Similarly, we found that Lcn2 expression was positively correlated with a worse HCC differentiation Selleckchem BGJ398 grade
before dedifferentiation. Thus, Lcn2 may also be a molecular marker for the progression of HCC before tumor metastasis or EMT. In HCC, the up-regulation and nuclear relocation of the EMT regulator Twist1 have been implicated in tumor invasion and metastasis.[31, 44] As a major regulator of EMT-mediated invasion and metastasis, Twist1 plays an important role through its regulation of E-cadherin expression, which is believed to be critical for tumor invasion. It is widely accepted that loss of E-cadherin plays a critical role in the EMT, an early event in cancer cell invasion and metastasis.[45] In our FK228 datasheet study, the effects of Lcn2 on cell invasion and metastasis were mediated through suppression of the transcription factor Twist1 and subsequent up-regulation
of E-cadherin. We found that Lcn2 can effectively translocate to the nucleus from the cytoplasm and bind to the promoter region of Twist1, which could result in the transcriptional down-regulation of Twist1. We also found that in HCC cells, EGF- or TGF-β1-mediated EMT resulted from the down-regulation of Lcn2 and subsequent up-regulation of Twist1. In conclusion, Lcn2 inhibits proliferation, invasion, and metastasis in vitro and in vivo through transcriptional suppression of Twist1 in HCC cells. Thus, Lcn2 may be a candidate metastasis suppressor due to its ability to reverse the EMT (MET) in HCC. Lcn2 is therefore a potential therapeutic target in HCC. We thank Jack B. Cowland for providing the reporter plasmids. Additional Supporting Information may be found in the online version of this article. “
“To assess the cost-effectiveness of hepatitis C virus treatment with pegylated interferon alfa-2a and ribavirin in current and former people who inject drugs (PWID). A decision analytic model simulated the lifetime costs and outcomes of four treatment medchemexpress options: early treatment with mild fibrosis, standard treatment with moderate
fibrosis, late treatment with compensated cirrhosis, and no treatment. Treatment modalities were simulated across current, former, and never-injector cohorts of 1000 hypothetical patients with chronic hepatitis C virus. The main outcome measures were incremental costs ($AUD) per quality-adjusted life years (QALYs) gained, and incremental cost-effectiveness ratios (ICERs) were calculated for each cohort. Treatment of current PWID during mild fibrosis resulted in a discounted average gain of 1.60 QALYs (95% confidence interval 0.93–2.26) for an added cost of $12 723 ($11 153–$14 396) compared with no treatment, yielding an ICER of $7941 per QALY gained ($6347–$12 017). Former PWID gained 1.80 QALYs (1.29–2.33) for $10 441 ($8843–$12 074) for early treatment compared with no treatment, resulting in an ICER of $5808 per QALY gained ($5189–$6849). Never-injectors gained 2.33 QALYs (1.87–2.