Castration-resistant prostate cancer (CRPC) remains difficult to treat with conventional chemotherapy. We evaluated a stem cell-based enzyme-prodrug strategy using hTERT-immortalized adipose-derived stem cells engineered to express rabbit carboxylesterase 2 (hTERT-ADSC.CE2) in combination with irinotecan (CPT-11). hTERT-ADSC.CE2 cells were generated via lentiviral transduction and confirmed to overexpress CE2. Their tumor-homing capacity toward PC3 prostate cancer cells was assessed, along with prodrug activation, apoptosis induction, and in vivo tumor suppression in a CRPC mouse model. hTERT-ADSC.CE2 cells demonstrated enhanced migration toward PC3 cells and higher expression of tumor-homing factors than the controls. Under CPT-11, they exhibited a strong “suicide” effect and induced selective killing of PC3 cells, with upregulation of BAX and cleaved caspase-3 and downregulation of BCL-2. By day 14, the combination arm showed significantly lower tumor burden than both the control and irinotecan-alone arms (p < 0.05). The pattern is consistent with intratumoral activation and localized SN-38 exposure. hTERT-ADSC.CE2 combined with irinotecan provides potent, tumor-targeted cytotoxicity and markedly suppresses CRPC progression. This cell-mediated prodrug activation system may represent a promising therapeutic approach for advanced prostate cancer.
Background/Objectives: This NGS-based study sought to identify novel molecular markers for prostate cancer by comparing miRNA expression in cancer and benign prostatic hyperplasia (BPH) tissues. Methods: Using high-throughput sequencing and stringent statistical criteria, the study identified eleven significantly dysregulated miRNAs (five downregulated, six upregulated) that differentiate the two conditions. Enrichment analyses linked these miRNAs to several key cancer-associated pathways, including PI3K–Akt and ErbB signaling. Results: Crucially, the protein vesicle-associated membrane protein-associated protein B (VAPB) was pinpointed as a central hub, regulated by three downregulated miRNAs (miR-143-3p, miR-221-3p, and miR-222-3p). Since VAPB has not been widely studied in prostate cancer, it represents a promising, novel candidate for both diagnosis and therapeutic targeting. Conclusions: Our NGS-based analysis revealed a distinct miRNA expression signature that differentiates prostate cancer from BPH. The downregulation of several tumor-suppressive miRNAs (with concomitant upregulation of oncogenic miRNAs) in prostate cancer may contribute to malignancy—including the de-repression of novel targets like VAPB, which we identify as a promising new biomarker and therapeutic target.
Purpose: Current therapies using midurethral sling mesh to treat stress urinary incontinence (SUI) are often considered insufficient. This study aims to evaluate the therapeutic efficacies of a minimally invasive implantable wireless electrical stimulator as an alternative treatment of SUI.Methods: SUI was induced in 12 female, 12-week-old Sprague-Dawley rats with a deteriorated urethral sphincter complex by mechanical dilatation of the vagina. Six rats underwent sham operations. Four weeks after inducing SUI, 12 rats with SUI were divided into 2 groups. One group received a transplantation of an implantable wireless electrical stimulator, and the other midline incision and suturing. A total of 4 electrical stimulations were applied for 30 minutes twice weekly for 4 weeks in implantation model. Cystometric parameters including leak point pressure, urethral pressure and electromyography, histological examinations, immunostaining for Masson trichrome stain were measured at 4 weeks after intervention.Results: After SUI induction, mean leak point pressure (LPP) was significantly lower in SUI groups than in controls (25.0±6.9 cm H2O vs. 62.6±4.1 cm H2O, P=0.012). At 4-week postintervention, the +ES group (SUI rat model with stimulation) demonstrated significantly higher LPP than the −ES group (48.8±8.4 cm H2O vs. 26.0±6.6 cm H2O, P=0.002). Urethral pressure showed a nonsignificant upward trend in the +ES group (SUI rat model without stimulation) compared with −ES (20.5±1.4 cm H2O vs. 18.1±1.1 cm H2O, P=0.070). Histology showed improved tissue organization with reduced inflammatory infiltration, and Masson staining demonstrated a trend toward higher collagen density in +ES (bladder: 28.3%±5.2% vs. 32.5%±7.6%, P=0.292; urethra: 44.2%±8.6% vs. 51.7%±8.2%, P=0.153).Conclusions: These results indicate that an implantation of a wireless electrical stimulator can help to improve urethral sphincter function in SUI rat model. Moreover, the minimally invasive wireless electrical strategy may represent a promising therapeutic modality for pelvic floor muscle rehabilitation in the treatment of SUI with potential for clinical translation.
