Intravitreal decorin preventing proliferative vitreoretinopathy in perforating injuries: a pilot study.

PURPOSE: To determine the short-term safety of human recombinant decorin protein in preventing proliferative vitreoretinopathy (PVR) in perforating injuries. METHODS: This is a prospective, single-center, open-label, interventional case series. Single intravitreal injection of decorin 200 µg (n = 4) or 400 µg (n = 8) was given 48 h after injury. At the tenth day, pars plana vitrectomy was done whenever indicated. Flash electroretinogram (ERG) was done before and 3 months post-injection. We assessed ocular inflammation, ERG changes, and retinal layer integrity by optical coherence tomography (OCT). Systemic and vitreous pharmacokinetics were also evaluated. RESULTS: Twelve patients (12 eyes) with perforating globe injuries (zone III) were included and followed for a median of 6 months. Intravitreal decorin injection was well tolerated with no ocular or systemic safety adverse events. Decorin retinal safety was demonstrated anatomically by intact retinal layer by OCT, and functionally by flash ERG which did not show any significant worsening during the study and the final mean logMAR best-corrected visual acuity (BCVA) which was 1.15 (20/280) and 0.7 (20/100) for groups A and B, respectively, and ≥ 20/200 in 75% of all eyes. Decorin serum and vitreous levels were elevated following trauma, with higher and extended levels following intravitreal injection. CONCLUSIONS: No short-term safety concerns were detected after a single intravitreal injection of decorin in patients with perforating injuries. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02865031.

Transforming growth factor-ß1 gene expression in hepatocellular carcinoma: a preliminary report.

BACKGROUND AND STUDY AIMS: The transforming growth factor (TGF)-ß signalling pathway plays a dual role in hepatocarcinogenesis. It has been recognised for its role as a tumour suppressor as well as a tumour promoter depending on the cellular context. The aim of this study was to investigate the clinical significance of serum TGF-ß1 level and TGF-ß1 messenger RNA (mRNA) in the peripheral blood of liver cirrhosis and hepatocellular carcinoma (HCC) patients as noninvasive biomarkers in diagnosing HCC. PATIENTS AND METHODS: Twenty patients were allocated to each of the liver cirrhosis and HCC groups, in addition to 20 healthy volunteers. TGF-ß1 gene expression in peripheral blood was quantitated using real-time polymerase chain reaction (PCR), while serum TGF-ß1 was analysed using enzyme-linked immunosorbent assay (ELISA). RESULTS: TGF-ß1 gene expression was significantly lower in HCC patients (median 0.401 (0.241-0.699) fold change) than in liver cirrhosis patients (median 0.595 (0.464-0.816)) (p=0.042) and normal controls (median 1.00 (0.706-1.426) fold change) (p=0.001). TGF-ß1 gene expression showed significant positive correlation with serum TGF-ß1 (r=0.272, p=0.036) and significant negative correlation with alpha-fetoprotein (AFP) (r=-0.528, p=0.001). Receiver operating characteristic (ROC) analysis was conducted for TGF-ß1 gene expression in comparison with AFP. The area under the curve for TGF-ß1 gene expression was 0.688 (95% CI=0.517-0.858) (p=0.042) and AFP was 0.869 (95% CI=0.761-0.976) (p=0.001). The sensitivity and specificity of TGF-ß1 gene expression were 65% and 75%, respectively, at a cutoff value of 0.462 fold change. CONCLUSION: TGF-ß1 gene expression in the peripheral blood may be used as a molecular marker for the diagnosis of HCC. Additional studies on a large-scale population are necessary to gain greater insight into the impact of TGF-ß1 gene expression in the pathogenesis of HCC.