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Among these samples, 59 (23%) were immunonegative, whereas the remaining 200 tumors (77%) demonstrated strong and homogeneous Msi1 expression (Figure 1C). Survival analysis by the Kaplan-Meier estimate and log-rank test revealed a significant association of Msi1 immunoreactivity with poor overall survival (P LY2109761 molecular weight survival (P cell implantation, tumors were treated with multiple injections of either a control (scrambled) or Msi1 siRNA. EPZ5676 order Tumor volume was measured at various time points, and tumor weight (Figure 2B) was determined on euthanasia. Tumors subjected to Msi1 siRNA treatment had a statistically significant decrease in tumor growth compared with the tumors injected with control siRNA and nontreated controls (P = 0.002) ( Figure 2C). Tumors treated with control siRNA had a slight increase compared with the nontreated control, a similar effect that was previously observed. 30 Xenografts were immunohistochemically MAPK stained for Msi1 and Notch1 to corroborate the effects of the siRNA knockdown ( Figure 2D). A decrease in Notch expression on Msi1 knockdown was expected based on the fact that Msi1 represses Numb, a Notch inhibitor. Previous data from our laboratory indicated that through its binding to multiple RNA species, Msi1 controls a complex network of genes from multiple biological processes.21 To investigate the impact of Msi1 in medulloblastoma, we conducted two genomic analyses. We started by mapping genes highly correlated (positively and negatively) with MSI1 expression by exploring the microarray data from our medulloblastoma cohort (n = 103, see Supplemental Table S1 at http://ajp.amjpathol.org). High correlation could indicate that the identified gene is a target or regulator of Msi1, the identified gene and Msi1 are co-regulated by the same factor, or the identified gene and Msi1 are functionally associated. Given the size of our data set, a Pearson correlation coefficient of ��0.5, corresponding to a P