The dog as a possible animal model for human non‐Hodgkin lymphoma: a review

Marconato, Laura; Gelain, Maria Elena; Comazzi, S.

doi:10.1002/hon.2017

Cited by 144 publications

(159 citation statements)

References 78 publications

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“…This suggests that, as some previous studies have suggested, the domestic dog is an ideal model for understanding human cancer (Marconato, Gelain & Comazzi, 2013; Rowell, McCarthy & Alvarez, 2011). However, when we analyzed the specific types of neoplasia associated with death in the two species, we found significant differences.…”

Section: Discussionmentioning

confidence: 62%

The companion dog as a model for human aging and mortality

et al. 2018

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SummaryAround the world, human populations have experienced large increases in average lifespan over the last 150 years, and while individuals are living longer, they are spending more years of life with multiple chronic morbidities. Researchers have used numerous laboratory animal models to understand the biological and environmental factors that influence aging, morbidity, and longevity. However, the most commonly studied animal species, laboratory mice and rats, do not experience environmental conditions similar to those to which humans are exposed, nor do we often diagnose them with many of the naturally occurring pathologies seen in humans. Recently, the companion dog has been proposed as a powerful model to better understand the genetic and environmental determinants of morbidity and mortality in humans. However, it is not known to what extent the age‐related dynamics of morbidity, comorbidity, and mortality are shared between humans and dogs. Here, we present the first large‐scale comparison of human and canine patterns of age‐specific morbidity and mortality. We find that many chronic conditions that commonly occur in human populations (obesity, arthritis, hypothyroidism, and diabetes), and which are associated with comorbidities, are also associated with similarly high levels of comorbidity in companion dogs. We also find significant similarities in the effect of age on disease risk in humans and dogs, with neoplastic, congenital, and metabolic causes of death showing similar age trajectories between the two species. Overall, our study suggests that the companion dog may be an ideal translational model to study the many complex facets of human morbidity and mortality.

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Section: Discussionmentioning

confidence: 62%

The companion dog as a model for human aging and mortality

et al. 2018

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“…Lymphoma is the most common haematopoietic malignancy in dogs, constituting up to 83% of cases (11). The main method of treating systemic malignancies like leukaemia and lymphoma is chemotherapy, because it elicits an initial response in the majority of patients.…”

Section: Introductionmentioning

confidence: 99%

In vitro drug sensitivity in canine lymphoma

Pawlak¹,

Obmińska-Mrukowicz²,

Zbyryt³

et al. 2016

Journal of Veterinary Research

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Introduction: Due to the high heterogeneity of canine lymphoma, the aim of the present study was to test in vitro the chemosensitivity of canine high-grade primary lymphoma cells to various cytostatic drugs commonly used to treat dogs: 4-HO-cyclophosphamide, doxorubicin, dexamethasone, prednisolone, vincristine, etoposide, chlorambucil, lomustine, and cytosine arabinoside. Material and Methods: To determine the cell viability and drug ability to induce apoptosis two different tests were used: an MTT assay and annexin V/propidium iodide staining. Results: Both in vitro tests were found to be useful tools. Significant differences in the sensitivity, depending on the drug type, between B-, T-and mixed/null-type lymphoma cells were found for the majority of the tested drugs. B-type cells were the most sensitive in vitro, whereas T-type cells seemed to be the most resistant. Doxorubicin, chlorambucil, etoposide, and vincristine most strongly reduced the cell viability and induced apoptosis. Conclusion: In vitro assays, such as the MTT test and especially the annexin V/PI assay, may be useful tools for predicting a response to the treatment of high-grade lymphoma in dogs or improving the treatment outcomes in individual animals.

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“…Dogs may be the most relevant animal model to study new therapies for this indication. Actually, naturally occurring lymphomas in dogs are closer to their human counterparts than any xenograft mice models, because of their growth over long periods of time in an intact immune system, interindividual and intratumoral heterogeneity, development of recurrent or resistant diseases, and metastasis (13). Clinical presentation, biologic behavior, tumor genetics, and treatment response are very similar between canine and human DLBCL (14,15).…”

Section: Introductionmentioning

confidence: 99%

Phase I Clinical Pharmacology Study of F14512, a New Polyamine-Vectorized Anticancer Drug, in Naturally Occurring Canine Lymphoma

Tierny

Serres

Segaoula

et al. 2015

Clinical Cancer Research

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Purpose: F14512 is a new topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells and increases topoisomerase II poisoning. F14512 is currently in a phase I/II clinical trial in patients with acute myeloid leukemia. The aim of this study was to investigate F14512 potential in a new clinical indication. Because of the many similarities between human and dog lymphomas, we sought to determine the tolerance, efficacy, pharmacokinetic/pharmacodynamic (PK/PD) relationship of F14512 in this indication, and potential biomarkers that could be translated into human trials. Experimental Design: Twenty-three dogs with stage III–IV naturally occurring lymphomas were enrolled in the phase I dose-escalation trial, which consisted of three cycles of F14512 i.v. injections. Endpoints included safety and therapeutic efficacy. Serial blood samples and tumor biopsies were obtained for PK/PD and biomarker studies. Results: Five dose levels were evaluated to determine the recommended dose. F14512 was well tolerated, with the expected dose-dependent hematologic toxicity. F14512 induced an early decrease of tumoral lymph node cells, and a high response rate of 91% (21/23) with 10 complete responses, 11 partial responses, 1 stable disease, and 1 progressive disease. Phosphorylation of histone H2AX was studied as a potential PD biomarker of F14512. Conclusions: This trial demonstrated that F14512 can be safely administered to dogs with lymphoma resulting in strong therapeutic efficacy. Additional evaluation of F14512 is needed to compare its efficacy with standards of care in dogs, and to translate biomarker and efficacy findings into clinical trials in humans. Clin Cancer Res; 21(23); 5314–23. ©2015 AACR.

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The dog as a possible animal model for human non‐Hodgkin lymphoma: a review

Cited by 144 publications

References 78 publications

The companion dog as a model for human aging and mortality

The companion dog as a model for human aging and mortality

In vitro drug sensitivity in canine lymphoma

Phase I Clinical Pharmacology Study of F14512, a New Polyamine-Vectorized Anticancer Drug, in Naturally Occurring Canine Lymphoma

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