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Combined Therapy with Chemotherapeutic Agents and Herpes Simplex Virus Type 1 ICP34.5 Mutant (HSV-1716) in Human Non-Small Cell Lung Cancer

Overview of attention for article published in Human Gene Therapy, December 1999
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Title
Combined Therapy with Chemotherapeutic Agents and Herpes Simplex Virus Type 1 ICP34.5 Mutant (HSV-1716) in Human Non-Small Cell Lung Cancer
Published in
Human Gene Therapy, December 1999
DOI 10.1089/10430349950016410
Pubmed ID
Authors

T Toyoizumi, R Mick, A E Abbas, E H Kang, L R Kaiser, K L Molnar-Kimber

Abstract

A replication-selective herpes simplex virus type 1 ICP34.5 mutant (HSV-1716) has shown efficacy both in vitro and in vivo against human non-small cell lung cancer (NSCLC) cell lines but complete eradication of tumor has not been accomplished with a single viral treatment in our murine xenograft models. Therefore, strategies to enhance the efficacy of this treatment were investigated. We determined the oncolytic activity of HSV-1716 in NCI-H460 cells in combination with each of four chemotherapeutic agents: mitomycin C (MMC), cis-platinum II (cis-DDP), methotrexate (MTX), or doxorubicin (ADR). Isobologram analysis was performed to evaluate the interaction between the viral and chemotherapeutic agents. The oncolytic effect of HSV-1716 in combination with MMC was synergistic in two of five NSCLC cell lines. In the other three cell lines, the combined effect appeared additive. No antagonism was observed. The in vivo effect of this combination was then examined in a murine xenograft model. NCI-H460 flank tumors were directly injected with HSV-1716 (4 x 106 PFU) followed by intravenous MMC administration (0.17 mg/kg) 24 hr later. After 3 weeks, the mean tumor weight in the combined treatment group was significantly less than either individual treatment in an additive manner. The synergistic dose of MMC neither augmented nor inhibited viral replication in vitro and HSV-1716 infection did not upregulate DT-diaphorase, which is the primary enzyme responsible for MMC activation. In summary, the combination of HSV-1716 with common chemotherapeutic agents may augment the effect of HSV-based therapy in the treatment of NSCLC.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 3%
Unknown 36 97%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 22%
Student > Master 7 19%
Student > Ph. D. Student 6 16%
Student > Bachelor 3 8%
Student > Doctoral Student 2 5%
Other 3 8%
Unknown 8 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 8 22%
Agricultural and Biological Sciences 8 22%
Medicine and Dentistry 4 11%
Mathematics 2 5%
Immunology and Microbiology 2 5%
Other 3 8%
Unknown 10 27%