Imatinib elicited a favorable response in a dog with a mast cell tumor carrying a c-kit c.1523A>T mutation via suppression of constitutive KIT activation

Target therapy using the tyrosine kinase inhibitor imatinib is one of the new therapeutic approaches for canine mast cell tumors (MCTs). In the present report, we demonstrate a clinical response to imatinib in a dog with MCT carrying a c-kit c.1523A>T mutation. Moreover, the effect of this mutation on the phosphorylation status of KIT and the inhibitory potency of imatinib on the phosphorylation of the mutant KIT were examined in vitro. A dog with a MCT tumor mass on the right forelimb sole with lymph node metastasis and mastocytemia was treated with imatinib. The MCT mass markedly shrank and mastocytemia became undetectable with 2 weeks of treatment. The lymph node enlarged by metastasis became normal in size with 5 weeks of treatment. From the sequencing analysis of c-kit in tumor cells, a substitution mutation c.1523A>T that alters the amino acid composition (p.Asn508Ile) within the extracellular domain of KIT was identified. The mutant KIT expressed on 293 cells showed ligand-independent phosphorylation and imatinib suppressed this phosphorylation in a dose-dependent manner. From these findings, imatinib was considered to elicit a clinical response in a canine case of MCT via inhibition of the constitutively activated KIT caused by a c-kit c.1523A>T mutation.     

Prevalence and characterization of Shiga toxin-producing Escherichia coli O157 and O26 in beef farms

Rectal content grab samples were collected from 2436 beef cattle reared on 406 beef farms in Japan between November 2007 and March 2008. STEC strains O157 and O26 were isolated from 110 (27.1%) and 7 (1.7%) farms, respectively. Farms that tested positive for STEC O157 were located in 35 out of all 47 Japanese prefectures. This indicates that STEC O157 strains are widespread on beef farms nationwide. Of the 2436 tested beef cattle, 218 (8.9%) and 10 (0.4%) had STEC strains O157 and O26 in the rectal content, respectively. The most common Shiga toxin genes detected in the isolated STEC O157 strains were: stx(2c) alone (32.1%), stx(2)/stx(2c) (27.2%), and stx(1)/stx(2) (21.8%). Almost all of the STEC O157 and STEC O26 strains expressed Shiga toxins (Stx). Most of the STEC O157 and STEC O26 strains possessed eaeA and EHEC-hlyA. These results strongly suggest that STEC strains O157 and O26 from beef cattle would be pathogenic to humans. Therefore, it is important to reduce STEC strains O157 and O26 in beef cattle in order to prevent foodborne disease caused by STEC. The presence of dogs and/or cats on a farm was significantly (P=0.02) associated with the prevalence of STEC O157. More research is needed to clarify the role of dogs and cats.     

Comparison between immunohistochemistry and genetic clonality analysis for cellular lineage determination in feline lymphomas

Clinical application of genetic clonality analysis by PCR has been available in feline lymphoma. However, it is in under dispute whether the analysis can be applied for cellular lineage determination. To evaluate utility of the analysis for lineage determination, the results between immunohistochemistry and the genetic analysis were compared. Based on the result with immunohistochemistry, sensitivity of the primer for IgH was 89% and specificity was 75%. Sensitivity of the primer for TCRγ was 25% and specificity was 100%. Cross-lineage IgH rearrangement was found in 25% of T-cell lymphomas. The present study suggests that the genetic analysis had better be applied as not a definite but an adjunctive tool for lineage determination in feline lymphomas.     

T-cell lymphoma in a wild Okinawa rail (Gallirallus okinawae)

The Okinawa rail (Gallirallus okinawae) is an endangered species that inhabits the northern part of Okinawa Main Island in southern Japan. A wild Okinawa rail was rescued from a road in Kunigami Village in Okinawa in October 2009. The bird subsequently died and underwent necropsy. Tumors were found in the liver, spleen and part of the small intestine. Microscopically, lymphoid neoplasm was confirmed in these tissues. The tumor cells were mainly positive for CD3 and CD8α by immunohistochemistry. No Marek's disease virus genes were detected by PCR of a liver tumor. This is the first report of T-cell lymphoma in the Okinawa rail.     

