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1.
Malignant melanoma (MM) is one of the most aggressive cancers in dogs and in humans. However, the molecular mechanisms of its development and progression remain unclear. Presently, we examined the expression profile of microRNAs (miRs) in canine oral MM tissues and paired normal oral mucosa tissues by using the microRNA‐microarray assay and quantitative RT‐PCR. Importantly, a decreased expression of miR‐203 was significantly associated with a shorter survival time. Also, miR‐203 and ‐205 were markedly down‐regulated in canine and human MM cell lines tested. Furthermore, the ectopic expression of miR‐205 had a significant inhibitory effect on the cell growth of canine and human melanoma cells tested by targeting erbb3. Our data suggest that miR‐203 is a new prognostic factor in canine oral MMs and that miR‐205 functions as a tumour suppressor by targeting erbb3 in both canine and human MM cells.  相似文献   

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Since companion dogs have the same living environment as humans, they are a good animal model for the study of human diseases; this is especially true of canine spontaneous mammary tumours models. A better understanding of the natural history and molecular mechanisms of canine mammary tumour is of great significance in comparative medicine. Here, we collected canine mammary tumour cases and then assayed the clinical cases by pathological examination and classification by HE staining and IHC. miRNA‐497 family members (miR‐497, miR‐16, miR‐195 and miR‐15) were positively correlated with the breast cancer marker genes p63 and PTEN. Modulation of the expression of miR‐497 in the canine mammary tumour cell lines CMT1211 and CMT 7364 induced apoptosis and inhibited cell proliferation. Mechanistically, IRAK2 was shown to be a functional target of miR‐497 that affects the characteristics of cancer cells by inhibiting the activity of the NF‐κB pathway. Overall, our work reveals the miR‐497/IRAK2/NF‐κB axis as a vital mechanism of canine mammary tumour progression and suggests this axis as a target in breast cancer.  相似文献   

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Summary

Adverse reactions to various trimethoprim‐sulphonamide (T‐S) combinations were studied retrospectively in dogs and cats referred to the Utrecht University Department of Clinical Sciences of Companion Animals during the period 1985–1994. Dermatological and systemic reactions were observed in 19 dogs and 2 cats. Specific histological reaction patterns were seen in 3 dogs with toxic epidermal necrolysis, in 1 dog and 1 cat with erythema multiforme, and in 1 dog with pemphigus foliaceus. Diagnostic criteria used in humans proved to be reliable in dogs and cats as well. Adverse reactions were observed within 7–14 days after administration and were most often due to sulphadiazine (76%) and sulphatroxazole (14%). The incidence of adverse reactions to T‐S was 0.25%.  相似文献   

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Background: Malignant melanoma of dogs is a highly aggressive neoplasm and is the 2nd most common digit tumor. Metastatic disease is a common sequela for which few effective treatment options exist. Studies show that xenogeneic tyrosinase DNA vaccination yields immune responses and prolongation of survival in dogs with oral malignant melanoma. Objectives/Hypothesis: Describe clinical findings and tumor characteristics of a cohort of dogs with digit malignant melanoma, and evaluate the prognostic utility of a proposed staging system. Determine if a novel xenogeneic DNA vaccine is safe and potentially effective for treatment of dogs with digit melanoma. Animals: Fifty‐eight dogs with digit malignant melanoma treated at the Animal Medical Center between 2004 and 2007. Methods: Retrospective, medical records review of dogs with digit melanoma treated with xenogeneic DNA vaccine. Results: Overall median survival time (MST) for dogs treated with loco‐regional control and xenogeneic DNA vaccine was 476 days with a 1‐year survival rate of 63%. MST for dogs presenting with metastasis was 105 days versus 533 days for dogs presenting without metastasis (P < .0001). Forty‐eight percent of the dogs in the latter group were alive at 2 and 3 years. A proposed staging system proved prognostic with stages I–IV dogs surviving >952, >1,093, 321, and 76 days, respectively. Conclusions and Clinical Importance: The xenogeneic murine tyrosinase DNA vaccine was safe and appears effective when used in conjunction with local and regional disease control. The proposed staging system was prognostic in this study and future studies might benefit from utilizing this staging system.  相似文献   

