Project description:Primary objectives: The primary objective is to investigate circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Primary endpoints: circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Project description:Longfin smelt (Spirinchus thaleichthys) is a threatened anadromous fish species that spawns in freshwater to moderately brackish (i.e. 5-10 ppt) reaches of the upper San Francisco Estuary and has declined to ~1% of its pre-1980s abundances. Despite 50+ years of population monitoring, the efficacy of 10+ years of conservation efforts for longfin smelt remain uncertain due to a limited understanding of how the species responds to environmental variation, such as salinity. For example, high mortality during larval stages has prevented culture efforts from closing the life cycle in captivity. Here, we investigated the effects of salinity on longfin smelt yolk-sac larvae. Newly hatched larvae from four single-pair crosses were acutely transferred to and reared at salinities of 0.4, 5, 10, 20 or 32 ppt. We compared whole-body water and sodium ion (Na+) content, notochord length and yolk-sac volume at 12, 24, 48, 72, and 96 hours post-transfer for each salinity treatment. We found that larvae maintained osmotic and ionic balance at 0.4-10 ppt, whereas salinities ˃10 ppt resulted in decreased water and increased whole-body Na+ content. We also found that larvae grew largest and survived the longest when reared at 5 and 10 ppt, respectively, and that yolk resorption stalled at 0.4 ppt. Finally, there were significant but small interclutch variations in responses to different salinities, with clutch accounting for <8% of the variance in our statistical models. Overall, our results indicate that longfin smelt yolk-sac larvae likely perform best at moderately brackish conditions, thus yielding a mechanism that explains their distribution in field surveys and providing key information for future conservation efforts.
Project description:The study is intended to collect specimens to support the application of genome analysis technologies, including large-scale genome sequencing. This study will ultimately provide cancer researchers with specimens that they can use to develop comprehensive catalogs of genomic information on at least 50 types of human cancer. The study will create a resource available to the worldwide research community that could be used to identify and accelerate the development of new diagnostic and prognostic markers, new targets for pharmaceutical interventions, and new cancer prevention and treatment strategies. This study will be a competitive enrollment study conducted at multiple institutions.
Project description:The rapid decline of longfin smelt Spirinchus thaleichthys, a threatened euryhaline forage fish in California, is a serious concern for scientists and resource managers. To recover and conserve this species, a captive culture program was initiated, focusing on the collection, captive rearing and breeding of wild broodstock, and the rearing of their offspring. Although progress has been made in the collection of broodstock and the production and culturing of larvae, no studies have evaluated the rearing of juvenile life stages in captivity. The present study examines methodological considerations for culturing F1 juvenile longfin smelt, specifically, the first efforts toward weaning juveniles to a dry commercial pellet feed. Cultured juvenile longfin smelt were fed live Artemia only or co-fed Artemia and dry feed for 62 days, and the effects of feed type on juvenile survival, growth, body condition, and fatty acid profiles were examined. No significant differences were observed between feeding treatments, despite an 80% reduction in Artemia in the co-feeding treatment. Furthermore, examination of fish stomach contents at the end of the trial confirmed the transition to dry feed. This is the first study to indicate successful feeding by longfin smelt on dry commercial pellets, and suggests that juvenile longfin smelt can be fully weaned onto dry feeds. Results of this study are critical for closing the lifecycle of longfin smelt in captivity and developing a successful conservation culture program for this imperiled species.