Limits...
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

The mean proliferation index (± SD) for Gd-permeable and Gd-impermeable brain metastases in the MDA-MB-231-BR-HER2 model. This quantifies tumor proliferation by Ki67 staining and indicates that there is significantly more proliferative nuclei in Gd-impermeable compared to Gd-permeable brain metastases (t[24] = 2.389, P < .05).
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4487267&req=5

f0025: The mean proliferation index (± SD) for Gd-permeable and Gd-impermeable brain metastases in the MDA-MB-231-BR-HER2 model. This quantifies tumor proliferation by Ki67 staining and indicates that there is significantly more proliferative nuclei in Gd-impermeable compared to Gd-permeable brain metastases (t[24] = 2.389, P < .05).

Mentions: Immunohistochemistry was performed and evaluated, including CD31, CD105, and Ki67 stains, in an effort to understand factors that might relate to differences between Gd-permeable and Gd-impermeable tumors. Individual tumors in whole brain sections were identified as either Gd permeable or Gd impermeable by comparing to MRI. For this analysis, Gd-impermeable tumors were assessed only from the MDA-MB-231-BR-HER2 model because of their low prevalence in the other models. Ki67 is a marker for proliferative nuclei and was used to calculate the mean proliferative index for Gd-permeable and Gd-impermeable brain metastases in the MDA-MB-231-BR-HER2 model. The proliferative index was determined as the percentage of positively stained nuclei among MDA-MB-231-BR-HER2 cells. The proliferative index for Gd-impermeable tumors was significantly higher than for Gd-permeable tumors (t[24] = 2.389, P < .05) (Figure 5). CD31 is a marker for endothelial cells, and CD105 marks proliferative endothelial cells. Together, these stains visualize vasculature patterns and can indicate where new vessels are being formed. This staining was only assessed qualitatively, and it is interesting to note the different staining patterns across the three models. In the SUM190-BR3 model, CD31 staining was strongly localized to the outer edge of the tumor rim, whereas CD105 staining was strongest on the inner edge of the tumor rim. This indicated the presence of vasculature around the tumor and new vasculature development inside, near the tumor core. The JIMT-1-BR3 and MDA-MB-231-BR-HER2 models had more similar patterns of CD31 and CD105 staining; the JIMT-1-BR3 model had existing and new vasculature dispersed throughout the tumor space, whereas in MDA-MB-231-BR-HER2 tumors, this appeared to be associated near areas of edema. Despite variance in vasculature patterns across the three models, no differences were observed between Gd-permeable and Gd-impermeable tumors (Figure 6).


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)

The mean proliferation index (± SD) for Gd-permeable and Gd-impermeable brain metastases in the MDA-MB-231-BR-HER2 model. This quantifies tumor proliferation by Ki67 staining and indicates that there is significantly more proliferative nuclei in Gd-impermeable compared to Gd-permeable brain metastases (t[24] = 2.389, P < .05).
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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

f0025: The mean proliferation index (± SD) for Gd-permeable and Gd-impermeable brain metastases in the MDA-MB-231-BR-HER2 model. This quantifies tumor proliferation by Ki67 staining and indicates that there is significantly more proliferative nuclei in Gd-impermeable compared to Gd-permeable brain metastases (t[24] = 2.389, P < .05).
Mentions: Immunohistochemistry was performed and evaluated, including CD31, CD105, and Ki67 stains, in an effort to understand factors that might relate to differences between Gd-permeable and Gd-impermeable tumors. Individual tumors in whole brain sections were identified as either Gd permeable or Gd impermeable by comparing to MRI. For this analysis, Gd-impermeable tumors were assessed only from the MDA-MB-231-BR-HER2 model because of their low prevalence in the other models. Ki67 is a marker for proliferative nuclei and was used to calculate the mean proliferative index for Gd-permeable and Gd-impermeable brain metastases in the MDA-MB-231-BR-HER2 model. The proliferative index was determined as the percentage of positively stained nuclei among MDA-MB-231-BR-HER2 cells. The proliferative index for Gd-impermeable tumors was significantly higher than for Gd-permeable tumors (t[24] = 2.389, P < .05) (Figure 5). CD31 is a marker for endothelial cells, and CD105 marks proliferative endothelial cells. Together, these stains visualize vasculature patterns and can indicate where new vessels are being formed. This staining was only assessed qualitatively, and it is interesting to note the different staining patterns across the three models. In the SUM190-BR3 model, CD31 staining was strongly localized to the outer edge of the tumor rim, whereas CD105 staining was strongest on the inner edge of the tumor rim. This indicated the presence of vasculature around the tumor and new vasculature development inside, near the tumor core. The JIMT-1-BR3 and MDA-MB-231-BR-HER2 models had more similar patterns of CD31 and CD105 staining; the JIMT-1-BR3 model had existing and new vasculature dispersed throughout the tumor space, whereas in MDA-MB-231-BR-HER2 tumors, this appeared to be associated near areas of edema. Despite variance in vasculature patterns across the three models, no differences were observed between Gd-permeable and Gd-impermeable tumors (Figure 6).

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