Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Hepatology International
Published in: Hepatology International 1/2013

01-03-2013 | Review Article

Adenoviral gene therapy in hepatocellular carcinoma: a review

Authors: Iván Lyra-González, Laura Esther Flores-Fong, Ignacio González-García, David Medina-Preciado, Juan Armendáriz-Borunda

Published in: Hepatology International | Issue 1/2013

Login to get access

Abstract

Background

Hepatocellular carcinoma is the third leading cause of cancer death. Single or multiple mutations in genes related to growth control, apoptosis, invasion and metastasis have been determined; so a better understanding of the molecular genetic basis of malignant transformation, tumor progression and host interaction has led to significant progress in the development of new therapeutic agents. The ability of adenovirus vectors to deliver and express genes at high yields in HCC treatment has been demonstrated and well documented over the last few years.

Objective

To overview and provide an update of what has been accomplished in the field of adenoviral gene therapy and its application in hepatocellular carcinoma treatment.

Methods

Original articles were searched using Pubmed and other medical databases to get the most representative and actual information to establish the current state of the investigation of Ad vectors in HCC.

Results

Good results have been accomplished in preclinical models using new Ad vectors and especially AAV vectors, it is important to motivate further clinical trials to corroborate all the experience obtained.

Conclusions

Ad and AAV must be considered as an opportunity to improve the quality of life and survival of HCC patients.

