Retrovirus-mediated transfer of prothymosin gene inhibits tumor growth and prolongs survival in murine bladder cancer

Shiau, Ai‐Li; Lin, Pey-Ru; Chang, Meng-Yao; Wu, Chao‐Liang

doi:10.1038/sj.gt.3301568

Cited by 14 publications

(13 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…‫,ء‬ p Ͻ 0.05; ‫,ءء‬ p Ͻ 0.01. of synovial fibroblasts. This result is in agreement with our earlier reports showing the abrogation of growth-promoting activity of ProT by deleting its NLS (27). In the rat CIA model, NLS-deleted ProT gene transfer ameliorated the clinical course of CIA.…”

Section: Figuresupporting

confidence: 93%

“…We have shown previously that NIH3T3 cells overexpressing ProT increase the proliferative activity by shortening the duration of the G 1 phase (9). We have also reported that cell growth is enhanced in ProT gene-transduced mouse bladder cancer cells, and that such growth-promoting activity of ProT can be abolished if its NLS is deleted (27). In this study, we found that the lining layer of synovial tissue from patients with RA expressed ProT.…”

Section: Discussionsupporting

confidence: 63%

“…Whereas AdProT encoding wild-type ProT enhanced synovial fibroblast proliferation in a dose-dependent manner, AdProT⌬NLS, like AdLacZ, had no effects on cell proliferation ( Fig. 2A), confirming the abolishment of the growthpromoting potential of ProT lacking the NLS (27). The facts that macrophages play an important role in the elaboration of chemotactic cytokines in RA and MIP-1␣ plays a role in the selective recruitment of macrophages in synovial inflammation associated with RA prompted us to investigate whether AdProT⌬NLS downregulated the MIP-1␣ promoter activity.…”

Section: Biological Behaviors Of Adprot⌬nls-treated Synovial Fibroblastsmentioning

confidence: 67%

“…Two adenoviral vectors, AdProT encoding wild-type ProT and AdProT⌬NLS encoding NLS-deleted ProT (27), were generated, as previously described (28). AdLacZ, an adenoviral vector encoding ␤-galactosidase, was also used as the control vector.…”

Section: Generation Of Adenoviral Vectorsmentioning

confidence: 99%

See 3 more Smart Citations

Prothymosin α Lacking the Nuclear Localization Signal as an Effective Gene Therapeutic Strategy in Collagen-Induced Arthritis

Shiau¹,

Chen²,

Chang³

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

Prothymosin α (ProT) is regulated by c-Myc, an oncoprotein overexpressed in synovium of rheumatoid arthritis, and is associated with cell proliferation. However, ProT also exerts immunomodulatory activities. The growth-promoting activity of ProT can be abolished by deleting its nuclear localization signal (NLS). In this study, we showed that AdProTΔNLS, an adenoviral vector encoding ProT lacking the NLS, did not enhance the proliferation of synovial fibroblasts. AdProTΔNLS treatment abolished the up-regulation of the MIP-1α promoter activity induced by TNF-α in synovial fibroblasts. AdProTΔNLS suppressed macrophage chemotaxis and reduced macrophage infiltration into the ankle joints in rats with collagen-induced arthritis (CIA). Neutralization test confirmed the involvement of MIP-1α in macrophage chemotaxis. Administration of AdProTΔNLS reduced the severity of CIA in the clinical, radiographic, and histological aspects. The levels of TNF-α (mean ± SEM, 1261.9 ± 107.9 vs 2880.1 ± 561.4 pg/mg total protein; p < 0.05), IL-1β (56.8 ± 8.0 vs 109.2 ± 4.9 pg/mg total protein; p < 0.01), and MIP-1α (41.7 ± 3.6 vs 55.2 ± 1.1 pg/mg total protein; p < 0.05) in the ankle joints were lower in the AdProTΔNLS-treated rats with CIA than those in their control counterparts. In the AdProTΔNLS-treated ankle joints, matrix metalloproteinase-9 expression was decreased by 40% and infiltrating macrophages reduced by 50%. Our results demonstrate that intra-articular delivery of AdProTΔNLS significantly ameliorated the clinical course of CIA in rats. This study is the first to suggest that ProT lacking the NLS may have therapeutic potential for the management of rheumatoid arthritis.

