A dose‐finding study with a novel water‐soluble formulation of paclitaxel for the treatment of malignant high‐grade solid tumours in dogs

A new formulation of water‐soluble paclitaxel (Paccal® Vet) has been developed for canine cancer patients, without the need for pre‐medication (traditionally required in non‐water‐soluble paclitaxel formulations). The objective of the study was to determine a clinically safe and efficacious dose of Paccal Vet and to estimate progression‐free and overall survival and to evaluate single‐dose pharmacokinetics in tumour‐bearing dogs. A positive risk:benefit ratio was established for Paccal Vet administered at 150 mg m^–2 intravenous (IV) for three or more treatment cycles. Preliminary efficacy was demonstrated by best objective response rate (86%), median time to response (14 days) and median progression‐free survival (131 days). Paccal Vet was associated with expected adverse events (AE) (e.g. myelosuppression), however the majority were transient, clinically silent and manageable. This is the first clinical report of a water‐soluble formulation of paclitaxel suggesting successful administration and being safely used without pre‐medication in dogs.     

Evaluation of an automated,homogeneous enzyme immunoassay for serum thyroxine measurement in dog and cat serum

A homogenous enzyme immunoassay (EIA) for measurement of serum thyroxine (T4) concentration was evaluated for use with canine and feline serum. The EIA method was linear from 0 to 150 nmol T4/L for human serum, 0 to 94 nmol T4/L for feline serum and 10 to 60 nmol T4/L for canine serum. Intra- and interassay precision studies yielded coefficients of variation 相似文献   

Development of a monoclonal antibody for the detection of anti-canine CD20 chimeric antigen receptor expression on canine CD20 chimeric antigen receptor-transduced T cells

Chimeric antigen receptor (CAR) CAR-T cell therapy targeting CD20 can be a novel adoptive cell therapy for canine patients with B-cell malignancy. After injection of the CAR-T cells in vivo, monitoring circulating CAR-T cells is essential to prove in vivo persistence of CAR-T cells. In this study, we developed a novel monoclonal antibody against canine CD20 CAR, whose single-chain variable fragment was derived from the our previously reported anti-canine CD20 therapeutic antibody. Furthermore, we proved that this monoclonal antibody can detect therapeutic anti-canine CD20 chimeric antibody in the serum from healthy beagle dogs injected with the therapeutic antibody for safety study. This monoclonal antibody is a useful tool for monitoring both canine CD20-CAR-T cells and anti-canine CD20 therapeutic antibody for canine lymphoma.     

Development of a limited‐sampling model for prediction of doxorubicin exposure in dogs

Understanding the relationship between drug dose and exposure (pharmacokinetics, PK) and the relationship between exposure and effect (pharmacodynamics) is an important component of pharmacology when attempting to predict clinical effects of anticancer drugs. PK studies can provide a better understanding of these relationships; however, they often involve intensive sampling over an extended period of time, resulting in increased cost and decreased compliance. Doxorubicin (DOX), one of the most widely used antineoplastic agents in veterinary cancer therapy, is characterized by large interpatient variability in overall drug exposure and the development and degree of myelosuppression following equivalent dosages. We have developed and validated a limited‐sampling strategy for DOX, in which three blood samples are obtained over 1 h post‐treatment, that accurately predicts patient exposure. This strategy could allow for refining of dosing variables and utilization of therapeutic drug monitoring to ensure optimized dosing.     

