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Perspective directions of bitches conservative treatment with breast tumors (review information)

The problem of treating tumors in dogs remains relevant due to the complexity of pathogenetic cascades, lack of common methodological approaches to diagnosis and treatment of cancer patients, insufficient number of animals in groups, the described nature of the results, incorrect "mechanical" borrowing of therapeutic protocols from human medicine. The proposed treatment regimens do not provide the desired results, there is a steady trend to increase the number of small pets with breast tumors. Therefore, it is important to find alternative treatments for dogs with breast neoplasms, among which, first of all, should be noted the use of nonsteroidal anti-inflammatory drugs, which cause a positive effect by inhibiting the expression of cyclooxygenase-2, activating apoptosis and inhibiting cancer cell migration. Potentially effective therapeutic methods are electroporation and electrochemotherapy, which can significantly increase the concentration of chemotherapeutic agents in cancer cells against the background of minimal toxicity to healthy tissues. The important role of hypercoagulation in the mechanisms of development and progression of breast tumors in dogs justifies the use of antithrombotic therapy in cancer patients, especially low molecular weight heparins, which can improve the effectiveness of therapeutic protocols and prevent tumor metastasis. It is shown that these methods as part of complex treatment regimens increase the effectiveness of conventional protocols of chemotherapy and radiation therapy, as well as surgery. However, further studies of the pathogenetic aspects of these treatments for breast tumors in bitches and the possibility of combining them with other therapeutic regimens are needed.

Key words: bitches, breast neoplasms, treatment protocols, nonsteroidal anti-inflammatory drugs, electroporation, antithrombotic therapy.

41. Impellizeri, J., Aurisicchio, L., Forde, P., Soden, D.M. (2016). Electroporation in veterinary oncology. Veterinary Journal. Vol. 217, pp. 18–25. Doi: 10.1016/j.tvjl.2016.05.015

42. Klein, N., Guenther, E., Mikus, P., Stehling, M.K., Rubinsky, B. (2017). Single exponential decay waveform; a synergistic combination of electroporation and electrolysis (E2) for tissue ablation. PeerJ. Vol. 5: e3190. Doi: 10.7717/ peerj.3190

43. Spugnini, E.P., Fanciulli, M., Citro, G., Baldi, A. (2012). Preclinical models in electrochemotherapy: the role of veterinary patients. Future Oncology. Vol. 8 (7), pp. 829–837. Doi: 10.2217/fon.12.64

44. Jourabchi, N., Beroukhim, K., Tafti, B.A., Kee, S.T., Lee, E.W. (2014). Irreversible electroporation (NanoKnife) in cancer treatment. Gastrointestinal Intervention. Vol. 3, pp. 8–18. Doi: 10.1016/j.gii.2014.02.002

45. Jarm, T., Cemazar, M., Miklavcic, D., Sersa, G. (2010). Antivascular effects of electrochemotherapy: implications in treatment of bleeding metastases. Expert review of anticancer therapy. Vol. 10 (5), pp. 729–746. Doi: 10.1586/era.10.43

46. Thomson, K.R., Kavnoudias, H., Neal, R.E. (2015). Introduction to Irreversible Electroporation-Principles and Techniques. Techniques in Vascular and Interventional Radiology. Vol. 18 (3), pp. 128–134. Doi: 10.1053/j. tvir.2015.06.002

47. Mercadal, B., Beitel-White, N., Aycock, K.N., Castellví, Q., Davalos, R.V. (2020). Dynamics of cell death after conventional IRE and H-FIRE treatments. Annals of Biomedical Engineering. Vol. 48 (5), pp. 1451–1462. Doi: 10.1007/s10439-020-02462-8

48. Sano, M.B., Fesmire, C.C., DeWitt, M.R., Xing, L. (2018). Burst and continuous high frequency irreversible electroporation protocols evaluated in a 3D tumor model. Physics in Medicine and Biology. Vol. 63 (13): 135022. Doi: 10.1088/1361-6560/aacb62

