Assessment of Epstein-Barr virus nucleic acids in gastric but not in breast cancer by next-generation sequencing of pooled Mexican samples

Gastric (GC) and breast (BrC) cancer are two of the most common and deadly tumours. Different lines of evidence suggest a possible causative role of viral infections for both GC and BrC. Wide genome sequencing (WGS) technologies allow searching for viral agents in tissues of patients with cancer. These technologies have already contributed to establish virus-cancer associations as well as to discovery new tumour viruses. The objective of this study was to document possible associations of viral infection with GC and BrC in Mexican patients. In order to gain idea about cost effective conditions of experimental sequencing, we first carried out an in silico simulation of WGS. The next-generation-platform IlluminaGallx was then used to sequence GC and BrC tumour samples. While we did not find viral sequences in tissues from BrC patients, multiple reads matching Epstein-Barr virus (EBV) sequences were found in GC tissues. An end-point polymerase chain reaction confirmed an enrichment of EBV sequences in one of the GC samples sequenced, validating the next-generation sequencing-bioinformatics pipeline.

Correlation between viral load of cytomegalovirus and tacrolimus and sirolimus levels in transplanted pediatric patients / Correlación entre la carga viral de citomegalovirus y los niveles de tacrolimus y sirolimus en pacientes pediátricos trasplantados

Abstract: Introduction: Survival of transplant patients and grafts depends largely on the use of immunosuppressive drugs. However, a balance remains to be established among immunosuppression, transplant rejection and cytomegalovirus (CMV) infection, which results in a high rate of morbidity and mortality. The aim of this study was to define a better strategy for monitoring transplanted patients based on the analysis of the blood concentration of sirolimus and tacrolimus and the burden of CMV. Methods: Fifty five post-transplant (kidney and liver) pediatric patients, nine treated with sirolimus and 46 treated with tacrolimus, were included. A total of 541 measurements were obtained. In each measurement the concentration of immunosuppressant in whole blood and CMV viral load in plasma and whole blood was quantified by real-time PCR. Pearson correlation coefficient (r) was estimated. Results: Values of r ≤ 0.0747 were found for the relationship between dose and concentration of immunosuppressant; r = 0.9406 for the relationship between viral load in whole blood and plasma, and r ≤ 0.4616 for the relationship between concentration of immunosuppressant and viral load. Conclusions: These data support that the doses of immunosuppressive drugs do not correlate with the levels of the same in whole blood. Therefore, systemic levels of immunosuppressant should be constantly monitored together with CMV load. Meanwhile, a high correlation between viral load measured in whole blood and plasma was found.

Resumen: Introducción: La supervivencia de pacientes trasplantados y de los injertos depende en gran medida del uso de fármacos inmunosupresores. Sin embargo, aún no se ha logrado establecer un balance entre la inmunosupresión, el rechazo al trasplante y la infección por citomegalovirus (CMV), lo cual deriva en una alta tasa de morbilidad y mortalidad. El objetivo de este trabajo fue definir una mejor estrategia de seguimiento de los pacientes trasplantados a partir del análisis de la concentración en sangre de sirolimus y tacrolimus y la carga de CMV. Métodos: Se incluyeron 55 pacientes pediátricos post-trasplante (riñón e hígado), nueve en tratamiento con sirolimus y 46 en tratamiento con tacrolimus. Se obtuvieron 541 mediciones en total. En cada medición se cuantificó la concentración de inmunosupresor en sangre total y la carga viral de CMV en plasma y sangre total mediante PCR en tiempo real. Se calculó el coeficiente de correlación de Pearson (r). Resultados: Se encontraron valores de r ≤ 0.0747 para la relación entre dosis y concentración del inmunosupresor; de r = 0.9406 para la relación de la carga viral entre suero y sangre total y de r ≤ 0.4616 para la relación entre concentración de inmunosupresor y carga viral. Conclusiones: Estos datos apoyan que la dosis de los fármacos inmunosupresores no correlaciona con los niveles de los mismos en sangre total. Por ello, deben ser constantemente monitoreados junto con la carga viral. Por su parte, se encontró alta correlación entre la carga viral medida en sangre total y plasma.

Clinical consequences of Helicobacter pylori infection in children and its relation with the response of the gastric mucosa to the infection

Helicobacter pylori is usually acquired during childhood and remains in the gastric mucosa for years, often lifelong if untreated. It can be concluded that the gastric mucosa of children actively responds to the presence of H. pylori. Current evidences suggest that whereas H. pylori infection rarely causes peptic ulcers or gastric atrophy in children, it seems to be associated with iron deficiency and iron deficiency anemia; the evidence also suggests the infection may cause growth retardation. In contrast, H. pylori infection has been associated with a reduced risk of asthma and allergy in children and adults; also, epidemiological studies suggest that there is an inverse association between H. pylori infection and risk for esophageal adenocarcinoma. The gastric mucosa of children elicits a significant inflammatory response in the site of infection, with increased expression of toll-like receptors (TLRs) and cytokines, and increased epithelial proliferation. This response may partly be responsible for the required "immune training" needed to protect for the development of esophageal cancer, asthma, allergy or even diabetes later in life. The response may as well be associated with growth retardation, iron deficiency and increased risk for enteric infections. It then seems that our co-evolution with H. pylori has rendered benefits for human health making clear that this relationship is complex and the decision to eradicate the infection should be taken with caution.

Infección, inflamación y cáncer gástrico / Infection, inflammation and gastric cancer

Existe una sólida relación entre la infección persistente, la inflamación crónica y el cáncer. Helicobacter pylori es la principal causa del cáncer gástrico, con 900 000 casos nuevos registrados cada año. Este patógeno estimula a las células del epitelio gástrico para secretar IL-8, un quimioatrayente de leucocitos que infiltra el tejido infectado de manera persistente. También se observan concentraciones elevadas de citocinas inflamatorias que promueven la pérdida de la homeostasis local debido a la alteración de la proliferación y apoptosis celular. No es claro el mecanismo por el cual esta reacción inflamatoria lleva al cáncer, pero los radicales libres de O2 y N2 podrían contribuir de modo directo al daño genómico de la mucosa. El virus de Epstein-Barr es otro microorganismo vinculado con el cáncer gástrico. En esta revisión se describen los mecanismos inflamatorios importantes que intervienen en el desarrollo de la tumoración, tal vez compartidos con otros patógenos, lo cual es de gran relevancia ya que alrededor de 25 por ciento de los cánceres se relaciona con infección.

A strong association between persistent infection, chronic inflammation and cancer has been described. Helicobacter pylori is the main cause of gastric cancer, with 900 000 new cases yearly. Helicobacter colonization triggers the gastric epithelial cells to secret IL-8, a chemoattractant of immune cells, which persistently infiltrate the infected tissue. High levels of inflammatory cytokines are found, leading to loss of local homeostasis due to altered cell proliferation and apoptosis. It is not known how this local inflammatory response leads to cancer but the expression of mutagenic O2 and N2 free radicals might directly contribute to the irreversible mucosal genomic damage. Epstein Barr Virus is another pathogen associated with gastric cancer. We review here our current knowledge of inflammatory mechanisms at the site of infection that could be important to the development of cancer and that could be shared by other pathogens. This is of great importance since around 25 percent of cancers are associated with infection.