Long non-coding RNAs (lncRNAs) can serve as blood-based biomarkers for cancer detection. To identify novel lncRNA biomarkers for gastric cancer (GC), we conducted, for the first time, genome-wide lncRNA screening analysis in two sets of samples: five paired preoperative and postoperative day 14 plasma samples from GC patients, and tissue samples from tumor and adjacent normal tissues. Candidate tumor-related lncRNAs were then quantitated and evaluated in three independent phases comprising 321 participants. The expression levels of lncRNAs were also measured in GC cell lines and the corresponding culture medium. Biomarker panels, lncRNA-based Index I and carcinoembryonic antigen (CEA)-based Index II, were constructed using logistic regression, and their diagnostic performance compared. Fagan's nomogram was plotted to facilitate clinical application. As a result, we identified five novel plasma lncRNAs (TINCR, CCAT2, AOC4P, BANCR and LINC00857), which, when combined in the lncRNA-based Index I, outperformed the CEA-based Index II (P < 0.001) and could distinguish GC patients from healthy controls with an area under the receiver-operating curve (AUC) of 0.91 (95% confidence interval (CI): 0.88-0.95). The lncRNA-based index decreased significantly by postoperative day 14 (P = 0.016), indicating its ability to monitor tumor dynamics. High values of the lncRNA-based index were correlated with tumor size (P = 0.036), depth of invasion (P = 0.025), lymphatic metastasis (P = 0.012) and more advanced tumor stages (P = 0.003). The lncRNA-based index was also able to discriminate GC patients from precancerous individuals and patients with gastrointestinal stromal tumor with AUC values of 0.82 (95% CI: 0.71-0.92) and 0.80 (95% CI: 0.68-0.91), respectively. Taken together, our findings demonstrate that this panel of five plasma lncRNAs could serve as a set of novel diagnostic biomarkers for GC detection.
Abnormal activation of the Sonic hedgehog (SHH) pathway has been described in a wide variety of human cancers and in cancer stem cells (CSCs), however, the role of SHH pathway in gastric CSCs has not been reported. In this study, we investigated the possibility that abnormal activation of the SHH pathway maintained the characteristics of gastric CSCs. First, we identified cancer stem-like cells (CSLCs) from human gastric cancer cell lines (HGC-27, MGC-803 and MKN-45) using tumorsphere culture. Compared with adherent cells, the floating tumorsphere cells had more self-renewing capacity and chemoresistance. The cells expressing CSCs markers (CD44, CD24 and CD133) were also significantly more in tumorsphere cells than in adherent cells. More importantly, in vivo xenograft studies showed that tumors could be generated with 2×104 tumorsphere cells, which was 100-fold less than those required for tumors seeding by adherent cells. Next, RT-PCR and Western blot showed that the expression levels of Ptch and Gli1 (SHH pathway target genes) were significantly higher in tumorsphere cells than in adherent cells. The results of quantitative real-time PCR were similar to those of RT-PCR and Western blot. Further analysis revealed that SHH pathway blocked by cyclopamine or 5E1 caused a higher reduction in self-renewing capacity of HGC-27 tumorsphere cells than that of adherent cells. We also found that SHH pathway blocking strongly enhanced the efficacy of chemotherapeutic drugs in HGC-27 tumorsphere cells in vitro and in vivo but had no significant effect in adherent cells. Finally, we isolated the tumorspheres from gastric cancer specimen, these cells also had chemoresistance and tumorigenic capacity, and SHH pathway maintained the gastric CSLCs characteristics of tumorsphere cells from primary tumor samples. In conclusion, our data suggested that SHH pathway was essential for maintenance of CSLCs in human gastric cancer.
BackgroundHealthcare in China has significantly improved, meanwhile many socio-economic risk factors and health conditions factors affect accessibility and utilization of health services in rural areas. Inequity of health service in China needs to be estimated and reduced. Andersen behavioral model is useful to assess the association of health service utilization with predisposing, enabling, and need factors.MethodsA survey was conducted among 4634 residents of 897 households in 2012. Logistic regression analysis was performed to explore the association of predisposing (age, gender, marital status, ethnicity and family size), enabling (education level, travel time to the nearest health facility, medical expense per capita, and health insurance coverage), and need factors (chronic disease) with the utilization of health services (i.e. physician visit and hospitalization).ResultsWe observed a significant association between need factor (chronic diseases) and health service unitization, after adjusting for all predisposing and enabling factors (physician visits: odds ratio (OR) = 5.87, 95 % confidence interval (CI) = 4.71–7.32; hospitalization: OR = 4.04, 95 % CI = 2.90–5.61, respectively). In addition, age, gender, marital status, family size and education level were significant predictors of health service utilization. The travel time to the nearest health facility was associated with the utilization of physician visits, and expenditure on healthcare was a hindering factor of hospitalization.ConclusionsThe predisposing and enabling factors had a minor impact on health service utilization, while the need factor was a dominant predictor of health service utilization among rural residents in China.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-016-1825-4) contains supplementary material, which is available to authorized users.
Eph receptor tyrosine kinases and their ephrin ligands are involved in various signalling pathways and mediate critical steps of a wide variety of physiological and pathological processes. Increasing experimental evidence demonstrates that both Eph receptor and ephrin ligands are overexpressed in a number of human tumours, and are associated with tumour growth, invasiveness and metastasis. In this regard, the Eph/ephrin system provides the foundation for potentially exciting new targets for anticancer therapies for Eph-expressing tumours. The purpose of this review is to outline current advances in the role of Eph receptors and ephrin ligands in cancer, and to discuss novel therapeutic approaches of anticancer therapies.
BackgroundMajor depressive disorder (MDD) is one of the important causes of disease burden in the general population. Given the experiencing rapid economic and social changes since the early 1990s and the internationally recognized diagnostic criteria and interview instruments across the surveys during 2001–2010 in china, the epidemiological studies on MDD got varied results. We performed this meta-analysis to investigate current, 12-month and lifetime prevalence rates of MDD in mainland China.MethodsPubMed, Embase, Chinese Biological Medical Literature database (CBM), Chinese National Knowledge Infrastructure database (CNKI), and the Chinese Wanfang and Chongqing VIP database were searched for associated studies. We estimated the overall prevalence of MDD using meta-analysis.ConclusionsSeventeen eligible studies were included. Our study showed that the overall estimation of current, 12-month and lifetime prevalence of MDD was 1.6, 2.3, 3.3%, respectively. The current prevalence was 2.0 and 1.7% in rural and urban areas, respectively; between female and male, it was 2.1 and 1.3%, respectively. In addition, the current prevalence of MDD diagnosed with SCID (Structured Clinical Interview for DSM-IV) was 1.8% and that diagnosed with CIDI (Composite International Diagnostic Interview) was 1.1%. In conclusion, our study revealed a relatively high prevalence rate in the lifetime prevalence of MDD. For current prevalence, MDD diagnosed with SCID had a higher prevalence rate than with CIDI; males showed a lower rate than females, rural residents seemed to have a greater risk of MDD than urban residents.
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