A growing body of evidence implicates macrophage migration inhibitory factor (MIF) in tumorigenesis and metastasis. In this study, we investigated whether MIF expression was associated with clinicopathologic features of colorectal carcinoma (CRC), especially in tumors with hepatic metastasis, and whether neutralization of endogenous MIF using anti-MIF therapeutics would inhibit tumor growth and/or decrease the frequency of colorectal hepatic metastases in a mouse colon carcinoma model. The concentration of serum MIF was positively correlated with an increased risk of hepatic metastasis in human patients with CRC (R = 1.25, 95% confidence internal = 1.02-1.52, P = 0.03). MIF was also dramatically upregulated in human colorectal tissue, with 20-40 times as many MIF-positive cells found in the mucosa of patients with CRC than in normal tissue (P < 0.001 ANOVA). Moreover, in those patients with metastatic colorectal cancer in the liver, MIF-positive cells were similarly increased in the diseased hepatic tissue. This increased MIF expression was restricted to diseased tissue and not found in areas of the liver with normal morphology. In subsequent in vitro experiments, we found that addition of recombinant MIF to colonic cell lines significantly increased their invasive properties and the expression of several genes (for example, matrix metalloproteinase 9 and vascular endothelial growth factor) known to be upregulated in cancerous tissue. Finally, we treated mice that had been given CT26 colon carcinoma cell transplants with anti-MIF therapeutics-either the MIF-specific inhibitor ISO-1 or neutralizing anti-MIF antibodies-and observed a significant reduction in tumor burden relative to vehicle-treated animals. Taken together, these data demonstrate that MIF expression was not only correlated with the presence of colorectal cancer but also may play a direct role in cancer development.
BackgroundThe objective of this study was to evaluate the imaging characteristics of pulmonary artery sarcoma (PAS) on pulmonary artery computed tomography angiography (PACTA) that can be used to differentiate between PAS and pulmonary thromboembolic diseases, including chronic thromboembolic pulmonary hypertension (CTEPH) and acute pulmonary embolism (APE).MethodsThe clinical data and imaging characteristics of 12 patients with PAS, 156 patients with CTEPH, and 426 patients with APE who were treated at Beijing Anzhen Hospital from January 2007 to August 2013 were retrospectively analyzed. All patients underwent PACTA before treatment, and the diagnoses of PAS and CTEPH were all confirmed by surgical biopsy.ResultsAll 12 PAS patients were initially misdiagnosed and received inappropriate thrombolytic and/or anticoagulant therapy before they were referred for surgical intervention. The mean time from PACTA to surgical intervention was 5.5±3.7 months (range 2–11 months). On PACTA, the PAS lesion always eclipsed the wall of the pulmonary artery before infiltrating outside the pulmonary artery, which was termed the wall eclipsing sign. This sign was observed in all PAS patients but was not observed in any CTEPH or APE patients.ConclusionsPAS is a rare neoplasm with a poor prognosis, and is easily misdiagnosed as thromboembolic disease. The wall eclipsing sign on PACTA is pathognomonic for PAS, and patients with this sign should be investigated to confirm the diagnosis and should undergo surgical intervention as soon as possible, rather than receiving thrombolytic or anticoagulant therapy.
The honeybee (Apis mellifera) is a social insect with strong sensory capacity and diverse behavioral repertoire and is recognized as a good model organism for studying the neurobiological basis of learning and memory. In this study, we analyzed the changes in microRNA (miRNA) and messenger RNA (mRNA) following maze-based visual learning using next-generation small RNA sequencing and Solexa/lllumina Digital Gene Expression tag profiling (DGE). For small RNA sequencing, we obtained 13 367 770 and 13 132 655 clean tags from the maze and control groups, respectively. A total of 40 differentially expressed known miRNAs were detected between these two samples, and all of them were up-regulated in the maze group compared to the control group. For DGE, 5 681 320 and 5 939 855 clean tags were detected from the maze and control groups, respectively. There were a total of 388 differentially expressed genes between these two samples, with 45 genes up-regulated and 343 genes down-regulated in the maze group, compared to the control group. Additionally, the expression levels of 10 differentially expressed genes were confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the expression trends of eight of them were consistent with the DGE result, although the degree of change was lower in amplitude. The integrative analysis of miRNA and mRNA expression showed that, among the 40 differentially expressed known miRNAs and 388 differentially expressed genes, 60 pairs of miRNA/mRNA were identified as co-expressed in our present study. These results suggest that both miRNA and mRNA may play a pivotal role in the process of learning and memory in honeybees. Our sequencing data provide comprehensive miRNA and gene expression information for maze-based visual learning, which will facilitate understanding of the molecular mechanisms of honeybee learning and memory.
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