Increased invasion of malignant gliomas after 15-LO-1 and HSV-tk/ganciclovir combination gene therapy

Pacholska, Agnieszka; Wirth, Thomas; Samaranayake, Haritha; Pikkarainen, Jere T.; Ahmad, Fadzil; Ylä‐Herttuala, Seppo

doi:10.1038/cgt.2012.76

Cited by 6 publications

(6 citation statements)

References 25 publications

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“…Therapeutic delivery of a lipoxygenase in a therapeutic context is a new approach. In recent studies, gene transfer of lipoxygenase 15-1 was used for inhibition of angiogenesis in different setting [ 27 , 28 ]. We expect that genetic transfer of AmbLOXe as an inducer of cellular growth is an important option for future therapeutic approaches, especially in the context of nerve regeneration.…”

Section: Discussionmentioning

confidence: 99%

Successful nucleofection of rat adipose-derived stroma cells with Ambystoma mexicanum epidermal lipoxygenase (AmbLOXe)

et al. 2014

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IntroductionAdipose-derived stroma cells (ASCs) are attractive cells for cell-based gene therapy but are generally difficult to transfect. Nucleofection has proven to be an efficient method for transfection of primary cells. Therefore, we used this technique to transfect ASCs with a vector encoding for Ambystoma mexicanum epidermal lipoxygenase (AmbLOXe) which is a promising bioactive enzyme in regenerative processes. Thereby, we thought to even further increase the large regenerative potential of the ASCs.MethodsASCs were isolated from the inguinal fat pad of Lewis rats and were subsequently transfected in passage 1 using Nucleofector® 2b and the hMSC Nucleofector kit. Transfection efficiency was determined measuring co-transfected green fluorescent protein (GFP) in a flow cytometer and gene expression in transfected cells was detected by reverse transcription polymerase chain reaction (RT-PCR). Moreover, cell migration was assessed using a scratch assay and results were tested for statistical significance with ANOVA followed by Bonferroni’s post hoc test.ResultsHigh initial transfection rates were achieved with an average of 79.8 ± 2.82% of GFP positive cells although longer cultivation periods reduced the number of positive cells to below 5% after four passages. Although successful production of AmbLOXe transcript could be proven the gene product had no measureable effect on cell migration.ConclusionsOur study demonstrates the feasibility of ASCs to serve as a vehicle of AmbLOXe transport for gene therapeutic purposes in regenerative medicine. One potential field of applications could be peripheral nerve injuries.

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Section: Discussionmentioning

confidence: 99%

Successful nucleofection of rat adipose-derived stroma cells with Ambystoma mexicanum epidermal lipoxygenase (AmbLOXe)

et al. 2014

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“…In order to overcome this problem, scientists have created certain vectors such as engineered adenoviral vectors and cationic liposomes (14,15). However, some vectors are not able to be expressed in various types of human cancer (31). In the present study, the pAV-murine cytomegalovirus-GFP-3FLAG vector was used to transport the therapeutic genes.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, the pAV-murine cytomegalovirus-GFP-3FLAG vector was used to transport the therapeutic genes. A previous study indicated that NIS expression is primarily controlled by the thyroid-selective transcription factors paired box gene 8 (Pax-8) and NK2 homeobox 1 (Nkx2.1) in thyroid cancer (31). Pax-8 and Nkx2.1 target the NIS upstream enhancer through the cardiac homeobox transcription factor Nkx2 (16,32).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effects of adenovirus‑mediated CD and NIS expression combined with Na131I/5‑FC on human thyroid cancer

