RENAL nephrometry scoring system in bilateral Wilms tumor: predictive application.

AIM: This study aims to explore the application of RENAL nephrometry scoring system in bilateral Wilms tumor (BWT). METHODS: A retrospective review of patients with BWT from January 2010 to June 2022 was performed. Each kidney unit of the BWT was evaluated independently and scored according to RENAL nephrometry scoring system by 2 blinded reviewers, and reviewers were blinded to what surgery the patients ultimately had. Discrepancies were evaluated by a third reviewer to reach a consensus. Tumor anatomical characteristics were summarized and compared. RESULTS: 29 patients with 53 kidney units were included in the study. 53 kidney units included 12 (22.6%) low-complexity, 9 (17.0%) intermediate-complexity, and 32 (60.4%) high-complexity. 2 kidney units (3.8%) had tumor thrombus, and 14 (26.4%) had multiple lesions. A total of 42 kidney units (79.2%) underwent initial nephron-sparing surgery (NSS) and 11 (20.8%) underwent radical nephrectomy. Less complexity tumors were observed in the NSS group. Of the 42 kidney units undergoing initial NSS, 26 were performed in vivo and 16 ex vivo via autotransplantation. The latter group featured a higher complexity. During follow-up, 22 patients survived and 7 died, no statistically significant tumor complexity was observed between the two groups. CONCLUSIONS: The anatomical characteristics of BWT are complex. Despite this study did not indicate that the complexity correlates with prognosis, low-complexity tumors were candidates for NSS, and kidney autotransplantation provided a feasible procedure for high-complexity tumors. A refined system is required due to multiple lesions and tumor thrombus.

[Corrigendum] Celecoxib inhibits the epithelial­to­mesenchymal transition in bladder cancer via the miRNA­145/TGFBR2/Smad3 axis.

Following the publication of the above article, an interested reader drew to the authors' attention that, for the Transwell migration assays shown in Figs. 1B and 3B on p. 685 and p. 688 respectively, the images selected for the '5637 / DMSO' experiment in Fig. 1B and the DMSO experiment in Fig. 3B were apparently the same, such that these data appeared to have been derived from the same original source. After having consulted their original data, the authors have realized that the 5637 DMSO data panel in Fig. 3B had been selected incorrectly. The revised version of Fig. 3, showing the correct data for the DMSO experiment in Fig. 3B, is shown on the next page. The authors regret that these errors went unnoticed prior to the publication of this article, and thank the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this corrigendum. All the authors agree with the publication of this corrigendum; furthermore, they also apologize to the readership of the journal for any inconvenience caused. [International Journal of Molecular Medicine 44: 683­683, 2019; DOI: 10.3892/ijmm.2019.4241].

Serum Soluble B Cell-Activating Factor Is a Non-Invasive Biomarker of Antibody-Mediated Rejection in Kidney Allograft With Satisfactory Risk Stratification Performance But Negligible Diagnostic Value.

Objectives: B cell-activating factor (BAFF), which is critical in the activation and differentiation of B cells, is a candidate diagnostic and predictive biomarker for antibody-mediated rejection (ABMR). We aimed to investigate the value of serum soluble BAFF (sBAFF) for the diagnosis and risk stratification of ABMR after kidney transplantation. Methods: In the diagnostic study, sBAFF level among ABMR (n = 25), T cell-mediated rejection (TCMR) (n = 14), 4 other pathological lesions (n = 21), and stable allograft function group (n = 15) were compared. In the nested case-control study, kidney allograft recipients with de novo donor-specific antibody (DSA) or ABMR (n = 16) vs. stable allograft function (n = 7) were enrolled, and sBAFF was measured preoperatively, at D7, M1, M3, M6, M9, M12, M18 posttransplant and at allograft biopsy. Results: There was no significant difference in sBAFF level at biopsy between ABMR and non-ABMR groups. Longitudinal study showed that the sBAFF levels decreased dramatically at D7 in both groups. The sBAFF level in the DSA group started to increase within M1, while in the stable group, it maintained a low level until M3 and M6. The sBAFF levels of the DSA group were significantly higher than that of the stable group at M1 [1,013.23 (633.97, 1,277.38) pg/ml vs. 462.69 (438.77, 586.48) pg/ml, P = 0.005], M3 [1,472.07 (912.79, 1,922.08) pg/ml vs. 561.63 (489.77, 630.00) pg/ml, P = 0.002], and M6 [1,217.95 (965.25, 1,321.43) pg/ml vs. 726.93 (604.77, 924.60) pg/ml, P = 0.027]. sBAFF levels at M3 had the best predictive value for the DSA/ABMR with the area under the receiver operating characteristic (AUROC) curve value of 0.908. The predictive performance of the maximum (max) change rate from D7 to the peak within M3 was also excellent (AUROC 0.949, P = 0.580). Conclusion: We clarified by a diagnostic study that sBAFF is not a diagnostic biomarker for ABMR in kidney transplantation and revealed by a nested case-control study that sBAFF values at M3 posttransplant and dynamic changes in sBAFF within M3 posttransplant have a good predictive value for the DSA/ABMR. It provides a useful tool for early screening of low-risk patients with negative preoperative DSA for the risk of developing postoperative DSA in kidney allograft recipients.

