Journal: CNS Spectrums

Article Title: Daytime sleepiness associated with lurasidone and quetiapine XR: results from a randomized double-blind, placebo-controlled trial in patients with schizophrenia

doi: 10.1017/S1092852913000904

Figure Lengend Snippet: Change in sleepiness ESS item ‘dozing while talking’ and change composite Z score: Mediation regression analysis.

Article Snippet: In patients whose neurocognitive testing results were evaluable (based on prespecified criteria for the validity of the cognitive tests, n = 267), the effect of lurasidone 160 mg/d on cognitive performance (LS mean change 0.5, SE 0.24) was superior to both placebo (–0.16, SE 0.23, p = 0.038) and quetiapine XR (–0.24, SE 0.23, p = 0.018), as assessed by the CogState composite Z-score.

Techniques:

Journal: Nature cancer

Article Title: Network-based assessment of HDAC6 activity predicts pre-clinical and clinical responses to the HDAC6 inhibitor ricolinostat in breast cancer

doi: 10.1038/s43018-022-00489-5

Figure Lengend Snippet: (a) Bubble plot representing GSEA analysis of MYC signatures during ricolinostat exposure in sensitive breast cancer cells. The size and intensity of the bubble indicate the statistical significance. N = 2 independent experiments for each time point of each BC cell line or mouse model. P value was estimated by two-tailed t test. The Z -scores were transformed from these P values and further combined using Stouffer’s method. (b) The upper panel (WT-blots) shows the reduction of MYC protein expression after ricolinostat treatment (2.5 μM) in sensitive but not resistant cancer cells. WT-blot results were reproduced n=3 times from independent experiments. The lower panel shows the summarized z-scores, comparing Ricolinostat-treated (6hrs) vs. untreated in the same cell lines shown in the upper panel. The Z -score was transformed from the P value estimated by two-tailed t test. (c) WT-blots showing the reduction of MYC in sensitive cell lines when HDAC6 was inhibited by the small molecule inhibitor CAY10603 (1μM, upper panel) or by RNAi (100nM, lower panel) (c=non-targeting siRNA control, H6=siRNA targeting HDAC6, M= siRNA targeting MYC). WT-blot results were reproduced n=3 times from independent experiments. (d) Cell viability (cell number) after MYC is silenced by siRNA in ricolinostat sensitive cell lines (notice that the western blot showing efficient silencing of MYC is shown in Fig. 5c ). N=3 independent experiments per siRNA and cell line. Data are presented as mean values +/−SD. P values was estimated by two-tailed t test.

Article Snippet: The Z-score was transformed from the P values and further combined by Stouffer’s method. (d) QRT-PCR of c-Myc mRNA expression after 6 hours of exposure to ricolinostat.

Techniques: Expressing, Activity Assay, Two Tailed Test, Transformation Assay, Control, Western Blot

Journal: Nature cancer

Article Title: Network-based assessment of HDAC6 activity predicts pre-clinical and clinical responses to the HDAC6 inhibitor ricolinostat in breast cancer

doi: 10.1038/s43018-022-00489-5

Figure Lengend Snippet: (a) Heatmap representing GSEA analysis of hallmark signatures during ricolinostat exposure in sensitive breast cancer cell lines and TgMMTV-Neu model. P value was estimated by two-tailed t test. The Z-scores were transformed from these P values and further combined using Stouffer’s method. Only significant (combined Z > 1.96 or < −1.96) sets are shown. (b) The graphic shows summarized z-scores in cell lines and TgMMTV-Neu sensitive to ricolinostat during a time curse treatment (6, 12, 24 hours and 4 weeks). For a and b N = 2 individual independent experiments for cell lines and N=3 individual tumors for TgMMTV-Neu. P value was estimated using two-tailed t test. (c) Bubble plot representing GSEA analysis of multiple MYC-associated signatures after ricolinostat in sensitive and resistant cells. N = 3 independent experiments per cell line. P value was estimated by two-tailed t test. The Z-score was transformed from the P values and further combined by Stouffer’s method. (d) QRT-PCR of c-Myc mRNA expression after 6 hours of exposure to ricolinostat. N = 3 independent experiments for each time point All effort bars represent Mean±SD. P value was estimated by two-tailed t test. (e) The WT-blot shows the changes in the protein expression of c-Myc and ac-Tubulin in SUM-149 cells after ricolinostat is added to the culture media. WT-blot results were reproduced n=3 times from independent experiments. (f) Graphic showing an efficient reduction in the HDAC6 score after treatment with ricolinostat in multiple cell lines, n≥2 independent experiments per time point. The center line indicates the median value. The lower and upper hinges represent the 25th and 75th percentiles, respectively, and whiskers denote 1.5x interquartile range.

Article Snippet: The Z-score was transformed from the P values and further combined by Stouffer’s method. (d) QRT-PCR of c-Myc mRNA expression after 6 hours of exposure to ricolinostat.

Techniques: Expressing, Two Tailed Test, Transformation Assay, Quantitative RT-PCR

Journal: Nature cancer

Article Title: Network-based assessment of HDAC6 activity predicts pre-clinical and clinical responses to the HDAC6 inhibitor ricolinostat in breast cancer

doi: 10.1038/s43018-022-00489-5

Figure Lengend Snippet: a) MA plots showing the peptides upregulated upon HDAC6 knockout (above) and HDAC6 catalytic domain 2 mutants (below). In the MA-plots, each dot represents a peptide. The significantly upregulated peptides were identified by fold change > 1.5 and p-value < 0.05 and highlighted in red. P value was estimated by two-tailed t test. (b) Scatter plot showing the correlation of the Z-score of the comparison between HDAC6 KO and wild type with that of the comparison between HDAC6 mutant and wild type. The curve was fitted by stat_smooth algorithm using lm smoothing method and y~x formula. The correlation coefficient (R) and P value were estimated using two-tailed Spearman correlation test. Each dot represents a peptide. For a and b the N = 2 independent proteomic replica studies per cell line. c) The western blot shows the accumulation of ac-K148-c-Myc after HDAC6 is inhibited by ricolinostat in MDA-MB-453 and SK-BR-3 BC lines. WT-blot results were reproduced n=3 times from independent experiments.

Article Snippet: The Z-score was transformed from the P values and further combined by Stouffer’s method. (d) QRT-PCR of c-Myc mRNA expression after 6 hours of exposure to ricolinostat.

Techniques: Inhibition, Knock-Out, Two Tailed Test, Comparison, Mutagenesis, Western Blot