Viability reduction and Rac1 gene downregulation of heterogeneous ex-vivo glioma acute slice infected by the oncolytic Newcastle Disease Virus strain V4UPM

Oncolytic viruses have been extensively evaluated for anticancer therapy because this virus preferentially infects cancer cells without interfering with normal cells. Newcastle Disease Virus (NDV) is an avian virus and one of the intensively studied oncolytic viruses affecting many types of cancer i...

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Main Authors: Mustafa, Zulkifli, Shamsuddin, Hilda Shazana, Ideris, Aini, Ibrahim, Rohaya, Jaafar, Hasnan, Ali, Abdul Manaf, Abdullah, Jafri Malin
Format: Article
Language:English
Published: Hindawi Publishing Corporation 2013
Online Access:http://psasir.upm.edu.my/id/eprint/29903/
http://psasir.upm.edu.my/id/eprint/29903/1/Viability%20reduction%20and%20Rac1%20gene%20downregulation%20of%20heterogeneous%20ex.pdf
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author Mustafa, Zulkifli
Shamsuddin, Hilda Shazana
Ideris, Aini
Ibrahim, Rohaya
Jaafar, Hasnan
Ali, Abdul Manaf
Abdullah, Jafri Malin
author_facet Mustafa, Zulkifli
Shamsuddin, Hilda Shazana
Ideris, Aini
Ibrahim, Rohaya
Jaafar, Hasnan
Ali, Abdul Manaf
Abdullah, Jafri Malin
author_sort Mustafa, Zulkifli
building UPM Institutional Repository
collection Online Access
description Oncolytic viruses have been extensively evaluated for anticancer therapy because this virus preferentially infects cancer cells without interfering with normal cells. Newcastle Disease Virus (NDV) is an avian virus and one of the intensively studied oncolytic viruses affecting many types of cancer including glioma. Nevertheless, the capability of NDV infection on heterogeneous glioma tissue in a cerebrospinal fluid atmosphere has never been reported. Recently, Rac1 is reported to be required for efficient NDV replication in human cancer cells and established a link between tumourigenesis and sensitivity to NDV. Rac1 is a member of the Rho GTPases involved in the regulation of the cell migration and cell-cycle progression. Rac1 knockdown leads to significant inhibition of viral replication. In this work, we demonstrated that NDV treatment led to significant reduction of tumour tissue viability of freshly isolated heterogeneous human brain tumour slice, known as an ex vivo glioma acute slice (EGAS). Analysis of gene expression indicated that reduced tissue viability was associated with downregulation of Rac1. However, the viability reduction was not persistent. We conclude that NDV treatment induced EGAS viability suppression, but subsequent downregulation of Rac1 gene may reduce the NDV replication and lead to regrowth of EGAS tissue.
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spelling upm-299032016-02-12T04:58:03Z http://psasir.upm.edu.my/id/eprint/29903/ Viability reduction and Rac1 gene downregulation of heterogeneous ex-vivo glioma acute slice infected by the oncolytic Newcastle Disease Virus strain V4UPM Mustafa, Zulkifli Shamsuddin, Hilda Shazana Ideris, Aini Ibrahim, Rohaya Jaafar, Hasnan Ali, Abdul Manaf Abdullah, Jafri Malin Oncolytic viruses have been extensively evaluated for anticancer therapy because this virus preferentially infects cancer cells without interfering with normal cells. Newcastle Disease Virus (NDV) is an avian virus and one of the intensively studied oncolytic viruses affecting many types of cancer including glioma. Nevertheless, the capability of NDV infection on heterogeneous glioma tissue in a cerebrospinal fluid atmosphere has never been reported. Recently, Rac1 is reported to be required for efficient NDV replication in human cancer cells and established a link between tumourigenesis and sensitivity to NDV. Rac1 is a member of the Rho GTPases involved in the regulation of the cell migration and cell-cycle progression. Rac1 knockdown leads to significant inhibition of viral replication. In this work, we demonstrated that NDV treatment led to significant reduction of tumour tissue viability of freshly isolated heterogeneous human brain tumour slice, known as an ex vivo glioma acute slice (EGAS). Analysis of gene expression indicated that reduced tissue viability was associated with downregulation of Rac1. However, the viability reduction was not persistent. We conclude that NDV treatment induced EGAS viability suppression, but subsequent downregulation of Rac1 gene may reduce the NDV replication and lead to regrowth of EGAS tissue. Hindawi Publishing Corporation 2013-02-24 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/29903/1/Viability%20reduction%20and%20Rac1%20gene%20downregulation%20of%20heterogeneous%20ex.pdf Mustafa, Zulkifli and Shamsuddin, Hilda Shazana and Ideris, Aini and Ibrahim, Rohaya and Jaafar, Hasnan and Ali, Abdul Manaf and Abdullah, Jafri Malin (2013) Viability reduction and Rac1 gene downregulation of heterogeneous ex-vivo glioma acute slice infected by the oncolytic Newcastle Disease Virus strain V4UPM. BioMed Research International, 2013. art. no. 248507. pp. 1-8. ISSN 2314-6133; ESSN: 2314-6141 http://dx.doi.org/10.1155/2013/248507 10.1155/2013/248507
spellingShingle Mustafa, Zulkifli
Shamsuddin, Hilda Shazana
Ideris, Aini
Ibrahim, Rohaya
Jaafar, Hasnan
Ali, Abdul Manaf
Abdullah, Jafri Malin
Viability reduction and Rac1 gene downregulation of heterogeneous ex-vivo glioma acute slice infected by the oncolytic Newcastle Disease Virus strain V4UPM
title Viability reduction and Rac1 gene downregulation of heterogeneous ex-vivo glioma acute slice infected by the oncolytic Newcastle Disease Virus strain V4UPM
title_full Viability reduction and Rac1 gene downregulation of heterogeneous ex-vivo glioma acute slice infected by the oncolytic Newcastle Disease Virus strain V4UPM
title_fullStr Viability reduction and Rac1 gene downregulation of heterogeneous ex-vivo glioma acute slice infected by the oncolytic Newcastle Disease Virus strain V4UPM
title_full_unstemmed Viability reduction and Rac1 gene downregulation of heterogeneous ex-vivo glioma acute slice infected by the oncolytic Newcastle Disease Virus strain V4UPM
title_short Viability reduction and Rac1 gene downregulation of heterogeneous ex-vivo glioma acute slice infected by the oncolytic Newcastle Disease Virus strain V4UPM
title_sort viability reduction and rac1 gene downregulation of heterogeneous ex-vivo glioma acute slice infected by the oncolytic newcastle disease virus strain v4upm
url http://psasir.upm.edu.my/id/eprint/29903/
http://psasir.upm.edu.my/id/eprint/29903/
http://psasir.upm.edu.my/id/eprint/29903/
http://psasir.upm.edu.my/id/eprint/29903/1/Viability%20reduction%20and%20Rac1%20gene%20downregulation%20of%20heterogeneous%20ex.pdf