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1.
Nature ; 632(8027): 1137-1144, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39085612

RESUMO

Exposure to environmental pollutants and human microbiome composition are important predisposition factors for tumour development1,2. Similar to drug molecules, pollutants are typically metabolized in the body, which can change their carcinogenic potential and affect tissue distribution through altered toxicokinetics3. Although recent studies demonstrated that human-associated microorganisms can chemically convert a wide range of xenobiotics and influence the profile and tissue exposure of resulting metabolites4,5, the effect of microbial biotransformation on chemical-induced tumour development remains unclear. Here we show that the depletion of the gut microbiota affects the toxicokinetics of nitrosamines, which markedly reduces the development and severity of nitrosamine-induced urinary bladder cancer in mice6,7. We causally linked this carcinogen biotransformation to specific gut bacterial isolates in vitro and in vivo using individualized bacterial culture collections and gnotobiotic mouse models, respectively. We tested gut communities from different human donors to demonstrate that microbial carcinogen metabolism varies between individuals and we showed that this metabolic activity applies to structurally related nitrosamine carcinogens. Altogether, these results indicate that gut microbiota carcinogen metabolism may be a contributing factor for chemical-induced carcinogenesis, which could open avenues to target the microbiome for improved predisposition risk assessment and prevention of cancer.


Assuntos
Carcinogênese , Carcinógenos , Microbioma Gastrointestinal , Nitrosaminas , Neoplasias da Bexiga Urinária , Animais , Feminino , Humanos , Masculino , Camundongos , Biotransformação , Carcinogênese/induzido quimicamente , Carcinogênese/metabolismo , Carcinogênese/patologia , Carcinógenos/química , Carcinógenos/metabolismo , Carcinógenos/farmacocinética , Carcinógenos/toxicidade , Microbioma Gastrointestinal/fisiologia , Vida Livre de Germes , Camundongos Endogâmicos C57BL , Nitrosaminas/química , Nitrosaminas/metabolismo , Nitrosaminas/farmacocinética , Nitrosaminas/toxicidade , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/etiologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/prevenção & controle , Suscetibilidade a Doenças
2.
Sci Rep ; 8(1): 12157, 2018 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-30108246

RESUMO

Recent findings suggest that human microbiome can influence the development of cancer, but the role of microorganisms in bladder cancer pathogenesis has not been explored yet. The aim of this study was to characterize and compare the urinary microbiome of bladder cancer patients with those of healthy controls. Bacterial communities present in urine specimens collected from 12 male patients diagnosed with bladder cancer, and from 11 healthy, age-matched individuals were analysed using 16S sequencing. Our results show that the most abundant phylum in both groups was Firmicutes, followed by Actinobacteria, Bacteroidetes and Proteobacteria. While microbial diversity and overall microbiome composition were not significantly different between groups, we could identify operational taxonomic units (OTUs) that were more abundant in either group. Among those that were significantly enriched in the bladder cancer group, we identified an OTU belonging to genus Fusobacterium, a possible protumorigenic pathogen. In an independent sample of 42 bladder cancer tissues, 11 had Fusobacterium nucleatum sequences detected by PCR. Three OTUs from genera Veillonella, Streptococcus and Corynebacterium were more abundant in healthy urines. However, due to the limited number of participants additional studies are needed to determine if urinary microbiome is associated with bladder cancer.


Assuntos
Microbiota , Neoplasias da Bexiga Urinária/microbiologia , Bexiga Urinária/microbiologia , Urina/microbiologia , Idoso , Idoso de 80 Anos ou mais , Bactérias/genética , Bactérias/isolamento & purificação , Estudos de Casos e Controles , DNA Bacteriano/isolamento & purificação , Voluntários Saudáveis , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/urina
3.
Front Plant Sci ; 9: 86, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29459878

RESUMO

Bemisia tabaci is one of the most devastating pests in tomato greenhouse production. Insecticide resistance management for B. tabaci requires a novel approach that maximizes non-chemical methods for pest control. The aim of this study was to test the effects of rootstocks on B. tabaci populations in hydroponically grown tomato plants. In order to contribute to the better understanding of the mechanisms defining the attractiveness of plant to the aerial pest, the effects of rootstocks on leaf anatomy and the amino acid composition of phloem sap were assessed. A two-factorial experimental design was adopted using cultivars (rootstock cultivars and Clarabella) grown as either non-grafted or grafted with cultivar Clarabella as a scion. The rootstock cultivars included Arnold, Buffon, Emperador, and Maxifort. A reduction in B. tabaci density was observed using all rootstock cultivars. The number of adult individuals per leaf was 2.7-5.4 times lower on rootstock cultivars than on Clarabella. The number of large nymphs per square centimeter was at least 24% higher on non-grafted Clarabella compared with all other treatments. The leaf lamina thickness and mesophyll thickness were lower in self-grafted Clarabella than in non-grafted or in one grafted on rootstock cultivars; however, the extent of this reduction depended on the rootstock. The leaves with thinner laminae were generally less attractive to B. tabaci. Eighteen amino acids were detected in the exudates of phloem sap. In all treatments, the most abundant amino acid was γ-aminobutyric acid (GABA), followed by proline, serine, alanine, and histidine. The scion cultivar Clarabella was the most attractive to B. tabaci and had a higher content of leucine than did rootstock cultivars, and a higher content of lysine compared to Buffon and Maxifort. The features modified by rootstock such are changes in leaf anatomy can affect the attractiveness of plants to B. tabaci. Thus, the grafting of tomato could constitute a valuable tool in an integrated management strategy against this aerial pest.

4.
Tumour Biol ; 35(1): 567-72, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23959475

RESUMO

As the seventh most common human malignancy, bladder cancer represents a global health problem. In addition to well-recognized risk factors such as smoking and exposure to chemicals, various infectious agents have been implicated as cofactors in the pathogenesis of urothelial malignancies. The aim of the present study was to assess the possible association of viral infection and bladder cancer in Croatian patients. Biopsy specimens were collected from a total of 55 patients diagnosed with different stages of bladder cancer. Initial screening of DNA extracts for the presence of viruses on Lawrence Livermore Microbial Detection Array revealed Kaposi's sarcoma-associated herpesvirus (KSHV) in each of three randomly chosen biopsy specimens. The prevalence of infection with KSHV among study population was then examined by KSHV-specific polymerase chain reaction (PCR) and immunoblotting. By nested PCR, KSHV DNA was detected in 55% of patients. KSHV, also known as human herpesvirus 8, is an infectious agent known to cause cancer. Its oncogenic potential is primarily recognized from its role in Kaposi's sarcoma, but it has also been involved in pathogenesis of two lymphoproliferative disorders. A high prevalence of KSHV infection in our study indicates that KSHV may play a role in tumorigenesis of bladder cancer and warrants further studies.


Assuntos
Infecções por Herpesviridae/complicações , Herpesvirus Humano 8 , Neoplasias da Bexiga Urinária/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Transformação Celular Viral/genética , Feminino , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismo
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