8.
MicroRNAs (miRNAs) are small non‐coding RNAs that participate in the regulation of gene expression. Their role during mammary gland development is still largely unknown. In this study, we performed a microarray analysis to identify miRNAs associated with high mammogenic potential of the bovine mammary gland. We identified 54 significantly differentially expressed miRNAs between the mammary tissue of dairy (Holstein‐Friesian, HF) and beef (Limousin, LM) postpubertal heifers. Fifty‐two miRNAs had higher expression in the mammary tissue of LM heifers. The expression of the top candidate miRNAs (bta‐miR‐10b, bta‐miR‐29b, bta‐miR‐101, bta‐miR‐375, bta‐miR‐2285t, bta‐miR‐146b, bta‐let7b, bta‐miR‐107, bta‐miR‐1434‐3p) identified in the microarray experiment was additionally evaluated by qPCR. Enrichment analyses for targeted genes revealed that the major differences between miRNA expression in the mammary gland of HF versus LM were associated with the regulation of signalling pathways that are crucial for mammary gland development, such as TGF‐beta, insulin, WNT and inflammatory pathways. Moreover, a number of genes potentially targeted by significantly differentially expressed miRNAs were associated with the activity of mammary stem cells. These data indicate that the high developmental potential of the mammary gland in dairy cattle, leading to high milk productivity, depends also on a specific miRNA expression pattern.  相似文献   

9.
Determination of an optimal number/set of endogenous control (EC) microRNA (miRNA) genes is a critical but often an underappreciated aspect of quantitative gene expression analysis. In this study, the expression stabilities of 13 selected porcine EC miRNA genes were compared in all 47 tissue‐specific normal tissues, 10 types of adipose tissue, and four types of muscle tissue using an EvaGreen quantitative PCR approach. Seven, 12, and 11 genes exhibited credible stability in the three groups, respectively. Our analysis clearly showed that three optimal EC genes are adequate for an accurate normalization, which correlated well with the theoretical optimal number (r ≥ 0.841). In terms of economical and experimental feasibility, we recommend the use of the three most stable EC miRNA genes for calculating the normalization factor, that is, ssc‐miR–17, −103 and −107 for all 47 different tissues. We also suggest that two sets of EC miRNA genes are appropriate for 10 types of adipose tissue (ssc‐miR–17, −107 and −24) and four types of muscle tissue (ssc‐miR–17, −23a and −103), respectively. We envision that these results will serve as a valuable reference for other studies aimed at measuring tissue‐specific miRNA abundance in porcine samples.  相似文献   

10.
The aim of this study was to explore the expression difference of miRNAs and mRNAs between the follicular phase (FP) and luteal phase (LP) in porcine ovaries and provide a theoretical basis for the research on mammalian reproductive regulation. RNA‐Seq and miRNA‐Seq were used to identify differentially expressed genes (DEGs) and miRNAs (DEMs) between the FP and LP in ovaries of six sows (3‐year‐old Yorkshire pigs with similar weights and same parities). Bioinformatic analysis was used to screen potential genes and miRNAs related to porcine ovarian function. Real‐time qualitative PCR was used to validate the sequencing results. RNA‐Seq results showed that 3,078 genes were up‐regulated, and 1,444 genes were down‐regulated in the LP compared with the FP, and DEGs were significantly enriched in 242 Gene Ontology (GO) terms and 33 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. miRNA‐Seq identified 112 DEMs, of which 25 were up‐regulated and 87 were down‐regulated in the LP compared with the FP. We obtained 186 intersection genes (IGs) between the 4,522 DEGs and 2,444 target genes predicted from the 112 DEMs. After constructing a miRNA‐gene‐pathway network, we identified key miRNAs and genes including miR‐17‐3p, miR‐214, miR‐221‐5p, miR‐125b, FGF1, YWHAG, YWHAZ, FDFT1 and DHCR24, which are enriched in Hippo and PI3K‐Akt signalling pathways, and various metabolic pathways. These results indicate that these key genes and miRNAs may play important roles in the developmental transition from FP to LP in porcine ovaries and represent candidate targets for further study.  相似文献   

