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1.
Cell Host Microbe ; 32(5): 755-767.e4, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38653242

RESUMO

Kaposi sarcoma (KS) is the most common cancer in persons living with HIV. It is caused by KS-associated herpesvirus (KSHV). There exists no animal model for KS. Pronuclear injection of the 170,000-bp viral genome induces early-onset, aggressive angiosarcoma in transgenic mice. The tumors are histopathologically indistinguishable from human KS. As in human KS, all tumor cells express the viral latency-associated nuclear antigen (LANA). The tumors transcribe most viral genes, whereas endothelial cells in other organs only transcribe the viral latent genes. The tumor cells are of endothelial lineage and exhibit the same molecular pattern of pathway activation as KS, namely phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR, interleukin-10 (IL-10), and vascular endothelial growth factor (VEGF). The KSHV-induced tumors are more aggressive than Ha-ras-induced angiosarcomas. Overall survival is increased by prophylactic ganciclovir. Thus, whole-virus KSHV-transgenic mice represent an accurate model for KS and open the door for the genetic dissection of KS pathogenesis and evaluation of therapies, including vaccines.


Assuntos
Modelos Animais de Doenças , Hemangiossarcoma , Herpesvirus Humano 8 , Camundongos Transgênicos , Sarcoma de Kaposi , Animais , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/patogenicidade , Camundongos , Hemangiossarcoma/virologia , Hemangiossarcoma/genética , Hemangiossarcoma/patologia , Sarcoma de Kaposi/virologia , Sarcoma de Kaposi/patologia , Genoma Viral , Humanos , Antígenos Virais/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Ganciclovir/uso terapêutico , Ganciclovir/farmacologia , Interleucina-10/genética
2.
J Vet Sci ; 24(5): e64, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37638712

RESUMO

Two Domestic Korean Shorthair cats presented with dyschezia and vomiting. Computed tomography revealed a colonic mass with calcification and lymph node metastasis in case 1, and a small intestinal mass with disseminated mesenteric metastasis and calcification in case 2. Histopathology revealed intestinal adenocarcinoma with osseous metaplasia. Case 1 died two months after surgery from distant metastasis; and case 2 showed no metastasis for five months but presented with anorexia, euthanized seven months after diagnosis. Metastatic intestinal adenocarcinoma with bone formation should be considered as differential diagnosis for calcification on imaging, and lymph node metastasis at diagnosis may indicate poor prognosis.


Assuntos
Adenocarcinoma , Doenças do Gato , Gatos , Animais , Metástase Linfática , Adenocarcinoma/veterinária , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Intestinos/patologia , Metaplasia/veterinária , República da Coreia , Doenças do Gato/diagnóstico por imagem
3.
J Vet Intern Med ; 37(2): 484-489, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36762697

RESUMO

BACKGROUND: Evaluating regeneration is essential for the classification and differential diagnosis of anemia in dogs. Early detection of regeneration is challenging in anemic dogs. OBJECTIVES: This study assessed the value of immature reticulocyte fraction (IRF) in differentiating preregenerative anemia (PRA) from nonregenerative anemia (NRA) in dogs. ANIMALS: Ninety-four dogs: 49 controls and 45 with anemia. METHODS: Case-control study. Fractions of low-, medium- (MFR), and high-fluorescence reticulocytes (HFR), were measured using the ADVIA 2120i hematology analyzer. The IRF was calculated as the sum of percentages of MFR and HFR. Data from dogs with regenerative anemia (RA, n = 19), PRA (n = 11), and NRA (n = 15) were retrospectively analyzed. The value of IRF was compared with reticulocyte production index (RPI) using the receiver operating characteristic (ROC) curve. RESULTS: The median of IRF was significantly higher in dogs with RA (46.5%; range, 40.9-53.6%; P < .001) and PRA (40.6%; range, 27.7-47.1%; P = .01) than in controls (22.1%; range, 16.9-29.3%). The IRF in dogs with PRA showed no difference compared to dogs with RA (P > .99) but was higher than dogs with NRA (18.7%; range, 8.8-24%; P = .00). The area under the ROC curve of IRF was superior to that of RPI (0.897 vs 0.818, P = .00) in differentiating dogs with PRA from NRA. CONCLUSIONS AND CLINICAL IMPORTANCE: The IRF is a reliable variable for detecting early regeneration in anemic dogs without reticulocytosis. The study suggests that the measurement of IRF could be useful in classifying anemic dogs.


