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Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease in cats. In most cases, the responsible abnormality is a nonsense single nucleotide polymorphism in exon 29 of thePKD1gene (chrE3:g.42858112C>A, the conventionalPKD1variant). Epidemiological studies on feline ADPKD caused by the conventionalPKD1variant have been conducted in several countries, including Japan. However, they were limited to Persian cats or cats already suspected of ADPKD. There are no data on the prevalence of the conventionalPKD1variant among a wider cat population in Japan that is not limited to certain breeds or clinical backgrounds. This large-scale epidemiological study involving 1,281 cats aimed to establish a new genotyping assay to detect the conventionalPKD1variant rapidly. Among the cats examined in this study, 1.8% (23/1,281) harbored the conventionalPKD1variant. The odds of having the conventionalPKD1variant were significantly higher in Persian cats, Scottish Folds, and Exotic Shorthairs than in the other breeds. Furthermore, targeted resequencing ofPKD1was performed in cats with ADPKD and healthy cats to search for new variants that may be involved in ADPKD. We identified four variants unique to ADPKD cats that were not found in healthy cats, all of which were in exon 15. This indicates that variants in exon 15 ofPKD1, in addition to the conventional variant in exon 29, are key factors in the pathogenesis of ADPKD in cats.

Canine histiocytic proliferative disorders include aggressive and fatal diseases, such as histiocytic sarcoma (HS) and histiocytosis (SyH). The molecular mechanisms underlying cell proliferation need to be elucidated for the development of effective treatments. In the present study, mRNA expression levels were comprehensively analysed in cell lines derived from localized HS, disseminated HS, SyH and Langerhans cell histiocytosis (LCH) in dogs. Based on the results obtained, the growth inhibitory effects of palbociclib, a CDK4/6 inhibitor, were verified with the cell lines in vitro and in xenograft mouse model. Hierarchical clustering and principal component analysis plots of mRNA expression profiles divided the cell lines into three groups: a localized HS group, disseminated HS/SyH group, and LCH. The results of an ingenuity pathway analysis suggested that the MAPK signalling pathway was activated in the localized HS and LCH cell lines, and the PI3K signalling pathway in the disseminated and localized HS cell lines. In all cell lines, the expression of the tumour suppressor genes TP53, CDKN2A and CDKN1A was down-regulated, whereas that of Rb was preserved. In vitro assessments revealed the growth inhibitory effects of palbociclib in all cell lines examined. In a xenograft mouse model using a cell line from disseminated HS, palbociclib exerted significant growth inhibitory effects. These results suggest the potential of palbociclib as a therapeutic drug candidate for the treatment of malignant histiocytic proliferative disorders of the dog.

Urethral sphincter mechanism incompetence (USMI) is a common cause of urinary incontinence in dogs. Although estrogen is often prescribed for the medical therapy of USMI for spayed female dogs, they are known to have limited effectiveness and potential adverse effects. In castrated male dogs with USMI, testosterone reagents have been attempted besides estrogen. In this study, the effect of testosterone drugs, mainly methyltestosterone, on spayed female dogs with USMI was retrospectively evaluated. Ten spayed female dogs with USMI were included. Diagnosis of USMI was based on the results of the dogs’ medical history, clinical signs, and no abnormalities in physical examinations, urinalysis, ultrasonography, X-ray imaging, and neurological examinations. Methyltestosterone was administered at doses of 0.32–1.27 mg/kg BW p.o. semel in die (sid.) to twice a week. Nine of the ten dogs had good or excellent responses 2 to 4 weeks after the start of treatment. The minimum effective dose was 0.32 mg/kg/day. Although no severe adverse symptoms occurred in any dog, a mild increase in alanine aminotransferase was temporally observed at doses of 1.0 and 1.1 mg/kg/day in the two dogs. After dose reduction or withdrawal, two of eight dogs had recurrence of urinary incontinence. Resumption of testosterone treatment clearly improved the symptoms in the two dogs. These results indicate that testosterone reagents might be an option for treating USMI in spayed female dogs as well.

