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This study aimed to investigate the roles and possible molecular mechanisms of long non-coding RNA HOTAIR in regulating resistance to trastuzumab in breast cancer. Trastuzumab-resistant breast cancer cell line SK-BR-3-TR was assayed for the expression of HOX antisense intergenic RNA (HOTAIR), epithelial-mesenchymal transition (EMT)-related proteins or genes. Methylation levels of TGF- β, PTEN and cyclin-dependent kinase inhibitor 1B (or P27) were determined. In trastuzumab-resistant cell line, the mRNA level of HOTAIR was significantly up-regulated; in addition, the expression of TGF-β, Snail and Vimentin was also up-regulated, E-cadherin was down-regulated while the expression of HER2, PI3K, AKT, mTOR and MAPK in the HER2 receptor pathway and phosphorylation level of HER2 receptor remained unchanged, the methylation levels of the PTEN gene and TGF-β were increased and decreased, respectively. RNA interference downregulated the HOTAIR level and sensitized the cells to trastuzumab. It also resulted in down-regulation of TGF-β, Snail, Vimentin, p-AKT, p-APK and CyclinD1 and up-regulation of E-cadherin, PTEN and P27. Besides, the methylation levels of the PTEN gene and TGF-β were reduced and increased, respectively. Mouse models grafted with SK-BR-3-TR grew faster than with SK-BR-3-TS and siHOTAIR-SK-BR-3-TR. [ABSTRACT FROM AUTHOR]

We performed a meta-analysis to elucidate the associations of the clinicopathological characteristics and prognostic factors of papillary thyroid cancer (PTC) with TERT promoter mutations. A literature search was performed of the PubMed and EMBASE databases using Medical Subject Headings and keywords. Individual study-specific odds ratios (ORs) and confidence intervals (CIs) were calculated. The average prevalence rate of TERT promoter mutations was 10.1%. TERT promoter mutations occurred more frequently in patients with larger tumors (p = 0.003). TERT promoter mutations were associated with advanced stage (OR = 3.11, 95% CI = 2.22-4.36), lymph node metastasis (OR = 1.82, 95% CI = 1.12-2.96), distant metastasis (OR = 4.18, 95% CI = 1.61-10.81), BRAF mutation positivity (OR = 2.71, 95% CI = 1.45-3.24), recurrence (OR = 3.91, 95% CI = 1.83-8.34), and mortality (OR = 8.13, 95% CI = 3.77-17.53). The associations of TERT promoter mutations with extrathyroidal invasion (OR = 1.98, 95% CI = 0.96-4.07), unifocality (OR = 1.36, 95% CI = 0.90-2.07), and vascular invasion (OR = 1.45, 95% CI = 0.92-2.30) were not significant. TERT promoter mutations are closely associated with aggressive clinicopathological characteristics and poorer prognosis in PTC. [ABSTRACT FROM AUTHOR]

Endothelial progenitor cells (EPCs) seeded on biomaterials can effectively promote diabetic ischemic wound healing. However, the function of transplanted EPCs is negatively affected by a high-glucose and ischemic microenvironment. Our experiments showed that EPC autophagy was inhibited and mitochondrial membrane potential (MMP) was increased in diabetic patients, while adenosine treatment decreased the energy requirements and increased the autophagy levels of EPCs. In animal experiments, we transplanted a biomaterial seeded with EPCs onto the surface of diabetic wounds and found that adenosine-stimulated EPCs effectively promoted wound healing. Increased microvascular genesis and survival of the transplanted cells were also observed in the adenosine-stimulated groups. Interestingly, our study showed that adenosine increased the autophagy of the transplanted EPCs seeded onto the biomaterial and maintained EPC survival at 48 and 96 hours. Moreover, we observed that adenosine induced EPC differentiation through increasing the level of autophagy. In conclusion, our study indicated that adenosine-stimulated EPCs seeded onto a biomaterial significantly improved wound healing in diabetic mice; mechanistically, adenosine might maintain EPC survival and differentiation by increasing high glucose-inhibited EPC autophagy and maintaining cellular energy metabolism. [ABSTRACT FROM AUTHOR]

