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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

Effects of transient doxycycline induction on inducible melanogenic VACV based oncolysis. Quantitative evaluation of plaque sizes in CV-1 cells infected with inducible melanogenic GLV-1h462, constitutively melanogenic GLV-1h460 and non-melanogenic GLV-1h312 incubated in presence (w/) or absence (w/o) of 1 µg/ml dox for 72 hours. CV-1 cells infected with GLV-1h462 were incubated for 2, 6, 8, 24, 48 and 72 hours with 1 µg/ml dox respectively. Data represent the average maximum plaque diameter plus standard deviation of at least 25 plaques/virus strain and dox exposure time.
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Figure 4: Effects of transient doxycycline induction on inducible melanogenic VACV based oncolysis. Quantitative evaluation of plaque sizes in CV-1 cells infected with inducible melanogenic GLV-1h462, constitutively melanogenic GLV-1h460 and non-melanogenic GLV-1h312 incubated in presence (w/) or absence (w/o) of 1 µg/ml dox for 72 hours. CV-1 cells infected with GLV-1h462 were incubated for 2, 6, 8, 24, 48 and 72 hours with 1 µg/ml dox respectively. Data represent the average maximum plaque diameter plus standard deviation of at least 25 plaques/virus strain and dox exposure time.

Mentions: Cells were therefore infected with a defined number of plaque forming units of GLV-1h462 and control strains respectively. The doxycycline containing overlay medium that was replaced with dox-free medium at different times post viral infection (at 0, 2, 6, 8, 24, 48 and 72 hpvi respectively). Consequently, tyrosinase (and therefore melanin)-production was transient. The infection was stopped simultaneously at 72 hours post viral infection and the maximum plaque diameter for at least 25 plaques/virus strain and dox-exposure time was measured (Fig. 4).


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)

Effects of transient doxycycline induction on inducible melanogenic VACV based oncolysis. Quantitative evaluation of plaque sizes in CV-1 cells infected with inducible melanogenic GLV-1h462, constitutively melanogenic GLV-1h460 and non-melanogenic GLV-1h312 incubated in presence (w/) or absence (w/o) of 1 µg/ml dox for 72 hours. CV-1 cells infected with GLV-1h462 were incubated for 2, 6, 8, 24, 48 and 72 hours with 1 µg/ml dox respectively. Data represent the average maximum plaque diameter plus standard deviation of at least 25 plaques/virus strain and dox exposure time.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4508495&req=5

Figure 4: Effects of transient doxycycline induction on inducible melanogenic VACV based oncolysis. Quantitative evaluation of plaque sizes in CV-1 cells infected with inducible melanogenic GLV-1h462, constitutively melanogenic GLV-1h460 and non-melanogenic GLV-1h312 incubated in presence (w/) or absence (w/o) of 1 µg/ml dox for 72 hours. CV-1 cells infected with GLV-1h462 were incubated for 2, 6, 8, 24, 48 and 72 hours with 1 µg/ml dox respectively. Data represent the average maximum plaque diameter plus standard deviation of at least 25 plaques/virus strain and dox exposure time.
Mentions: Cells were therefore infected with a defined number of plaque forming units of GLV-1h462 and control strains respectively. The doxycycline containing overlay medium that was replaced with dox-free medium at different times post viral infection (at 0, 2, 6, 8, 24, 48 and 72 hpvi respectively). Consequently, tyrosinase (and therefore melanin)-production was transient. The infection was stopped simultaneously at 72 hours post viral infection and the maximum plaque diameter for at least 25 plaques/virus strain and dox-exposure time was measured (Fig. 4).

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