External validation of a subset of upregulated genes in cohort 2 that validated in cohort 1

<p><b>Copyright information:</b></p><p>Taken from "An integrative model for recurrence in ovarian cancer"</p><p>http://www.molecular-cancer.com/content/7/1/8</p><p>Molecular Cancer 2008;7():8-8.</p><p>Published online 22 Jan 2008</p><p>PMCID:PMC2248209.</p><p></p> Bars indicate the relative overexpression of target genes in recurrent vs primary tumors. IL1R2 and ZNF218 gave the best distinction between recurrent and primary tumors with greater than twofold changes

Gene families involved in the molecular regulation of recurrence in ovarian cancer

<p><b>Copyright information:</b></p><p>Taken from "An integrative model for recurrence in ovarian cancer"</p><p>http://www.molecular-cancer.com/content/7/1/8</p><p>Molecular Cancer 2008;7():8-8.</p><p>Published online 22 Jan 2008</p><p>PMCID:PMC2248209.</p><p></p> Some of the upregulated genes in recurrent compared to primary ovarian carcinomas that we validated in cohort 2 belong in the same gene families with some of the upregulated genes validated in cohort 1. Upregulation of tight junction proteins and EGFR ligands, development of a cytokine response via interleukin receptors and intracellular signaling via calcium binding S100 proteins seem to contribute to the "recurrent" signature and possibly have a role in drug resistance

Figure illustrating common biological pathways identified when the lists of predicted targets for miR-9 and miR-223 were exported in the Panther classification system and examined against the H

sapiens reference list to determine the percentage of genes compared to what expected. Common pathways between the top dysregulated genes were significant at a p < 0.05 as highlighted by the orange bars.<p><b>Copyright information:</b></p><p>Taken from "Potential role of miR-9 and miR-223 in recurrent ovarian cancer"</p><p>http://www.molecular-cancer.com/content/7/1/35</p><p>Molecular Cancer 2008;7():35-35.</p><p>Published online 28 Apr 2008</p><p>PMCID:PMC2383925.</p><p></p

Differentially expressed miRNAs in recurrent versus primary ovarian cancers

Relative fold changes are displayed on the y axis and the miRNAs are on the x axis. The most significant altered expression was observed for mir-223 (up) and mir-9 (down).<p><b>Copyright information:</b></p><p>Taken from "Potential role of miR-9 and miR-223 in recurrent ovarian cancer"</p><p>http://www.molecular-cancer.com/content/7/1/35</p><p>Molecular Cancer 2008;7():35-35.</p><p>Published online 28 Apr 2008</p><p>PMCID:PMC2383925.</p><p></p

Global staining pattern for eIF6 (e) and Dicer (f) in a TMA of primary serous papillary ovarian adenocarcinomas

Global staining pattern for eiF6 and Dicer in the TMA of recurrent ovarian tumours is not shown. Analysis was based on relative expression levels of eIF6 and Dicer in primary vs recurrent tumours.<p><b>Copyright information:</b></p><p>Taken from "Potential role of miR-9 and miR-223 in recurrent ovarian cancer"</p><p>http://www.molecular-cancer.com/content/7/1/35</p><p>Molecular Cancer 2008;7():35-35.</p><p>Published online 28 Apr 2008</p><p>PMCID:PMC2383925.</p><p></p

Unsupervised hierarchical cluster heatmap based on differential miRNA expression patterns identified in the initial cohort

Vertical bars represent the samples and the horizontal bars represent the miRNA genes. Green bars reflect downregulated genes and red bars upregulated genes. Interestingly, P3 clusters with the recurrent samples on the left of the heatmap. P3 relapsed within 6 months post completion of treatment and should be considered "chemoresistant" P, primary tumours; R, recurrent tumors.<p><b>Copyright information:</b></p><p>Taken from "Potential role of miR-9 and miR-223 in recurrent ovarian cancer"</p><p>http://www.molecular-cancer.com/content/7/1/35</p><p>Molecular Cancer 2008;7():35-35.</p><p>Published online 28 Apr 2008</p><p>PMCID:PMC2383925.</p><p></p

The effect of silencing MyD88 and TLR4 mRNA on the chemoresponsive properties of SKOV-3 cells.

<p>SKOV-3 cells were left untransfected (Unt), transfected with negative control siRNA (siNeg), MyD88 targeting siRNA (siMyD88) or TLR4 targeting siRNA (siTLR4). The transfected cells were incubated for 72 hrs before either harvesting for mRNA analysis (A), for protein analysis (B) or treatment with paclitaxel (C). (A) MyD88 and TLR4 mRNA expression levels were evaluated by TaqMan RT-PCR. MyD88 and TLR4 mRNA expression was normalised to that of an endogenous control, B2M, and calibrated to that of untreated cells to establish the relative percentage of mRNA expression (n = 3, mean +SD). (B) MyD88 and TLR4 mRNA expression levels were evaluated by western blot analysis. GAPDH was used as a loading control. (C) Transfected cells were either left untreated, treated with DMSO (vehicle control) or 3.5 nM of paclitaxel (IC25). 48 hrs post treatment, cell viability was assessed by means of the CCK-8 assay. % cell viability rate was calculated by comparing the absorbance values for the vehicle control to the corresponding paclitaxel treated samples. Results are expressed as mean +SD, n = 3; *p<0.05, **p<0.01 (un-paired Student's t-test).</p

MyD88 expression and survival (Kaplan-Meier curves: median survival time shown in months).

<p>MyD88 positive tumours (n = 12) had significantly reduced progression-free survival (A) and overall survival (B) (p = 0.018 and p = 0.008, respectively).</p

Heterogeneous expression of monoclonal anti-TLR4.

<p>A: variable staining observed in adjacent epithelium within a benign serous cystadenoma (20x). B: focal strong staining within a serous carcinoma (40x).</p

TLR4/MyD88 and progression-free survival (Kaplan-Meier curves; median survival shown in months).

<p>TLR4 (A) or MyD88 (B) negative cases had significantly better PFS (15 & 18 months longer; p<0.05).</p