ADRM1-amplified metastasis gene in gastric cancer.

The proteasome ubiquitin receptor ADRM1 has been shown to be a driver for 20q13.3 amplification in epithelial cancers including ovarian and colon cancer. We performed array-CGH on 16 gastric cancer cell lines and found 20q13.

Silica network improve the effect of fludarabine and paclitaxel on HCT8 cell line.

This paper reports the potential of silica network to sensitize tumor cells and stimulate antitumor toxicity of fludarabine (FLU) and paclitaxel (PAC) against HCT8 cells. SiO₂, SiO₂/FLU and SiO₂/PAC nanostructured materials were characterized by X-Ray Diffraction, Scanning Electron Microscopy, InfraRed Microscopy and in vitro biological assays. When using SiO₂/PAC, it can be observed that the cytostatic effect of PAC is boosted only at high concentrations of this material.

Morphine treatment selectively regulates expression of rat pituitary POMC and the prohormone convertases PC1/3 and PC2.

The prohormone convertases, PC1/3 and PC2 are thought to be responsible for the activation of many prohormones through processing including the endogenous opioid peptides. We propose that maintenance of hormonal homeostasis can be achieved, in part, via alterations in levels of these enzymes that control the ratio of active hormone to prohormone. In order to test the hypothesis that exogenous opioids regulate the endogenous opioid system and the enzymes responsible for their biosynthesis, we studied the effect of short-term morphine or naltrexone treatment on pituitary PC1/3 and PC2 as well as on the level of pro-opiomelanocortin (POMC), the precursor gene for the biosynthesis of the endogenous opioid peptide, β-endorphin.

Inhibition of HSP90 with AUY922 induces synergy in HER2-amplified trastuzumab-resistant breast and gastric cancer.

HSP90 enables the activation of many client proteins of which the most clinically validated is HER2. NVP-AUY922, a potent HSP90 inhibitor, is currently in phase II clinical trials. To explore its potential clinical use in HER2-amplified breast and gastric cancers, we evaluated the effect of AUY922 alone and in combination with trastuzumab in both trastuzumab-sensitive and -resistant models.

Lapatinib, a dual EGFR and HER2 kinase inhibitor, selectively inhibits HER2-amplified human gastric cancer cells and is synergistic with trastuzumab in vitro and in vivo.

Purpose: HER2 amplification occurs in 18% to 27% of gastric and gastroesophageal junction cancers. Lapatinib, a potent ATP-competitive inhibitor simultaneously inhibits both EGFR and HER2. To explore the role of HER family biology in upper gastrointestinal cancers, we evaluated the effect of lapatinib, erlotinib, and trastuzumab in a panel of molecularly characterized human upper gastrointestinal cancer cell lines and xenografts.

Repeated stress alters the ability of nicotine to activate the hypothalamic-pituitary-adrenal axis.

Acute nicotine administration has been shown to activate the hypothalamic-pituitary-adrenal (HPA) axis and stimulate secretion of adrenocorticotrophic hormone (ACTH), corticosterone/cortisol and beta-endorphin (beta-END) in both rodents and humans, raising the possibility that activation of the HPA axis by nicotine may mediate some of the effects of nicotine. Since stress can increase the risk of drug use and abuse, we hypothesized that repeated stress would increase the ability of nicotine to stimulate the secretion of HPA hormones. To test our hypothesis, mice were exposed to repeated stress (swimming in 15 degrees C water for 3 min/day for 5 days) and killed 15 min after injection of saline or nicotine (0.

Liver X receptor agonist T0901317 inhibition of glucocorticoid receptor expression in hepatocytes may contribute to the amelioration of diabetic syndrome in db/db mice.

The glucocorticoid receptor (GR) is a crucial target gene for glucocorticoid-induced insulin resistance and hepatic gluconeogenesis linked to the development of type 2 diabetes. The liver X receptors (LXRs) are nuclear receptors that play an important role in the regulation of the metabolic gene linked to carbohydrate homeostasis. To assess the tissue-specific interaction of LXR with GR in the development of type 2 diabetes, we examined the possible effect of LXR agonist T0901317 on GR gene expression in vivo and in vitro in hepatocytes from db/db mice (a model of type 2 diabetes).