No abstract

BACKGROUND: SIRT1 is a longevity gene that forestalls aging and age-related diseases including cancer, and has recently attracted widespread attention due to its overexpression in some cancers. We previously identified the overexpression of SIRT1 in ovarian carcinoma (OvCa) as a poor prognostic factor. However, mechanistic insights into the function of SIRT1 in OvCa have yet to be elucidated. METHODS: Quantitative real-time reverse PCR (qRT-PCR) and Western blotting were employed to examine the expression of SIRT1 in a panel of human OvCa cell lines. si-RNA or sh-RNA and cDNA technologies were utilized to knockdown or overexpress SIRT1, respectively. The effects of SIRT1 on proliferation and chemoresistance were examined using a WST-1 assay, and the underlying mechanisms were confirmed using an apoptotic assay, and the quantification of glutathione (GSH), and reactive oxygen species (ROS). The aggressiveness of SIRT1 was analyzed using in vitro invasion and migration assays. RESULTS: SIRT1 was more strongly expressed in OvCa cell lines than in the immortalized ovarian epithelium at the gene and protein levels. Stress up-regulated the expression of SIRT1 in dose- and time-dependent manners. SIRT1 significantly enhanced the proliferation (P < .05), chemoresistance (P < .05), and aggressiveness of OvCa cells by up-regulating multiple antioxidant pathways to inhibit oxidative stress. Further study into the overexpression of SIRT1 demonstrated the up-regulation of several stemness-associated genes and enrichment of CD44v9 via an as-yet-unidentified pathway. CONCLUSIONS: Our results suggest that SIRT1 plays a role in the acquisition of aggressiveness and chemoresistance by OvCa, and has potential as a therapeutic target for OvCa.

Purpose To assess changes in left ventricular function and tissue composition by using MRI after chemotherapy-radiation therapy in participants with esophageal cancer. Materials and Methods Between January 2013 and April 2015, this prospective study enrolled 24 participants (42% women; mean age, 63 years; range, 49-73 years) scheduled for chemotherapy-radiation therapy. 3.0-T MRI examinations were performed before, at 0.5 year, and at 1.5 years after chemotherapy-radiation therapy. Myocardial native T1, postcontrast T1, and extracellular volume were measured in basal septum (as irradiated areas) and apical lateral wall (as nonirradiated areas). Left ventricular function, prevalence of late gadolinium enhancement, and T1 and extracellular volume values were compared over the follow-up period by using Friedman or Cochran Q tests, followed by Dunn test. Results In 14 participants who were followed up for 1.5 years, native T1 and extracellular volume in the septum were elevated at 0.5 year compared with baseline (1183 msec ± 46 [standard deviation] vs 1257 msec ± 35; 26% ± 3 vs 32% ± 3; adjusted P < .01 for both), but not in the lateral wall. Left ventricular stroke volume index and late gadolinium enhancement changed at 1.5 years compared with baseline (41 mL/m ± 11 vs 36 mL/m ± 9; P = .046; 7% [one of 14] vs 78% [11 of 14]; P < .01). Other measures of left ventricular function did not change during the follow-up period (P > .10 for all). Conclusion Native T1 and extracellular volume could detect early changes in myocardium at 0.5 year after chemotherapy-radiation therapy, whereas left ventricular stroke volume index and late gadolinium enhancement showed abnormality at 1.5 years. © RSNA, 2018 Online supplemental material is available for this article.

PurposeLipocalin 2 (LCN2) is a secretory protein that is involved in various physiological processes including iron transport. We previously identified LCN2 as an up-regulated gene in endometrial carcinoma, and found that the overexpression of LCN2 and its receptor, SLC22A17, was associated with a poor prognosis. However, the functions and mechanism of action of LCN2 currently remain unclear.MethodsThe LCN2-overexpressing endometrial carcinoma cell lines, HHUA and RL95-2, and LCN2-low-expressing one, HEC1B, were used. The effects of LCN2 on cell migration, cell viability, and apoptosis under various stresses, including ultraviolet (UV) irradiation and cisplatin treatment, were examined using the scratch wound healing assay, WST-1 assay, and Apostrand assay, respectively.ResultsLCN2-silencing using shRNA method significantly reduced the migration ability of cells (p<0.05). Cytotoxic stresses significantly decreased the viability of LCN2-silenced cells more than that of control cells. In contrast, LCN2 overexpression was significantly increased cisplatin resistance. These effects were canceled by the addition of the iron chelator, deferoxamine. After UV irradiation, the expression of phosphorylated Akt (pAkt) was decreased in LCN2-silenced cells, and the PI3K inhibitor canceled the difference induced in UV sensitivity by LCN2. The cisplatin-induced expression of pAkt was not affected by LCN2; however, the expression of p53 and p21 was increased by LCN2-silencing.ConclusionsThese results indicated that LCN2 was involved in the migration and survival of endometrial carcinoma cells under various stresses in an iron-dependent manner. The survival function of LCN2 may be exerted through the PI3K pathway and suppression of the p53-p21 pathway. These functions of LCN2 may increase the malignant potential of endometrial carcinoma cells.

