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| 1 | Novel hepatocellular carcinoma molecules with prognostic and therapeutic potentials显示文摘Hepatocellular carcinoma(HCC), the predominant form of primary liver cancer, is the sixth most common cancer worldwide and the third leading cause of cancerrelated death. The difficulty to diagnose early cancer stages, the aggressive behaviors of HCC, and the poor effectiveness of therapeutic treatments, represent the reasons for the quite similar deaths per year and incidence number. Considering the fact that the diagnosis of HCC typically occurs in the advanced stages of the disease when the therapeutic options have only modest efficacy, the possibility to identify early diagnostic markers could be of significant benefit. So far, a large number of biomarkers have been associated to HCC progression and aggressiveness, but many of them turned out not to be of practical utility. This is the reason why active investigations are ongoing in this field. Given the huge amount of published works aimed at the identification of HCC biomarkers, in this review we mainly focused on the data published in the last year, with particular attention to the role of(1) molecular and biochemical cellular markers;(2) micro-interfering RNAs;(3) epigenetic variations; and(4) tumor stroma. It is worth mentioning that a significant number of the HCC markers described in the present review may be utilized also as targets for novel therapeutic approaches, indicating the tight relation between diagnosis and therapy. In conclusion, we believe that integrated researches among the different lines of investigation indicated above should represent the winning strategies to identify effective HCC markers and therapeutic targets. | Bruna Scaggiante Maryam Kazemi Gabriele Pozzato Barbara Dapas Rosella Farra Mario Grassi Fabrizio Zanconati Gabriele Grassi | 2014 | World Journal of Gastroenterology2014，20，5： | 13 |
| 2 | Therapeutic potential of small interfering RNAs/micro interfering RNA in hepatocellular carcinoma显示文摘Hepatocellular carcinoma(HCC) is the predominant form of primary liver cancer and represents the third leading cause of cancer-related death worldwide. Current available therapeutic approaches are poorly effective,especially for the advanced forms of the disease. In the last year,short double stranded RNA molecules termed small interfering RNAs(si RNAs) and micro interfering RNAs(mi RNA),emerged as interesting molecules with potential therapeutic value for HCC. The practical use of these molecules is however limited by the identification of optimal molecular targets and especially by the lack of effective and targeted HCC delivery systems. Here we focus our discussion on the most recent advances in the identification of si RNAs/mi RNAs molecular targets and on the development of suitable si RNA/mi RNAs delivery systems. | Rossella Farra Mario Grassi Gabriele Grassi Barbara Dapas | 2015 | World Journal of Gastroenterology2015，21，30： | 5 |
| 3 | Proliferation of human primary vascular smooth muscle cells depends on serum response factor显示文摘 | Daniela Werth Gabriele Grassi Nina Konjer Barbara Dapas Rossella Farra Carlo Giansante Reinhard Kandolf Gianfranco Guarnieri Alfred Nordheim Olaf Heidenreich | 2010 | European Journal of Cell Biology2010，，2： | 1 |
| 4 | Features of vulnerable plaques and clinical outcome of UA/NSTEMI: Relationship with matrix metalloproteinase functional polymorphisms显示文摘 | Nicola Fiotti Michèle Emilia Moretti Rossana Bussani Nicola Altamura Francesca Zamolo Riccardo Gerloni Laura Ukovich Elisa Ober Furio Silvestri Gabriele Grassi Roberto Adovasio Carlo Giansante | 2011 | Atherosclerosis2011，，1： | 1 |
| 5 | Effects of E2F1–cyclin E1–E2 circuit down regulation in hepatocellular carcinoma cells显示文摘 | Rossella Farra Barbara Dapas Gabriele Pozzato Bruna Scaggiante Francesco Agostini Cristina Zennaro Mario Grassi Natalia Rosso Carlo Giansante Nicola Fiotti Gabriele Grassi | 2011 | Digestive and Liver Disease2011，，12： | 1 |
| 6 | Bortezomib arrests the proliferation of hepatocellular carcinoma cells HepG2 and JHH6 by differentially affecting E2F1, p21 and p27 levels显示文摘 | Daniele Baiz Gabriele Pozzato Barbara Dapas Rossella Farra Bruna Scaggiante Mario Grassi Laura Uxa Carlo Giansante Cristina Zennaro Gianfranco Guarnieri Gabriele Grassi | 2008 | Biochimie2008，，3： | 1 |
| 7 | Bortezomib effect on E2F and cyclin family members in human hepatocellular carcinoma cell lines显示文摘AIM:To evaluate the effects of the proteasome inhibitor bortezomib(BZB)on E2Fs and related genes in hepatocellular carcinoma(HCC)cells.METHODS:The mRNA levels of the E2F family members(pro-proliferative:E2F1-3 and anti-proliferative:E2F4-8)and of their related genes cyclins and cyclindependent kinases(cdks)were evaluated in two HCC cell lines following a single BZB administration.mRNA levels of the epithelial-mesenchymal transition(EMT)genes were also measured in both cell lines after BZB treatment.The BZB concentration(40 nmol/L)used was chosen to stay well below the maximal amount/cm2recommended for in vivo application,and 2 d incubation was chosen as this time point has been found optimal to detect BZB effects in our previous studies.The HCC cell lines,HepG2 and JHH6,were chosen as they display different phenotypes,hepatocyte-like for HepG2and undifferentiated for JHH6,thus representing an in vitro model of low and high aggressive forms of HCC,respectively.The mRNA levels of the target genes were measured by two-color microarray-based gene expression analysis,performed according to Agilent Technologies protocol and using an Agilent Scan B.For the E2F family members,mRNA levels were quantified by realtime reverse transcription polymerase chain reaction(RT-PCR).Using small interfering RNA’s,the effects of E2F8 depletion on cell number was also evaluated.RESULTS:After BZB treatment,microarray analysis of the undifferentiated JHH6 revealed a significant decrease in the expression of the pro-proliferative E2F member E2F2.Quantitative RT-PCR data were in keeping with the microarray analysis,and showed a significant increase and decrease in E2F8 and E2F2 mRNA levels,respectively.In contrast,BZB treatment of the hepatocyte-like HCC cell line HepG2 had a significant impact on mRNA levels of 5 of the 8 E2F members.In particular,mRNA levels of the pro-proliferative E2F members E2F1,E2F2,and of the anti-proliferative member E2F8,decreased over 80%.Notably,a reduction in E2F8 expression in HepG2 and JHH6 cells following siRNA treatment had no impact on cell proliferation.As observed with JHH6,BZB treatment of HepG2cells induced a significant increase in mRNA levels of an anti-proliferative E2F member,E2F6 in this case.As was observed with E2F’s,more dramatic changes in mRNA levels of the E2F related genes cyclins and Cdks and EMT genes were observed after BZB treatment of HepG2 compared to JHH6.CONCLUSION:The differential expression of E2Fs and related genes induced by BZB in diverse HCC cell phenotypes contribute to bortezomib’s mechanism of action in hepatocellular carcinoma. | Daniele Baiz Barbara Dapas Rossella Farra Bruna Scaggiante Gabriele Pozzato Fabrizio Zanconati Nicola Fiotti Lara Consoloni Sara Chiaretti Gabriele Grassi | 2014 | World Journal of Gastroenterology2014，20，3： | 0 |
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