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The past decade has witnessed an exponential increase in research on exosomes. For many years considered to be extracellular debris, exosomes are now considered important mediators in intercellular communication. The capability of exosomes to transfer proteins, DNA, mRNA, as well as non-coding RNAs has made them an attractive focus of research into the pathogenesis of different diseases, including cancer. Increasing evidence suggests that tumor cells release a large sum of exosomes, which may not only influence proximal tumor cells and stromal cells in local microenvironment, but also can exert systemic effects when participating in blood circulation. In this study, we review the current understanding on this topic. The literature outlines two broad facets of exosomes in cancer: 1) promotion of tumor growth, tumorigenesis, tumor angiogenesis, tumor immune escape, drug resistance, and metastasis and 2) their role as promising biomarkers for cancer diagnosis and even as potential treatment targets for cancer patients.

BackgroundEsophageal squamous cell carcinoma (ESCC) is an aggressive malignancy, with a high incidence and poor prognosis. In the past several decades, hundreds of proteins have been reported to be associated with the prognosis of ESCC, but none has been widely accepted to guide clinical care. This study aimed to identify proteins with great potential for predicting prognosis of ESCC.MethodsWe conducted a systematic review on immunohistochemical (IHC) prognostic markers of ESCC according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. Literature related to IHC prognostic markers of ESCC were searched from PubMed, Embase, Web of Science, and Cochrane Library until January 30th, 2017. The risk of bias of these original studies was evaluated using the Quality in Prognosis Studies (QUIPS) tool.ResultsWe identified 11 emerging IHC markers with reproducible results, including eight markers [epidermal growth factor receptor (EGFR), Cyclin D1, vascular endothelial growth factor (VEGF), Survivin, Podoplanin, Fascin, phosphorylated mammalian target of rapamycin (p-mTOR), and pyruvate kinase M2 (PKM2)] indicating unfavorable prognosis and 3 markers (P27, P16, and E-cadherin) indicating favorable prognosis of ESCC.ConclusionStrong evidence supports that these 11 emerging IHC markers or their combinations may be useful in predicting prognosis and aiding personalized therapy decision-making for ESCC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s40880-017-0232-5) contains supplementary material, which is available to authorized users.

Complex electrical activities in cardiac tissue can set up time-varying electromagnetic field. Magnetic flux is introduced into the Fitzhugh-Nagumo model to describe the effect of electromagnetic induction, and then memristor is used to realize the feedback of magnetic flux on the membrane potential in cardiac tissue. It is found that a spiral wave can be triggered and developed by setting specific initials in the media, that is to say, the media still support the survival of standing spiral waves under electromagnetic induction. Furthermore, electromagnetic radiation is considered on this model as external stimuli, it is found that spiral waves encounter breakup and turbulent electrical activities are observed, and it can give guidance to understand the occurrence of sudden heart disorder subjected to heavily electromagnetic radiation.Accompanied by rhythmical relaxation of heart, complex electrophysiological activities 1-9 can be detected in cardiac tissue. Spatial pattern 10-14 can be reproduced and observed by collecting the sampled membrane potentials in different areas of cardiac tissue, and many theoretical models [15][16][17][18][19][20][21] have been proposed to investigate the emergence, phase transition and selection of these spatial patterns. It is believed that local heart ischemia can generate "defects" which can block the propagation of target wave emitted from the sinoatrial node 22 ; as a result, self-sustained spiral wave can be induced to block the normal wave propagation. Furthermore, the instability and breakup of spiral wave [23][24][25] in cardiac tissue and can cause possible heart disease. Therefore, many schemes [26][27][28][29][30][31] have been proposed to remove and suppress the spiral wave in cardiac tissue and chemical media. As mentioned in ref. 29, the external forcing can change the excitability of the media thus the spiral wave can be suppressed in a possible way. On the other hand, external field has also been confirmed to be effective in suppressing spiral wave and turbulence, and the possible mechanism can be associated with depolarization effect. The authors in refs 30 and 31 proposed a scheme of phase compression to suppress the spiral wave in excitable and oscillatory media, particularly, the control mechanism is confirmed as a class of intermittent feedback scheme. Indeed, it is more difficult to suppress and control the pinned spiral wave than the meandering spiral wave because these pinned spiral waves are often attracted to a local area such as heterogeneity. As a result, Zhang and Chen et al. [32][33][34][35] proposed some effective schemes to suppress the pinned spiral wave, and the tip dynamics of spiral wave 36 has also been discussed.Indeed, these cardiac tissue models used to emphasize the effect of ion currents across trans-membrane and the membrane potential is calculated, while the effect of electromagnetic induction is left out. As mentioned in refs 37 and 38, complex electrophysiological activities can induce time-varying electromagnetic field and thus the ...

BackgroundOesophageal cancer is one of the most common malignancies worldwide,and oesophageal squamous cell carcinoma (ESCC) is the predominant histological type both globally and in China. Collagen triple helix repeat containing 1 (CTHRC1) has been found to be upregulated in ESCC. However, its role in tumourigenesis and progression of ESCC remains unclear.MethodsUsing our previous ESCC mRNA profiling data, we screened upregulated genes to identify those required for proliferation. Immunohistochemistry was performed to determine the level of CTHRC1 protein expression in 204 ESCC patients. Correlations between CTHRC1 expression and clinicopathological characteristics were assessed. In addition, pyrosequencing and 5-aza-dC treatment were performed to evaluate methylation status of CTHRC1 promoter. In vitro and in vivo analyses were also conducted to determine the role of CTHRC1 in ESCC cell proliferation, migration and invasion, and RNA sequencing and molecular experiments were performed to study the underlying mechanisms.ResultsBased on mRNA profiling data, CTHRC1 was identified as one of the most significantly upregulated genes in ESCC tissues (n = 119, fold change = 20.5, P = 2.12E-66). RNA interference screening also showed that CTHRC1 was required for cell proliferation. Immunohistochemistry confirmed markedly high CTHRC1 protein expression in tumour tissues, and high CTHRC1 expression was positively correlated with advanced T stage (P = 0.043), lymph node metastasis (P = 0.023), TNM stage (P = 0.024) and poor overall survival (P = 0.020). Promoter hypomethylation at cg07757887 may contribute to increased CTHRC1 expression in ESCC cells and tumours. Forced overexpression of CTHRC1 significantly enhanced cell proliferation, migration and invasion, whereas depletion of CTHRC1 suppressed these cellular functions in three ESCC cell lines and xenografts. CTHRC1 was found to activate FRA-1 (Fos-related antigen 1, also known as FOSL1) through the MAPK/MEK/ERK cascade, which led to upregulation of cyclin D1 and thus promoted cell proliferation. FRA-1 also induced snail1-mediated MMP14 (matrix metallopeptidase 14, also known as MT1-MMP) expression to facilitate ESCC cell invasion, migration, and metastasis.ConclusionsOur data suggest that CTHRC1 may act as an oncogenic driver in progression and metastasis of ESCC, and may serve as a potential biomarker for prognosis and personalized therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0555-8) contains supplementary material, which is available to authorized users.