H&E sections of brachial lymph nodes from C57B/l6, Nude and C.B.-17 SCID mice.

<p>Whole nodes are shown at 5x magnification. The T cell rich paracortex (arrowsheads) and B cell rich follicles (arrows) can be easily seen in the nodes of C57B/l6 mice, where as in Nude mouse lymph nodes, only the B cell rich follicles can be seen (arrows). In the areas of the paracortex where T cells should be found, vacant areas are detected (arrowheads), helping to explain the hyperintense appearance of many of these nodes in MR images. Nodes in SCID mice lack both the paracortex and follicles, leaving these nodes underdeveloped and significantly smaller in size.</p

bSSFP images of the spleen.

<p>(A) C57Bl/6 mice. (B) Nude mice. (C) CB-17 SCID mice. (D) NOG mice. (E) Spleen volume in C57Bl/6, Nude, CB-17 SCID and NOG mice. (*) Spleen volumes were significantly smaller in CB-17 SCID and NOG mice (p<0.0001) compared to C57Bl/6 and nude mice. One way ANOVA test was used. Error bars represent the standard deviation.</p

MR images of a nude mouse brachial lymph node acquired with different pulse sequences.

<p>(A) bSSFP image of whole mouse body, (B) bSSFP image of lymph node, (C) T1w SE of lymph node (TR = 600 ms, TE = 25 ms), (D) T2w SE of lymph node (TR = 2000 ms, TE = 80 ms)</p

Lymph node volumes of C57Bl/6, Nude and CB-17 SCID mice. All volumes listed as mean ± standard deviation.

<p>Lymph node volumes of C57Bl/6, Nude and CB-17 SCID mice. All volumes listed as mean ± standard deviation.</p

Location of lymph nodes within the mouse body.

<p>(A) Whole mouse body bSSFP image of a C57Bl/6 mouse showing both the brachial and inguinal lymph nodes (arrows) and (B) 3D reconstruction showing the location of various lymph nodes within the mouse; 1 – axillary node, 2 – brachial node, 3 – inguinal node, 4 – popliteal node.</p

Lymph node volumes over time.

<p>(A) C57Bl/6 mice. (B) Nude mice. (C) CB-17 SCID mice. Significant differences were found in the inguinal (p = 0.0071) nodes of C57Bl/6 mice. Significant differences were also found in the axillary (p = 0.0104), inguinal (p = 0.0155) and popliteal (p = 0.0046) nodes of nude mice. Significant differences were also found in SCID mice in the brachial (p = 0.0130) and inguinal nodes (p = 0.0225). (*) Significantly different compared to day 7. Repeated measures ANOVA test was used. Error bars represent the standard deviation.</p

Nude mouse axillary node with hyperintense center.

<p>(A) MR image. (B) Corresponding histology. The hyperintense area within the lymph node (arrow) corresponds to a cavity that is visible in the histology.</p

MR appearance and volumes of lymph nodes various mouse strains.

<p>(A) MR appearance of the axillary, brachial, inguinal and popliteal lymph nodes in C57Bl/6, Nude, CB-17 SCID and NOG mice. The brachial, inguinal and popliteal lymph nodes are easiest to visualize due to their location within a fat pad. Lymphatic vessels are also visible in acquired images (arrowhead). Images for the NOG mice are included for completeness although there were no MRI detectable lymph nodes. (B) Volumes of the axillary, brachial, inguinal and popliteal lymph nodes in C57Bl/6, Nude and CB-17 SCID mice. The brachial, inguinal and popliteal lymph nodes in CB-17 SCID mice were found to be significantly smaller than those in both C57Bl/6 and Nude mice (*, p<0.0001 for brachial and inguinal and p = 0.0128 for popliteal). The axillary node in Nude mice was significantly larger than those in both CB-17 SCID and C57Bl/6 mice (**, p<0.0001). One way ANOVA test was used. Error bars represent the standard deviation.</p

DataSheet_1_Inhibition of Anti-Inflammatory Macrophage Phenotype Reduces Tumour Growth in Mouse Models of Brain Metastasis.pdf

Breast cancer brain metastasis is a significant clinical problem and carries a poor prognosis. Although it is well-established that macrophages are a primary component of the brain metastasis microenvironment, the role of blood-derived macrophages (BDM) and brain-resident microglia in the progression of brain metastases remains uncertain. The aim of this study, therefore, was to determine the role, specifically, of pro- and anti-inflammatory BDM and microglial phenotypes on metastasis progression. Initial in vitro studies demonstrated decreased migration of EO771 metastatic breast cancer cells in the presence of pro-inflammatory, but not anti-inflammatory, stimulated RAW 264.7 macrophages. In vivo, suppression of the anti-inflammatory BDM phenotype, specifically, via myeloid knock out of Krüppel-like Factor 4 (KLF4) significantly reduced EO771 tumour growth in the brains of C57BL/6 mice. Further, pharmacological inhibition of the anti-inflammatory BDM and/or microglial phenotypes, via either Colony Stimulating Factor 1 Receptor (CSF-1R) or STAT6 pathways, significantly decreased tumour burden in two different syngeneic mouse models of breast cancer brain metastasis. These findings suggest that switching BDM and microglia towards a more pro-inflammatory phenotype may be an effective therapeutic strategy in brain metastasis.</p