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Articles by Y Fong
Total Records ( 2 ) for Y Fong
  D. L Price , S. F Lin , Z Han , G Simpson , R. S Coffin , J Wong , S Li , Y Fong and R. J. Wong
 

Objective  To determine if prodrug conversion of fluorocytosine to fluorouracil by an engineered herpes virus, OncoVEXGALV/CD, enhances oncolytic therapy of head and neck squamous cell carcinoma.

Design  We assessed the ability of OncoVEXGALV/CD and OncoVEXGFP to infect, replicate within, and lyse 4 head and neck squamous cell carcinoma lines in vitro. The effects of adding fluorocytosine with OncoVEXGALV/CD were evaluated.

Results  Head and neck squamous cell carcinoma was permissive to green fluorescent protein expression in100% of cells by OncoVEXGFP at a multiplicity of infection of 1 after 48 hours and supported logarithmic viral replication. Virus caused more than 60% cell death 6 days after exposure to virus at a multiplicity of infection of 0.1 in 3 of the 4 cell lines. Fluorocytosine did not enhance cytotoxicity induced by OncoVEXGALV/CD at a multiplicity of infection of 0.1. However, for the least-sensitive SCC25 cell line, virus at a multiplicity of infection of 0.01 was cytotoxic to only 4% of cells after 6 days but was cytotoxic to 35% of cells with fluorocytosine.

Conclusions  OncoVEXGALV/CD efficiently infects, replicates within, and lyses head and neck squamous cell carcinoma at relatively low viral doses. Prodrug conversion by cytosine deaminase did not enhance therapy at viral doses that cause efficient cytotoxicity but may have beneficial effects in less-sensitive cell lines at low viral doses.

  P Brader , K. J Kelly , N Chen , Y. A Yu , Q Zhang , P Zanzonico , E. M Burnazi , R. E Ghani , I Serganova , H Hricak , A. A Szalay , Y Fong and R. G. Blasberg
 

Purpose: Oncolytic viral therapy continues to be investigated for the treatment of cancer, and future studies in patients would benefit greatly from a noninvasive modality for assessing virus dissemination, targeting, and persistence. The purpose of this study was to determine if a genetically modified vaccinia virus, GLV-1h99, containing a human norepinephrine transporter (hNET) reporter gene, could be sequentially monitored by [123I]metaiodobenzylguanidine (MIBG) -camera and [124I]MIBG positron emission tomography (PET) imaging.

Experimental Design: GLV-1h99 was tested in human malignant mesothelioma and pancreatic cancer cell lines for cytotoxicity, expression of the hNET protein using immunoblot analysis, and [123I]MIBG uptake in cell culture assays. In vivo [123I]MIBG -camera and serial [124I]MIBG PET imaging was done in MSTO-211H orthotopic pleural mesothelioma tumors.

Results: GLV-1h99 successfully infected and provided dose-dependent levels of transgene hNET expression in human malignant mesothelioma and pancreatic cancer cells. The time course of [123I]MIBG accumulation showed a peak of radiotracer uptake at 48 hours after virus infection in vitro. In vivo hNET expression in MSTO-211H pleural tumors could be imaged by [123I]MIBG scintigraphy and [124I]MIBG PET 48 and 72 hours after GLV-1h99 virus administration. Histologic analysis confirmed the presence of GLV-1h99 in tumors.

Conclusion: GLV-1h99 shows high mesothelioma tumor cell infectivity and cytotoxic efficacy. The feasibility of imaging virus-targeted tumor using the hNET reporter system with [123I]MIBG -camera and [124I]MIBG PET was shown in an orthotopic pleural mesothelioma tumor model. The inclusion of human reporter genes into recombinant oncolytic viruses enhances the potential for translation to clinical monitoring of oncolytic viral therapy.

 
 
 
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