Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Background: To analyze the expression of karyopherin alpha 2 (KPNA2) in upper tract urothelial carcinoma (UTUC) and to investigate whether the KPNA2 expression provides additional prognostic information following radical nephroureterectomy (RNU).
Methods: A tissue microarray (TMA) containing samples from 176 patients with UTUC who underwent RNU at our institute was analyzed for KPNA2 expression using immunohistochemistry. KPNA2 expression in normal urothelial cell line and urothelial carcinoma cell lines was evaluated by western blot analysis. Using RNA interference in vitro, the effects of KPNA2 inhibition on cellular viability, migration and apoptosis were determined.
Results: KPNA2 expression was significantly upregulated in the UTUC samples compared with the adjacent normal urothelial tissues. High KPNA2 immunoreactivity was identified as a predictor of bladder recurrence (hazard ratio [HR]: 2.017, 95% CI 1.13-3.61, p = 0.018), poor disease-free survival (DFS, HR: 2.754, 95% CI 1.68-4.51, p = 0.001) and poor overall survival (OS, HR: 4.480, 95% CI 1.84-10.89, p = 0.001) for patients with UTUC after RNU. Furthermore, high KPNA2 immunoreactivity was independent of the conventional predictive factors in a multivariate analysis. Additional in vitro experiments revealed that KPNA2 expression was higher in urothelial carcinoma cell lines than in normal urothelial cell line. KPNA2 inhibition with a specific siRNA decreased cell viability and migration and increased apoptosis in urothelial carcinoma cell lines.
Conclusions: KPNA2 is a novel independent prognostic marker for bladder recurrence, DFS and OS of UTUC patients who have undergone RNU. Moreover, these data suggest that KPNA2 may be a promising therapeutic target for UTUC.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432830 | PMC |
| http://dx.doi.org/10.1186/s12885-015-1369-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Low-grade non-muscle-invasive bladder cancer: molecular landscape, treatment strategies and emerging therapies.
Nat Rev Urol
September 2025
Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Low-grade non-muscle invasive bladder cancer is a specific category of bladder cancer with a favourable prognosis; however, its management presents several challenges. The risk of stage progression is very low, but approximately half of patients will experience recurrence within the first 5 years after diagnosis. This high propensity for recurrence, coupled with the threat of progression, mandates ongoing surveillance.
View Article and Find Full Text PDFModulating the PPARγ pathway upregulates NECTIN4 and enhances chimeric antigen receptor (CAR) T cell therapy in bladder cancer.
Nat Commun
September 2025
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
With the approval of the antibody-drug conjugate enfortumab vedotin (EV), NECTIN4 has emerged as a bona fide therapeutic target in urothelial carcinoma (UC). Here, we report the development of a NECTIN4-directed chimeric antigen receptor (CAR) T cell, which exhibits reactivity across cells expressing a range of endogenous NECTIN4, with enhanced activity in high expressors. We demonstrate that the PPARγ pathway, critical for luminal differentiation, transcriptionally controls NECTIN4, and that the PPARγ agonist rosiglitazone primes and augments NECTIN4 expression, thereby increasing sensitivity to NECTIN4-CAR T cell-mediated killing.
View Article and Find Full Text PDFThe Pretreatment Neutrophil-to-Eosinophil Ratio Can Predict Immune-Related Adverse Events and Outcomes in Patients With Advanced Urothelial Carcinoma Treated With Immune Checkpoint Inhibitors.
Cureus
August 2025
Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, JPN.
Introduction Currently, treatment regimens incorporating immune checkpoint inhibitors (ICIs) are the standard of care for locally advanced or metastatic urothelial carcinoma (la/mUC). This study aimed to investigate the association between the neutrophil-to-eosinophil ratio (NER) and the occurrence of immune-related adverse events (irAEs) as well as treatment outcomes. Methods This multicenter retrospective study examined patients with la/mUC treated with ICIs between January 2017 and December 2022.
View Article and Find Full Text PDFA Literature Review and Management Approach for Severe Skin Toxicity Induced by Enfortumab Vedotin Through Sequential Adaptation and Combination With Immune Checkpoint Inhibitors.
Cureus
August 2025
Department of Urology, The Institute of Medical Science, The University of Tokyo, Tokyo, JPN.
In patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy, enfortumab vedotin (EV) improves overall survival compared to standard chemotherapy. Additionally, for treatment-naïve patients with locally advanced or metastatic urothelial carcinoma, the combination of pembrolizumab and EV demonstrates superior efficacy over platinum-based chemotherapy. Hence, EV becomes a standard treatment option.
View Article and Find Full Text PDFPrimary bladder diffuse large B-cell lymphoma: A rare case report.
Int J Surg Case Rep
September 2025
Department of Urology, The Second Affiliated Hospital, Kunming Medical University, Yunnan Province, China. Electronic address:
Introduction: Diffuse large B-cell lymphoma (DLBCL), a common subtype of non-Hodgkin lymphoma (NHL), originates primarily from lymph nodes, with a small proportion arising extranodally in sites such as the gastrointestinal tract and central nervous system. Given the general absence of lymphoid tissue in the bladder, primary bladder DLBCL is exceptionally rare.
Case Presentation: This case report describes an 83-year-old male patient with a bladder mass, initially suspected as cystitis glandularis, ultimately diagnosed via pathological examination as DLBCL.