show abstract

Section: Figuresupporting

confidence: 93%

Section: Discussionsupporting

confidence: 63%

Section: Biological Behaviors Of Adprot⌬nls-treated Synovial Fibroblastsmentioning

confidence: 67%

Section: Generation Of Adenoviral Vectorsmentioning

confidence: 99%

See 2 more Smart Citations

Prothymosin α Lacking the Nuclear Localization Signal as an Effective Gene Therapeutic Strategy in Collagen-Induced Arthritis

Shiau¹,

Chen²,

Chang³

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…We next produced an rAAV/ProT vector expressing ProT by using the PS virus system and tested its ability to mediate gene transfer. ProT, a putative thymic hormone, has been shown to exert antitumor effects on murine bladder cancer when delivered by retroviral vectors (32). Expression of the ProT protein was detected in rAAV/ProT-infected NIH 3T3 cells by immunohistochemistry at 72 h postinfection (Fig.…”

Section: Generation Of Recombinant Packaging-helper Prvmentioning

confidence: 95%

Novel Strategy for Generation and Titration of Recombinant Adeno-Associated Virus Vectors

Shiau

Liu

2005

J Virol

View full text Add to dashboard Cite

Recombinant adeno-associated virus (rAAV) vectors have many advantages for gene therapeutic applications compared with other vector systems. Several methods that use plasmids or helper viruses have been reported for the generation of rAAV vectors. Unfortunately, the preparation of large-scale rAAV stocks is labor-intensive. Moreover, the biological titration of rAAV is still difficult, which may limit its preclinical and clinical applications. For this study, we developed a novel strategy to generate and biologically titrate rAAV vectors. A recombinant pseudorabies virus (PrV) with defects in its gD, gE, and thymidine kinase genes was engineered to express the AAV rep and cap genes, yielding PS virus, which served as a packaging and helper virus for the generation of rAAV vectors. PS virus was useful not only for generating high-titer rAAV vectors by cotransfection with an rAAV vector plasmid, but also for amplifying rAAV stocks. Notably, the biological titration of rAAV vectors was also feasible when cells were coinfected with rAAV and PS virus. Based on this strategy, we produced an rAAV that expresses prothymosin ␣ (ProT). Expression of the ProT protein in vitro and in vivo mediated by rAAV/ProT gene transfer was detected by immunohistochemistry and a bioassay. Taken together, our results demonstrate that the PrV vector-based system is useful for generating rAAV vectors carrying various transgenes.

show abstract

Viral vector‐based cancer treatment and current clinical applications

Xie,

Han,

Liu

et al. 2023

MedComm – Oncology

View full text Add to dashboard Cite

Owing to the limitations of conventional cancer therapies, including chemotherapy, radiotherapy, and surgery, gene therapy has become a prominent strategy for cancer treatment over the past few decades. Gene therapy is a medical approach for targeting and destroying cancer cells by delivering exogenous genes into the target cancerous cells or surrounding tissues. However, successful delivery of foreign genes into target cells and tissues remains a key issue in such therapy. Efficient gene delivery systems would undoubtedly be important for improving the medical outcomes of gene therapy. With genetic modifications, viral vectors can target specific cells with high gene transduction efficiency, thus, the use of viral vectors is a promising technology for improving foreign gene delivery. Currently, four viral vectors—adenovirus, adeno‐associated virus, herpes simplex virus, and retrovirus—are dominantly being investigated and used in preclinical and clinical trials. In this review, we provide an overview of the mechanisms and latest applications of the four above‐mentioned viral vectors, and summarize the current development of several other viral vectors. In addition, we discuss the challenges and provide insights into future development of viral vectors in cancer treatment.

show abstract

Retrovirus-mediated transfer of prothymosin gene inhibits tumor growth and prolongs survival in murine bladder cancer

Abstract: To explore the potential use of prothymosin α(ProT) ,

Cited by 14 publications

References 22 publications

Prothymosin α Lacking the Nuclear Localization Signal as an Effective Gene Therapeutic Strategy in Collagen-Induced Arthritis

Prothymosin α Lacking the Nuclear Localization Signal as an Effective Gene Therapeutic Strategy in Collagen-Induced Arthritis

Novel Strategy for Generation and Titration of Recombinant Adeno-Associated Virus Vectors

Viral vector‐based cancer treatment and current clinical applications

Contact Info

Product

Resources

About