Monitoring And Evaluation Of The Progression And Metastasis Of Hepatocellular Carcinoma By Living Flow Cytometry And Live Imaging Technique

Cancer is one of the major problems which endanger human public health worldwide. Hepatocellular carcinoma (HCC) is one of the prevalent human cancers worldwide. The prognosis of HCC has been significantly improved in recent years due to earlier diagnosis and more effective treatments. However, tumor recurrence and metastasis are still the major obstacles for long-term survival. In the processes of tumor metastasis, CTC condition is one of the most important issues. The quantification of CTCs is an emerging tool used to diagnose, stratify and monitor patients with metastatic diseases. In vivo flow cytometry (IVFC) has the capability to measure the dynamics of fluorescently labeled CTCs continuously and non-invasively. Combined with IVFC and other in vivo imaging techniques, as well as an EGFP-transfected orthotopic HCC model, we comprehensively and dynamically monitored the processes of tumor growth, development and metastasis. We compared tumor behaviors in both orthotopic and subcutaneous (s.c.) tumor model and found out that there are significant differences in metastasis. These differences caused by the differences of tumor micro-environments. Thus, Orthotopic tumor model is better to assess the tumor growth, development and metastasis characteristics under clinically relevant conditions. Then, we assess the curative effect of both tumor resection therapy and sorafenib treatment therapy. We found out that resection can cut off the supply of CTCs and significant decrease the CTC number, following by the decrease of early metastases and the restriction of advance metastases in lung. Sorafenib treatment can restrict tumor growth, CTCs and distant metastases through inhibiting tumor proliferation and tumor angiogenesis, inducing tumor necrosis and apoptosis. Meanwhile, based on all our results, we found out that CTC numbers correlated with tumor growth in the orthotopic tumor model, including the number and size of distant metastases. That indicates that the number of CTCs might be an independent predictor to assess tumor metastasis and recurrence. We also found out that neither tumor resection nor sorafenib treatment can cure cancer individually. That indicates that the combination therapy of both methods might realize better curative effect. Our study is helpful to knowing the mechism of tumor metastasis and guiding to clinic.