RETRACTED ARTICLE: Oncolysis of pancreatic tumour cells by a
                γ34.5-deleted HSV-1 does not rely upon
              Ras-activation, but on the PI 3-kinase pathway

Sarinella, Federica; Calistri, Arianna; Sette, Paola; Palù, Giorgio; Parolin, Cristina

doi:10.1038/sj.gt.3302770

Cited by 25 publications

(13 citation statements)

References 30 publications

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“…OV therapy with several viruses, including adenoviruses (28,33,41), herpesviruses (17,36,52,61,71), and reoviruses (18,(29)(30), has recently shown promise in several PDA tumor models. However, there are several advantages of using VSV as an anticancer therapy.…”

mentioning

confidence: 99%

Vesicular Stomatitis Virus as an Oncolytic Agent against Pancreatic Ductal Adenocarcinoma

Murphy

Besmer

Moerdyk-Schauwecker

et al. 2012

J Virol

108

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bVesicular stomatitis virus (VSV) is a promising oncolytic agent against a variety of cancers. However, it has never been tested in any pancreatic cancer model. Pancreatic ductal adenocarcinoma (PDA) is the most common and aggressive form of pancreatic cancer. In this study, the oncolytic potentials of several VSV variants were analyzed in a panel of 13 clinically relevant human PDA cell lines and compared to conditionally replicative adenoviruses (CRAds), Sendai virus and respiratory syncytial virus. VSV variants showed oncolytic abilities superior to those of other viruses, and some cell lines that exhibited resistance to other viruses were successfully killed by VSV. However, PDA cells were highly heterogeneous in their susceptibility to virus-induced oncolysis, and several cell lines were resistant to all tested viruses. Resistant cells showed low levels of very early VSV RNA synthesis, indicating possible defects at initial stages of infection. In addition, unlike permissive PDA cell lines, most of the resistant cell lines were able to both produce and respond to interferon, suggesting that intact type I interferon responses contributed to their resistance phenotype. Four cell lines that varied in their permissiveness to VSV-⌬M51 and CRAd dl1520 were tested in mice, and the in vivo results closely mimicked those in vitro. While our results demonstrate that VSV is a promising oncolytic agent against PDA, further studies are needed to better understand the molecular mechanisms of resistance of some PDAs to oncolytic virotherapy.

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mentioning

confidence: 99%

Vesicular Stomatitis Virus as an Oncolytic Agent against Pancreatic Ductal Adenocarcinoma

Murphy

Besmer

Moerdyk-Schauwecker

et al. 2012

J Virol

108

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“…Thus, essentially ICP34.5 has an antagonistic role to that of PKR (Wylie et al, 2009). mtHSV and another famous ICP34.5-deleted HSV-1 strain (R3616), lacking the ICP34.5 function, cannot revert the effects of PKR activation on protein synthesis and therefore its lytic replication might be expected to be limited to tumor cells that display a Ras-activated pathway (Farassati et al, 2001;Garcin et al, 1990;Sarinella et al, 2006). How is this signaling pathway triggered?…”

Section: Discussionmentioning

confidence: 99%

Rasgrp2 regulates the permissiveness of NIH3T3 cells to a herpes simplex virus 1 mutant with inactivated ICP34.5 gene

Xiao¹,

Y²,

Zhou³

et al. 2013

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Summary. -We have previously reported that mtHSV, a herpes simplex virus 1 (HSV-1) mutant with an inactivated gene for β-galactosidase, can efficiently lyse tumor but not normal cells. However, the mechanism of this selective oncolytic activity is so far unclear. In this study, using the phage display screening we identified the cellular protein binding to HSV-1 mutant (mtHSV) as (Ras guanyl releasing protein 2) Rasgrp2 which regulates the Ras signaling pathway. Rasgrp2 was found to bind directly to purified mtHSV as well as to mtHSV present within infected HeLa cells where it aggregated on the cell membrane. NIH3T3 cells were found nonpermissive to mtHSV but they became permissive following transformation with the Rasgrp2 gene. This effect was linked to the activation of the Ras-PKR signaling pathway. These observations indicate a key role of Rasgrp2 in the mtHSV infection of NIH3T3 cells and are important for the potential use of mtHSV in cancer therapy.Keywords: herpes simplex virus 1 mutant; RAS guanyl releasing protein 2; NIH3T3 cells; permissiveness * Corresponding author. E-mail: qiyipeng@whu.edu.cn; phone: +86-27-68754131. Abbreviations: β-gal = β-galactosidase; HSV-1 = herpes simplex virus 1; MBP = maltose-binding protein; mtHSV = HSV-1 mutant; PKR = dsRNA-activated protein kinase R; Rasgrp2 = RAS guanyl releasing protein 2; siFTa = siRNA against farnesyltransferase

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“…HSV-1 protein encoded by the g 1 34.5 gene is involved in neurovirulence. It also counteracts the doublestranded RNA dependant kinase (PKR)-mediated inhibition of RNA translation, which can also be achieved by overactivation of the Ras pathway in tumor cells [42].…”

Section: Replication-attenuated Hsv Mutantsmentioning

confidence: 99%

Medical application of herpes simplex virus

Watanabe

2010

Journal of Dermatological Science

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RETRACTED ARTICLE: Oncolysis of pancreatic tumour cells by a γ34.5-deleted HSV-1 does not rely upon Ras-activation, but on the PI 3-kinase pathway

Cited by 25 publications

References 30 publications

Vesicular Stomatitis Virus as an Oncolytic Agent against Pancreatic Ductal Adenocarcinoma

Vesicular Stomatitis Virus as an Oncolytic Agent against Pancreatic Ductal Adenocarcinoma

Rasgrp2 regulates the permissiveness of NIH3T3 cells to a herpes simplex virus 1 mutant with inactivated ICP34.5 gene

Medical application of herpes simplex virus

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