Literature
  1. Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin 2005;55(2):74–108PubMedView Article
  2. Gomma AI, Khan SA, Toledano MB, et al. Hepatocellular carcinoma: epidemiology, risk factors and pathogenesis. World J Gastroenterol 2008;14(27):4300–4308View Article
  3. Farazi PA, Glickman J, Jiang S, et al. Differential impact of telomere dysfunction on initiation and progression of hepatocellular carcinoma. Cancer Res 2003;63(16):5021–5027PubMed
  4. Trevisani F, Cantarini MC, Wands JR, et al. Recent advances in the natural history of hepatocellular carcinoma. Carcinogenesis 2008;29(7):1299–1305PubMedView Article
  5. Rampone B, Schiavone B, Martino A, et al. Current management strategy of hepatocelluar carcinoma. World J Gastroenterol 2009;15(26):3210–3216PubMedView Article
  6. Abou-Alfa GK, Huitzil-Melendez FD, O’Reilly EM, et al. Current management of advanced hepatocellular carcinoma. Gastrointest Cancer Res 2008;2:64–70PubMed
  7. Starley BQ, Calcagno CJ, Harrison SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology 2010;51(5):1820–3182PubMedView Article
  8. Elmberg M, Hultcrantz R, Ekbom A, et al. Cancer risk in patients with hereditary hemochromatosis and in their first-degree relatives. Gastroenterology 2003;125:1733–1742PubMedView Article
  9. Hsing AW, McLaughlin JK, Olsen HJ, et al. Cancer risk following primary hemochromatosis: a population-based cohort study in Denmark. Int J Cancer 1995;60:160–162PubMedView Article
  10. Fracanzani AL, Conte D, Fraquelli M, et al. Increased cancer risk in a cohort of 230 patients with hereditary hemochromatosis in comparison to matched control patients with non-iron-related chronic liver disease. Hepatology 2001;33:647–651PubMedView Article
  11. Nussbaum T, Samarin J, Ehemann V, et al. Autocrine insulin-like growth factor-II stimulation of tumor cell migration is a progression step in human hepatocarcinogenesis. Hepatology 2008;48(1):146–156PubMedView Article
  12. Adami HO, Chow WH, Nyren O, et al. Excess risk of primary liver cancer in patients with diabetes mellitus. J Natl Cancer Inst 1996;88(20):1472–1477PubMedView Article
  13. Donato F, Tagger A, Gelatti U, et al. Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am J Epidemiol 2002;155:323–331PubMedView Article
  14. Hsiao PC, Chen MK, Su SC, et al. Hypoxia inducible factor-1alpha gene polymorphism G1790A and its interaction with tobacco and alcohol consumptions increase susceptibility to hepatocellular carcinoma. J Surg Oncol 2010;102(2):163–169PubMedView Article
  15. Maheshwari S, Sarraj A, Kramer J, et al. Oral contraception and the risk of hepatocellular carcinoma. J Hepatol 2007;47(4):506–513PubMedView Article
  16. Wu HC, Wang Q, Yang HI, et al. Aflatoxin B1 exposure, hepatitis B virus infection, and hepatocellular carcinoma in Taiwan. Cancer Epidemiol Biomarkers Prev 2009;18(3):846–853PubMedView Article
  17. Mondragon-Sanchez R, Gomez-Gomez E, Martinez-Gonzalez MN. Hepatocarcinoma: Algoritmo de conducta terapéutica. Rev Gastroenterol Mex 2004;69(3):155–159PubMed
  18. Ryder SD. Guidelines for the diagnosis and treatment of hepatocellular carcinoma (HCC) in adults. Gut 2003;52(3):1–8View Article
  19. Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 2005;42(5):1208–1236PubMedView Article
  20. Aljabiri MR, Lodato F, Burroughs AK. Surveillance and diagnosis for hepatocellular carcinoma. Liver Transpl 2007;13(11 suppl 2):s2–12PubMedView Article
  21. Voiculescu M, Winkler RE, Moscovici M, et al. Chemotherapies and targeted therapies in advanced hepatocellular carcinoma: from laboratory to clinic. J Gastrointest Liver Dis 2008;17(3):315–322
  22. Yau T, Chan P, Epstein R, et al. Evolution of systemic therapy of advanced hepatocellular carcinoma. World J Gastroenterol 2008;14(42):6437–6441PubMedView Article
  23. Parikh S, Hyman D. Hepatocellular cancer: a guide for the internist. Am J Med 2007;120:194–202PubMedView Article
