F-18 FDG PET/CT, although less sensitive, showed high specificity, PPV, NPV, and accuracy and therefore can be useful for the patients with negative diagnostic radioiodine scan and elevated serum Tg or positive TgAb. In addition, FDG PET/CT under ETS does not seem to have an additive role in detecting recurrence in these patients.
O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification which occurs on the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins. It has been reported that the presence of this single sugar motif regulates various biological events by altering the fate of target proteins, such as their function, localization, and degradation. This study identified SMAD4 as a novel O-GlcNAc-modified protein. SMAD4 is a component of the SMAD transcriptional complex, a major regulator of the signaling pathway for the transforming growth factor-β (TGF-β). TGF-β is a powerful promoter of cancer EMT and metastasis. This study showed that the amount of SMAD4 proteins changes according to cellular O-GlcNAc levels in human lung cancer cells. This observation was made based on the prolonged half-life of SMAD4 proteins. The mechanism behind this interaction was that O-GlcNAc impeded interactions between SMAD4 and GSK-3β which promote proteasomal degradation of SMAD4. In addition, O-GlcNAc modification on SMAD4 Thr63 was responsible for stabilization. As a result, defects in O-GlcNAcylation on SMAD4 Thr63 attenuated the reporter activity of luciferase, the TGF-β-responsive SMAD binding element (SBE). This study’s findings imply that cellular O-GlcNAc may regulate the TGF-β/SMAD signaling pathway by stabilizing SMAD4.
O-GlcNAc transferase (OGT) is an enzyme that catalyzes the O-GlcNAc modification of nucleocytoplasmic proteins and is highly expressed in many types of cancer. However, the mechanism regulating its expression in cancer cells is not well understood. This study shows that OGT is a substrate of the E3 ubiquitin ligase X-linked inhibitor of apoptosis (XIAP) which plays an important role in cancer pathogenesis. Although LSD2 histone demethylase has already been reported as an E3 ubiquitin ligase in lung cancer cells, we identified XIAP as the main E3 ubiquitin ligase in colon cancer cells. Interestingly, OGT catalyzes the O-GlcNAc modification of XIAP at serine 406 and this modification is required for the E3 ubiquitin ligase activity of XIAP toward specifically OGT. Moreover, O-GlcNAcylation of XIAP suppresses colon cancer cell growth and invasion by promoting the proteasomal degradation of OGT. Therefore, our findings regarding the reciprocal regulation of OGT and XIAP provide a novel molecular mechanism for controlling cancer growth and invasion regulated by OGT and O-GlcNAc modification.
Objective: To evaluate the effect of female sex hormones on the clinical outcomes of coronavirus disease 2019 patients using national claims data. Methods: This retrospective cohort study used the Health Insurance Review and Assessment data of 5,061 adult patients with laboratory-confirmed coronavirus disease 2019 in South Korea from January 20 to April 8, 2020. To evaluate the effect of hormone therapy on clinical outcomes among women, subgroup analyses using age-matched case-control data were performed. Results: Coronavirus disease 2019 was most prevalent in women in the 20-39 years age group (1,250 [44.14%]). Men were more likely to receive oxygen therapy (144 [6.46%] vs 131 [4.63%], P = 0.004), be admitted to the intensive care unit (60 [2.69%] vs 53 [1.87%], P = 0.049), and have a longer length of stay after admission to the intensive care unit (19.70 ± 11.80 vs 14.75 ± 9.23, P = 0.016). However, there was no significant difference in the mortality rate (men vs women: 42 [1.88%] vs 42 [1.48%], P = 0.267). In the multivariable Cox analysis, older age and underlying comorbidities, but not sex, were independent risk factors for mortality. Hormone therapy was not significantly associated with clinical outcomes. Conclusions: This study, using nationwide data, suggests that female sex hormones are not associated with the morbidity and clinical outcomes of coronavirus disease 2019 in South Korea.
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