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Abstract Background Microsatellite instability (MSI) is a type of genomic instability caused by mismatch repair deficiency (dMMR) in tumors. Studies on dMMR/MSI are limited, and the relationship between dMMR and MSI is unknown in tumors of dogs. Objectives We aimed to identify the frequency of dMMR/MSI by tumor type and evaluate the relationship between dMMR and MSI in tumors of dogs. Animals In total, 101 dogs with 11 types of malignant tumors were included. Methods We extracted DNA from fresh normal and tumor tissues. Twelve microsatellite loci from both normal and tumor DNA were amplified by PCR and detected by capillary electrophoresis. Each microsatellite (MS) was defined as MSI if a difference in product size between the tumor and normal DNA was detected. The dMMR was evaluated by immunohistochemistry with formalin‐fixed paraffin‐embedded tumor tissues. Next, we confirmed whether dMMR induces MSI by serial passaging of MMR gene knockout cell lines for 3 months. Results Microsatellite instability was detected frequently in oral malignant melanoma. The number of MSI‐positive markers was higher in cases with dMMR than in those with proficient MMR (P

The African pygmy hedgehog (Atelerix albiventris) is known to have a high incidence of tumor. However, investigating the tumors of this species has been constrained by the limited availability of research materials such as cell lines and genome information. In this study, we successfully established a novel cell line from a histiocytic sarcoma (HS) of an African pygmy hedgehog, allowing us to conduct a drug screening. We investigated using FDA-approved drug library screening to determine which anticancer drug this tumor cell line is sensitive to, and as a result of apoptosis experiments, bortezomib among the three proteasome inhibitors was found to induce cell death of cancer cells by significantly increasing caspase-3 cleavage (P<0.01). Thus, we elucidated that the proteasome inhibitors, particularly bortezomib, exhibit anti-tumor effects on a cell line derived from an HS in an African pygmy hedgehog through a mechanism comparable to that described in human tumors. This study reports the first characterized cell line from the African pygmy hedgehog and also highlights the potential utility of bortezomib as an anti-tumor treatment for HS in this species. [ABSTRACT FROM AUTHOR]

Background: The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear. Objective: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM. Methods: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group. Results: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%). Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively. Conclusions: The present study demonstrated that ca-4F12-E6 was well-tolerated in non-OMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs. [ABSTRACT FROM AUTHOR]