  24. Walzer N, Kulik LM. Hepatocellular carcinoma: latest developments. Curr Opin Gastroenterol 2008;24:312–319PubMedView Article
  25. Wang Y, Huang F, Cai H, et al. The efficacy of combination therapy using adeno-associated virus-TRIAL targeting to telomerase activity and cisplatin in a mice model of hepatocellular carcinoma. J Cancer Res Clin Oncol 2010;136:1827–1837PubMedView Article
  26. Szlosarek PW, Dalgleish AG. Potential applications of gene therapy in a patient with cancer. Drugs Aging 2000;17:121–132PubMedView Article
  27. Xu CT, Pan BR. Current status of gene therapy in gastroenterology. World J Gastroenterol 1998;4:85–89PubMed
  28. Knudson AG. Two genetic hits (more or less) to cancer. Nat Rev Cancer 2001;1:157–162PubMedView Article
  29. Lachenmayer A, Alsinet C, Chang CY, et al. Molecular approaches to treatment of hepatocellular carcinoma. Dig Liver Dis 2010;42(suppl 3):s264–s272PubMedView Article
  30. Minguez B, Tovar V, Chiang D, et al. Pathogenesis of hepatocellular carcinoma and molecular therapies. Curr Opin Gastroenterol 2009;25(3):186–194PubMedView Article
  31. Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer 2006;6:674–687PubMedView Article
  32. Thorgeirsson SS, Grisham JW. Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet 2002;31:339–346PubMedView Article
  33. Bruix J, Boix L, Sala M, et al. Focus on hepatocellular carcinoma. Cancer Cell 2004;5:215–219PubMedView Article
  34. Villanueva A, Newell P, Chiang D, et al. Genes and signaling pathways involved in the pathogenesis of HCC. Semin Liver Dis 2007;27:55–76PubMedView Article
  35. Bartel DP. MicroRNAs: genomics, biogenesis, mechanisms, and function. Cell 2004;116:281–297PubMedView Article
  36. Fabbri M, Calin GA. Epigenetics and miRNAs in human cancer. Adv Genet 2010;70:87–99PubMedView Article
  37. Viswanathan SR, Daley GQ. Lin28: a microRNA regulator with a macro role. Cell 2010;140(4):445–449PubMedView Article
  38. Elyakim E, Sitbon E, Faerman A, et al. hsa-miR-191 is a candidate oncogene target for hepatocellular carcinoma therapy. Cancer Res 2010;70(20):8077–8087PubMedView Article
  39. Kirn D, Niculescu-Duvaz I, Hallden G, et al. The emerging fields of suicide gene therapy and virotherapy. Trends Mol Med 2002;8(suppl 4):S68–S73PubMedView Article
  40. Hermiston TW, Kuhn I. Armed therapeutic viruses: strategies and challenges to arming oncolytic viruses with therapeutic genes. Cancer Gene Ther 2002;9(12):1022–1035PubMedView Article
  41. Walther W, Stein U. Therapeutic genes for cancer gene therapy. Mol Biotechnol 1999;13:21–28PubMedView Article
  42. Somia N, Verma IM. Gene therapy: trials and tribulations. Nat Rev Genet 2000;1:91–99PubMedView Article
  43. Anklesaria P. Gene therapy: a molecular approach to cancer treatment. Curr Opin Mol Ther 2000;2:426–432PubMed
  44. Pandha HS, Martin LA, Rigg AS, et al. Gene therapy: recent progress in the clinical oncology arena. Curr Opin Mol Ther 2000;2:362–375PubMed
  45. Hernandez-Alcoceba R, Sangro B, Prieto J. Gene therapy of liver cáncer. World J Gastroenterol 2006;12(38):6085–6097PubMed
  46. Rothmann T, Hengstermann A, Whitaker NJ, et al. Replication of ONYX-015, a potential anticancer adenovirus, is independent of p53 status in tumor cells. J Virol 1998;72(12):9470–9478PubMed
  47. Engelhardt JF, Ye X, Doranz B, et al. Ablation of E2 in recombinant adenoviruses improves transgene persistence and decrease inflammatory response in mouse liver. Proc Natl Acad Sci USA 1994;91(13):6196–6200PubMedView Article
  48. Crowther C, Ely A, Hornby J, et al. Efficient inhibition of hepatitis B virus replication in vivo, using polyethylene glycol-modified adenovirus vectors. Hum Gene Ther 2008;19(11):1325–1331PubMedView Article
  49. Cui Q, Jiang W, Wang Y, et al. Transfer of suppressor of cytokine signaling 3 by an oncolytic adenovirus induces potential antitumor activities in hepatocellular carcinoma. Hepatology 2008;47(1):105–112PubMedView Article