No abstract

Sirtuin 1 (SIRT1), originally identified as a longevity gene, regulates DNA repair and metabolism by deacetylating target proteins such as p53. SIRT1 plays a key role in the pathophysiology of metabolic diseases and neurodegenerative disorders, and is considered to protect against age-related diseases including cancer. In contrast, SIRT1 may be oncogenic because its overexpression has been detected in many cancers. The aim of the present study was to clarify the expression and the role of SIRT1 in ovarian carcinoma (OvCa). The expression of SIRT1 was evaluated immunohistochemically in 16 cases of normal ovaries, 35 cases of endometriosis with/without carcinoma, and 68 cases of OvCa (endometrioid, 16; clear cell, 20; mucinous, 16; serous, 16). Staining results were evaluated semiquantitatively by the Immunoreactive Scoring System, and the relationships with clinicopathologic features and outcomes of patients were analyzed. The expression of SIRT1 was higher in endometrioid, mucinous, and clear-cell carcinomas than in the inclusion cysts of normal ovaries, but not in serous carcinoma (P=0.038). The expression of SIRT1 on OvCa did not correlate with age, stage, location of metastasis, or capsular penetration. However, elevated SIRT1 expression was a significant predictor of shorter survival in univariate (P=0.038) and multivariate (P=0.037) survival analyses, regardless of the tumor stage. Results of the present study suggest a positive role for SIRT1 in the development of OvCa and its potential as a novel therapeutic target.

No abstract

Background: Percutaneous coronary intervention (PCI) is safe and effective in very elderly patients, defined as those who are age ≥85 years, with acute coronary syndrome (ACS). However, the prognostic factors remain unknown. The association between activities of daily living (ADL) and the prognosis after PCI has not yet been investigated. Hypothesis: Better ADL is associated with better 1-year prognosis. Methods: This retrospective study included 91 consecutive very elderly patients with ACS. We calculated the Barthel Index (BI) as an indicator for ADL. Patients were classified into 2 groups according to BI: high BI (≥85) and low BI (<85). The BI was assessed both on admission (pre-BI) and at discharge (post-BI). Results: In the 91 patients (mean age, 88.2 ± 3.0 years, 52% male), 1-year mortality was 33%. The Cox regression model demonstrated that low pre-BI was not a risk factor for 1-year mortality (hazard ratio: 0.73, 95% confidence interval [CI]: 0.30-1.78, P = 0.490). However, post-BI was significantly associated with 1-year mortality (hazard ratio: 0.25, 95% CI: 0.11-0.57, P = 0.001). The 1-year mortality of the high and the low post-BI group was estimated as 21% (95% CI: 12%-35%) and 62% (95% CI: 42%-82%), respectively. A 5-unit decrease in post-BI was related to a 1.10-fold increased risk for 1-year mortality (95% CI: 1.05-1.15, P < 0.001). Conclusions: Activities of daily living at discharge, although not before admission, may be a useful predictor for 1-year mortality in very elderly patients undergoing PCI for ACS. IntroductionIn elderly patients who are affected by comorbidities, primary percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) seems to be a promising strategy. 1 As PCI has become a safer and less invasive procedure, the very elderly population-defined as those age ≥85 years-is increasingly being referred for PCI, particularly in the setting of ACS. Although evidence on ACS in very elderly patients is scarce, a few studies have reported clinical outcomes related to this topic. A retrospective cohort study reported that long-term survival of patients age ≥90 years who underwent PCI was not inferior to those who were included in a Minnesota cohort matched by age and sex.2 Other studies have also reportedThe authors have no funding, financial relationships, or conflicts of interest to disclose.that PCI for patients with ACS who were ≥85 years was safe, feasible, and effective. 3,4 However, most patients with advanced age have disabilities such as dementia, cerebral infarction sequelae, and muscle weakness, all of which can influence their prognosis. This study aimed to confirm the hypothesis that better activities of daily living (ADL) is associated with better prognosis in very elderly patients with ACS who underwent PCI. Methods Study DesignThis study retrospectively included 91 consecutive patients, age ≥85 years, who were admitted to our hospital for ACS and underwent primary PCI between January 2007 and January 2014. We reviewed the medical records of all patients ...