11.
Use of cyclosporine to treat granulomatous meningoencephalitis in three dogs Three dogs with a presumptive diagnosis of granulomatous meningoencephalitis were treated with orally administered cyclosporine. In 2 dogs, cyclosporine administration replaced initial corticosteroid administration, and in 1 dog, cyclosporine was the only treatment used. One dog had the focal form of the disease in the brainstem, 1 dog had the focal form in the forebrain associated with a concurrent ocular form, and 1 dog had the disseminated form of disease. At 12-month follow-up, the 2 dogs with the focal form of the disease had no clinical signs. The dog with the disseminated form improved only partially, and euthanasia was performed 3 weeks after initial evaluation. Cyclosporine was considered effective at an initial dosage of 6 mg/kg (2.7 mg/lb) every 12 hours. Adverse effects associated with cyclosporine administration included transient lymphopenia, excessive shedding, and focal symmetric hair discoloration.  相似文献   

12.
The purpose of this study was to evaluate Soft Coated Wheaten Terriers (SCWTs) affected with protein-losing enteropathy (PLE) or protein-losing nephropathy (PLN) or both for allergy to food. We performed gastroscopic food-sensitivity testing, a provocative dietary trial, and measurement of fecal immunoglobulin E (IgE) in 6 SCWTs affected with PLE or PLN or both. Positive gastroscopic food-sensitivity test reactions were noted in 5 of 6 dogs. Positive reactions were found to milk in 4 dogs, to lamb in 2 dogs, and to wheat and chicken each in 1 dog. Adverse reactions to food (diarrhea, vomiting, or pruritus) were detected in all 6 dogs during the provocative dietary trial. Adverse reactions were found to corn in 5 dogs, to tofu in 3 dogs, to cottage cheese in 2 dogs, to milk in 2 dogs, to farina cream of wheat in 2 dogs, and to lamb in 2 dogs. Serum albumin concentrations significantly decreased and fecal alpha1-protease inhibitor concentration significantly increased 4 days after the provocative trial when compared with baseline values. Antigen-specific fecal IgE varied throughout the provocative trial, with peak levels following ingestion of test meals. We conclude that food hypersensitivities are present in SCWTs affected with the syndrome of PLE/PLN. Mild inflammatory bowel disease was already established in the 6 SCWTs of this report at the time of study, making it impossible to determine if food allergies were the cause or result of the enteric disease.  相似文献   

13.
The objective of this open pilot study was to evaluate the efficacy of topical tacrolimus ointment for treatment of plantar fistulae in German shepherd dogs. Seven dogs (four males, three females) were included. All subjects had a 6‐month to 2‐year history of plantar fistulae involving the plantar aspect of two to four metatarsi/metacarpi. No other skin lesions were present and the dogs appeared otherwise healthy. Before treatment with tacrolimus, all dogs received antibiotics for 4–8 weeks. Hair was clipped to visualise the lesions. The presence of erythematous papules, oedema and fistulae was recorded for each foot. All dogs served as their own controls. Dogs with four legs involved had one front and one hind leg treated. Dogs with two to three feet affected had only one foot treated. Tacrolimus 0.1% ointment (Protopic®) was applied twice daily onto the site of lesions. Partial improvement of treated lesions was seen in all cases within 3 weeks. After 6 weeks, treated lesions were in complete remission in four dogs, while the other three subjects had palpable but invisible lesions. Signs had not improved on the untreated legs. Follow‐up varied between 4 months and 2 years. Lesion remission persisted in six dogs with the intermittent application of tacrolimus. Adverse effects of treatment were not seen. In conclusion, the application of topical tacrolimus seems to provide a safe and effective treatment option for plantar fistulae in German shepherd dogs. Funding: Self‐funded.  相似文献   

