Background:To verify whether the concentrations and integrity index of circulating cell-free DNA (ccf-DNA) in serum may be clinically useful for the diagnosis and progression monitoring of colorectal cancer (CRC) patients.Methods:Serum samples were collected from 104 with primary CRC, 85 with operated CRC, 16 with recurrent/metastatic CRC, 63 patients with intestinal polyps and 110 normal controls. Long (247 bp) and short (115 bp) DNA fragments in serum were detected by real-time quantitative PCR by amplifying the ALU repeats (ALU-qPCR). Serum carcinoembryonic antigen (CEA) level was detected by ARCHITECT assay.Results:The median absolute serum ALU115 and ALU247/115 in primary CRC group was significantly higher than those in intestinal polyp and normal control groups (both P<0.0001), in recurrent/metastatic CRC was significantly higher compared with primary CRC (P=0.0021, P=0.0018) or operated CRC (P<0.0001, respectively) and during follow-up, ALU115 and ALU247/115 were increased before surgery and decreased significantly after surgery.Conclusions:Combined detection of ALU115, ALU247/115 and CEA could improve the diagnostic efficiency for CRC. Serum DNA concentrations and integrity index may be valuable in early complementary diagnosis and monitoring of progression and prognosis of CRC.
Early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (SAH) contributes to high morbidity and mortality. Although it is well recognized that acute neuroinflammation reaction is one of the most important triggers of EBI, pharmacotherapy proved to be clinically effective against the initiating of neuroinflammation after SAH is lacking. The resident microglia and infiltrated peripheral monocyte are two main types of immune cells in central nervous system (CNS) and control the inflammation process in brain after SAH. But the time course and relative contributions of these two immune cell activations after SAH are unknown. The p75 neurotrophin receptor (p75NTR), member of TNF receptor superfamily, expresses on infiltrated peripheral monocytes and suppresses their proinflammatory action after brain insults. But the p75NTR expression on resident microglia in vivo is rarely explored and their function keeps elusive. Therefore, we designed this study to investigate the time course of resident microglia activation and peripheral monocyte infiltration, as well as the microglial expression of p75NTR by using CX3C-chemokine receptor 1 (Cx3cr1) and chemokine receptor 2 (Ccr2) double transgenic mice (Cx3cr1Ccr2) after SAH. The results showed activated microglia was observed in cortex as early as 24 h and further increased at 48 and 72 h post SAH, while the infiltrated monocyte was not found until 72h. In addition, activated microglia expressed p75NTR acutely and p75NTR specific antagonist TAT-Pep5 significantly reduced microglia activation, neuroinflammation and EBI from 24 to 72 h. Together, these data suggest that the early neuroinflammation reaction might be initiated and intensified mainly by resident microglia rather than infiltrated monocyte at least in the first 48 h after SAH and p75NTR blockading by TAT-Pep5P might alleviate EBI through mediating microglial activation.
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Weixiang Shi and Ying He should both be regarded as first authors.Objective: This meta-analysis aims to analyze the usefulness of contrast-enhanced ultrasonography (CEUS) for posttreatment responses evaluation of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) management. Methods: Literature retrieval in three databases PubMed, Embase and Cochrane Library was conducted up to September 2015, with pre-defined criteria. The technical success rate, local tumour recurrence and local tumour progression were the measurement indexes. Cochran's Q test and I 2 were used for heterogeneity detection. Subgroup analyses were performed for complete ablation rate stratified by study designs, contrast agents and post-operative testing time points. Statistical analyses were conducted using Stata® 12.0 software (Stata Corporation, College Station, TX). Results: 12 studies consisting of 772 patients were included in this study. The CEUS-evaluated success rate of RFA for HCCs was 91%. The proportion of ablative margin ,5 mm was 53%. The local tumour recurrence rate and local tumour progression rate were 4% and 8%, respectively. Subgroup analysis indicated that the CEUS-assessed technical success rate with Sonazoid™ (Daiichi-Sankyo, Tokyo, Japan) as the contrast agent was higher (95%) than those with other agents [SH U 508A (Schering AG, Berlin, Germany) 86%; SonoVue (Bracco SpA, Milan, Italy) 87%]. The success rate assessed within 24 h (94%) after treatment was higher than longer time (1-3 days 86%; 1 month 91%). Conclusion:The meta-analysis showed that the CEUSevaluated success rate of RFA for HCCs was 91%. The local tumour recurrence rate and local tumour progression rate were 4% and 8%, respectively. Advances in knowledge: Using meta-analysis, the study provided more reliable assessment of usefulness of CEUS, which could provide guidelines for HCC treatment.
Abstract. The present study aimed to explore the mechanisms behind the development and progression of hepatocellular carcinoma (HCC) and identify information regarding HCC-related microRNAs (miRNAs) or marker genes for the gene therapy of HCC. Gene expression profile of GSE67882, generated from 4 hepatitis B virus infected HCC tissue samples (HCC group) and 8 chronic hepatitis B tissue samples with no fibrosis (control group) were downloaded from the Gene Expression Omnibus database. The differentially expressed miRNAs functional enrichment and pathway analyses of HCC were revealed, followed by transcription factor-miRNA interaction network construction and analyses. A total of 14 upregulated miRNAs and 16 downregulated miRNAs between HCC and control samples were obtained. Differentially expressed miRNAs were mainly involved in biological processes like the regulation of histone H3-K9 methylation, and the KEGG pathways in cancer map05200 demonstrates their involvement in cancer. A total of 3 outstanding regulatory networks of miRNAs: hsa-miR-15a, hsa-miR-125b and hsa-miR-122 were revealed. A total of 11 differentially expressed miRNAs including hsa-miR-146p-5b that regulated the marker genes of HCC were explored. miRNAs such as hsa -miR-15a, hsa-miR-125b, hsa-miR-122 and hsa-miR-146b-5p may be new biomarkers for the gene therapy of HCC. Furthermore, histone H3-K9 methylation and other pathways in cancer observed in the KEGG map05200 may be closely related with the development of HCC.
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