49. Ringel-Scaia, V.M., Beitel-White, N., Lorenzo, M.F., Brock, R.M., Huie, K.E., Coutermarsh-Ott, S., Eden, K., McDaniel, D.K., Verbridge, S.S., Rossmeisl, J.H., Oestreich, K.J., Davalos, R.V., Allen, I.C. (2019). High-frequency irreversible electroporation is an effective tumor ablation strategy that induces immunologic cell death and promotes systemic antitumor immunity. EBioMedicine. Vol. 44, pp. 112–125. Doi: 10.1016/j.ebiom.2019.05.036

50. Neal, R.E., Garcia, P.A., Rossmeisl, J.H., Davalos, R.V. (2010). A study using irreversible electroporation to treat large, irregular tumors in a canine patient. Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference. Piscataway, pp. 2747– 2750. (United States). Doi: 10.1109/IEMBS.2010.5626372

51. Perkons, N.R., Stein, E.J., Nwaezeapu, C., Wildenberg, J.C., Saleh, K. (2018). Electrolytic ablation enables cancer cell targeting through pH modulation. Communications Biology. Vol. 1, 48 p. Doi: 10.1038/ s42003-018-0047-1

52. Phillips, M., Krishnan, H., Raju, N., Rubinsky, B. (2016). Tissue ablation by a synergistic combination of electroporation and electrolysis delivered by a single pulse. Annals of Biomedical Engineering. Vol. 44 (10), pp. 3144– 3154. Doi: 10.1007/s10439-016-1624-4

53. Guenther, E., Klein, N., Mikus, P., Botea, F., Pautov, M., Lugnani, F., Macchioro, M., Popescu, I., Stehling, M.K., Rubinsky, B. (2020). Toward a clinical real time tissue ablation technology: combining electroporation and electrolysis (E2). PeerJ. Vol. 8: e7985. Doi: 10.7717/peerj.7985

54. Spugnini, E. P., Baldi, F., Mellone, P., Feroce, F., D'Avino, A., Bonetto, F., Vincenzi, B., Citro, G., Baldi, A. (2007). Patterns of tumor response in canine and feline cancer patients treated with electrochemotherapy: preclinicaldata for the standardization of this treatment in pets and humans. Journal of Translational Medicine. Vol. 5: 48. Doi: 10.1186/1479-5876-5-48

55. Calvet, C.Y., Mir, L.M. (2016). The promising alliance of anti-cancer electrochemotherapy with immunotherapy. Cancer Metastasis Reviews. Vol. 35 (2), pp. 165–177. Doi: 10.1007/s10555-016-9615-3

56. Spugnini, E.P., Baldi, A. (2019). Electrochemotherapy in veterinary oncology: state-of-the-art and perspectives. The Veterinary Clinics of North America. Small Animal Practice. Vol. 49 (5), pp. 967–979. Doi: 10.1016/j.cvsm.2019.04.006

57. Giardino, R., Fini, M., Bonazzi, V., Cadossi, R., Nicolini, A., Carpi, A. (2006). Electrochemotherapy a novel approach to the treatment of metastatic nodules on the skin and subcutaneous tissues. Biomedicine & Pharmacotherapy. Vol. 60 (8), pp. 458–462. Doi: 10.1016/j.biopha.2006.07.016

58. Kodre, V., Cemazar, M., Pecar, J., Sersa, G., Cor, A., Tozon, N. (2009). Electrochemotherapy compared to surgery for treatment of canine mast cell tumours. In Vivo. Vol. 23 (1), pp. 55–62. PMID: 19368125

59. Heller, L.C., Heller, R. (2010). Electroporation gene therapy preclinical and clinical trials for melanoma. Current Gene Therapy. Vol. 10 (4), pp. 312–317. Doi: 10.2174/156652310791823489

60. Pavlin, D., Cemazar, M., Sersa, G., Tozon, N. (2012). IL-12 based gene therapy in veterinary medicine. Journal of Translational Medicine. Vol. 10:234. Doi: 10.1186/1479- 5876-10-234

61. Cutrera, J., King, G., Jones, P., Kicenuik, K., Gumpel, E., Xia, X., Li, S. (2015). Safety and efficacy of tumor-targeted interleukin 12 gene therapy in treated and non-treated, metastatic lesions. Current Gene Therapy. 2015. Vol. 15 (1), pp. 44–54. Doi: 10.2174/156652321466614112 7093654

