Raloxifene inhibits pancreatic adenocarcinoma growth by interfering with ERβ and IL-6/gp130/STAT3 signaling.

Purpose: Currently, the exact role of estrogen receptor (ER) signaling in pancreatic cancer is unknown. Recently, we showed that expression of phosphorylated ERβ correlates with a poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). Here, we hypothesized that raloxifene, a FDA-approved selective ER modulator (SERM), may suppress PDAC tumor growth by interfering with ERβ signaling.

Elevated interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) is a poor prognostic marker in pancreatic ductal adenocarcinoma.

Purpose: Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) gene from IFITs family is one gene among hundreds of IFN-stimulated genes. The potential role of IFIT3 in cancer is scarcely understood. In addition, the clinical relevance of IFIT3 is not yet known in pancreatic ductal adenocarcinoma (PDAC).

miR-221 Mediates Chemoresistance of Esophageal Adenocarcinoma by Direct Targeting of DKK2 Expression.

Background: Chemoresistance is a main obstacle to effective esophageal cancer (EC) therapy. We hypothesize that altered expression of microRNAs (miRNAs) play a role in EC cancer progression and resistance to 5-fluorouracil (5-FU) based chemotherapeutic strategies.

Methods: Four pairs of esophageal adenocarcinoma (EAC) cell lines and corresponding 5-FU resistant variants were established.

Verapamil inhibits tumor progression of chemotherapy-resistant pancreatic cancer side population cells.

Tumor side population (SP) cells display stem-like properties that can be modulated by treatment with the calcium channel blocker verapamil. Verapamil can enhance the cytotoxic effects of chemotherapeutic drugs and multidrug resistance by targeting the transport function of the P-glycoprotein (P-gp). This study focused on the therapeutic potential of verapamil on stem-like SP tumor cells, and further investigated its chemosensitizing effects using L3.

KRAS exon 2 mutations influence activity of regorafenib in an SW48-based disease model of colorectal cancer.

Aim: To investigate the impact of KRAS mutation variants on the activity of regorafenib in SW48 colorectal cancer cells.

Materials & Methods: Activity of regorafenib was evaluated in isogenic SW48 KRAS wild-type (WT) and mutant cells. Subcutaneous xenografts (KRAS WT and G12C mutant variants) in NOD/SCID mice were analyzed to elucidate the effect of regorafenib treatment in vivo.

Overexpression of IFN-induced protein with tetratricopeptide repeats 3 (IFIT3) in pancreatic cancer: cellular "pseudoinflammation" contributing to an aggressive phenotype.

Inflammation contributes to important traits that cancer cells acquire during malignant progression. Gene array data recently identified upregulation of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in aggressive pancreatic cancer cells. IFIT3 belongs to the group of interferon stimulated genes (ISG), can be induced by several cellular stress stimuli and by its tetratricopeptide repeats interacts with a multitude of cellular proteins.

Antisense inhibition of microRNA-21 and microRNA-221 in tumor-initiating stem-like cells modulates tumorigenesis, metastasis, and chemotherapy resistance in pancreatic cancer.

Our preliminary studies identified a small population side population (SP) cells in pancreatic cancer cells with stem cell-like properties, which were able to induce fast and aggressive tumor formation in nude mice. Gene expression analysis showed a significant difference in the expression of more than 1,300 genes in SP cells, among which a highly significant difference in microRNA expression of miR-21 and miR-221 between SP and NSP cells was identified. SP cells were identified and characterized by flow cytometry using Hoechst 33342 dye staining from a highly metastatic human pancreatic cancer cell line (L3.

Effect of KRAS exon 2 mutations on antitumor activity of afatinib and gefitinib.

The aim of this study was to investigate the impact of different KRAS mutations on the inhibitory potential of afatinib and gefitinib in SW48 colorectal cancer cells. The influence of afatinib/gefitinib on cell viability and cell cycle was evaluated in isogenic SW48 KRAS wild-type/mutant cells. Protein levels of phosphorylated/total EGFR, HER-2, HER-3, ERK, and AKT were compared between treated/untreated samples using western blotting.

Side population cells of pancreatic cancer show characteristics of cancer stem cells responsible for resistance and metastasis.

Cancer stem cells (CSCs) have been proposed to underlie the initiation and maintenance of tumor growth and the development of chemoresistance in solid tumors. The identification and role of these important cells in pancreatic cancer remains controversial. Here, we isolate side population (SP) cells from the highly aggressive and metastatic human pancreatic cancer cell line L3.

Hypoxia-independent gene expression mediated by SOX9 promotes aggressive pancreatic tumor biology.

Unlabelled: Pancreatic cancer aggressiveness is characterized by its high capacity for local invasion, ability to promote angiogenesis, and potential to metastasize. Hypoxia is known to represent a crucial step in the development of aggressive malignant features of many human cancers. However, micrometastatic tumors are not typically subjected to hypoxic events during early stages of dissemination; therefore, it is unclear how these tumors are able to maintain their aggressive phenotype.

Stem cell-like side populations in esophageal cancer: a source of chemotherapy resistance and metastases.

Dye-effluxing side population (SP) cells can be resistant to chemotherapy and are thought to resemble cancer stem cells. We characterized the relevance of the SP subpopulation in esophageal cancer cell lines and their relation to chemotherapy resistance and metastasis. The SP subpopulation was detected using Hoechst 33342 staining in five esophageal cancer cell lines OE19, OE21, OE33, PT1590, and LN1590.

Cancer stem cells and angiogenesis.

Cancer stem cells (CSCs) or tumor initiating cells were identified and characterized as a unique subpopulation with stem cell features in many types of cancer. Current CSC studies provide novel insights regarding tumor initiation, progression, angiogenesis, resistance to therapy and interplay with the tumor micro-environment. A cancer stem cell niche has been proposed based on these findings.

EFEMP1 binds the EGF receptor and activates MAPK and Akt pathways in pancreatic carcinoma cells.

The EGF-related protein EFEMP1 (EGF-containing fibulin-like extracellular matrix protein 1) has been shown to promote tumor growth in human adenocarcinoma. To understand the mechanism of this action, the signal transduction activated upon treatment with this protein has been investigated. We show that EFEMP1 binds EGF receptor (EGFR) in a competitive manner relative to epidermal growth factor (EGF), implicating that EFEMP1 and EGF share the same or adjacent binding sites on the EGFR.

EFEMP1 expression promotes in vivo tumor growth in human pancreatic adenocarcinoma.

The progression of pancreatic cancer is dependent on local tumor growth, angiogenesis, and metastasis. EFEMP1, a recently discovered member of the fibulin family, was characterized with regard to these key elements of pancreatic cancer progression. Differential gene expression was assessed by mRNA microarray hybridization in FG human pancreatic adenocarcinoma cells and L3.

P60-c-src suppresses apoptosis through inhibition of caspase 8 activation in hepatoma cells, but not in primary hepatocytes.

Background/aims: Failure to induce apoptosis triggered by members of the death receptor family has been described in hepatocellular carcinoma (HCC) and sensitization of malignant cells to pro-apoptotic molecules such as TRAIL has been proposed as an alternative cancer therapy. Limiting to this approach are the resistance of many tumor cells to TRAIL and safety concerns about the toxicity of TRAIL in normal hepatocytes.

Methods: We here explored the possibility that the protooncogene c-Src, known to be overexpressed in a variety of tumors, could be specifically responsible for the loss of response to receptor-mediated apoptosis.