VP22 and cytosine deaminase fusion gene modified tissue-engineered neural stem cells for glioma therapy

Jin, Guishan; Zhou, Yiqiang; Chai, Qiang; Zhu, Gui‐Dong; Xu, Fu‐Jian; Liu, Fusheng

doi:10.1007/s00432-012-1347-3

Cited by 10 publications

(11 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, there was no significant difference in tumor volumes or lifespans between the two experimental groups, indicating the absence of any substantial effect of fused VP22 protein. This result contradicts the existing data showing a substantial increase in therapy efficiency upon fusion of CDA with VP22 . This may be the result of a high CDA expression level ensured by transient expression plasmid (compared to virus vectors).…”

Section: Discussioncontrasting

confidence: 83%

“…One approach is to improve the level of gene expression, by increasing the expression of therapeutic genes, choosing different promoters or by creating the constructs with new more efficient genes . Other studies try to enhance the cytotoxicity using fusions of proteins, which provide efficient spread from the original expressing cells to numerous neighboring tumor cells, locally concentrating at the tumor site . Several studies have used an approach related to the enhancement of certain properties of MSCs; for example, the tumor tropism of MSCs by inducing the over expression of CXCR1 or pre‐exposure of MSCs to soluble factors .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Combined treatment, based on lysomustine administration with mesenchymal stem cells expressing cytosine deaminase therapy, leads to pronounced murine Lewis lung carcinoma growth inhibition

Krassikova

Karshieva

Cheglakov

et al. 2016

The Journal of Gene Medicine

View full text Add to dashboard Cite

show abstract

Section: Discussioncontrasting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Combined treatment, based on lysomustine administration with mesenchymal stem cells expressing cytosine deaminase therapy, leads to pronounced murine Lewis lung carcinoma growth inhibition

Krassikova

Karshieva

Cheglakov

et al. 2016

The Journal of Gene Medicine

View full text Add to dashboard Cite

show abstract

“…It has also been associated with interactions with cellular membranes, microtubules and nucleic acids ( Brignati et al , 2003 ; Elliott & O’Hare, 1998 ; Martin et al , 2002 ; Sciortino et al , 2002 ). Interestingly VP22 exhibits transfection potential and has been used successfully in several studies to target therapeutic DNA to specific cells of interest, such as stem cells ( Bennett et al , 2002 ; Elliott & O’Hare, 1999 ; Jin et al , 2013 ; Lai et al , 2000 ).…”

Section: Introductionmentioning

confidence: 99%

VP22 core domain from Herpes simplex virus 1 reveals a surprising structural conservation in both the Alpha- and Gammaherpesvirinae subfamilies

Hew

Dahlroth

Pan

et al. 2015

Journal of General Virology

View full text Add to dashboard Cite

The viral tegument is a layer of proteins between the herpesvirus capsid and its outer envelope. According to phylogenetic studies, only a third of these proteins are conserved amongst the three subfamilies (Alpha-, Beta- and Gammaherpesvirinae) of the family Herpesviridae. Although some of these tegument proteins have been studied in more detail, the structure and function of the majority of them are still poorly characterized. VP22 from Herpes simplex virus 1 (subfamily Alphaherpesvirinae) is a highly interacting tegument protein that has been associated with tegument assembly. We have determined the crystal structure of the conserved core domain of VP22, which reveals an elongated dimer with several potential protein–protein interaction regions and a peptide-binding site. The structure provides us with the structural basics to understand the numerous functional mutagenesis studies of VP22 found in the literature. It also establishes an unexpected structural homology to the tegument protein ORF52 from Murid herpesvirus 68 (subfamily Gammaherpesvirinae). Homologues for both VP22 and ORF52 have been identified in their respective subfamilies. Although there is no obvious sequence overlap in the two subfamilies, this structural conservation provides compelling structural evidence for shared ancestry and functional conservation.

show abstract

“…exogenous molecules into living cells. Tegument protein VP22 of herpes simplex virus type 1 (HSV-1) is a CPP that is capable of transporting heterologous proteins, such as p53, p27, cytosine deaminase, and Hsp70, across the cell membrane, thereby enhancing the biological functions of these proteins (17)(18)(19)(20). However, the mechanisms involved in the delivery of these proteins by VP22 have not been fully characterized.…”

Section: Herpes Simplex Virus Type 1 Vp22-mediated Intercellular Delimentioning

confidence: 99%

Herpes simplex virus type 1 VP22-mediated intercellular delivery of PTEN increases the antitumor activity of PTEN in esophageal squamous cell carcinoma cells in vitro and in vivo

Xia

et al. 2016

Oncology Reports

View full text Add to dashboard Cite

In the past decade, studies have revealed that the phosphatase and tensin homolog (PTEN) protein, a tumor suppressor, comprises a potential biological marker and therapeutic target for esophageal squamous cell carcinoma (ESCC). As such, the delivery of the PTEN gene represents a powerful strategy for ESCC therapy. The tegument protein VP22 of herpes simplex virus type 1 (HSV-1) has been reported to act as a transporter of heterologous proteins across the host cell membrane, thereby enhancing the biological functions of these proteins. In the present study, the intercellular delivery and antitumor activity of the fusion protein PTEN-VP22 were examined in the esophageal squamous cell carcinoma cell line Eca109 both in vitro and in vivo. VP22-mediated PTEN intercellular delivery was confirmed in the Eca109 cells by western blot analysis and by quantitation of immunofluorescence. VP22 alone did not exert antiproliferative effects or induce cell cycle arrest, induction of apoptosis, blockage of the Akt and focal adhesion kinase (FAK) pathways, tumor growth inhibition, or antiangiogenic effects in Eca109 cells. However, compared with PTEN alone, PTEN-VP22 exerted significantly higher antiproliferative effects and induced cell cycle arrest at G1 stage, apoptosis and antiangiogenic effects in Eca109 cells. Together, our findings demonstrate that VP22 alone does not exert antitumor activity directly; however, this protein mediates the intercellular delivery of PTEN and thereby increases its intracellular concentration to achieve a therapeutic steady state, leading to an overall increase in the antitumor activity of PTEN. This study provides further experimental data to confirm the potential of VP22-based intercellular delivery strategies for enhancing the efficacy of gene therapy for cancer treatment.

show abstract

VP22 and cytosine deaminase fusion gene modified tissue-engineered neural stem cells for glioma therapy

Cited by 10 publications

References 28 publications

Combined treatment, based on lysomustine administration with mesenchymal stem cells expressing cytosine deaminase therapy, leads to pronounced murine Lewis lung carcinoma growth inhibition

Combined treatment, based on lysomustine administration with mesenchymal stem cells expressing cytosine deaminase therapy, leads to pronounced murine Lewis lung carcinoma growth inhibition

VP22 core domain from Herpes simplex virus 1 reveals a surprising structural conservation in both the Alpha- and Gammaherpesvirinae subfamilies

Herpes simplex virus type 1 VP22-mediated intercellular delivery of PTEN increases the antitumor activity of PTEN in esophageal squamous cell carcinoma cells in vitro and in vivo

Contact Info

Product

Resources

About