Slater S

References (3)

Title : A randomised phase III trial of the pharmacokinetic biomodulation of irinotecan using oral ciclosporin in advanced colorectal cancer: Results of the Panitumumab, Irinotecan &\; Ciclosporin in COLOrectal cancer therapy trial (PICCOLO) - Middleton_2013_Eur.J.Cancer_49_3507
Author(s) : Middleton G , Brown S , Lowe C , Maughan T , Gwyther S , Oliver A , Richman S , Blake D , Napp V , Marshall H , Wadsley J , Maisey N , Chau I , Hill M , Gollins S , Myint S , Slater S , Wagstaff J , Bridgewater J , Seymour M
Ref : Eur J Cancer , 49 :3507 , 2013
Abstract : BACKGROUND: The main toxicity of irinotecan in advanced colorectal cancer (CRC) is delayed diarrhoea. Intestinal SN-38, released by deconjugation of the parent glucuronide excreted into the bile or produced in situ by intestinal carboxylesterase, is toxic to the intestinal epithelium. The canalicular transport of irinotecan and SN-38G is mediated by ABCC2 (MRP2) and ABCB1 (MDR1) which are both inhibited by ciclosporin. We tested whether irinotecan and ciclosporin was non-inferior for anti-cancer efficacy and superior for toxicity compared with single-agent irinotecan.
METHODS: Six hundred and seventy-two patients with advanced, measurable CRC following prior fluoropyrimidine-containing chemotherapy were randomised to either irinotecan 3-weekly 350mg/m2 (or 300mg/m2 if age >70 or performance status (PS)=2) or 3-weekly irinotecan at 140mg/m2 (120mg/m2 if age >70 or PS=2) with ciclosporin 3mg/kg t.d.s. for three days by mouth starting on the morning before irinotecan. The primary end-point was the proportion of patients alive and progression-free at 12 weeks. The key secondary end-point was the incidence of grade 3 diarrhoea within 12 weeks of randomisation.
RESULTS: The proportion of patients progression-free at 12 weeks with irinotecan was 53.4% compared to 47.2% with irinotecan plus ciclosporin (difference=-6.3%, 95% confidence interval (CI) [-13.8%, 1.3%]). Since the lower limit of the 95% CI crossed the pre-specified non-inferiority margin of -10.6%, non-inferiority of irinotecan plus ciclosporin compared to irinotecan alone was not statistically demonstrated. 15.0% patients developed severe diarrhoea on irinotecan compared to 13.8% on irinotecan plus ciclosporin, a non-significant difference. INTERPRETATION: The pharmacokinetic biomodulation of irinotecan using oral ciclosporin does not improve the therapeutic index of irinotecan in advanced CRC. FUNDING: The trial was funded by Cancer Research UK and supported by Amgen Pharma.
ESTHER : Middleton_2013_Eur.J.Cancer_49_3507
PubMedSearch : Middleton_2013_Eur.J.Cancer_49_3507
PubMedID: 23953030

Title : Genome sequence of Azotobacter vinelandii, an obligate aerobe specialized to support diverse anaerobic metabolic processes - Setubal_2009_J.Bacteriol_191_4534
Author(s) : Setubal JC , dos Santos P , Goldman BS , Ertesvag H , Espin G , Rubio LM , Valla S , Almeida NF , Balasubramanian D , Cromes L , Curatti L , Du Z , Godsy E , Goodner B , Hellner-Burris K , Hernandez JA , Houmiel K , Imperial J , Kennedy C , Larson TJ , Latreille P , Ligon LS , Lu J , Maerk M , Miller NM , Norton S , O'Carroll IP , Paulsen I , Raulfs EC , Roemer R , Rosser J , Segura D , Slater S , Stricklin SL , Studholme DJ , Sun J , Viana CJ , Wallin E , Wang B , Wheeler C , Zhu H , Dean DR , Dixon R , Wood D
Ref : Journal of Bacteriology , 191 :4534 , 2009
Abstract : Azotobacter vinelandii is a soil bacterium related to the Pseudomonas genus that fixes nitrogen under aerobic conditions while simultaneously protecting nitrogenase from oxygen damage. In response to carbon availability, this organism undergoes a simple differentiation process to form cysts that are resistant to drought and other physical and chemical agents. Here we report the complete genome sequence of A. vinelandii DJ, which has a single circular genome of 5,365,318 bp. In order to reconcile an obligate aerobic lifestyle with exquisitely oxygen-sensitive processes, A. vinelandii is specialized in terms of its complement of respiratory proteins. It is able to produce alginate, a polymer that further protects the organism from excess exogenous oxygen, and it has multiple duplications of alginate modification genes, which may alter alginate composition in response to oxygen availability. The genome analysis identified the chromosomal locations of the genes coding for the three known oxygen-sensitive nitrogenases, as well as genes coding for other oxygen-sensitive enzymes, such as carbon monoxide dehydrogenase and formate dehydrogenase. These findings offer new prospects for the wider application of A. vinelandii as a host for the production and characterization of oxygen-sensitive proteins.
ESTHER : Setubal_2009_J.Bacteriol_191_4534
PubMedSearch : Setubal_2009_J.Bacteriol_191_4534
PubMedID: 19429624
Gene_locus related to this paper: azovd-c1dex6 , azovd-c1df21 , azovd-c1dfb5 , azovd-c1dg75 , azovd-c1dgm6 , azovd-c1dh91 , azovd-c1di03 , azovd-c1dib3 , azovd-c1dif2 , azovd-c1dIq5 , azovd-c1dir1 , azovd-c1dis2 , azovd-c1djq5 , azovd-c1djw3 , azovd-c1dk37 , azovd-c1dkb2 , azovd-c1dkj0 , azovd-c1dli6 , azovd-c1dng8 , azovd-c1dni5 , azovd-c1dpr0 , azovd-c1dqu3 , azovd-c1dri5 , azovd-c1drx0 , azovd-c1dsl7 , azovd-c1dsq7 , azovd-c1dss1 , azovd-metx , azovi-PHBC , azovd-c1dem4

