Protein farnesyltransferase (FTase) inhibitors, generally called "FTIs," block the farnesylation of prelamin A, inhibiting the biogenesis of mature lamin A and leading to an accumulation of prelamin A within cells. A recent report found that a GGTI, an inhibitor of protein geranylgeranyltransferase-I (GGTase-I), caused an exaggerated accumulation of prelamin A in the presence of low amounts of ...

BACKGROUND Bronchial fibroblasts contribute to airway remodelling, including airway wall fibrosis. Transforming growth factor (TGF)-β1 plays a major role in this process. We previously revealed the importance of the mevalonate cascade in the fibrotic response of human airway smooth muscle cells. We now investigate mevalonate cascade-associated signaling in TGFβ1-induced fibronectin expression b...

BACKGROUND AND PURPOSE Mitogen-activated protein kinase (MAPK) has been shown to be involved in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). In the present study we examined the role of Ras protein, an upstream regulator of MAPK, and the effects of the inhibitors of Ras farnesyltransferase (FTase), FTI-277 and FTase inhibitor I, on angiographic vasospasm and clini...

All trans retinoic acid (ATRA) is a potent inducer of differentiation of HL-60 cell line. The pretreatment of the cells by compactin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl (HMG) CoA reductase, during 24 hours, enhances the ATRA-induced cell differentiation. At 50 nM, the percentage of cell differentiation is 34.9% +/- 2 and 73% +/- 2.96 in the control and compactin-treated cells...

Cross-talk between receptor tyrosine kinases and estrogen receptor is at least partly responsible for the development of acquired resistance to endocrine therapies. Hence, targeting receptor tyrosine kinases and their downstream partners with inhibitors/antagonists may reverse this resistance. Although ras mutations are rare in breast cancer (2%), aberrant function of Ras signal transduction pa...

The performance characteristics of assays is reported for thyroxine (T4), triiodothyronine (T3), and T3-uptake (T3U) using the GAMMAFLOTM Automated Assay System. A comparison of calculated free thyroxine index (FTI) values is also presented. This automated radioimmunoassay (RIA) system utilizes a combination of continuous-flow methodology and chromatographic separation techniques. The T4 assay ...

The aims of this study were to assess the repeatability of the Emed ST4 system and identify the range of pressure values observed in the normal foot. Fifty-three healthy subjects, 17 females (32%) and 36 males (68%), were recruited. Measurements were performed on two occasions approximately 12 days apart. Peak pressure (PP), contact area (CA), contact time (CT), pressure-time integral (PTI), fo...

Farnesyltransferase inhibitors (FTIs) were developed to target abnormal signaling pathways that are commonly activated in neoplastic cells. Five FTIs have recently undergone Phase I testing; and two are currently in Phase II clinical trials. As part of the development of these agents, there has been interest in determining their cellular effects in the clinical setting. Several approaches have ...