RESUMO
Retinoblastoma (RB) constitutes a prevalent malignancy in clinic and usually occurs in children under the age of 5 years old. The increased frequency of malignant tumor metastases and the delayed diagnosis and treatment caused unsatisfactory therapeutic efficiency. Quercetin was formerly identified to impede tumor growth in certain malignancies. Our study attempted to investigate the effects and mechanisms of quercetin in Rb development, in order to provide an effective clinical therapeutic approach. Rb cell lines (WER1-RB1 and Y79) were incubated with different concentrations of quercetin, and then cell proliferation, invasion, apoptosis, and oxidative stress were determined. It was showed that quercetin restrained Rb cell proliferation and invasion, and induced cell apoptosis and oxidative stress in a dose dependent manner. Moreover, we found that quercetin incubation upregulated miR-137 expression in Rb cells. MiR-137 inhibition abrogated quercetin-mediated inhibition of Rb cell progression. Furthermore, dual-luciferase reporter gene assay validated that fibronectin type III domain-containing protein 5 (FNDC5) was a target for miR-137. MiR-137 overexpression restrained proliferation and invasion, and enhanced apoptosis and oxidative stress in Rb cells, whereas FNDC5 overexpression abrogated these effects. Additionally, nude mice were injected with WER1-RB1 cells to establish a xenograft tumor model, and then treated with 50 or 100 mg/kg quercetin. Quercetin treatment mitigated xenograft tumor growth in nude mice. In conclusion, quercetin restrained proliferation and invasion, and induced apoptosis and oxidative stress in Rb cells through regulating the miR-137/FNDC5 pathway. We expected that our study could provide an effective approach for Rb treatment. However, quercetin and miR-137 may have off-target effects in Rb cells, and our study still has certain limitations. Therefore, we will investigate the effects of quercetin on other signaling pathways in Rb cells and explore the application of combination therapy in follow-up experiments, in order to provide a rigorous research basis for the treatment of Rb with quercetin.
RESUMO
Purpose: Our study aims to compare the diagnostic value of 18F-NaF positron emission tomography-computed tomography (PET/CT), 18F-NaF PET, and planar 99mTc-MDP bone scintigraphy for detection of bone metastases in patients with newly diagnosed nasopharyngeal carcinoma (NPC). Methods: Our study retrospectively analyzed 58 patients with pathologically proven NPC. They all underwent both 18F-NaF PET/CT and planar 99mTc-MDP bone scintigraphy within a 7-day interval. Bone metastases were confirmed by follow-up using PET/CT, contrast-enhanced computed tomography (CT), and magnetic resonance imaging (MRI). These three examinations were compared using per-patient-based analysis and per-lesion-based analysis. Results: 19 patients (32.7%) were classified as having bone metastatic disease in their final diagnosis. The patient-based diagnostic performances (sensitivity, specificity, and overall accuracy) were as follows: 18F-NaF PET/CT (100%, 92.3%, and 94.8%), 18F-NaF PET (100%, 53.8%, and 69.0%), and planar 99mTc-MDP bone scintigraphy (78.9%, 74.4%, and 75.9%). The overall accuracy of 18F-NaF PET/CT was significantly more favorable compared to 18F-NaF PET (p=0.002) and to planar 99mTc-MDP bone scintigraphy (p=0.044). The lesion-based diagnostic performances (sensitivity, specificity, and overall accuracy) were as follows: 18F-NaF PET/CT (98.5%, 93.9%, and 96.6%), 18F-NaF PET (98.5%, 57.1%, and 81.1%), and planar 99mTc-MDP bone scintigraphy (69.9%, 85.7%, and 76.4%). Conclusion: 18F-NaF PET/CT outperforms 18F-NaF PET or planar 99mTc-MDP bone scintigraphy in detecting bone metastases with newly diagnosed NPC on a patient-based and lesion-based analysis.