Title : Genome sequence of the plant pathogen and biotechnology agent Agrobacterium tumefaciens C58 - Goodner_2001_Science_294_2323
Author(s) : Goodner B , Hinkle G , Gattung S , Miller N , Blanchard M , Qurollo B , Goldman BS , Cao Y , Askenazi M , Halling C , Mullin L , Houmiel K , Gordon J , Vaudin M , Iartchouk O , Epp A , Liu F , Wollam C , Allinger M , Doughty D , Scott C , Lappas C , Markelz B , Flanagan C , Crowell C , Gurson J , Lomo C , Sear C , Strub G , Cielo C , Slater S
Ref : Science , 294 :2323 , 2001
Abstract : Agrobacterium tumefaciens is a plant pathogen capable of transferring a defined segment of DNA to a host plant, generating a gall tumor. Replacing the transferred tumor-inducing genes with exogenous DNA allows the introduction of any desired gene into the plant. Thus, A. tumefaciens has been critical for the development of modern plant genetics and agricultural biotechnology. Here we describe the genome of A. tumefaciens strain C58, which has an unusual structure consisting of one circular and one linear chromosome. We discuss genome architecture and evolution and additional genes potentially involved in virulence and metabolic parasitism of host plants.
ESTHER : Goodner_2001_Science_294_2323
PubMedSearch : Goodner_2001_Science_294_2323
PubMedID: 11743194
Gene_locus related to this paper: agrt5-a9cf94 , agrt5-a9cfa9 , agrt5-a9cfs8 , agrt5-a9cfu7 , agrt5-a9cie7 , agrt5-a9cj11 , agrt5-a9cjp2 , agrt5-a9cki2 , agrt5-a9ckr2 , agrt5-a9ckt2 , agrt5-a9cle4 , agrt5-a9clq8 , agrt5-a9clq9 , agrt5-q7cx24 , agrt5-q7d1j0 , agrt5-q7d1j3 , agrt5-q7d3m5 , agrt5-q7d3t6 , agrt5-y5261 , agrtu-ACVB , agrtu-ATTS , agrtu-ATU0253 , agrtu-ATU0403 , agrtu-ATU0841 , agrtu-ATU1045 , agrtu-ATU1102 , agrtu-ATU1572 , agrtu-ATU1617 , agrtu-ATU1826 , agrtu-ATU1842 , agrtu-ATU2061 , agrtu-ATU2126 , agrtu-ATU2171 , agrtu-ATU2409 , agrtu-ATU2452 , agrtu-ATU2481 , agrtu-ATU2497 , agrtu-ATU2576 , agrtu-ATU3428 , agrtu-ATU3651 , agrtu-ATU3652 , agrtu-ATU4238 , agrtu-ATU5190 , agrtu-ATU5193 , agrtu-ATU5275 , agrtu-ATU5296 , agrtu-ATU5348 , agrtu-ATU5389 , agrtu-ATU5446 , agrtu-ATU5495 , agrtu-CPO , agrtu-DHAA , agrtu-DLHH , agrtu-EPHA , agrtu-GRST , agrtu-PCA , agrtu-PCAD , agrtu-PHBC , agrtu-PTRB , agrt5-a9cji8