Staphylococcal enterotoxin A (SEA) stimulates STAT3 activation and IL-17 expression in cutaneous T-cell lymphoma

Cutaneous T-cell lymphoma (CTCL) is characterized by proliferation of malignant T cells in a chronic inflammatory environment. With disease progression, bacteria colonize the compromised skin barrier and half of CTCL patients die of infection rather than from direct organ involvement by the malignancy. Clinical data indicate that bacteria play a direct role in disease progression, but little is known about the mechanisms involved. Here, we demonstrate that bacterial isolates containing staphylococcal enterotoxin A (SEA) from the affected skin of CTCL patients, as well as recombinant SEA, stimulate activation of signal transducer and activator of transcription 3 (STAT3) and upregulation of interleukin (IL)-17 in immortalized and primary patient-derived malignant and nonmalignant T cells. Importantly, SEA induces STAT3 activation and IL-17 expression in malignant T cells when cocultured with nonmalignant T cells, indicating an indirect mode of action. In accordance, malignant T cells expressing an SEA-nonresponsive T-cell receptor variable region β chain are nonresponsive to SEA in monoculture but display strong STAT3 activation and IL-17 expression in cocultures with SEA-responsive nonmalignant T cells. The response is induced via IL-2 receptor common γ chain cytokines and a Janus kinase 3 (JAK3)-dependent pathway in malignant T cells, and blocked by tofacitinib, a clinical-grade JAK3 inhibitor. In conclusion, we demonstrate that SEA induces cell cross talk-dependent activation of STAT3 and expression of IL-17 in malignant T cells, suggesting a mechanism whereby SEA-producing bacteria promote activation of an established oncogenic pathway previously implicated in carcinogenesis

The proportion of cancer-related entries in PubMed has increased considerably; is cancer truly "The Emperor of All Maladies"?

In this work, the public database of biomedical literature PubMed was mined using queries with combinations of keywords and year restrictions. It was found that the proportion of Cancer-related entries per year in PubMed has risen from around 6% in 1950 to more than 16% in 2016. This increase is not shared by other conditions such as AIDS, Malaria, Tuberculosis, Diabetes, Cardiovascular, Stroke and Infection some of which have, on the contrary, decreased as a proportion of the total entries per year. Organ-related queries were performed to analyse the variation of some specific cancers. A series of queries related to incidence, funding, and relationship with DNA, Computing and Mathematics, were performed to test correlation between the keywords, with the hope of elucidating the cause behind the rise of Cancer in PubMed. Interestingly, the proportion of Cancer-related entries that contain "DNA", "Computational" or "Mathematical" have increased, which suggests that the impact of these scientific advances on Cancer has been stronger than in other conditions. It is important to highlight that the results obtained with the data mining approach here presented are limited to the presence or absence of the keywords on a single, yet extensive, database. Therefore, results should be observed with caution. All the data used for this work is publicly available through PubMed and the UK's Office for National Statistics. All queries and figures were generated with the software platform Matlab and the files are available as supplementary material

Development and calibration of a dietary nitrate and nitrite database in the NIH–AARP Diet and Health Study

Nitrate and nitrite are probable human carcinogens when ingested under conditions that increase the formation of N-nitroso compounds. There have been limited efforts to develop US databases of dietary nitrate and nitrite for standard FFQ. Here we describe the development of a dietary nitrate and nitrite database and its calibration. We analysed data from a calibration study of 1942 members of the NIH–AARP (NIH–AARP, National Institutes of Health–AARP) Diet and Health Study who reported all foods and beverages consumed on the preceding day in two non-consecutive 24 h dietary recalls (24HR) and completed an FFQ. Based on a literature review, we developed a database of nitrate and nitrite contents for foods reported on these 24HR and for food category line items on the FFQ. We calculated daily nitrate and nitrite intakes for both instruments, and used a measurement error model to compute correlation coefficients and attenuation factors for the FFQ-based intake estimates using 24HR-based values as reference data. FFQ-based median nitrate intake was 68·9 and 74·1 mg/d, and nitrite intake was 1·3 and 1·0 mg/d, in men and women, respectively. These values were similar to 24HR-based intake estimates. Energy-adjusted correlation coefficients between FFQ- and 24HR-based values for men and women respectively were 0·59 and 0·57 for nitrate and 0·59 and 0·58 for nitrite; energy-adjusted attenuation factors were 0·59 and 0·57 for nitrate and 0·47 and 0·38 for nitrite. The performance of the FFQ in assessing dietary nitrate and nitrite intakes is comparable to that for many other macro- and micronutrients