Assuntos
Anemia , Doenças do Cão , Cães , Animais , Reticulócitos , Estudos de Casos e Controles , Estudos Retrospectivos , Anemia/diagnóstico , Anemia/veterinária , Contagem de Reticulócitos/veterinária , Eritrócitos , Doenças do Cão/diagnóstico
6.
Vet Ophthalmol ; 26(5): 458-463, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36537865

RESUMO

OBJECTIVE: To present the clinical signs and treatment methods for atypical tumor-like meibomitis in two dogs. ANIMALS STUDIED: A 4-year-old castrated-male Coton de Tulear (Case 1) and a 6-year-old spayed-female Maltese dog (Case 2). PROCEDURE: Full ophthalmic examination revealed a well-circumscribed, firm, and raised solitary mass on the upper eyelid of the left (Case 1) and right eye (Case 2). Case 1 showed a recurrent mass with a diameter of 2-3 mm, which was excised by the referring veterinarian. The possibility of meibomian gland involvement was suggested histopathologically. Case 2 had a history of blepharitis treated with systemic corticosteroids 4 years ago. RESULTS: Topical and systemic antibiotics and anti-inflammatory drugs were administered to reduce inflammation and prevent secondary infections. In Case 1, the mass appeared static at the beginning of medication; however, after stopping antibiotics while tapering steroids, the mass increased in size and was associated with suppurative discharge. In Case 2, the mass continued to grow despite treatment, showing a similar infection pattern. Cytological examination revealed neutrophilic inflammation with cocci infection, and bacterial culture confirmed the presence of Staphylococcus pseudintermedius in both cases. When steroid administration was stopped and antibiotic administration was initiated according to the results of the antibiotic susceptibility test, the mass rapidly decreased in size and completely disappeared. There was no recurrence on follow-up. CONCLUSIONS: A unilateral antibiotic-responsive tumor-like solitary mass on the upper eyelid resolved without surgical treatment. Medical treatment must be considered when treating atypical eyelid masses, and the use of appropriate antibiotics through antibiotic susceptibility testing is important.


Assuntos
Doenças do Cão , Meibomite , Neoplasias , Cães , Masculino , Feminino , Animais , Antibacterianos/uso terapêutico , Meibomite/veterinária , Glândulas Tarsais , Inflamação/tratamento farmacológico , Inflamação/veterinária , Neoplasias/veterinária , Doenças do Cão/tratamento farmacológico , Doenças do Cão/microbiologia
7.
Cancer Cell Int ; 22(1): 404, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36514170

RESUMO

BACKGROUND: Cancer-associated fibroblasts (CAFs) coordinate the malignancy of cancer cells via secretory materials. Reprogrammed lipid metabolism and signaling play critical roles in cancer biology. Oleic acid (OA) serves as a source of energy under glucose-deficient conditions, but its function in cancer progression remains unclear. The present study investigated that CAFs in xenografted tumors had higher amounts of fatty acids, particularly OA, compared to normal fibroblasts, and promoted the cancer cell stemness in lung adenocarcinoma cells under glucose-deficient condition. METHODS: Xenografts were established in immunodeficient mice by injection of NCI-H460 (H460) cells. Lipids and fatty acids were evaluated using the BODIPY staining and fatty-acid methyl esters analysis. The expression levels of markers for lipid metabolism and cancer stemness were determined by western blot, flow cytometry, and real-time PCR. Cancer cell subclones against stearoyl-CoA desaturase (SCD) were produced by lentiviral vector and CRISPR/cas9 systems. The expression of SCD was examined immunochemically in human adenocarcinoma tissues, and its clinical relevance to survival rate in lung adenocarcinoma patients was assessed by Kaplan-Meier analysis. RESULTS: Transferred CAF-derived OA through lipid transporter upregulated SCD in cancer cells under glucose-deficient conditions, resulting in enhanced lipid metabolism and autophagosome maturation. By OA treatment under glucose deficient condition, cancer cell stemness was significantly enhanced through sequential activation of SCD, F-actin polymerization and nuclear translocation of yes-associated protein. These findings were confirmed by experiments using chemical inhibitors, SCD-overexpressing cells and SCD-knockout (KO) cells. When xenografted, SCD-overexpressing cells produced larger tumors compared with parental cells, while SCD-KO cells generated much smaller tumors. Analysis of tumor tissue microarray from lung adenocarcinoma patients revealed that SCD expression was the marker for poor prognosis involving tumor grade, clinical stage and survival rate. CONCLUSION: Our data indicate that CAFs-derived OA activated lipid metabolism in lung adenocarcinoma cells under glucose-deficient conditions, subsequently enhancing stemness and progression toward malignancy.

