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:Concerted metabolic shifts give new insights into the syntrophic mechanism between propionate-fermenting Pelotomaculum thermopropionicum and hydrogenotrophic Methanocella conradii
Project description:In the syntrophic interaction between fermentative bacteria (Pelotomaculum thermopropionicum) and methanogenic archaea (methanogens: Methanothemobacter thermautotrophicus), reducing equivalents (e.g., H2) produced by fermentative bacteria should efficiently be consumed by methanogens in order for the fermentation of volatile fatty acids (VFA, e.g., butyrate, propionate, and acetate) to be thermodynamically feasible. It has been known that physical approximation (e.g., coaggregation) between VFA-fermenting syntrophic bacteria (syntrophs) and hydrogenotrophic methanogens is necessary for efficient H2 transfer between them. Our previous study has shown that, at an early exponential growth phase of syntrophic coculture, cells of Pelotomaculum thermopropionicum (syntroph) were connected to cells of Methanothermobacter thermautotrophicus (methanogen) via unidentified extracellular filamentous appendages, after which they started to coaggregate, suggesting that the filamentous appendages may have been important for their syntrophic interaction. The filamentous appendages seemed to specifically connect these syntrophic partners, since such pairwise connection has been observed neither in single-species cultures (monocultures) nor in mixtures with other microbes.<br>We found that P. thermopropionicum has putative gene clusters for flagellum and pilus, while no extracellular filament gene was identified in the M. thermautotrophicus genome. So we examined transcriptome responses of M. thermautotrophicus to the contact with flagellar filament protein (FliC) and flagellar cap protein (FliD) of P. thermopropionicum.
Project description:In the syntrophic interaction between fermentative bacteria (Pelotomaculum thermopropionicum) and methanogenic archaea (methanogens: Methanothemobacter thermautotrophicus), reducing equivalents (e.g., H2) produced by fermentative bacteria should efficiently be consumed by methanogens in order for the fermentation of volatile fatty acids (VFA, e.g., butyrate, propionate, and acetate) to be thermodynamically feasible. It has been known that physical approximation (e.g., coaggregation) between VFA-fermenting syntrophic bacteria (syntrophs) and hydrogenotrophic methanogens is necessary for efficient H2 transfer between them. Our previous study has shown that, at an early exponential growth phase of syntrophic coculture, cells of Pelotomaculum thermopropionicum (syntroph) were connected to cells of Methanothermobacter thermautotrophicus (methanogen) via unidentified extracellular filamentous appendages, after which they started to coaggregate, suggesting that the filamentous appendages may have been important for their syntrophic interaction. The filamentous appendages seemed to specifically connect these syntrophic partners, since such pairwise connection has been observed neither in single-species cultures (monocultures) nor in mixtures with other microbes. <br> We found that P. thermopropionicum has putative gene clusters for flagellum and pilus, while no extracellular filament gene was identified in the M. thermautotrophicus genome. So we examined transcriptome responses of M. thermautotrophicus to the contact with flagellar filament protein (FliC) and flagellar cap protein (FliD) of P. thermopropionicum.
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.