One of the major problems influencing the therapeutic efficacy of stem cell therapy is the poor cell survival following transplantation. This is partly attributed to insufficient resistance of transplanted stem cells to oxidative and inflammatory stresses at the injured sites. In the current study, we demonstrated the pivotal role of antioxidant levels in human umbilical cord mesenchymal stem cells (hUCMSCs) dynamic in vitro anti-stress abilities against lipopolysaccharide (LPS)/H2O2 intoxication and in vivo therapeutic efficacy in a murine acute liver failure model induced by D-galactosamine/LPS (Gal/LPS) by either reducing the antioxidant levels with diethyl maleate (DEM) or increasing antioxidant levels with edaravone. Both the anti- and pro-oxidant treatments dramatically influenced the survival, apoptosis, and reactive oxygen species (ROS) production of hUCMSCs through the MAPK-PKC-Nrf2 pathway in vitro. When compared with untreated and DEM-treated cells, edaravone-treated hUCMSCs rescued NOD/SCID mice from Gal/LPS-induced death, significantly improved hepatic functions and promoted host liver regeneration. These effects were probably from increased stem cell homing, promoted proliferation, decreased apoptosis and enhanced secretion of hepatocyte growth factor (HGF) under hepatic stress environment. In conclusion, elevating levels of antioxidants in hUCMSCs with edaravone can significantly influence their hepatic tissue repair capacity. [ABSTRACT FROM AUTHOR]

The prognostic significance of gender remains controversial for papillary thyroid carcinoma (PTC). In this study, we investigated the associations between gender and prognosis in a large cohort of patients with PTC or PTMC that was diagnosed in 2010-2013 and recorded in the Surveillance, Epidemiology, and End Results cancer registry. The mean ± standard deviation duration of survival for all patients with PTC during the study period was 21.47 ± 14.04 months. In Kaplan-Meier analyses of the entire cohort of PTC patients, survival curves for all-cause death and cancer-specific death declined more sharply for men than for women. Similar results were observed in analyses of patients with PTCs > 1 cm and PTMC. After adjusting for potential confounders, hazard rates indicated significantly elevated all-cause mortality for men in analyses of all PTCs, PTCs > 1 cm, and PTMCs. However, in a confounder-adjusted analysis of patients with PTMC, the hazard rate did not indicate significantly higher mortality for men than for women. Our study demonstrated that male gender is an independent poor prognostic factor for all PTCs and for PTCs > 1 cm. However, gender is not an independent prognostic factor for cause-specific survival in PTMC.

The current American Joint Committee (AJCC) on Cancer TNM classification does not describe the treatment of multifocal papillary thyroid microcarcinomas (PTMCs) with a total tumour diameter (TTD) >1 cm. Herein, we investigated this PTMC subgroup in terms of extrathyroidal extension (ETE), local infiltration, central lymph node metastasis (LNM), and prognosis. Consecutive patients (n = 1102) were identified and the proportions of LNM, ETE, and local infiltration were similar between PTCs with a unifocal tumour diameter >1 cm and ≤2 cm and PTMCs with a multifocal TTD >1 cm and ≤2 cm. The proportions of LNM, ETE, and local infiltration were also similar between PTMCs with a unifocal diameter ≤1 cm vs. multifocal TTD ≤1 cm. However, when comparing PTMCs with a unifocal diameter ≤1 cm vs. multifocal TTD >1 cm, significant differences were observed. In the Kaplan-Meier analysis, significant differences were observed between PTMCs with a unifocal diameter ≤1 cm vs. multifocal TTD >1 cm and multifocal TTD ≤1 cm vs. multifocal TTD >1 cm. Accordingly, TTD may represent a more accurate criterion for tumour size of PTCs and should be considered in the revised AJCC staging system.