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1.
J Transl Med ; 20(1): 183, 2022 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-35468793

RESUMO

In this study we aimed to investigate signaling pathways that drive therapy resistance in esophageal adenocarcinoma (EAC). Paraffin-embedded material was analyzed in two patient cohorts: (i) 236 EAC patients with a primary tumor biopsy and corresponding post neoadjuvant chemoradiotherapy (nCRT) resection; (ii) 66 EAC patients with resection and corresponding recurrence. Activity of six key cancer-related signaling pathways was inferred using the Bayesian inference method. When assessing pre- and post-nCRT samples, lower FOXO transcriptional activity was observed in poor nCRT responders compared to good nCRT responders (p = 0.0017). This poor responder profile was preserved in recurrences compared to matched resections (p = 0.0007). PI3K pathway activity, inversely linked with FOXO activity, was higher in CRT poor responder cell lines compared to CRT good responders. Poor CRT responder cell lines could be sensitized to CRT using PI3K inhibitors. To conclude, by using a novel method to measure signaling pathway activity on clinically available material, we identified an association of low FOXO transcriptional activity with poor response to nCRT. Targeting this pathway sensitized cells for nCRT, underlining its feasibility to select appropriate targeted therapies.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Adenocarcinoma/genética , Adenocarcinoma/terapia , Teorema de Bayes , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Humanos , Fosfatidilinositol 3-Quinases
2.
Int J Syst Evol Microbiol ; 54(Pt 6): 2155-2162, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15545451

RESUMO

In an ecological survey of nitrogen-fixing bacteria isolated from the rhizosphere and as endophytes of sugarcane, maize and teosinte plants in Brazil, Mexico and South Africa, a new phylogenetically homogeneous group of N(2)-fixing bacteria was identified within the genus Burkholderia. This polyphasic taxonomic study included microscopic and colony morphology, API 20NE tests and growth on different culture media at different pH and temperatures, as well as carbon source assimilation tests and whole-cell protein pattern analysis. Analysis of 16S rRNA gene sequences showed 99.2-99.9 % similarity within the novel species and 97.2 % similarity to the closest related species, Burkholderia sacchari. The novel species was composed of four distinct amplified 16S rDNA restriction analysis groups. The DNA-DNA reassociation values within the novel species were greater than 70 % and less than 42 % for the closest related species, B. sacchari. Based on these results and on many phenotypic characteristics, a novel N(2)-fixing species is proposed for the genus Burkholderia, Burkholderia tropica sp. nov., with the type strain Ppe8(T) (=ATCC BAA-831(T)=LMG 22274(T)=DSM 15359(T)). B. tropica was isolated from plants grown in geographical regions with climates ranging from temperate subhumid to hot humid.


Assuntos
Burkholderia/classificação , Burkholderia/isolamento & purificação , Fixação de Nitrogênio/fisiologia , Poaceae/microbiologia , Proteínas de Bactérias/análise , Proteínas de Bactérias/isolamento & purificação , Técnicas de Tipagem Bacteriana , Brasil , Burkholderia/citologia , Burkholderia/fisiologia , Meios de Cultura/química , DNA Bacteriano/química , DNA Bacteriano/isolamento & purificação , DNA Ribossômico/química , DNA Ribossômico/isolamento & purificação , Metabolismo Energético , Flagelos , Genes de RNAr , Concentração de Íons de Hidrogênio , México , Dados de Sequência Molecular , Movimento , Hibridização de Ácido Nucleico , Filogenia , Proteoma/análise , Proteoma/isolamento & purificação , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Saccharum/microbiologia , África do Sul , Temperatura , Zea mays/microbiologia
3.
Int J Syst Evol Microbiol ; 51(Pt 1): 17-26, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11211255

RESUMO

A new group of nitrogen-fixing Azospirillum sp. bacteria was isolated from the roots of the C4-gramineous plant Miscanthus. Polyphasic taxonomy was performed, including auxanography using API galleries, physiological tests and 16S rRNA sequence comparison. The ability of the isolates to fix dinitrogen was evaluated by amplification of the nifD gene, immunodetection of the dinitrogenase reductase and acetylene-reduction assay. On the basis of these results, the nitrogen-fixing isolates represent a new species within the genus Azospirillum. Its closest phylogenetic neighbours, as deduced by 16S rDNA-based analysis, are Azospirillum lipoferum, Azospirillum largimobile and Azospirillum brasilense with 96.6, 96.6 and 95.9% sequence similarity, respectively. Two 16S rRNA-targeting oligonucleotide probes were developed which differentiate the new species from the other Azospirillum species by whole-cell fluorescence hybridization. Strains of the new species are curved rods or S-shaped, 1.0-1.5 microm in width and 2,0-3.0 microm in length, Gram-negative and motile with a single polar flagellum. Optimum growth occurs at 30 degrees C and at pH values between 6.0 and 7.0. No growth takes place at 37 degrees C. They have a respiratory type of metabolism, grow well on arabinose, D-fructose, gluconate, glucose, glycerol, malate, mannitol and sorbitol. They differ from A. largimobile and A. lipoferum by their inability to use N-acetylglucosamine and D-ribose, from A. lipoferum by their ability to grow without biotin supplementation and from A. brasilense by their growth with D-mannitol and D-sorbitol as sole carbon sources. Nitrogen fixation occurs in microaerobic nitrogen-limited conditions. For this species, the name Azospirillum doebereinerae sp. nov. is suggested, with strain GSF71T as the type strain (= DSM 13131T; reference strain Ma4 = DSM 13400). Its G+C content is 70.7 mol%.


Assuntos
Azospirillum/classificação , Fixação de Nitrogênio , Poaceae/microbiologia , Azospirillum/genética , Azospirillum/isolamento & purificação , Azospirillum/fisiologia , Composição de Bases , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Hibridização in Situ Fluorescente , Dados de Sequência Molecular , Fixação de Nitrogênio/genética , Sondas de Oligonucleotídeos , Fenótipo , Filogenia , Raízes de Plantas/microbiologia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
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