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Doxycycline Inducible Melanogenic Vaccinia Virus as Theranostic Anti-Cancer Agent.

Kirscher L, Deán-Ben XL, Scadeng M, Zaremba A, Zhang Q, Kober C, Fehm TF, Razansky D, Ntziachristos V, Stritzker J, Szalay AA - Theranostics (2015)

Bottom Line: In this study melanin production was detected after exogenous addition of doxycycline in two different tumor xenograft mouse models.Furthermore, it was confirmed that this novel vaccinia virus strain still facilitated signal enhancement as detected by MRI and optoacoustic tomography.At the same time we demonstrated an enhanced oncolytic potential compared to the constitutively melanin synthesizing rVACV system.

View Article: PubMed Central - PubMed

Affiliation: 1. University of Würzburg, Department of Biochemistry, Am Hubland, 97074 Würzburg, Germany.

ABSTRACT
We reported earlier the diagnostic potential of a melanogenic vaccinia virus based system in magnetic resonance (MRI) and optoacoustic deep tissue imaging (MSOT). Since melanin overproduction lead to attenuated virus replication, we constructed a novel recombinant vaccinia virus strain (rVACV), GLV-1h462, which expressed the key enzyme of melanogenesis (tyrosinase) under the control of an inducible promoter-system. In this study melanin production was detected after exogenous addition of doxycycline in two different tumor xenograft mouse models. Furthermore, it was confirmed that this novel vaccinia virus strain still facilitated signal enhancement as detected by MRI and optoacoustic tomography. At the same time we demonstrated an enhanced oncolytic potential compared to the constitutively melanin synthesizing rVACV system.

No MeSH data available.


Related in: MedlinePlus

Viral activity and oncolytic potential of tested rVACV in PANC-1 xenograft bearing nude mice A) Tumor volume measurements of PANC-1 tumors untreated (PBS) or treated with GLV-1h460, GLV-1h312 and GLV-1h462 (n=3-5). Significant smaller tumor volume of uninduced non-melanogenic GLV-1h462 colonized PANC-1 tumors 55 dpvi compared to GLV-1h460 infected tumors and 63 dpvi compared to dox induced melanin synthesizing GLV-1h462 injected PANC-1 tumor bearing mice (p <0.05). B) Escherichia coli beta-glucuronidase activity assay of blood serum samples of PANC-1 xenograft bearing mice injected with GLV-1h462. GusA-activities are normalized by tumor volume as a correction factor.
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Figure 5: Viral activity and oncolytic potential of tested rVACV in PANC-1 xenograft bearing nude mice A) Tumor volume measurements of PANC-1 tumors untreated (PBS) or treated with GLV-1h460, GLV-1h312 and GLV-1h462 (n=3-5). Significant smaller tumor volume of uninduced non-melanogenic GLV-1h462 colonized PANC-1 tumors 55 dpvi compared to GLV-1h460 infected tumors and 63 dpvi compared to dox induced melanin synthesizing GLV-1h462 injected PANC-1 tumor bearing mice (p <0.05). B) Escherichia coli beta-glucuronidase activity assay of blood serum samples of PANC-1 xenograft bearing mice injected with GLV-1h462. GusA-activities are normalized by tumor volume as a correction factor.

Mentions: Following the characterization in cell cultures we analyzed the effect of the different virus strains on xenograft tumor regression in mice. Therefore, nude mice bearing PANC-1 tumors (~200mm³) were injected with GLV-1h312, GLV-1h460 and GLV-1h462 respectively (Fig. 5). Five GLV-1h462 injected mice received 100 µg/ml dox in the drinking water while the other mice (n = 5 per group) did not receive dox supplement. The tumor growth over time showed that the non induced GLV-1h462 infected tumors had a similar tumor volume as non‑melanogenic GLV-1h312 treated tumors. Also, the tumor volume in those mice decreased over time.


Doxycycline Inducible Melanogenic Vaccinia Virus as Theranostic Anti-Cancer Agent.

Kirscher L, Deán-Ben XL, Scadeng M, Zaremba A, Zhang Q, Kober C, Fehm TF, Razansky D, Ntziachristos V, Stritzker J, Szalay AA - Theranostics (2015)

Viral activity and oncolytic potential of tested rVACV in PANC-1 xenograft bearing nude mice A) Tumor volume measurements of PANC-1 tumors untreated (PBS) or treated with GLV-1h460, GLV-1h312 and GLV-1h462 (n=3-5). Significant smaller tumor volume of uninduced non-melanogenic GLV-1h462 colonized PANC-1 tumors 55 dpvi compared to GLV-1h460 infected tumors and 63 dpvi compared to dox induced melanin synthesizing GLV-1h462 injected PANC-1 tumor bearing mice (p <0.05). B) Escherichia coli beta-glucuronidase activity assay of blood serum samples of PANC-1 xenograft bearing mice injected with GLV-1h462. GusA-activities are normalized by tumor volume as a correction factor.
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Related In: Results  -  Collection

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Figure 5: Viral activity and oncolytic potential of tested rVACV in PANC-1 xenograft bearing nude mice A) Tumor volume measurements of PANC-1 tumors untreated (PBS) or treated with GLV-1h460, GLV-1h312 and GLV-1h462 (n=3-5). Significant smaller tumor volume of uninduced non-melanogenic GLV-1h462 colonized PANC-1 tumors 55 dpvi compared to GLV-1h460 infected tumors and 63 dpvi compared to dox induced melanin synthesizing GLV-1h462 injected PANC-1 tumor bearing mice (p <0.05). B) Escherichia coli beta-glucuronidase activity assay of blood serum samples of PANC-1 xenograft bearing mice injected with GLV-1h462. GusA-activities are normalized by tumor volume as a correction factor.
Mentions: Following the characterization in cell cultures we analyzed the effect of the different virus strains on xenograft tumor regression in mice. Therefore, nude mice bearing PANC-1 tumors (~200mm³) were injected with GLV-1h312, GLV-1h460 and GLV-1h462 respectively (Fig. 5). Five GLV-1h462 injected mice received 100 µg/ml dox in the drinking water while the other mice (n = 5 per group) did not receive dox supplement. The tumor growth over time showed that the non induced GLV-1h462 infected tumors had a similar tumor volume as non‑melanogenic GLV-1h312 treated tumors. Also, the tumor volume in those mice decreased over time.

Bottom Line: In this study melanin production was detected after exogenous addition of doxycycline in two different tumor xenograft mouse models.Furthermore, it was confirmed that this novel vaccinia virus strain still facilitated signal enhancement as detected by MRI and optoacoustic tomography.At the same time we demonstrated an enhanced oncolytic potential compared to the constitutively melanin synthesizing rVACV system.

View Article: PubMed Central - PubMed

Affiliation: 1. University of Würzburg, Department of Biochemistry, Am Hubland, 97074 Würzburg, Germany.

ABSTRACT
We reported earlier the diagnostic potential of a melanogenic vaccinia virus based system in magnetic resonance (MRI) and optoacoustic deep tissue imaging (MSOT). Since melanin overproduction lead to attenuated virus replication, we constructed a novel recombinant vaccinia virus strain (rVACV), GLV-1h462, which expressed the key enzyme of melanogenesis (tyrosinase) under the control of an inducible promoter-system. In this study melanin production was detected after exogenous addition of doxycycline in two different tumor xenograft mouse models. Furthermore, it was confirmed that this novel vaccinia virus strain still facilitated signal enhancement as detected by MRI and optoacoustic tomography. At the same time we demonstrated an enhanced oncolytic potential compared to the constitutively melanin synthesizing rVACV system.

No MeSH data available.


Related in: MedlinePlus