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1.
Vet Med Sci ; 10(5): e70003, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39177283

RESUMEN

A 12-year-old male domestic cat with multiple subcutaneous mast cell tumours (MCTs) presented with a 2-week history of pruritus and raw/bleeding skin from self-trauma at Kagoshima University Veterinary Teaching Hospital. Polymerase chain reaction (PCR) and histopathological analyses revealed intertumoral heterogeneity among tumour locations based on the mutation status of KIT. In addition, the expression pattern of KIT was characterized. After failed treatment with vinblastine (2.0-2.2 mg/m2, intravenous administration, two doses in total) or nimustine (25 mg/m2, intravenous administration, two doses in total), toceranib (2.2-2.6 mg/kg, orally administered, every other day) was administered to treat recurrent MCTs harbouring the KIT exon eight internal tandem duplication mutation, achieving a complete response. However, toceranib resistance developed 2 months after treatment initiation. Subsequent PCR analysis was conducted to identify the mutational status of KIT in each MCT and to detect the presence of secondary mutations associated with the acquisition of toceranib resistance. Secondary KIT mutations (c.998G>C and c.2383G>C), which were not initially detected in tumour cells at diagnosis, were identified after the development of resistance to toceranib. This indicates that the tumour cells in feline MCTs in the same case have diverse characteristics. Our findings encourage further investigation into the development of therapeutic strategies for feline MCTs, particularly focusing on the heterogeneous nature of KIT/KIT and overcoming acquired resistance to toceranib.


Asunto(s)
Enfermedades de los Gatos , Resistencia a Antineoplásicos , Indoles , Mutación , Proteínas Proto-Oncogénicas c-kit , Pirroles , Animales , Masculino , Gatos , Enfermedades de los Gatos/tratamiento farmacológico , Enfermedades de los Gatos/genética , Indoles/farmacología , Indoles/uso terapéutico , Pirroles/farmacología , Pirroles/uso terapéutico , Proteínas Proto-Oncogénicas c-kit/genética , Resistencia a Antineoplásicos/genética , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología
2.
Can Vet J ; 65(4): 367-370, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38562979

RESUMEN

A 14-year-old intact male Chihuahua dog was presented with masses located between the biceps femoris and adductor muscles in both hind limbs. Based on histopathological, immunohistochemical, and ultrastructural findings, we diagnosed these masses as bilateral hibernomas in the femoral regions. The dog had no evidence of recurrence or metastasis of the hibernomas through a 4-month postoperative follow-up. This is apparently the first report of bilateral hibernomas in the femoral regions of a dog. Key clinical message: Bilateral hibernomas should be considered as a differential diagnosis for masses occurring in the femoral regions of dogs.


Hibernomes bilatéraux dans les régions fémorales d'un chien. Un chien Chihuahua mâle intact de 14 ans a été présenté avec des masses situées entre le biceps fémoral et les muscles adducteurs des deux membres postérieurs. Sur la base des résultats histopathologiques, immunohistochimiques et ultrastructuraux, nous avons diagnostiqué ces masses comme des hibernomes bilatéraux dans les régions fémorales. Le chien n'avait aucun signe de récidive ou de métastases des hibernomes au cours d'un suivi postopératoire de 4 mois. Il s'agit apparemment du premier rapport d'hibernome bilatéral dans les régions fémorales d'un chien.Message clinique clé:Les hibernomes bilatéraux doivent être considérés comme un diagnostic différentiel pour les masses survenant dans les régions fémorales des chiens.(Traduit par Dr Serge Messier).


