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Understanding Heterogeneity and Permeability of Brain Metastases in Murine Models of HER2-Positive Breast Cancer Through Magnetic Resonance Imaging: Implications for Detection and Therapy.

Murrell DH, Hamilton AM, Mallett CL, van Gorkum R, Chambers AF, Foster PJ - Transl Oncol (2015)

Bottom Line: The mean volume of an MDA-MB-231-BR-HER2 tumor was significantly larger compared to other models (F2,12 = 5.845, P < .05); interestingly, this model also had a significantly higher proportion of Gd-impermeable tumors (F2,12 = 22.18, P < .0001).Ki67 staining indicated that Gd-impermeable tumors had significantly more proliferative nuclei compared to Gd-permeable tumors (t[24] = 2.389, P < .05) in the MDA-MB-231-BR-HER2 model.Understanding this heterogeneity, especially as it relates to BBB permeability, is important for improvement in brain metastasis detection and treatment delivery.

View Article: PubMed Central - PubMed

Affiliation: Imaging, Robarts Research Institute, London, Ontario, Canada; Medical Biophysics, Western University, London, Ontario, Canada. Electronic address: dmurrell@robarts.ca.

No MeSH data available.


Related in: MedlinePlus

Quantification of mean volume per tumor (± SEM) at end point in SUM190-BR3, JIMT-1-BR3, and MDA-MB-231-BR-HER2 models. The average volume of a tumor was significantly different between groups (F2,12 = 5.845, P < .05), and MDA-MB-231-BR-HER2 tumors were significantly larger in size compared to JIMT-1-BR3 or SUM190-BR3 tumors. No other significant differences were observed.
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f0010: Quantification of mean volume per tumor (± SEM) at end point in SUM190-BR3, JIMT-1-BR3, and MDA-MB-231-BR-HER2 models. The average volume of a tumor was significantly different between groups (F2,12 = 5.845, P < .05), and MDA-MB-231-BR-HER2 tumors were significantly larger in size compared to JIMT-1-BR3 or SUM190-BR3 tumors. No other significant differences were observed.

Mentions: The 3D high-resolution nature of MRI allowed us to quantify metastasis volume and permeability in the whole mouse brain for each animal in all three models. We evaluated 198 tumors at experimental end point across the three models. Tumor incidence and total tumor burden are shown in Table 1. The SUM190-BR3 model grew few tumors, and the total tumor volume per brain was relatively low despite having the most cells injected. The MDA-MB-231-BR-HER2 model was injected with the least cells, yet grew the most tumors and had the highest total tumor volume. The study end point was decided when mice displayed clinical symptoms of the disease and deteriorating health. The time to end point was different for each model: day 28 for JIMT-1-BR3, day 36 for MDA-MB-231-BR-HER2, and day 64 for SUM190-BR3. The mean volume of each tumor was calculated at these times for all mice in each of the three models (Figure 2). The average volume of a tumor was significantly different between models (F2,12 = 5.845, P < .05); but interestingly, a longer experiment did not mean larger tumors. Post hoc Tukey tests showed that MDA-MB-231-BR-HER2 tumors were significantly larger in size compared to JIMT-1-BR3 or SUM190-BR3 tumors despite the fact that the SUM190-BR3 model grew for longer. No significant difference in tumor volume was observed between JIMT-1-BR3 and SUM190-BR3 models, yet the SUM190-BR3 model grew for more than twice as long before the mice were noted to have neurological symptoms.


Understanding Heterogeneity and Permeability of Brain Metastases in Murine Models of HER2-Positive Breast Cancer Through Magnetic Resonance Imaging: Implications for Detection and Therapy.

Murrell DH, Hamilton AM, Mallett CL, van Gorkum R, Chambers AF, Foster PJ - Transl Oncol (2015)

Quantification of mean volume per tumor (± SEM) at end point in SUM190-BR3, JIMT-1-BR3, and MDA-MB-231-BR-HER2 models. The average volume of a tumor was significantly different between groups (F2,12 = 5.845, P < .05), and MDA-MB-231-BR-HER2 tumors were significantly larger in size compared to JIMT-1-BR3 or SUM190-BR3 tumors. No other significant differences were observed.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4487267&req=5

f0010: Quantification of mean volume per tumor (± SEM) at end point in SUM190-BR3, JIMT-1-BR3, and MDA-MB-231-BR-HER2 models. The average volume of a tumor was significantly different between groups (F2,12 = 5.845, P < .05), and MDA-MB-231-BR-HER2 tumors were significantly larger in size compared to JIMT-1-BR3 or SUM190-BR3 tumors. No other significant differences were observed.
Mentions: The 3D high-resolution nature of MRI allowed us to quantify metastasis volume and permeability in the whole mouse brain for each animal in all three models. We evaluated 198 tumors at experimental end point across the three models. Tumor incidence and total tumor burden are shown in Table 1. The SUM190-BR3 model grew few tumors, and the total tumor volume per brain was relatively low despite having the most cells injected. The MDA-MB-231-BR-HER2 model was injected with the least cells, yet grew the most tumors and had the highest total tumor volume. The study end point was decided when mice displayed clinical symptoms of the disease and deteriorating health. The time to end point was different for each model: day 28 for JIMT-1-BR3, day 36 for MDA-MB-231-BR-HER2, and day 64 for SUM190-BR3. The mean volume of each tumor was calculated at these times for all mice in each of the three models (Figure 2). The average volume of a tumor was significantly different between models (F2,12 = 5.845, P < .05); but interestingly, a longer experiment did not mean larger tumors. Post hoc Tukey tests showed that MDA-MB-231-BR-HER2 tumors were significantly larger in size compared to JIMT-1-BR3 or SUM190-BR3 tumors despite the fact that the SUM190-BR3 model grew for longer. No significant difference in tumor volume was observed between JIMT-1-BR3 and SUM190-BR3 models, yet the SUM190-BR3 model grew for more than twice as long before the mice were noted to have neurological symptoms.

Bottom Line: The mean volume of an MDA-MB-231-BR-HER2 tumor was significantly larger compared to other models (F2,12 = 5.845, P < .05); interestingly, this model also had a significantly higher proportion of Gd-impermeable tumors (F2,12 = 22.18, P < .0001).Ki67 staining indicated that Gd-impermeable tumors had significantly more proliferative nuclei compared to Gd-permeable tumors (t[24] = 2.389, P < .05) in the MDA-MB-231-BR-HER2 model.Understanding this heterogeneity, especially as it relates to BBB permeability, is important for improvement in brain metastasis detection and treatment delivery.

View Article: PubMed Central - PubMed

Affiliation: Imaging, Robarts Research Institute, London, Ontario, Canada; Medical Biophysics, Western University, London, Ontario, Canada. Electronic address: dmurrell@robarts.ca.

No MeSH data available.


Related in: MedlinePlus