Paclitaxel (Taxol) upregulates expression of functional interleukin-6 in human ovarian cancer cells through multiple signaling pathways.

Paclitaxel (Taxol) is an antineoplastic agent that specifically targets microtubules and arrests cells at the G2/M phase of the cell cycle. In addition to mitotic arrest, the activation of c-Jun N-terminal kinase (JNK) signaling pathway has been demonstrated to be involved in the process leading to apoptosis. In an attempt to explore what genes are transcriptionally regulated by the activated JNK signaling pathway upon paclitaxel treatment, we used cDNA microarrays to analyse the changes of gene expression in human ovarian cancer cells that were treated with paclitaxel and/or the JNK inhibitor SP600125. Among 20 genes that were specifically regulated by the paclitaxel-activated JNK pathway, interleukin (IL)-6 was shown to elicit function through the JAK-STAT signaling pathway in an autocrine and/or paracrine fashion. Subsequently, we identified that 87.5% of eight tested ovarian cancer lines secreted detectable levels of IL-6, which could be further upregulated 2-3.2 fold by 1 microM paclitaxel. Dissection on regulatory pathways for IL-6 indicated that (i) when ovarian cancer cells were treated with paclitaxel at low but clinically achievable concentrations (exemplified by 1 microM in this study), the JNK signaling pathway was the major stimulator of IL-6 gene regulation and (ii) at suprapharmacologically high concentrations (exemplified by 50 microM), paclitaxel exerted lipopolysaccharide-like effects, most likely through the Toll-like receptor 4 signaling pathway. Collectively, these results suggest that paclitaxel upregulates functional IL-6 expression in human ovarian cancer cells through multiple signaling pathways.

Renal parenchymal malacoplakia: a rare cause of ARF with a review of recent literature.

Renal parenchymal malacoplakia is a rare cause of acute renal failure. Traditionally, it was associated with a high mortality rate and commonly resulted in renal failure requiring renal replacement therapy. The authors report on a 70-year-old woman who presented with acute renal failure caused by renal parenchymal malacoplakia. Her renal function recovered after levofloxacin treatment. All cases reported in the English-language literature since 1990, when fluoroquinolone was first used to treat malacoplakia, were reviewed. Although some patients still had renal failure, with renal biopsy and fluoroquinolone treatment, the patient mortality rate from renal parenchymal malacoplakia is remarkably low.

Crystallization and preliminary X-ray data of proteins derived from prothrombin.

Crystals of bovine prothrombin fragment 1 and deglycosylated fragment 1 have been grown from polyethylene glycol, Tris/maleate solutions and the crystals scatter x-rays at 2.8 A resolution. The crystals of both are tetragonal, space group P41212 or P43212, with 1 molecule per asymmetric unit. Moreover, the two appear to be isomorphous. Since the mother liquor can support Ca2+ ion without precipitation, crystals have been soaked with Ca2+ ion and preliminary results indicate that these remain closely isomorphous with parent crystals. Isomorphous heavy atom derivatives of mercury and platinum have been prepared of glycosylated fragment 1. In addition, crystals of human prothrombin fragment 1 have also been grown.