Asunto(s)
Enfermedades de los Perros , Lipoma , Masculino , Perros , Animales , Lipoma/diagnóstico , Lipoma/cirugía , Lipoma/veterinaria , Músculo Esquelético/patología , Diagnóstico Diferencial , Miembro Posterior/patología , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/cirugía , Enfermedades de los Perros/patología
3.
Food Waterborne Parasitol ; 34: e00219, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38298421

RESUMEN

Alveolar echinococcosis is a zoonotic disease caused by a larval-stage Echinococcus multilocularis infection. Geographical haplotyping targeting the parasite's mitochondrial cytochrome b (cob) gene has been reported for isolates from definitive and intermediate hosts (wild canids and rodents); however, there are limited reports on strain typing for the dead-end host, the horse, which could act as a sentinel for E. multilocularis. Accordingly, we investigated the diversity of E. multilocularis in isolates obtained from slaughtered Japanese and Canadian horses originating from the Iburi and Hidaka regions in Hokkaido and from Alberta, respectively, with PCR and haplogroup analyses targeting cob gene sequences obtained. Seventy horses were diagnosed with alveolar echinococcosis based on histopathology and cob-gene PCR testing. The E. multilocularis detected in these horses was classified as either an Asian (for Hokkaido-raised horses) or a European (for Alberta-raised horses) haplogroup, based on the obtained cob-gene sequence analysis. In addition, haplotype network analysis revealed that E. multilocularis isolated from Hokkaido-raised horses is highly homologous to Kazakhstan isolates, and E. multilocularis isolated from Alberta-raised horses is highly homologous to Austrian isolates. The results of this study suggest that cob-gene-targeted PCR analysis could be useful for the geographical genetic characterization of E. multilocularis isolated from horses.

4.
Arch Virol ; 168(12): 298, 2023 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-38010495

RESUMEN

This study focused on the involvement of koala retrovirus (KoRV) in pneumonia in koalas. Three deceased pneumonic koalas from a Japanese zoo were examined in this study. Hematological and histopathological findings were assessed, and KoRV proviral DNA loads in the blood and tissues were compared with those of eight other KoRV-infected koalas from different zoos. Demographic data and routine blood profiles were collected, and blood and tissue samples were analyzed to rule out concurrent infections in pneumonic koalas. KoRV subtyping and measurement of the KoRV proviral DNA load were performed by polymerase chain reaction (PCR) using specific primers targeting the pol and env genes. The results showed that the koalas had histopathologically suppurative and fibrinous pneumonia. Chlamydiosis was not detected in any of the animals. PCR analysis revealed KoRV-A, -B, and -C infections in all koalas, except for animals K10-11, which lacked KoRV-B. Significant variations in the proviral DNA loads of these KoRV subtypes were observed in all tissues and disease groups. Most tissues showed reduced KoRV loads in koalas with pneumonia, except in the spleen, which had significantly higher loads of total KoRV (2.54 × 107/µg DNA) and KoRV-A (4.74 × 107/µg DNA), suggesting potential immunosuppression. This study revealed the intricate dynamics of KoRV in various tissues, indicating its potential role in koala pneumonia via immunosuppression and opportunistic infections. Analysis of the levels of KoRV proviral DNA in different tissues will shed light on viral replication and the resulting pathogenesis in future studies.


Asunto(s)
Gammaretrovirus , Phascolarctidae , Neumonía , Infecciones por Retroviridae , Animales , Infecciones por Retroviridae/veterinaria , Gammaretrovirus/genética , Retroviridae/genética , Provirus/genética , Neumonía/veterinaria , ADN
5.
J Comp Pathol ; 207: 14-17, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37871535

RESUMEN

Oxidative stress is a well-known cause of chronic kidney disease (CKD). In this study, renal oxidative damage in azotaemic and non-azotaemic aged cats with naturally occurring CKD was investigated using immunohistochemistry for 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 4-hydroxynonenal (4-HNE) as markers of oxidative tissue damage. Kidneys were obtained from aged (>10 years old) azotaemic (n = 13) and non-azotaemic (n = 7) cats. Immunoreactivity for 8-OHdG was found in the nuclei of glomeruli, proximal and distal tubules, loops of Henle and collecting ducts, whereas 4-HNE-positive signals were detected in the cytoplasm of distal nephrons in azotaemic and non-azotaemic cats. Quantitative analysis did not identify any significant differences between the azotaemic and non-azotaemic groups for any of the parameters examined. These results indicate that renal oxidative damage occurs in the kidneys of aged cats with CKD, regardless of whether they are azotaemic or non-azotaemic, emphasizing the importance of oxidative stress during early-stage CKD in senior and geriatric cats.