  50. Li J, Shi L, Zhang X, et al. Recombinant adenovirus IL-24-Bax promotes apoptosis of hepatocellular carcinoma cells in vitro and in vivo. Cancer Gene Ther 2010;17(11):771–779PubMedView Article
  51. Son G, Hirano T, Seki E, et al. Blockage of HGF/c-Met system by gene therapy (adenovirus-mediated NK4 gene) suppresses hepatocellular carcinoma in mice. J Hepatol 2006;45:688–695PubMedView Article
  52. Zhao J, Zhang X, Shi M, et al. TIP30 inhibits growth of HCC cell lines and inhibits HCC xenografts in mice in combination with 5-FU. Hepatology 2006;44:205–215PubMedView Article
  53. Yin C, Lin Y, Zhang X, et al. Differentiation therapy of hepatocellular carcinoma in mice with recombinant adenovirus carrying hepatocyte nuclear factor-4α gene. Hepatology 2008;48:1528–139PubMedView Article
  54. Gan Y, Gu J, Cai X, et al. Adenovirus-mediated HCCS1 overexpression elicits a potent antitumor efficacy on human colorectal cáncer and hepatoma cells both in vitro and in vivo. Cancer Gene Ther 2008;15(12):808–816PubMedView Article
  55. Song MS, Jeong JS, Ban G, et al. Validation of tissue-specific promoter-driven tumor-targeting trans-splicing ribozyme system as a multifunctional cancer gene therapy device in vivo. Cancer Gene Ther 2009;16(2):113–125PubMedView Article
  56. Iida T, Shiba H, Misawa T, et al. Adenovirus-mediated CD40L gene therapy induced both humoral and cellular immunity against rat model of hepatocellular carcinoma. Cancer Sci 2008;99:2097–2103PubMedView Article
  57. Shashkova EV, Spencer JF, Wold WSM, et al. Targeting interferon-alpha increases antitumor efficacy and reduces hepatotoxicity of E1A-mutated spread-enhanced oncolytic adenovirus. Mol Ther 2007;15(3):598–607PubMedView Article
  58. Mera H, Kawashima H, Yoshizawa T, et al. Chondromodulin-1 directly suppresses growth of human cancer cells. BMC Cancer 2009;9:166PubMedView Article
  59. Folmer Y, Schneider M, Blum HE, et al. Reversal of drug resistance of hepatocellular carcinoma cells by adenoviral delivery of anti-ABCC2 antisense constructs. Cancer Gene Ther 2007;14:875–884PubMedView Article
  60. Tian G, Liu J, Sui J. A patient with huge hepatocellular carcinoma who had a complete clinical response to p53 gene combined with chemotherapy and transcatheter arterial chemoembolization. Anticancer Drugs 2009;20:403–407PubMedView Article
  61. Hu J, Dong A, Fernandez-Ruiz V, et al. Blockade of Wnt signaling inhibits angiogenesis and tumor growth in hepatocellular carcinoma. Cancer Res 2009;69(17):6951–6959PubMedView Article
  62. Roh V, Laemmle A, Von Holzen U, et al. Dual induction of PKR with E2F-1 and IFN-alpha to enhance gene therapy against hepatocellular carcinoma. Cancer Gene Ther 2008;15(10):636–644PubMedView Article
  63. Schmitz V, Raskopf E, Gonzalez-Carmona MA, et al. Plasminogen fragment K1-5 improves survival in a murine hepatocellular carcinoma model. Gut 2007;56:271–278PubMedView Article
  64. Atorrasagasti C, Malvicini M, Aquino JB, et al. Overexpression of SPARC obliterates the in vivo tumorigenicity of human hepatocellular carcinoma cells. Int J Cancer 2010;126:2726–2740PubMed
  65. Rodríguez MM, Ryu SM, Qian C, et al. Immunotherapy of murine hepatocellular carcinoma by alpha-fetoprotein DNA vaccination combined with adenovirus-mediated chemokine and cytokine expression. Hum Gene Ther 2008;19(7):753–759PubMedView Article
  66. Boozari B, Mundt B, Woller N, et al. Antitumoural immunity by virus-mediated immunogenic apoptosis inhibits metastatic growth of hepatocellular carcinoma. Gut 2010;59:1416–1426PubMedView Article
  67. Cheng P, Li Y, Yang L, et al. Hepatitis B virus X protein (HBx) induces G2/M arrest and apoptosis through sustained activation of cyclin B1-CDK1 kinase. Oncol Rep 2009;22:1101–1107PubMed
  68. Fan R, Li X, Du W, et al. Adenoviral-mediated RNa interference targeting URG11 inhibits growth of human hepatocellular carcinoma. Int J Cancer 2011;128(12):2980–2993PubMedView Article
