RESUMEN
Background & Objective: Cell surface expression of sortilin in different types of cancer signifies it as a therapeutic target for cancer therapy. The aim of this study was to detect sortilin expression in bladder cancer cells using an anti-sortilin monoclonal antibody (mAb) to evaluate sortilin as a target for developing diagnostic and therapeutic agents against bladder carcinoma. Methods: The protein expression of sortilin in bladder cancer tissues and cell lines (5637 and EJ138) was investigated by immunohistochemistry (IHC), immune-cytochemistry (ICC), and flow cytometry. Furthermore, the capability of anti-sortilin mAb in apoptosis induction in bladder cancer cells was evaluated. Results: A high expression level was observed in bladder carcinoma tissues (P≤0.001) and cell lines, using IHC and ICC, respectively. Flow cytometry results showed cell surface expression of 27.5±3% (P≤0.01), 74.4±7.8% (P≤0.001), and 4.2±0.4% of sortilin in EJ138, 5637, and HFFF cells, respectively. In EJ138 anti-sortilin mAb induced apoptosis in 25.2±11.5% (P≤0.05) (early) and 4.5±1.1% (P>0.05) (late) after 6 h incubation, while for 12 h, the values of 11.6±3.8% (P>0.05) and 20.7±4.4% (P≤0.05) were achieved. In 5637 cells, 6 h incubation resulted in 10.2±0.3% (P>0.05) and 6.6±1.4% (P>0.05) apoptosis induction, while these values were 12.1±0.8% (P>0.05) and 27.4±4.5% (P≤0.01) after 12 h. The HFFF cells did not show significant apoptosis. Conclusion: The overexpression of sortilin in bladder tumor cells and its potential in inducing apoptosis via directed targeting with the specific monoclonal antibody may represent this protein as a potential candidate of targeted therapy in bladder carcinoma.
RESUMEN
PURPOSE: A comparison of the LeadCare II (LCII) point-of-care (POC) device with the gold standard graphite furnace atomic absorption spectroscopy (GFAAS) device was done in the context of post-mortem blood lead concentrations to determine comparability for screening value. METHODS: Consecutive autopsy cases from March 2018 to March 2019 were examined by the forensic medicine center. Blood samples with lead concentrations <10 µg dL-1 by LCII analysis were excluded from GFAAS analysis. Samples were collected from femoral veins or cardiac chambers. Bland-Altman analysis was conducted to evaluate the agreement between both GFAAS and LCII lead values. Linear regression modeling was performed to predict GFAAS results based on LCII results. Five-hundred post-mortem blood samples were evaluated by LCII for blood lead. For 46 cases with LCII blood lead level (BLL) values more than 10 µg dL-1, further analysis was performed by GFAAS. RESULTS: Mean difference of BLL between the two methods was 5.92 µg dL-1 (SD = 7.51; range: -14 to 23.7). GFAAS BLL values were significantly higher than LCII values (p = 0.029). Moreover, substance-user samples had significantly higher GFAAS BLLs (p = 0.006; mean difference = 11.62 µg dL-1). A significant regression equation was found (F [1, 44] = 108.44, p < 0.001, with an R2 of 0.711). Based on Bland-Altman plot averages for both predicted GFAAS BLL and measured GFASS BLL showed a mean difference was 0.014 (SD = 7.51; range: -17.9 to 20). CONCLUSION: In conclusion, on post-mortem BLL samples, LCII and GFAAS show favorable correlation. LCII can be used as a screening technique for post-mortem blood lead analysis.
