Oncolytic Herpes Viral Therapy is Effective in the Treatment of Hepatocellular Carcinoma Cell Lines

Song, Tae Kwang; Eisenberg, David P.; Adusumilli, Prasad S.; Hezel, Michael; Fong, Yuman

doi:10.1016/j.gassur.2005.08.036

Cited by 21 publications

(9 citation statements)

References 53 publications

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“…This differential in infectivity may be attributed to the overexpression of glypican-3 (GPC3) which is a cell surface heparin sulfate proteoglycan required by the HSV-1 viruses for adsorption (43). Increasing studies have reported on the use of replication-competent HSV-1 against hepatocellular carcinoma (44,45) and hepatic metastases (46). We and others (47,48) have shown that replication-defective HSV-1 amplicon viral vectors are equally efficient in delivering genes to the cells of hepatic origin.…”

Section: Discussionmentioning

confidence: 99%

Preclinical Evaluation of Transcriptional Targeting Strategy for Human Hepatocellular Carcinoma in an Orthotopic Xenograft Mouse Model

Sia

Huynh

Chung

et al. 2013

Molecular Cancer Therapeutics

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Gene regulation of many key cell-cycle players in S-, G 2 phase, and mitosis results from transcriptional repression in their respective promoter regions during the G 0 and G 1 phases of cell cycle. Within these promoter regions are phylogenetically conserved sequences known as the cell-cycle-dependent element (CDE) and cellcycle genes homology regions (CHR) sites. Thus, we hypothesize that transcriptional regulation of cell-cycle regulation via the CDE/CHR region together with liver-specific apolipoprotein E (apoE)-hAAT promoter could bring about a selective transgene expression in proliferating human hepatocellular carcinoma. We show that the newly generated vector AH-6CC-L2C could mediate hepatocyte-targeted luciferase gene expression in tumor cells and freshly isolated short-term hepatocellular carcinoma cultures from patient biopsy. In contrast, normal murine and human hepatocytes infected with AH-6CC-L2C expressed minimal or low luciferase activities. In the presence of prodrug 5-fluorocytosine (5-FC), AH-6CC-L2C effectively suppressed the growth of orthotopic hepatocellular carcinoma patient-derived xenograft mouse model via the expression of yeast cytosine deaminase (yCD) that converts 5-FC to anticancer metabolite 5-fluoruracil. More importantly, we show that combination treatment of AH-6CC-L2C with an EZH2 inhibitor, DZNep, that targets EpCAMpositive hepatocellular carcinoma, can bring about a greater therapeutic efficacy compared with a single treatment of virus or inhibitor. Our study showed that targeting proliferating human hepatocellular carcinoma cells through the transcriptional control of therapeutic gene could represent a feasible approach against hepatocellular carcinoma.

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Section: Discussionmentioning

confidence: 99%

Preclinical Evaluation of Transcriptional Targeting Strategy for Human Hepatocellular Carcinoma in an Orthotopic Xenograft Mouse Model

Sia

Huynh

Chung

et al. 2013

Molecular Cancer Therapeutics

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“…SNU-354, SNU-739, HepG2 cell lines are not tumorigenic (15). The AFP and TGF-β1, which represent the aggressiveness of the cell lines, were determined by immunoassay from the supernatant (16)(17)(18). AFP is expressed only in HepG2 and Hep3B.…”

Section: Hcc Cell Linesmentioning

confidence: 99%

Characterization of hepatocellular carcinoma cell lines based on cell adhesion molecules

et al. 2012

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Abstract. Many studies which focus on the molecules and mechanisms related to the characteristics of the cancer have been performed. In particular, cell adhesion molecules (CAMs) are known to play a central role in the adhesion of cancer cells to vascular endothelial cells. In this study, the expression of CAMs in hepatocellular carcinoma (HCC) cell lines was analyzed and correlated with the characteristics of various HCC cell lines. Eight human HCC cell lines were used in this study. We analyzed the expression of ICAM-1, E-selectin and the integrin subunits of HCC cell lines by western blot analysis and ELISA kit. We estimated the expression of integrin-α5 using western blot analysis and RT-PCR to compare the expression at the gene level with the protein level. In addition, we determined the expression of TGF-β1, as one of the markers for the cellular activity compared to the levels of expression with the expression of integrin-α3 and -α5. ICAM-1 was highly expressed in all of the cell lines except SNU398 and Hep3B, which exhibit a more aggressive nature among the studied HCC cell lines. E-selectin and integrin subunits varied in all HCC cell lines. In particular, integrin-β2 was highly expressed on all HCC cell lines. In conclusion, the levels of expression of the CAMs may not affect cellular activity, morphology or tumorigenicity. However, most HCC cell lines show various expressions of CAMs, suggesting that HCC cell lines expressing the major CAMs remain candidates for molecular targeted therapy, which may need to be patienttailored for therapy according to the molecular profile.

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“…Sia et al, [170] used as a viral vector the HSV-1 amplicon in HCC and non-HCC cell lines in vitro and in vivo with promising results. Several other reports characterized different kinds of HSV-1 vectors as platforms for virotherapy against liver cancer [167,168,[171][172][173].…”

Section: Inhibition Of Oncogenes and Restoration Of Tumor-suppressor mentioning

confidence: 99%

Gene Therapy in Liver Diseases: State-of-the-Art and Future Perspectives

Domvri¹,

Porpodis²,

Koffa³

et al. 2012

CGT

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Gene therapy is a fundamentally novel therapeutic approach that involves introducing genetic material into target cells in order to fight or prevent disease. A number of different strategies of gene therapy are tested at experimental and clinical levels, including: a) replacing a mutated gene that causes disease with a healthy copy of the gene, b) inactivating a mutated gene that its improper function causes pathogenesis, c) introducing a new gene coding a therapeutic compound to fight a disease, d) introducing to the target organ an enzyme converting an inactive pro-drug to its cytotoxic metabolite. In gene therapy, the transcriptional machinery of the patient is used to produce the active factor that exerts the intended therapeutic effect, ideally in a permanent, tissue-specific and manageable way. The liver is a major target for gene therapy, presenting inherited metabolic defects of single-gene etiology, but also severe multifactorial pathologies with limited therapeutic options such as hepatocellular carcinoma. The initial promising results from gene therapy strategies in liver diseases were followed by skepticism on the actual clinical value due to specificity, efficacy, toxicity and immune limitations, but are recently re-evaluated due to progress in vector technology and monitoring techniques. The significant amount of experimental data along with the available information from clinical trials are systematically reviewed here and presented per pathological entity. Finally, future perspectives of gene therapy protocols in hepatology are summarized.

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Oncolytic Herpes Viral Therapy is Effective in the Treatment of Hepatocellular Carcinoma Cell Lines

Cited by 21 publications

References 53 publications

Preclinical Evaluation of Transcriptional Targeting Strategy for Human Hepatocellular Carcinoma in an Orthotopic Xenograft Mouse Model

Preclinical Evaluation of Transcriptional Targeting Strategy for Human Hepatocellular Carcinoma in an Orthotopic Xenograft Mouse Model

Characterization of hepatocellular carcinoma cell lines based on cell adhesion molecules

Gene Therapy in Liver Diseases: State-of-the-Art and Future Perspectives

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