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:BackgroundCannabinoids; tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN), might show antibacterial activity. Trema orientalis is a species in the Cannabaceae that is closely related to Cannabis through plastome phylogenetic evidence. This species is widely distributed throughout tropical Asia and is used as traditional medicine, particularly for the treatment of infectious diseases. However, no studies on the antibacterial activity of cannabinoid-containing inflorescences extracts are available. Thus, the aim of this study was to determine cannabinoid content and antibacterial activity of inflorescences fractions from T. orientalis native to Thailand.MethodsWe hypothesized that inflorescences from T. orientalis might display cannabinoids similar to Cannabis because of their close taxonomic relationship. We extracted the mature inflorescences and infructescence of T. orientalis in three disparate populations from different Thailand floristic regions. Extractions were subsequently partitioned into hydrophilic and lipophilic fractions using distilled water and chloroform. The lipophilic extracts were further fractionated by the column chromatography with gradient elution and analyzed by gas chromatography-mass spectrometry (GC-MS). Characterized cannabinoids were used in bioassays with multidrug-resistance bacteria.ResultsLipophilic extracts and fractions of inflorescences from all Thailand floristic regions consistently displayed cannabinoids (THC, CBD and CBN) in various quantities. These extracts exhibited inhibitory activity for Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii strains with minimum inhibitory concentration values varying from 31.25 to 125 µg/mL.ConclusionOur study is the first to report cannabinoid detection in extracts from inflorescences of T. orientalis, a species in the Cannabaceae. These extracts and their fractions containing cannabinoids showed pronounced antibacterial activity. The use of analytic methods also demonstrated reproducible cannabinoid extraction.
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:Establishing the genetic diversity and population structure of a species can guide the selection of appropriate conservation and sustainable utilization strategies. Next-generation sequencing (NGS) approaches are increasingly being used to generate multi-locus data for genetic structure determination. This study presents the genetic structure of a fodder species -Trema orientalis based on two genome-wide high-throughput diversity array technology (DArT) markers; silicoDArT and single nucleotide polymorphisms (SNPs). Genotyping of 119 individuals generated 40,650 silicoDArT and 4767 SNP markers. Both marker types had a high average scoring reproducibility (>99%). Genetic relationships explored by principal coordinates analysis (PCoA) showed that the first principal coordinate axis explained most of the variation in both the SilicoDArT (34.2%) and SNP (89.6%) marker data. The average polymorphic information content did not highly differ between silicoDArT (0.22) and SNPs (0.17) suggesting minimal differences in informativeness in the two groups of markers. The, mean observed (Ho) and expected (He) heterozygosity were low and differed between the silicoDArT and SNPs respectively, estimated at Ho = 0.08 and He = 0.05 for silicoDArT and Ho = 0.23 and He = 0.19 for SNPs. The population of T. orientalis was moderately differentiated (FST = 0.20-0.53) and formed 2 distinct clusters based on maximum likelihood and principal coordinates analysis. Analysis of molecular variance revealed that clusters contributed more to the variation (46.3-60.8%) than individuals (32.9-31.2%). Overall, the results suggest a high relatedness of the individuals sampled and a threatened genetic potential of T. orientalis in the wild. Therefore, genetic management activities such as ex-situ germplasm management are required for the sustainability of the species. Ex-situ conservation efforts should involve core collection of individuals from different populations to capture efficient diversity. This study demonstrates the importance of silicoDArT and SNP makers in population structure and genetic diversity analysis of Trema orientalis, useful for future genome wide studies in the species.