35 research outputs found

    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.

    No full text
    <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.

    No full text
    <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.

    No full text
    <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

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

    No full text
    <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

    Histological assessment of tumour response to MLN0518.

    No full text
    <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

    Engraftment and growth of U266<sup>luciferase</sup> cells as monitored by BLI, serum paraprotein and MRI. A.

    No full text
    <p>(i) Dorsal and (ii) ventral BLI acquired from IVIS over weeks 3–7 post-inoculation. <b>B.</b> Quantitative measurement of radiance from BLI. Radiance reflects the intensity of luciferase luminescence and therefore number of luciferase-tagged cells present. Results show that radiance increases in a time-dependent manner over the course of the experiment and that a significant increase in radiance occurs over weeks 5–7 (p<0.05, 1-way ANOVA with Bonferroni post-test). <b>C.</b> Paraprotein levels in the serum increases in a time dependent manner and correlates with the increase seen in BLI. MRI-derived tumour volumes determined at approximately weeks 5 and 10 confirmed tumour progression seen with BLI.</p

    CD138 expression changes in response to therapy.

    No full text
    <p><b>A.</b> Percentage of CD138<sup>+</sup> human myeloma cells measured by flow cytometry in bone aspirates of mice (n = 3), showing a significantly lower percentage of positive cells in both tibias and spine of mice in the two treatment groups than in untreated mice (p<0.05, 2-way ANOVA with Bonferroni post-test). No CD138<sup>+</sup> cells were observed in the organs of any of the mice. <b>B.</b> Histological analysis of sections from the tibias of mice from each group showed distinct differences. (i) Sections from healthy mice displayed classical architecture, with no CD138<sup>+</sup> cells. (ii) In comparison, sections from untreated myeloma mice showed a high infiltration of CD138<sup>+</sup> cells with loss of normal architecture. (iii) Treatment of mice with BZB resulted in the return of normal architecture and loss of CD138<sup>+</sup> cells. (iv) A similar result was observed in mice treated with tosedostat, but with occasional scattered CD138<sup>+</sup> cells.</p

    BLI and serum paraprotein changes in response to therapy.

    No full text
    <p><b>A.</b> (i) Pre-treatment and (ii) post-treatment BLI of mice at weeks 5 and 9. <b>B.</b> Quantitative measurement of radiance from BLI. (i) No significant difference in radiance between treatment groups was seen at the start of the treatment schedule. (ii) Post-treatment radiance levels revealed a significant attenuation of tumour spread by both BZB and tosedostat (p<0.05, 1-way ANOVA with Bonferroni post-test). <b>C.</b> Paraprotein levels during treatment schedule. Positive control mice showed an exponential increase in serum levels of Igλ over 9 weeks. In comparison, both treatment groups did not exhibit the same increase, with significantly lower levels by the end of treatment (p<0.05).</p

    MRI changes in response to therapy.

    No full text
    <p>MRI-derived tumour volumes. <b>A.</b> Tumour was identified as a hyperintense signal enclosed within the cortical bone on T<sub>2</sub>-weighted images. MRI images showed a reduction in signal intensity in both treatment groups compared to positive control in both the tibia (T) and femur (F). <b>B.</b> Tumour volume was quantified from regions of interest drawn on the periphery of the hyperintense signal. Data are mean ± SEM, n≥6. Both BZB and tosedostat (TDT) treatment resulted in a significantly lower tumour volume compared to control (p<0.05, 1-way ANOVA with Bonferroni post-test). In addition, there was no significant difference in tumour volume between the BZB treated and negative control group.</p
    corecore