A retrospective analysis of radiation oncology related scientific articles in the journal Veterinary Radiology and Ultrasound: Trends over 40 years (1976‐2015)

The journal Veterinary Radiology & Ultrasound is a veterinary specialty journal devoted to the fields of veterinary diagnostic imaging and radiation oncology. The purpose of this retrospective, observational study is to evaluate progressive trends in radiation oncology articles published in Veterinary Radiology & Ultrasound during the 40‐year period (1976‐2015) and describe a shift of trends through several viewpoints. This 40‐year period was divided into four subperiods: Period 1 (1976‐1985), Period 2 (1986‐1995), Period 3 (1996‐2005), and Period 4 (2006‐2015). These articles were divided into six categories based on the nature of the study: 1) studies related to teletherapy with endpoints being patient outcome, 2) radiation therapy dosimetry/planning, 3) patient setup, 4) reviews, 5) case reports, and 6) others. The number of radiation oncology articles in Veterinary Radiology & Ultrasound has increased over the 40‐year period. The number of authors per article has increased between Periods 1 and 3. The number of articles related to linear accelerator has increased between Periods 3 and 4. The median number of treated patients per clinical article related to teletherapy ranged from 15 to 21, which has not changed significantly over the 40‐year period. The most commonly used radiation therapy protocols during Periods 2 and 3 were fine‐fractionated protocols (defined as 10 or more fractions), whereas coarse‐fractionated protocols were more common during Periods 1 and 4. Findings from this study highlight the notable changes of trends in veterinary radiation oncology articles published in Veterinary Radiology & Ultrasound, which clearly reflect changes in the field of veterinary radiation oncology during the past 40 years.     

Association of tumour‐infiltrating regulatory T cells with adverse outcomes in dogs with malignant tumours

Regulatory T cells (Tregs) infiltrate into a variety of tumour tissues and associate with poor prognosis in humans. However, data on association of Treg infiltration with prognosis is limited in canine tumours. The purpose of this study was to examine the number of tumour‐infiltrating Tregs and its association with overall survival (OS) in dogs with malignant tumours. The following 168 canine tumours were included: 37 oral malignant melanomas (OMMs); 14 oral squamous cell carcinomas (OSCCs); 16 pulmonary adenocarcinomas (PAs); 37 mammary carcinomas (MCs); 36 mast cell tumours (MCTs) and 28 hepatocellular carcinomas (HCCs). Normal tissues were obtained from 8 healthy dogs as controls. The number of forkhead box P3 (Foxp3)‐positive Tregs in intratumoral and peritumoral areas was investigated by immunohistochemistry. OS was compared between high and low Treg groups. The number of intratumoral and peritumoral Foxp3‐positive Tregs was significantly higher in OMM, OSCC, PA and MC compared with each normal tissue. There were few Foxp3‐positive Tregs in MCT and HCC. With intratumoral Tregs, the OS in the high Treg group was significantly shorter than that in the low Treg group in OMM, OSCC and PA. With peritumoral Tregs, there was no significant difference for OS between the 2 groups in each tumour type. These results suggest that Tregs infiltrate into a variety of canine tumours and the abundance of Tregs are associated with poor prognosis in some solid tumour types.     

Development of genetic evaluation for milk production traits of Holsteins in Japan

The procedure used for the genetic evaluation of dairy cattle in Japan has developed from a lactation sire–MGS model to a multiple‐lactation random regression test‐day animal model. Genetic evaluation of Holstein bulls in Japan began in 1989 with the use of field‐style progeny testing; dairy herd improvement program data from all over Japan were used, along with a sire and maternal grandsire model. In 1993, an animal model was introduced to estimate breeding values for yield and type traits. A random regression test‐day model was first applied in 2010. In the business of breeding dairy cattle, it is very important to users that estimated breeding values are reliable and stable among subsequent routine evaluations. With experience in the genetic evaluation of dairy cattle in Japan, Japanese researchers have found ways to improve the stability of estimated breeding values. These modifications involve changes in data editing, development of evaluation models, changes to the structures of unknown‐parent groups, awareness of the problems of predicting lactation yield from partial test‐day records, and adjustment for heterogeneity within herd variances. Here, I introduce developments in, and our experiences with, the genetic evaluation of yield traits of Holstein cattle in Japan.