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Purpose: To elucidate the effect of IFN-α treatment on tumor growth and metastasis of hepatocellular carcinoma (HCC). Methods: IFN-α administration was conducted in nude mice using an orthotopic implantation model of human HCC, and the key molecular markers in the IFN-α treatment was detected by immunohistochemistry staining and PCR array. Results: Up to 12 weeks of IFN-α treatment significantly suppressed tumor growth of HCC, but relatively increased the number of circulating tumor cells, which might be due to the enhanced tumor hypoxia as well as up-regulation of metastasis-related genes, such as HIF-1α, c-met, u-PA, PDGF-A, and IL-8. However, IFN-α had no direct effect on migration and invasion of HCC cells. Conclusions: IFN-α has janus face of consistently suppressing HCC growth, however, promoting tumor metastasis capacity, which is of clinical indication for the scientific administration of IFN-α and the similar antiangiogenesis drugs for their dual effect on tumor growth and metastasis. [ABSTRACT FROM AUTHOR]

To examine expression profile and prognostic significance of vascular endothelial growth factor (VEGF) and its receptors in hepatocellular carcinoma (HCC) and peritumoral tissue. Expression of VEGF-A, VEGF-C, and VEGF receptor 1(VEGFR-1), VEGFR-2, and VEGFR-3 in tumor and peritumoral liver tissue was studied by immunohistochemistry in a tissue microarray from 107 patients with HCC. Unsupervised hierarchical cluster analyses were conducted to identify relevant clusters. Staining of VEGF-A, VEGF-C, VEGFR-2, and VEGFR-3 was mostly found on the tumor cells and peritumoral hepatocytes, but VEGFR-1 was mostly expressed in stromal cells. In most of the cases, the expression of VEGF-A, VEGFR-1, VEGFR-2, and VEGFR-3 in was higher in peritumoral liver tissue, while VEGF-C expression was higher in tumor. Unsupervised hierarchical clustering analysis identified four prognostically different clusters, of which cluster A was classified into the “poor prognosis group,” and the other three clusters were classified into the “good prognosis group” ( P = 0.047). Further analysis with a set of seven markers reproduced the same four cluster groups with significantly different recurrence free probability (RFP) ( P = 0.018), and the low RFP group was associated with more intrahepatic satellite lesions. Multivariate analysis showed that classification defined by seven biomarkers was of prognostic significance ( P = 0.000). Expression of VEGF and its receptors was higher in peritumoral tissue than in tumor in HCC. Seven biomarkers predicted patients’ RFP, which consisted of tumoral expression of VEGF-A, VEGFR-1, and VEGF-C as well as peritumoral expression of VEGF-A, VEGFR-1, VEGFR-2, and VEGFR-3. [ABSTRACT FROM AUTHOR]

Staphylococcus Aureus Filtrate Preparation (SAFP) is a preparation of low-virulence strain of Staphylococcus aureus. In our study, we aimed to determine the anti-tumor activity of SAFP in vivo and explore the potential mechanism. Our study evaluated the anti-tumor activity of SAFP in four cancer cell models in vivo and determined its up-regulatory effects on mice immune system in vivo. It showed that 7.2 ng/10 g SAFP could inhibit the progression of murine hepatoma H22 and sarcoma S180, and the tumor inhibition rates achieved 48.1 and 35.7%, respectively. In human non-small cell lung cancer A549 and hepatoma BEL7402 xenograft athymic mice models, T/C of 7.2 ng/10 g SAFP group reached 41.0% in A549 model and 21.0% in BEL7402 model. Meanwhile, SAFP also significantly increased the proliferation of cultured mice splenocytes to 162.1%, and 7.2 ng/kg SAFP significantly ( P < 0.001) raised the activity of NK cells, elevated the serum level of IL-2, TNF-α and IFN-γ in mice. SAFP exhibited high efficiency in inhibiting the growth of cancer cells in a dose-dependent manner, which possibly attributed to its regulatory effects of immune system. [ABSTRACT FROM AUTHOR]