5 research outputs found

    Diffusion-weighted and susceptibility contrast MRI of C6 tumours treated with MLN0518.

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    <p>Parametric maps of apparent diffusion coefficient (ADC, top panel), fractional blood volume (fBV, middle panel) and vessel size index (R<sub>v</sub>, bottom panel) from C6 xenografts in mice treated with vehicle or 20 mg/kg MLN0518 for 10 days show no clear differences between vehicle and treated tumours. Representative maps are shown.</p

    Summary of the quantitative MRI biomarkers acquired from intrinsic susceptibility MRI of C6 xenografts in mice treated with vehicle or 20 mg/kg MLN0518 for 10 days.

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    <p>Mean of median R<sub>2</sub>* and ΔR<sub>2</sub>* values from each tumour ± 1s.e.m. (n≥5 per treatment group). The proportion of voxels in which R<sub>2</sub>* changed significantly, either negatively (ΔR<sub>2</sub>* <0) or positively (ΔR<sub>2</sub>* >0), with carbogen breathing are also shown.</p

    C6 tumour growth is slowed by MLN0518 treatment.

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    <p>The growth rate of tumours in mice treated with 20 mg/kg MLN0518 was significantly slower than tumours in vehicle treated mice over 10 days. Tumour doubling times were calculated on an individual tumour basis (n = 15 per treatment group). Mean ±1s.e.m.</p

    Dynamic contrast-enhanced MRI is sensitive to the response of C6 tumours to MLN0518.

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    <p>Representative parametric maps and quantification of initial area under the gadolinium concentration curve (IAUGC) demonstrate a reduction in tumour blood vessel permeability/flow in mice treated with 20 mg/kg MLN0518 for 3 days compared to controls. Mean parameter values from each tumour ± 1s.e.m. (n≥6 per treatment group), * p<0.05.</p

    Histological assessment of tumour response to MLN0518.

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    <p><b>A.</b> Tumour sections stained for the perfusion marker Hoechst 33342 (blue), endothelial marker CD31 (red) and pimonidazole adduct formation, a marker of hypoxia (green) demonstrate that the hypoxic area was lower in tumours treated with 20 mg/kg MLN0518 for 10 days than vehicle treated controls. The percentage of the total vessels perfused and the overall perfused vessel area was also lower in treated versus control tumours. Representative composite images are shown. <b>B.</b> Alpha smooth muscle actin (α-SMA) immunohistochemistry demonstrates a significant reduction in α-SMA positive blood vessels in MLN0518 treated tumours compared to controls. Magnification ×200.</p
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