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OBJECTIVE To assess whether the volume of extruded materials is correlated with neurologic severity in dogs with type I thoracolumbar intervertebral disk herniation (TL-IVDH). ANIMALS 70 client-owned small-breed dogs with type I TL-IVDH diagnosed between July 1, 2016, and June 30, 2018. PROCEDURES For this retrospective cohort study, the medical records of 70 dogs with surgically confirmed type I TL-IVDH were reviewed. The volume and height of the intervertebral disk and the area of the maximal transverse compressed spinal cord were measured using CT myelographic images. For each dog, the volume of the disk immediately cranial to the herniated disk was an internal control. Dogs were grouped on the basis of grade of neurologic severity. RESULTS Preoperative grades of neurologic severity were grade 2 in 7 (10%) dogs, grade 3 in 16 (23%) dogs, grade 4 in 28 (40%) dogs, and grade 5 in 19 (27%) dogs. The total volume of the affected intervertebral disks was significantly larger than the internal control. Weak positive correlation was found between the volume of the extruded materials into the vertebral canal and the grade of neurologic severity. CLINICAL RELEVANCE Our findings indicated that the total volume of the affected intervertebral disks is larger in dogs with type I TL-IVDH, and the volume of the extruded materials into the vertebral canal is weakly correlated with the neurologic severity.

The transcription factor hypoxia-inducible factor 1α (HIF-1α) is expressed in several cancers under intratumoral hypoxic stress that arises during pathogenic processes, resulting in malignant progression. We previously reported that hypoxic stimulation enhances the growth potential of canine lymphoma cells by activating the HIF-1α signaling pathway. In contrast, evofosfamide (Evo) releases a DNA-alkylating moiety within hypoxic tumor regions, suggesting that Evo could serve as a hypoxia-targeting drug in canine lymphoma. This study aimed to use Evo to evaluate hypoxia-targeted therapy in dogs with gastrointestinal lymphoma (GIL) and investigate how Evo affects antitumor efficacy and adverse events in three type of murine xenograft models using T-cell GIL cells. In vitro tests, the sensitivity to Evo of three T-cell GIL cell lines under hypoxic culture was significantly higher than that under normoxic culture. Our metabolic analysis suggested that the three murine models might have high reproducibility as clinical cases in canine GIL. Our data showed that Evo showed significantly higher tumor growth potential and fewer adverse events in three type of murine models compared to lomustine; CeeNu (CCNU). Additionally, Evo suppressed the expression of HIF-1α protein in tumor tissues, suggesting that it may preferentially target and inhibit tumor cells in a hypoxic region. The evidence presented here supports the favorable preclinical evaluation that Evo may be effective for GIL in dogs.

The transcription factor hypoxia-inducible factor 1α (HIF-1α) is activated in response to oxygen deficiency, and is expressed in several cancers under intratumoral hypoxic stress that arises during pathogenic processes. Hypoxic stimulation enhanced the growth potential of canine lymphoma cells by activating the HIF-1α signalling pathway in a previously reported study. The aim of this study was to establish a molecular design strategy for a novel hypoxia-targeting therapy for intestinal T-cell lymphoma (ITL) in dogs. We assessed the relationship between immunohistochemistry-based HIF-1α expression and clinical information, including signalment, tumour area, clinical signs, systemic diseases, treatment protocol, follow-up information, chemotherapy response and overall survivals (OS), using 48 tissue samples from dogs with ITL. We investigated the effects of hypoxic stimulation on the biological behaviour of cell lines from three different types of canine ITL. We assessed the effects of evofosfamide (Evo; hypoxia-activated prodrug) on cell lines cultured under hypoxic conditions. Our data showed that treatment response and overall survival might be significantly decreased in dogs with higher HIF-1α expression than in those with lower HIF-1α expression. Hypoxic culture (1% O

