MMP Inhibition in Prostate Cancer

Matrix metalloproteinases (MMPs) play a significant role during the development and metastasis of prostate cancer (CaP). CaP cells secrete high levels of MMPs and low levels of endogenous MMP inhibitors (TIMPs), thus creating an excess balance of MMPs. Established CaP cell lines that express high levels of MMPs frequently metastasize to the bone and the lungs. Drugs such as Taxol and alendronate that reduce cell motility and calcium metabolism reduce bony metastasis of xenografted CaP tumors. We tested several synthetic, nontoxic inhibitors of MMPs that can be administered orally, including doxycycline (DC) and chemically modified tetracyclines (CMTs) on CaP cells in vitro and on a rat CaP model in vivo. Among several anti‐MMP agents tested, CMT‐3 (6‐deoxy, 6‐demethyl,4‐de‐dimethylamino tetracycline) showed highest activity against CaP cell invasion and cell proliferation. Micromolar concentration of CMT‐3 and DC inhibited both the secretion and activity of MMPs by CaP cells. When tested for in vivo efficacy in the Dunning rat CaP model by daily oral gavage, CMT‐3 and DC both reduced the lung metastases (> 50%). CMT‐3, but not DC, inhibited tumor incidence (55 ± 9%) and also reduced the tumor growth rate (27 ± 9.3%). More significantly, the drugs showed minimum systemic toxicity. Ongoing studies indicate that CMT‐3 may inhibit the skeletal metastases of CaP cells and delay the onset of paraplegia due to lumbar metastases. These preclinical studies provide the basis for clinical trials of CMT‐3 for the treatment of metastatic disease

Contrasted responses of two understorey species to direct and indirect effects of a canopy gap

Positive associations between adult trees and understorey species have been explained either by direct or indirect facilitation. We tested both models by comparing the performance of two understorey species with contrasted stress-tolerance abilities Galium odoratum and Deschampsia flexuosa. Individuals of both species were transplanted in the four combinations of two treatments (gap and removal of an herbaceous competitor, Molinia caerulea). Our experiment demonstrated that direct facilitation of adult trees may explain the restricted occurrence of the shade-demanding Galium within closed forest communities. In contrast, the shade-tolerant Deschampsia was subjected to additional competition within the forest, likely because adult trees had a higher negative effect on light availability and a similar negative effect on nitrogen availability within the forest than did Molinia in the gaps

Space Applications

Signals transmitted by global navigation satellite system (GNSS) satellites are not confined to the surface of the Earth but can likewise be used for navigation in space. Satellites in low Earth orbits, in particular, benefit from a similar signal strength and experience a full-sky visibility. On the other hand, the harsh space environment, long-term reliability requirements and the high dynamics of the host platform pose specific challenges to the design and operation of space-borne GNSS receivers. Despite these constraints, satellite manufacturers and scientists have early on started to exploit the benefits of GNSS technology. From the first flight of a Global Positioning System (GPS) receiver on Landsat-4, GNSS receivers have evolved into indispensable and ubiquitous tools for navigation and control of space vehicles. Following a general introduction, the chapter first describes the specific aspects of GNSS signal tracking in space and highlights the technological challenges of space-borne receiver design. Subsequently, the use of GNSS for spacecraft navigation is discussed taking into account both real-time navigation and precise orbit determination. Relevant algorithms and software tools are discussed and the currently achieved performance is presented based on actual missions and flight results. A dedicated section is devoted to the use of spaceborne GNSS for relative navigation of formation flying satellites. The chapter concludes with an outlook on special applications such as spacecraft attitude determination, GNSS tracking of ballistic vehicles as well as GNSS radio science