<p>Role of metabolic pathways imparting gemcitabine resistance in pancreatic cancer</p>

PDF file - 325K, Nuclear p53 expression correlates positively with loss of wild type allele in serous epithelial ovarian carcinomas in p53m/+ mutant mice

<p>Effects of glutamine deprivation on cell viability and NRF2 expression</p>

Abstract MicroRNA (miRNA) expression profiling studies revealed a number of miRNAs dysregulated in the malignant brain tumor glioblastoma. Molecular functions of these miRNAs in gliomagenesis are mainly unknown. We show that inhibition of miR-10b, a miRNA not expressed in human brain and strongly upregulated in both low-grade and high-grade gliomas, reduces glioma cell growth by cell-cycle arrest and apoptosis. These cellular responses are mediated by augmented expression of the direct targets of miR-10b, including BCL2L11/Bim, TFAP2C/AP-2γ, CDKN1A/p21, and CDKN2A/p16, which normally protect cells from uncontrolled growth. Analysis of The Cancer Genome Atlas expression data set reveals a strong positive correlation between numerous genes sustaining cellular growth and miR-10b levels in human glioblastomas, while proapoptotic genes anticorrelate with the expression of miR-10b. Furthermore, survival of glioblastoma patients expressing high levels of miR-10 family members is significantly reduced in comparison to patients with low miR-10 levels, indicating that miR-10 may contribute to glioma growth in vivo. Finally, inhibition of miR-10b in a mouse model of human glioma results in significant reduction of tumor growth. Altogether, our experiments validate an important role of miR-10b in gliomagenesis, reveal a novel mechanism of miR-10b–mediated regulation, and suggest the possibility of its future use as a therapeutic target in gliomas. Cancer Res; 71(10); 3563–72. ©2011 AACR.

<p>Isotype control for NRF2 in IHC and survival measure for NRF2</p>

Cell cycle analysis of PDAC cells upon NRF2 activation

<p>Effects of NRF2 activation on metabolomics</p>

<p>Gemcitabine IC50 Values</p>

PDF file - 267K, Widespread metabolomic alterations consistent with tumor development are found in blood of SEOC mice compared to wild type mice

PDF file - 161K, Analysis of recombination efficiency of targeted alleles in mutant mice

Knockdown and over-expression of NRF2 in PDAC cells

PDF file - 307K, lntrabursal injection of Adeno-Cre activates conditional alleles in OSE cells and induces histopathological changes of murine OSE post induction

NRF2-mediated pathway is upregulated in KRAS mutant PDAC

<p>Glutamine starvation regulates cell growth and assembly of stress granules</p>

PDF file - 253K, Gene expression analysis

PDF file - 53K, Tumor spectrum in Adeno-Cre injected mice

PDF file - 255K, Immunohistochemical staining for CA125, WT1 and calretinin

<p>Clinical characteristics of NRF2 expression in pancreatic cancer patients</p>

Supplementary Methods, Figures 1-10, Table 1 from Human Glioma Growth Is Controlled by MicroRNA-10b

<p>Metabolic Pathway Enrichment in PDAC Patients Treated with Gemcitabine (Data Pooled from TCGA)</p>