Additional file 1: Figure S1. of Histone deacetylase inhibitors potentiate photodynamic therapy in colon cancer cells marked by chromatin-mediated epigenetic regulation of CDKN1A

Mitochondrial membrane dissipation potential by HDACis ± HY-PDT. Mitochondrial membrane dissipation (TMRE+) was measured in HT-29 cells after a sequential treatment starting with HDACis (A) Saha, (B) Tsa, (C) Vpa, and (D) NaPB (for 24 h) followed by activation with hypericin (for 24 or 48 h, as indicated). Samples treated with drug-free vehicle solvents (<0.1% DMSO) were used as the reference control. The results are expressed as the percentage of control and represent the average ± SD of four independent experiments each done in singlets. Data was analyzed using one-way ANOVA with the Tukey post hoc test. All conditions were compared to the reference control (*p < 0.05, **p < 0.01, ***p < 0.001), and the combined treatments were compared to HY-PDT alone (ǂp < 0.05, ǂǂp < 0.01, ǂǂǂp < 0.001) and to correspondingly equal concentrations of HDACis alone (▲p < 0.05, ▲▲p < 0.01, ▲▲▲p < 0.001) (PPTX 55 kb)

Lessons learned from the discovery and development of the sesquiterpene lactones in cancer therapy and prevention

Sesquiterpene lactones (SLs) are one of the most diverse bioactive secondary metabolites found in plants and exhibit a broad range of therapeutic properties . SLs have been showing promising potential in cancer clinical trials, and the molecular mechanisms underlying their anticancer potential are being uncovered. Recent evidence also points to a potential utility of SLs in cancer prevention. This work evaluates SLs with promising anticancer potential based on cell, animal, and clinical models: Artemisinin, micheliolide, thapsigargin dehydrocostuslactone, arglabin, parthenolide, costunolide, deoxyelephantopin, alantolactone, isoalantolactone, atractylenolide 1, and xanthatin as well as their synthetic derivatives. We highlight actionable molecular targets and biological mechanisms underlying the anticancer therapeutic properties of SLs. This is complemented by a unique assessment of SL mechanisms of action that can be exploited in cancer prevention. We also provide insights into structure-activity and pharmacokinetic properties of SLs and their potential use in combination therapies. We extract seven major lessons learned and present evidence-based solutions that can circumvent some scientific limitations or logistic impediments in SL anticancer research. SLs continue to be at the forefront of cancer drug discovery and are worth a joint interdisciplinary effort in order to leverage their potential in cancer therapy and prevention.</p

Arsenic combined with IFN induced capase-dependent apoptosis and latent viral proteins downregulation in BC-3 cells.

<p>(<b>A</b>) Western blot analysis of BC-3 cells treated for 48h using PARP-specific antibody. (<b>B</b>) Western blot analysis of <i>ex-vivo</i> treated (48h) ascites derived BC-3 cells using LANA-1 and LANA-2 specific antibodies.</p

Arsenic/IFN synergistically inhibited proliferation and induced apoptosis of ascites-derived BC3 (left) and BCBL-1 cells (right).

<p>(<b>A</b>) Cell Proliferation: Cells were plated in a 96 well format and treated with the single agent drugs or their combinations for 24, 48, and 72h. Results are expressed as percent of control, plotted as mean ± SD, and are representative of two independent experiments. (<b>B</b>) Annexin V staining: BC-3 and BCBL-1 ascites were treated for 48h. Histograms represent the proportion of apoptotic cells. Results are plotted as mean ± SD and are representative of at least 2 independent experiments. (<b>C</b>) TUNEL assay: BC-3 and BCBL-1 cells derived from PEL ascites were treated for 72h. Histograms represent apoptotic cells as percentage of the untreated controls and are plotted as mean ± SD.</p

Arsenic and IFN synergistically prolonged survival in PEL mice.

<p>(<b>A</b>) Mice phenotype before and after treatment with arsenic/IFN. (<b>B</b>) Solid PEL tumors in untreated mice. (<b>C</b>) PCR for V-FLIP gene expression in different organs. (<b>D</b>) Kaplan–Meier analysis of overall survival curves of PEL NOD/SCID mice. Mice (<i>n</i> = 10 for each condition) were inoculated with 2x10⁶ of BC-3 (left) and BCBL-1 (right) cells, respectively. Treatment with the single agent drugs or their combinations was initiated at 2 days post-inoculation of PEL cells for a total of 21 days. The symbol * was used to compare treatment groups to control, while the symbol ‡ was used to compare combination treatments to single treatments. (*, ‡) indicates p< 0.05; (**, ‡‡) indicates p< 0.01; and (***, ‡‡‡) indicates p< 0.001.</p

Arsenic and IFN delayed ascites formation in PEL mice.

<p>Peritoneal volume on day 45 post-treatment. PEL NOD/SCID mice (n=10 per condition) were visually monitored. Peritoneal diameter (d) was measured with a caliber to assess ascites development. Peritoneal volume was calculated according to the formula: v=4/3π(d/2)³. The symbol * was used to compare treatment groups to control (*, **, and *** indicates p< 0.05, p< 0.01, and p< 0.001, respectively).</p

Arsenic/IFN synergistically inhibited expression of latent viral transcripts.

<p>Relative expression levels of different samples were calculated by standardization of the amount of target transcript for (A) LANA-1, (B) v-Cyclin or (C) v-FLIP, in a sample to the amount of housekeeping Glucose-6-phosphate dehydrogenase (G6PDH) RNA analyzed in the same sample. In addition, the averages of the normalized control values of Glucose-6-phosphate dehydrogenase (G6PDH) for each sample were used to determine the relative changes in gene expression of the KSHV latency protein LANA-1 by the comparative CT method (2^-ΔΔC_T) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079474#B12" target="_blank">12</a>]. Untreated BC3 and BCBL-1 ascites were used as a calibrator for viral gene expression. The Y-axis represents the relative quantities expressed as percent of the control. The symbol * was used to compare treatment groups to control, while the symbol ‡ was used to compare combination treatments to single treatments. (*, ‡) indicates p< 0.05; (**, ‡‡) indicates p< 0.01; and (***, ‡‡‡) indicates p< 0.001.</p

ガウス型通信路の最近の問題について(応用函数解析の研究)

Supplementary tables. (XLSX 808 kb

Additional file 6 of Buffy coat signatures of breast cancer risk in a prospective cohort study

Additional file 6. Supplementary Table 6. Top GO Biological Processes, GO Cellular Components, GO Molecular Functions, Reactome, and KEGG Pathways enriched from significantly differentially methylated regions (FDR 0.075) identified when overlapping DMRs identified in the main analysis with DMRs identified when samples were limited to participants aged 50 and above at recruitment

Additional file 3: of Identifying and correcting epigenetics measurements for systematic sources of variation

Figure S3. Quantile-quantile (QQ) plots for CpG site-specific analysis with respect to smoking using standard adjustment (a), residuals (b), ComBat (c) and SVA (d) correcting methods for the M values. The inflation factor λ is defined as the ratio of the median of the observed log10 transformed p values from the CpG site-specific analysis and the median of the expected log10 transformed p values. (PDF 110 kb