A 6-mo-old female Chihuahua was presented with recurrent episodes of hypoglycemia and collapse. Physical examination revealed proportionate dwarfism, retained puppy hair coat, retained deciduous teeth, and open fontanelles. Routine blood tests revealed hypoglycemia, thrombocytosis, hypoproteinemia, and elevated alkaline phosphatase activity. The urinalysis, radiographs, and ultrasonographs were unremarkable. Endocrine testing revealed that insulin-like growth factor 1 was below the detection limit; concentrations of total thyroxine, baseline cortisol, and cortisol stimulated by tetracosactide acetate were within their reference intervals. The pituitary gland showed no organic abnormalities on magnetic resonance imaging. For definitive diagnosis, we conducted the stimulation test for growth hormone (GH) release and diagnosed isolated GH deficiency. Genetic investigation revealed that the present case had 4 point mutations in intronic regions and a 6-bp deletion in exon 5 of GH1. The bioinformatics tool PROVEAN algorithm predicted that the deletion in exon 5 could be deleterious to the function of GH1.

BackgroundTargeting regulatory T cell (Treg) infiltration is an emerging strategy for cancer immunotherapy. However, its efficacy in advanced prostate cancer remains unclear. Here, we showed the therapeutic efficacy of anti-Treg treatment in a canine model of advanced prostate cancer.MethodsWe used dogs with naturally occurring prostate cancer to study the molecular mechanism underlying Treg infiltration and the effect of anti-Treg treatment. Tumor-infiltrating Tregs was evaluated by immunohistochemistry, and the association with prognosis was examined in dogs with spontaneous prostate cancer. The molecular mechanism of Treg infiltration was explored by RNA sequencing and protein analyses. A non-randomized canine clinical trial was conducted to define the therapeutic potential of anti-Treg treatment for advanced prostate cancer. Human prostate cancer datasets were analyzed to compare gene expression in dogs and humans.ResultsTumor-infiltrating Tregs were associated with poor prognosis in dogs bearing spontaneous prostate cancer. RNA sequencing and protein analyses showed a possible link between the CCL17–CCR4 pathway and the increase of tumor-infiltrating Tregs. Dogs with advanced prostate cancer responded to mogamulizumab, a monoclonal antibody targeting CCR4, with decreased circulating Tregs, improved survival, and low incidence of clinically relevant adverse events. Urinary CCL17 concentration and BRAFV595E mutation were independently predictive of the response to mogamulizumab. Analysis of a transcriptomic dataset of human prostate cancer showed that the CCL17–CCR4 axis correlated with Foxp3. In silico survival analyses revealed that high expression of CCL17 was associated with poor prognosis. Immunohistochemistry confirmed that tumor-infiltrating Tregs expressed CCR4 in human patients with prostate cancer.ConclusionsAnti-Treg treatment, through CCR4 blockade, may be a promising therapeutic approach for advanced prostate cancer in dogs and some population of human patients.

ObjectiveAlthough genome-wide association studies (GWAS) have identified approximately 100 loci for rheumatoid arthritis (RA), the disease mechanisms are not completely understood. We evaluated the pathogenesis of RA by focusing on rare coding variants.MethodsThe coding regions of 98 candidate genes identified by GWAS were sequenced in 2294 patients with RA and 4461 controls in Japan. An association analysis was performed using cases and controls for variants, genes and domains of TYK2. Cytokine responses for two associated variants (R231W, rs201917359; and R703W, rs55882956) in TYK2 as well as a previously reported risk variant (P1004A, rs34536443) for multiple autoimmune diseases were evaluated by reporter assays.ResultsA variant in TYK2 (R703W) showed a suggestive association (p=5.47×10−8, OR=0.48). We observed more accumulation of rare coding variants in controls in TYK2 (p=3.94×10−12, OR=0.56). The four-point-one, ezrin, radixin, moesin (FERM; 2.14×10−3, OR=0.66) and pseudokinase domains (1.63×10−8, OR=0.52) of TYK2 also showed enrichment of variants in controls. R231W in FERM domain especially reduced interleukin (IL)-6 and interferon (IFN)-γ signalling, whereas P1104A in kinase domain reduced IL-12, IL-23 and IFN-α signalling. R703W in pseudokinase domain reduced cytokine signals similarly to P1104A, but the effects were weaker than those of P1104A.ConclusionsThe FERM and pseudokinase domains in TYK2 were associated with the risk of RA in the Japanese population. Variants in TYK2 had different effects on cytokine signalling, suggesting that the regulation of selective cytokine signalling is a target for RA treatment.

The present study aimed to verify the changes in the expression levels of 13 candidate genes associated with chemotherapy resistance and to construct a scoring system to predict resistance to these drugs. The expression levels of the 13 candidate genes were compared between 20 dogs with lymphoma that were sensitive to drugs used in CHOP-based protocol and 16 dogs with lymphoma that were resistant to these drugs. The expression levels of six genes; ASNS, CCR3, CALCA, FCER1A, LOC448801, and EDNRB were significantly different between the two groups. A scoring system to predict resistance to cyclophosphamide, doxorubicin and vincristine, which are used in CHOP-based protocol, was constructed based on expression levels of the six genes in these 36 dogs using logistic regression models. After internal validation, sensitivity and specificity of the scoring system were 0.759 and 0.853, respectively. External validation was conducted in another cohort of 33 dogs with lymphoma, and sensitivity and specificity of the scoring system were 0.800 and 0.696, respectively. In conclusion, this study identified six genes associated with resistance to drugs used in CHOP-based protocol in canine lymphoma and proposed a novel scoring system to predict resistance to these drugs. This system might be beneficial in selecting the most appropriate chemotherapy protocol for individual dogs with lymphoma.

Oclacitinib is an effective systemic therapy for dogs with atopic dermatitis (AD). Few studies have evaluated concurrent topical treatment with oclacitinib in dogs.To evaluate the efficacy and safety of combination therapy of oclacitinib and 0.0584% hydrocortisone aceponate (HCA) spray in dogs with AD.Eighteen dogs with AD.This study was a randomized, double-blinded, placebo-controlled trial. All dogs were treated with oclacitinib (0.4-0.6 mg/kg twice daily for 14 days, then once daily for 14 days) and randomized to receive either HCA spray or placebo spray, applied once daily for seven days then every other day through to Day (D)28. Clinical assessments included the Canine Atopic Dermatitis Extent and Severity Index, 4The mean CADESI-4 and PVAS scores were significantly reduced on D7 and D14 compared to D0 in both groups (P 0.05). From D14 to D21, CADESI-4 and PVAS scores were significantly increased in the placebo group (P 0.005), and not in the HCA-treated group. The mean reduction from baseline of the HCA-treated group was significantly higher than that of the placebo group for the PVAS and CADESI-4 on D21 (59.9% versus 27.6%, P = 0.0216) and D28 (56.0% versus 30.5%, P = 0.0109), respectively. One dog in the HCA-treated group was withdrawn as a consequence of developing diarrhoea.Topical application of 0.0584% HCA spray may be useful for preventing exacerbation of pruritus and clinical lesions when tapering oclacitinib therapy in dogs with AD.L’oclacitinib est un traitement systémique efficace pour les chiens atteints de dermatite atopiques (cAD). Peu d’études ont évaluées un traitement topique concomitant à l’administration d’oclacitinib chez le chien.Evaluer l’efficacité et l’innocuité de traitement combiné d’oclacitinib et d’un spray de 0,0584% d’acéponate d’hydrocortisone (HCA) chez les chiens avec cAD.Dix-huit chiens avec cAD. MATÉRIELS ET MÉTHODES: Cette étude est randomisée, en double aveugle, contre placebo. Tous les chiens ont été traités avec de l’oclacitinib (0.4-0.6 mg/kg deux fois par jour pendant 14 jours, puis une fois par jour pendant 14 jours) et randomisés pour recevoir soit le spray d’HCA soit le placebo, appliqué une fois par jour pendant sept