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Protein dysregulation in graft versus host disease

第一作者:Qian, LR

期刊: ONCOTARGET, 2018; 9 (无)

Allogeneic hematopoietic stem cell transplantation is a well-established treatment for many malignant and non-malignant hematological disorders. As a frequent complication in up to 50% of all patients, graft-versus-host disease is still the main cause for morbidity and non-relapse mortality. Diagnosis is usually done clinically, even though confirmation by pathology is often used to support the clinical findings. Effective treatment requires intensified immunosuppression as early as possible. Although several promising biomarkers have been proposed for an early diagnosis, no internationally-recognized consensus has yet been established. Protein-based biomarkers represent an interesting tool since they have been recently reported to be an important regulator of various cells, including immune cells such as T cells. Therefore, we assume that protein dysregulation is important in the pathogenesis of acute graft versus host disease and their detection might be an possibility in the early diagnosis and monitoring. In this review, we aim to summarize the previous reports of protein biomarkers, focusing on the pathogenesis of the disease and possible implications in diagnostic approaches.

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Circular RNAs: clinical relevance in cancer

第一作者:Xu, ZJ

期刊: ONCOTARGET, 2018; 9 (无)

Circular RNAs, as recently discovered new endogenous non-coding RNAs, are important gene modulators with critical roles in tumor initiation and malignant progression. With the development of RNA sequencing and microarray technologies, numerous of functional circRNAs have been identified in cancerous tissues and cell lines. Mechanistically, circRNAs function as miRNA sponges, miRNA reservoirs or parental gene expression regulators. In this review, we discuss the properties and functions of circRNAs and their clinical implication as promising biomarkers for cancer research. Moreover, some emerging fields, such as exosome-loaded and immune response-associated circRNAs, are also discussed, suggesting novel insights into the carcinogenesis and therapy associated with these molecules.

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LncRNAs regulate cancer metastasis via binding to functional proteins

第一作者:Yang, LT

期刊: ONCOTARGET, 2018; 9 (无)

Cancer is one of the leading causes of death worldwide, and metastasis is a crucial characteristic of malignancy. Recent studies have shown that lncRNAs play an important role in regulating cancer metastasis through various molecular mechanisms. We briefly summarize four known molecular functions of lncRNAs, including their role as a signal, decoy, guide and scaffold. No matter which pattern lncRNAs follow to carry out their functions, the proteins that lncRNAs bind to are important for them to exhibit their gene-regulating properties. We further illustrate that lncRNAs regulate the localization, stabilization or modification of their binding proteins to realize the binding role of lncRNAs. In this review, we focus on the interactions between lncRNAs and their binding proteins; moreover, we focus on the mechanisms of the collaborative work of lncRNAs and their binding proteins in cancer metastasis, thus evaluating the potential of lncRNAs as prospective novel therapeutic targets in cancer.

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Current research on head and neck cancer-associated long noncoding RNAs

第一作者:Song, W

期刊: ONCOTARGET, 2018; 9 (无)

Head and neck cancers (HNC) are one of the ten leading cancers worldwide, including a range of malignant tumors arising from the upper neck. Due to the complex mechanisms of HNC and lack of effective biomarkers, the 5-year survival rate of HNC has been low and the mortality rate has been high in recent decades. Long noncoding RNAs (lncRNAs), noncoding RNAs longer than 200 bps, are a focus of current cancer research, closely related to tumor biology. LncRNAs have been revealed to be aberrantly expressed in various types of HNC, and the dysregulated lncRNAs participate in HNC progression and induce malignant behavior by modulating gene expression at diverse levels. This review will focus on the functions and molecular mechanisms of dysregulated lncRNAs in HNC tumorigenesis and progression, as well as their diagnostic, therapeutic or prognostic implications in HNC.

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Equine infectious anemia virus in China

第一作者:Wang, HN

期刊: ONCOTARGET, 2018; 9 (无)

Equine infectious anemia is an equine disease caused by equine infectious anemia virus, which was first reported in 1840. Equine infectious anemia virus research in China started in the 1960s, focusing on etiology, pathology, diagnosis, and immunology. Notably, in 1978 an attenuated vaccine was successfully developed for equine infectious anemia virus, effectively preventing equine infectious anemia virus in China. This article will review equine infectious anemia virus in China, including past and recent research, and commemorate scientists who have made great contributions to equine infectious anemia virus prevention.