Genetic diversity of Cambodian melon was evaluated by the analysis of 12 RAPD and seven SSR markers using 62 accessions of melon landraces, and compared with 231 accessions from other areas for genetic characterization of Cambodian melon. Among 62 accessions, 56 accessions were morphologically classified as small-seed type whose seed length was shorter than 9mm as like groups Conomon and Makuwa. Gene diversity of Cambodian melon was 0.228 which was equivalent to those of groups Conomon and Makuwa and smaller than those of Vietnamese and Central Asian landraces. Phylogenetic tree constructed from genetic distance matrix classified 293 accessions into three major clusters. Small-seed type accessions from east and southeast Asia formed clusters I and II, which were distantly related with cluster III consisted of large-seed type melon from other areas. All of Cambodian melon belonged to cluster I except three accessions, along with those from Thailand, Myanmar, Yunnan (China) and “Dua thom” from northwestern part of Vietnam, indicating genetic similarity in these areas. In addition, Cambodian melon was not differentiated among geographical populations. Conomon and Makuwa were classified into cluster II, together with melon groups from plain areas of Vietnam. The presence of two groups of melon in southeast Asia was also indicated by population structure and PCO analysis. These results indicated close genetic relationship between Cambodia and the neighboring countries, and suggested that Cambodian melon is not directly related with the establishment of Conomon and Makuwa.

To understand the genetic diversity and differentiation of Vietnamese melon (Cucumis melo L.), we collected 64 landraces from the central and southern parts of the country and assessed molecular polymorphism using simple sequence repeat and random amplified polymorphic DNA markers. The Vietnamese melon was divided into seven cultivar groups, namely “Dua le”, “Dua vang”, “Dua bo”, “Dua gang-andromonoecious”, “Dua gang-monoecious”, “Dua thom”, “Montok”, and the weedy-type melon “Dua dai”. Among these, Dua le, Dua vang, Dua bo, and Dua gang-andromonoecious are cultivated on plains and they formed cluster II along with the reference accessions of Conomon and Makuwa. Based on genetic distance, Dua le and Dua vang were regarded as Makuwa and Dua bo and Dua gang-andromonoecious as Conomon. In contrast, Dua thom and Montok are cultivated in highlands, and they formed cluster III along with landraces from the southern and eastern foot of the Himalayas. Dua gang-monoecious which is commonly cultivated in the southern parts of Vietnam, exhibited the greatest genetic diversity, as explained by its possible origin through the hybridization between Dua gang-andromonoecious and Montok. Genetic differences in melon landraces between plains and highlands and hybridization between these two geographical groups have contributed to the enhancement of genetic diversity in Vietnamese melon.

Case series summary The ultrasonographic findings of many feline intestinal tumours are similar. This study evaluated the CT features of intermediate- and high-grade alimentary lymphoma and adenocarcinoma in cats. CT was performed on six cats with adenocarcinoma and 14 cats with lymphoma. Comparisons between tumour types were conducted, focusing on CT features, including obstruction (present or absent), growth patterns of lesions (symmetry or asymmetry), layering enhancement (present or absent), location of the lesion, number of lesions (solitary or multiple), lymphadenopathy (present or absent), location of lymphadenopathy, pulmonary metastasis (present or absent) and maximum thickness (mm) of the lesion. The cats with adenocarcinoma (n = 5/6 [83%]) experienced intestinal obstruction significantly more often than cats with lymphoma (n = 0/14 [0%]; P = 0.0004). Layering enhancement was observed significantly more often in cats with adenocarcinoma (n = 6/6 [100%]) than in cats with lymphoma (n = 1/14 [7%]; P = 0.0002). Lymphadenopathy was detected significantly more often in cats with lymphoma (n = 14/14 [100%]) than in cats with adenocarcinoma (n = 2/6 [33%]) ( P = 0.003). In cats with lymphoma, the intestine (12.1 ± 3.9 mm) was significantly thicker than that in cats with adenocarcinoma (6.4 ± 2.3 mm; P = 0.005). Relevance and novel information To the best of our knowledge, no reports have described the characteristics of feline intestinal tumours using CT. Layering enhancement was observed in cats with intestinal adenocarcinomas. No layering enhancement was observed in alimentary lymphoma in cats, but enlarged regional nodes were noted. Lesions with lymphoma were thicker than those with adenocarcinoma. These findings may help differentiate between adenocarcinomas and lymphomas.

