Lysophosphatidic acid (LPA), produced extracellularly by autotaxin (ATX), has diverse biological activities implicated in tumor initiation and progression, including increasing cell survival, angiogenesis, invasion and metastasis. ATX, LPA and the matrix metalloproteinase (MMP)-9 have all been implicated in hepatocellular carcinoma (HCC) invasion and metastasis. We, thus sought to determine whether ATX with subsequent LPA production and action, including induction of MMP-9 could provide a unifying mechanism. ATX transcripts and LPA receptor type 1 (LPA1) protein are elevated in HCC compared with normal tissues. Silencing or pharmacological inhibition of LPA1 significantly attenuated LPA-induced MMP-9 expression and HCC cell invasion. Further, reducing MMP-9 activity or expression significantly inhibits LPA-induced HCC cell invasion, demonstrating that MMP-9 is downstream of LPA1. Inhibition of phosphoinositide-3 kinase (PI3K) signaling or dominantnegative mutants of protein kinase Cd and p38 mitogenactivated protein kinase (MAPK) abrogated LPA-induced MMP-9 expression and subsequent invasion. We thus demonstrate a mechanistic cascade of ATX-producing LPA with LPA activating LPA1 and inducing MMP-9 through coordinate activation of the PI3K and the p38 MPAK signaling cascades, providing novel biomarkers and potential therapeutic targets for HCC.

No abstract

Herbicide-tolerant Zoysia grass (Zoysia japonica Steud.) has been generated previously through Agrobacterium tumefaciens-mediated transformation. The genetically modified (GM) Zoysia grass survived Basta spraying and grew to maturity normally while the wild-type (WT) grass stopped growing and died. GM Zoysia grass will permit more efficient weed control for various turf grass plantings such as home lawns, golf courses, and parks. We examined the environmental/biodiversity risks of herbicide-tolerant GM Zoysia before applying to regulatory agencies for approval for commercial release. The GM and WT Zoysia grass' substantial trait equivalence, ability to cross-pollinate, and gene flow in confined and unconfined test fields were selectively analyzed for environmental/biodiversity effects. No difference between GM and WT Zoysia grass in substantial traits was found. To assess the potential for cross-pollination and gene flow, a non-selective herbicide, Basta, was used. Results showed that unintended cross-pollination with and gene flow from GM Zoysia grass were not detected in neighboring weed species examined, but were observed in WT Zoysia grass (on average, 6% at proximity, 1.2% at a distance of 0.5 m and 0.12% at a radius of 3 m, and 0% at distances over 3 m). On the basis of these initial studies, we conclude that the GM Zoysia grass generated in our laboratory and tested in the Nam Jeju County field does not appear to pose a significant risk when cultivated outside of test fields.

Ethyl acetate and diethyl ether extracts, previously extracted with methanol, were obtained from flesh and skin of Eptatretus burgeri (hag fish) and Enedrias nebulosus (white spotted eel). Eight different extracts (4 mg/mL) were tested for DPPH free radical scavenging activity and the values were compared with commercial antioxidants (α-tocopherol and BHT). All extracts of E. burgeri exhibited significantly positive results (> 65%) in scavenging DPPH radicals compared to E. nebulosus. Thus, only E. burgeri extracts were tested for dose effect, hydrogen peroxide, hydroxyl radical, superoxide scavenging assays and heat stability at 25, 50, 75 and 100 °C for 30 min. All extracts of E. burgeri showed higher DPPH radical scavenging activities by increasing concentration. Significantly higher results were observed for hydroxyl radical scavenging activity when compared with commercial antioxidants. Relatively moderate activity and very low activity were exhibited for superoxide scavenging and hydrogen peroxide activities, respectively. Diethyl ether extracts of E. burgeri were stable with increased temperature, while ethyl acetate extracts were stable up to 75 °C. Thus, there is a high potential for E. burgeri being rich with heat-stable antioxidants that can scavenge hydroxyl radicals.

No abstract