Asunto(s)
Enfermedades de los Gatos , Insuficiencia Renal Crónica , Animales , Inmunohistoquímica , Glomérulos Renales/patología , Estrés Oxidativo , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/veterinaria , Gatos , Enfermedades de los Gatos/diagnóstico , Enfermedades de los Gatos/patología
6.
Vet Anim Sci ; 20: 100291, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36936549

RESUMEN

Alveolar echinococcosis in slaughtered horses remains a public health issue. This study aimed to develop a Recombinase polymerase amplification (RPA) assay targeting the mitochondrial NADH dehydrogenase subunit 5 (Nad5) gene of Echinococcus multilocularis for the rapid detection of equine alveolar echinococcosis. Thirty-six hepatic solid nodules obtained from each horse (n = 36) were evaluated based on histopathological examination and Nad5-targeted PCR and then submitted to the RPA assay. The results of the developed RPA assay were 94.4% consistent with those of Nad5 PCR and Cohen's kappa coefficient value was 0.89 statistically, indicating high agreement. In addition, the RPA assay using the plasmid samples was one hundredfold more sensitive than PCR testing. Consequently, these results suggest that the performance of the RPA assay developed in this study is equal to that of conventional PCR testing.

7.
Vet Sci ; 10(2)2023 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-36851457

RESUMEN

Immunocytochemistry is an advanced diagnostic tool for identifying the origin of tumor cells. This study aimed to highlight the usefulness of cryopreserved, air-dried cytological samples in detecting cytokeratin and vimentin. Air-dried cytological smear samples were prepared from a total of 39 resected canine tumors and stored in a medical freezer without fixation. The duration of cryopreservation ranged from 2 to 56 months. The same tumors were processed for routine histopathological examination. Based on the morphological diagnosis, cryopreserved FNA smears from epithelial tumors were stained by enzymatic immunocytochemistry (ICC) for cytokeratin; those from mesenchymal and melanocytic tumors were stained by ICC for vimentin. To ascertain the positivity of tumor cells to the selected markers, tissue paraffin-embedded sections were also stained by immunohistochemistry (IHC) for the same markers. Immunoreactivity for cytokeratin was detected in cryopreserved cytological smears for a maximum of 46 months. Immunoreactivity for vimentin was clearly detected for 33 months. Smears stored at room temperature for 1 week did not show any signals under immunocytochemical examination. Thus, immunocytochemistry for cytokeratin and vimentin can be safely applied to air-dried smears cryopreserved in a freezer for at least 33 months.

8.
In Vivo ; 36(4): 1628-1636, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35738588

RESUMEN

BACKGROUND/AIM: Canine mammary gland tumors (MGTs), as a potential model of human breast cancer, have a well-defined histological classification system. MicroRNA (miRNA) expression is a key part of the molecular signatures of both MGTs and human breast cancer, although the signatures alone do not yet provide a sufficient basis for definitive diagnosis. In this study, we investigated the association between miRNA expression patterns and histological classification. MATERIALS AND METHODS: Mammary gland tissue was collected from healthy dogs (n=7) and dog patients (n=80). Further samples (n=5) were obtained from established MGT cell lines. We targeted miRNAs differentially expressed in metastatic tumor tissue versus non-metastatic and normal tissue. A subset of samples was analyzed using small RNA next generation sequencing (NGS) with subsequent qPCR. RESULTS: Six differentially expressed miRNAs were selected from the NGS analysis and submitted for large-scale qPCR. The large-scale qPCR analysis revealed greater alternations in miRNA expression. Large-scale analysis, based on 79 samples, revealed a hierarchical clustering based on selected miRNAs that did not strikingly match the histopathological subtype classification. CONCLUSION: We successfully investigated the large-scale miRNA expression pattern in canine MGT and provided the whole miRNA expression. The selected miRNA demonstrated that there is no straightforward mapping between molecular signatures and histological classification of canine MGTs at the miRNA level.


