Journal: Cancer Research Communications

Article Title: Targeting Tumor Angiogenesis with the Selective VEGFR-3 Inhibitor EVT801 in Combination with Cancer Immunotherapy

doi: 10.1158/2767-9764.CRC-22-0151

Figure Lengend Snippet: EVT801 blocks hypoxia-driven immunosuppression and enhances ICT efficacy. A, Tumor volume progression over time of subcutaneous CT26 tumors in BALB/c mice in presence of vehicle, anti-PD-1 (twice per week), 30 mg/kg EVT801 (twice per day) or a combination of anti-PD-1 and EVT801 (15 mice per group). B, Individual CT26 tumors in BALB/c mice for each of the four treatment groups. C, Representative IHC images of hypoxic zones (via hypoxyprobe) in CT26 tumors at endpoint after treatment with vehicle, anti-PD-1, EVT801, or both anti-PD-1 and EVT801. D, Hypoxyprobe signal in individual tumors at endpoint for each of the four treatment groups. E, Tumor volume progression over time of orthotopic 4T1 tumors in BALB/c mice in presence of vehicle, anti-PD-1 (twice per week), 30 mg/kg EVT801 (twice per day) or a combination of anti-PD-1 and EVT801 (15 mice per group). F, Representative hematoxylin-eosin staining of 4T1 lung metastasis at endpoint for each of the four treatment groups. G, Quantitation of lung metastasis in individual mice at endpoint for each of the four treatment groups. H, Representative IHC images of CD8 + T cells via CD8 expression in 4T1 tumors at endpoint for each of the four treatment groups. I, Frequency of CD8 + T cells in 4T1 tumors at endpoint for each of the four treatment groups. The highlighted datapoint (in blue) refers to the samples that was used for IHC imaging in H .

Article Snippet: 4T1 mouse mammary adenocarcinoma cells (ATCC CRL-2539) were maintained in RPMI1640 containing 10% heat-inactivated FCS and 2 mmol/L Glutamax as described previously ( ).

Techniques: Staining, Quantitation Assay, Expressing, Imaging

Journal: Cancer Research Communications

Article Title: Targeting Tumor Angiogenesis with the Selective VEGFR-3 Inhibitor EVT801 in Combination with Cancer Immunotherapy

doi: 10.1158/2767-9764.CRC-22-0151

Figure Lengend Snippet: EVT801 reduces circulation of chemokines and MDSCs in the blood. A, Tumor volume progression over time of orthotopic 4T1 tumors in BALB/c mice in presence of vehicle, isotype control, anti-CTLA-4 (twice per week), 30 mg/kg EVT801 (twice per day), or a combination of anti-PD-1 and EVT801. B, Individual plasma concentrations of CCL3/MIP-1α, CCL4/MIP-1β, and CCL5/Rantes at endpoint for each of the four treatment groups. C, Individual blood concentration of CD124 + PMN-MDSCs at endpoint for each of the four treatment groups. D, Individual blood concentration of CD124 + M-MDSCs at endpoint for each of the four treatment groups. E, Individual blood concentration of CD8 + T cells at endpoint for each of the four treatment groups. F, Correlation between circulating CCL4 and PMN-MDSC levels. G, Correlation between circulating CCL4 and tumor weight. H, Inverse correlation between CD8 + T-cell/PMN-MDSC ratio and tumor weight.

Article Snippet: 4T1 mouse mammary adenocarcinoma cells (ATCC CRL-2539) were maintained in RPMI1640 containing 10% heat-inactivated FCS and 2 mmol/L Glutamax as described previously ( ).

Techniques: Control, Clinical Proteomics, Concentration Assay

Journal: Journal of controlled release : official journal of the Controlled Release Society

Article Title: Multimodal Imaging Demonstrates Enhanced Tumor Exposure of PEGylated FUD Peptide in Breast Cancer

doi: 10.1016/j.jconrel.2022.08.028

Figure Lengend Snippet: Whole-body imaging of tumor-bearing mice with difference sizes of tumors after SC injection of Cy5-peptides. (A) Experimental design of fluorescence imaging with Cy5-FUD, Cy5-PEG-FUD, and Cy5-PEG-mFUD. (B) Representative images of fluorescence imaging of 4T1 tumor-bearing mice subcutaneously injected with Cy5-FUD, Cy5-PEG-FUD, and Cy5-PEG-mFUD at 1, 2, and 3 weeks after the tumor (green arrows) implantation. The images were acquired at 24 h post-injection. (C) Quantification of fluorescence intensity in tumors of the images from Fig. 4B . Net radiant efficiency was obtained by subtracting the background fluorescence intensity before injection each week (means ± SD, n = 4–5). (D) Ex vivo images of the organs harvested after the 3-week whole animal imaging time points. (E) Quantification of fluorescence intensity of the images from Fig. 4D (means ± SD, n = 4–5 per group). *: P < 0.05, **: P < 0.01, ***: P < 0.001. Fig. 4A created with BioRender.com .