Pyloric outflow obstructions can be caused by several types of lesions. When a thickened gastric wall and pyloric mass are detected, malignant neoplasia must be differentiated from chronic hypertrophic pyloric gastropathy. CT can characterize gastric tumors. However, based on the authors' review of the literature, there is limited information about the CT findings of pyloric lesions. The purpose of this retrospective case series study was to assess the CT findings of canine pyloric lesions. The following CT parameters were recorded: anatomical area, involved area, lesion shape, growth patterns of wall thickening lesions, enhancement pattern of the lesion in the early and delayed phases, lymphomegaly, and pulmonary metastasis. Seventeen dogs were included in this study and had the following final diagnoses: hyperplasia (five dogs), adenoma (five dogs), adenocarcinoma (three dogs), gastrointestinal stromal tumor (GIST; two dogs), polyposis (one dog), and pyogenic granuloma (one dog). Hyperplasia, adenoma, and polyposis formed mass lesions that involved the mucosal layer. Lymphomegaly was detected in two Jack Russell terriers with hyperplasia; however, the causes were unknown because we did not perform biopsies. All adenocarcinomas formed wall-thickened lesion that involved the outer layer, with lymphomegaly. All GISTs formed mass lesion that involved the outer layer. The pyogenic granulomas formed symmetric wall-thickened lesion that involved the mucosal and outer layers. CT facilitated the characterization of canine pyloric lesions using contrast enhancement, based on the involved area and lesion shape. However, polyposis may require caution in diagnosis based on CT findings alone.

Objectives Primary nasal tumours in cats are rare, with lymphoma being the most common feline nasal tumour, followed by adenocarcinoma. Although CT can reliably detect feline nasal tumours, there are no specific CT features that identify each tumour type. To our knowledge, there have been no reports describing MRI findings, including diffusion-weighted imaging (DWI), for nasal lymphomas and adenocarcinomas in cats. Therefore, this retrospective study aimed to evaluate the MRI findings of nasal lymphoma and adenocarcinoma, including qualitative and quantitative analysis of DWI. Methods MRI examination was performed on seven cats with histologically confirmed lymphoma and on two with adenocarcinoma. The MRI protocol included T2-weighted imaging (T2WI), T1-weighted imaging (T1WI) and DWI. Apparent diffusion coefficient (ADC) values were measured using DWI. Contrast agent was not used in one cat with lymphoma. Results Of the cats with lymphoma, three (43%) were iso- and hyperintense on T2WI, seven (100%) were isointense on T1WI, five (83%) exhibited mild heterogeneous enhancement, including a prominent region of non-enhancement on post-contrast T1WI, and seven (100%) cats exhibited hyperintensity on DWI. The median ADC values were 0.45 × 10−3 mm2/s (range 0.37–0.53 × 10−3 mm2/s). For adenocarcinoma, two (100%) were iso- and hyperintense on T2WI, two (100%) were isointense on T1WI, two (100%) exhibited marked heterogeneous enhancement on post-contrast T1WI and two (100%) were isointense on DWI. The median ADC values were 1.08 × 10−3 mm2/s (range 0.88–1.27 × 10−3 mm2/s). The median ADC values of lymphoma tended to be lower than adenocarcinoma ( P = 0.056). Conclusions and relevance Determining ADC value and tumours with a large area of non-enhancement may be helpful in differentiating nasal lymphoma from nasal adenocarcinoma.

A 5-month-old intact female mixed cat presented with repetitive paraplegia and drainage of pus from the back despite continuous antibiotic medication. Neurologic examination was consistent with below T3-L3 myelopathy. Computed tomography and magnetic resonance imaging revealed a contrast-enhanced mass in the L1-3 spinal canal, and bone fragments in the T13 and L1 spinal canal. Spinal epidural empyema was suspected, and hemilaminectomy was performed for T12-L2 on the right side and T11-12 on the left side. Bone fragments were diagnosed as sequestrum infected with Bacteroides sp. The cat recovered enough to ambulate next day. One month after surgery, there was no deficit in neurological function. This is the first report of spinal epidural empyema concurrent with sequestrum in a cat.

