Changes of tumor vascularity during gene therapy monitored with color Doppler US.
Using contrast-enhanced color Doppler (CD) sonography, we assessed alterations of tumor blood flow induced in 25 murine Morris hepatomas transfected with a gancyclovir- (GCV-)sensitizing Herpes simplex virus thymidine kinase (HSVtk) suicide gene in combination with systemic GCV treatment and compared findings with a control tumor. CD measurements were quantified by the color pixel density (CPD) and the mean encoded flow velocity (mean color value, MCV), using computer-assisted image analysis, and compared with histologic arteriole counts. During 5 days, the tumor volume remained constant. In HSVtk-expressing tumors, the median CPD dropped from 16% at baseline to 5% on day 5 (p = 0.001), remaining constant in controls. The MCV decreased from 1.9 cm/s to 1.6 cm/s in the HSVtk-expressing tumors (p = 0.001) and rose from 1.8 cm/s to 2.0 cm/s in the controls (p = 0.002). In an accompanying histologic arteriole assay, we found no alterations attributable to treatment.
Delorme
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S
German Cancer Research Center (DKFZ), Department of Oncological Diagnostics and Therapy, Im Neuenheimer Feld 280, D 69120 Heidelberg, Germany. s.delorme@dkfz.de
Haberkorn
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Kinscherf
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Zuna
I
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Bahner
M L
ML
van Kaick
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G
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000000981:diagnostic imaging* / Q000235:genetics; D015774:Ganciclovir / Q000494:pharmacology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging* / Q000235:genetics; D051379:Mice; D018139:Simplexvirus / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D018615:Ultrasonography, Doppler, Color
D013937:Thymidine Kinase; D015774:Ganciclovir