jours puis un jour sur deux jusqu’à jour (J) 28. Les évaluations cliniques comprennent un CADESI-04 (Canine Atopic Dermatitis Extent and Severity Index, 4L’application topique d’un spray d’HCA à 0,0584% peut être utile pour prévenir l’aggravation du prurit et des lésions cliniques au cours de la diminution de dose d’oclacitinib chez les chiens avec cAD.INTRODUCCIÓN: el oclacitinib es una terapia sistémica eficaz para perros con dermatitis atópica canina (cAD). Pocos estudios han evaluado el tratamiento tópico concomitante con oclacitinib en perros. OBJETIVOS: Evaluar la eficacia y seguridad de la terapia combinada de oclacitinib y el aerosol de aceponato de hidrocortisona (HCA) al 0,0584% en perros con cAD. ANIMALES: dieciocho perros con cAD. MÉTODOS Y MATERIALES: este estudio fue aleatorio, doble ciego y controlado con placebo. Todos los perros fueron tratados con oclacitinib (0,4-0,6 mg/kg dos veces al día durante 14 días, luego una vez al día durante 14 días) y fueron asignados al azar para recibir aerosol de HCA o aerosol placebo, aplicado una vez al día durante siete días y luego cada dos días hasta el día (D) 28. Las evaluaciones clínicas incluyeron el índice de gravedad y extensión de la dermatitis atópica canina, cuarta revisión (CADESI-04) y la escala analógica visual de prurito (pVAS) cada siete días, y análisis de sangre y orina cada 14 días. RESULTADOS: las puntuaciones medias de CADESI-04 y pVAS se redujeron significativamente en D7 y D14 en comparación con D0 en ambos grupos (P0,05). De D14 a D21, las puntuaciones de CADESI-04 y pVAS aumentaron significativamente en el grupo de placebo (P0,005) y no en el grupo tratado con HCA. La reducción media desde el inicio del grupo tratado con HCA fue significativamente mayor que la del grupo de placebo para pVAS y CADESI-04 en D21 (59,9% versus 27,6%, P = 0,0216) y D28 (56,0% versus 30,5%, P = 0.0109), respectivamente. Un perro en el grupo tratado con HCA fue retirado como consecuencia del desarrollo de diarrea. CONCLUSIÓN: la aplicación tópica de un aerosol de HCA al 0,0584% puede ser útil para prevenir la exacerbación del prurito y las lesiones clínicas cuando se reduce el tratamiento con oclacitinib en perros con cAD.Oclacitinib ist eine wirksame systemische Therapie für Hunde mit caniner atopischer Dermatitis (cAD). Nur wenige Studien haben eine gleichzeitige topische Behandlung bei Oclacitinib Verabreichung bei Hunden untersucht.Eine Evaluierung der Wirksamkeit und Sicherheit der Kombinationstherapie von Oclacitinib und 0,0584%igem Hydrocortison Aceponate (HCA) Spray bei Hunden mit cAD.Achtzehn Hunde mit cAD.Es handelte sich hierbei um eine randomisierte, doppel-blinde, Plazebo-kontrollierte Studie. Es wurden alle Hunde mit Oclacitinib (0,4-0,6 mg/kg zweimal täglich für 14 Tage, danach einmal täglich für 14 Tage behandelt) und erhielten zufällig entweder HCA oder Plazebo Spray, welcher zunächst sieben Tage lang einmal täglich, dann jeden zweiten Tag bis zum Tag (D) 28 angewendet wurde. Die klinische Beurteilung erfolgte mittels Canine Atopic Dermatitis Extent and Severity Index, 4. Iteration (CADESI-04) und der Pruritus Visual Analog Scale (pVAS) alle sieben Tage, sowie einer Blut- und Urinuntersuchung alle 14 Tage.Die durchschnittlichen CADESI-04 und pVAS Scores waren am D7 und am D14 im Vergleich zu D0 in beiden Gruppen (P0,05) signifikant reduziert. Von D14 bis D21 waren die CADESI-04 und die pVAS Scores in der Plazebogruppe signifikant erhöht (P0,005), allerdings nicht in der mit HCA-behandelten Gruppe. Die durchschnittliche Verminderung vom Ausgangspunkt der HCA-behandelten Gruppe lag am D21 (59,9% versus 27,6%, P = 0,0216) bzw am D28 (56,0% versus 30,5%, P = 0,0109) signifikant höher für pVAS und CADESI-04 als jene der Plazebogruppe. Ein Hund aus der HCA-behandelten Gruppe entwickelte Durchfall und wurde aus der Studie genommen.Die topische Verabreichung von 0,0584%igem HCA Spray könnte sich bei Hunden mit cAD gut auf eine Verschlimmerung des Pruritus und der klinischen Läsionen auswirken, wenn die Behandlungsdosis mit Oclacitinib langsam reduziert wird.