Feline restrictive orbital myofibroblastic sarcoma treated with toceranib phosphate (Palladia) as adjuvant chemotherapy: A case study of one cat.

Key Clinical Message: This is the first case report of treatment with toceranib phosphate as postsurgical adjuvant chemotherapy for advanced FROMS. This reported case highlights the need for further studies on the efficacy of toceranib phosphate as adjuvant chemotherapy for FROMS. Abstract: Feline restrictive orbital myofibroblastic sarcoma (FROMS) is a rare aggressive tumor in cats. We explored the effectiveness of using toceranib phosphate as postsurgical adjuvant chemotherapy for advanced FROMS in a 7-year-old cat. Despite treatment, the cat died 4 months after surgery. This report highlights the need for further studies on the efficacy of toceranib phosphate as adjuvant chemotherapy for FROMS.

Lymphoma in Miniature Dachshunds: A retrospective multicenter study of 108 cases (2006-2018) in Japan.

BACKGROUND: Miniature Dachshunds (MD) are predisposed to lymphoma with disease onset of young age and long-term survival. OBJECTIVES: To compare clinical features and survival time of lymphoma in MD and non-MD. ANIMALS: One hundred and eight MDs with lymphoma and 149 non-MD breed dogs with lymphoma were included in the study. METHODS: This was a retrospective multicenter observational study. Lymphoma was classified based on signalment, histopathology/cytology, and anatomical site of the disease. For each type of lymphoma, median survival time was analyzed by Kaplan-Meier estimates and life table analysis. Prognostic factors for large-cell gastrointestinal lymphoma (LGIL) were analyzed using Cox regression. RESULTS: Gastrointestinal lymphomas were more common in MDs (53/108) compared to non-MDs (41/149). The multicentric lymphoma was most common in non-MD breed dogs (74/149) compared to MDs (33/108). The median age that dog developed lymphoma in MD and non-MD were both 10 years old; however, lymphomas were more frequently observed in younger dogs (<4 years) in MDs (20/108) compared to non-MDs (9/149; P = .002). Seventy percent were diagnosed with B-cell with median age of diagnosis was 3 (1-14) years. Mott cell differentiation was observed in 6 dogs. Age <4 years and B-cell phenotype were significant factors for longer survival time in MD with LGIL. CONCLUSIONS AND CLINICAL IMPORTANCE: Lymphomas in MDs involved gastrointestinal lesions at higher frequency compared to other dog breeds examined. B-cell lymphoma was more common in early-onset LGIL in MD and cases that involved Mott cell differentiation were observed. Awareness of this specific presentation of lymphoma in dogs will possibly affect the treatment decision process for the owners of MD with LGIL.

mRNA sequencing analysis and growth inhibitory effects of palbociclib on cell lines from canine histiocytic proliferative disorders.

Canine histiocytic proliferative disorders include aggressive and fatal diseases, such as histiocytic sarcoma (HS) and histiocytosis (SyH). The molecular mechanisms underlying cell proliferation need to be elucidated for the development of effective treatments. In the present study, mRNA expression levels were comprehensively analysed in cell lines derived from localized HS, disseminated HS, SyH and Langerhans cell histiocytosis (LCH) in dogs. Based on the results obtained, the growth inhibitory effects of palbociclib, a CDK4/6 inhibitor, were verified with the cell lines in vitro and in xenograft mouse model. Hierarchical clustering and principal component analysis plots of mRNA expression profiles divided the cell lines into three groups: a localized HS group, disseminated HS/SyH group, and LCH. The results of an ingenuity pathway analysis suggested that the MAPK signalling pathway was activated in the localized HS and LCH cell lines, and the PI3K signalling pathway in the disseminated and localized HS cell lines. In all cell lines, the expression of the tumour suppressor genes TP53, CDKN2A and CDKN1A was down-regulated, whereas that of Rb was preserved. In vitro assessments revealed the growth inhibitory effects of palbociclib in all cell lines examined. In a xenograft mouse model using a cell line from disseminated HS, palbociclib exerted significant growth inhibitory effects. These results suggest the potential of palbociclib as a therapeutic drug candidate for the treatment of malignant histiocytic proliferative disorders of the dog.

Establishment and characterisation of cell lines and xenograft mouse models of canine systemic histiocytosis and disseminated histiocytic sarcoma.

Canine histiocytic proliferative disorders include reactive diseases (histiocytosis) and neoplastic diseases (histiocytic sarcoma [HS]), however discrimination is challenging due to their overlapping pathological features. In the present study, novel cell lines and xenograft mouse models of systemic histiocytosis (SyH) and disseminated HS were established, and examined together with cell lines previously established from localized HS and Langerhans cell histiocytosis (LCH). The chromosomal numbers of the SyH and HS cell lines were abnormal, and their population doubling time and morphological features were comparable. Immunophenotypically, SyH and HS cells were CD204+/E-cadherin+ in vitro and in vivo, like their original tissues. Western blot analysis for E-cadherin revealed an immunopositive band of full-length E-cadherin (120 kDa) in cultured cells of localized HS and LCH but not in disseminated HS and SyH; expression level was weaker in localized HS than in LCH. An immunopositive band of fragmented E-cadherin (45 kDa) was detected in cell lines of disseminated HS and SyH. These results suggest that cultured SyH cells have features that are similar to disseminated HS, including chromosomal aberration, high proliferation activity, weak cell adhesion, and expression of fragmented E-cadherin. Fragmentation of the E-cadherin cell adhesion molecule may be associated with the loss of cell adhesion and increased abilities of invasion and migration of neoplastic cells. The established cell lines and xenograft mouse models will aid in understanding the pathogenesis and developing novel treatments of canine histiocytic proliferative disorders.

Thrombin-antithrombin complex measurement using a point-of-care testing device for diagnosis of disseminated intravascular coagulation in dogs.

Reference interval for thrombin-antithrombin complex (TAT) level was determined using an in-house TAT measurement device, and its validity for diagnosis of disseminated intravascular coagulation (DIC) was evaluated in dogs. One hundred and two clinically healthy dogs and 247 diseased dogs with conditions that potentially caused DIC were recruited in the study. Six diagnostic testing for DIC were evaluated in diseased dogs and the diseased dogs were categorized into five groups depending on abnormal findings. TAT was measured in all study animals and between-group differences were evaluated. TAT level was positively associated with severity of DIC. There were no significant differences in TAT levels among clinically healthy dogs, diseased dogs without any abnormal finding and diseased dogs with one abnormal finding in the DIC diagnostic testing. TAT levels in groups with two or more abnormal findings were significantly higher than clinically healthy dogs. Reference interval of TAT level for clinically healthy dogs was ≤ 0.25 ng/ml. Validity of using TAT for early detection of DIC was evaluated. In-house TAT measurement was suggested to be a clinically relevant and useful tool for early detection of canine DIC.