8.
J Vet Intern Med ; 36(6): 2071-2078, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36330885

RESUMO

BACKGROUND: Serum uromodulin concentration has been described as a novel biomarker of chronic kidney disease (CKD) in humans but not dogs. OBJECTIVE: To evaluate the serum uromodulin concentration in dogs with CKD and assess its diagnostic performance in distinguishing dogs with CKD from healthy dogs. ANIMALS: Forty-nine dogs with CKD (International Renal Interest Society [IRIS] Stage 1, n = 23; Stage 2, n = 20; Stage 3-4, n = 6) and 25 healthy controls. METHODS: Prospective, observational study. Serum uromodulin concentration was measured using a canine-specific enzyme-linked immunosorbent assay (ELISA), and its correlation with conventional renal markers was analyzed. RESULTS: Serum uromodulin concentrations were significantly lower in the CKD group than in the control group (P < .001), but no significant difference was observed among stages of CKD. A negative correlation was observed between serum uromodulin concentration and conventional renal markers (blood urea nitrogen concentration, r = -.60, P < .0001; serum creatinine concentration, r = -.46, P < .0001; serum symmetric dimethylarginine concentration [SDMA], r = -.65, P < .0001). In receiver operating characteristic analysis, the area under the curve (AUC) of uromodulin (AUC, 0.97; 95% confidence interval [CI], 0.94-1.00) was higher than that of SDMA (AUC, 0.87; 95% CI, 0.79-0.95) for CKD diagnosis (P = .01). The AUC of uromodulin (AUC, 0.95; 95% CI, 0.89-1.00) also was higher than that of SDMA (AUC, 0.72; 95% CI, 0.58-0.87) in distinguishing dogs with Stage 1 CKD from controls (P = .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Serum uromodulin concentration is decreased in dogs with CKD. Thus, serum uromodulin may be a valuable diagnostic marker for CKD in dogs, particularly in identifying early-stage CKD.


Assuntos
Doenças do Cão , Insuficiência Renal Crônica , Animais , Cães , Biomarcadores , Nitrogênio da Ureia Sanguínea , Creatinina , Doenças do Cão/diagnóstico , Estudos Prospectivos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/veterinária , Uromodulina
9.
J Comp Pathol ; 194: 50-53, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35577459

RESUMO

An 11-year-old spayed female Miniature Schnauzer dog was presented with loss of a claw caused by a nail bed mass. Histopathological evaluation revealed that the mass comprised neoplastic squamous cells with abundant cytoplasmic melanin pigment. Immunohistochemically, the neoplastic cells were positive for cytokeratin and negative for vimentin and ionized calcium-binding adaptor molecule 1, supporting a diagnosis of pigmented squamous cell carcinoma. To our knowledge, this is the first report of subungual pigmented squamous cell carcinoma in animals.


Assuntos
Carcinoma de Células Escamosas , Doenças do Cão , Doenças da Unha , Dermatopatias , Neoplasias Cutâneas , Animais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/veterinária , Cães , Feminino , Queratinas , Doenças da Unha/diagnóstico , Doenças da Unha/patologia , Doenças da Unha/veterinária , Dermatopatias/veterinária , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/veterinária
10.
Can Vet J ; 63(2): 139-142, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35110769

RESUMO

A 12-year-old, spayed female, Maltese dog with a round and firm mass on the dorsal part of the left rear paw and a cervical mass was brought to the clinic. The paw mass was contiguous to the adjacent tendon; it was composed of neoplastic mesenchymal cells and had scattered foci of calcification with chondroid differentiation microscopically. The neoplastic cells were positive for vimentin and S100, but negative for desmin and smooth muscle actin. Microscopic features and immunohistochemistry results were consistent with calcifying aponeurotic fibroma (CAF). The cervical mass was composed of polygonal cells forming acini with marked anisocytosis and anisokaryosis and diagnosed as thyroid follicular carcinoma. No recurrence or metastasis occurred during follow-up. To the best of our knowledge, this is the first case of canine CAF with features identical to its human counterparts. Key clinical message: This report describes the rare case of calcifying aponeurotic fibroma on the paw in a dog. This is apparently the first case in the veterinary literature with identical clinical and pathological features to the human counterpart.


