Companion Animals as Models for Inhibition of STAT3 and STAT5
<p>Advantages and disadvantages of different models during drug discovery. (<b>A</b>) Companion animals can be used as an intermediate step between the mechanistic work in murine models and clinical studies in humans, particularly with regard to comparative aspects of tumor biology. (<b>B</b>) Advantages and disadvantages of the individual models for translation into human clinical studies.</p> "> Figure 2
<p>Cross-species conservation of STAT protein domains. (<b>A</b>) STAT1, STAT3, STAT5a and STAT5b from dog, cat and mouse are analyzed for their overall homology compared to the respective human protein (grey boxes, left). In the schematic representation of STAT protein domains, the amino acid positions are indicated above. All proteins share the same domain positions, except for murine STAT1, which has a five amino acid insertion in the DNA binding domain (numbers below the scheme indicate the aa position in this case). Percentages in the domain boxes of dog, cat and mouse STAT proteins show the homology of each domain to the human counterpart. Analyses were carried out using ClustalX. (<b>B</b>) Comparison of key phosphorylation sites in the transactivation domain of STAT1, STAT3, STAT5a and STAT5b from dog, cat and mouse to the human sequence. Amino acid sequence is shown, with phosphorylation sites in green and position indicated; positive amino acid exchanges (conserving protein function) are indicated in yellow, other exchanges in red. (STAT1: human NP_009330.1, dog XP_848353.1, cat XP_006935505.1, mouse NP_001192242.1; STAT3: human NP_644805.1, dog XP_005624514.1, cat XP_003996930.1, mouse NP_998824.1; STAT5a: human NP_001275647.1, dog XP_548091.2, cat XP_023099834.1, mouse NP_001157534.1; STAT5b: human NP_036580.2, dog XP_548092.1, cat XP_023100377.1, mouse NP_035619.3).</p> ">
Abstract
:1. Introduction
2. Preclinical Models
3. Advantages and Disadvantages of Canine Tumor Models
4. Relevance and Conservation of the JAK-STAT Signaling Pathway
5. Inhibition of STAT3 and STAT5 in Companion Animals: Current Status/Future Perspectives
6. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
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Tissue | Human | Dog | Cat |
---|---|---|---|
Mammary | 127.5 [7] | 250 [8] | 13–25 [9] |
Melanoma | 22.2 [7] | 19.8 [10] | ND |
Testes | 5.9 [7] | 16.7 [11] | ND |
Connective Tissue | 3.5 [7] | 40.1 [10] | 17.0 [1] |
Skin | 98.85 [12] | 103.3 [10] | 34.7 [1] |
Oral | 11.3 [7] | 20.4 [1] | 11.6 [1] |
NHL/Leukemia | 33.7 [7] | 76.3 [13] | 41 [14] |
Bone | 1.0 [7] | 27.2 [15] | 3.1–4.9 [16] |
Breeds | Most Frequent Tumor Types |
---|---|
Bernese Mountain Dog | Histiocytic sarcoma [68], Lymphoma [68,69], Osteosarcoma [68] |
Boxer | Glioma [67,69], Mast cell tumor [10,67] |
Flat-Coated Retriever | Soft tissue sarcoma, Histiocytic sarcoma, Hemangiosarcoma [70] |
Golden Retriever | Mast cell tumor, Lymphoma, Oral Melanoma, Fibrosarcoma [67] |
Magyar Viszla | Mast cell tumor, Hemangiosarcoma, Lymphoma [10,71] |
Giant Schnauzer | Epidermal tumor, Hair follicle tumor, Melanocytic tumor [10] |
Airedale Terrier | Melanoma [72], Lymphoma [67], Prostatic carcinoma [67] |
Bullmastiff | Mast cell tumor, Lymphoma [67] |
St. Bernard | Lymphoma [67], Osteosarcoma [73] |
Irish Wolfhound | Osteosarcoma [67,74], Lymphoma [75] |
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Kieslinger, M.; Swoboda, A.; Kramer, N.; Pratscher, B.; Wolfesberger, B.; Burgener, I.A. Companion Animals as Models for Inhibition of STAT3 and STAT5. Cancers 2019, 11, 2035. https://doi.org/10.3390/cancers11122035
Kieslinger M, Swoboda A, Kramer N, Pratscher B, Wolfesberger B, Burgener IA. Companion Animals as Models for Inhibition of STAT3 and STAT5. Cancers. 2019; 11(12):2035. https://doi.org/10.3390/cancers11122035
Chicago/Turabian StyleKieslinger, Matthias, Alexander Swoboda, Nina Kramer, Barbara Pratscher, Birgitt Wolfesberger, and Iwan A. Burgener. 2019. "Companion Animals as Models for Inhibition of STAT3 and STAT5" Cancers 11, no. 12: 2035. https://doi.org/10.3390/cancers11122035