5 research outputs found

    BLI and serum paraprotein changes in response to therapy.

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    <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

    CD138 expression changes in response to therapy.

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    <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

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

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    <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

    MRI changes in response to therapy.

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    <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
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