62. Cemazar, M., Jarm, T., Sersa, G. (2010). Cancer electrogene therapy with interleukin-12. Current Gene Therapy. Vol. 10 (4), pp. 300–311. Doi: 10.2174/156652310791823425

63. Cutrera, J., King, G., Jones, P., Kicenuik, K., Gumpel, E., Xia, X., Li, S. (2015). Safe and effective treatment of spontaneous neoplasms with interleukin 12 electro-chemo-gene therapy. Journal of Cellular and Molecular Medicine. Vol. 19 (3), pp. 664–675. Doi: https:// Doi.org/10.1111/jcmm.12382

64. Mali, B., Jarm, T., Snoj, M., Sersa, G., Miklavcic, D. (2013). Antitumor effectiveness of electrochemotherapy: a systematic review and meta-analysis. European Journal of Surgical Oncology: The Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. Vol. 39 (1), pp. 4–16. Doi: 10.1016/j. ejso.2012.08.016

65. Tozon, N., Sersa, G., Cemazar, M. (2001). Electrochemotherapy: potentiation of local antitumour effectiveness of cisplatin in dogs and cats. Anticancer Research. Vol. 21 (4A), pp. 2483–2488. PMID: 11724311

66. Sedlar, A., Dolinsek, T., Markelc, B., Prosen, L., Kranjc, S., Bosnjak, M., Blagus, T., Cemazar, M., Sersa, G. (2012). Potentiation of electrochemotherapy by intramuscular IL-12 gene electrotransfer in murine sarcoma and carcinoma with different immunogenicity. Radiology and Oncology. Vol. 46 (4), pp. 302–311. Doi: 10.2478/v10019-012-0044-9

67. Milevoj, N., Tozon, N., Licen, S., Lampreht Tratar, U., Sersa, G., Cemazar, M. (2020). Health-related quality of life in dogs treated with electrochemotherapy and/or interleukin-12 gene electrotransfer. Veterinary Medicine and Science. Vol. 6 (3), pp. 290–298. Doi: https:// Doi.org/10.1002/vms3.232

68. Tozon, N., Lampreht Tratar, U., Znidar, K., Sersa, G., Teissie, J., Cemazar, M. (2016). Operating procedures of the electrochemotherapy for treatment of tumor in dogs and cats. Journal of Visualized Experiments. Vol. 116: 54760. Doi: 10.3791/54760

69. Escoffre, J.M., Rols, M.P. (2012). Electrochemotherapy: progress and prospects. Current Pharmaceutical Design. Vol. 18 (23), pp. 3406–3415. PMID: 22663554

70. Bely, D.D., Rublenko, M.V., Samoyuluk, V.V., Yevtushenko, I.D., Maslikov, S.N. (2019). Breast tumour size as a predictor of hemostatic system status and endothelial function in dog. Regulatory Mechanisms in Biosystems. Vol. 10 (3), pp. 300–305. Doi: https: //Doi.org/10.15421/021946

71. Wojtukiewicz, M.Z., Hempel, D., Sierko, E., Tucker, S.C., Honn, K.V. (2017). Antiplatelet agents for cancer treatment: a real perspective or just an echo from the past? Cancer Metastasis Reviews. Vol. 36 (2), pp. 305–329. Doi: 10.1007/s10555-017-9683-z

72. Placencio, V.R., DeClerck, Y.A. (2015). Plasminogen activator inhibitor-1 in cancer: rationale and insight for future therapeutic testing. Cancer Research. Vol. 75 (15), pp. 2969– 2974. Doi: 10.1158/0008-5472.CAN-15-0876

73. Tieken, C., Versteeg, H.H. (2016). Anticoagulants versus cancer. Thrombosis research. Vol. 140 (1), pp. 148– 153. Doi: 10.1016/S0049-3848(16)30114-1

74. Lanzi, C., Cassinelli, G. (2018). Heparan sulfate mimetics in cancer therapy: the challenge to define structural determinants and the relevance of targets for optimal activity. Molecules. Vol. 23 (11): 2915. Doi: 10.3390/ molecules23112915

75. Franchini, M., Mannucci, P.M. (2016). Direct oral anticoagulants and venous thromboembolism. European respiratory review: an official journal of the European Respiratory Society. 2016. Vol. 25 (141), pp. 295–302. Doi: 10.1183/16000617.0025-2016

