Circulating full-length cytokeratin 18 for predicting prognosis of hepatitis B virus-related acute-on-chronic liver failure patients with lamivudine treatment.

AIM: The predictive value of circulating full-length cytokeratin 18 (M65) on prognosis of hepatitis B virus-related liver failure is still not well investigated. The aim of this study was to reveal the association between serum M65 levels and outcomes of hepatitis B virus-related acute-on-chronic liver failure, and to further clarify clinical significance of M65 in lamivudine treatment. METHODS: Ninety-six patients with hepatitis B virus-related acute-on-chronic liver failure were recruited between January 2011 and December 2013, and 52 of them received lamivudine treatment. Blood were obtained from participants at admission, and M65 were determined by enzyme-linked immunosorbent assay. Other necessary data were collected from medical records. RESULTS: The liver failure patients were divided into high and low level groups according to the serum M65 levels. After 24-week follow up, survival incidences were significantly higher in the low level group than that in the high level group (odds ratio [OR] = 0.3, 95% confidence interval = 0.1-0.7). In addition, the survival incidences and albumin levels improved in the patients with lamivudine treatment compared with the patients without lamivudine treatment in the low level group (OR = 5.4, 95% CI = 1.1-26.0 and OR = 4.2, 95% CI = 1.3-13.2). A similar improvement was not observed in the high level group. CONCLUSION: The study suggested that the circulating M65 may serve as a relatively independent prognostic parameter for liver failure. If prospectively validated in further studies, M65 measurement may also be a useful method for optimizing antiviral therapy.

TESTIN suppresses tumor growth and invasion via manipulating cell cycle progression in endometrial carcinoma.

BACKGROUND: The TESTIN gene was demonstrated to be a tumor suppressor in prostate and breast cancer through inhibiting tumor growth and invasion. Herein, we aimed to investigate the detailed functions of TESTIN in the highly sexual hormone (estrogen)-dependent malignancy, endometrial carcinoma. MATERIAL AND METHODS: TESTIN mRNA and protein expression were measured by qRT-PCR, Western blot and immunohistochemistry. Upregulation of TESTIN was achieved by transfecting the pcDNA3.1-TESTIN plasmids into AN3CA cells. Knockdown of TESTIN was achieved by transfecting the shRNA-TESTIN into Ishikawa cells. MTT assay, colony formation assay, and Transwell assay were used to investigate the effects of TESTIN on cellular proliferation and invasion. The apoptotic status and cell cycle were analyzed using flow cytometry. MMP2 secretion was determined by ELISA assay. The xenograft assay was used to investigate the functions of TESTIN in nude mice. RESULTS: Compared to the non-malignant adjacent endometrium, 54% of tumor samples presented downregulation of TESTIN (P<0.001). Loss of TESTIN protein was correlated with advanced tumor stage (P=0.047), high grade (P=0.034), and lymphatic vascular space invasion (P=0.036). In vitro, overexpression of TESTIN suppressed cell proliferation, induced dramatic G1 arrest, and inhibited tumor invasion through blocking the secretion of MMP2. Loss of TESTIN accelerated cellular proliferation, promoted cell cycle progression, and enhanced tumor invasion by increasing the secretion of MMP2. Consistently, TESTIN could significantly delay the growth of xenografts in nude mice. CONCLUSIONS: TESTIN was commonly downregulated in human endometrial carcinoma and was associated with poor prognostic markers. Moreover, TESTIN significantly inhibited tumor growth and invasion via arresting cell cycle in in vitro and in vivo experiments. Therefore, we propose that TESTIN might be a prognostic marker and therapeutic target for endometrial carcinoma.

MicroRNA-424 is down-regulated in hepatocellular carcinoma and suppresses cell migration and invasion through c-Myb.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs) are important regulators of multiple cellular processes, and the aberrant miRNAs expressions have been observed in different types of cancer including HCC. Their pathysiologic role and their relevance to tumorigenesis are still largely unknown. In this study, we demonstrated the down-regulation of miR-424 in HCC cell lines and tissues by quantitative RT-PCR analyses. Overexpression of miR-424 reduced the HCC cell prolifetation, migration, and invasion. Conversely, inhibiton of miR-424 expression significantly accelerated the cell proliferation, migration, and invasion. In addition, we further identified c-Myb as a functional downstream target of miR-424 by directly targeting the 3'UTR of c-Myb. Furthermore, overexpression of c-Myb impaired miR-424-induced inhibition of proliferation and invasion in HCC cells. Our results demonstrated that miR-424 was involved in tumorigenesis of HCC at least in part by suppression of c-Myb.

High dose combination pertussis toxin induces autoimmune inner ear disease in Sprague-Dawley rats.

CONCLUSION: A better animal model of autoimmune inner ear disease (AIED) in Sprague-Dawley rats has been developed by combination with high dose of pertussis toxin. This study also indicated that inner ear-specific antigens can be involved in autoimmune reactions. Cell-mediated immune injury can play an important role in the induction of AIED, at least in the earlier stage. OBJECTIVES: The purpose of this study was to develop a more suitable rat model that demonstrated closer resemblance to the pathophysiological process in AIED. METHODS: Ninety-six female Sprague-Dawley rats were divided into four groups. They were subcutaneously immunized with crude inner ear antigen/complete Freund's adjuvant (CIEAg/CFA), or intraperitoneal injection of 500 ng pertussis toxin (PT), or injection of CIEAg/CFA+PT, or phosphate-buffered saline (PBS) alone. The auditory function, histopathology of the inner ear, and autoantibodies were examined. RESULTS: Significant differences in the time course of auditory brainstem response (ABR) threshold and mean score of cellular infiltration were demonstrated in the CIEAg/CFA+PT group of animals. Missing hair cells, degeneration of the spiral ganglion cells, endolymphatic hydrops, and autoantibodies were all noted after immunization. There were no significant differences in ABR threshold or histopathology in any other group of animals.