Asunto(s)
Neoplasias de la Mama , Neoplasias Mamarias Animales , MicroARNs , Animales , Neoplasias de la Mama/patología , Perros , Femenino , Perfilación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Neoplasias Mamarias Animales/genética , Neoplasias Mamarias Animales/metabolismo , MicroARNs/genética
9.
J Vet Med Sci ; 84(7): 978-981, 2022 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-35613871

RESUMEN

A 36-day-old Japanese Black calf exhibited wheezing associated with dyspnea from birth. Arterial blood gas analysis revealed a low oxygen partial pressure of 51 mmHg, low oxygen saturation of 83%, and high carbon dioxide partial pressure of 58.8 mmHg. Computed tomography, endoscopy, and ultrasonography showed cyst formation under the epiglottis. When the cyst was aspirated under ultrasonic guidance to secure the airway, 30 ml of viscous white turbid content was aspirated. The cyst shrank immediately after aspiration, but the wheezing and respiratory symptoms resumed 7 days after aspiration. Therefore, the cyst was surgically removed from the ventral side of the neck. No cyst remodeling was observed 30 days after surgical removal.


Asunto(s)
Enfermedades de los Bovinos , Quistes , Animales , Bovinos , Enfermedades de los Bovinos/diagnóstico por imagen , Enfermedades de los Bovinos/cirugía , Quistes/diagnóstico por imagen , Quistes/cirugía , Quistes/veterinaria , Epiglotis/cirugía , Cuello , Ruidos Respiratorios/veterinaria , Tomografía Computarizada por Rayos X/veterinaria
10.
Vet Parasitol ; 299: 109573, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34521042

RESUMEN

Alveolar echinococcosis, which is caused by a larval-stage infection of Echinococcus multilocularis, is a zoonosis with public health importance. Recently, alveolar echinococcosis in slaughtered horses has been reported in Japan and Poland. In terms of public health, a highly sensitive and specific diagnostic method is essential for early detection during meat inspection. In this study, the loop-mediated isothermal amplification (LAMP) assay was developed and validated to target the mitochondrial cytochrome b (cob) gene of E. multilocularis. Forty-one hepatic solid nodules obtained from each horse were evaluated based on histopathological examination and cob-targeted PCR and then submitted to the LAMP assay. The optimal condition of the developed LAMP assay was 64℃ for 30 min. The results of the developed LAMP assay were completely consistent with those of cob PCR. In addition, the detection limit for the number of copies of the cob gene was 135 copies/µL in the LAMP assay. These findings suggest that the ability of the LAMP assay developed in this study is equivalent to that of the conventional PCR testing. The LAMP assay developed in this study can be used as an alternative to PCR testing for the routine genetic diagnosis of alveolar echinococcosis in horses.


Asunto(s)
Equinococosis , Enfermedades de los Caballos , Animales , Citocromos b/genética , Equinococosis/veterinaria , Enfermedades de los Caballos/diagnóstico , Caballos , Técnicas de Diagnóstico Molecular , Técnicas de Amplificación de Ácido Nucleico/veterinaria , Sensibilidad y Especificidad
11.
J Vet Med Sci ; 83(9): 1363-1368, 2021 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-34234057

RESUMEN

Epithelial-mesenchymal transition (EMT) plays a crucial role in metastasis of epithelial tumors; however, it is challenging to detect EMT by cytology. In the present study, EMT was visualized by fluorescence-immunocytochemistry (FICC). Air-dried smears from epithelial tumors of dogs (n=22) and cats (n=9) were stained using mouse monoclonal anti-E-cadherin and rabbit monoclonal anti-vimentin antibodies. Enzymatic immunohistochemistry (IHC) revealed that 51.6% (8/22 in dogs, 8/9 in cats) of the cases showed EMT. In dogs, FICC could detect EMT in 62.5% (5/8) of those cases. In cats, FICC could detect EMT in 100% (8/8) of the cases. In conclusion, the present FICC method could successfully detect EMT using conventional air-dried cytology smear slides.