et al. 2017

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Abstract. Thyroid cancer is the most common type of malignant endocrine tumor diagnosed. Previous studies have indicated that gene therapy is the most promising and effective therapeutic method for thyroid cancer. Therefore, in the present study, Na 131 I/5-fluorocytosine (5-FC) treatment was combined with cytosine deaminase (CD, encoded by the CDA gene) and sodium iodide symporter (NIS, encoded by the SLC5A5 gene) to act together as a therapeutic tool for thyroid cancer. The present study explored the combined cytotoxic effects of adenovirus-mediated CD and NIS under the control of the progression elevated gene-3 (PEG-3) promoter (Ad-PEG-3-CD-NIS) with Na 131 I/5-FC against the human thyroid cancer TT cell line in vitro. The PEG-3 fragment was obtained by polymerase chain reaction (PCR) using rat genomic DNA as the template, and then Ad-PEG-3-CDA-SLC5A5 was constructed using XbaI. TT cells were transfected by recombinant adenovirus. The method of reverse transcription-quantitative PCR was performed to test the expression of CD and NIS at the level of transcription. The morphological change was assessed by fluorescence microscopy and investigated by western blot analysis. An MTT assay was used to determine the number of living cells inhibited by single or combination therapies on TT cells. The results indicated that the PEG-3 was successfully cloned, and was also positively regulated in 293 cells. CDA and SLC5A5 genes were highly expressed in TT cells. Na 131 I combined with 5-FC significantly decreased the human thyroid cancer cells. In conclusion, combination therapy of Ad-PEG3-CDA-SLC5A5 and Na 131 I/5-FC induces significantly more apoptotic characteristics than either single treatment with Ad-PEG-3-CDA-SLC5A5 or Na 131 I/5-FC, and low doses of Ad-PEG-3-CDA-SLC5A5 enhanced the cytotoxic effects.

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“…HSV vectors have been developed for human gene therapy of brain tumors, such as glioblastoma multiforme, and for conditions such as chronic pain (37)(38)(39)(40)(41)(42)(43)(44). The greatest number of trials have been done for malignant brain tumors, where HSV vectors have been used to deliver prodrug-activating enzymes, resulting in so-called "suicide gene" therapy and in some cases resulting in the release of tumor-specific antigens at a locus at which inflammation was triggered by the viral components of the vector (45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55).…”

Section: Herpesvirus Vectorsmentioning

confidence: 99%

The rapidly evolving state of gene therapy

Gruntman

Flotte

2018

FASEB j.

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Gene therapy is emerging as a viable option for clinical therapy of monogenic disorders and other genetically defined diseases, with approved gene therapies available in Europe and newly approved gene therapies in the United States. In the past 10 years, gene therapy has moved from a distant possibility, even in the minds of much of the scientific community, to being widely realized as a valuable therapeutic tool with wide‐ranging potential. The U.S. Food and Drug Administration has recently approved Luxturna (Spark Therapeutics Inc, Philadelphia, PA, USA), a recombinant adeno‐associated virus (rAAV) 2 gene therapy for one type of Leber congenital amaurosis 2 (1, 2). The European Medicines Agency (EMA) has approved 3 recombinant viral vector products: Glybera (UniQure, Amsterdam, The Netherlands), an rAAV vector for lipoprotein lipase deficiency; Strimvelis (Glaxo Smith‐Kline, Brentford, United Kingdom), an ex vivo gammaretrovirus‐based therapy for patients with adenosine deaminase‐deficient severe combined immune deficiency (ADA‐SCID); and Kymriah (Novartis, Basel, Switzerland), an ex vivo lentivirus‐based therapy to engineer autologous chimeric antigen‐receptor T (CAR‐T) cells targeting CD19–positive cells in acute lymphoblastic leukemia. These examples will be followed by the clinical approval of other gene therapy products as this field matures. In this review we provide an overview of the state of gene therapy by discussing where the field stands with respect to the different gene therapy vector platforms and the types of therapies that are available.— Gruntman, A. M., Flotte, T. R. The rapidly evolving state of gene therapy. FASEB J. 32, 1733–1740 (2018). http://www.fasebj.org

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Increased invasion of malignant gliomas after 15-LO-1 and HSV-tk/ganciclovir combination gene therapy

Cited by 6 publications

References 25 publications

Successful nucleofection of rat adipose-derived stroma cells with Ambystoma mexicanum epidermal lipoxygenase (AmbLOXe)

Successful nucleofection of rat adipose-derived stroma cells with Ambystoma mexicanum epidermal lipoxygenase (AmbLOXe)

Therapeutic effects of adenovirus‑mediated CD and NIS expression combined with Na131I/5‑FC on human thyroid cancer

The rapidly evolving state of gene therapy

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