Celecoxib inhibits the epithelial-to-mesenchymal transition in bladder cancer via the miRNA-145/TGFBR2/Smad3 axis.

Celecoxib, a selective cyclooxygenase­2 inhibitor, has chemo­preventive activity against different cancer types, including bladder cancer (BC). However, the mechanisms by which celecoxib exerts its cancer preventative effects have yet to be completely understood. In the present study, the effect of celecoxib on the epithelial­to­mesenchymal transition (EMT) of BC cells and its potential molecular mechanisms were investigated. The results of the present study demonstrated that celecoxib inhibited the proliferation, migration, invasion and EMT of BC cells. Further investigation of the underlying mechanism revealed that celecoxib inhibited EMT by upregulating microRNA (miR)­145 and downregulating the expression of transforming growth factor ß receptor 2 and SMAD family member 3. Furthermore, the combination of celecoxib with miR­145 mimics demonstrated an additive migration and invasion­inhibitory effect in BC cell lines.

NCK1 promotes the angiogenesis of cervical squamous carcinoma via Rac1/PAK1/MMP2 signal pathway.

OBJECTIVE: The study was to explore the roles of Nck1 in the angiogenesis of cervical squamous cell carcinoma (CSCC). METHODS: mRNA and protein levels were evaluated with real-time quantitative PCR and immunohistochemisty/western blotting respectively. The cancer microvessel density (MVD) was assayed with CD34 endothelial labeling. Nck1 gene knock-in (SiHa-Nck1+) and knock-down (SiHa-Nck1-) were achieved by gene transfection and siRNA respectively. Protein level from cellular supernatant was measured with ELISA. Proliferation, migration and tube formation of the Human Umbilical Vein Endothelial cells (HUVECs) were evaluated by CCK-8 cell viability assay, transwell chamber assay and in vitro Matrigel tubulation assay respectively. RESULTS: Nck1 level gradually increased from normal cervical epithelia to high-grade CIN, overexpressed in CSCC and was associated with cancer MVD. The ability of proliferation, migration and tube formation of HUVECs was enhanced in SiHa-Nck1+-treated while decreased in SiHa-NcK1--treated cells compared to SiHa-control-treated cells. Mechanistically, RAC1-GTP, p-PAK1 and MMP2 were increased in SiHa-NCK1+ cells and pretreatment with the Rac1 inhibitor (NSC23766) significantly decreased their levels. Furthermore, inhibition of PAK1 reduced MMP2 level in SiHa-Nck1+ cells whereas the level of Rac1-GTP was unaltered. Also, inhibition of Rac1 or PAK1 impaired angiogenesis-inducing capacity of cancer cells. CONCLUSIONS: Nck1 promotes the angiogenesis-inducing capacity of CSCC via the Rac1/PAK1/MMP2 signal pathway.

CCL18 enhances migration, invasion and EMT by binding CCR8 in bladder cancer cells.

Increased expression of CCL18 has been observed in various malignancies and in the urine samples of patients with bladder cancer (BC). However, the roles of CCL18 in the development, progression and metastasis of BC remain unclear. The present study demonstrated that CCL18 expression was significantly associated with advanced clinical stages of BC. Furthermore, exogenous CCL18 promoted cell invasion and migration, and induced cell epithelial­mesenchymal transition (EMT) in BC cells. Western blotting demonstrated that E­cadherin, an epithelial marker, was decreased, whereas matrix metalloproteinase (MMP)­2 and vascular endothelial growth factor (VEGF)­C were increased in CCL18­treated cells. Blocking CCR8 via a small molecule inhibitor or short hairpin (sh)RNA mitigated the decrease in E­cadherin, and increase in MMP­2 and VEGF­C, caused by human recombinant (r)CCL18. CCR8 knockdown by shRNA reversed rCCL18­induced cancer cell invasion, migration and EMT. In conclusion, these data suggested that CCL18 may promote migration, invasion and EMT by binding CCR8 in BC cells. Inhibition of CCL18 activity by blocking CCR8 could be a potential therapeutic strategy for preventing the progression of BC.