New therapeutic targets in veterinary oncology: Man and dog definitely are best friends

Casteleyn, Christophe; Sleeckx, N.; Spiegelaere, Ward De; Heindryckx, Femke; Coulon, S.; Steenkiste, Christophe Van

doi:10.1016/j.tvjl.2012.06.011

Cited by 11 publications

(5 citation statements)

References 6 publications

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“…For example, dogs with cancer are sometimes enrolled in oncology research protocols. This research has the potential to deliver therapeutic benefit to dogs with cancer for whom no other effective therapies are available [28]. …”

Section: Which Remedies Are Available?mentioning

confidence: 99%

Chimpanzees as vulnerable subjects in research

Johnson

Barnard

2014

Theor Med Bioeth

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Using an approach developed in the context of human bioethics, we argue that chimpanzees in research can be regarded as vulnerable subjects. This vulnerability is primarily due to communication barriers and situational factors—confinement and dependency—that make chimpanzees particularly susceptible to risks of harm and exploitation in experimental settings. In human research, individuals who are deemed vulnerable are accorded special protections. Using conceptual and moral resources developed in the context of research with vulnerable humans, we show how chimpanzees warrant additional safeguards against harm and exploitation paralleling those for human subjects. These safeguards should include empowering third parties to act as surrogate decision makers for chimpanzees, ensuring participant “assent,” and avoiding recruitment of animal subjects based merely on convenience.

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Section: Which Remedies Are Available?mentioning

confidence: 99%

Chimpanzees as vulnerable subjects in research

Johnson

Barnard

2014

Theor Med Bioeth

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“…Osteosarcoma (OSA) is the most common primary malignant bone tumour in dogs [ 3 , 4 , 5 ], being characterised by a high metastatic potential and poor prognosis [ 1 , 6 , 7 ]. Most dogs that develop canine OSA die because of lung metastases.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory Effects of a Reengineered Anthrax Toxin on Canine and Human Osteosarcoma Cells

Fonseca

Nagamine

et al. 2020

Toxins

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Canine and human osteosarcomas (OSA) share similarities. Novel therapies are necessary for these tumours. The Bacillus anthracis toxin was reengineered to target and kill cells with high expressions of matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA). Since canine OSA express MMPs and uPA, we assessed whether the reengineered toxin could show efficacy against these tumours. Two OSA cell lines (canine D17 and human MG63) and a non-neoplastic canine osteoblastic cell line (COBS) were used. Cells were treated with different concentrations of the reengineered anthrax toxin and cell viability was quantified using MTT assay. The cell cycle, apoptosis, and necrosis were analysed by flow cytometry. The wound-healing assay was performed to quantify the migration capacity of treated cells. D17 and MG63 cells had significantly decreased viability after 24 h of treatment. Cell cycle analysis revealed that OSA cells underwent apoptosis when treated with the toxin, whereas COBS cells arrested in the G1 phase. The wound-healing assay showed that D17 and MG63 cells had a significantly reduced migration capacity after treatment. These results point for the first time towards the in vitro inhibitory effects of the reengineered anthrax toxin on OSA cells; this reengineered toxin could be further tested as a new therapy for OSA.

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“…Considering the high similarity at the clinical, histopathological and molecular levels, spontaneous tumours in dogs are considered excellent models for human diseases, representing an alternative to rodents for studying cancer biology and therapy . Canine osteosarcoma (OSA) represents the most common primary malignant bone tumour in dogs, accounting for more than 80% of all bone tumours; it is locally aggressive and is characterized by a high metastatic potential and poor prognosis . Furthermore, the role of several tyrosine kinase receptors (TKRs) in the pathogenesis of canine OSA was recently demonstrated, which reveals the utility of tyrosine kinase inhibitors (TKIs) against specific targets …”

Section: Introductionmentioning

confidence: 99%

“…1,2 Canine osteosarcoma (OSA) represents the most common primary malignant bone tumour in dogs, accounting for more than 80% of all bone tumours; it is locally aggressive and is characterized by a high metastatic potential and poor prognosis. 1,3,4 Furthermore, the role of several tyrosine kinase receptors (TKRs) in the pathogenesis of canine OSA was recently demonstrated, [5][6][7] which reveals the utility of tyrosine kinase inhibitors (TKIs) against specific targets. 8,9 TKIs have radically changed the treatment approach and prognosis of several human tumours 10,11 ; further, in veterinary medicine, this class of molecules has been shown to be promising in the treatment of a few cancer histotypes.…”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo effects of toceranib phosphate on canine osteosarcoma cell lines and xenograft orthotopic models

Sánchez-Céspedes

Accornero

Miretti

et al. 2019

Vet Comparative Oncology

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Canine osteosarcoma (OSA) is the most common primary malignant bone tumour in dogs, and it has a high metastatic rate and poor prognosis. Toceranib phosphate (TOC; Palladia, Zoetis) is a veterinary tyrosine kinase inhibitor that selectively inhibits VEGFR‐2, PDGFRs and c‐Kit, but its efficacy is not yet fully understood in the treatment of canine OSA. Here, we evaluated the functional effects of TOC on six OSA cell lines by transwell, wound healing and colony formation assays. Subsequently, two cell lines (Wall and Penny) were selected and were inoculated in mice by intrafemoral injection to develop an orthotopic xenograft model of canine OSA. For each cell line, 30 mice were xenografted; half of them were used as controls, and the other half were treated with TOC at 40 mg/kg body weight for 20 days. TOC inhibited cell growth of all cell lines, but reduced invasion and migration was only observed in Penny and Wall cell lines. In mice engrafted with Penny cells and subjected to TOC treatment, decreased tumour growth was observed, and PDGFRs and c‐Kit mRNA were downregulated. Immunohistochemical analyses demonstrated a significant reduction of Ki67 staining in treated mice when compared to controls. The results obtained here demonstrate that TOC is able to slightly inhibit cell growth in vitro, while its effect is evident only in a Penny cell xenograft model, in which TOC significantly reduced tumour size and the Ki67 index without modifying apoptosis markers.

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New therapeutic targets in veterinary oncology: Man and dog definitely are best friends

Cited by 11 publications

References 6 publications

Chimpanzees as vulnerable subjects in research

Chimpanzees as vulnerable subjects in research

Inhibitory Effects of a Reengineered Anthrax Toxin on Canine and Human Osteosarcoma Cells

In vitro and in vivo effects of toceranib phosphate on canine osteosarcoma cell lines and xenograft orthotopic models

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