: Ubiquitin-specific peptidase 10 (USP10) stabilizes both tumor suppressors and oncogenes in a context-dependent manner. However, the nature of USP10’s role in non-small cell lung cancer (NSCLC) remains unclear. By analyzing The Cancer Genome Atlas (TCGA) database, we have shown that high levels of USP10 are associated with poor overall survival in NSCLC with mutant p53, but not with wild-type p53. Consistently, genetic depletion or pharmacological inhibition of USP10 dramatically reduces the growth of lung cancer xenografts lacking wild-type p53 and sensitizes them to cisplatin. Mechanistically, USP10 interacts with, deubiquitinates, and stabilizes oncogenic protein histone deacetylase 6 (HDAC6). Furthermore, reintroducing either USP10 or HDAC6 into a USP10-knockdown NSCLC H1299 cell line with null-p53 renders cisplatin resistance. This result suggests the existence of a “USP10-HDAC6-cisplatin resistance” axis. Clinically, we have found a positive correlation between USP10 and HDAC6 expression in a cohort of NSCLC patient samples. Moreover, we have shown that high levels of USP10 mRNA correlate with poor overall survival in a cohort of advanced NSCLC patients who received platinum-based chemotherapy. Overall, our studies suggest that USP10 could be a potential biomarker for predicting patient response to platinum, and that targeting USP10 could sensitize lung cancer patients lacking wild-type p53 to platinum-based therapy.

Petroleum coke, or petcoke, is a granular coal-like industrial by-product that is separated during the refinement of heavy crude oil. Recently, the processing of material from Canadian oil sands in U.S. refineries has led to the appearance of large petcoke piles adjacent to urban communities in Detroit and Chicago. The purpose of this literature review is to assess what is known about the effects of petcoke exposure on human health. Toxicological studies in animals indicate that dermal or inhalation petcoke exposure does not lead to a significant risk for cancer development or reproductive and developmental effects. However, pulmonary inflammation was observed in long-term inhalation exposure studies. Epidemiological studies in coke oven workers have shown increased risk for cancer and chronic obstructive pulmonary diseases, but these studies are confounded by multiple industrial exposures, most notably to polycyclic aromatic hydrocarbons that are generated during petcoke production. The main threat to urban populations in the vicinity of petcoke piles is most likely fugitive dust emissions in the form of fine particulate matter. More research is required to determine whether petcoke fine particulate matter causes or exacerbates disease, either alone or in conjunction with other environmental contaminants.

This work focuses on phytochelatins (PCs) in plants chronically exposed to low or moderate metal concentrations in soil, which commonly occurs in natural environments. The original approach was to evaluate PCs in nopal (Opuntia ficus) in relation to the plant and soil levels of Cd, Pb, Cu and Ag. These four metals were selected because of their known capability to induce PCs in plants and also because of their abundance in the region of Guanajuato (Mexico), where the nopal plants were collected. ICP-MS determination of metals in nopal roots, stems and in soil fractions provided information relevant to their bioavailability in soil as well as their uptake by nopal. In search of a possible relationship between the parameters measured, correlation analysis was carried out (Cd was not considered owing to its low levels found in the plant tissues). The results obtained indicate that sequential metal leaching from soil does not always provide direct information on metal bioavailability. The uptake of metals by nopal roots correlated with metals in the organic matter and sulfides fraction. Since low levels of humic substances were found in soil collected at cactus roots and because of the low solubility of Pb, Cu and Ag sulfides, the participation of rizosphere processes was suggested in facilitating metal uptake. Metal distribution in PC molecular mass fractions were studied by SEC-ICP-MS and the results compared with the total phytochelatin pool in plants as determined by reversed phase HPLC with spectrofluorimetric detection. The two procedures provide complementary analytical information when the global effect of all metals/metalloids present in soil on PC production is to be studied. Correlation analysis revealed the strong association of Pb with PCs both in roots and in stems, which demonstrates that Pb is important in nopal PCs and suggests that Pb bound to PCs might be transported from roots to stems. For Cu, the correlation between metal-free PCs and metal bound to high molecular mass fraction of plant PC-rich extract was observed only in roots, suggesting differences in the transport of Pb and Cu. In contrast to these metals, no correlation was found for silver, suggesting no association with PCs, even though its elution with a high molecular mass fraction was observed in PC-rich plant extracts. The results obtained from this study indicate the complex role environmental conditions play in the accumulation of heavy metals and in phytochelatin production in the Opuntia genus.

The effects of various matrix constituents, Co, Pb and synthetic ocean water, on analyte signal have been studied. Suppression of the ¹³⁸Ba⁺ signal was observed in the presence of each matrix, with the Pb matrix having the greatest effect. These matrix-induced suppressions of analyte signal were compensated for in part by the use of In as an internal standard, and by initially tuning the ion lenses for maximum analyte signal in the presence of the matrix, rather than for a simple acidified standard solution. The severity of matrix-induced suppression was compared for flow injection and continuous sample introduction. No significant differences in suppression of analyte signal between the two methods were observed because of the relatively large sample volume used for flow injection. The experimental procedure adopted, continual reference of analyte signals with and without the matrix present, effectively eliminated any bias in the results due to nebuliser and cone blockage.