Adenovirus-mediated REIC/Dkk-3 gene therapy: Development of an autologous cancer vaccination therapy (Review)

Watanabe, Masami; Nasu, Yasutomo; Kumon, Hiromi

doi:10.3892/ol.2013.1777

Cited by 33 publications

(51 citation statements)

References 43 publications

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“…REIC/Dkk-3 protein is a secretory protein and its overexpression in response to Ad-REIC treatment efficiently leads to endoplasmic reticulum (ER) stress-induced apoptosis in cancer cells (4). ER stress-induced apoptosis is triggered due to a failure in the folding of large amounts of REIC/Dkk-3 protein in the lumen of the ER, and the phosphorylation of JNK occurs downstream of ER stress signaling (4,5). The levels of phosphorylated JNK and c-Jun following Ad-REIC treatment in bladder cancer cells were therefore analyzed in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…The associations between CD147 expression, phosphorylation of MAPK pathway components, and the expression of c-Myc following Ad-REIC treatment was examined. In addition, since JNK-dependent signaling has been reported to be a critical step in Ad-REIC-induced cancer cell death (4,5), the phosphorylation of JNK and c-Jun was investigated. Western blotting was performed to analyze the expression levels of the indicated factors following Ad-LacZ and Ad-REIC treatment (Fig.…”

Section: Ad-reic Downregulates the Expression Of Cd147 Without Dependmentioning

confidence: 99%

“…With the expectation that the overexpression of REIC/Dkk-3 could promote anticancer effects, our group previously developed an adenovirus vector encoding the human REIC/Dkk3 gene (Ad-REIC) and demonstrated that the Ad-REIC agent induced cancer-specific apoptosis in a number of cancer cell lines (4), and the phosphorylation of c-Jun N-terminal kinase (JNK) was revealed to be an important step in inducing cancer cell apoptosis (3)(4)(5). In addition, Ad-REIC inhibits cell motility and invasion in various cancer cells; however, the molecular mechanisms underlying these multiple therapeutic effects remain unclear (4).…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of REIC/Dkk-3 suppresses the expression of CD147 and inhibits the proliferation of human bladder cancer cells

et al. 2017

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Abstract. Our group previously developed an adenoviral vector encoding the REIC/Dkk-3 gene (Ad-REIC), a tumor suppressor, for cancer gene therapy. The Ad-REIC agent induces apoptosis and inhibits invasion in a number of cancer cell lines; however, the molecular mechanisms underlying its effects remain unclear. Cluster of differentiation 147 (CD147), also known as extracellular matrix metalloproteinase inducer (EMMPRIN), is a key molecule that promotes cancer proliferation and invasion. In order to elucidate the therapeutic mechanism of Ad-REIC, its effect on the expression of CD147 in human bladder cancer KK47 cells was investigated. Treatment with Ad-REIC markedly downregulated the expression of CD147 and significantly inhibited cellular proliferation. Since the expression of CD147 is reported to be under the positive control of mitogen-activated protein kinase (MAPK) signaling and the c-Myc protein, the correlations between the expression of CD147 and the activation of MAPKs or the expression of c-Myc were examined. Unexpectedly, no positive correlation was observed between the level of CD147 and the potential regulators that were assessed, indicating that another signaling pathway is responsible for the downregulation of CD147. The results from the present study demonstrate that Ad-REIC treatment can significantly downregulate the expression of CD147 in bladder cancer cells. Downregulation of the cancer-progression factor CD147 may be a novel mechanism that underlies the therapeutic effects of Ad-REIC treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Ad-reic Downregulates the Expression Of Cd147 Without Dependmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Overexpression of REIC/Dkk-3 suppresses the expression of CD147 and inhibits the proliferation of human bladder cancer cells

et al. 2017

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“…Adenovirus, Newcastle disease virus and herpes simplex virus are the most commonly used gene therapy oncolytic viral vectors, as vectors that specifically mutate and selectively replicate faster in cancer cells (56). The Adeno-X expression system is the most commonly used and >250 patients have been treated with ONYX-015 (a replicating adenovirus) (57). In the present study, the Adeno-X expression system was used to deliver an antibody of PD-1 to assess the oncolytic effects of a recombinant virus in melanoma in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Recombinant adenovirus expressing a dendritic cell‑targeted melanoma surface antigen for tumor‑specific immunotherapy in melanoma mice model

Guo

Wang

et al. 2018

Exp Ther Med

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Abstract. Viral vectors represent a potential strategy for the treatment of human malignant tumors. Currently, recombinant adenovirus vectors are commonly used as gene therapy vehicles, as it possesses a proven safety profile in normal human cells. The recombinant adenovirus system has an ability to highly express exogenous genes and increase the stability of the carrier, which is only transiently expressed in the host cell genome, without integrating. Malignant melanoma cells are produced by the skin, and melanocyte tumors that exhibit higher malignant degrees lead to earlier transfer and higher mortality. In the present study, a recombinant adenovirus (rAd) was generated to express Anti-programmed death-1 (rAd-Anti-PD-1) and used to investigate the efficacy in melanoma cells and tumors. The results demonstrated that B16-F10 cell growth was significantly inhibited and the apoptosis incidence rate was markedly promoted following rAd-PD-1 treatment. The present study demonstrated that the production of α and β interferon was increased, which led to the induction of dendritic cell (DCs) maturation in rAd-anti-PD-1-treated mice. The present study indicated that rAd-anti-PD-1 exhibited the ability to generate more cluster of differentiation (CD)4 + CD8 + T cells and induce a PD-1-specific cytotoxic T lymphocyte through DC-targeted surface antigens in mice. This resulted in a further enhanced recognition of melanoma cells due to DCs being targeted by the rAd-anti-PD-1-encoded PD-1. Notably, mice treated with the rAd-anti-PD-1-targeted PD-1 demonstrated an improved protection compared with tumor-bearing mice from the challenge group treated with a recombinant gutless adenovirus and Anti-PD-1. In conclusion, the present study demonstrated that targeting the melanoma surface antigens via the rAd-anti-PD-1-infected tumor cells enhanced the ability of recombinant adenovirus to induce a potent tumor-inhibitory effect and antigen-specific immune response.

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“…The uracil phosphoribosyl transferase (UPRT) gene from Escherichia coli encodes uracil phosphoribosyltransferase, which converts uracil and 5-phosphoribosyl-1-R-diphosphate to uridine monophosphate (UMP). This protein is a potential target in cancer therapy, but not present in mammalian genomes when combining with UPRT (33,34).…”

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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Adenovirus-mediated REIC/Dkk-3 gene therapy: Development of an autologous cancer vaccination therapy (Review)

Cited by 33 publications

References 43 publications

Overexpression of REIC/Dkk-3 suppresses the expression of CD147 and inhibits the proliferation of human bladder cancer cells

Overexpression of REIC/Dkk-3 suppresses the expression of CD147 and inhibits the proliferation of human bladder cancer cells

Recombinant adenovirus expressing a dendritic cell‑targeted melanoma surface antigen for tumor‑specific immunotherapy in melanoma mice model

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

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