Soil respiration was measured throughout the year (June 1992 to May 1993) in a mature, deciduous, broad-leaved forest and an adjacent, clear-felled stand which was made in November 1991, in Hiroshima Prefecture, west Japan. The same soil temperature and soil moisture content as those in the forest stand were maintained in two frame boxes covered with sheers of white netting in the dear-felled stand to observe soil respiration. A herbicide was applied to the cut end of all stumps in one of the two frame boxes in order to kill the root system. There was no significant difference in the aboveground biomass and soil environmental conditions between the forest and the frame boxes in the clear-felled stands. The difference in soil respiration rate between the forest and the frame box, in which the root system was killed by the herbicide, was considered to be due largely to the contribution of root respiration. Taking into consideration CO 2 evolution due to the decomposition of roots killed and the change in A o layer respiration rate after clear-felling, the proportion of root respiration to the total soil respiration before dear-felling was estimated to be 5 i% annually, which coincides closely with those values estimated previously in mature forests by other methods. The difference in the soil respiration rate between the two frame boxes (one with killed roots and the other with undisturbed roots) suggested that the annual root respiration rate just after clear-felling dropped to about two-thirds (70%) of that before clear-felling.

No abstract

Abstract. Stored amounts and flow rates of soil carbon were measured simultaneously with soil environmental conditions (temperature and moisture content) periodically during the growing seasons from 1994 to 1995 at two plots (plot A was a dry soil condition, and plot B was a wet condition) in a black spruce (Picea mariana) forest stand in the Prince

SU6668 (TSU-68) is a small-molecule synthetic inhibitor of the angiogenic related receptor tyrosine kinases Flk-1/KDR, PDGFR␤, and FGFR1. Using a mouse model of peritoneally disseminated ovarian cancer, we investigated whether SU6668 inhibits peritoneal dissemination and prolongs survival time. BALB/c nude mice were intraperitoneally (i.p.) inoculated with SHIN-3 (VEGF-hypersecretory) or KOC-2S (PDGF-hypersecretory) ovarian serous adenocarcinoma cells with marked peritoneal dissemination ability. From the day after i.p. inoculation of tumor cells, SU6668 was orally administered 6 times weekly at a daily dose of 100 mg/kg or 400 mg/kg. The SU6668-administered group and the vehicle-administered control group were compared for the number of tumor vascular endothelial cells, weight of peritoneally disseminated tumors, amount of ascitic fluid and survival time. As a result, these 3 parameters were significantly smaller in the SHIN-3-inoculated, SU6668-administered mice than in the control group (p ‫؍‬ 0.03, p ‫؍‬ 0.002, and p ‫؍‬ 0.02, respectively). The mean survival time was significantly longer, at 58.1 ؎ 11.2 days, in the SU6668-administered mice than that (34.5 ؎ 8.8 days) in the control group (p ‫؍‬ 0.002). Similarly, in the KOC-2S-inoculated mice, the oral administration of SU6668 significantly reduced these 3 parameters (p ‫؍‬ 0.04, p ‫؍‬ 0.04, and p ‫؍‬ 0.03, respectively), and significantly prolonged survival (16.6 ؎ 1.7 days vs. 11.0 ؎ 0.7 days, p ‫؍‬ 0.008). Thus, the oral administration of SU6668 inhibited angiogenesis and peritoneal dissemination and prolonged survival in mice with peritoneally disseminated ovarian cancer. These effects were observed with both the VEGF-and PDGF-hypersecretory cell lines. Our results suggest that molecular targeting with oral SU6668 will become a new therapeutic strategy targeting peritoneally disseminated ovarian cancer.

Vascular endothelial growth factor (VEGF) is known to play a major role in angiogenesis in a variety of tumors. A soluble form of Flt-1 (sFlt-1), a VEGF receptor, is potentially useful as an antagonist of VEGF, and accumulating evidences suggest the applicability of sFlt-1 in tumor suppression by means of anti-angiogenesis. We previously demonstrated the efficacy of sflt-1 gene expression in situ to suppress tumor growth and ascites in ovarian cancer. Here, we demonstrate the therapeutic applicability of muscle-mediated expression of sFlt-1 in tumor-bearing mice. Initially, tumor suppressive action was confirmed by inoculating sFlt-1-expressing ovarian cancer (SHIN-3) cells into mice, both subcutaneously and intraperitoneally. To validate the therapeutic efficacy in a more clinically relevant model, adeno-associated virus vectors encoding sflt-1 were introduced into mouse skeletal muscles and were subsequently inoculated with tumor cells. As a result, high serum sFlt-1 levels were constantly observed, and the growth of both subcutaneously-and intraperitoneally-inoculated tumors was significantly suppressed. No delay in wound healing or adverse events of neuromuscular damage were noted, body weight did not change, and laboratory data, such as those representing liver and renal functions, were not affected. These results indicate that sFlt-1 suppresses growth and peritoneal dissemination of ovarian cancer by the inhibition of angiogenesis, and thus suggest the usefulness of gene therapy for ovarian cancer. ' 2006 Wiley-Liss, Inc.