Urinary metabolomic signature of esophageal cancer and Barrett’s esophagus

<p>Abstract</p> <p>Background</p> <p>Esophageal adenocarcinoma (EAC) often presents at a late, incurable stage, and mortality has increased substantially, due to an increase in incidence of EAC arising out of Barrett’s esophagus. When diagnosed early, however, the combination of surgery and adjuvant therapies is associated with high cure rates. Metabolomics provides a means for non- invasive screening of early tumor-associated perturbations in cellular metabolism.</p> <p>Methods</p> <p>Urine samples from patients with esophageal carcinoma (n = 44), Barrett’s esophagus (n = 31), and healthy controls (n = 75) were examined using ¹H-NMR spectroscopy. Targeted profiling of spectra using Chenomx software permitted quantification of 66 distinct metabolites. Unsupervised (principal component analysis) and supervised (orthogonal partial least-squares discriminant analysis OPLS-DA) multivariate pattern recognition techniques were applied to discriminate between samples using SIMCA-P⁺ software. Model specificity was also confirmed through comparison with a pancreatic cancer cohort (n = 32).</p> <p>Results</p> <p>Clear distinctions between esophageal cancer, Barrett’s esophagus and healthy controls were noted when OPLS-DA was applied. Model validity was confirmed using two established methods of internal validation, cross-validation and response permutation. Sensitivity and specificity of the multivariate OPLS-DA models were summarized using a receiver operating characteristic curve analysis and revealed excellent predictive power (area under the curve = 0.9810 and 0.9627 for esophageal cancer and Barrett’s esophagus, respectively). The metabolite expression profiles of esophageal cancer and pancreatic cancer were also clearly distinguishable with an area under the receiver operating characteristics curve (AUROC) = 0.8954.</p> <p>Conclusions</p> <p>Urinary metabolomics identified discrete metabolic signatures that clearly distinguished both Barrett’s esophagus and esophageal cancer from controls. The metabolite expression profile of esophageal cancer was also discrete from its precursor lesion, Barrett’s esophagus. The cancer-specific nature of this profile was confirmed through comparison with pancreatic cancer. These preliminary results suggest that urinary metabolomics may have a future potential role in non-invasive screening in these conditions.</p

Wheat curl mite, Aceria tosichella, and transmitted viruses: an expanding pest complex affecting cereal crops

The wheat curl mite (WCM), Aceria tosichella, and the plant viruses it transmits represent an invasive mite-virus complex that has affected cereal crops worldwide. The main damage caused by WCM comes from its ability to transmit and spread multiple damaging viruses to cereal crops, with Wheat streak mosaic virus (WSMV) and Wheat mosaic virus (WMoV) being the most important. Although WCM and transmitted viruses have been of concern to cereal growers and researchers for at least six decades, they continue to represent a challenge. In older affected areas, for example in North America, this mite-virus complex still has significant economic impact. In Australia and South America, where this problem has only emerged in the last decade, it represents a new threat to winter cereal production. The difficulties encountered in making progress towards managing WCM and its transmitted viruses stem from the complexity of the pathosystem. The most effective methods for minimizing losses from WCM transmitted viruses in cereal crops have previously focused on cultural and plant resistance methods. This paper brings together information on biological and ecological aspects of WCM, including its taxonomic status, occurrence, host plant range, damage symptoms and economic impact. Information about the main viruses transmitted by WCM is also included and the epidemiological relationships involved in this vectored complex of viruses are also addressed. Management strategies that have been directed at this mite-virus complex are presented, including plant resistance, its history, difficulties and advances. Current research perspectives to address this invasive mite-virus complex and minimize cereal crop losses worldwide are also discussed.Instituto de Patología VegetalFil: Navia, Denise. Embrapa Recursos Genéticos e Biotecnologia; BrasilFil: Mendonça, Renata Santos de. Embrapa Recursos Genéticos e Biotecnologia; BrasilFil: Skoracka, Anna. Adam Mickiewicz University. Faculty of Biology. Institute of Environmental Biology. Department of Animal Taxonomy and Ecology; PoloniaFil: Szydło, Wiktoria. Adam Mickiewicz University. Faculty of Biology. Institute of Environmental Biology. Department of Animal Taxonomy and Ecology; PoloniaFil: Knihinicki, Danuta. Orange Agricultural Institute. Agricultural Scientific Collections Unit. NSW Department of Primary Industries; AustraliaFil: Hein, Gary L. University of Nebraska at Lincoln; Estados UnidosFil: Pereira, Paulo Roberto Valle da Silva. Embrapa Trigo; BrasilFil: Truol, Graciela Ana Maria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; ArgentinaFil: Lau, Douglas. Embrapa Trigo; Brasi

Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls.

International audienceNF-kB transcription factors have a key role in many physiological processes, such as innate and adaptive immune responses, cell proliferation, cell death, and inflammation. It has become clear that aberrant regulation of NF-kB and the signaling pathways that control its activity are involved in cancer development and progression, as well as in resistance to chemotherapy and radiotherapy. This article discusses recent evidence from cancer genetics and cancer genome studies that support the involvement of NF-kB in human cancer, particularly in multiple myeloma. The therapeutic potential and benefit of targeting NF-kB in cancer, and the possible complications and pitfalls of such an approach, are explored