Asunto(s)
Enfermedades de los Gatos , Enfermedades de los Perros , Neoplasias Glandulares y Epiteliales , Enfermedades de los Roedores , Animales , Gatos , Enfermedades de los Perros/diagnóstico , Perros , Transición Epitelial-Mesenquimal , Ratones , Neoplasias Glandulares y Epiteliales/veterinaria , Vimentina
12.
J Vet Med Sci ; 83(5): 837-840, 2021 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-33814522

RESUMEN

Renin and neuronal nitric oxide synthase in the kidney control the renin-angiotensin and tubuloglomerular feedback systems. The present study investigated the expression of renin and neuronal nitric oxide synthase in the dysplastic kidneys of three young dogs. Renin-immunoreactivity, which occurs in the juxtaglomerular and tubular cells of dysplastic kidneys, did not differ from that in the normal kidneys of young dogs. Macula densa cells in the normal kidneys showed neuronal nitric oxide synthase -immunoreactivity, but those in the dysplastic kidneys showed no apparent signals. This observation may be correlated with the pathological mechanisms of renal failure in young dogs.


Asunto(s)
Óxido Nítrico Sintasa , Renina , Animales , Presión Sanguínea , Perros , Riñón , Óxido Nítrico , Óxido Nítrico Sintasa de Tipo I
13.
Can Vet J ; 62(3): 285-288, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33692585

RESUMEN

Histopathological and genetic examinations were conducted on grayish-white solid hepatic nodules in 150 horses imported from Canada, in order to investigate larval Echinococcus multilocularis infection. Ten of the 150 horses (6.7%) were diagnosed with alveolar hydatid disease. The sequences of the mitochondrial cytochrome b genes obtained from all 10 polymerase chain reaction positive samples had 99 to 100% identity with the European haplotype E1 of E. multilocularis. Therefore, we concluded that the infections likely originated in Canada.


Relation entre les nodules hépatiques solides blanc-grisâtre trouvés chez des chevaux importés du Canada et l'infection larvaire à Echinococcus multilocularis . Des examens histopathologiques et génétiques ont été effectués sur des nodules hépatiques solides blanc-grisâtre observés chez 150 chevaux importés du Canada afin d'étudier l'infection larvaire à Echinococcus multilocularis. Dix des 150 chevaux (6,7 %) ont reçu un diagnostic de maladie hydatique alvéolaire. Les séquences des gènes mitochondriaux du cytochrome b obtenus à partir des 10 échantillons positifs par réaction d'amplification en chaîne par la polymérase ont montré une identité de 99 à 100 % avec l'haplotype européen E1 d'E. multilocularis. L'haplotype d'E. multilocularis obtenu à partir de cette étude suggère que les infections sont probablement originaires du Canada.(Traduit par Dr Serge Messier).


Asunto(s)
Equinococosis Hepática , Equinococosis , Echinococcus multilocularis , Enfermedades de los Caballos , Animales , Canadá , Equinococosis/veterinaria , Equinococosis Hepática/veterinaria , Echinococcus multilocularis/genética , Caballos , Larva
14.
J Vet Diagn Invest ; 33(2): 379-383, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33292086

RESUMEN

A 27-y-old Anglo-Arabian gelding with bay coat color was presented with a swelling of the left maxillary region. Fenestration on the left maxilla revealed that the left maxillary sinus was filled with black-red tissue. A portion of the tissue was excised and diagnosed histologically as malignant melanoma. Genotyping of the STX17 gene for gray coat color revealed that the horse did not have the "gray" factor. The horse was euthanized ~3 mo after first presentation. During autopsy, a black-to-gray mass extended from the left nasal cavity to the surrounding paranasal sinus and invaded the hard palate, cribriform plate, and the cranial portion of the left olfactory bulb. Moreover, identical black nodules were present in lymph nodes from the mandible to the larynx, and in the spleen, liver, kidney, and adrenal glands. However, masses were not found in the skin, perineal region, or pelvic cavity. All of the black-to-gray nodules were malignant melanomas that were histologically identical to the initial biopsy; tumor emboli were also found in the kidney. Sinonasal mucosal melanoma is a rare disease in horses.


