Background: The relationship between glioblastoma (GBM) and fatty acid metabolism could be the key to elucidate more effective therapeutic targets. 15-lipoxygenase-1 (15-LOX), a linolenic acid and arachidonic acid metabolizing enzyme, induces both pro- and antitumorigenic effects in different cancer types. Its role in glioma activity has not yet been clearly described. The objective of this study was to identify the influence of 15-LOX and its metabolites on glioblastoma cell activity. Methods: GBM cell lines were examined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to identify 15-LOX metabolites. GBM cells treated with 15-LOX metabolites, 13-hydroxyoctadecadeinoic acid (HODE) and 9-HODE, and two 15-LOX inhibitors (luteolin and nordihydroguaiaretic acid) were also examined. Dose response/viability curves, RT-PCRs, flow cytometry, migration assays, and zymograms were performed to analyze GBM growth, migration, and invasion. Results: Higher quantities of 13-HODE were observed in five GBM cell lines compared to other lipids analyzed. Both 13-HODE and 9-HODE increased cell count in U87MG. 15-LOX inhibition decreased migration and increased cell cycle arrest in the G2/M phase. Conclusion: 15-LOX and its linoleic acid (LA)-derived metabolites exercise a protumorigenic influence on GBM cells in vitro. Elevated endogenous levels of 13-HODE called attention to the relationship between linoleic acid metabolism and GBM cell activity.

Prostaglandin E₂ (PGE₂) is known to increase glioblastoma (GBM) cell proliferation and migration while cyclooxygenase (COX) inhibition decreases proliferation and migration. The present study investigated the effects of COX inhibitors and PGE₂ receptor antagonists on GBM cell biology. Cells were grown with inhibitors and dose response, viable cell counting, flow cytometry, cell migration, gene expression, Western blotting, and gelatin zymography studies were performed. The stimulatory effects of PGE₂ and the inhibitory effects of ibuprofen (IBP) were confirmed in GBM cells. The EP2 and EP4 receptors were identified as important mediators of the actions of PGE₂ in GBM cells. The concomitant inhibition of EP2 and EP4 caused a significant decrease in cell migration which was not reverted by exogenous PGE₂. In T98G cells exogenous PGE₂ increased latent MMP2 gelatinolytic activity. The inhibition of COX1 or COX2 caused significant alterations in MMP2 expression and gelatinolytic activity in GBM cells. These findings provide further evidence for the importance of PGE₂ signalling through the EP2 and the EP4 receptor in the control of GBM cell biology. They also support the hypothesis that a relationship exists between COX1 and MMP2 in GBM cells which merits further investigation as a novel therapeutic target for drug development.

Background and Aims: Correctly characterizing malnutrition is a challenge. Transthyretin (TTR) rapidly responds to adequate protein intake/infusion, which could be used as a marker to identify malnutrition. Nutritional therapy is used to prevent malnutrition. Parenteral nutrition (PN) requires daily monitoring to determine whether what is being offered is adequate. This article aims to investigate whether the practice of measuring TTR is justified. Methods: Data from patients admitted to the ward or intensive care unit (ICU) were collected at three different times: within the first 72 h (T1) of PN use, on the 7th day (T2), and the 14th day (T3) after the initial assessment. Results: 302 patients were included; the average age was 48.3 years old; the prevalence of death was 22.2%, and 61.6% of the sample were male. TTR values and the effectiveness of nutritional support in these patients were not associated with the outcome; however, meeting caloric needs was related to the outcome (p = 0.047). No association was found when TTR values were compared to the nutritional status. Thus, TTR was not a good indicator of nutritional risk or nutritional status in hospitalized patients. Conclusions: Undoubtedly, the TTR measurement was inversely proportional to CRP measurements. It was possible to conclude in this follow-up cohort of hospitalized patients that TTR values were not useful for determining whether the patient was malnourished, predicting death or effectiveness of nutritional support, yet based upon our analyses, a decrease in TTR greater than 0.024 units for every 1 unit increase in CRP might be due to ineffective nutritional supply.

Is plasma selenium correlated to transthyretin levels in critically ill patients?