort E. Investigator-assessed ORR was 39.4% in Cohort A, 12.5% in Cohort C, and 16.7% in Cohort E; corresponding median PFS values were 9.6, 4.1, and 4.0 months. The most common treatment-related adverse events (TRAEs) were increased alanine aminotransferase (13.8%), proteinuria (12.6%), rash (12.6%), and increased aspartate aminotransferase (10.3%). No TRAEs leading to death were reported.

SG001 demonstrated promising activity in patients with pretreated advanced solid tumors, especially those with PD-L1-positive NSCLC. The safety profile was well tolerated.

ClinicalTrials.gov identifier: NCT03852823.

Granulosa cell tumors (GCTs) represent the most common ovarian neoplasms in mares, yet data on their epidemiology, risk factors, and clinical outcomes in Arabian horses are limited. Understanding their prevalence and diagnostic features is crucial for improving fertility management in this breed.

Clinical records from 807 Arabian mares housed on 35 stud farms in central Saudi Arabia were retrospectively reviewed to determine the prevalence of GCT and potential risk factors, including age, parity, and anabolic steroid use. Twenty-four confirmed cases were further investigated using clinical examination, ultrasonography, endocrine profiling, and histopathology. Surgical management by unilateral ovariectomy was performed in 20 mares, and postoperative fertility outcomes were documented.

The overall prevalence of GCT was 0.6%. Logistic regression analysis identified anabolic steroid use as a significant risk factor (Odds Ratio = 13.21, p = 0.0001). Stallion-like behavior was the most frequent clinical manifestation (58.3%), followed by anestrus (33.3%) and persistent estrus (8.3%). Ultrasonography revealed four distinct tumor morphologies, with contralateral ovarian atrophy present in 75% of cases. Histopathology classified tumors into adult type (76.5%) and juvenile type (23.5%). Preoperative testosterone concentrations were elevated and decreased postoperatively in 72.7% of mares. Ovariectomy resulted in an 80% recovery rate, with 68.8% of mares regaining fertility.

This study demonstrates that anabolic steroid administration markedly increases the risk of GCT in Arabian mares. Behavioral changes, ultrasonographic appearance, and hormonal profiles remain key diagnostic indicators, while histopathology confirms tumor classification. Surgical excision proved effective, with favorable fertility outcomes in most mares. These findings underscore the importance of early diagnosis and highlight the need for judicious use of anabolic steroids in breeding programs.

Clinical signs due to distant bony metastasis from a malignant pheochromocytoma are rare in dogs, with the majority of reported cases presenting as single-limb lameness. This case report describes a 6-year-old neutered male mixed-breed dog presenting with multiple limb lameness and joint swelling that occurred over 3 weeks. Computed tomography revealed a mass in the right adrenal gland with extensive intrathoracic, intra-abdominal, and skeletal metastases. Because of the poor prognosis, the dog was humanely euthanized. A postmortem examination revealed a primary neoplasm of the right adrenal gland with metastases affecting the contralateral adrenal gland, kidneys, lungs, liver, and bones of the appendicular and axial skeletons. Immunohistochemistry confirmed a metastatic neuroendocrine carcinoma of the right adrenal gland, consistent with a pheochromocytoma. This case is a unique presentation of polyostotic metastases from a pheochromocytoma and emphasizes the importance of including this tumor in the differential diagnosis of dogs presenting with symptoms identical to those of polyarthritis.

Targeted alpha therapy (TAT) has emerged as a promising strategy for cancer treatment by selectively delivering high linear energy transfer (LET) alpha-emitters to tumor cells while minimizing off-target toxicity. However, the clinical translation of alpha-emitters, particularly radium-223 (²²³Ra), remains challenging due to inefficient targeted delivery and uncontrolled release of recoil daughter products, leading to systemic toxicity.

Herein, a dual-locked pretargeted strategy was developed integrating platinum^IV (Pt^IV)-loaded hydrogel nanoparticles (HNPs) (HAQ@HNPs) and ²²³Ra-loaded HNPs (²²³Ra@HNPs) into an inverse electron demand Diels-Alder (IEDDA)-activated drug delivery system. In vitro cytotoxicity, ROS, and apoptosis, together with in vivo biodistribution, imaging, and therapeutic studies, were performed to evaluate the therapeutic efficacy and immune activation.

