Enhanced growth suppression in esophageal carcinoma cells using adenovirus-mediated fusion gene transfer (uracil phosphoribosyl transferase and herpes simplex virus thymidine kinase)

Shimizu, Takanori; Shimada, Hideaki; Ochiai, Takenori; Hamada, Hirofumi

doi:10.1038/sj.cgt.7700336

Cited by 13 publications

(5 citation statements)

References 24 publications

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“…The most common gene-editing strategies to treat GC are "tumor-suppressor actions," by which an irreversible gene KO leads to cell growth inhibition or to lose metastatic ability, "suicide gene therapy," i.e., the transduction of a gene processing a non-toxic "pro-drug" into a toxic one and the "immunomodulation" by which we can potentiate the host immune response against cancer cells. Being p53 one of the master regulator of the genome integrity and resulting mutated in about 60% of gastric cancer, its replacement with a wildtype version is fascinating and in 1999, Ohashi M et al reported that such reintroduction, through AVs, led to a significant growth inhibition showing to be of clinical interest [109], while the two most common suicide gene therapies are based on the conversion of 5-fluorocytosine to 5-fluorouracil (5-FU), through expression of cytosine deaminase and the phosphorylation of ganciclovir, throughout the herpes simplex virus thymidine kinase, both used in combination with a CEA promoter to make their expression cancer-specific [110,111]. It is our opinion that currently, molecular research needs to take several steps forward to use gene therapy constantly in clinical practice, especially by uncovering specific surface molecular targets to make such therapies more selective and avoiding any off-target effects.…”

Section: Discussionmentioning

confidence: 99%

Update on gastric cancer treatments and gene therapies

Biagioni

Skalamera

Peri

et al. 2019

Cancer Metastasis Rev

146

100

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Gastric cancer is an active topic of clinical and basic research due to high morbidity and mortality. To date, gastrectomy and chemotherapy are the only therapeutic options for gastric cancer patients, but drug resistance, either acquired or primary, is the main cause for treatment failure. Differences in development and response to cancer treatments have been observed among ethnically diverse GC patient populations. In spite of major incidence, GC Asian patients have a significantly better prognosis and response to treatments than Caucasian ones due to genetic discordances between the two populations. Gene therapy could be an alternative strategy to overcome such issues and especially CRISPR/Cas9 represents one of the most intriguing gene-editing system. Thus, in this review article, we want to provide an update on the currently used therapies for the treatment of advanced GC.

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Section: Discussionmentioning

confidence: 99%

Update on gastric cancer treatments and gene therapies

Biagioni

Skalamera

Peri

et al. 2019

Cancer Metastasis Rev

146

100

View full text Add to dashboard Cite

show abstract

“…It combines complementary advantages of differential gene expression to potentiate the therapeutic effects. Certain studies have integrated 4 target genes, including B7-1 , GM-CSF , p53 and IL-2 , into a single adenoviral vector, which was imported into liver tumor cells and subsequently achieved satisfactory efficacy (19,20). Su et al (21) also evaluated the synergistic effect of the HSV-tk and IL-2 genes in a liver cancer mouse model and confirmed that joint application of the HSV-tk and IL-2 genes had an improved therapeutic efficacy over gene therapy using any of the genes alone.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic targeting of liver cancer with a recombinant DNA vaccine containing the hemagglutinin-neuraminidase gene of Newcastle disease virus via apoptotic-dependent pathways

et al. 2016

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A total of ~38.6 million mortalities occur due to liver cancer annually, worldwide. Although a variety of therapeutic methods are available, the efficacy of treatment at present is extremely limited due to an increased risk of malignancy and inherently poor prognosis of liver cancer. Gene therapy is considered a promising option, and has shown notable potential for the comprehensive therapy of liver cancer, in keeping with advances that have been made in the development of cancer molecular biology. The present study aimed to investigate the synergistic effects of the abilities of the hemagglutinin neuraminidase protein of Newcastle disease virus (NDV), the pro-apoptotic factor apoptin from chicken anaemia virus, and the interferon-γ inducer interleukin-18 (IL-18) in antagonizing liver cancer. Therefore, a recombinant DNA plasmid expressing the three exogenous genes, VP3, IL-18 and hemagglutinin neuraminidase (HN), was constructed. Flow cytometry, acridine orange/ethidium bromide staining and analysis of caspase-3 activity were performed in H22 cell lines transfected with the recombinant DNA plasmid. In addition, 6-week-old C57BL/6 mice were used to establish a H22 hepatoma-bearing mouse model. Mice tumor tissue was analyzed by immunohistochemistry and scanning electron microscopy. The results of the present study revealed that the recombinant DNA vaccine containing the VP3, IL-18 and HN genes inhibited cell proliferation and induced autophagy via the mitochondrial pathway in vivo and in vitro.

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“…AxCAUT was produced by inserting pCAUT, which contains the cDNAs of UPRT and HSV-tk with the CAG promoter, into the Swa I cloning site of pAdex1cw. The details of the vector construction have been described elsewhere [12]. AxCALacZ was produced by inserting the Escherichia coli b-galactosidase cDNA with the CAG promoter into the Swa I cloning site of the cosmid vector (pAxcwit).…”

Section: Recombinant Adenovectorsmentioning

confidence: 99%