背景: 对于特应性皮炎(cAD)患犬, 奥拉替尼是一种有效的全身性治疗药物。很少有研究评估犬同时接受奥拉替尼和外部治疗的效果。 目的: 评估奥拉替尼和0.0584%氢化可的松丙酸酯(HCA)喷雾剂联合治疗, cAD犬的有效性和安全性。 动物: 18只cAD犬。 方法和材料: 本研究是一项随机、双盲、安慰剂对照试验。所有犬均接受奥拉替尼治疗 (0.4-0.6 mg/kg, 每日两次, 持续14天, 然后每日一次, 持续14天) , 并随机接受HCA喷雾剂或安慰剂喷雾剂, 每日一次, 持续7天, 然后隔日一次, 直至第28天(D)。临床评估包括第4版犬特应性皮炎严重程度和指数 (CADESI-04)和瘙痒视觉模拟量表(pVAS), 每7天一次, 以及血液和尿液检查, 每14天一次。 结果: 与D0相比, 两组中D7和D14的平均CADESI-04和pVAS评分显著降低(P0.05)。从D14至D21, 安慰剂组的CADESI-04和pVAS评分显著增加(P0.005), 而HCA治疗组无显著增加。D21(59.9%与27.6%,P = 0.0216) 和D28(56.0%与30.5%,P = 0.0109) 时, HCA治疗组的pVAS和CADESI-04相对于基线的平均下降程度显著高于安慰剂组。HCA治疗组中的1只犬因发生腹泻而退出研究。 结论: 在cAD犬逐渐减少奥拉替尼治疗时, 外部应用0.0584%HCA喷雾剂可能有助于预防瘙痒和临床病变加重。.背景: オクラシチニブは、犬アトピー性皮膚炎（cAD）の犬に効果的な全身療法である。犬におけるオクラシチニブとの併用外用療法を評価した研究はほとんどない。 目的: 本研究の目的は、cADの犬におけるオクラシチニブ及び0.0584％アセポン酸ヒドロコルチゾン（HCA）スプレーの併用療法の有効性及び安全性を評価することであった。 被験動物: cADを有する18頭の犬。 材料と方法: 本研究は、無作為化二重盲検プラセボ対照試験であった。すべての犬をオクラシチニブ（0.4〜0.6 mg / kg、1日2回14日間、その後1日1回14日間）で治療し、HCAスプレーまたはプラセボスプレーのいずれかをランダムに投与し、1日1回7日間、その後隔日で28日目まで適用した。臨床評価に、犬アトピー性皮膚炎の程度及び重症度指数、4回反復（CADESI-04）及び視覚的掻痒アナログ尺度（pVAS）を7日ごとに、血液及び尿検査を14日ごとに実施した。 結果: 平均CADESI-04およびpVASスコアは、両グループのD0と比較してD7およびD14で有意に減少した（P0.05）。 D14からD21まで、CADESI-04およびpVASスコアはプラセボ群で有意に増加し（P0.005）、HCA治療群では増加しなかった。 HCA治療群のベースラインからの平均減少は、D21（59.9％対27.6％、P = 0.0216）およびD28（56.0％対30.5％、P = 0.0109）でプラセボ群のpVASおよびCADESI-04よりもそれぞれ有意に高かった。 HCA治療群の1頭の犬は、下痢を発症し、結果として離脱した。 結論: 0.0584％HCAスプレーによる外用塗布は、cADの犬のオクラシチニブ療法を漸減する際の掻痒症および臨床病変の悪化防止に役立つ可能性がある。.O oclacitinib é uma terapia sistêmica eficaz para cães com dermatite atópica canina (DAC). Poucos estudos avaliaram o tratamento tópico concomitante com oclacitinib em cães.Avaliar a eficácia e segurança da terapia combinada de oclacitinib e spray de aceponato de hidrocortisona a 0,0584% (HCA) em cães com DAC.Dezoito cães com DAC. MÉTODOS E MATERIAIS: Este estudo foi um ensaio randomizado, duplo-cego e placebo-controle. Todos os cães foram tratados com oclacitinib (0,4-0,6 mg/kg duas vezes ao dia por 14 dias, depois uma vez ao dia por 14 dias) e randomizados para receber spray de HCA ou spray de placebo, aplicado uma vez ao dia por sete dias, em seguida, a cada dois dias até o dia (D) 28. As avaliações clínicas incluíram o Índice de Gravidade e Extensão da Dermatite Atópica Canina, 4ª iteração (CADESI-04) e a Escala Visual Analógica de prurido (pVAS) a cada sete dias, e exames de sangue e urina a cada 14 dias.Os escores médios do CADESI-04 e pVAS foram significativamente reduzidos no D7 e D14 em comparação ao D0 em ambos os grupos (P0,05). De D14 a D21, os escores CADESI-04 e pVAS aumentaram significativamente no grupo de placebo (P0,005), e não no grupo tratado com HCA. A redução média em relação ao escore inicial do grupo tratado com HCA foi significativamente maior do que a do grupo placebo para o pVAS e o CADESI-04 no D21 (59,9% versus 27,6%, P = 0,0216) e no D28 (56,0% versus 30,5%, P = 0,0109), respectivamente. Um cão do grupo tratado com HCA foi retirado do estudo devido ao desenvolvimento de diarreia. CONCLUSÃO: A aplicação tópica de 0,0584% de HCA spray pode ser útil para prevenir a exacerbação do prurido e lesões clínicas ao reduzir a terapia com oclacitinib em cães com DAC.

