Diseases of the Hemolymphatic System

Meuten, Donald J.; Buergelt, C. D.

doi:10.1002/9781118695104.ch15

Cited by 1 publication

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“…Multicentric lymphoma is the most common anatomic form accounting for over 80% of all diagnosed cases [2]. A common manifestation of multicentric lymphoma is the development of non-painful generalized lymphadenopathy with peripheral lymph nodes often bilaterally and symmetrically enlarged [3]. The treatment approach for canine lymphoma is determined by the stage of the disease.…”

Section: Introductionmentioning

confidence: 99%

Preliminary Metabolism of Lomustine in Dogs and Comparative Cytotoxicity of Lomustine and Its Major Metabolites in Canine Cells

Chakkath

Lavergne

Fan

et al. 2014

Veterinary Sciences

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Abstract:The nitrosourea drug lomustine is used clinically for treating a wide variety of malignancies, most commonly brain tumors and lymphoma. Lomustine undergoes hydrolysis in vivo to form isomeric metabolites, primarily trans-4-hydroxylomustine (trans-4) and cis-4-hydroxylomustine (cis-4) in various animal species including humans. Despite its widespread usage to treat canine lymphoma, the metabolism of lomustine has not been studied in dogs. It is reported that 4'-hydroxylation products of lomustine (trans-4 and cis-4) have enhanced alkylating activity and reduced toxic effects relative to lomustine, resulting in a better therapeutic index of each of the metabolites relative to the parent compound. Our results show that the metabolic profile of lomustine in dogs is similar to that in humans with trans-4 being the major metabolite and cis-4 as the minor metabolite. Comparative cytotoxicity studies of lomustine and its trans-4 and cis-4 metabolites in canine lymphoma cell lines 17-71 and GL-1 show that there is no difference in the cytotoxicity of the three compounds. In addition, a concentration and time-dependent cell killing was seen in both of these cell lines. Also, primary canine cells like peripheral blood mononuclear cells (PBMC) from lymphoma dogs did not show any sensitivity towards lomustine and its metabolites. OPEN ACCESSVet. Sci. 2014, 1 160

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Section: Introductionmentioning

confidence: 99%