Evaluation of circulating IGF-I and IGFBP-3 as biomarkers for tumors in dogs

Background@#Serum-based parameters are considered non-invasive biomarkers for cancer detection. In human studies, insulin-like growth factor-I and II (IGF-I and IGF-II) and insulin-like growth factor binding protein-3 (IGFBP-3) are useful as diagnostic or prognostic markers and potential therapeutic targets. @*Objectives@#This study examined the diagnostic utility of circulating IGF-I, IGF-II, and IGFBP-3 levels in healthy dogs and dogs with tumors. @*Methods@#The serum concentrations of these biomarkers in 86 dogs with tumors were compared with those in 30 healthy dogs using an enzyme-linked immunosorbent assay (ELISA). @*Results@#The ELISA results showed no difference between healthy dogs and dogs with tumors in the serum IGF-II concentrations. On the other hand, there was a significant difference in the circulating IGF-I and IGFBP-3 levels between healthy dogs and dogs with tumors. The concentrations of serum IGF-I (median [interquartile range], 103.4 [59.5–175] ng/mL) in dogs with epithelial tumors were higher than those (58.4 ng/mL [43.5–79.9]) in healthy dogs.Thus, the concentrations of serum IGFBP-3 (43.4 ng/mL [33.2–57.2]) in dogs with malignant mesenchymal tumors were lower than those (60.8 ng/mL [47.6–70.5]) in healthy dogs. @*Conclusions@#The serum IGF-I and IGFBP-3 levels can be used as diagnostic biomarkers in dogs with tumors.

Evaluation of circulating PD-1 and PD-L1 as diagnostic biomarkers in dogs with tumors

Background@#Programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have important roles in tumor evasion of the immune system. @*Objectives@#This study aimed to assess the diagnostic utility of circulating PD-1 and PD-L1 levels in healthy dogs and dogs with tumors. @*Methods@#Circulating PD-1 and PD-L1 levels in the serum of 71 dogs with tumors were compared with those of 52 healthy dogs by performing enzyme-linked immunosorbent assay (ELISA). @*Results@#The ELISA results revealed higher circulating PD-1 and PD-L1 levels in dogs with tumors (2.9 [2.2–3.7] ng/mL; median [IQR] and 2.4 [1.4–4.4] ng/mL, respectively) than in healthy dogs (2.4 [1.9–3.0] ng/mL; p = 0.012 and 1.4 [0.9–2.1] ng/mL; p < 0.001, respectively). Especially, there was a significant difference in circulating PD-1 levels between healthy dogs and dogs with malignant epithelial tumors (2.4 [1.9–3.0] ng/mL and 3.1 [2.6–4.4] ng/mL, respectively; p < 0.01). In addition, there was a significant difference in circulating PD-L1 levels between healthy dogs and dogs with lymphomas (1.4 [0.9–2.1] ng/mL and 2.7 [1.6–5.8] ng/mL, respectively; p < 0.001). @*Conclusion@#This study indicates that circulating PD-1 and PD-L1 have potential as tumor diagnostic biomarkers in dogs with tumors.

Evaluation of circulating PD-1 and PD-L1 as diagnostic biomarkers in dogs with tumors

Background@#Programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have important roles in tumor evasion of the immune system. @*Objectives@#This study aimed to assess the diagnostic utility of circulating PD-1 and PD-L1 levels in healthy dogs and dogs with tumors. @*Methods@#Circulating PD-1 and PD-L1 levels in the serum of 71 dogs with tumors were compared with those of 52 healthy dogs by performing enzyme-linked immunosorbent assay (ELISA). @*Results@#The ELISA results revealed higher circulating PD-1 and PD-L1 levels in dogs with tumors (2.9 [2.2–3.7] ng/mL; median [IQR] and 2.4 [1.4–4.4] ng/mL, respectively) than in healthy dogs (2.4 [1.9–3.0] ng/mL; p = 0.012 and 1.4 [0.9–2.1] ng/mL; p < 0.001, respectively). Especially, there was a significant difference in circulating PD-1 levels between healthy dogs and dogs with malignant epithelial tumors (2.4 [1.9–3.0] ng/mL and 3.1 [2.6–4.4] ng/mL, respectively; p < 0.01). In addition, there was a significant difference in circulating PD-L1 levels between healthy dogs and dogs with lymphomas (1.4 [0.9–2.1] ng/mL and 2.7 [1.6–5.8] ng/mL, respectively; p < 0.001). @*Conclusion@#This study indicates that circulating PD-1 and PD-L1 have potential as tumor diagnostic biomarkers in dogs with tumors.

Genome-wide association study of degenerative mitral valve disease in Maltese dogs

Genome-wide association study (GWAS) is a powerful tool for identifying the genetic causes of various diseases. This study was conducted to identify genomic variation in Maltese dog genomes associated with degenerative mitral valve disease (DMVD) development and to evaluate the association of each biological condition with DMVD in Maltese dogs. DNA was extracted from blood samples obtained from 48 Maltese dogs (32 with DMVD and 16 controls). Genome-wide single nucleotide polymorphism (SNP) genotyping was performed. The top 30 SNPs from each association of various conditions and genetic variations were mapped to their gene locations. A total of 173,662 loci were successfully genotyped, with an overall genotype completion rate of 99.41%. Quality control analysis excluded 46,610 of these SNPs. Manhattan plots were produced using allelic tests with various candidate clinical conditions. A significant peak of association was observed between mitral valve prolapse (MVP) and SNPs on chromosome 17. The present study revealed significant SNPs in several genes associated with cardiac function, including PDZ2, Armadillo repeat protein detected in velo-cardio-facial syndrome, catenin (cadherin-associated protein) alpha 3, low-density lipoprotein receptor class A domain containing protein 4, and sterile alpha motif domain containing protein 3. To our knowledge, this is the first study of a genetic predisposition to DMVD in Maltese dogs. Although only a limited number of cases were analyzed, these data could be the basis for further research on the genetic predisposition to MVP and DMVD in Maltese dogs.

Prolonged reflex bradycardia after occlusion of patent ductus arteriosus with an Amplatz canine duct occluder in a dog

A 9-month-old intact male Maltese dog (1.52 kg) was diagnosed with a patent ductus arteriosus (PDA). Transcatheter occlusion of the PDA was performed by using the Amplatz canine duct occluder (ACDO). After occlusion, reflex bradycardia occurred and lasted for at least 15 h with normal systolic arterial pressure and slightly increased diastolic arterial pressure. The bradycardia slowly resolved, and the heart rate was normal in re-examinations after 7 and 30 days. This is the first case of reflex bradycardia after ACDO implantation, in which the bradycardia continued for a long time, even after recovery from anesthesia.