Enhanced prostate cancer gene transfer and therapy using a novel serotype chimera cancer terminator virus (Ad.5/3-<i>CTV</i>)

Azab, Belal; Dash, Rupesh; Das, Swadesh K.; Bhutia, Sujit K.; Sarkar, Siddik; Shen, Xue‐Ning; Quinn, Bridget A.; Dent, Paul; Dmitriev, Igor; Wang, Xiangyang; Curiel, David T.; Pellecchia, Maurizio; Reed, John C.; Sarkar, Devanand; Fisher, Paul B.

doi:10.1002/jcp.24408

Cited by 20 publications

(44 citation statements)

References 66 publications

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“…Level of significance: *P , 0.05; **P , 0.01; ***P , 0.001. et al, 2010b;Azab et al, 2012Azab et al, , 2014. Western blotting showed similar results, with Ad.5/3-mda-7 inducing greater MDA-7/IL-24 protein expression, both with and without the addition of D-limonene compared with Ad.5-mda-7 (Fig.…”

Section: Resultssupporting

confidence: 56%

“…receptors as a means of introducing their genetic material into target cells (Bergelson et al, 1998;Pearson et al, 1999;Dash et al, 2010b;Wang et al, 2011;Azab et al, 2012Azab et al, , 2014. Ad.5-mda-7, the traditional type 5 adenovirus serotype used in our prior work, is dependent on the expression of Coxsackie and adenovirus receptors (CAR) for efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, cancer cells, including pancreatic cancer cells, often downregulate these receptors, which leads to inefficient viral infectivity (Pearson et al, 1999). Using alternate viral serotypes to create chimeric viruses can help with this issue (Dash et al, 2010b(Dash et al, , 2011Hamed et al, 2010Hamed et al, , 2013Azab et al, 2012Azab et al, , 2014. The Ad.3 serotype relies on expression of CD46 and desmoglein for viral entry into cells .…”

Section: Introductionmentioning

confidence: 99%

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Reversing Translational Suppression and Induction of Toxicity in Pancreatic Cancer Cells Using a Chemoprevention Gene Therapy Approach

et al. 2014

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Pancreatic cancer is an aggressive disease with limited therapeutic options. Melanoma differentiation-associated gene-7/ interleukin-24 (mda-7/IL-24), a potent antitumor cytokine, shows cancer-specific toxicity in a vast array of human cancers, inducing endoplasmic reticulum stress and apoptosis, toxic autophagy, an antitumor immune response, an antiangiogenic effect, and a significant "bystander" anticancer effect that leads to enhanced production of this cytokine through autocrine and paracrine loops. Unfortunately, mda-7/IL-24 application in pancreatic cancer has been restricted because of a "translational block" occurring after Ad.5-mda-7 gene delivery. Our previous research focused on developing approaches to overcome this block and increase the translation of the MDA-7/IL-24 protein, thereby promoting its subsequent toxic effects in pancreatic cancer cells. We demonstrated that inducing reactive oxygen species (ROS) after adenoviral infection of mda-7/IL-24 leads to greater translation into MDA-7/IL-24 protein and results in toxicity in pancreatic cancer cells. In this study we demonstrate that a novel chimeric serotype adenovirus, Ad.5/3-mda-7, displays greater efficacy in delivering mda-7/IL-24 compared with Ad.5-mda-7, although overall translation of the protein still remains low. We additionally show that D-limonene, a dietary monoterpene known to induce ROS, is capable of overcoming the translational block when used in combination with adenoviral gene delivery. This novel combination results in increased polysome association of mda-7/IL-24 mRNA, activation of the preinitiation complex of the translational machinery in pancreatic cancer cells, and culminates in mda-7/IL-24-mediated toxicity.

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Section: Resultssupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Reversing Translational Suppression and Induction of Toxicity in Pancreatic Cancer Cells Using a Chemoprevention Gene Therapy Approach

et al. 2014

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“…Overexpression of human MDA-7/IL-24 causes growth arrest and induces apoptosis or toxic autophagy in a variety of tumor cells including malignant gliomas (Lebedeva et al, 2002; Su et al, 2003; Yacoub et al, 2008; Yacoub et al, 2010a; Hamed et al, 2013b), melanomas (Lebedeva et al, 2002; Chada et al, 2006; Sarkar et al, 2008) and carcinomas of breast (Su et al, 1998; Sarkar et al, 2005; Chada et al, 2006; Bhutia et al, 2013; Li et al, 2013), lung (Kawabe et al, 2002; Nishikawa et al, 2004; Inoue et al, 2007; Gupta et al, 2008), ovary (Leath et al, 2004; Gopalan et al, 2005; Gopalan et al, 2007; Yacoub et al, 2010b), kidney (Park et al, 2009; Eulitt et al, 2010; Park et al, 2011; Hamed et al, 2013a), colon (Emdad et al, 2007; Lebedeva et al, 2007; Azab B, In press) and prostate (Lebedeva et al, 2003; Sarkar et al, 2007; Dash et al, 2011; Azab B, In press). Importantly, none of the normal cells tested underwent apoptosis when exposed to MDA-7/IL-24, indicating that its effects are cancer-specific (Jiang et al, 1996; Fisher, 2005; Dash et al, 2010a; Dent et al, 2010a; Dent et al, 2010b).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the canine mda-7 gene, transcripts and expression patterns

Sandey

Bird

Das

et al. 2014

Gene

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Human melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) displays potent growth suppressing and cell killing activity against a wide variety of human and rodent cancer cells. In this study, we identified a canine ortholog of the human mda-7/IL-24 gene located within a cluster of IL-10 family members on chromosome 7. The full-length mRNA sequence of canine mda-7 was determined, which encodes a 186-amino acid protein that has 66% similarity to human MDA-7/IL-24. Canine MDA-7 is constitutively expressed in cultured normal canine epidermal keratinocytes (NCEKs), and its expression levels are increased after lipopolysaccharide stimulation. In cultured NCEKs, the canine mda-7 pre-mRNA is differentially spliced, via exon skipping and alternate 5′-splice donor sites, to yield five splice variants (canine mda-7sv1, canine mda-7sv2, canine mda-7sv3, canine mda-7sv4 and canine mda-7sv5) that encode four protein isoforms of the canine MDA-7 protein. These protein isoforms have a conserved N-terminus (signal peptide sequence) and are dissimilar in amino acid sequences at their C-terminus. Canine MDA-7 is not expressed in primary canine tumor samples, and most tumor derived cancer cell lines tested, like its human counterpart. Unlike human MDA-7/IL-24, canine mda-7 mRNA is not expressed in unstimulated or lipopolysaccharide (LPS), concanavalin A (ConA) or phytohemagglutinin (PHA) stimulated canine peripheral blood mononuclear cells (PBMCs). Furthermore, in-silico analysis revealed that canonical canine MDA-7 has a potential 28 amino acid signal peptide sequence that can target it for active secretion. This data suggests that canine mda-7 is indeed an ortholog of human mda-7/IL-24, its protein product has high amino acid similarity to human MDA-7/IL-24 protein and it may possess similar biological properties to human MDA-7/IL-24, but its expression pattern is more restricted than its human ortholog.

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“…2 Gene therapy is the direct transfer of DNA or RNA into diseased cells for the purpose of therapy. [3][4][5] In our earlier study, 6 we constructed an efficient target gene delivery system mediated by the second-generation aptamer A10-3.…”

Section: Introductionmentioning

confidence: 99%

Study on the prostate cancer-targeting mechanism of aptamer-modified nanoparticles and their potential anticancer effect in vivo

Tai

Fan

et al. 2014

IJN

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Ligand-mediated prostate cancer (PCa)-targeting gene delivery is one of the focuses of research in recent years. Our previous study reported the successful preparation of aptamer-modified nanoparticles (APT-NPs) in our laboratory and demonstrated their PCa-targeting ability in vitro. However, the mechanism underlying this PCa-targeting effect and their anticancer ability in vivo have not yet been elucidated. The objective of this study was to assess the feasibility of using APT-NPs to deliver micro RNA (miRNA) systemically to PCa cells, to testify their tumor-targeting efficiency, and to observe their biodistribution after systemic administration to a xenograft mouse model of PCa. In addition, the effect of APT depletion and endocytosis inhibitors on cellular uptake was also evaluated quantitatively in LNCaP cells to explore the internalization mechanism of APT-NPs. Finally, blood chemistry, and renal and liver function parameters were measured in the xenograft mouse model of PCa to see whether APT-NPs had any demonstrable toxicity in mice in vivo. The results showed that APT-NPs prolonged the survival duration of the PCa tumor-bearing mice as compared with the unmodified NPs. In addition, they had a potential PCa-targeting effect in vivo. In conclusion, this research provides a prototype for the safe and efficient delivery of miRNA expression vectors to PCa cells, which may prove useful for preclinical and clinical studies on the treatment of PCa.

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Enhanced prostate cancer gene transfer and therapy using a novel serotype chimera cancer terminator virus (Ad.5/3-CTV)

Abstract: Few options are available for treating patients with advanced prostate cancer

Cited by 20 publications

References 66 publications

Reversing Translational Suppression and Induction of Toxicity in Pancreatic Cancer Cells Using a Chemoprevention Gene Therapy Approach

Reversing Translational Suppression and Induction of Toxicity in Pancreatic Cancer Cells Using a Chemoprevention Gene Therapy Approach

Characterization of the canine mda-7 gene, transcripts and expression patterns

Study on the prostate cancer-targeting mechanism of aptamer-modified nanoparticles and their potential anticancer effect in vivo

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Enhanced prostate cancer gene transfer and therapy using a novel serotype chimera cancer terminator virus (Ad.5/3-CTV)

Abstract: Few options are available for treating patients with advanced prostate cancer

Cited by 20 publications

References 66 publications

Reversing Translational Suppression and Induction of Toxicity in Pancreatic Cancer Cells Using a Chemoprevention Gene Therapy Approach

Reversing Translational Suppression and Induction of Toxicity in Pancreatic Cancer Cells Using a Chemoprevention Gene Therapy Approach

Characterization of the canine mda-7 gene, transcripts and expression patterns

Study on the prostate cancer-targeting mechanism&nbsp;of aptamer-modified nanoparticles and their potential anticancer effect in vivo

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Product

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Study on the prostate cancer-targeting mechanism of aptamer-modified nanoparticles and their potential anticancer effect in vivo