Introduction In-body tissue architecture (iBTA) technology, based on cell-free tissue engineering, can produces collagenous tissues for implantation by subcutaneous embedding a designed mold. The aim of this study was to evaluate the biocompatibility of iBTA-induced “Biosheet®” collagenous sheets, as scaffold materials for bladder reconstruction. Methods Canine Biosheet® implants were prepared by embedding molds into subcutaneous pouches in beagles for 8 weeks. A part of canine bladder wall was excised (2 × 2 cm) and repaired by patching the same sized autologous Biosheet®. The Biosheet® implants were harvested 4 weeks (n = 1) and 12 weeks (n = 3) after the implantation and evaluated histologically. Results No disruption of the patched Biosheet® implants or urinary leakage into the peritoneal cavity was observed during the entire observation periods. There were no signs of chronic inflammation or Biosheet® rejection. The urine-contacting surface of luminal surface of the Biosheet® was covered with a multicellular layer of urothelium cells 4 weeks after implantation. α-SMA-positive muscle cells were observed at the margin of the Biosheet® implants at 12 weeks after the implantation. In addition, in the center of the Biosheet® implants, the formation of microvessels stained as α-SMA-positive was observed. Conclusion Biosheet® implants have biocompatibility as a scaffold for bladder reconstruction, indicating that they may be applicable for full-thickness bladder wall substitution. Further studies are required for definitive evaluation as a scaffold for bladder reconstruction.

This study aimed to determine a reliable therapeutic biomarker for localized small intestinal lymphoma (SIL) in dogs based on clinical and histopathological features. We retrospectively investigated 84 dogs with localized SIL, including 36 dogs receiving surgery and 48 dogs receiving chemotherapy. The dogs receiving surgery were divided into two subgroups: 18 dogs (group 1) with overall survival (OS)

Background Toceranib phosphate (TOC) could be made widely available for treating tumors in dogs if evidence shows that TOC inhibits recurrence after surgery. Objectives To investigate how postoperative adjuvant treatment with TOC modulates the tumor microenvironment (TME), by assessing effects on angiogenic activity, tumor-infiltrating regulatory T cells (Tregs), and intratumoral hypoxia. Animals Ninety-two client-owned dogs were included: 28 with apocrine gland anal sac adenocarcinoma, 24 with small intestinal adenocarcinoma, 22 with lung adenocarcinoma, and 18 with renal cell carcinoma. Methods Retrospective, multicenter study comparing time to progression (TTP) between 42 dogs treated by surgery and TOC and 50 dogs treated by surgery alone. Differences were analyzed in the expression of vascular endothelial growth factor receptor-2 (VEGFR2) and the number of Foxp3+ Tregs and hypoxia-inducible factor (HIF)-1α+ cells in tumor tissues sampled at the first and second (recurrence) surgeries. Results Median TTP for dogs treated by surgery and TOC (360 days) was higher than that for dogs treated by surgery alone (298 days; hazard ratio, 0.82; 95% confidence interval [CI], 0.65-0.96; P = .02). In dogs treated by surgery and TOC, VEGFR2 expression and the number of Tregs and HIF-1α+ cells were significantly lower in tissues sampled at the second surgery than in those sampled after the first surgery. In dogs treated by surgery alone, significant differences were found between samples from the 2 surgeries. Conclusions and clinical importance Toceranib phosphate could prove to be a useful postoperative adjuvant treatment because of its modulation of the TME.

OBJECTIVE To measure expression of microRNAs (miRNAs) in plasma and in extracellular vesicles (EVs) derived from plasma for dogs with glioma and dogs with other brain diseases. SAMPLE Plasma samples from 11 dogs with glioma and 19 control dogs with various other brain diseases. PROCEDURES EVs were isolated from plasma samples by means of ultracentrifugation. Expression of 4 candidate reference miRNAs (let-7a, miR-16, miR-26a, and miR-103) and 4 candidate target miRNAs (miR-15b, miR-21, miR-155, and miR-342-3p) was quantified with reverse transcription PCR assays. Three software programs were used to select the most suitable reference miRNAs from among the 4 candidate reference miRNAs. Expression of the 4 target miRNAs was then calculated relative to expression of the reference genes in plasma and EVs, and relative expression was compared between dogs with glioma and control dogs with other brain diseases. RESULTS The most suitable reference miRNAs were miR-16 for plasma and let-7a for EVs. Relative expression of miR-15b in plasma and in EVs was significantly higher in dogs with glioma than in control dogs. Relative expression of miR-342-3p in EVs was significantly higher in dogs with glioma than in control dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that miR-15b and miR-342-3p have potential as noninvasive biomarkers for differentiating glioma from other intracranial diseases in dogs. However, more extensive analysis of expression in specific glioma subtypes and grades, compared with expression in more defined control populations, will be necessary to assess their clinical relevance.

