Long-term Treatment of Malignant Gliomas with Intramuscularly Administered Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose: An Open Pilot Study

Salazar, Andrés M.; Levy, Hilton B.; Ondra, Steven; Kende, Meir; Scherokman, Barbara; Brown, D.S.; Mena, Hernando; Martin, N. S.; Schwab, Karen; Donovan, Daniel; Dougherty, D. S.; Pulliam, Morris W.; Ippolito, Mark; Graves, Maria; Brown, Herbert R.; Ommaya, Alex

doi:10.1227/00006123-199606000-00006

Cited by 101 publications

(54 citation statements)

References 26 publications

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“…Clinical-grade TLR3 ligands are being considered as immunostimulatory and antiviral agents for in vivo applications (6,10,52,53). Early studies demonstrated promise for poly(I:C) treatment in reducing the viral burden in HIV-infected individuals (10,52).…”

Section: Discussionmentioning

confidence: 99%

Double-Stranded RNA Analog Poly(I:C) Inhibits Human Immunodeficiency Virus Amplification in Dendritic Cells via Type I Interferon-Mediated Activation of APOBEC3G

Trapp

Derby

Singer

et al. 2009

J Virol

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Section: Discussionmentioning

confidence: 99%

Double-Stranded RNA Analog Poly(I:C) Inhibits Human Immunodeficiency Virus Amplification in Dendritic Cells via Type I Interferon-Mediated Activation of APOBEC3G

Trapp

Derby

Singer

et al. 2009

J Virol

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“…tested in a clinical trial for direct treatment of glioblastoma (29). Both IFN and poly(I:C) protected normal brain cells from recombinant VSVs.…”

Section: Discussionmentioning

confidence: 99%

Variable Deficiencies in the Interferon Response Enhance Susceptibility to Vesicular Stomatitis Virus Oncolytic Actions in Glioblastoma Cells but Not in Normal Human Glial Cells

Wollmann¹,

Robek

Pol³

2007

J Virol

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“…We have addressed this issue using two strategies: the ®rst takes advantage of a VV recombinant that expresses PKR under regulation of the E. coli lacI operator/repressor system, the second is based on treating cells with a synthetic dsRNA polymer composed of alternating riboinosinic and ribocytidilic subunits (pIC), usually used as a model of viral infection or dsRNA-triggered processes. Characterizing this apoptosisinvolved pathway is of particular importance, since pIC is being used in dierent clinical trials for tumour treatments (Robinson et al, 1976;Salazar et al, 1996) and PKR has been invoked as a tumour suppresser gene (Meurs et al, 1993;Koromilas et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Activation of NF-κB by the dsRNA-dependent protein kinase, PKR involves the IκB kinase complex

2000

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Besides its known role as a translational controlling factor, the double stranded RNA-dependent protein kinase (PKR) is a key transcriptional regulator exerting antiviral and antitumoural activities. We have recently described that induction of NF-kB by PKR is involved in apoptosis commitment. To de®ne how PKR mediates NF-kB activation by dsRNA, we have used two dierent approaches, one based on expression of PKR by a vaccinia virus (VV) recombinant and the other based on induction of endogenous PKR by poly I:C (pIC) treatment. We found that NF-kB complexes induced by PKR are composed primarily of p50-p65 heterodimers and also of crel-p50 heterodimers. As described for other stimuli, following pIC treatment, PKR phosphorylates the NF-kB inhibitor IkBa at serine 32 before degradation. Expression by VV recombinants of IKK1 or IKK2 dominant negative mutants together with PKR showed inhibition of PKR-induced NF-kB activation, as measured both by gel shift and luciferase reporter assays. Immunoprecipitation analysis revealed that PKR interacts with the IKK complex. Our ®ndings demonstrate that physiological function(s) of PKR involve activation of the IkB kinase complex.

show abstract

Long-term Treatment of Malignant Gliomas with Intramuscularly Administered Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose: An Open Pilot Study

Cited by 101 publications

References 26 publications

Double-Stranded RNA Analog Poly(I:C) Inhibits Human Immunodeficiency Virus Amplification in Dendritic Cells via Type I Interferon-Mediated Activation of APOBEC3G

Double-Stranded RNA Analog Poly(I:C) Inhibits Human Immunodeficiency Virus Amplification in Dendritic Cells via Type I Interferon-Mediated Activation of APOBEC3G

Variable Deficiencies in the Interferon Response Enhance Susceptibility to Vesicular Stomatitis Virus Oncolytic Actions in Glioblastoma Cells but Not in Normal Human Glial Cells

Activation of NF-κB by the dsRNA-dependent protein kinase, PKR involves the IκB kinase complex

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