  69. Hsieh JL, Lee CH, Teo ML, et al. Transthyretin-driven oncolytic adenovirus suppresses tumor growth in orthotopic and ascites model of hepatocellular carcinoma. Cancer Sci 2009;100(3):537–545PubMedView Article
  70. Huang KW, Huang YC, Tai KF, et al. Dual therapeutic effects of interferon-α gene therapy in a rat hepatocellular carcinoma model with liver cirrhosis. Mol Ther 2008;16(10):1681–1687PubMedView Article
  71. Lu Q, Yu DH, Fang C, et al. Influence of E3 region on conditionally replicative adenovirus mediated cytotoxicity in hepatocellular carcinoma cells. Cancer Biol Ther 2009;8(12):1125–1132PubMedView Article
  72. Ma L, Liu J, Shen J, et al. Expression of miR-122 mediated by adenoviral vector induces apoptosis and cell cycle arrest of cancer cells. Cancer Biol Ther 2010;9(7):554–561PubMedView Article
  73. Ma SH, Chen GG, Yip J, et al. Therapeutic effect of α-fetoprotein promoter-mediated tBid and chemotherapeutic agents on orthotopic liver tumor in mice. Gene Ther 2010;17(7):905–912PubMedView Article
  74. Tian G, Liu J, Sui J, et al. Multiple hepatic arterial injections of recombinant adenovirus p53 and 5-fluorouracil after transcatheter arterial chemoembolization for unresecable hepatocellular carcinoma: a pilot phase II trial. Anticancer Drugs 2009;20:389–395PubMedView Article
  75. Xue XB, Chen K, Wang CJ, et al. Adenovirus vector expressing mda-7 selectively kills hepatocellular carcinoma cell line Hep3B. Hepatobiliary Pancreat Dis Int 2008;7:509–514PubMed
  76. Yu J, Shen B, Chu ESH, et al. Inhibitory role of peroxisome proliferator-activated receptor gamma in hepatocarcinogenesis in mice and in vitro. Hepatology 2010;51:2008–2019PubMedView Article
  77. Zhang R, Ma L, Zheng M, et al. Survivin knockdown by short hairpin RNA abrogated the growth of human hepatocellular carcinoma xenografts in nude mice. Cancer Gene Ther 2010;17:275–288PubMedView Article
  78. Sangro B, Mazzolini G, Ruiz M, et al. A phase I clinical trial of thymidine kinase-based gene therapy in advanced hepatocellular carcinoma. Cancer Gene Ther 2010;17(12):837–843PubMedView Article
  79. Yang X, Zhu H, Hu Z. Dendritic cells transduced with TEM8 recombinant adenovirus prevents hepatocellular carcinoma angiogenesis and inhibits cells growth. Vaccine 2010;28:7130–7135PubMedView Article
  80. Oloumi A, McPhee T, Dedhar S. Regulation of E-cadherin expression and beta-catenin/Tcf transcriptional activity by integrin-linked kinase. Biochim Biophys Acta 2004;1691:1–15PubMedView Article
  81. Ye QH, Qin LX, Forgues M, et al. Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nat Med 2003;9(4):416–423PubMedView Article
  82. Huang S, He J, Zhang X, et al. Activation of the hedgehog pathway in human hepatocellular carcinomas. Carcinogenesis 2006;27(7):1334–1340PubMedView Article
  83. Tanaka S, Mori M, Sakamoto Y, et al. Biologic significance of angiopoietin-2 expression in human hepatocellular carcinoma. J Clin Invest 1999;103:341–345PubMedView Article
  84. Torimura T, Ueno T, Kin M, et al. Overexpression of angiopoietin-1 and angiopoietin-2 in hepatocellular carcinoma. J Hepatol 2004;40(5):799–807PubMedView Article
  85. De Souza AT, Hankins GR, Washington MK, et al. M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity. Nat Genet 1995;11(4):447–449PubMedView Article
  86. Cui J, Zhou X, Liu Y, et al. Wtn signaling in hepatocellular carcinoma: analysis of mutation and expression of beta-catenin, T-cell factor-4 and glycogen synthase kinase 3-beta genes. J Gastroenterol Hepatol 2003;18:280–287PubMedView Article
  87. Elmileik H, Paterson AC, Kew MC. Beta-catenin mutations and expression, 249serine p53 tumor suppressor gene mutation, and hepatitis B virus infection in southern African Blacks with hepatocellular carcinoma. J Surg Oncol 2005;91:258–263PubMedView Article
  88. Taniguchi K, Roberts LR, Aderca IN, et al. Mutational spectrum of beta-catenin, AXIN1, and AXIN2 in hepatocellular carcinomas and hepatoblastoma. Oncogene 2002;21(31):4863–4871PubMedView Article
