Abstract

Due to their significant impact on human and animal health, cancer diseases are an area of considerable concern for both human and veterinary medicine. Research on the cancer pathogenesis in companion animals, such as dogs, allows not only for improving canine cancer treatment, but also for translating the results into human oncology. Disruption of apoptosis in tumor-transformed cells is a well-known mechanism leading to the development of cancer. One of the main factors involved in this process are proteins belonging to the B-cell lymphoma 2 (Bcl-2) family, and the imbalance between pro-apoptotic and anti-apoptotic members of this family contributes to the development of cancer. Studies on the function of these proteins, including B-cell lymphoma-extra large (Bcl-xL), have also been intensively conducted in companion animals. The Bcl-xL gene was sequenced and found to share over 99% homology with the human protein. Research showed that the Bcl-2 family plays the same role in human and canine cells, and data from studies in dogs are fully translatable to other species, including humans. The role of this protein family in cancer development was also confirmed. The article presents the current state of knowledge on the importance of the Bcl-xL protein in veterinary oncology.

Highlights

  • B-cell lymphoma-extra large (Bcl-xL) and B-cell lymphoma 2 (Bcl-2) prevent the apoptosis by sequestering the activator Bcl-2 homology (BH)-3s from BAX–BAK, while after an apoptotic stimuli BH-3-only sensitizers enable interactions between the multi-domain pro-apoptotic executioner proteins and their activators by displacing the anti-apoptotic proteins from the activators [22,23]

  • This study described experimental conditions that allow gene silencing in the canine cells and showed considerable cytotoxicity of oligofectamine medium itself

  • The increasing number of specialized research tools available in veterinary experimental oncology makes it possible to conduct studies in canine or feline cancer cells, which are an irreplaceable model for preclinical research

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Summary

Comparative Oncology—Canine Models in Cancer Biology and Therapy

Due to the similarity between dog and human cancers, the importance of comparative oncology has increased significantly in recent times It is a rapidly developing discipline aimed at integrating studies on naturally occurring animal cancers and employing these data in a more general research on cancer biology and therapy [1]. The most important types of cancer that can be studied using canine disease models include, e.g., bone tumors, such as osteosarcoma, hematopoietic cancers—especially leukemia and non-Hodgkin’s lymphoma, melanoma, various carcinomas of the lung, bladder, head and neck, prostate or mammary gland, soft tissue sarcomas, and multiple brain cancer types [7] These types of cancer, in addition to similar genetic background and clinical course in dogs and humans, share a similar clinical approach. The Bcl-xL (B-cell lymphoma-extra large) protein is the subject of the presented research and one of the most important components of the apoptotic process

Role of Bcl-xL Protein in Apoptosis
Bcl-xL Protein and Its Canine Version
Findings
Conclusions

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