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3D modeling of cancer stem cell niche

第一作者:He, J

期刊: ONCOTARGET, 2018; 9 (无)

Cancer stem cells reside in a distinct microenvironment called niche. The reciprocal interactions between cancer stem cells and niche contribute to the maintenance and enrichment of cancer stem cells. In order to simulate the interactions between cancer stem cells and niche, three-dimensional models have been developed. These in vitro culture systems recapitulate the spatial dimension, cellular heterogeneity, and the molecular networks of the tumor microenvironment and show great promise in elucidating the pathophysiology of cancer stem cells and designing more clinically relavant treatment modalites.

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TNFR/TNF-alpha signaling pathway regulates apoptosis of alveolar macrophages in coal workers' pneumoconiosis

第一作者:Qian, QZ

期刊: ONCOTARGET, 2018; 9 (无)

We explored the role of TNFR/TNF-alpha signalingin apoptosis among alveolar macrophages (AM) and its relevance to the development of coal workers' pneumoconiosis (CWP). Purified alveolar macrophages (AMs) were prepared from bronchoalveolar lavage fluid harvested from 366 CWP patients and 120 healthy subjects enrolled inthe study. The purified AMs were then divided into control, SOD, anti-TNFR, TNFR and NFkB inhibitor groups and analyzed for apoptosis usingflow cytometry (sub-diploid peak) and western blotting (Bcl-2, Caspase-3 and Caspase-8 expression). We found thatAM apoptosis washigher amongCWP patients than thehealthycontrols. Expression ofBcl-2, Caspase-3 and Caspase-8 was higher inAMs from CWP patientsthan in those from the controlsand correlated with increased AM apoptosis. Univariate and multivariate analyses suggested that CWP grade, initial exposure time, exposure time inyears, and CWP onset agewereall associated with altered levels of Bcl-2, Caspase-3 and Caspase-8. Inhibition of TNFR/TNF-alpha signaling usinganti-TNFR antibody, SOD or NFkB inhibitionreduced AM apoptosisand decreased Bcl-2, Caspase-3 and Caspase-8 expression. These data suggestinhibition of a TNFR/TNF-alpha signaling pathway is a potentiallyeffective means ofalleviating CWP by inhibiting AM apoptosis.

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Association between hypertensive disorders of pregnancy and risk of autism in offspring: a systematic review and meta-analysis of observational studies

第一作者:Xu, RT

期刊: ONCOTARGET, 2018; 9 (无)

Background: Autism spectrum disorder (ASD) is a common severe pervasive neurodevelopmental disorder of undetermined etiology. Environmental exposures, especially pregnancy complications, have been increasingly recognized as a potential risk factor for ASD. Our aim was to (1) systematically evaluate the association between hypertensive disorders of pregnancy (HDP) and the risk of ASD in offspring, (2) specifically draw a subgroup analysis of disease severity in patients with HDP to achieve more sufficient evidence on this issue. Results: A total of 21 studies were identified with more than 6.5 million participants, including 31,027 ASD probands. A comparative meta-analysis established that offspring born premature to HDP were significantly associated with ASD than matched controls (OR = 1.42, 95% CI: 1.34-1.50). Subgroup analysis of clinical classification include: (1) gestational hypertension, (2) pre-eclampsia, (3) chronic hypertension complicating pregnancy (CHP). The offspring of mothers with pre-eclampsia and CHP have slightly higher risk (OR = 1.43; OR = 1.48, respectively) of ASD than those of mothers with gestational hypertension (OR = 1.37). In consistence with most previous researches, higher ASD prevalence was observed in male than female (OR = 1.38), indicating a potential role for gender in the pathophysiology of ASD. Materials and Methods: We conducted a systematic literature search on PubMed, EMBASE, Web of Science, PsycINFO database and China National Knowledge Infrastructure up to Jun. 2017. Statistical analysis was performed using Stata 10.0. Conclusions: This meta-analysis implies a possible link between HDP and the risk of ASD in offspring. However, further investigation should be conducted to confirm this conclusion, and intensive prenatal surveillance and early prediction for ASD is needed.