We examined the paracrine action of canine mesenchymal stromal cells (MSCs) derived from bone marrow on the survival and differentiation of neural stem cells (NSCs) in vitro. MSCs were collected from the proximal end of the diaphysis of femur of healthy beagle dogs. The 70-80% confluent MSCs were re-fed with serum-free DMEM. The MSCs were incubated for 48 hr and the supernatant was collected as the conditioned medium (MSC-CM). The survival rate of NSCs in MSC-CM was significantly greater than in the medium without MSC-CM. The percentage of differentiated neurons and neurite length in MSC-CM was also significantly higher than in the medium without MSC-CM. These results suggested that canine MSC-CM promotes stem cell survival and neural differentiation of NSCs.

Objective The aim of this study was to evaluate objective limb function using force plate gait analysis after tibial plateau levelling osteotomy (TPLO) in small breed dogs with cranial cruciate ligament rupture (CCLR). Materials and Methods Small breed dogs (15 kg or less) with unilateral CCLR treated with TPLO were evaluated using symmetry index (SI) of peak vertical force (PVF), vertical impulse and vector magnitude at PVF performed preoperatively and at 1, 2, 4 and 6 months postoperatively after routine TPLO surgery. Results Twelve dogs met the inclusion criteria. Hindlimb function was markedly improved after TPLO, with all three postoperative SI significantly higher after a month than preoperative values (p Conclusion The objective limb function of the affected hindlimb improved continuously after surgery and reached a near normal value at 6 months after surgery. It was suggested that TPLO for small breed dogs had good outcomes based on force plate gait analysis.

A 9-year-old neutered male Wire Fox Terrier presented with an 1-month history of hindlimb paresis. Magnetic resonance imaging revealed a contrast-enhanced mass at the level of the L2 vertebral canal. The dog became paraplegic with no deep perception of the hindlimbs, and the mass was surgically removed. The histopathological diagnosis was of a malignant peripheral nerve sheath tumor (MPNST). The dog suffered a relapse of right hindlimb ataxia at 225 days after the surgery. The dog died 434 days after the surgery. Necropsy found a large mass in the abdominal cavity invading from the L2-nerve. This is the first report of MPNST invading the abdominal cavity through the nerve root.

Thoracolumbar intervertebral disk herniation (TL-IVDH) with caudal articular process anomalies has been reported in Pugs. It currently remains unclear whether congenital caudal articular process aplasia/hypoplasia predisposes to the development of TL-IVDH. However, there are difficulties in proving the causal relationship between caudal articular process anomalies and TL-IVDH. The aim of this study was to describe the prevalence of TL-IVDH at the vertebral space containing anomalous and normal caudal articular processes in Pugs. Fifty-seven pugs were eligible to be included in this study. Caudal articular process aplasia/hypoplasia affected 52/57 (91.2%) dogs. The caudal articular process anomalies were most frequently located between T10 and T13. Colocalization of caudal articular process aplasia/hypoplasia and TL-IVDH was detected in 11 dogs (19.3%). The prevalence of TL-IVDH at vertebral spaces containing abnormal caudal articular processes was 12.3%, whereas the prevalence of TL-IVDH at vertebral spaces containing normal articular processes was 2.4%. With the increase in the number of vertebrae with caudal articular process anomalies, the prevalence of TL-IVDH also increased. The results of this study suggested the prevalence of caudal articular process anomalies was high in Pugs. The caudal articular process anomalies could be associated with TL-IVDH. A large cohort is needed to prove the causal relationship between caudal articular process anomalies and TL-IVDH.