76. Kim, J., Kim, W.J., Park, J., Shin, J., Yoon, H.Y. (2016). Canine mammary anaplastic carcinoma with concurrent aortoiliac thrombosis in a dog: a case report. Veterinarni Medicina. Vol. 60, pp. 391–398. Doi: 10.17221/8388-VETMED

77. Losonczy, H., Nagy, Á., Tar, A. (2016). A kórházi és az ambuláns kemoterápiában részesülő onkológiai betegek vénásthromboembolia-profilaxisának aktuális kérdései. Actual questions about the prevention of venous thromboembolism in cancer patients receiving chemotherapy. Orvosi hetilap. Vol. 157 (6), pp. 203–211. Doi: 10.1556/650.2016.30357

78. Fletcher, D.J., Blackstock, K.J., Epstein, K., Brainard, B.M. (2014). Evaluation of tranexamic acid and ϵ-aminocaproic acid concentrations required to inhibit fibrinolysis in plasma of dogs and humans. American Journal of Veterinary Research. Vol. 75, pp. 731–738. Doi: 10.2460/ ajvr.75.8.731

79. Posch, F., Königsbrügge, O., Zielinski, C., Pabinger, I., Ay, C. (2015). Treatment of venous thromboembolism in patients with cancer: A network meta-analysis comparing efficacy and safety of anticoagulants. Thrombosis Research. Vol. 136 (3), pp. 582–589. Doi: https:// Doi.org/10.1016/j. thromres.2015.07.011

80. van der Hulle, T., den Exter, P.L., Kooiman, J., van der Hoeven, J.J., Huisman, M.V., Klok, F.A. (2014). Meta-analysis of the efficacy and safety of new oral anticoagulants in patients with cancer-associated acute venous thromboembolism. Journal of Thrombosis and Haemostasis. Vol. 12 (7), pp. 1116–1120. Doi: 10.1111/jth.12605

81. Kirkilesis, G.I., Kakkos, S.K., Tsolakis, I.A. (2019). Editor's choice – a systematic review and meta-analysis of the efficacy and safety of anticoagulation in the treatment of venous thromboembolism in patients with cancer. European Journal of Vascular and Endovascular Surgery. Vol. 57 (5), pp. 685–701. Doi: 10.1016/j.ejvs.2018.11.004

82. Osekavage, K.E., Brainard, B.M., Lane, S.L., Almoslem, M., Arnold, R.D., Koenig, A. (2018). Pharmacokinetics of tranexamic acid in healthy dogs and assessment of its antifibrinolytic properties in canine blood. American Journal of Veterinary Research. Vol. 79 (10), pp. 1057–1063. Doi: 10.2460/ajvr.79.10.1057

83. Garona, J., Pifano, M., Scursoni, A., Gomez, D., Alonso, D., Ripoll, G.V. (2014). Insight into the effect of the vasopressin analog desmopressin on lung colonization by mammary carcinoma cells in BALB/c mice. Anticancer Research. Vol. 34 (9), pp. 4761–4765. PMID: 25202055

84. Kim, J.H., Kim, W.J., Park, J., Shin, J.I., Yoon, H.Y. (2015). Canine mammary anaplastic carcinoma with concurrent aorto-iliac thrombosis in a dog: a case report. Veterinarni Medicina. Vol. 60, pp. 391–398. Doi: 10.17221/8388-VETMED

85. Kim, J.H., Park, H.M. (2012). Unilateral femoral arterial thrombosis in a dog with malignant mammary gland tumor: clinical and thermographic findings, and successful treatment with local intra-arterial administration of streptokinase. Journal of Veterinary Medical Science. Vol. 74 (5), pp. 657–661. Doi: 10.1292/jvms.11-0432

86. Yin, W., Zhang, J.G., Jiang, Y., Juan, S.A. (2014). Combination therapy with low molecular weight heparin and Adriamycin results in decreased breast cancer cell metastasis in C3H mice. Experimental and Therapeutic Medicine. Vol. 8, pp. 1213–1218. Doi: 10.3892/etm.2014.1911