  89. Ishizaki Y, Ikeda S, Fujimori M, et al. Immunohistochemical analysis and mutational analyses of beta-catenin, Axin family and APC genes in hepatocellular carcinomas. Int J Oncol 2004;24(5):1077–1083PubMed
  90. Samuels Y, Wang Z, Bardelli A, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science 2004;304(5670):554PubMedView Article
  91. Tanaka Y, Kanai F, Tada M, et al. Absence of PIK3CA hotspot mutations in hepatocellular carcinoma in Japanese patients. Oncogene 2006;25(20):2950–2952PubMedView Article
  92. Yeh KT, Chang JG, Chen YJ, et al. Mutation analysis of the putative tumor suppressor gene PTEN/MMAC1 in hepatocellular carcinoma. Cancer Invest 2000;18(2):123–129PubMedView Article
  93. Weihrauch M, Benicke M, Lehnert G, et al. Frequent k-ras-2 mutations and p16(INK4A) methylation in hepatocellular carcinomas in workers exposed to vinyl chloride. Br J Cancer 2001;84:982–989PubMedView Article
  94. Anzola M, Sainz A, Cuevas N, et al. High levels of p53 protein expression do not correlate with p53 mutations in hepatocellular carcinoma. J Viral Hepat 2004;11:502–510PubMedView Article
  95. Farazi PA, Glickman J, Horner J, et al. Cooperative interactions of p53 mutation, telomere dysfunction, and chronic liver damage in hepatocellular carcinoma progression. Cancer Res 2006;66:4766–4773PubMedView Article
  96. Maeta Y, Shiota G, Okano J, et al. Effect of promoter methylation of the p16 gene on phosphorylation of retinoblastoma gene product and growth of hepatocellular carcinoma cells. Tumour Biol 2005;26:300–305PubMedView Article
  97. Chaubert P, Gayer R, Zimmermann A, et al. Germ-line mutations of the p16INK4(MTS1) gene occur in a subset of patients with hepatocellular carcinoma. Hepatology 1997;25(6):1376–1381PubMedView Article
  98. Azechi H, Nishida N, Fukuda Y, et al. Disruption of the p16/cyclin D1/retinoblastoma protein pathway in the majority of human hepatocellular carcinoma. Oncology 2001;60(4):346–354PubMedView Article
  99. Huang J, Sheng HH, Shen T, et al. Correlation between genomic DNA copy number alterations and transcriptional expression in hepatitis B virus-associated hepatocellular carcinoma. FEBS Lett 2006;580(15):3571–3581PubMedView Article
  100. Marchio A, Meddeb M, Pineau P, et al. Recurrent chromosomal abnormalities in hepatocellular carcinoma detected by comparative genomic hybridization. Genes Chromosomes Cancer 1997;18(1):59–65PubMedView Article
  101. Pang A, Ng IO, Fan ST, et al. Clinicopathologic significance of genetic alterations in hepatocellular carcinoma. Cancer Genet Cytogenet 2003;146:8–15PubMedView Article
  102. Hanafusa T, Yumoto Y, Nouso K, et al. Reduced expression of insulin-like growth factor binding protein-3 and its promoter hypermethylation in human hepatocellular carcinoma. Cancer Lett 2002;176(2):149–158PubMedView Article
  103. Calvisi DF, Ladu S, Gorden A, et al. Ubiquitous activation of Ras and Jak/Stat pathways in human HCC. Gastroenterology 2006;130:1117–1128PubMedView Article
  104. Shih YL, Shyu RY, Hsieh CB, et al. Promoter methylation of the secreted frizzled-related protein 1 gene SFRP1 is frequent in hepatocellular carcinoma. Cancer 2006;107(3):579–590PubMedView Article
  105. Fukai K, Yokosuka O, Imazeki F, et al. Methylation status of p14ARF, p15INK4b, and p16INK4a genes in human hepatocellular carcinoma. Liver Int 2005;25(6):1209–1216PubMedView Article
  106. Prangue W, Breuhahn K, Fischer F, et al. Beta-catenin accumulation in the progression of human hepatocarcinogenesis correlates with loss of E-cadherin and accumulation of p53, but not with expression of conventional WNT-1 target genes. J Pathol 2003;201(2):250–259View Article
  107. Ogata H, Kobayashi T, Chinen T, et al. Deletion of the SOCS3 gene in liver parenchymal cells promotes hepatitis-induces hepatocarcinogenesis. Gastroenterology 2006;131(1):179–193PubMedView Article
  108. Nagao K, Tomimatsu M, Endo H, et al. Telomerase reverse transcriptase mRNA expression and telomerase activity in hepatocellular carcinoma. J Gastroenterol 1999;34:83–87PubMedView Article
