There exists an urgent medical demand at present to develop therapeutic strategies which can improve the treatment outcome of hepatocellular carcinoma (HCC). Here, we explore the biological functions and clinical significance of PBOV1 in HCC in order to push forward the diagnosis and treatment of HCC. Using theranostical nanomedicines, PBOV1 is verified to be a key oncogene which greatly promotes HCC proliferation, epithelial-to-mesenchymal transition, and stemness by activating the Wnt/β-catenin signaling pathway. Therefore, single-chain antibody for epidermal growth factor receptor (scAb-EGFR)-targeted nanomedicine effectively silencing the PBOV1 gene exhibits potent anticancer effects. In vivo HCC-targeting siRNA delivery mediated by the theranostical nanomedicine remarkably inhibits the tumor growth and metastasis. In addition, the superparamagnetic iron oxide nanocrystals (SPION)-encapsulated nanomedicines possess high MRI detection sensitivity, which endows them with the potential for MRI diagnosis of HCC. This study shows that PBOV1 represents a prognostic biomarker and therapeutic target for HCC.

To prospectively evaluate magnetic resonance (MR) signal abnormalities and the time course of T1 and T2 values in a rabbit model of acute nerve traction injury with histologic and functional recovery correlation. All experimental protocols were approved by the institutional animal use and care committee. Acute traction injury was produced in the sciatic nerve of one hind limb in each of 28 rabbits. The contralateral sham-operated nerves served as controls. Sequential MR imaging and T1 and T2 measurements, as well as measurements of functional changes, were obtained over a 70-day follow-up period, with histologic assessments performed at regular intervals. Signal abnormalities and the time course of T1 and T2 values were observed in the proximal, traction, and distal portions of the injured nerves and the sham-operated nerves, and were compared with each other. Nerves with acute traction injury showed visible hyperintense signals on T2-weighted images and had prolonged T1 and T2 values. Differences of T1 and T2 values were dependent on the sites along the same injured nerve, with the most pronounced and prolonged phase of T1 and T2 increases (peak values of 1333 msec +/- 46 and 79 msec +/- 3.7, respectively) observed in the most severely damaged portion of the injured nerve. T1 and T2 values and functional changes after nerve injury showed a similar time course. A return of T1 and T2 signals to normal values correlated with functional improvement. MR imaging could be used to help predict the degree of nerve damage and monitor the process of nerve recovery in acute peripheral nerve traction injury. (c) RSNA, 2010.

Because the primary surgical treatment options for hepatocellular carcinoma (HCC)—including hepatic resection and liver transplantation—often fail due to recurrence and metastasis, identifying early prognostic biomarkers and therapeutic targets for HCC is of great importance. This study shows that transducin β‐like protein 1–related protein (TBLR1) is a key HCC oncogene that plays important roles in HCC proliferation, antiapoptosis, and angiogenesis by regulating the Wnt/β‐catenin pathway. The folate‐targeted theranostic small interfering RNA (siRNA) nanomedicine Fa‐PEG‐g‐PEI‐SPION/psiRNA‐TBLR1 effectively silences the TBLR1 gene in different human HCC cell lines in vitro and in human HCC samples in vivo, resulting in the simultaneous suppression of HCC cell proliferation, antiapoptosis, and angiogenesis. Because of its multi‐anticancer functions against HCC, intravenous injection of the folate‐targeted siRNA nanomedicine into nude mice bearing intrahepatic or subcutaneous xenografts of human HCC has a significant therapeutic effect. Tumor growth in those animals was almost completely inhibited by treatment with Fa‐PEG‐g‐PEI‐SPION/psiRNA‐TBLR1. Moreover, the SPION‐encapsulated polyplexes possess high magnetic resonance imaging (MRI) detection sensitivity, which makes tumor‐targeted siRNA delivery easily trackable using the clinical MRI technique. Conclusion: The theranostic siRNA nanomedicine examined here possesses great theranostic potential for combined gene therapy and MRI diagnosis of HCC. (Hepatology 2016;63:1240–1255)