BACKGROUND Triple-phase CT and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) MRI have been used to differentiate hepatocellular carcinomas (HCCs) in dogs. METHODS This retrospective case series aimed to compare the CT findings with MRI findings of 20 canine hepatocellular lesions, including eight poorly/moderately-differentiated HCCs, eight well-differentiated HCCs and four hyperplasias. CT data were analysed, and the following parameters were noted: vessel enhancement, enhancement pattern in the equilibrium phase, maximal transverse diameter, the lowest enhancement, and the attenuation values of each hepatocellular lesion in the precontrast and triple-phase series, including the arterial phase, portal phase and equilibrium phase. MRI data were analysed, and the following parameters were noted: signal intensities of each hepatocellular lesion on T2-weighted images and T1-weighted images, and signal intensity ratio of the hepatocellular lesions in the hepatobiliary phase. RESULTS In 62.5% of poorly/moderately-differentiated HCC and 75% of well-differentiated HCC, presumptive necrosis was detected on CT and MRI. In the hepatobiliary phase on MRI, the median signal intensity ratio of poorly/moderately-differentiated HCC (0.54 [range: 0.3-0.71]) was significantly lower than that of well-differentiated HCC (0.75 [range: 0.6-0.96]) and hyperplasia (0.79 [range: 071-0.98]; p = 0.02 and p = 0.02, respectively). CONCLUSION Gd-EOB-DTPA-enhanced MRI may be a superior modality for differentiating hepatocellular origin lesions.

Canine degenerative myelopathy (DM) is a fatal progressive neurodegenerative disease. Mutations in the superoxide dismutase 1 (SOD1) gene have been shown to be the major risk factor for DM, and it is hypothesized that neural degeneration is caused by a “gain of toxic function” of mutant SOD1. In this study, the spinal cord microRNA (miRNA) profiles of DM-affected dogs were investigated to elucidate the pathomechanisms of DM. Quantification of 277 miRNAs identified three up-regulated miRNAs and 18 down-regulated miRNAs in the spinal cords of DM-affected dogs. Based on gene ontology analysis, the target cluster of up-regulated miRNAs was associated with protein expression or modification and cellular response, and that of down-regulated miRNAs was associated with tissue development. In these clusters, we focused on the mechanism of protein ubiquitination. Polyubiquitination assay demonstrated that canine SOD1 proteins were polyubiquitinated and degraded by proteasomes. Immunohistochemistry of the spinal cords of DM-affected dogs showed that mutant SOD1 aggregations were not ubiquitin immunopositive. Using cultured cells, co-transfection of canine SOD1 and up-regulated miRNA in DM-affected dogs demonstrated that miR-23a, miR-142 and miR-221 significantly increased the proportion of cells with mutant SOD1 aggregation. These results suggested that up-regulated miRNAs in the spinal cords of DM-affected dogs may inhibit ubiquitination of misfolded SOD1 protein and induce mutant SOD1 aggregations, leading to further progression of degenerative processes in the DM pathology.

Canine degenerative myelopathy (DM) is an adult-onset fatal disease characterized by progressive degeneration of the spinal cord. Affected dogs have homozygous mutations in superoxide dismutase 1, and thus DM is a potential spontaneous animal model of human familial amyotrophic lateral sclerosis (ALS). Neuroinflammation is the pathological hallmark of ALS, whereby proinflammatory cytokines and chemokines are overproduced by activated glial cells such as astrocytes and microglia. However, the detailed pathogenesis of spinal cord degeneration in DM remains unknown. To further characterize the pathological mechanism of DM, we analyzed the caudal cervical cords of ten Pembroke Welsh Corgis pathologically diagnosed with DM by quantitative real-time reverse transcription polymerase chain reaction, immunohistochemistry (IHC), and double immunofluorescence. Compared to control spinal cord tissues, we found significantly enhanced transcriptions of interleukin-1β, tumor necrosis factor-α, CC motif chemokine ligand (CCL) 2 and vascular cell adhesion molecule -1 mRNA in the spinal cords of DM dogs. Moreover, IHC for the class II major histocompatibility complex molecules HLA-DR and CCL2 indicated that the immunopositive areas of activated macrophages/microglia and CCL2 protein were significantly increased in DM, and CCL2 protein was mainly overproduced by astrocytes. Our results suggest a proinflammatory state of the microenvironment in the DM spinal cord in which activated microglia and astrocytes play important roles by secreting a set of cytokines, chemokines, and expressing adhesion molecules.