Request for paper/comments

[Muckerheide <muckerheide@attbi.com>]

> Group,

> 

> Do you have access to the following paper?

> Comments?

> 

> Thank you.

> Regards, Jim Muckerheide

> ===========================

> 

> Surgery 2002 Aug;132(2):353-9

> 

> Ionizing radiation potentiates the antitumor efficacy of oncolytic herpes

> simplex virus G207 by upregulating ribonucleotide reductase.

> 

> Stanziale SF, Petrowsky H, Joe JK, Roberts GD, Zager JS, Gusani NJ, Ben-Porat

> L, Gonen M, Fong Y.

> Hepatobiliary Division, Department of Surgery, and the Department of

> Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New

> York, NY.

> 

> Background. Replication-competent herpes simplex virus-1 (HSV-1) mutants have

> an oncolytic effect on human and animal cancers. The aim of this study was to

> determine whether G207, an HSV-1 mutant, can be combined with ionizing

> radiation (IR) to increase antitumor activity while decreasing

> treatment-associated toxicity. Methods. This study was performed by using

> G207, a replication-competent HSV-1 mutant deficient in viral ribonucleotide

> reductase (RR) and the gamma(1)34.5 neurovirulence protein. The antitumor

> activity of G207 or IR was tested against HCT-8 human colorectal cancer cells

> in vitro and in an in vivo mouse subcutaneous tumor model. Results. We

> demonstrated that G207 has significant oncolytic effect on HCT-8 cells in

> vitro in a cytotoxicity assay and in vivo in a mouse flank tumor model and

> that these effects are improved with low-dose IR. We further illustrated that

> the increased tumoricidal effect is dependent on the up-regulation of cellular

> RR by IR measured by a functional bioassay for RR activity. Chemical

> inhibition of RR by hydroxyurea abrogates the enhanced effect. In contrast to

> G207, R3616, the parent virus of G207 that expresses functional RR, does not

> exhibit enhanced oncolysis when combined with IR. Conclusions. These data

> encourage clinical investigation of combination radiation therapy and HSV

> oncolytic therapy.



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