To investigate the feasibility and safety of surgical treatment for Peyronie’s disease (PD) by excising and repairing plaque using autologous tunica vaginalis of testis. From March 2007 to December 2012, total 19 patients with PD underwent surgical treatment at our center. All patients had significant phallocampsis during erection. All patients complained of decreased sexual function. During the operation, the fibrotic plaque was excised and neurovascular bundle (NVB) was spared. A size-matching autologous tunica vaginalis of testis was harvested as the graft and patched to the defect. All patients received follow up every 3 months in the first year and 6 months in the following years. Data on sexual function before and after the operation was collected and compared. All operations were completed successfully without serious complications. The mean operative time was 74 min. The mean size of excised plaque was 3.0 cm2. Postoperative pathological studies revealed the fibroplastic hyperplasia of excised tissue. All patients had satisfactory correction of penile appearance. The erectile penile length between pre- and post-operation didn’t show significant difference. Postoperative intercourse satisfaction and overall satisfaction measured by IIEF-5 were significant improved. Our surgical treatment is feasible and safe for patients with PD. It can effectively improve the penile cosmetic appearance and patients’ intercourse/overall satisfaction on sexual life.

Background: Apolipoprotein C1 (APOC1) has been proved to play a critical role in gastric, breast, lung, and pancreatic cancer. However, the relationship between APOC1 and urinary tumors remains unclear. This study aimed to assess the diagnostic and prognostic value of APOC1 in urinary tumors. Methods: We performed a pan analysis of APOC1 mRNA expression in urinary cancer using the Gene Expression Profiling Interactive Analysis (GEPIA) database. To further investigate the prognostic value of APOC1 expression in urinary cancers, the Kaplan-Meier plotter database was used. Furthermore, we collected the tumor and adjacent normal samples of 32 ccRCC patients to perform qRT-PCR and western blotting assays. A total of 72 cases with ccRCC were analyzed using tissue microarrays (TMAs). Results: Our results based on Kaplan-Meier plotter database indicated that a high expression of APOC1 may lead to poor overall survival (OS, p = 0.0019) in patients with ccRCC. Furthermore, the cancer stages and tumor grade of ccRCC appeared to be strongly linked with APOC1 expression according to UALCAN database. Hence, we reached a preliminary conclusion that APOC1 may play a key role in the tumorigenesis and progression of ccRCC. Furthermore, the Kaplan-Meier survival curve analyses of 72 clinical patients indicated that high expression of APOC1 was associated with poor progression-free survival (PFS, p = 0.007) and OS (p = 0.022). In addition, univariate Cox regression analysis confirmed the significant relationship between APOC1 expression and survival (p = 0.038). The TMAs analysis in combination with the patients' clinicopathological features was also performed. The expression of APOC1 was found to be significantly correlated with the tumor size (p = 0.018) and histological grade (p = 0.016). Conclusions: In conclusion, the findings of our study suggest that APOC1 may serve as a novel diagnostic and prognostic biomarker for ccRCC. Further evidence on the mechanism of APOC1 promoting tumor progression may transform it to a new therapeutic target for the treatment of ccRCC.

Background: Ubiquitylation modification is one of the multiple post-transcriptional process to regulate cellular physiology, including cell signaling, cycle regulation, DNA repair and transcriptional regulation. Members of TRIM family proteins could be defined as E3 ubiquitin ligases as they contain a RING-finger domain, and alterations of TRIM proteins are involved into a broad range of diverse disorders including cancer. TRIM37 is a novel discovered E3 ubiquitin ligase and acts as a oncoprotein in multiple human neoplasms, however its biological role in RCC still remains elusive.Methods: RCC microarray chips and public datasets were screened to identify novel TRIMs member as TRIM37, which was dysregulated in RCC. Gain or loss of functional cancer cell models were constructed, and in vitro and in vivo assays were performed to elucidate its tumorigenic phenotypes. Interactive network analyses were utilized to define intrinsic mechanism.Results: We identified TRIM37 was upregulated in RCC tumors, and its aberrant function predicted aggressive neoplastic phenotypes, poorer survival endings. TRIM37 promoted RCC cells EMT and malignant progression via TGF-β1 signaling activation, as a consequence of directly mediated by ubiquitinating-H2A modifications.Conclusions: Our findings identified a previously unappreciated role of TRIM37 in RCC progression and prognostic prediction. Importantly, we declared a novel ubiquitination-dependent link between TRIM ubiquitin ligases and TGF-β1 signaling in regulating cancerous malignancies.

Most advanced prostate cancer (PCa) patients initially respond well to androgen deprivation therapy, but almost all eventually develop castration-resistant prostate cancer (CRPC). Early studies indicated the bipolar androgen therapy via a cycling of high dose and low dose of androgen to suppress PCa growth might be effective in a select patient population. The detailed mechanisms, however, remain unclear. Here we found the capacity of natural killer (NK) cells to suppress the CRPC cells could be suppressed by a high dose of dihydrotestosterone (DHT). Mechanism dissection indicates that transactivated AR can increase circularRNA-FKBP5 (circFKBP5) expression, which could sponge/inhibit miR-513a-5p that suppresses the PD-L1 expression via direct binding to its 3ʹUTR to negatively impact immune surveillance from NK cells. Preclinical data from in vitro cell lines and an in vivo mouse model indicate that targeting PD-L1 with sh-RNA or anti-PD-L1 antibody can enhance the high dose DHT effect to better suppress CRPC cell growth. These findings may help us to develop novel therapies via combination of high dose androgen with PD-1/PD-L1 checkpoint inhibitors to better suppress CRPC progression.

Advanced prostate cancer (PCa) is associated with a poor prognosis, particularly in patients who progress to castration-resistant prostate cancer (CRPC). The emergence of enzalutamide (Enz), a second-generation androgen receptor inhibitor, has effectively extended the median survival of these patients. However, drug resistance frequently develops during clinical use. Multiple studies have suggested that ferroptosis inducers can reverse cancer resistance to Enz, though the exact mechanisms remain unclear. In this study, we found that CRPC cells exhibit a concentration-dependent decrease in ferroptosis in response to Enz. This change is attributed to the upregulation of the protein level of SLC7A11. Protein stability assays and database analyses showed that SLC7A11 undergoes post-translational modification, likely connected to Enz-mediated downregulation of the SLC7A11-specific E3 ubiquitin ligase NEDD4L. This phenomenon was significantly reversed by the addition of erastin, a targeted inhibitor of the cystine/glutamate transport system Xc-. The data from both in vitro and in vivo experiments indicate that combining Enz with erastin significantly inhibits the proliferation of drug-resistant CRPC cells, thereby enhancing tumor suppression. These findings offer novel insights into targeting SLC7A11 with erastin as a potential strategy to overcome Enz resistance.