Cell-specific expression of the diphtheria toxin A-chain coding sequence under the control of the upstream region of the human alpha-fetoprotein gene

Murayama, Yoshihiko; Tadakuma, Takushi; Kunitomi, Michito; Kumai, Koichiro; Tsutsui, Ken; Yasuda, Tatsuji; Kitajima, Masaki

doi:10.1002/(sici)1096-9098(199903)70:3<145::aid-jso1>3.0.co;2-o

Cited by 18 publications

(6 citation statements)

References 30 publications

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“…In this study, we attempted to express HSV-tk genes in NuE cells, which are low AFPproducing liver tumor cells. 37 L nanoparticles carrying HSV-tk genes were injected into tumor-bearing rats intravenously, and growth of NuE-derived hepatic tumors in the experimental group was suppressed in conjunction with GCV administration (Figure 1c), whereas WiDrderived non-hepatic tumors showed progression during the course of the experiment (Figure 1d). The suppression of tumor-growth was strictly depending on the L nanoparticles since injection of HSV-tk/GCV without nanoparticles had no effect on tumor growth (Figure 1c).…”

Section: Discussionmentioning

confidence: 99%

Gene therapy of liver tumors with human liver-specific nanoparticles

et al. 2006

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The development of safe and efficient liver-specific gene delivery approaches offers new perspectives for the treatment of liver disease, in particular, liver cancer. We evaluated the therapeutic potential of hepatotropic nanoparticles for gene therapy of liver tumor. These nanoparticles do not contain a viral genome and display the hepatitis B virus L antigen, which is essential to confer hepatic specificity. It has not been shown whether a therapeutic effect could be obtained using L nanoparticles in a human liver tumor xenograft model. Rats bearing human hepatic (NuE) and non-hepatic tumors were injected with L nanoparticles containing a green fluorescent protein (GFP) expression plasmid. GFP expression was observed only in NuE-derived tumors but not in the nonhepatic tumor. The potential for treatment of liver tumors was analyzed using L nanoparticles containing the herpes simplex virus thymidine kinase gene, in conjunction with ganciclovir pro-drug administration. The growth of NuE-derived tumors in L particleinjected rats was significantly suppressed, but not of the non-hepatic tumor control. In summary, this is the first demonstration that nanoparticles could be used for delivery of therapeutic genes with anti-tumor activity into human liver tumors. This intravenous delivery system may be one of the major advantages as compared to many other viral vector systems.

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Section: Discussionmentioning

confidence: 99%

Gene therapy of liver tumors with human liver-specific nanoparticles

et al. 2006

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“…The α‐fetal protein gene is normally expressed in fetal liver and is transcriptionally silent in adult liver. It is also expressed in approximately 70% of hepatocellular carcinomas and, hence, the α‐fetal protein promoter has been used to target these types of tumors for expression of cytokines, such as IL‐2 30, diphtheria toxin A 31 and cytosine deaminase 32. The promoter is selective but weak compared to the non‐selective viral promoters.…”

Section: Discussionmentioning

confidence: 99%

Development and characterization of a synthetic promoter for selective expression in proliferating endothelial cells

Szymanski¹,

Anwer

Sullivan

2006

The Journal of Gene Medicine

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“…Ishikawa et al have also shown that by placing the AFP promoter/enhancer in the reverse orientation to the long terminal repeats with a retroviral construct dramatically increases both HSV- tk transgene expression and GCV-mediated cytotoxicity in a HepG2 tumour in vivo [107]. The AFP promoter has also been used to drive CD [108], IL-2 [109, 110], diphtheria toxin A [111], and interestingly, a replication-competent adenovirus has been constructed using the AFP promoter to drive an attenuated E1B gene. Systemic delivery of this virus resulted in tumour-specific regression [112].…”

Section: Tumour-specific Promotersmentioning

confidence: 99%

Transcriptional Targeting in Cancer Gene Therapy

Robson

Hirst

2003

BioMed Research International

113

104

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Cancer gene therapy has been one of the most exciting areas of therapeutic research in the past decade. In this review, we discuss strategies to restrict transcription of transgenes to tumour cells. A range of promoters which are tissue-specific, tumour-specific, or inducible by exogenous agents are presented. Transcriptional targeting should prevent normal tissue toxicities associated with other cancer treatments, such as radiation and chemotherapy. In addition, the specificity of these strategies should provide improved targeting of metastatic tumours following systemic gene delivery. Rapid progress in the ability to specifically control transgenes will allow systemic gene delivery for cancer therapy to become a real possibility in the near future.

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Cell-specific expression of the diphtheria toxin A-chain coding sequence under the control of the upstream region of the human alpha-fetoprotein gene

Cited by 18 publications

References 30 publications

Gene therapy of liver tumors with human liver-specific nanoparticles

Gene therapy of liver tumors with human liver-specific nanoparticles

Development and characterization of a synthetic promoter for selective expression in proliferating endothelial cells

Transcriptional Targeting in Cancer Gene Therapy

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