A 6-mo-old female Chihuahua was presented with recurrent episodes of hypoglycemia and collapse. Physical examination revealed proportionate dwarfism, retained puppy hair coat, retained deciduous teeth, and open fontanelles. Routine blood tests revealed hypoglycemia, thrombocytosis, hypoproteinemia, and elevated alkaline phosphatase activity. The urinalysis, radiographs, and ultrasonographs were unremarkable. Endocrine testing revealed that insulin-like growth factor 1 was below the detection limit; concentrations of total thyroxine, baseline cortisol, and cortisol stimulated by tetracosactide acetate were within their reference intervals. The pituitary gland showed no organic abnormalities on magnetic resonance imaging. For definitive diagnosis, we conducted the stimulation test for growth hormone (GH) release and diagnosed isolated GH deficiency. Genetic investigation revealed that the present case had 4 point mutations in intronic regions and a 6-bp deletion in exon 5 of GH1. The bioinformatics tool PROVEAN algorithm predicted that the deletion in exon 5 could be deleterious to the function of GH1.

A 10 yr old intact female German shepherd dog presented with a large peripheral odontogenic fibroma and malignant melanoma on her lower jaw. The tumor was resected with a unilateral subtotal rostral hemimandibulectomy. After the mandible was removed, it was devitalized intraoperatively by freezing it in liquid nitrogen. It was subsequently reimplanted. New bone tissue formed in the gap between the frozen bone and the host bone. The regenerated bone contained osteocytes, osteoblasts, and blood vessels. The cosmetic appearance of the dog was preserved. The dog had normal mastication. The malignant melanoma recurred rostral of the left canine tooth at 159 days after the reconstruction surgery. A subtotal hemimandibulectomy was consequently performed. This is the first reported case of mandibular reconstruction using a liquid nitrogen-treated autograft in a dog with oral tumors.