Asunto(s)
Enfermedades de los Caballos/diagnóstico , Melanoma/veterinaria , Neoplasias Nasales/veterinaria , Animales , Enfermedades de los Caballos/patología , Caballos , Masculino , Melanoma/diagnóstico , Melanoma/patología , Metástasis de la Neoplasia , Neoplasias Nasales/diagnóstico , Neoplasias Nasales/patología
15.
Virus Res ; 290: 198191, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33049308

RESUMEN

Chronic hepatitis B virus (HBV) infection constitutes a global health issue with limited current therapeutic efficacy owing to the persistence of viral episomal DNA (cccDNA). The CRISPR/Cas9 system, a newly developed, powerful tool for genome editing and potential gene therapy, requires efficient delivery of CRISPR components for successful therapeutic application. Here, we investigated the effects of lentiviral- or adeno-associated virus 2 (AAV2) vector-mediated delivery of 3 guide (g)RNAs/Cas9 selected from 16 gRNAs. These significantly suppressed HBV replication in cells, with WJ11/Cas9 exhibiting highest efficacy and chosen for in vivo study. AAV2/WJ11-Cas9 also significantly inhibited HBV replication and significantly reduced cccDNA in the tested cells. Moreover, AAV2/WJ11-Cas9 enhanced entecavir effects when used in combination, indicative of different modes of action. Notably, in humanized chimeric mice, AAV2/WJ11-Cas9 significantly suppressed HBcAg, HBsAg, and HBV DNA along with cccDNA in the liver tissues without significant cytotoxicity; accordingly, next generation sequencing data showed no significant genomic mutations. To our knowledge, this represents the first evaluation of the CRISPR/Cas9 system using an HBV natural infection mode. Therefore, WJ11/Cas9 delivered by comparatively safer AAV2 vectors may provide a new therapeutic strategy for eliminating HBV infection and serve as an effective platform for curing chronic HBV infection.


Asunto(s)
Proteína 9 Asociada a CRISPR/genética , Sistemas CRISPR-Cas , ADN Circular/genética , Técnicas de Transferencia de Gen , Vectores Genéticos , Virus de la Hepatitis B/genética , ARN Guía de Kinetoplastida/genética , Adenoviridae/genética , Animales , Animales Modificados Genéticamente , Proteína 9 Asociada a CRISPR/administración & dosificación , ADN Viral/genética , Guanina/análogos & derivados , Guanina/farmacología , Células HEK293 , Células Hep G2 , Hepatitis B/terapia , Hepatitis B/virología , Antígenos de Superficie de la Hepatitis B/genética , Virus de la Hepatitis B/efectos de los fármacos , Humanos , Masculino , Ratones , Plásmidos/genética
16.
J Vet Med Sci ; 82(8): 1146-1150, 2020 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-32565524

RESUMEN

Alveolar rhabdomyosarcoma (ARMS) is a rare mesenchymal tumor with differentiation toward the skeletal muscle. Although several cases of canine ARMS have been reported in veterinary medicine, only one case of abdominal ARMS has been reported in a cow. A 13-month-old, Japanese black heifer was referred for pus-like nasal discharge. On autopsy, an 11 × 7 × 4.5-cm pedunculated mass closed to the left palatine tonsillar sinus that occupied the laryngopharynx. Histopathological and immunohistochemical analyses indicated that the tumor was a typical ARMS. To the best of our knowledge, this has been the first case of primary pharyngeal ARMS in a Japanese black heifer, which is rare among cows. Nonetheless, its characteristics, including site, age and subtype, are identical to those among humans and dogs.


Asunto(s)
Enfermedades de los Bovinos/patología , Neoplasias Faríngeas/veterinaria , Rabdomiosarcoma Alveolar/veterinaria , Animales , Bovinos , Femenino , Inmunohistoquímica/veterinaria , Neoplasias Faríngeas/patología , Rabdomiosarcoma Alveolar/patología
17.
PLoS One ; 15(5): e0233232, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32421739

RESUMEN

Mammary gland cancer is the most common cancer occurring in women globally. Incidences of this cancer in Japan are on the increase. Annually, more than 70,000 new cases are recorded in Japan and about 1.7 million in the world. Many cases are still difficult to cure completely, and animal models are required for the characterization of the biology, therapeutic strategy, and preventive measures for spontaneous mammary tumor. The mouse model used currently has some limitations owing to structural differences between mouse and human mammary glands. Tupaia belangeri (tree shrew), which belongs to the Tupaiidae family, shows relatively high genetic homology and structural similarity to human mammary glands. Here, we characterized the spontaneous mammary tumors in 61 female tree shrews of different ages. The incidence rate was 24.6% (15/61), and the rate of simultaneous or metachronous multiplex tumors was 60% (9/15). From the incidence pattern, some cases seemed to be of familial mammary gland tumor, as the offspring of female tree shrews No. 3 and 9 and male tree shrew No. 11 showed a high incidence rate, of 73.3% (11/15). Average incidence age for tumor development was 2 years and 3 months, and the earliest was 10 months. Histochemical analysis indicated that spontaneous mammary gland tumors in the tree shrew show the features of intraductal papillary adenomas (22 cases), except 2 tubulopapillary carcinoma cases (No. 75 and 131). All the cases were positive for the progesterone receptor, whereas 91.3% were positive for the estrogen receptor, and 4.3% were HER-2 positive. We have also confirmed the expression of nectin-4 in some mammary tumor cells. Additionally, we subjected tree shrews to cytodiagnosis or X-ray CT. Thus, the findings of this study highlight the potential of the tree shrew as a valuable new animal model for mammary gland tumor study.


Asunto(s)
Neoplasias Mamarias Animales/genética , Neoplasias Mamarias Animales/patología , Tupaiidae/genética , Animales , Modelos Animales de Enfermedad , Femenino , Incidencia , Japón , Masculino , Glándulas Mamarias Animales/patología , Papiloma Intraductal , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Tupaia/genética , Tupaiidae/fisiología
18.
Oncol Rep ; 43(1): 16-30, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31661138

RESUMEN

Dogs have been considered as an excellent immunocompetent model for human melanoma due to the same tumor location and the common clinical and pathological features with human melanoma. However, the differences in the melanoma transcriptome between the two species have not been yet fully determined. Considering the role of oncogenes in melanoma development, in this study, we first characterized the transcriptome in canine oral melanoma and then compared the transcriptome with that of human melanoma. The global transcriptome from 8 canine oral melanoma samples and 3 healthy oral tissues were compared by RNA­Seq followed by RT­qPCR validation. The results revealed 2,555 annotated differentially expressed genes, as well as 364 novel differentially expressed genes. Dog chromosomes 1 and 9 were enriched with downregulated and upregulated genes, respectively. Along with 10 significant transcription site binding motifs; the NF­κB and ATF1 binding motifs were the most significant and 4 significant unknown motifs were indentified among the upregulated differentially expressed genes. Moreover, it was found that canine oral melanoma shared >80% significant oncogenes (upregulated genes) with human melanoma, and JAK­STAT was the most common significant pathway between the species. The results identified a 429 gene signature in melanoma, which was up­regulated in both species; these genes may be good candidates for therapeutic development. Furthermore, this study demonstrates that as regards oncogene expression, human melanoma contains an oncogene group that bears similarities with dog oral melanoma, which supports the use of dogs as a model for the development of novel therapeutics and experimental trials before human application.


Asunto(s)
Enfermedades de los Perros/genética , Perfilación de la Expresión Génica/veterinaria , Redes Reguladoras de Genes , Melanoma/genética , Neoplasias de la Boca/genética , Animales , Estudios de Casos y Controles , Cromosomas de los Mamíferos/genética , Perros , Regulación Neoplásica de la Expresión Génica , Humanos , Melanoma/veterinaria , Neoplasias de la Boca/veterinaria , Análisis de Secuencia de ARN
19.
Vet Comp Oncol ; 18(3): 353-361, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31769925

RESUMEN

Among small non-coding RNAs (sncRNAs/sRNAs), the functional regulation of microRNAs (miRNAs) has been studied in canine oral melanoma (COM). However, the expression level of other sncRNAs, like small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs), transfer RNA-derived fragments (tRFs) and PIWI-interacting RNAs (piRNAs), in COM is unknown. The aim of this study was to investigate sncRNAs other than miRNAs in COM from our small RNA sequencing project (PRJNA516252). We found that several snRNAs and piRNAs were upregulated, whereas tRFs and snoRNAs were downregulated in COM. Upregulation of U1 snRNA and piR-972, and downregulation of tRNA-ser (1) and snoRA24 was confirmed in dog melanoma tissue and cell lines by quantitative reverse transcription PCR. Consistently, the expression of tRNA-ser (1) and snoRA24 in plasma of COM cases was also decreased. Finally, we found a similar expression trend of U1 and snoRA24 in the human cutaneous melanoma cell line, MEWO, compared with human epidermal melanocyte cells (HEMa-Lp). In our study, snRNA, snoRNA, tRFs and piRNA were dysregulated during melanoma progression. Moreover, the melanoma-associated expression of U1 and snoRA24 was similar in human and dog melanoma.


Asunto(s)
Enfermedades de los Perros/genética , Melanoma/veterinaria , Neoplasias de la Boca/veterinaria , ARN Interferente Pequeño/genética , ARN Nuclear Pequeño/genética , ARN de Transferencia/genética , Animales , Línea Celular Tumoral , Bases de Datos Genéticas , Enfermedades de los Perros/metabolismo , Perros , Humanos , Melanoma/genética , Melanoma/patología , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , ARN Interferente Pequeño/metabolismo , ARN Nuclear Pequeño/metabolismo , ARN Nucleolar Pequeño/genética , ARN de Transferencia/metabolismo , Análisis de Secuencia de ARN/veterinaria , Regulación hacia Arriba
20.
Int J Mol Sci ; 20(19)2019 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-31569419

RESUMEN

MicroRNAs (miRNAs) dysregulation contribute the cancer pathogenesis. However, the miRNA profile of canine oral melanoma (COM), one of the frequent malignant melanoma in dogs is still unrevealed. The aim of this study is to reveal the miRNA profile in canine oral melanoma. MiRNAs profile of oral tissues from normal healthy dogs and COM patients were compared by next-generation sequencing. Along with tumour suppressor miRNAs, we report 30 oncogenic miRNAs in COM. The expressions of miRNAs were further confirmed by quantitative real-time PCR (qPCR). Pathway analysis showed that deregulated miRNAs impact on cancer and signalling pathways. Three oncogenic miRNAs targets (miR-450b, 301a, and 223) from human study also were down-regulated in COM and had a significant negative correlation with their respective miRNA. Furthermore, we found that miR-450b expression is higher in metastatic cells and regulated MMP9 expression through a PAX9-BMP4-MMP9 axis. In silico analysis indicated that miR-126, miR-20b, and miR-106a regulated the highest numbers of differentially expressed transcription factors with respect to human melanoma. Chromosomal enrichment analysis revealed the X chromosome was enriched with oncogenic miRNAs. We comprehensively analyzed the miRNA's profile in COM which will be a useful resource for developing therapeutic interventions in both species.


Asunto(s)
Enfermedades de los Perros/genética , Melanoma/veterinaria , MicroARNs/genética , Neoplasias de la Boca/veterinaria , Transcriptoma , Animales , Perros , Perfilación de la Expresión Génica , Ontología de Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Reproducibilidad de los Resultados
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