Canine diffuse large B-cell lymphoma (DLBCL), the most common hematologic malignancy of dogs, is associated with poor overall survival. The lack of conventional chemotherapies with sustainable efficacy warrants investigation of novel therapies. Pevonedistat (MLN4924) is a potent and selective small molecule NEDD8-activating enzyme inhibitor. In human activated B-cell-like (ABC) diffuse large B-cell lymphoma, pevonedistat induces lymphoma cell apoptosis, DNA damage and G1 cell cycle arrest by inhibiting the nuclear factor-κB (NF-κB) pathway. Genomic and transcriptomic studies showed that the NF-κB pathway is deregulated in canine DLBCL. Our results showed that pevonedistat treatment significantly reduces the viability of canine DLBCL cells by inducing G1 cell cycle arrest and apoptosis. Pevonedistat treatment inhibits NF-κB pathway activation and downregulates NF-κB target genes in canine DLBCL. Moreover, administration of pevonedistat to mice bearing canine DLBCL xenograft tumours resulted in tumour regression. Our in vivo and in vitro studies provide justification for future clinical application of pevonedistat as a potential new anti-cancer therapy that may benefit both canine and human species.
Liposarcomas are rare malignant tumors showing adipocytic differentiation. We report a well-differentiated liposarcoma in a 6-y-old, male neutered cat with a prominent inflammatory component and metastatic spread to the lungs. The patient was initially presented because of fever, lethargy, and a firm subcutaneous inguinal mass. A Tru-cut biopsy of the mass revealed a mixture of well-differentiated adipocytes and lymphoplasmacytic-histiocytic inflammation, interpreted as panniculitis. The mass was surgically excised but recurred 4 mo later. A second excisional biopsy yielded similar histologic findings. A third recurrence of the mass was associated with lung nodules. Histopathology of the recurring and metastatic masses confirmed the diagnosis of well-differentiated inflammatory liposarcoma with pulmonary metastases. The neoplasm had an intense inflammatory component, which obscured the underlying features of liposarcoma and made differentiation from steatitis difficult. This inflammatory variant of a well-differentiated liposarcoma should be considered as a differential in tumorous steatitis-like lesions.
The purpose of this prospective study was to determine the incidence and character of bacteraemia and bacteruria in afebrile and febrile neutropaenic dogs undergoing cytotoxic chemotherapy. Fifty‐five neutropaenic dogs presenting to the University of Wisconsin Veterinary Medical Teaching Hospital were enrolled for a total of 57 neutropaenic episodes. The overall incidence of bacteraemia was 12.3% (n = 7/57). Three afebrile dogs and four febrile dogs were bacteraemic; this difference was not significant (P = 0.6968). The overall incidence of bacteruria was 7.5% (n = 4/53). Two afebrile dogs and two febrile dogs were bacteruric; this difference was not significant (P = 1.0). Of the positive blood cultures, the majority of organisms cultured (n = 6/7) were gram‐positive organisms with one gram‐negative organism. Three of the positive blood cultures showed in vitro resistance to more than one antimicrobial agent. Clinical parameters (age, body weight, heart rate, rectal temperature, neutrophil count, haematocrit and platelet count) were not predictive of bacteraemia. The results of this study were not sufficient to justify the use of blood cultures as a first‐line diagnostic test for neutropaenic patients. Blood cultures may have utility in individual case management for a minority of patients in guiding antibiotic choice in the case of resistant bacterial infections. Blood cultures may serve as a tool for antimicrobial de‐escalation, although further study is needed.
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