This study focuses on investigation of cryptorchidism induced by flutamide (Flu) and its histopathological damage, and detects retinoic acid concentration in testicle tissue, in order to find a new method for clinical treatment to infertility caused by cryptorchidism. Twenty SD (Sprague Dawley) pregnant rats were randomly divided into Flu cryptorchidism group (n = 10) and normal control group (n = 10). HE stained for observing morphological difference. Transmission electron microscope (TEM) was used for observing the tight junction structure between Sertoli cells. Epididymal caudal sperms were counted and observed in morphology. The expression of stimulated by retinoic acid gene 8 (Stra8) was detected using immunohistochemistry, western blot, and Q-PCR. High performance liquid chromatography (HPLC) analysis was made on retinoic acid content. Sperm count and morphology observation confirmed cryptorchidism group was lower than normal group in sperm quantity and quality. The observation by TEM showed a loose structure of tight junctions between Sertoli cells. Immunohistochemistry, western blot, and Q-PCR showed that cryptorchidism group was significantly lower than normal group in the expression of Stra8. HPLC showed that retinoic acid content was significantly lower in cryptorchid testis than in normal testis. In the cryptorchidism model, retinoic acid content in testicular tissue has a significant reduction; testicles have significant pathological changes; damage exists in the structure of tight junctions between Sertoli cells; Stra8 expression has a significant reduction, perhaps mainly contributing to spermatogenesis disorder.
Glioblastomas are brain tumors with extensive vascularization that are associated with tumor malignancy. The phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT) signaling pathway is activated in endothelial cell tumors, although its exact function in glioblastoma neovascularization is poorly characterized. The present study identified that endothelial cells derived from human glioblastomas exhibit increased permeability and motility compared with normal brain vascular endothelial cells. Furthermore, the phosphorylation of AKT was significantly induced in glioblastoma‑derived endothelial cells and glioblastoma vessels. To the best of our knowledge, the present study demonstrated for the first time that the cell‑cell adhesion junction protein Afadin is phosphorylated and re‑localized in glioblastoma‑derived endothelial cells, and the phosphorylation and re‑localization of Afadin is PI3K/AKT pathway‑dependent. AKT‑mediated phosphorylation and re‑localization of Afadin may be critically involved in the modulation of brain endothelial permeability and migration. Therapies targeting the PI3K/AKT/Afadin pathway may therefore be beneficial for reducing the angiogenic potential of glioblastoma.
Wilms’ tumor (WT) is a common renal malignancy in children. Although certain patient groups exhibit high survival rates, those experiencing recurrence, metastasis, or chemoresistance face significant challenges. The identification of reliable prognostic markers is essential for adapting treatment strategies to enhance survival rates and reduce chemotherapy-related adverse events (CRAEs). This study included patients diagnosed with WT at our institution. Inflammatory biomarkers were measured from pre-treatment blood tests, and their associations with event-free survival (EFS) and overall survival (OS) were evaluated using Kaplan-Meier and Cox regression analyses. The relationship between biomarkers and CRAEs was examined through logistic regression. Multifactorial Cox regression analysis identified tumor stage (HR = 4.68, 95% CI: 1.58–13.87, p = 0.005), pan-immune-inflammation value (PIV) (HR = 3.94, 95% CI: 1.80–8.60, p < 0.001), and neutrophil-to-lymphocyte ratio (NLR) (HR = 0.40, 95% CI: 0.18–0.90, p = 0.027) as independent prognostic factors for EFS. Multivariate Cox regression revealed that stage IV (HR = 12.24, 95% CI: 1.56–95.85, p = 0.017) and PIV levels exceeding 246.4 (HR = 5.50, 95% CI: 2.13–14.19, p < 0.001) were significant predictors for OS. Additionally, high PIV (OR 2.32, 95% CI: 1.15–4.67, p = 0.018) independently predicted the occurrence of CRAEs. WT patients with higher PIV levels showed significant associations with poorer EFS, worse OS, and an increased likelihood of developing CRAEs during treatment.
Background: Wilms tumor (WT), which represents about 90% of kidney tumors in children, is the most prevalent type of renal tumor among children. In developed countries, advancements in treatments such as chemotherapy and radiotherapy have led to high survival rates. However, developing countries face significant challenges, including late-stage diagnosis, metastasis at presentation, and high rates of treatment abandonment.Methods: This retrospective study included all patients diagnosed with WT at a tertiary hospital in Western China from 2007 to 2021. It involved the collection of sociodemographic and clinical details, including data on patients who abandoned treatment. Follow-up continued until July 2024.Results: This study consisted of 301 WT patients. Of the 259 who completed the treatment, the 5-year event-free survival (EFS) and overall survival (OS) rates were 77.9% and 81.2%. Of the 42 patients who abandoned treatment, 13 refused further care immediately after diagnosis and signed a refusal document, 16 discontinued treatments during preoperative neoadjuvant chemotherapy, and 13 failed to complete the prescribed chemotherapy or radiotherapy.Conclusion: Survival rates for WT patients at our institution approach those reported in developed countries. Challenges include late-stage diagnosis, metastasis at initial presentation, and treatment abandonment. To address these issues, implementing pediatric screening is critical for early detection and timely intervention, particularly for families vulnerable to abandoning treatment. For high-risk cases, oncologists need develop targeted strategies to enhance clinical outcomes.