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BACKGROUND AND PURPOSE: Colorectal cancer (CRC) frequently metastasizes to the liver, which involves the participation of multiple cytokines. Tumor microenvironment (TME) composed of cancer-associated fibroblasts (CAFs) and tumor cells acts as an essential factor in cancer metastasis. Transforming growth factor ß1 (TGFß1) is a vital cytokine involved in migration and invasion of cancer cells. However, the underlying mechanisms remain unclear. In the present study, we aimed to investigate the role and molecular mechanisms of TGFß1 in TME. METHODS: The conditioned medium prepared from colorectal cancer HCT116 and HT29 cells was used to culture mesenchymal stem cells (MSCs). The differentiation of MSCs to CAFs was detected by flow cytometry. The role of TGFß1 in colorectal cancer cells metastasis was examined by wound-healing assay and transwell assay. And the activation of the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway was measured by Western blot assay. RESULTS: TGFß1 induced the differentiation of MSCs to CAFs and improved HCT116 and HT29 cells migration and invasion. Meanwhile, TGFß1 also upregulated the phosphorylation of STAT3 and enhanced the nuclear localization of p-STAT3, which activated JAK/STAT3 signaling pathway. CONCLUSION: TGFß1 induced the differentiation of MSCs into CAFs and promoted the migration and invasion of HCT116 and HT29 cells, which depended on the activation of JAK/STAT3 signaling pathway.
RESUMO
OBJECTIVE: To investigate the clinical application, feasibility and value of 3 T whole-heart contrast enhanced free-breathing navigator-gated three-dimensional coronary magnetic resonance angiography (CE-CMRA). METHODS: 3 T CE-CMRA was used to examine patients with suspected coronary heart disease (CAD). Gd-BOPTA (0.2 mmol/kg) was injected intravenously with slow infusion rate (0.3 ml/s) to perform enhancement. Data were post-processed to obtain principal branches of coronary artery and picture quality was evaluated. According to results of selective coronary arteriography (SCAG), the diagnostic accuracy of CE-CMRA for diagnosing CAD was judged by means of detecting significant stenosis (> 50%) of the principal branches based on the 9 segments of coronary artery. RESULTS: Twenty-three out of 26 patients successfully completed the examination. The mean scanning time was (10.4 ± 2.1) minutes, 178 out of 202 (88.1%) SCAG demonstrated segments could be evaluated by CE-CMRA. The imaging quality was superior in proximal and middle segments of coronary artery principal branches than in distal segments. Based on patient-level, there were 9 positive cases and 14 negative cases examined by CE-CMRA compared with 11 positive cases and 12 negative cases examined by SCAG, respectively. The whole diagnose accordance rate of CE-CMRA was 91.3% (21/23) compared with SCAG. The sensitivity, specificity and negative predictive values were 81.8% (9/11), 88.5% (169/191) and 98.8% (9/31) respectively. CONCLUSIONS: 3 T CE-CMRA is a feasible non-invasive imaging modality for diagnosing CAD, especially to detect significant stenosis in proximal and middle segments of coronary artery principal branches. However, the detecting efficacy is limited in assessing stenosis of distal segment and small branches of coronary artery.
