Results: 5

1.
Figure 2

Figure 2. From: Integrated genomics of ovarian xenograft tumor progression and chemotherapy response.

Hierarchical clustering of mRNA expression in each tumor suggests MT19c treatment is the defining feature of the panel of xenograft tumors. A. All samples were clustered by HCE Hierarchical Clustering Explorer revealing four major groups. Outliers are in black. B. Tumors collected after 16 days were removed from the clustering revealing two distinct classes defined by MT19c treatment.

Ashley Stuckey, et al. BMC Cancer. 2011;11:308-308.
2.
Figure 3

Figure 3. From: Integrated genomics of ovarian xenograft tumor progression and chemotherapy response.

Genes associated with double strand break repair are up-regulated by MT19c. Enrichment plot of the double strand break repair gene set identified by GSEA and corresponding heat map for MT19c and naïve tumors. Expression level is represented as a gradient from high (red) to low (blue).

Ashley Stuckey, et al. BMC Cancer. 2011;11:308-308.
3.
Figure 1

Figure 1. From: Integrated genomics of ovarian xenograft tumor progression and chemotherapy response.

MT19c reduces growth of SKOV-3 xenograft tumors and induces apoptosis. A. MT19c significantly reduced the growth of xenograft tumors on average. The size of each tumor was measured with calipers, average for each time point and plotted. Error bars are standard deviations of the mean tumor measurements. B. Individual growth curves for the naïve (N16A, B, C) and MT19c treated (T16A, B, C) xenograft tumors C. Purified DNA reveals MT19c induced degradation of DNA. One μg of DNA from each specimen was purified and run on an agarose gel. All MT19c treated tumors had significantly degraded DNA while the majority of the DNA from naïve tumors is in a distinct upper band indicative of high molecular weight DNA.

Ashley Stuckey, et al. BMC Cancer. 2011;11:308-308.
4.
Figure 4

Figure 4. From: Integrated genomics of ovarian xenograft tumor progression and chemotherapy response.

Rosiglitazone reduces cisplatin and MT19c efficacy in SKOV-3. A. PPARγ network enriched in MT19c treated tumors. Ingenuity Pathway Analysis (IPA) of significantly up and down MT19c (Fold change > 1.4, p < 0.05) regulated genes comparing 16 day treated and naïve tumors identifies a network including PPARγ including PPARγ itself. Red indicates stimulated by MT19c and green indicates down regulation by MT19c. B. Addition of 10 μM Rosiglitazone increases the number of viable SKOV-3 cells when treated with MT19c (left panel) in a dose dependent manner (right panel). The number of viable cells was determined by a modified MTT assay using Wst-1. The y-axis represents percent of viable cells normalized to DMSO treated cells. Error bars represent standard deviation. * indicates p < 0.05 from a Student's t-test comparing MT19c treated and Rosiglitazone-MT19c treated cells. 10 μm Rosiglitazone has a range of effects on the NCI-60 panel of six ovarian cancer cell lines. Viability effects of Rosiglitazone in with cisplatin. - indicates < 20% decrease in number viable cells, - - indicates > 20% decrease in number viable cells, + indicates < 20% increase in number viable cells, + + indicates > 20% increase in number viable cells, o indicates no change in number of viable cells. C. Insulin centered network identified by IPA. Red indicates stimulated by MT19c and green indicates down regulation by MT19c. Ingenuity Pathway Analysis (IPA) of significantly up and down MT19c (Fold change > 1.4, p < 0.05) regulated genes comparing 16 day treated and naïve tumors identifies a network centered around insulin regulation.

Ashley Stuckey, et al. BMC Cancer. 2011;11:308-308.
5.
Figure 5

Figure 5. From: Integrated genomics of ovarian xenograft tumor progression and chemotherapy response.

Genes in copy number gain or loss regions mediate gene expression and are significantly affected by MT19c treatment. A. GSEA Enrichment plots suggest that amplified genes are significantly down-regulated by MT19c compared to naïve tumors while copy number loss genes are significantly up-regulated by MT19c. Significantly amplified (log ratio > 0.3) or deleted genes (log ratio < -0.3) with concomitant high or low expression were selected to define the gene sets. The black lines demonstrate where each gene in the gene set falls within the 15,000 probe sets probing RefSeq transcripts ordered from left to right based on the expression level in MT19c treated or naïve tumors with gene #1 the most highly expressed in MT19c treated tumors. The green line represents the running ES score that becomes more negative as probe sets are identified toward the bottom of the list. More black lines are observed near the top of the rankings in untreated tumors (right side) than in the treated tumors (left side) for amplified genes while genes in LOH regions are biased towards treated tumors (right side). The genes that are most significantly affected by MT19c may be the most important genes mediating SKOV-3 tumor growth and survival. B. qPCR of selected genes within CNAs validates microarray observations. Copy loss genes include PBEF1, STEAP1, and ZNF32. Copy gain genes are PNMT, GRN, PAPLN, and SLC25A6.

Ashley Stuckey, et al. BMC Cancer. 2011;11:308-308.

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