Purpose: To evaluate the pilot clinical feasibility of an automatic urinary suction device in mobility-limited older adults, focusing on usability, functional performance, and perceived safety, and a secondary exploratory assessment of agreement between device-collected and reference urine specimens.Methods: A 2-cohort clinical evaluation was conducted. The primary usability cohort assessed functional performance, perceived safety, and user satisfaction using structured 5-point Likert-scale questionnaires administered before and after device implementation. A secondary diagnostic cohort compared paired urine samples obtained using the automated suction device and standard-of-care reference urine collection methods to assess bacterial detection agreement, species concordance, and urine pH agreement. Paired statistical analyses with nonparametric sensitivity testing were used for usability outcomes, and diagnostic metrics were calculated with Wilson confidence intervals and Bland-Altman analysis.Results: Seven participants completed paired usability assessments. Significant improvements were observed in operation and functionality (2.97±0.52 vs. 3.83±0.18, P=0.007) and ease of use (2.14±0.48 vs. 3.71±0.39, P=0.001), suggesting improved practicality of urinary management. Scores in the infection/skin complication domain decreased significantly. Product safety and overall satisfaction showed favorable but nonsignificant trends. In a secondary exploratory diagnostic analysis of 12 paired urine samples, bacterial detection agreement was acceptable at the presence/absence level (sensitivity 80.0%, specificity 100.0%, accuracy 91.7%), whereas species-level concordance was limited (40.0%), indicating restricted microbiologic reliability. Urine pH showed close numerical agreement. However, these findings should be interpreted cautiously, as key preanalytical variables were not controlled, and therefore should be regarded as exploratory rather than confirmatory.Conclusions: This pilot study suggests that the automated urinary suction device may improve usability and functional handling in mobility-limited older adults. Skin-related findings remain preliminary, and the diagnostic applicability of device-collected urine should be interpreted cautiously pending further validation.
Purpose: Prostate cancer is one of the most common malignancies in men, yet current prognostic methods remain suboptimal. Emerging evidence indicates that microRNAs (miRNAs) play critical roles in prostate cancer progression. This study aimed to identify miRNAs associated with adverse clinical outcomes by comparing miRNA expression profiles between prostate tumors with unfavorable versus favorable prognostic features. Materials and Methods: High-throughput next-generation sequencing (NGS) was used to analyze miRNA expression in formalin-fixed, paraffin-embedded prostate cancer tissue samples. Patients were classified into favorable or unfavorable prognosis groups based on risk stratification scores, Gleason grade group, and biochemical recurrence. Differentially expressed miRNAs were identified using a fold-change threshold ≥2 and a false discovery rate (FDR) <0.05. Predicted target genes and pathway analyses were conducted to generate candidate regulatory hypotheses rather than confirm mechanistic relationships. Results: Several miRNAs were differentially expressed according to prognostic category. miR-206 was significantly downregulated in high-risk tumors compared with low-risk tumors. High-Gleason-grade tumors showed reduced expression of miR-7704 and miR-4454, while miR-25-3p and let-7f-5p were upregulated. In patients with early biochemical recurrence, miR-7704 and miR-10400-5p were downregulated relative to those with prolonged recurrence-free survival. Target prediction analysis identified CPEB3, HAND1, PTAR1, and SPRYD4 as shared candidate targets, with CPEB3 emerging as a prioritized candidate supported by consistency in external datasets rather than a confirmed molecular target. Conclusions: Distinct miRNA expression patterns correlate with prostate cancer aggressiveness and clinical outcomes. miR-206, miR-7704, miR-4454, miR-25-3p, and let-7f-5p represent candidate prognostic biomarkers. Their shared target CPEB3 should be interpreted as a prioritized candidate for future investigation. Given the very small sample size and the lack of qRT-PCR and functional validation, these findings should be considered preliminary and hypothesis-generating, requiring validation in larger independent cohorts and experimental studies.
Ubiquitin-specific protease 13 (USP13) is a deubiquitinating enzyme that stabilizes phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a well-established tumor suppressor involved in PI3K/AKT signaling. This study aimed to evaluate the relationship between USP13 immunohistochemical staining intensity and clinicopathological factors associated with prostate cancer progression. USP13 staining was scored as grade 0 (negative), 1 (weak), 2 (moderate), or 3 (strong) in 242 prostate cancer tissues and 22 adjacent non-neoplastic control tissues. Higher USP13 grades were exhibited by adjacent non-neoplastic tissues than prostate carcinoma. In comparison, lower USP13 grades were observed in 88.6% of the neoplastic regions (p < 0.001). No differences in PSA level, Gleason’s score, disease stage, involvement of either the seminal vesicle or lymph nodes, surgical margin positivity, biochemical or clinical recurrence rates, or overall survival statistics were found. Cox proportional hazards modeling showed no significant association between USP13 expression and biochemical recurrence-free survival or overall survival. Kaplan–Meier analysis demonstrated no statistically significant differences in survival outcomes according to USP13 expression, although a descriptive trend was observed. USP13 immunohistochemical staining distinguished malignant prostate tissue from adjacent non-neoplastic tissue in tissue microarrays. However, USP13 expression was not independently associated with pathological aggressiveness or survival outcomes in this cohort.