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Song N.,Chinese Academy of Agricultural Sciences | Song N.,Vrije Universiteit Brussel | Xu J.,State Key Laboratory for Oncogenes and Related Genes | Li Z.,Chinese Academy of Agricultural Sciences | And 2 more authors.

To investigate whether plasmid-free cells of pathogenic Escherichia coli can be isolated by disrupting a single gene in an endogenous plasmid without further treatment, the effect of the disruption of partitioning genes on the inheritance of the endogenous plasmid pUTI89 of the uropathogenic E. coli strain UTI89 was studied. We found that mutation of parB, which encodes a type Ib partitioning protein, could cause loss of the endogenous plasmid at a ratio of about 1%. Clones derived from parB mutants, identified by antibiotic sensitivity, were all plasmid free. Plasmid instability caused by the parB mutation was found to correlate with a negative effect on host cell growth. Thus, in this pathogenic E. coli, an endogenous plasmid as large as 114. kbp could be cured effectively by targeting a single type Ib partitioning gene followed by passaging, which may facilitate further investigations on the function of endogenous plasmids in their natural hosts. © 2015 Elsevier B.V. Source

Xu J.,State Key Laboratory for Oncogenes and Related Genes | Li Z.,Vrije Universiteit Brussel | Wang J.,Shanghai Institute of Digestive Disease | Chen H.,State Key Laboratory for Oncogenes and Related Genes | And 3 more authors.
Translational Oncology

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor commonly inactivated in glioblastoma multiforme (GBM), but the prognostic significance of PTEN remains controversial. Here, we demon- strate significant prognostic value of combined PTEN mutation and expression for the survival of patients with GBM on the basis of analysis of large-scale cancer genomic data. PTEN nonsense mutations associated with significantly shorter disease-free survival and overexpression of PTEN protein linked to shorter disease-free and overall survival of patients with GBM. PTEN nonsense mutations correlated with decreased p53 and Gata3 protein levels and increased genomic instability in human GBM tissues. Expression of nonsense PTEN mutant decreased p53 and Gata3 levels, producing increased DNA damage both in vitro and in vivo. Mice carrying xenograft tumors with nonsense PTEN mutant displayed significantly shorter survival. Our data demonstrated the prognostic value of combined PTEN mutation and protein expression for patients with GBM and highlighted distinct biologic effects of nonsense and missense mutations of PTEN. © 2014 Neoplasia Press. All rights reserved. Source

Liang L.,State Key Laboratory for Oncogenes and Related Genes | Fang J.-Y.,State Key Laboratory for Oncogenes and Related Genes | Xu J.,State Key Laboratory for Oncogenes and Related Genes

Gastric cancer (GC) is among the most common malignancy in the world with poor prognosis and limited treatment options. It has been established that gastric carcinogenesis is caused by a complex interaction between host and environmental factors. Copy number variation (CNV) refers to a form of genomic structural variation that results in abnormal gene copy numbers, including gene amplification, gain, loss and deletion. DNA CNV is an important influential factor for the expression of both protein-coding and non-coding genes, affecting the activity of various signaling pathways. CNV arises as a result of preferential selection that favors cancer development, and thus, targeting the amplified 'driver genes' in GC may provide novel opportunities for personalized therapy. The detection of CNVs in chromosomal or mitochondrial DNA from tissue or blood samples may assist the diagnosis, prognosis and targeted therapy of GC. In this review, we discuss the recent CNV discoveries that shed light on the molecular pathogenesis of GC, with a specific emphasis on CNVs that display diagnostic, prognostic or therapeutic significances in GC.Oncogene advance online publication, 15 June 2015; doi:10.1038/onc.2015.209. © 2015 Macmillan Publishers Limited Source

Wang H.,State Key Laboratory for Oncogenes and Related Genes | Liang L.,State Key Laboratory for Oncogenes and Related Genes | Fang J.-Y.,State Key Laboratory for Oncogenes and Related Genes | Xu J.,State Key Laboratory for Oncogenes and Related Genes

Colorectal cancer (CRC) results from the accumulation of genetic alterations, and somatic copy number alterations (CNAs) are crucial for the development of CRC. Genome-wide survey of CNAs provides opportunities for identifying cancer driver genes in an unbiased manner. The detection of aberrant CNAs may provide novel markers for the early diagnosis and personalized treatment of CRC. A major challenge in array-based profiling of CNAs is to distinguish the alterations that play causative roles from the random alterations that accumulate during colorectal carcinogenesis. In this view, we systematically discuss the frequent CNAs in CRC, focusing on functional genes that have potential diagnostic, prognostic and therapeutic significance.Oncogene advance online publication, 10 August 2015; doi:10.1038/onc.2015.304. © 2015 Macmillan Publishers Limited Source

Li Y.-T.,Shanghai JiaoTong University | Li Y.-T.,Key Laboratory of Gastroenterology and Hepatology | Li Y.-T.,State Key Laboratory for Oncogenes and Related Genes | Cai H.-F.,Shanghai JiaoTong University | And 11 more authors.
Alimentary Pharmacology and Therapeutics

Background Clostridium difficile infection is a major cause of nosocomial diarrhoea. Aim To evaluate long-term (≥90 days) efficacy and safety of faecal microbiota transplantation for C. difficile infection and explore the factors affecting the faecal microbiota transplantation outcomes. Methods MEDLINE, the Cochrane Library and EMBASE were searched and only observational studies that utilised faecal microbiota transplantation for C. difficile infection with long-term follow-up duration (≥90 days) were included. Primary cure rate, overall recurrence rate and early (<90 days) and late (≥90 days) recurrence rate were calculated. Results Eighteen observational studies with 611 patients were included. The primary cure rate was 91.2% (95% confidence interval, CI 86.7-94.8%). The overall recurrence rate was 5.5% (95% CI 2.2-10.3%). The early recurrence rate and late recurrence rate were 2.7% (95% CI 0.7-6.0%) and 1.7% (95% CI 0.4-4.2%) respectively. Most adverse events were expected, short-lived, self-limited and manageable. The association between faecal microbiota transplantation therapy and adverse events such as inflammatory bowel disease flare, infectious disease and autoimmune disease was a concern but remained insignificant. Old age (≥65 years) was identified as a risk factor for after faecal microbiota transplantation therapy. Upper gastrointestinal administration also results in less frequent primary cure. Conclusions Faecal microbiota transplantation seems to be a highly effective and robust therapy for recurrent C. difficile infection. However, more quality studies, such as randomised controlled trials and cohort studies with control groups, are needed to confirm its long-term efficacy and safety. © 2015 John Wiley & Sons Ltd. Source

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