87. Hermo, G.A., Turic, E., Angelico, D., Scursoni, A.M., Gomez, D.E., Gobello, C., Alonso, D.F. (2011). Effect of adjuvant perioperative desmopressin in locally advanced canine mammary carcinoma and its relation to histologic grade. Journal of the American Animal Hospital Association. Vol. 47 (1), pp. 21–27. Doi: 10.5326/JAAHA-MS-5509

88. Alonso, D.F., Ripoll, G.V., Garona, J., Iannucci, N.B., Gomez, D.E. (2011). Metastasis: recent discoveries and novel perioperative treatment strategies with particular interest in the hemostatic compound desmopressin. Current Рharmaceutical Biotechnology. Vol. 12 (11), pp. 1974–1980. Doi: 10.2174/138920111798377076

89. Frere, C., Lejeune, M., Kubicek, P., Faille, D., Marjanovic, Z. (2019). Antiplatelet Agents for Cancer Prevention: Current Evidences and Continuing Controversies. Cancers. Vol. 11 (11): 1639. Doi: 10.3390/cancers11111639

90. Ibrahim, S.S., Osman, R., Awad, G.A., Mortada, N.D., Geneidy, A.S. (2016). Low molecular weight heparins for current and future uses: approaches for micro- and nanoparticulate delivery. Drug Delivery. Vol. 23 (8), pp. 2661–2667. Doi: 10.3109/10717544.2015.1046570

91. Sun, H., Cao, D., Wu, H., Liu, H., Ke, X., Ci, T. (2018). Development of low molecular weight heparin based nanoparticles for metastatic breast cancer therapy. International Journal of Biological Macromolecules. Vol. 112, pp. 343–355. Doi: 10.1016/j.ijbiomac.2018.01.195

92. Bae, S.M., Kim, J.H., Chung, S.W., Byun, Y., Kim, S.Y., Kim, I.S., Park, R.W. (2013). An apoptosishoming peptide-conjugated low molecular weight heparin-taurocholate conjugate with antitumor properties. Biomaterials. Vol. 34 (8), pp. 2077–2086. Doi:10.1016/j. biomaterials.2012.11.020

93. Tang, B., Qian, Y., Fang, G. (2020). Development of lipid-polymer hybrid nanoparticles for improving oral absorption of enoxaparin. Pharmaceutics. Vol. 12 (7): 607. Doi: 10.3390/pharmaceutics12070607

94. Elaskalani, O., Berndt, M.C., Falasca, M., Metharom, P. (2017). Targeting platelets for the treatment of cancer. Cancers. Vol. 9 (7): 94. Doi:10.3390/cancers9070094

95. Rossi, G.R., Gonçalves, J.P., McCulloch, T., Delconte, R.B., Hennessy, R.J., Huntington, N.D., Trindade, E.S., Souza-Fonseca-Guimaraes, F. (2020). The antitumor effect of heparin is not mediated by direct NK cell activation. Journal of Clinical Medicine. Vol. 9 (8): E2666. Doi: 10.3390/jcm9082666

96. Bely, D.D., Rublenko, M.V., Rublenko, S.V., Yevtushenko, I.D., Suslova, N.I., Samoyuluk, V.V. (2018). Pharmacological correction of the hemostasis system for the surgical treatment of females tumors of the mammary gland. Regulatory Mechanisms in Biosystems. Vol. 9 (3), pp. 353– 362. Doi: 10.15421/021852

97. Serebruany, V.L., Cherepanov, V., Cabrera-Fuentes, H.A., Kim, M.H. (2015). Solid cancers after antiplatelet therapy: Confirmations, controversies, and challenges. Thrombosis and Haemostasis. Vol. 114 (6), pp. 1104–1112. Doi:10.1160/TH15-01-0077

98. Gómez-Outes, A., Suárez-Gea, M.L., Lecumberri, R., Terleira-Fernández, A.I., Vargas-Castrillón, E., Rocha, E. (2013). Potential role of new anticoagulants for prevention and treatment of venous thromboembolism in cancer patients. Vascular Health and Risk Management. Vol. 9, pp. 207–228. Doi: 10.2147/VHRM.S35843

99. Lunsford, K., Mackin, A. (2007). Thromboembolic therapies in dogs and cats: an evidence-based approach. The Veterinary Clinics of North America. Small Animal Practice. Vol. 37 (3), pp. 579–609. Doi: 10.1016/j.cvsm.2007.01.010

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