Article Snippet: To generate the 4T1 mouse breast cancer model, 8–10-week-old female Balb/C mice were purchased from Jackson Labs. For tumor cell inoculation, cells were harvested, washed in DPBS, then enumerated.

Techniques: Imaging, Injection, Fluorescence, Ex Vivo

Journal: Journal of controlled release : official journal of the Controlled Release Society

Article Title: Multimodal Imaging Demonstrates Enhanced Tumor Exposure of PEGylated FUD Peptide in Breast Cancer

doi: 10.1016/j.jconrel.2022.08.028

Figure Lengend Snippet: Intravital imaging of Cy5-FUD and Cy5-PEG-FUD in 4T1 mouse mammary carcinoma. After two weeks of tumor growth, images were acquired pre and post- 24 h SC injection of Cy5- peptides. SHG (collagen fibers) shown in grey, Cy5 (peptide) shown in cyan and vasculature in red. (A) Representative image of Cy5-FUD and Cy5-PEG-FUD in the TME pre-injection and 24 h post-injection, respectively. Scale bar = 150 μm. (B) Quantification of mean intensity of Cy5-labeled peptides. (C) Zoomed inset of Cy5-PEG-FUD 24 h p.i. Yellow arrows indicate Cy5-peptides localizing to cellular structures. Scale bar = 50 μm, ns: non-significant, ***: P < 0.001.

Article Snippet: To generate the 4T1 mouse breast cancer model, 8–10-week-old female Balb/C mice were purchased from Jackson Labs. For tumor cell inoculation, cells were harvested, washed in DPBS, then enumerated.

Techniques: Imaging, Injection, Labeling

Journal: Journal of controlled release : official journal of the Controlled Release Society

Article Title: Multimodal Imaging Demonstrates Enhanced Tumor Exposure of PEGylated FUD Peptide in Breast Cancer

doi: 10.1016/j.jconrel.2022.08.028

Figure Lengend Snippet: (A) A schematic diagram of the experimental design of μPET/CT imaging. (B) Longitudinal PET images of 4T1 tumor-bearing mice after IV injection of 64 Cu-FUD, 64 Cu-PEG-FUD, and 64 Cu-PEG-mFUD (5 mg/kg). The images were acquired 2, 24, and 48 h p.i. The white arrows indicate the locations of the major organs, i.e., tumor, heart, liver, and kidneys. Fig. 7A created with BioRender.com .

Article Snippet: To generate the 4T1 mouse breast cancer model, 8–10-week-old female Balb/C mice were purchased from Jackson Labs. For tumor cell inoculation, cells were harvested, washed in DPBS, then enumerated.

Techniques: Imaging, IV Injection

Journal: Journal of controlled release : official journal of the Controlled Release Society

Article Title: Multimodal Imaging Demonstrates Enhanced Tumor Exposure of PEGylated FUD Peptide in Breast Cancer

doi: 10.1016/j.jconrel.2022.08.028

Figure Lengend Snippet: (A) In vivo μPET imaging analysis of 4T1 tumor-bearing mice after IV injection of 64 Cu-FUD, 64 Cu-PEG-FUD, and 64 Cu-PEG-mFUD shown in time-activity curves for heart, lung, tumor, kidneys, and liver (means ± SD, n = 4). (B) Analysis of ex vivo biodistribution of 64 Cu-FUD, 64 Cu-PEG-FUD, and 64 Cu-PEG-mFUD after IV injection. The activity remaining in organs at each time point at 48 h was presented as the percent injected activity per gram (%IA/g). *: P < 0.05, **: P <0.01, ***: P <

Article Snippet: To generate the 4T1 mouse breast cancer model, 8–10-week-old female Balb/C mice were purchased from Jackson Labs. For tumor cell inoculation, cells were harvested, washed in DPBS, then enumerated.

Techniques: In Vivo, Imaging, IV Injection, Activity Assay, Ex Vivo, Injection