14.
Dairy cow mastitis is a detrimental factor in milk quality and food safety. Mastitis generally refers to inflammation caused by infection by pathogenic microorganisms. Our studies in recent years have revealed the role of miRNA regulation in Staphylococcus aureus‐induced mastitis. In the present study, we overexpressed and suppressed miR‐145 to investigate the function of miR‐145 in Mac‐T cells. Flow cytometry, ELISA and EdU staining were used to detect changes in the secretion of several Mac‐T cytokines and in cell proliferation. We found that overexpression of miR‐145 in Mac‐T cells significantly reduced the secretion of IL‐12 and TNF‐α, but increased the secretion of IFN‐γ; the proliferation of bovine mammary epithelial cells was also inhibited. Using quantitative real‐time PCR (qRT‐PCR), Western blotting and luciferase multiplex verification techniques, we found that miR‐145 targeted and regulated FSCN1. Knock‐down of FSCN1 significantly increased the secretion of IL‐12, while the secretion of TNF‐α was significantly downregulated in Mac‐T cells. Upon S. aureus infection of mammary gland tissue, the body initiated inflammatory responses; Bta‐miR‐145 expression was downregulated, which reduced the inhibitory effect on the FSCN1 gene; and upregulation of FSCN1 expression promoted mammary epithelial cell proliferation to allow the recovery of damaged tissue. The results of the present study will aid in understanding the immune mechanism opposing S. aureus infection in dairy cows and will provide a laboratory research basis for the prevention and treatment of mastitis.  相似文献   

15.
The pharmacokinetic profile, tolerability and efficacy of benzene‐poly‐carboxylic acids complex with cis‐diammineplatinum (II) dichloride (BP‐C1) were studied in dogs with mammary cancer. A three‐level response surface pathway designed trial was performed on seven dogs. At each level BP‐C1 was administered subcutaneously daily for 7 days followed by a 7‐day rest period in a dose escalating manner. Adverse events according to VCOG‐CTCAE, performance status and tumour progression were recorded. The pharmacokinetic profile followed a two‐compartment model with rapid absorption, short distribution, and a slow elimination phase. The overall elimination half‐life was 125 h. The maximum tolerated dose of BP‐C1 was estimated to be above 0.46 mg kg?1. A significant reduction in VCOG‐CTCAE toxicity which correlated negatively with increasing dose was found. The dogs' general performance status remained unchanged. No decrease in total tumour burden was found, although temporary tumour reduction was seen in some target tumours.  相似文献   

16.
Efficacious therapies for measurable metastatic canine osteosarcoma (OSA) are generally lacking. Preliminary retrospective studies suggested that approximately 50% of dogs with measurable metastatic OSA experienced clinical benefit (objective response or clinically meaningful disease stabilisation) following toceranib (TOC) treatment. The purpose of this clinical trial was to prospectively evaluate the clinical outcome following TOC treatment in dogs with measurable pulmonary metastatic OSA. A secondary goal was to identify potential biomarkers of clinical benefit by measuring changes in plasma vascular endothelial growth factor (VEGF) and circulating regulatory T‐cell (Treg) percentage. Twenty‐two dogs with pulmonary metastasis from appendicular OSA having undergone previous amputation were treated prospectively with TOC. Adverse events (AEs) were common but predominantly low grade. Nine patients were withdrawn from the study prior to the week 8 assessment of response either due to progressive disease (PD), decreased quality of life or owner perceived unacceptable AEs. Of the patients evaluable for disease progression at week 8 (or earlier), 3/17 (17.6 %) had stable disease with the remainder having PD. The median progression‐free survival time for all patients was 57 days (range 7‐176 days) with a median overall survival time of 89 days (range 7‐574 days). Plasma VEGF concentrations were significantly elevated in patients after 4 weeks of TOC treatment, but no changes were observed in percentage of Treg in peripheral blood. Overall, the results of this clinical trial do not support the use of TOC as single agent therapy for canine metastatic OSA.  相似文献   

