OBJECTIVES This study was designed to investigate the activation of the unfolded protein response (UPR) in tumor associated endothelial cells (TECs) and its association with chemoresistance during acidic pH stress. MATERIALS AND METHODS Endothelial cells from human oral squamous cell carcinomas (OSCC) were excised by laser capture microdissection (LCM) followed by analysis of UPR markers (Grp...

OBJECTIVE To investigate the role of the endoplasmic reticulum (ER) chaperone glucose-regulated protein (GRP) 78/BiP in the pathogenesis of obesity, insulin resistance, and type 2 diabetes. RESEARCH DESIGN AND METHODS Male Grp78(+/-) mice and their wild-type littermates were subjected to a high-fat diet (HFD) regimen. Pathogenesis of obesity and type 2 diabetes was examined by multiple approa...

Chrysin is a natural and biologically active flavonoid with anticancer effects. However, little is known about the adaptive response of cancer cells to chrysin. Chrysin reportedly has proteasome inhibitor activity. Previous studies demonstrated that proteasome inhibitors might induce endoplasmic reticulum (ER) stress response. In this study, we aimed to determine the effects of chrysin on hepat...

There is scant knowledge regarding how cell surface lipid-anchored T-cadherin (T-cad) transmits signals through the plasma membrane to its intracellular targets. This study aimed to identify membrane proteins colocalizing with atypical glycosylphosphatidylinositol (GPI)-anchored T-cad on the surface of endothelial cells and to evaluate their role as signaling adaptors for T-cad. Application of ...

BACKGROUND Previous studies have shown the central role of 78 kDa glucose-regulated protein (GRP78) in colorectal cancer (CRC) survival and chemoresistance. In the present study, we aimed to design a GRP78 inhibitor and test its potential to inhibit CRC cells growth. MATERIALS AND METHODS Computer-aided drug design was used to establish novel compounds as potential inhibitors of GRP78. Discov...

We have recently demonstrated that cell lines deficient in poly(ADP ribose)synthesisdue to deficiencyin the enzymepoly(ADP-rlbose) po lymerase (PADPRP) or depletion of its substrate NAD@ overexpress GRP78. Furthermore, this overexpression ofGRP78 is assodated with the acquisition of resistanceto topoisomerase11-directeddrugs such as eta poside (VP-16); (S. Chatterjee et aL, Cancer Res., 54: 440...

Differential display polymerase chain reaction was used to identify genes regulated by the mood-stabilizing drug valproate (VPA). Four differentially displayed valproate-regulated gene fragments were isolated in rat cerebral cortex after i.p. injection of sodium VPA (300 mg/kg) for 3 weeks, and their expression was confirmed by Northern and slot blot analysis in rat cerebral cortex and C6 gliom...

Brefeldin A, an agent that disrupts protein transport from the endoplasmic reticulum to the Golgi, induces the expression of GRP78 and the activation of nuclear factor (NF)-kappaB in cells. Treatment of cells with brefeldin A causes the development of resistance to topoisomerase II-directed agents, such as etoposide and doxorubicin. In this study, we show that treatment of EMT6 mouse mammary tu...

Resistance of colorectal cancer cells to paclitaxelinduced apoptosis is largely mediated by the activation of MEK/ERK signalling pathway. Inhibition of MEK/ERK pathway sensitized CRC cells to paclitaxel-induced apoptosis by down-regulation of GRP78. In the present study, we report that induction of apoptosis by paclitaxel when GRP78 is down-regulated involves activation of the caspase cascade. ...

OBJECTIVE To investigate the effect of rosuvastatin on platelet deposition under controlled shear rate conditions and to identify new platelet proteins involved in the interaction with the activating substrate. METHODS AND RESULTS Platelet-vessel wall interaction and thrombosis take place under dynamic conditions involving the interaction of the exposed damaged vascular wall with the circulat...