This caged dual-locked approach enables precise pretargeted accumulation at the tumor site, followed by rapid dissociation and controlled release of ²²³Ra and Pt^IV upon IEDDA-triggered activation, thereby ensuring high tumor specificity while minimizing systemic exposure. The synergistic combination of TAT and chemotherapy effectively disrupts redox homeostasis, induces immunogenic cell death (ICD), and elicits a robust antitumor immune response. Furthermore, when combined with programmed death-ligand 1 (PD-L1) blockade, this strategy significantly enhances systemic antitumor immunity, leading to robust inhibition of tumor growth and metastasis.

These findings underscore the potential of dual-locked pretargeted strategies to advance TAT by improving therapeutic efficacy and addressing the critical challenge of radionuclide leakage, paving the way for next-generation precision-targeted radiopharmaceuticals.

Radiation therapy (RT) is a key treatment strategy for lung cancer, yet its efficacy is frequently compromised by radioresistance. The combination of RT with targeted therapies enhances treatment outcomes for non-small cell lung cancer (NSCLC). This study aims to investigate new mechanisms of metastasis after RT for NSCLC and improve the durability of the benefits of radiotherapy for lung cancer patients. This integrative study utilized human NSCLC tissue arrays, bulk RNA-sequencing, CUT&Tag sequencing, and single-cell RNA-sequencing to identify gene alterations induced by RT. In vitro experiments and animal studies were used to investigate the role of Jumonji domain-containing 6 (JMJD6)/ETS homologous factor (EHF) axis in post-RT metastasis of NSCLC. RT triggered the upregulation of JMJD6 in NSCLC tissues. This upregulation led to the activation of EHF and the subsequent transcription of pluripotency factor genes through the demethylation of H4R3me2s. JMJD6/EHF axis plays a critical role in NSCLC cell metastasis, potentially through the TGF-β/SMAD and AKT/ERK signaling pathways. These findings suggest JMJD6 as a potential therapeutic target to combat post-RT metastasis in NSCLC.

Personalized cancer vaccines targeting tumor-specific neoantigens (nAgs) are an emerging therapeutic strategy, particularly effective in early-stage disease before immune suppression is established. Immune checkpoint inhibitors have demonstrated benefit in the adjuvant setting (postsurgery), and recent evidence suggests neoadjuvant administration (before surgery) may further enhance antitumor immunity. This study evaluated the efficacy of a multiepitope nAg vaccine in a preclinical melanoma model resistant to checkpoint inhibition, comparing neoadjuvant and adjuvant treatment, alone or in combination with anti-programmed cell death protein 1 (PD1) therapy.

A viral vector nAg vaccine was developed and administered in the B16F10 murine melanoma model. Mice received the vaccine either before (neoadjuvant) or after (adjuvant) tumor resection alone or in combination with anti-PD1. Tumor recurrence and survival were assessed. Immune profiling was performed to evaluate T cell phenotypes, and CD8⁺ T cell depletion experiments were conducted to assess the role of this population. Protection against tumor rechallenge was considered to evaluate long-term immunity.

Neoadjuvant vaccination alone provided approximately 70% protection against tumor recurrence. When combined with anti-PD1, protection increased to 90%. Notably, anti-PD1 alone conferred 60% protection when used in a neoadjuvant setting. In contrast, adjuvant vaccination was ineffective as monotherapy and required combination with anti-PD1 to prevent relapse. The efficacy of neoadjuvant vaccination was dependent on CD8⁺ T cells and associated with robust effector memory T cell responses. Long-term protection against tumor rechallenge was superior in the neoadjuvant vaccine group compared with anti-PD1 alone.

Neoadjuvant nAg vaccination elicits potent CD8⁺ T cell-mediated immunity and offers superior protection against tumor recurrence and rechallenge compared with adjuvant approaches or checkpoint blockade alone. These findings support the clinical evaluation of neoadjuvant cancer vaccines, particularly in settings where tumors are resistant to conventional immunotherapy.