17.
OBJECTIVE: To evaluate effects of anesthesia, surgery, and intravenous administration of fluids on plasma concentrations of antidiuretic hormone (ADH), concentration of total solids (TS), PCV, arterial blood pressure (BP), plasma osmolality, and urine output in healthy dogs. ANIMALS: 22 healthy Beagles. PROCEDURE: 11 dogs did not receive fluids, and 11 received 20 ml of lactated Ringer's solution/kg of body weight/h. Plasma ADH adn TS concentrations, PCV, osmolality, and arterial BP were measured before anesthesia (T0) and after administration of preanesthetic agents (T1), induction of anesthesia (T2), and 1 and 2 hours of surgery (T3 and T4, respectively). Urine output was measured at T3 and T4. RESULTS: ADH concentrations increased at T1, T3, and T4, compared with concentrations at T0. Concentration of TS and PCV decreased at all times after administration of preanesthetic drugs. Plasma ADH concentration was less at T3 in dogs that received fluids, compared with those that did not. Blood pressure did not differ between groups, and osmolality did not increase > 1% from To value at any time. At T4, rate of urine production was less in dogs that did not receive fluids, compared with those that did. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma ADH concentration increased and PCV and TS concentration decreased in response to anesthesia and surgery. Intravenous administration of fluids resulted in increased urine output but had no effect on ADH concentration or arterial BP. The causes and effects of increased plasma ADH concentrations may affect efficacious administration of fluids during the perioperative period in dogs.  相似文献   

18.
Oral malignant melanoma (OMM) in the dog is often locally aggressive with a high metastatic potential and there are few treatment options that have been demonstrated to improve outcome of this disease. The purpose of this study was to determine whether adjunctive treatment with the Oncept melanoma vaccine affected the outcome of dogs with OMM that had achieved loco‐regional cancer control. Medical records from 45 dogs that presented to the Animal Cancer and Imaging Center were reviewed, including 30 dogs with stage II and III disease. Dogs that received the vaccine did not achieve a greater progression‐free survival, disease‐free interval or median survival time than dogs that did not receive the vaccine.  相似文献   

19.
The goal of this study was to evaluate the anti‐tumour activity and toxicoses of vinorelbine as a palliative rescue therapy for dogs with primary urinary bladder carcinoma. Thirteen dogs refractory to prior chemotherapeutics and one dog naïve to chemotherapeutic treatment were enrolled. Vinorelbine (15 mg m?2 IV) was administered intravenously along with concurrent oral anti‐inflammatory drugs, if tolerated. A median of six doses of vinorelbine (range: 1–16) was administered. Two dogs (14%) had partial responses, and eight (57%) experienced stable disease. Subjective improvement in clinical signs was noted in 11 dogs (78%). Adverse events were mild and primarily haematological in nature. Median time to progression was 93 days (range: 20–239 days). Median survival time for all dogs was 187 days; median survival for 13 pre‐treated dogs was 207 days. Vinorelbine may have utility in the management of canine primary urinary bladder carcinoma and should be evaluated in a prospective study.  相似文献   

20.
BACKGROUND: Hemangiosarcoma (HSA) is a highly metastatic and often rapidly fatal tumor in dogs. At present, conventional adjuvant chemotherapy provides only a modest survival benefit for treated dogs. Continuous oral administration of low-dose chemotherapy (LDC) has been suggested as an alternative to conventional chemotherapy protocols. Therefore, we evaluated the safety and effectiveness of LDC using a combination of cyclophosphamide, etoposide, and piroxicam as adjuvant therapy for dogs with stage II HSA. HYPOTHESIS: We hypothesized that oral adjuvant therapy with LDC could be safely administered to dogs with HSA and that survival times would be comparable to those attained with conventional doxorubicin (DOX) chemotherapy. ANIMALS: Nine dogs with stage II splenic HSA were enrolled in the LDC study. Treatment outcomes were also evaluated retrospectively for 24 dogs with stage II splenic HSA treated with DOX chemotherapy. METHODS: Nine dogs with stage II splenic HSA were treated with LDC over a 6-month period. Adverse effects and treatment outcomes were determined. The pharmacokinetics of orally administered etoposide were determined in 3 dogs. Overall survival times and disease-free intervals were compared between the 9 LDC-treated dogs and 24 DOX-treated dogs. RESULTS: Dogs treated with LDC did not develop severe adverse effects, and long-term treatment over 6 months was well-tolerated. Oral administration of etoposide resulted in detectable plasma concentrations that peaked between 30 and 60 minutes after dosing. Both the median overall survival time and the median disease-free interval in dogs treated with LDC were 178 days. By comparison, the overall survival time and disease-free interval in dogs treated with DOX were 133 and 126 days, respectively. CONCLUSIONS: Continuous orally administered LDC may be an effective alternative to conventional high-dose chemotherapy for adjuvant therapy of dogs with HSA.  相似文献   

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