  109. Seiler MP, Cerullo V, Lee B. Immune response to helper dependent adenoviral mediated liver gene therapy: challenges and prospects. Curr Gene Ther 2007;7:297–305PubMedView Article
  110. Flotte TR. Gene therapy: the first two decades and the current state-of-the-art. J Cell Physiol 2007;213:301–315PubMedView Article
  111. Nayak S, Herzog RW. Progress and prospects: immune responses to viral vectors. Gene Ther 2010;17:295–304PubMedView Article
  112. Sobrevals L, Enguita M, Rodriguez C, et al. AAV vectors transduce hepatocytes in vivo as efficiently in cirrhotic as in healthy rat livers. Gene Ther 2012;19(4):411–417
  113. Jacobs F, Wisse E, De Geest B. The role of liver sinusoidal cells in hepatocyte-directed gene transfer. Am J Pathol 2010;176:14–21PubMedView Article
  114. Brunetti-Pierri N, Stapleton GE, Palmer DJ, et al. Pseudo-hydrodynamic delivery of helper-dependent adenoviral vectors into non-human primates for liver-directed gene therapy. Mol Ther 2007;15:732–740PubMed
  115. Donsante A, Miller DG, Li Y, et al. AAV vector integration sites in mouse hepatocellular carcinoma. Science 2007;317:477PubMedView Article
  116. Daya S, Berns KI. Gene therapy using adeno-associated virus vectors. Clin Microbiol Rev 2008;21:583–593PubMedView Article
  117. Zaiss AK, Muruve DA. Immunity to adeno-associated virus vectors in animals and humans: a continued challenge. Gene Ther 2008;15:808–816PubMedView Article
  118. Lee K, Yun YG, Kim YG, et al. Adeno-associated virus-mediated expression of apoliprotein (a) kringles suppresses hepatocellular carcinoma growth in mice. Hepatology 2006;43:1063–1073PubMedView Article
  119. Shen Z, Wong OG, Yao RY, et al. A novel and effective hepatocyte growth factor kringle 1 domain and p53 cocktail viral gene therapy for the treatment of hepatocellular carcinoma. Cancer Lett 2008;272:168–276View Article
  120. Tse LY, Sun X, Jiang H, et al. Adeno-associated virus-mediated expression of kallistatin suppresses local and remote hepatocellular carcinomas. J Gene Med 2008;10:508–517PubMedView Article
  121. Wang Y, Huang F, Cai H, et al. The efficacy of combination therapy using adeno-associated virus-TRIAL targeting to telomerase activity and cisplatin in a mice model of hepatocellular carcinoma. J Cancer Res Clin Oncol 2010;136:1827–1837PubMedView Article
  122. Mueller C, Flotte TR. Clinical gene therapy using recombinant adeno-associated virus vectors. Gene Ther 2008;15:858–863PubMedView Article
Metadata
Title
Adenoviral gene therapy in hepatocellular carcinoma: a review
Authors
Iván Lyra-González
Laura Esther Flores-Fong
Ignacio González-García
David Medina-Preciado
Juan Armendáriz-Borunda
Publication date
01-03-2013
Publisher
Springer-Verlag
Published in
Hepatology International / Issue 1/2013
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-012-9367-2

Other articles of this Issue 1/2013

Hepatology International 1/2013 Go to the issue

Original Article

A comparison of clevudine and entecavir for treatment-naïve patients with chronic hepatitis B: results after 2 years of treatment

Original Article

Obesity, type 2 diabetes, age, and female gender: significant risk factors in the development of alcoholic liver cirrhosis

Editorial

Are we ready to use the hepatitis B surface antigen level to guide peginterferon treatment in HBeAg-negative chronic hepatitis B?

Original Article

The safety and efficacy of peginterferon plus ribavirin in hepatitis C patients concomitant with malignancy other than hepatocellular carcinoma: a multicenter study

Review Article

Recently introduced biomarkers for screening of hepatocellular carcinoma: a systematic review and meta-analysis

Original Article

Short- and long-term clinical outcome after balloon-occluded retrograde transvenous obliteration: is pretreatment portal flow direction a predictive factor?

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits