A simplified system for generating oncolytic adenovirus vector carrying one or two transgenes

Zb, Hu; Wu, Chen-Tu; Wang, H; Qw, Zhang; Wang, L; Rl, Wang; Zz, Lu; Ls, Wang

doi:10.1038/sj.cgt.7701105

Cited by 24 publications

(11 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recombinant adenoviral vector delivery is one of the most efficient and widely used approaches to introduce exogenous genes into target cells [29, 30]. By employing the AdEasy-1 technique, we successfully constructed the recombinant adenoviruses of rAd- vpr , which expresses Vpr and GFP independently, as well as the vector control, rAd-vector, which expresses GFP only.…”

Section: Resultsmentioning

confidence: 99%

Endogenous HIV-1 Vpr-mediated apoptosis and proteome alteration of human T-cell leukemia virus-1 transformed C8166 cells

Zeng

et al. 2009

Apoptosis

View full text Add to dashboard Cite

HIV-1 viral protein R (Vpr) can induce cell cycle arrest and cell death, and may be beneficial in cancer therapy to suppress malignantly proliferative cell types, such as adult T-cell leukemia (ATL) cells. In this study we examined the feasibility of employing the HIV-vpr gene, via targeted gene transfer, as a potential new therapy to kill ATL cells. We infected C8166 cells with a recombinant adenovirus carrying both vpr and GFP genes (rAd-vpr), as well as the vector control virus (rAd-vector). G2/M phase cell cycle arrest was observed in the rAd-vpr infected cells. Typical characteristics of apoptosis were detected in rAd-vpr infected cells, including sub-diploid peak exhibition in DNA content assay, the Hoechst 33342 accumulation, apoptotic body formation, mitochondrial membrane potential and plasma membrane integrity loss. The proteomic assay revealed apoptosis related protein changes, exhibiting the regulation of caspase-3 activity indicator proteins (vimentin and Rho GDP-dissociation inhibitor 2), mitochondrial protein (prohibitin) and other regulatory proteins. In addition, the up-regulation of anti-inflammatory redox protein, thioredoxin, was identified in the rAd-vpr infected group. Further supporting these findings, the increase of caspase 3&7 activity in the rAd-vpr infected group was observed. In conclusion, endogenous Vpr is able to kill HTLV-1 transformed C8166 cells, and may avoid the risks of inducing severe inflammatory responses through apoptosis-inducing and anti-inflammatory activities.

show abstract

Section: Resultsmentioning

confidence: 99%

Endogenous HIV-1 Vpr-mediated apoptosis and proteome alteration of human T-cell leukemia virus-1 transformed C8166 cells

Zeng

et al. 2009

Apoptosis

View full text Add to dashboard Cite

show abstract

“…A chemic fiber-modified and replication-deficient adenovirus-expressing SENP1, Ad5/F11p.SENP1, and control vector, Ad5/F11p.Null, were constructed as previously described [29]. Wild type SMAD4 gene and mutated SMAD4 gene with two mutations (K113R and K159R) was synthesized (AuGCT, Beijing, China), and inserted into the multiple cloning sites to generate pcDNA3.0-SMAD4 and pcDNA3.0-mutSMAD4, respectively.…”

Section: Methodsmentioning

confidence: 99%

SUMO-Specific Cysteine Protease 1 Promotes Epithelial Mesenchymal Transition of Prostate Cancer Cells via Regulating SMAD4 deSUMOylation

Zhang¹,

Wang²,

Wang³

et al. 2017

IJMS

View full text Add to dashboard Cite

In advanced prostate cancer, small ubiquitin-like modifier (SUMO)-specific cysteine protease 1 (SENP1) is up-regulated. However, the role of SENP1 in regulating deSUMOylation of TGF-β/SMADs signaling is unknown. In this study, we developed a lentiviral vector, PLKO.1-shSENP1, to silence SENP1 in prostate cancer cells with high metastatic characteristics (PC3M). Likewise, we also created an adenovirus vector, Ad5/F11p-SENP1 to over-express SENP1 in prostate cancer cells with low metastatic potential (LNCaP). We showed that silencing of SENP1 promoted cellular apoptosis, and inhibited proliferation and migration of PC3M cells. Moreover, SENP1 silencing increased the SMAD4 expression at protein level, up-regulated E-cadherin and down-regulated Vimentin expression, indicating the inhibition of epithelial mesenchymal transition (EMT). Furthermore, SMAD4 interference abolished SENP1-mediated up-regulation of E-cadherin, suggesting that SENP1 regulated E-cadherin expression via SMAD4. SENP1 over-expression in LNCaP cells reduced SMAD4 protein, and promoted EMT via decreasing E-cadherin and increasing Vimentin. Moreover, down-regulation of SMAD4 and E-cadherin were blocked, after transfection with two SUMOylation sites mutated SMAD4, suggesting that SENP1 might reduce SMAD4 levels to regulate E-cadherin expression via deSUMOylation of SMAD4. In conclusion, SENP1 deSUMOylated SMAD4 to promote EMT via up-regulating E-cadherin in prostate cancer cells. Therefore, SENP1 is a potential target for treatment of advanced prostate cancer.

show abstract

“…Because the hTERT promoter is expected to be active in the majority (~90%) of human cancer cells with upregulated telomerase expression, (6) the hTERT promoter is used to control the essential gene E1A for adenovirus replication in a series of CRAd. (7)(8)(9) Hypoxia occurs in virtually all solid tumors as they outgrow their blood supply. Hypoxia augments cellular levels of HIF, a transcription factor that regulates target genes through the binding of HRE.…”

mentioning

confidence: 99%

Potent antitumor activity of double‐regulated oncolytic adenovirus‐mediated ST13 for colorectal cancer

Zhong

Yang

et al. 2009

Cancer Science

View full text Add to dashboard Cite

Following targeted gene virotherapy, the suppression of tumorigenicity 13 (ST13) gene was inserted into the doubleregulated oncolytic adenovirus SG500 to ensure more safety and potent antitumor activity against colorectal cancer in vitro and in vivo. We generated the ST13-expressing oncolytic adenovirus SG500-ST13, with which colorectal carcinoma cell lines SW620 and HCT116, and the lung fibroblast cell line WI38, were infected. Crystal violet staining was carried out to detect the cytopathic effect in cells, and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method was used to assay cell viability. The effect of apoptosis induced by SG500-ST13 was confirmed by Hoechst staining and the TdT-mediated dUTP-biotin nick-end labeling method. To further identify the antitumor effects of SG500-ST13 on HCT116 xenografts in Balb/c nude mice, the induction of cell death was assessed by hematoxylin-eosin staining. Immunohistochemical study was also carried out. (Cancer Sci 2009; 100: 678-683) C olorectal cancer ranks second in both morbidity and mortality in developed countries. Nearly 945 000 new colorectal cancer cases are diagnosed worldwide each year and its mortality rate is approximately 492 000.(1) Despite advanced progress in technologies for diagnosis and therapy, around 50% of newly diagnosed colorectal cancer patients will die of this disease due to metastases.(2) Surgical resection or surgery coupled with systemic chemotherapy of liver metastasis is the treatment currently available for these patients.(3) These findings underscore the need for improved therapeutic approaches to more efficaciously control this aggressive type of cancer and reduce its metastatic spread.Conditional replicative adenoviruses appear to be attractive anticancer agents that are currently being evaluated in clinical trials.(4,5) CRAd exerts intrinsic anticancer activity through its selective replication in and lysis of cancer cells. In addition, release of CRAd progeny by infected tumor cells provides a potential to amplify the oncolytic effect and its lateral spread through solid tumors.One strategy to ensure tumor targeting is to place the virual essential genes under the control of tumor-specific promoters. Because the hTERT promoter is expected to be active in the majority (~90%) of human cancer cells with upregulated telomerase expression, (6) the hTERT promoter is used to control the essential gene E1A for adenovirus replication in a series of CRAd.(7-9) Hypoxia occurs in virtually all solid tumors as they outgrow their blood supply. Hypoxia augments cellular levels of HIF, a transcription factor that regulates target genes through the binding of HRE. Activation of the HIF pathway enables cancer cells to survive and proliferate in a hypoxic environment and contributes to a more aggressive phenotype.(10,11) Therefore, the HIF-HRE system of gene regulation under hypoxia, or as a result of genetic alterations during cell transformation, is particularly attractive to specifically target solid tumors. Therefore, HRE ha...

show abstract

A simplified system for generating oncolytic adenovirus vector carrying one or two transgenes

Cited by 24 publications

References 37 publications

Endogenous HIV-1 Vpr-mediated apoptosis and proteome alteration of human T-cell leukemia virus-1 transformed C8166 cells

Endogenous HIV-1 Vpr-mediated apoptosis and proteome alteration of human T-cell leukemia virus-1 transformed C8166 cells

SUMO-Specific Cysteine Protease 1 Promotes Epithelial Mesenchymal Transition of Prostate Cancer Cells via Regulating SMAD4 deSUMOylation

Potent antitumor activity of double‐regulated oncolytic adenovirus‐mediated ST13 for colorectal cancer

Contact Info

Product

Resources

About