IL-17A promots IL-23expression in HCC.

<p>(<b>A</b>) Expression of IL-23 was detected by western blot analysis in HCC cells treated with or without rhIL-17A (50 ng/mL) for 24 hours. (<b>B</b>) Transcriptional expressions of both subunits of IL-23 were compared by qPCR between cells treated with and without rhIL-17A (50 ng/mL) for 12 hours. *, <i>P</i><0.05. (<b>C</b>) Transcriptional expression of IL-23p40 was detected by qPCR in PLC8024 and MHCC-97L cells with different treatment. Control: without rhIL-17A treatment; rhIL-17A: treated with rhIL-17A (50 ng/mL); Helenalin+rhIL-17A: treated with helenalin (0.l µM) and rhIL-17A (50 ng/mL). *, <i>P</i><0.05.</p

Correlation of IL-23 expression¹ with clinicopathological features in 81 HCC patients.

1<p>Expressions of p19 and p40 were detected by qPCR. Values are expressed as mean±SD.</p>2<p>Partial data unavailable, statistics was done on the available data. Difference is considered significant when <i>P</i><0.05 (shown in bold).</p

Expression of IL-23 in HCC and HCC cell lines.

<p>(<b>A</b>) Compare of IL-23 mRNA expression in 28 primary HCC with metastasis (M+) and 53 primary HCC without metastasis (M−) as well as their expression in tumor (T) and non-tumor (N) area. *, P<0.05; **, P<0.01. (<b>B</b>) Representative of IL-23 expression in non-tumor, primary HCC and metastasis HCC by IHC staining (magnification 200×). (<b>C</b>) Representative of IL-23 expression in HCC by IHC staining (magnification 200×). (<b>D</b>) Protein expression of IL-23 in HCC cell lines detected by western blot. β–actin was used as loading control.</p

IL-23 upregulates MMP9 expression via activating NF-κB.

<p>(<b>A</b>) IL-23 promoted MMP9 mRNA expression at a dose and time dependent manner shown by qPCR. (<b>B</b>) Expression of MMP9 was detected by western blot analysis in HCC cells treated with rhIL-23 (50 ng/mL) or BSA buffer control for 24 hours. (<b>C</b>) Western blot analysis was used to detect whole cell, cytoplasm and nucleus level of P-P65 (active form of NF-κB) expression in PLC8024 and QGY-7703 cells treated with rhIL-23 (50 ng/mL) at indicated time. (<b>D</b>) Expression of MMP9 detected by qPCR in PLC8024 and QGY-7703 cells with different treatment. BSA: treated with BSA buffer control; rhIL-23: treated with rhIL-23 (50 ng/mL); Helenalin+rhIL-23: treated with helenalin (0.l µM) and rhIL-23 (50 ng/mL). *, <i>P</i><0.05.</p

Knocking down IL-23 expression inhibits cell motility.

<p>(<b>A</b>), (<b>B</b>) IL-23 p40 expression was efficiently silenced by IL-23p40 shRNA as determined by RT-PCR, qPCR (<b>A</b>) and western blot (<b>B</b>) in MHCC-97L cell. 18S and β-actin were used as loading control respectively. (<b>C</b>) and (<b>D</b>) Compared to vector control the migration (<b>C</b>) and invasion (<b>D</b>) ability of IL-23 silenced cells were greatly decreased in MHCC-97L cell. *, P<0.05.</p

IL-23 correlates with IL-17A and MMP9 expression in HCC clinical samples.

<p>Expression of IL-23 was positively associated with IL-17A and MMP9 expressions in 81 pair clinical HCC specimens (shown only by sample that have been detected). Analyzed with linear regression lines and pearson correlation by SPSS16.0.</p

IL-23 promotes HCC cell migration and invasion.

<p>(<b>A</b>) RhIL-23 treated HCC cells (PLC8024 and QGY-7703) showed higher motility in wound-healing assay, compared with BSA buffer control treated cells. (<b>B</b>) RhIL-23 increased cell invasion as detected by cell invasive assay. Representatives of cells migrated through Matrigel-coated transwell were shown in the left panel (magnification 100). Total invasive cell number in each chamber was summarized in the right panel. *, <i>P</i><0.05.</p

Will Sofosbuvir/Ledipasvir (Harvoni) Be Cost-Effective and Affordable for Chinese Patients Infected with Hepatitis C Virus? An Economic Analysis Using Real-World Data

<div><p>Background</p><p>Little is known on the cost-effectiveness of novel regimens for hepatitis C virus (HCV) compared with standard-of-care with pegylated interferon (pegIFN) and ribavirin (RBV) therapy in developing countries. We evaluated cost-effectiveness of sofosbuvir/ledipasvir for 12 weeks compared with a 48-week pegIFN-RBV regimen in Chinese patients with genotype 1b HCV infection by economic regions.</p><p>Methods</p><p>A decision analytic Markov model was developed to estimate quality-adjusted-life-years, lifetime cost of HCV infection and incremental cost-effectiveness ratios (ICERs). SVR rates and direct medical costs were obtained from real-world data. Parameter uncertainty was assessed by one-way and probabilistic sensitivity analyses. Threshold analysis was conducted to estimate the price which can make the regimen cost-effective and affordable.</p><p>Results</p><p>Sofosbuvir/ledipasvir was cost-effective in treatment-experienced patients with an ICER of US$21,612. It varied by economic regions. The probability of cost-effectiveness was 18$18,185 to make the regimen cost-effective in all patients at WTP of one time GDP per capita. The price has to be US$105 to make the regimen affordable in average patients in China.</p><p>Conclusion</p><p>Sofosbuvir/ledipasvir regimen is not cost-effective in most Chinese patients with genotype 1b HCV infection. The results vary by economic regions. Drug price of sofosbuvir/ledipasvir needs to be substantially reduced when entering the market in China to ensure the widest accessibility.</p></div

Will Sofosbuvir/Ledipasvir (Harvoni) Be Cost-Effective and Affordable for Chinese Patients Infected with Hepatitis C Virus? An Economic Analysis Using Real-World Data - Fig 2

<p><b>Probability of Cost-effectiveness in A: Treatment-Naïve and B: Treatment-Experienced patients, by economic regions in China.</b> The probability was at the willingness-to-pay of 3 GDP per capita in each region.</p

Model transition probabilities, cost inputs and utilities.

<p>Model transition probabilities, cost inputs and utilities.</p