GRP78/Dna K Is a Target for Nexavar/Stivarga/Votrient in the Treatment of Human Malignancies, Viral Infections and Bacterial Diseases.

Prior tumor cell studies have shown that the drugs sorafenib (Nexavar) and regorafenib (Stivarga) reduce expression of the chaperone GRP78. Sorafenib/regorafenib and the multi-kinase inhibitor pazopanib (Votrient) interacted with sildenafil (Viagra) to further rapidly reduce GRP78 levels in eukaryotes and as single agents to reduce Dna K levels in prokaryotes. Similar data were obtained in tumor cells in vitro and in drug-treated mice for: HSP70, mitochondrial HSP70, HSP60, HSP56, HSP40, HSP10, and cyclophilin A.

Identification of a novel two-partner secretion locus in Moraxella catarrhalis.

Although Moraxella catarrhalis continues to be a significant cause of disease in both children and adults, the steps involved in pathogenesis remain poorly understood. We have identified three open reading frames in the M. catarrhalis genome that encode homologues of the two-partner secretion system (TPS).

Cytokines link osteoblasts and inflammation: microarray analysis of interleukin-17- and TNF-alpha-induced genes in bone cells.

The novel cytokine interleukin (IL)-17 has been implicated in many infectious and autoimmune settings, especially rheumatoid arthritis. Consistent with its proinflammatory effects on bone, osteoblast cells are highly responsive to IL-17, particularly in combination with other inflammatory cytokines. To better understand the spectrum of activities controlled by IL-17, we globally profiled genes regulated by IL-17 and tumor necrosis factor alpha (TNF-alpha) in the preosteoblast cell line MC3T3-E1.

Binding of pro-matrix metalloproteinase 9 by Fusobacterium nucleatum subsp. nucleatum as a mechanism to promote the invasion of a reconstituted basement membrane.

In this study, we investigated the ability of Fusobacterium nucleatum subsp. nucleatum to increase its tissue-invasive potential by acquiring cell-associated human matrix metalloproteinase 9 (MMP-9) activity. Binding of pro-MMP-9 to fusobacteria was demonstrated by enzyme-linked immunosorbent assay.

Effect of inactivation of the Arg- and/or Lys-gingipain gene on selected virulence and physiological properties of Porphyromonas gingivalis.

Proteolytic enzymes produced by Porphyromonas gingivalis are thought to play critical roles in the pathogenesis of periodontitis. The aim of this study was to investigate the effect of gingipain cysteine proteinase gene inactivation on selected pathological and physiological functions of P. gingivalis.

The collagenase activity of Porphyromonas gingivalis is due to Arg-gingipain.

Degradation of type I collagen by Porphyromonas gingivalis was monitored by fluorogenic, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and growth assays. All three assays showed that inactivation of both the rgpA and rgpB genes was necessary to completely eliminate the capacity of P. gingivalis to cleave type I collagen.