ABSTRACT
Purpose@#This study was performed to establish and validate a nomogram for predicting the overall survival in children with neuroblastoma. @*Methods@#The latest clinical data of neuroblastoma in Surveillance, Epidemiology, and End Results (SEER) database was extracted from 2000 to 2016. The cases included were randomly divided into training and validation cohorts. The survival curves were drawn with a Kaplan-Meier estimator to investigate the influences of certain single factors on overall survival. Also, least absolute shrinkage and selection operator regression was applied to further select the prognostic variables for neuroblastoma. Additionally, receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the accuracy of the nomogram. @*Results@#In total, 1,262 patients were collected and 8 independent prognostic factors were achieved, including patients’ age, sex, race, tumor grade, radiotherapy, chemotherapy, tumor site, and tumor size. Then we constructed a nomogram by using the data of the training cohort with 886 cases. Subsequently, the nomogram was validated internally and externally with 886 and 376 cases, respectively. The internal validation revealed that the area under the curves (AUC) of ROC curves of 1-, 3-, and 5-year overall survival were 0.69, 0.78, and 0.81, respectively. Accordingly, the external validation also showed that the AUC of 1-, 3-, and 5-year overall survival were all ≥0.69. Both methods of validation demonstrated that the predictive calibration curves were consistent with standard curves. @*Conclusion@#The nomogram possess the potential to be a new tool in predicting the survival rate of neuroblastoma patients.
ABSTRACT
Purpose@#This study was performed to establish and validate a nomogram for predicting the overall survival in children with neuroblastoma. @*Methods@#The latest clinical data of neuroblastoma in Surveillance, Epidemiology, and End Results (SEER) database was extracted from 2000 to 2016. The cases included were randomly divided into training and validation cohorts. The survival curves were drawn with a Kaplan-Meier estimator to investigate the influences of certain single factors on overall survival. Also, least absolute shrinkage and selection operator regression was applied to further select the prognostic variables for neuroblastoma. Additionally, receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the accuracy of the nomogram. @*Results@#In total, 1,262 patients were collected and 8 independent prognostic factors were achieved, including patients’ age, sex, race, tumor grade, radiotherapy, chemotherapy, tumor site, and tumor size. Then we constructed a nomogram by using the data of the training cohort with 886 cases. Subsequently, the nomogram was validated internally and externally with 886 and 376 cases, respectively. The internal validation revealed that the area under the curves (AUC) of ROC curves of 1-, 3-, and 5-year overall survival were 0.69, 0.78, and 0.81, respectively. Accordingly, the external validation also showed that the AUC of 1-, 3-, and 5-year overall survival were all ≥0.69. Both methods of validation demonstrated that the predictive calibration curves were consistent with standard curves. @*Conclusion@#The nomogram possess the potential to be a new tool in predicting the survival rate of neuroblastoma patients.
ABSTRACT
OBJECTIVE Leukotriene B4 (LTB4) biosynthesis and subsequently neutrophilic inflam?mation may provide a potential strategy for the treatment of acute lung injury (ALI) or idiopathic pulmonary fibrosis (IPF). To provide a potential strategy for the treatment of ALI or IPF, we identified potent inhibi?tors of Leukotriene A4 hydrolase (LTA4H), a key enzyme in the biosynthesis of LTB4. METHODS In this study, we identified two known histone deacetylase (HDAC) inhibitors, suberanilohydroxamic acid (SAHA) and its analogue 4-(dimethylamino)-N-〔7-(hydroxyamino)-7-oxoheptyl〕benzamide (M344), as effective inhibitors of LTA4H using enzymatic assay, thermofluor assay, and X- ray crystallographic investigation. We next tested the effect of SAHA and M344 on endogenous LTB4 biosynthesis in neutrophils by ELISA and neutrophil migration by transwell migration assay. A murine experimental model of ALI was induced by lipopolysaccharide(LPS) inhalation. Histopathological analysis of lung tissue using H&E staining revealed the serious pulmonary damage caused by LPS treatment and the effect of the SAHA. We next examined mRNA and protein levels of pro-inflammatory cytokines in lung tissue and bronchoalveolar lavage fluid using qRT- PCR and ELISA to further investigate the underlying mechanisms of anti-inflammatory activities by SAHA. We also investigated the effects of SAHA and M344 on a murine experimental model of bleomycin (BLM)-induced IPF model. RESULTS The results of enzymatic assay and X-ray crystallography showed that both SAHA and M344 bind to LTA4H, signif?icantly decrease LTB4 levels in neutrophil, and markedly diminish early neutrophilic inflammation in mouse models of ALI and IPF under a clinical safety dose. CONCLUSION Collectively, SAHA and M344 would provide promising agents with well-known clinical safety for potential treatment in patients with ALI and IPF via pharmacologically inhibiting LAT4H and blocking LTB4 biosynthesis.
ABSTRACT
To investigate the effect of microRNA-221 (miR-221) on cell viability and apoptosis of hepatocellular carcinoma HepG2 cells. MiR-221 inhibitors and mimics were transfected into HepG2 cells. The expression of miR-221 was detected by real time quantitative RT-PCR. CellTiter-blue cell viability kit, Hoechst 33342/propidium iodide (PI) double staining assay, flow cytometry and Apo-ONE homogeneous caspase-3/7 kit were used to measure cell viability and apoptosis. MiR-221 inhibitors significantly inhibited the cell growth and miR-221 mimics increased cell viability 48 hours post-transfection measured by both CellTiter-blue cell viability kit and Hoechst 33342/PI assay (P is less than to 0.05). There was a positive correlation between these two assays (r = 0.993, P is less than to 0.01). With miR-221 mimics, the number of G1 stage cells (47.67%+/-1.53%) was significantly reduced as compared to the blank control (59.00%+/-1.00%) and the negative control (58.00%+/-1.00%, F = 81.77, P is less than to 0.01), and it was significantly raised in S stage (20.33%+/-1.15%) than in blank control (11.00%+/-1.00%) and negative control (12.00%+/-1.00%, F = 70.9, P is less than to 0.01) with flow cytometry analysis. More cell apoptosis and necrosis were significantly induced by miR-221 inhibitors 48 hours post-transfection detected by both Hoechst 33342/PI assay and flow cytometry PE Annexin V kit (P is less than to 0.05). The result from Apo-ONE homogeneous caspase-3/7 kit was consistent with the above two apoptotic assays, which showed that with miR-221 inhibitors, the activity of caspase-3/7 was significantly enhanced (P is less than to 0.05). MiR-221 contributes to the growth of hepatocellular carcinoma cells and miR-221 inhibition can induce cell apoptosis. miR-221 has the potential to become one of the new molecular targets for liver cancer therapy.