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Prognostic and clinicopathological significance of microRNA-494 overexpression in cancers: a meta-analysis

第一作者:Xiang, ZX

期刊: ONCOTARGET, 2018; 9 (无)

MicroRNA-494 was revealed as an attractive prognostic biomarker in recent studies. Nevertheless, the prognostic value of microRNA-494 in cancers remains controversial. Current meta-analysis aims to elucidate the precise predictive value of microRNA-494 in various cancers. Eligible studies were identified through multiple search strategies, the hazard ratios (HRs) and their confidence interval (CI) for patient prognostic outcomes were extracted and estimated. The pooled results of fifteen studies indicated that elevated expression of microRNA-494 implies a good overall survival of cancer patients (HR = 0.58, 95% CI: 0.36-0.91); While no significant association was found between the high expression of microRNA-494 and clinicopathological characteristic. Additionally, subgroup analysis revealed that overexpression of microRNA-494 predicted a worse overall survival in non-small cell lung cancer (HR = 2.35, 95% CI: 1.05-5.24) and colorectal cancer (HR = 2.59, 95% CI: 1.62-4.14). As per the subgroup analysis, the cancer type, the anatomy system classification and the ethnic background had influence on the overall survival result. Our findings indicate that elevated expression of microRNA-494 might predict a good overall survival in most cancers, while in non-small cell lung cancer and colorectal cancer, overexpression of microRNA-494 might predict a worse overall survival.

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Serum levels of adipokines and cytokines in psoriasis patients: a systematic review and meta-analysis

第一作者:Bai, F

期刊: ONCOTARGET, 2018; 9 (无)

Purpose: To evaluate the association of serum levels of adipokines and cytokines with psoriasis. Materials and Methods: A comprehensive literature search was performed in PubMed, ScienceDirect and Web of Science for the available relevant studies published before December 1, 2016. Differences in serum marker levels between patients and controls were pooled as standardized mean differences (SMDs) with 95% confidence interval to combine the effect estimations. We also conducted stratified analysis, meta-regression analysis and sensitivity an alysis. Results: Sixty-three studies containing 2876 psoriasis patients and 2237 healthy controls were included in this meta-analysis. The pooled serum levels of TNF-alpha, IFN-gamma, IL-2, IL-6, IL-8, IL-18, IL-22, chemerin, lipocalin-2, resistin, sE-selectin, fibrinogen and C3 were higher in psoriasis patients compared with healthy controls (all P < 0.05). In contrast, adiponectin levels were lower. Serum levels of IL-1 beta, IL-4, IL-10, IL-12, IL-17, IL-21, IL-23, visfatin and omentin were not significantly different between psoriasis patients and controls (all P > 0.05). However, increased serum levels of IL-17 correlated with psoriasis in men. For other biomarkers, age, gender and psoriasis area and severity index did not explain the differences in effect size between the studies. Conclusions: Serum levels of TNF-alpha, IFN-gamma, IL-2, IL-6, IL-8, IL-18, IL-22, chemerin, lipocalin-2, resistin, sE-selectin, fibrinogen, complement 3, and adiponectin correlate with psoriasis and can be used as potential biomarkers for psoriasis and response to the treatment. Future studies are needed to identify additional players involved in the pathogenesis of psoriasis and to fully decipher the underlying mechanism.

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The prognostic value of NRF2 in solid tumor patients: a meta-analysis

第一作者:Wang, LL

期刊: ONCOTARGET, 2018; 9 (无)

Nuclear factor E2-related factor 2 (NRF2), a transcription factor, is known as a potential therapeutic target of solid tumor for that it is a master regulator of the injury and inflammation response, including controlling antioxidant cell progress. Recent studies showed that NRF2 played significant roles in tumorigenesis and tumor progression, however no association and relationship between NRF2 expression and different clinical manifestation of solid tumor had been accurately evaluated. The present meta-analysis picked up 17 suitable articles from EMBASE, PubMed, and ISI Web of Science databases, including 2238 patients. Combined with results of hazard ratios (HRs) and 95% confidence intervals (CIs), we concluded that a higher expression of NRF2 would have worse impact on overall survival (HR = 2.29, 95% CI 1.80-2.91, P < 0.05) and disease-free survival (HR = 2.34, 95% CI 1.36-4.00, P < 0.05) by a random-effect model. Moreover, further results were positively correlated to the clinical diagnosis, curative effect observation and prognosis, including tumor differentiation, lymph node metastasis, distant metastasis and clinical stage. Consequently, our data shown that NRF2 is a potential poor prognostic factor in a variety of solid tumors.