Although genome-wide association studies (GWAS) have identified approximately 100 loci for rheumatoid arthritis (RA), the disease mechanisms are not completely understood. We evaluated the pathogenesis of RA by focusing on rare coding variants.The coding regions of 98 candidate genes identified by GWAS were sequenced in 2294 patients with RA and 4461 controls in Japan. An association analysis was performed using cases and controls for variants, genes and domains of TYK2. Cytokine responses for two associated variants (R231W, rs201917359; and R703W, rs55882956) inA variant inThe FERM and pseudokinase domains in TYK2 were associated with the risk of RA in the Japanese population. Variants in

OBJECTIVE To determine the prognostic value of CD44 variant isoform expression in dogs with multicentric high-grade B-cell lymphoma (BCL). ANIMALS 45 dogs with multicentric BCL and 10 healthy control Beagles. PROCEDURES The medical record database of a veterinary teaching hospital was searched to identify dogs with BCL that were treated between November 2005 and April 2015. Information regarding overall response to chemotherapy, progression-free survival (PFS) time, and overall survival time was extracted from each record. Archived lymph node aspirate specimens from dogs with BCL and lymph node aspirate specimens from the 10 control dogs underwent real-time PCR analysis to determine mRNA expression of CD44 variant isoforms of exons 3, 6, and 7 and the CD44 whole isoform. For each isoform, mRNA expression was compared between dogs with BCL and control dogs. The mean relative expression of each isoform was used to classify dogs with BCL into either a high- or low-expression group, and overall response rate, PFS time, and overall survival time (ie, indices of prognosis) were compared between the 2 groups. RESULTS For all isoforms evaluated, mean relative mRNA expression for dogs with BCL was numerically lower than that for control dogs. Dogs with BCL and high CD44 isoform expression had a lower overall response rate, median PFS time, and median overall survival time, compared with dogs with BCL and low CD44 isoform expression. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that, for dogs with BCL, high expression of exons 3, 6, and 7 was associated with a poor prognosis.

The molecular mechanisms of acquisition of chemotherapy resistance in canine lymphoma have not been elucidated. The aim of the present study was to identify novel molecular mechanisms of chemotherapy resistance by a comprehensive analysis of changes in gene expression profiles (GEPs). Tumor samples were obtained from 10 dogs with lymphoma at chemotherapy sensitive and chemotherapy resistant phases. During chemotherapy resistance, the expression of genes associated with immune responses and inflammatory reactions was decreased compared to chemotherapy sensitive phases. In addition, 11 genes, with significant changes in expression (P

Methylxanthine derivatives increase cAMP and are known to have diuretic, cardiac, and central nervous system stimulatory effects. Moreover, caffeine inhibits the development of tumors induced by various carcinogens. The aim of this work was to elucidate the anticancer effects on apoptosis of xanthine derivatives alone and with doxorubicin in canine hemangiosarcoma cells. Xanthine derivatives with or without doxorubicin were administered to cells, and the effects were investigated by measuring tumor cell proliferation, cell death (cytotoxicity) induction, and apoptosis by the expression of annexin V or caspase 3/7. Both caffeine and theophylline induced apoptosis, and the treated cells expressed annexin V and caspase 3/7. Both drugs enhanced doxorubicin-induced cytotoxicity; however, hypoxanthine showed no effect. These results indicate that theophylline is similar to caffeine; both drugs may enhance doxorubicin-induced cytotoxicity by inhibiting ATM/ATR kinases. Our data suggest that caffeine and theophylline have anticancer effects and can improve the treatment effect in canine hemangiosarcoma patients.

Phosphate-buffered sucrose (PBSc) solution is effective for short-term hypothermic preservation of tissue during feline kidney transplantation. A high-molecular-weight polyethylene glycol (35,000 Da, PEG35) reportedly enhanced the protective effects against cold-induced tubular injuries in animal kidney transplantation models. We investigated the ability of PBSc solution containing PEG35 to preserve cultured feline kidney cells using in vitro WST-8 cell proliferation assays. PEG35 significantly improved cell viability during 24 hr of cold preservation. PBSc containing 20 g/l PEG35 achieved an effect almost equal to that of University of Wisconsin (UW) solution, the gold standard preservation solution used in human clinical kidney transplantation, for up to 24 hr of preservation. Our results suggest that PBSc containing PEG35 provides an excellent medium for graft cold storage during feline kidney transplantation.