Evaluation of a monoclonal antibody-based dot-blot ELISA for detection of Leptospira spp in bovine urine samples

OBJECTIVE: To evaluate the efficacy of a novel monoclonal antibody (MAb)-based dot-blot ELISA for detection of Leptospira antigens in urine samples of cattle. SAMPLE POPULATION: Blood and urine samples of 45 test cattle from 5 farms in Chonburi province and 20 control cattle from 2 farms in Khon Kaen province in Thailand. PROCEDURE: Blood and urine samples were assayed (microscopic agglutination test and urine antigen test) for Leptospira infection by use of an MAb-based dot-blot ELISA, and results for the ELISA were compared with those for dark-field microscopy (DFM), microbial culture, and a polymerase chain reaction (PCR) assay. RESULTS: All urine samples with positive results for DFM, microbial culture, PCR assay, or > 1 of these tests also had positive results when tested by use of the MAb-based dot-blot ELISA, except for 1 sample that had positive results only for the PCR assay. Detection limits of the dot-blot ELISA were 10(3) leptospires/mL of urine and 9.3 ng of Leptospira homogenate. Comparison revealed that the diagnostic sensitivity, specificity, efficacy (accuracy), positive predictive value, and negative predictive value for the ELISA were in agreement with results for DFM (100%, 72.72%, 80%, 57.14%, and 100%, respectively), microbial culture (100%, 61.54%, 66.62%, 28.57%, and 100%, respectively), and PCR assay (95.45%, 100%, 91.77%, 100%, and 95.83%, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: The MAb-based dot-blot ELISA is suitable as a tool for detecting leptospires in urine samples of cattle.     

Positive association between a glutathione‐S‐transferase polymorphism and lymphoma in dogs

Glutathione‐S‐transferase enzymes (GSTs) play an important role in the detoxification of environmental carcinogens. Defective GST genotypes are over‐represented in human cancers; in particular, low activity GSTT1 genotypes are risk factors for non‐Hodgkin lymphoma. We hypothesized that defective GSTT1 genotypes would be associated with lymphoma risk in dogs. To address this, we resequenced the exons, splice junctions, and 3′‐UTR of canine GSTT1 in dogs with lymphoma (n = 93) and age‐matched unaffected dogs (n = 86). Of 27 canine GSTT1 variants identified, the I2+28 G>A was significantly associated with lymphoma [odds ratio (OR) 6.26, 95% confidence interval (CI), 1.77–22.2], with the AA genotype found in 18.3% of affected dogs but only 3.5% of controls (P = 0.002). This intronic variant was predicted to perturb GSTT1 mRNA splicing, and may increase lymphoma risk by impairing detoxification of environmental chemicals. Confirmation of this finding in a larger population of dogs may support the inclusion of GSTT1 genotyping in epidemiologic studies of canine lymphoma risk.     

First case of a dog infected with Aspergillus (Phialosimplex) caninus in Australasia

ABSTRACT

Case history: A 2-year-old Rottweiler dog from Perth (WA, Australia) was referred for assessment of a chronic productive cough and weight loss.

Clinical findings: Severely enlarged bilateral superficial cervical lymph nodes and severely enlarged abdominal organs were present. The body condition score was poor and there was moderate muscle wasting. Thoracic and abdominal computed tomography images revealed severe diffuse enlargement of thoracic and abdominal lymph nodes, hepatomegaly and diffuse splenomegaly. A diffuse bronchial pattern with severe multifocal saccular bronchiectasis was identified in the lungs.

Diagnostic findings: Fungal organisms were seen within macrophages on cytological preparations and on histopathological sections of biopsies of the superficial cervical lymph node. Macrophages contained intracytoplasmic, non-filamentous round-to-ovoid organisms, which varied in size from 5–30?µm in diameter with variable morphology. Budding was not observed, and no hyphae were present. Fungal culture of lymph node tissue resulted in growth of Aspergillus (Phialosimplex) caninus which was confirmed by amplification and sequencing of a segment of the 16S-23S rRNA internal transcribed spacer. Concurrent bacterial bronchitis was diagnosed on culture of broncho-alveolar fluid.

Diagnosis: Disseminated aspergillosis caused by Aspergillus caninus.

Clinical relevance: This is believed to be the first report of infection caused by A. caninus in a dog in Australasia. The dog was treated with itraconazole for 7 months and was still alive 7 months after the start of treatment.