CD4 and CD8 double-negative immunophenotype of thymoma-associated lymphocytes in a dog.

Persistent small-cell lymphocytosis in dogs with a concurrent mediastinal mass has been associated with both thymoma and small-cell lymphoma. In thymomas, neoplastic thymic epithelial cells induce overproduction and release of polyclonal lymphocytes, whereas thymic lymphoma results in thymic effacement by a clonal expansion of neoplastic lymphocytes and subsequent leukemic phase of lymphoma. Flow cytometry has been used to differentiate these 2 entities by immunophenotyping mediastinal mass aspirates. It has been reported that cases with mediastinal masses in which ≥ 10% of the associated small-cell lymphocytes were double positive for CD4 and CD8 were thymomas, whereas masses associated with < 10% were suggestive of lymphoma. We report a unique case of thymoma-associated lymphocytosis lacking the classic CD4+CD8+ immunophenotype. Our findings suggest that there may be more diversity in the thymoma-associated lymphocyte immunophenotype than has been identified previously; immunophenotyping alone might not be sufficient to differentiate thymic small-cell lymphoma from thymoma-associated lymphocytosis. In dogs with mediastinal masses and peripheral lymphocytosis, employing a variety of testing modalities to avoid misdiagnosis is prudent. These modalities include cytologic and/or histologic evaluation, immunophenotyping, and clonality assessment.

Carboplatin-induced myelosuppression as related to body weight in dogs.

Smaller dogs are known to have an increased risk of chemotherapy-induced myelosuppression for doxorubicin, mitoxantrone and melphalan. This retrospective study aimed to determine if dogs <15 kg and <10 kg experienced greater degrees of myelosuppression following treatment with carboplatin chemotherapy compared with dogs ≥15 kg. One hundred and one dogs treated with carboplatin for a variety of malignancies were retrospectively analysed. Eight dogs (61%) weighing <10 kg, three (38%) weighing 10 kg to <15 kg and 14 (17%) weighing ≥15 kg experienced a grade 3 or 4 neutropenia. Five dogs (38%) weighing <10 kg, two (25%) weighing 10 kg to <15 kg and 13 (16%) weighing ≥15 kg experienced a grade 3 or 4 thrombocytopenia. Dogs <10 kg were significantly more likely to develop a grade 3 or 4 neutropenia following carboplatin than dogs ≥10 kg (3.5 RR; 95% CI, 1.9-6.3; P < .001). Dogs <15 kg were also significantly more likely to develop a grade 3 or 4 neutropenia than dogs ≥15 kg (3 RR; 95% CI, 1.6-5.6; P = .004). Dogs <10 kg were significantly more likely to develop a grade 3 or 4 thrombocytopenia than those dogs ≥10 kg (2.5 RR; 95% CI, 1.1-5.6; P = .006). Hospitalization was significantly more likely for dogs <10 kg vs ≥10 kg (P = .014) as well as for dogs <15 kg vs ≥15 kg (P = .039). This study demonstrates an increased risk of carboplatin-induced myelosuppression in dogs <15 kg, and particularly those <10 kg. This information should be considered by clinicians when making decisions regarding the initial carboplatin dose for smaller canine patients, especially those <15 kg.

Translating Nanomedicine to Comparative Oncology-the Case for Combining Zinc Oxide Nanomaterials with Nucleic Acid Therapeutic and Protein Delivery for Treating Metastatic Cancer.

The unique anticancer, biochemical, and immunologic properties of nanomaterials are becoming a new tool in biomedical research. Their translation into the clinic promises a new wave of targeted therapies. One nanomaterial of particular interest are zinc oxide (ZnO) nanoparticles (NPs), which has distinct mechanisms of anticancer activity including unique surface, induction of reactive oxygen species, lipid oxidation, pH, and also ionic gradients within cancer cells and the tumor microenvironment. It is recognized that ZnO NPs can serve as a direct enzyme inhibitor. Significantly, ZnO NPs inhibit extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) associated with melanoma progression, drug resistance, and metastasis. Indeed, direct intratumoral injection of ZnO NPs or a complex of ZnO with RNA significantly suppresses ERK and AKT phosphorylation. These data suggest ZnO NPs and their complexes or conjugates with nucleic acid therapeutic or anticancer protein may represent a potential new strategy for the treatment of metastatic melanoma, and potentially other cancers. This review focuses on the anticancer mechanisms of ZnO NPs and what is currently known about its biochemical effects on melanoma, biologic activity, and pharmacokinetics in rodents and its potential for translation into large animal, spontaneously developing models of melanoma and other cancers, which represent models of comparative oncology.