TP53 Targeted Deep Sequencing of Cell-Free DNA in Esophageal Squamous Cell Carcinoma Using Low-Quality Serum: Concordance with Tumor Mutation

Circulating cell-free DNA (cfDNA) is emerging as a potential tumor biomarker. CfDNA-based biomarkers may be applicable in tumors without an available non-invasive screening method among at-risk populations. Esophageal squamous cell carcinoma (ESCC) and residents of the Asian cancer belt are examples of those malignancies and populations. Previous epidemiological studies using cfDNA have pointed to the need for high volumes of good quality plasma (i.e., >1 mL plasma with 0 or 1 cycles of freeze-thaw) rather than archival serum, which is often the main available source of cfDNA in retrospective studies. Here, we have investigated the concordance of TP53 mutations in tumor tissue and cfDNA extracted from archival serum left-over from 42 cases and 39 matched controls (age, gender, residence) in a high-risk area of Northern Iran (Golestan). Deep sequencing of TP53 coding regions was complemented with a specialized variant caller (Needlestack). Overall, 23% to 31% of mutations were concordantly detected in tumor and serum cfDNA (based on two false discovery rate thresholds). Concordance was positively correlated with high cfDNA concentration, smoking history (p-value = 0.02) and mutations with a high potential of neoantigen formation (OR; 95%CI = 1.9 (1.11–3.29)), suggesting that tumor DNA release in the bloodstream might reflect the effects of immune and inflammatory context on tumor cell turnover. We identified TP53 mutations in five controls, one of whom was subsequently diagnosed with ESCC. Overall, the results showed that cfDNA mutations can be reliably identified by deep sequencing of archival serum, with a rate of success comparable to plasma. Nonetheless, 70% non-identifiable mutations among cancer patients and 12% mutation detection in controls are the main challenges in applying cfDNA to detect tumor-related variants when blindly targeting whole coding regions of the TP53 gene in ESCC.     

Characterization of airborne particles during production of carbonaceous nanomaterials

Despite the rapid growth in nanotechnology, very little is known about the unintended health or environmental effects of manufactured nanomaterials. The development of nanotechnology risk assessments and regulations requires quantitative information on the potential for exposure to nanomaterials. The objective of this research isto characterize airborne particle concentrations during the production of carbonaceous nanomaterials, such as fullerenes and carbon nanotubes, in a commercial nanotechnology facility. We measured fine particle mass concentrations (PM2.5), submicrometer size distributions, and photoionization potential, an indicator of the particles' carbonaceous content, at three locations inside the facility: inside the fume hood where nanomaterials were produced, just outside the fume hood, and in the background. The measurements were not selective for engineered nanomaterials and may have included both engineered nanomaterials and naturally occurring or incidental particles. Average PM2.5 and particle number concentrations were not significantly different inside the facility versus outdoors. However, large, short-term increases in PM2.5 and particle number concentrations were associated with physical handling of nanomaterials and other production activities. In many cases, an increase in the number of sub-100 nm particles accounted for the majority of the increase in total number concentrations. Photoionization results indicate that the particles suspended during nanomaterial handling inside the fume hood were carbonaceous and therefore likely to include engineered nanoparticles, whereas those suspended by other production activities taking place outside the fume hood were not. Based on the measurements in this study, the engineering controls at the facility appear to be effective at limiting exposure to nanomaterials.     

Influence of lipid composition on physicochemical properties of nanoliposomes encapsulating natural dipeptide antioxidant l-carnosine

Natural dipeptide antioxidants (l-carnosine) are recieving increasing attention because of their noticeable potential as biopreservatives in food recent technology. Encapsulation of antioxidants by nanoliposomes could represent an ameliorative approach to overcome the problems related to the direct application of these antioxidant peptides in food.