Long-chain polyphosphate in osteoblast matrix vesicles: Enrichment and inhibition of mineralization.

Background: Inorganic polyphosphate (polyP) is a fundamental and ubiquitous molecule in prokaryotes and eukaryotes. PolyP has been found in mammalian tissues with particularly high levels of long-chain polyP in bone and cartilage where critical questions remain as to its localization and function. Here, we investigated polyP presence and function in osteoblast-like SaOS-2 cells and cell-derived matrix vesicles (MVs), the initial sites of bone mineral formation.

Notch1-Snail1-E-cadherin pathway in metastatic hepatocellular carcinoma.

Notch signaling, a critical pathway for tissue development, also contributes to tumorigenesis in many cancers, but its pathological function in liver cancer is not well defined. In our study, Notch1 expression and its clinicopathological parameters were evaluated in 82 human hepatocellular carcinoma (HCC) patients. Plasmid-based siNotch1 shRNA was transiently or stably transfected into metastatic HCC cells and subsequently evaluated for the effects on orthotopic liver tumor metastasis in a mouse model as well as the effects on downstream pathways.

Aptamer-mediated inhibition of Mycobacterium tuberculosis polyphosphate kinase 2.

Inorganic polyphosphate (polyP) plays a number of critical roles in bacterial persistence, stress, and virulence. PolyP intracellular metabolism is regulated by the polyphosphate kinase (PPK) protein families, and inhibition of PPK activity is a potential approach to disrupting polyP-dependent processes in pathogenic organisms. Here, we biochemically characterized Mycobacterium tuberculosis (MTB) PPK2 and developed DNA-based aptamers that inhibit the enzyme's catalytic activities.

Inhibition of PDGF, TGF-β, and Abl signaling and reduction of liver fibrosis by the small molecule Bcr-Abl tyrosine kinase antagonist Nilotinib.

Background & Aims: Nilotinib is a novel tyrosine kinase inhibitor of Bcr-Abl and other kinases. In this study, we have examined its activity as an anti-fibrotic agent.

Methods: The in vitro effect of Nilotinib on rat and human HSCs was assessed using proliferation assays and Western blotting.

Therapeutic targeting of the PDGF and TGF-beta-signaling pathways in hepatic stellate cells by PTK787/ZK22258.

Stimulation of hepatic stellate cells (HSCs) by platelet-derived growth factor (PDGF) and transforming growth factor-beta1 (TGF-beta1) is an essential pathway of proliferation and fibrogenesis, respectively, in liver fibrosis. We provide evidence that PTK787/ZK222584 (PTK/ZK), a potent tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor (VEGFR), significantly inhibits PDGF receptor expression, as well as PDGF-simulated HSC proliferation, migration and phosphorylation of ERK1/2, Akt and p70S6 kinase. Interestingly, PTK/ZK also antagonizes the TGF-beta1-induced expression of VEGF and VEGFR1.

PTK787/ZK22258 attenuates stellate cell activation and hepatic fibrosis in vivo by inhibiting VEGF signaling.

Liver fibrosis due to hepatic stellate cell (HSC) activation represents a common response to chronic liver injury. PTK787/ZK222584 (PTK/ZK) is a pan-VEGFR tyrosine kinase inhibitor. The aim of this study was to examine the effect of PTK/ZK in liver fibrosis.

p27Kip1 promotes migration of metastatic hepatocellular carcinoma cells.

Background/aim: p27(Kip1) (p27) is a member of the Cip/Kip family of cyclin/cyclin-dependent kinase inhibitors (CKIs), and its CKI-independent function regarding cell motility modulation has been discovered. However, it is controversial whether p27 promotes or inhibits cell migration. This study investigates the migration regulatory role of p27 in metastatic hepatocellular carcinoma (HCC) cells.