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Chinese C allele carriers of the ERCC5 rs1047768 polymorphism are more sensitive to platinum-based chemotherapy: a meta-analysis

第一作者:Xu, MZ

期刊: ONCOTARGET, 2018; 9 (无)

It is suspected that ERCC5 rs1047768 and rs17655 polymorphisms influence the response to platinum-based chemotherapy. This meta-analysis was performed to summarize the scattered evidence regarding the association between these two polymorphisms and sensitivity to platinum-based treatment. Thirteen studies were included after a comprehensive literature search. The pooled odds ratios and 95% confidence intervals suggested that the C allele of the ERCC5 rs1047768 polymorphism is associated with elevated sensitivity to platinating agents, especially for Chinese patients. However, no difference among rs17655 genotypes could be detected.

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High mobility group protein A2 overexpression indicates poor prognosis for cancer patients: a meta-analysis

第一作者:Nie, D

期刊: ONCOTARGET, 2018; 9 (无)

Overexpression of the high mobility group protein A2 (HMGA2), an architectural transcription factor, has been linked to poor prognosis in many malignancies, although this remains controversial. Herein, we conducted a meta-analysis to investigate whether HMGA2 has prognostic value, and evaluated the association between HMGA2 and clinicopathologic factors in malignancies. A total of 29 studies involving 4114 patients were included in this meta-analysis. The pooled results demonstrated that elevated HMGA2 predicted a poor overall survival (OS) (hazard ratio [HR] = 1.82; 95% confidence interval [CI] = 1.62-2.05; P < 0.001) and disease-free survival/progression-free survival/recurrence-free survival (HR = 1.94; 95% CI = 1.27-2.98; P = 0.002). Subgroup analysis conducted by study region, sample size, detection method, and analysis method indicated that HMGA2 overexpression correlated with poor OS. Furthermore, HMGA2 overexpression was found to be linked to poor OS in various cancers except ovarian cancer (pooled HR = 1.14; 95% CI = 0.62-2.09; P = 0.673). High HMGA2 expression level also correlated with advanced TNM stage (OR = 2.44; 95% CI = 1.87-3.2; P < 0.001), lymphovascular invasion (OR = 2.46, 95% CI = 1.67-3.64; P < 0.001), distant metastasis (OR = 2.66; 95% CI = 1.51-4.69; P < 0.001), and lymph node metastasis (OR = 1.83; 95% CI = 1.27-2.64; P = 0.001). In conclusion, HMGA2 overexpression indicates a worse prognosis and may serve as a prognostic predictor in cancer patients.

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Molecular regulation of ERK5 in development of diabetic retinopathy

第一作者:Zhao, Q

期刊: ONCOTARGET, 2018; 9 (无)

Diabetic retinopathy (DR) is a major complication of diabetes, and causes pathological changes in retina blood vessels, as the most common cause of vision loss. Extracellular-signal-regulated kinase 5 (ERK5) is the newest discovered member in the mitogen-activated protein kinases (MAPKs) family, and recent evidence demonstrates an essential role of ERK5 signaling in the angiogenesis. However, whether ERK5 signaling may regulate DR development is unknown. Here, we used a streptozocin (STZ)-induce mouse DR model to investigate this question. We detected significant increases in the phosphorylation of ERK5, a signature of ERK5 activation in the purified retinal endothelial cells in DR mice, compared to control mice. In vivo suppression of ERK5 phosphorylation through administration of a specific inhibitor of ERK5 activation, BIX02189, did not prevent the occurrence of STZ-induced diabetes in mice, but significantly alleviated the severity of DR, seemingly through attenuating the retina neovascularization. Thus, our study suggests a previously unappreciated role of ERK5 signaling in DR development.

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No differences in brain microstructure between young KIBRA-C carriers and non-carriers

第一作者:Hu, L

期刊: ONCOTARGET, 2018; 9 (无)

KIBRA rs17070145 polymorphism is associated with variations in memory function and the microstructure of related brain areas. Diffusion kurtosis imaging (DKI) as an extension of diffusion tensor imaging that can provide more information about changes in microstructure, based on the idea that water diffusion in biological tissues is heterogeneous due to structural hindrance and restriction. We used DKI to explore the relationship between KIBRA gene polymorphism and brain microstructure in young adults. We recruited 100 healthy young volunteers, including 53 TT carriers and 47 C allele carriers. No differences were detected between the TT homozygotes and C-allele carriers for any diffusion and kurtosis parameter. These results indicate KIBRA rs17070145 polymorphism likely has little or no effect on brain microstructure in young adults.

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