Combination therapy using the cyclooxygenase-2 inhibitor Parecoxib and radioimmunotherapy in nude mice with small peritoneal metastases of colonic origin.

Contains fulltext : 51280.pdf (publisher's version ) (Closed access)BACKGROUND: Inhibition of the COX-2 enzyme has been shown to have a radiosensitizing effect in epithelial cancers. The aim of this study was to investigate whether the efficacy of radioimmunotherapy (RIT) using 131I-labeled anti-CEA monoclonal antibody MN-14 could be enhanced by co-administration of the selective COX-2 inhibitor Parecoxib in mice with small volume (1-3 mm) peritoneal carcinomatosis of colonic origin. METHODS: First, the efficacy of 14 daily injections of Parecoxib monotherapy (0-0.2-1.0-5.0-25.0 mg/kg) was determined in mice with intraperitoneal LS174T xenografts. Second, the influence of Parecoxib (1.0 or 5.0 mg/kg) on the biodistribution of 125I-MN-14 was assessed. Finally, the efficacy of RIT alone [125 microCi 131I-MN-14/mouse approximately 1/4 of the maximal tolerated dose (MTD)] was compared with that of Parecoxib monotherapy and RIT combined with daily injections of Parecoxib (1.0 or 5.0 mg/kg). RESULTS: Parecoxib had no measurable antitumor effect up to the highest dose level (25 mg/kg). Parecoxib had no effect on the uptake of 125I-MN-14 in the intraperitoneal tumor xenografts or on normal tissue distribution. Median survival of the control mice and the mice treated with Parecoxib monotherapy (1.0 or 5.0 mg/kg) was 48.5 days, 52 days and 52 days (P=0.47). RIT alone significantly delayed the growth of the intraperitoneal xenografts resulting in a median survival of 87 days (P<0.0001). Mice treated with RIT + Parecoxib at 1.0 or 5.0 mg/kg had a median survival of 73.5 days and 76 days, respectively, which was not statistically different from survival after RIT alone (P=0.15). CONCLUSION: The COX-2 inhibitor Parecoxib does not enhance the therapeutic efficacy of RIT of experimental small volume peritoneal carcinomatosis of colonic origin

Observations of climate change among subsistence-oriented communities around the world

The study of climate change has been based strongly on data collected from instruments, but how local people perceive such changes remains poorly quantified. We conducted a meta-analysis of climatic changes observed by subsistence-oriented communities. Our review of 10,660 observations from 2,230 localities in 137 countries shows that increases in temperature and changes in seasonality and rainfall patterns are widespread (≈70% of localities across 122 countries). Observations of increased temperature show patterns consistent with simulated trends in surface air temperature taken from the ensemble average of CMIP5 models, for the period 1955-2005. Secondary impacts of climatic changes on both wild and domesticated plants and animals are extensive and threaten the food security of subsistence-oriented communities. Collectively, our results suggest that climate change is having profound disruptive effects at local levels and that local observations can make an important contribution to understanding the pervasiveness of climate change on ecosystems and societies