BackgroundOsteosarcoma is the most common primary bone malignancy with high local aggressiveness and rapid metastasizing potential, resulting in poor survival. Increasing reports suggest that deregulated microRNAs (miRNAs) might provide novel therapeutic targets for cancers. However, the expression of miR-26a and miR-27a in osteosarcoma need further investigation in clinical samples. In our study, we evaluate the expression of these miRNAs in osteosarcoma tissues and compared with paired adjacent non-tumor bone tissues using RT-qPCR.MethodsTotal RNA was purified from patients with osteosarcoma and noncancerous bone tissues. Real-time PCR was applied to quantify the expression level of miR-26a and miR-27a. Moreover, the correlation of these markers with clinicopathological characteristics was also evaluated in osteosarcoma patients. A cox proportional hazards model was performed to assess multivariate analyses of prognostic values.ResultsOur result suggested that miR-26aexpression level in osteosarcoma bone tissue was significantly lower than that in the paired noncancerous bone tissues. MiR-27a expression was higher in osteosarcoma bone tissue in comparison with paired noncancerous bone tissues. The results indicated that low expression level of miR-26a and high expression of miR-27a were associated with high TNM stage (P = 0.001; P = 0.012), tumor grade (P = 0.007; P = 0.016), and distant metastasis (P = 0.004; P = 0.001). Kaplan-Meier analysis and log-rank test indicated that patients with low expression of miR-26a and high expression of miR-27a had shorter overall survival (log-rank test: P < 0.001). Multivariate Cox proportional hazards model analysis showed that low expression of miR-26a and high expression of miR-27a (P = 0.021; P = 0.011), high TNM stage (P = 0.001; P = 0.003), tumor grade (P = 0.005; P = 0.01), and distant metastasis.(P = 0.002; P = 0.005) were independent prognostic factors for overall survival patients with osteosarcoma cancer.ConclusionsIn conclusion, our findings suggested that expression level of miR-26a and miR-27a contributes to aggressive progression of this malignancy. Therefore, may have clinical potentials as a non-invasive diagnostic/prognostic biomarker for osteosarcoma patients.
Background:Renal ischemia/reperfusion injury (IRI) is a major problem in renal transplantation, which occurs during the process of organ retrieval and storage, and is closely associated with acute rejection episodes and late allograft failure. Recent studies have revealed a new phenomenon called “chemical preconditioning” that can induce tolerance against the ischemic stress via a variety of proposed pathways especially nitric oxide (NO) system. Propylthiouracil (PTU) is suggested to modulate the intracellular NO signaling.Objectives:In this study, we investigated the preconditioning properties of chronic pretreatment with PTU in preventing renal IRI. In addition, we evaluated the involvement of NO pathway.Materials and Methods:Sixty adult male Wistar rats were allocated into six groups. All groups underwent right nephrectomy 15 days before intervention. In groups 1 (Chronic PTU + L-NG-nitro arginine methyl ester [L-NAME]) and 2 (Chronic PTU) oral PTU (500 mg/L in water) treatment was started 15 days before right nephrectomy to achieve the therapeutic plasma level of PTU. Fourteen days after nephrectomy, animals received either L-NAME (10 mg/kg) or its vehicle and renal IRI was induced 45 minutes later. Groups 3 and 4 (Control) received respectively L-NAME (10 mg/kg) and its vehicle 45 minutes before IRI. The last two groups were normal sham operated rats and PTU + sham. Rats were killed 24 hours after IRI. The blood samples were collected and assessed for serum blood urea nitrogen (BUN) and creatinine (Cr) level, and tissue samples were fixed in formalin for histopathologic scoring of tubular damage (H-score).Results:The mean BUN, Cr, and H-score of control group were 176.66 ± 12.24 mmol/L, 4.45 ± 0.44 μmol/L, and 83.5% ± 3.5%, respectively. Chronic pretreatment with PTU significantly improved BUN (40.4 ± 6.1 mmol/L), Cr (0.96 ± 0.068 μmol/L), and H-score (7.83% ± 4.02%) in IRI animals in comparison to those that were not treated with chronic PTU (P < 0.001) and L-NAME; however, it did not completely reversed the chronic PTU-induced protection (BUN, 93.33 ± 12.22 mmol/L; Cr, 2.7 ± 1.15 μmol/L, and H-score, 24.83% ± 3.5%). There was no significant difference between rats that were treated with L-NAME alone (group 5) and the control group.Conclusions:Our study demonstrates that preconditioning of kidney with chronic PTU administration protects renal tissue against IRI and this phenomenon was mediated through NO system. The results suggest a potential indication for using PTU to protect the kidney before transplantations and to reduce the risk of tissue rejection afterwards.
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