Inhibitory Effects of a Reengineered Anthrax Toxin on Canine Oral Mucosal Melanomas - PubMed (original) (raw)

doi: 10.3390/toxins12030157.

Marcia Kazumi Nagamine 1, Ivone Izabel Mackowiak da Fonseca 1, Andrea Caringi Miraldo 1, Nayra Villar Scattone 1, José Luiz Guerra 1, José Guilherme Xavier 2, Mário Santos 2, Cristina Oliveira Massoco de Salles Gomes 1, Jerrold Michael Ward 3, Shihui Liu 4, Stephen Howard Leppla 5, Thomas Henrik Bugge 6, Maria Lucia Zaidan Dagli 1

Affiliations

Inhibitory Effects of a Reengineered Anthrax Toxin on Canine Oral Mucosal Melanomas

Adriana Tomoko Nishiya et al. Toxins (Basel). 2020.

Abstract

Canine oral mucosal melanomas (OMM) are the most common oral malignancy in dogs and few treatments are available. Thus, new treatment modalities are needed for this disease. Bacillus anthracis (anthrax) toxin has been reengineered to target tumor cells that express urokinase plasminogen activator (uPA) and metalloproteinases (MMP-2), and has shown antineoplastic effects both, in vitro and in vivo. This study aimed to evaluate the effects of a reengineered anthrax toxin on canine OMM. Five dogs bearing OMM without lung metastasis were included in the clinical study. Tumor tissue was analyzed by immunohistochemistry for expression of uPA, uPA receptor, MMP-2, MT1-MMP and TIMP-2. Animals received either three or six intratumoral injections of the reengineered anthrax toxin prior to surgical tumor excision. OMM samples from the five dogs were positive for all antibodies. After intratumoral treatment, all dogs showed stable disease according to the canine Response Evaluation Criteria in Solid Tumors (cRECIST), and tumors had decreased bleeding. Histopathology has shown necrosis of tumor cells and blood vessel walls after treatment. No significant systemic side effects were noted. In conclusion, the reengineered anthrax toxin exerted inhibitory effects when administered intratumorally, and systemic administration of this toxin is a promising therapy for canine OMM.

Keywords: Bacillus anthracis; anthrax; dog; oral melanoma; toxin.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1

Figure 1

Tumoral volume of canine OMM in 5 dogs after intratumoral treatment with the reengineered anthrax toxin.

Figure 2

Figure 2

Photomicrographs of canine OMM biopsy samples from dogs 1 (a,b), 2 (c,d), 3 (e,f), 4 (g,h) and 5 (i,j), obtained before (a,c,e,g,i) and after (b,d,f,h,j) the intratumoral treatment with the reengineered anthrax toxin. In samples obtained after the treatment, it is possible to see necrotic areas (arrows), as well as edema and hemorrhage. All photomicrographs were obtained in a stereo microscope (Nikon®), with a magnification of 5×. (H&E, Scale bar = 0.5 mm.).

Figure 3

Figure 3

Detail of histopathological sample of OMM from dog 4, showing necrosis of the blood vessel walls (arrows). (H&E, Scale bar = 100 μm.).

Similar articles

Cited by

References

    1. Bergman P.J. Canine Oral Melanoma. Clin. Tech. Small Anim. Pract. 2007;22:55–60. doi: 10.1053/j.ctsap.2007.03.004. - DOI - PubMed
    1. Nishiya A.T., Massoco C.O., Felizzola C.R., Perlmann E., Batschinski K., Tedardi M.V., Garcia J.S., Mendonça P.P., Teixeira T.F., Dagli M.L.Z. Comparative Aspects of Canine Melanoma. Vet. Sci. 2016;3:7. doi: 10.3390/vetsci3010007. - DOI - PMC - PubMed
    1. Williams L.E., Packer R.A. Association between lymph node size and metastasis in dogs with oral malignant melanoma: 100 cases (1987–2001) J. Am. Vet. Med. Assoc. 2003;222:1234–1236. doi: 10.2460/javma.2003.222.1234. - DOI - PubMed
    1. Tuohy J.L., Milgram J., Worley D.R., Dernell W.S. A review of sentinel lymph node evaluation and the need for its incorporation into veterinary oncology. Vet. Comp. Oncol. 2009;7:81–91. doi: 10.1111/j.1476-5829.2009.00183.x. - DOI - PubMed
    1. Esplin D.G. Survival of dogs following surgical excision of histologically well differentiated melanocytic neoplasms of the mucous membranes of the lips and oral cavity. Vet. Pathol. 2008;45:889–896. doi: 10.1354/vp.45-6-889. - DOI - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources