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1.
Tissue Cell ; 84: 102188, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37567074

RESUMO

Diclofenac, a non-steroidal anti-inflammatory drug, reportedly targets mitochondria and induces nephrotoxicity via reactive oxygen species. However, there are few detailed reports of pathological analyses of mitochondria and the factors that cause acute kidney injury (AKI) as a result of nephrotoxicity. In this study, we investigated mitochondrial damage in the proximal tubule in AKI mice at 6, 12, and 24 h after administration of diclofenac. Statistical analysis of immunohistochemistry results confirmed that expression of p62 and LC3, which is associated with autophagy, reached a maximum level in the degenerated proximal renal tubule 12 h after diclofenac treatment, with high autophagy activity. Electron microscopy images provided clear evidence that confirmed mitochondrial degeneration and injury as well as autophagy (mitophagy) in mitochondria treated with diclofenac. The purpose of this study was to pathologically characterize both mitochondrial damage in the proximal renal tubules induced by diclofenac and the course of mitophagy to remove the damaged mitochondria. This report provides important information regarding mitochondrial damage in the proximal tubules in diclofenac-induced nephropathy.


Assuntos
Injúria Renal Aguda , Túbulos Renais Proximais , Camundongos , Animais , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Diclofenaco/toxicidade , Diclofenaco/metabolismo , Injúria Renal Aguda/induzido quimicamente , Mitocôndrias/metabolismo , Autofagia
2.
FEBS J ; 290(17): 4268-4280, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37098812

RESUMO

Mast cells are a significant source of cytokines and chemokines that play a role in pathological processes. Gangliosides, which are complex lipids with a sugar chain, are present in all eukaryotic cell membranes and comprise lipid rafts. Ganglioside GM3, the first ganglioside in the synthetic pathway, is a common precursor of the specifying derivatives and is well known for its various functions in biosystems. Mast cells contain high levels of gangliosides; however, the involvement of GM3 in mast cell sensitivity is unclear. Therefore, in this study, we elucidated the role of ganglioside GM3 in mast cells and skin inflammation. GM3 synthase (GM3S)-deficient mast cells showed cytosolic granule topological changes and hyperactivation upon IgE-DNP stimulation without affecting proliferation and differentiation. Additionally, inflammatory cytokine levels increased in GM3S-deficient bone marrow-derived mast cells (BMMC). Furthermore, GM3S-KO mice and GM3S-KO BMMC transplantation showed increased skin allergic reactions. Besides mast cell hypersensitivity caused by GM3S deficiency, membrane integrity decreased and GM3 supplementation rescued this loss of membrane integrity. Additionally, GM3S deficiency increased the phosphorylation of p38 mitogen-activated protein kinase. These results suggest that GM3 increases membrane integrity, leading to the suppression of the p38 signalling pathway in BMMC and contributing to skin allergic reaction.


Assuntos
Gangliosídeo G(M3) , Mastócitos , Camundongos , Animais , Gangliosídeo G(M3)/metabolismo , Mastócitos/metabolismo , Diferenciação Celular , Citocinas
3.
J Vet Med Sci ; 84(8): 1111-1117, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35753782

RESUMO

L-type amino acid transporter 1 (LAT1) is upregulated in various malignant tumors in humans. LAT1 expression correlates with the grade of cancer and prognosis. LAT1 is responsible for the supply of many essential amino acids to cancer cells. Inhibition of LAT1 reduces the amino acids that enter the cell and inhibits cancer cell growth. Therefore, novel anticancer drugs targeting LAT1 have attracted much attention in recent years. In this study, to explore the applicability of using LAT1 expression in intracranial tumors as a prognostic factor and therapeutic target, we investigated the expression of LAT1 in surgically resected primary and secondary intracranial tumor tissues from dogs and cats. Immunohistochemical analysis of LAT1 was performed on intracranial tumor tissue from 14 dogs and 3 cats. Primary intracranial tumors were seen in 10 dogs and included meningiomas, histiocytic sarcomas, pituitary tumors, and gliomas, and 9 out of 10 cases were positive for LAT1. Primary intracranial tumors were seen in 2 cats and included meningioma and lymphoma; both cases were positive for LAT1. Secondary intracranial tumors were positive for LAT1 in 3 out of 4 cases in dogs and 1 out of 1 in cats. Since the majority of intracranial tumors in dogs and cats were positive for LAT1, immunostaining for LAT1 is expected to be a prognostic indicator and therapeutic target in the future.


Assuntos
Neoplasias Encefálicas , Doenças do Gato , Doenças do Cão , Animais , Neoplasias Encefálicas/veterinária , Gatos , Doenças do Cão/metabolismo , Cães , Transportador 1 de Aminoácidos Neutros Grandes/análise , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Prognóstico
4.
J Vet Med Sci ; 84(6): 760-765, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35400671

RESUMO

A cell line (PL38PB) was established from blood samples of a 6-month-old pig that was diagnosed with lymphoma with CD5 expression. Histopathological examination revealed neoplastic lesions in the spleen, liver and lymph nodes. Tumor cells were immunohistochemically positive for CD20 and immunoglobulin heavy chains (µ, γ and α). Membranous CD5 and cytoplasmic Immunoglobulin M (IgM), ​Immunoglobulin G (IgG) and ​Immunoglobulin A (IgA) were detected in PL38PB cells by flow cytometry. In addition, the cytoplasm of PL38PB cells were positive for IgM, IgG and IgA by immunofluorescent. However, no Ig secretion was detected in culture supernatant by Ouchterlony gel diffusion method. Results suggest that PL38PB cells express three Ig isotypes that are produced but not secreted.


Assuntos
Linfoma , Doenças dos Suínos , Animais , Linhagem Celular , Imunoglobulina A , Imunoglobulina G , Imunoglobulina M , Linfoma/veterinária , Suínos
5.
J Vet Med Sci ; 83(6): 1016-1021, 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-33907057

RESUMO

A 23-year-old Falabella gelding kept in Tochigi, Japan, for more than 20 years presented with a recurrent mass of the glans penis that was first noticed about a year earlier. Partial phallectomy was performed with no adjunctive therapy for local regrowth of the mass. The horse was euthanized 3 months after surgery for urinary retention due to suspected regrowth. The resected mass affected the genital and urethral mucosa of the glans penis, and was diagnosed as equine sarcoid by histopathology and identification of bovine papillomavirus (BPV) DNA. Phylogenetic analysis of the BPV genome of the sarcoid showed high sequence homology to BPV type 1 (BPV-1) from Hokkaido, Japan, suggesting a geographical relationship for BPV-1 in Japan.


Assuntos
Papillomavirus Bovino 1 , Doenças dos Cavalos , Infecções por Papillomavirus , Neoplasias Cutâneas , Animais , Papillomavirus Bovino 1/genética , DNA Viral , Cavalos , Japão , Masculino , Infecções por Papillomavirus/veterinária , Pênis/cirurgia , Filogenia , Neoplasias Cutâneas/veterinária
6.
Biomed Res ; 41(6): 289-293, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33268673

RESUMO

We recently revealed that increases in particle sizes of very-low-density lipoproteins (VLDL) are highly correlated with the progression of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), and VLDL particle size may be a minimally invasive indicator of these hepatic disorders. Methionine and choline-deficient (MCD) diet fed animals are usually used as a NASH model; however, the application of this minimally invasive biomarker in MCD diet fed animals remains unclear. In the present study, we measured the levels of liver disease markers and plasma lipoprotein profiles in MCD diet fed rats, and compared them with those of normal diet fed rats. Assessing lipoprotein profiles showed marked increases in VLDL particle sizes in MCD diet fed rats with pathologically and biochemically NASH-like features.


Assuntos
Deficiência de Colina/sangue , Lipoproteínas VLDL/sangue , Metionina/deficiência , Hepatopatia Gordurosa não Alcoólica/sangue , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Peso Corporal/fisiologia , Deficiência de Colina/induzido quimicamente , Deficiência de Colina/patologia , Quilomícrons/sangue , Dieta/métodos , Modelos Animais de Doenças , Ingestão de Alimentos/fisiologia , Insulina/sangue , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Fígado/metabolismo , Fígado/patologia , Masculino , Metionina/sangue , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/patologia , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Triglicerídeos/sangue
7.
Biomed Res ; 41(4): 169-178, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801266

RESUMO

Theileria orientalis (T. orientalis) is a bovine protozoal disease similar to malaria in humans. Although the common outcome of malaria in humans and T. orientalis infection in cattle is hepatic disorder, the mechanisms of its development remain unknown. In this study, we investigated hepatocyte injury characterized by accumulation of macrophages with ingested erythrocytes in sinusoid and extramedullary hematopoiesis in cattle and mice experimentally infected with T. orientalis (T. orientalis-infected cattle and T. orientalis-infected mice). Vacuolization of hepatic cells was frequently observed in the vicinity of the aggregated macrophages in the liver sinusoids of T. orientalis-infected mice. A significant percentage of the macrophages accumulated in the liver sinusoids of the severely infected cattle and mice (14.6% and 24.2 to 53.2%, respectively) reacted positively with interleukin-1, interleukin-6 and TNF-α antibodies. Increase in the production of these cytokines was confirmed in T. orientalis-infected cattle and mice by real-time RT-PCR. These findings strongly suggest that increased cytokine production by the macrophages that have phagocytosed T. orientalis-infected erythrocytes causes hepatic disorder in T. orientalis-infected animals.


Assuntos
Eritrócitos/parasitologia , Hepatócitos/patologia , Fígado/patologia , Macrófagos/parasitologia , Theileria/patogenicidade , Theileriose/patologia , Animais , Bovinos , Transfusão de Eritrócitos , Eritrócitos/patologia , Feminino , Expressão Gênica , Hematopoese/genética , Hematopoese/imunologia , Hepatócitos/parasitologia , Interleucina-1/genética , Interleucina-1/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Fígado/imunologia , Fígado/parasitologia , Testes de Função Hepática , Macrófagos/imunologia , Masculino , Camundongos , Camundongos SCID , Esplenectomia , Theileria/crescimento & desenvolvimento , Theileriose/genética , Theileriose/imunologia , Theileriose/parasitologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
8.
J Vet Med Sci ; 82(9): 1395-1399, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32655098

RESUMO

A four-and-a-half-year-old female Scottish Fold cat underwent partial pancreatectomy with en-bloc splenectomy. The resected specimen was a biphasic tumor that was diagnosed histologically and immunohistochemically as pancreatic adenosquamous carcinoma (ASC), a ductal carcinoma variant according to the WHO classification of tumors in humans. There was a gradual transition between the adenocarcinoma component and the squamous cell carcinoma component. The squamous cell carcinoma component comprised approximately 30-40% of the tumor. A pancreatic tumor infiltrated into the gastrosplenic ligament and spleen with regional lymph node and mesenteric metastases. Pancreatic ASC has not been reported in animals. This is a case report of feline pancreatic ASC with splenic involvement.


Assuntos
Carcinoma Adenoescamoso , Doenças do Gato , Neoplasias Pancreáticas , Animais , Carcinoma Adenoescamoso/cirurgia , Carcinoma Adenoescamoso/veterinária , Doenças do Gato/cirurgia , Gatos , Feminino , Pancreatectomia/veterinária , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/veterinária , Baço , Esplenectomia/veterinária
9.
Vet Sci ; 6(3)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480326

RESUMO

Silicosis, caused by the inhalation of crystalline silicon dioxide or silica, is one of the most severe occupational diseases. Persistent inflammation and progressive massive pulmonary fibrosis are the most common histological changes caused by silicosis. Association of epithelial-mesenchymal transition (EMT) of hyperplastic type II epithelial cells with the fibrotic events of pulmonary fibrosis has been suggested in in vitro silica-exposed cultured cell models, patients with idiopathic pulmonary fibrosis, and bleomycin-induced experimental models. Histological features of EMT, however, are not fully described in silicotic lungs in in vivo. The purpose of this study was to demonstrate EMT of hyperplastic type II epithelial cells in the developmental process of progressive massive pulmonary fibrosis in the lungs of rats exposed to silica. F344 female rats were intratracheally instilled with 20 mg of crystalline silica (Min-U-Sil-5), followed by sacrifice at 1, 3, 6, and 12 months after instillation. Fibrosis, characterized by the formation of silicotic nodules, progressive massive fibrosis, and diffuse interstitial fibrosis, was observed in the lungs of the treated rats; the effects of fibrosis intensified in a time-dependent manner. Hyperplasia of the type II epithelial cells, observed in the massive fibrotic lesions, dominated in the lungs of rats at 6 and 12 months after the treatment. Immunohistochemistry of the serial sections of the lung tissues demonstrated positive labeling for cytokeratin, vimentin, and α-smooth muscle actin in spindle cells close to the foci of hyperplasia of type II epithelial cells. Spindle cells, which exhibited features of both epithelial cells and fibroblasts, were also demonstrated with bundles of collagen fibers in the fibrotic lesions, using electron microscopy. Increased expression of TGF-ß was shown by Western blotting and immunohistochemistry in the lungs of the treated rats. These findings suggested that enhanced TGF-ß expression and EMT of hyperplastic type II epithelial cells are involved in the development process of progressive massive pulmonary fibrosis during silicosis.

10.
Tohoku J Exp Med ; 246(1): 1-8, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30175722

RESUMO

Cisplatin is a chemotherapeutic widely used in the treatment of various types of solid tumors. Acute kidney injury is the most critical dose-limiting factor in cancer patients treated with cisplatin; mitochondrial dysfunction and resultant cell damage by reactive oxygen species released from damaged mitochondria are suspected to be involved in the kidney injury. Pathological features of mitochondrial damage in relation to cisplatin-mediated nephrotoxicity, however, is not fully described. The purpose of this study was to demonstrate mitochondrial damage and clearance of damaged mitochondria by mitophagy in cisplatin-mediated nephrotoxicity. Three groups of rats received a single intraperitoneal injection of cisplatin at 20 mg/kg and were sacrificed at 24, 48 and 72 hours after the treatment. A time-dependent increase in the number of damaged renal tubules and the serum levels of blood urea nitrogen, creatinine, and mitochondrial aspartate transaminase was observed in rats after the treatment. We showed the increased numbers of swollen and fragmented mitochondria, observed by electron microscopy, and of cytochrome c oxidase IV- and 8-nitroguanosine-positive intracytoplasmic granules, detected by immunohistochemistry, in the degenerated renal tubules of the treated animals. Moreover, activated autophagy process was indicated in the degenerated renal epithelial cells, based on the findings of immunohistochemistry of microtubule-associated protein 1 light chain 3 (LC3), an autophagy marker, and lysosomal-associated membrane protein 1 (LAMP-1), a lysosome marker, and swollen and fragmented mitochondria in autophagosomes. These results suggest that mitochondrial damage and clearance of damaged mitochondria by mitophagy is involved in cisplatin-mediated nephrotoxicity.


Assuntos
Cisplatino/efeitos adversos , Rim/patologia , Mitocôndrias/patologia , Mitofagia , Animais , Aspartato Aminotransferases/sangue , Proteínas Relacionadas à Autofagia/metabolismo , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Guanosina/análogos & derivados , Guanosina/metabolismo , Rim/efeitos dos fármacos , Rim/ultraestrutura , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Nitrocompostos/metabolismo , Ratos Wistar
11.
Vet Microbiol ; 220: 90-96, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29885807

RESUMO

Mycobacterium sp. strain MFM001 (MFM001), a new strain of slow-growing nontuberculous mycobacteria not associated with the Mycobacterium avium complex, led to disseminated mycobacterial disease characterized by transmural granulomatous gastroenterocolitis of lepromatous type in a cat treated with immunosuppressive medication. MFM001 was found to be closely related to M. kyorinense or M. celatum by partial sequence of 16S rDNA, and identical with an unspecified M. sp. strain B10-07.09.0206 isolated from a human pulmonary infection in Germany. MFM001 should be considered as a pathogenic organism in cats, especially in immunocompromised animals.


Assuntos
Gatos/microbiologia , Infecções por Mycobacterium não Tuberculosas/veterinária , Micobactérias não Tuberculosas/isolamento & purificação , Animais , Proteínas de Bactérias/genética , Técnicas de Tipagem Bacteriana , Colite/microbiologia , DNA Bacteriano , DNA Ribossômico , Gastroenterite/microbiologia , Alemanha/epidemiologia , Hospedeiro Imunocomprometido , Masculino , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium avium/genética , Micobactérias não Tuberculosas/classificação , Micobactérias não Tuberculosas/genética , RNA Ribossômico 16S
12.
Folia Histochem Cytobiol ; 56(1): 38-48, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29577227

RESUMO

I: NTRODUCTION: We have previously reported that Asian sand dust (ASD) induced acute and chronic inflammatory changes in the lung of mice. Zinc (Zn) is reported to influence inflammation and wound healing. The purpose of the study was to assess the effects of lowered serum Zn levels on the lung toxicity induced by ASD. MATERIAL AND METHODS: Mice that were fed diets containing normal (group 1) or low (group 2) content of Zn for 8 weeks were intratracheally instilled with 3.0 mg of ASD, followed by sacrifice at 24 hours, 2 weeks, and 1, 2 and 3 months after instillation. Paraffin sections of lung tissues were stained by hematoxylin and eosin and by immunohistochemistry to detect tumor necrosis factor (TNF) and interleukin (IL)-1ß as well as inflammasome (NALP3), autophagy (LC-3) and lysosome (LAMP-1) markers. Selected samples of lung tissue were examined by electron microscopy. RESULTS: Following histological examination of the lung, similar patterns of inflammatory changes were observed in mice with normal and low serum Zn concentrations; however, they were more prominent and persistent in mice with low serum Zn level. These changes were both purulent (acute) and pyogranulomatous (chronic) in nature. In the lung lesions of group 2 mice the changes within the cytoplasmic vacuoles of enlarged ASD-containing macrophages (Mo) were clearly visible. The macrophages expressed TNF and IL-1ß, and semi-quantitative analysis revealed a larger number of TNF-positive Mo in mice with normal level of serum Zn and a larger number of IL-1ß-positive Mo in mice with low level of serum Zn. Decreased positive LC-3 staining and dilated lysosomes containing ASD particles were observed in the cytoplasm of Mo in mice with low serum Zn concentration. CONCLUSIONS: These findings suggest that low serum zinc concentration may induce the modulation of cytokine expression and lysosomal malfunction by phagocytotic and/or autophagic mechanisms, and may result in interstitial pyogranulomatous inflammation in the lungs of mice treated with ASD.


Assuntos
Poeira , Pulmão/efeitos dos fármacos , Dióxido de Silício/toxicidade , Zinco/sangue , Animais , Citocinas/metabolismo , Imuno-Histoquímica , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Microscopia Eletrônica de Transmissão , Traqueia/efeitos dos fármacos
13.
J Vet Med Sci ; 80(3): 473-479, 2018 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-29415922

RESUMO

Canine squamous cell carcinoma (SCC) shows highly invasive and locally destructive growth. In animal models and human cancer cases, periostin plays a critical role in the enhancement of cancer growth; however, the mechanism of involvement in canine cancers remains unknown. The aim of this study was to examine the involvement of periostin in the pathophysiology of SCC in dogs. We examined the localization of periostin and periostin-producing cells in 20 SCC and three squamous papilloma specimens. Furthermore, we focused on transforming growth factor (TGF)-ß1, which was assumed to be an inducing factor of periostin, using culture cells. By immunohistochemistry, limited periostin expression in the stroma was observed in all squamous papillomas. In SCC, periostin protein diffusely expressed at the tumor invasion front of cancer growth. In situ hybridization revealed that periostin mRNA was expressed in the stromal fibroblasts in SCC. In vitro analysis determined that canine SCC cells expressed significantly higher levels of TGF-ß1 mRNA compared with canine keratinocytes. In addition, recombinant TGF-ß1 induced secretion of periostin from cultured dermal fibroblasts. These data suggest that periostin produced by stromal fibroblasts may be involved in the pathophysiology of canine SCC. TGF-ß1 derived from SCC cells may stimulate fibroblasts to produce periostin.


Assuntos
Carcinoma de Células Escamosas/veterinária , Moléculas de Adesão Celular/metabolismo , Doenças do Cão/metabolismo , Animais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Doenças do Cão/patologia , Cães , Feminino , Fibroblastos/metabolismo , Hibridização In Situ , Masculino , Fator de Crescimento Transformador beta1/metabolismo
14.
J Comp Pathol ; 157(4): 241-245, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29169617

RESUMO

A 2.5-year-old African hedgehog (Atelerix albiventris) with signs of progressive paresis/paralysis for approximately 6 months was diagnosed with 'wobbly hedgehog syndrome' (WHS). Post-mortem examination revealed a primary central nervous system (CNS) histiocytic sarcoma (HS) associated with neurodegenerative changes of the CNS and skeletal muscle atrophy. Grossly, a spherical mass infiltrated the left forebrain and was located between the frontal lobe and thalamus in coronal sections. Microscopically, the neoplastic cells had eccentrically located anisokaryotic nuclei and abundant eosinophilic cytoplasm. Immunohistochemically, they were positive for calcium-binding adapter molecule 1, lysozyme, CD68 and vimentin. Ultrastructurally, the neoplastic cells had varying amounts of bundles and whorls of intermediate filaments and scattered lysosomes. This report represents the first documentation of primary CNS HS in this species. Primary CNS HS should be considered as a differential diagnoses for hedgehogs that present with neurological signs of WHS.


Assuntos
Neoplasias Encefálicas/veterinária , Ouriços , Sarcoma Histiocítico/veterinária , Animais , Feminino
15.
Vet Microbiol ; 204: 43-45, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28532804

RESUMO

A 33-month old, neutered female Abyssinian cat died. The cat had sudden onset of widespread neurologic signs about half a year after birth. Mycobacterium avium subsp. hominissuis (MAH) group was isolated and identified from the brain of a cat affected with pyogranulomatous meningoencephalitis. The central nervous system (CNS) was involved in the disseminated MAH infection. MAH infection should be considered in cats with neurologic signs in regard to zoonotic aspects. Comparatively, this is a first case of MAH infection observed in the brain in either humans or animals.


Assuntos
Doenças do Gato/microbiologia , Meningoencefalite/veterinária , Mycobacterium avium/classificação , Tuberculose/veterinária , Animais , Encéfalo/microbiologia , Encéfalo/patologia , Gatos , Evolução Fatal , Feminino , Meningoencefalite/microbiologia , Mycobacterium avium/isolamento & purificação
16.
Mol Ther Oncolytics ; 3: 15022, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27119113

RESUMO

Oncolytic virotherapy is a promising treatment strategy for cancer. We previously generated a recombinant measles virus (rMV-SLAMblind) that selectively uses a poliovirus receptor-related 4 (PVRL4/Nectin4) receptor, but not signaling lymphocyte activation molecule (SLAM). We demonstrated that the virus exerts therapeutic effects against human breast cancer cells. Here, we examined the applicability of rMV-SLAMblind to treating canine mammary cancers (CMCs). We found that the susceptibilities of host cells to rMV-SLAMblind were dependent on canine Nectin-4 expression. Nectin-4 was detected in four of nine CMC cell lines. The rMV-SLAMblind efficiently infected those four Nectin-4-positive cell lines and was cytotoxic for three of them (CF33, CHMm, and CTBm). In vivo experiment showed that the administration of rMV-SLAMblind greatly suppressed the progression of tumors in mice xenografted with a CMC cell line (CF33). Immunohistochemistry revealed that canine Nectin-4 was expressed in 45% of canine mammary tumors, and the tumor cells derived from one clinical specimen were efficiently infected with rMV-SLAMblind. These results suggest that rMV-SLAMblind infects CMC cells and displays antitumor activity in vitro, in xenografts, and ex vivo. Therefore, oncolytic virotherapy with rMV-SLAMblind can be a novel method for treating CMCs.

17.
J Vet Med Sci ; 77(7): e1-2, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26234626

RESUMO

p. 527, lines 5 to 1 from the bottom in the right column. While Kadosawa et al. reported the LAT1 expression in the canine mammary gland tumor and melanoma in the veterinary clinic [9-11], little information is available concerning LAT expression in hepatocellular carcinoma cells (HCCs) of dog; should have been While Fukumoto et al. reported the LAT1 expression in the canine mammary gland tumor and melanoma in the veterinary clinic [9-11], little information is available concerning LAT expression in hepatocellular carcinoma cells (HCCs) of dog.

18.
J Vet Med Sci ; 77(5): 527-34, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25649314

RESUMO

Analysis of L-type amino acid transport expression of hepatocellular carcinoma cells (HCCs) of the dog was performed. The leucine transport activity of canine HCCs was 0.628 ± 0.018 nmol/mg protein/min. The inhibitor of LAT 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (BCH) reduced 90% of the activity at 1 mM. The deduced amino acid sequences of canine LAT2, LAT3 and LAT4 were well conserved in mammalians, exhibiting 89, 88 and 77% homology, respectively. RT-PCR revealed distinct LAT1 expression compared with normal hepatocytes. Western blotting analysis confirmed the potent LAT1 expression in canine HCCs but not hepatocytes, and real-time RT-PCR analysis indicated that canine HCCs possessed 28 times higher LAT1 expression than hepatocytes. These results indicated that the leucine transport activity of canine HCCs was due to LAT1.


Assuntos
Carcinoma Hepatocelular/veterinária , Doenças do Cão/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Neoplasias Hepáticas/veterinária , Proteínas de Neoplasias/metabolismo , Sequência de Aminoácidos , Animais , Carcinoma Hepatocelular/metabolismo , Cães , Transportador 1 de Aminoácidos Neutros Grandes/química , Transportador 1 de Aminoácidos Neutros Grandes/genética , Neoplasias Hepáticas/metabolismo , Dados de Sequência Molecular , Proteínas de Neoplasias/genética
19.
J Vet Med Sci ; 77(1): 85-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25252639

RESUMO

L-type amino acid transporter 1 (LAT1), the first isotype of amino acid transport system L, transports aromatic and branched amino acids pivotal for fundamental cellular activities such cellular growth and proliferation. LAT1 expression was high only in the brain in contrast to its limited distribution and low level of expression in normal tissues. We found potent LAT1 expression in canine caput epididymis by quantitative RT-PCR and Western blotting analysis. Immnuno-histochemical examination revealed observable LAT1 in microvillous epithelial cells.


Assuntos
Cães/fisiologia , Epididimo/metabolismo , Regulação da Expressão Gênica/fisiologia , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Animais , Epididimo/anatomia & histologia , Imuno-Histoquímica , Transportador 1 de Aminoácidos Neutros Grandes/genética , Masculino
20.
Springerplus ; 3: 632, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25392802

RESUMO

Canine melanoma is the most common oral malignant tumor reported in the field of veterinary medicine. We found that lupeol, a lupine triterpene, inhibited mouse melanoma cell growth in vitro and in vivo by inducing cell differentiation. In the present study, we examined the differentiation-inducing activities of lupeol on 4 canine melanoma cells in vitro and in vivo. The induction of canine melanoma cell differentiation by lupeol was confirmed by evaluating some differentiation markers such as tyrosinase with real-time RT-PCR. Furthermore, we transplanted canine melanoma cells into a severe combined immunodeficiency mouse, and studied the anti-progressive effects of lupeol on tumor tissue. The gene expression of microphthalmia-associated transcription factor, tyrosinase, and tyrosinase-related protein-2, which are markers of pigment cell differentiation, was induced in 4 canine oral malignant melanoma cells by lupeol, and the agent markedly inhibited tumor progression in canine melanoma-bearing mice.

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