Fibrome aponévrotique calcifiant sur la patte chez un chien. Une chienne maltaise stérilisée âgée de 12 ans avec une masse ronde et ferme sur la partie dorsale de la patte arrière gauche et une masse cervicale a été amenée à la clinique. La masse de la patte était contiguë au tendon adjacent; il était composé de cellules mésenchymateuses néoplasiques et présentait des foyers de calcification dispersés avec une différenciation chondroïde au microscope. Les cellules néoplasiques étaient positives pour la vimentine et le S100, mais négatives pour la desmine et l'actine des muscles lisses. Les caractéristiques microscopiques et les résultats d'immunohistochimie étaient compatibles avec un fibrome aponévrotique calcifiant (CAF). La masse cervicale était composée de cellules polygonales formant des acini avec une anisocytose et une anisocaryose marquées et diagnostiquée comme un carcinome folliculaire de la thyroïde. Aucune récidive ou métastase n'est survenue au cours du suivi. À notre connaissance, il s'agit du premier cas de CAF canin avec des caractéristiques identiques à ses homologues humains.Message clinique clé :Ce rapport décrit le cas rare de fibrome aponévrotique calcifiant sur la patte chez un chien. C'est apparemment le premier cas dans la littérature vétérinaire avec des caractéristiques cliniques et pathologiques identiques à son homologue humain.(Traduit par Dr Serge Messier).


Assuntos
Calcinose , Doenças do Cão , Fibroma Ossificante , Fibroma , Neoplasias de Tecidos Moles , Animais , Calcinose/patologia , Calcinose/cirurgia , Calcinose/veterinária , Doenças do Cão/cirurgia , Cães , Feminino , Fibroma/patologia , Fibroma/cirurgia , Fibroma/veterinária , Fibroma Ossificante/veterinária , Neoplasias de Tecidos Moles/veterinária
11.
J Vet Sci ; 23(2): e19, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35187877

RESUMO

BACKGROUND: Gastric ulcer is one of the prevalent diseases in racehorses. However, it has not been recognized as important in Korea, and drugs used to treat gastric ulcers are included in the doping test list, so they are not allowed to be administered to racehorses in training. OBJECTIVES: This study was performed 1) to investigate the prevalence and the severity of gastric ulcers in Thoroughbred racehorses in Korea, 2) to confirm the therapeutic effect of ranitidine and omeprazole, and 3) to compare the efficacy between ranitidine and omeprazole. METHODS: Forty-nine horses were randomly recruited, and gastroscopy was performed within two days after racing. Twelve horses with a sum grade of five or higher were randomly assigned to two treatment groups. Seven horses were administered ranitidine, and five horses were administered omeprazole. Follow-up gastroscopy was scheduled within one to five days after finishing the treatment. RESULTS: The prevalence of gastric ulcer in Korean Thoroughbred racehorses after racing was 100%, and the grade was more severe in the non-glandular region than in the pyloric region. There was no correlation between the severity of gastric ulcer in the two regions. Omeprazole had a greater therapeutic effect than ranitidine. CONCLUSIONS: This study shows the importance of recognizing gastric ulcers as an important factor, and omeprazole as a possible treatment option in Korea, as it has been removed from the list of prohibited substances for racehorses. Thus, the use of omeprazole is currently recommended until one day before the race.


Assuntos
Antiulcerosos , Doenças dos Cavalos , Úlcera Gástrica , Animais , Antiulcerosos/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/epidemiologia , Cavalos , Omeprazol/uso terapêutico , Prevalência , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/epidemiologia , Úlcera Gástrica/veterinária
12.
Oncol Lett ; 22(6): 845, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34733363

RESUMO

Patients with advanced urothelial carcinoma (UC) generally have poor prognoses due to therapeutic resistance. Furthermore, there are limited treatment options for advanced UC. Therefore, novel or effective chemotherapeutic agents are needed to improve patient survival. The present study was conducted to investigate the effect of temozolomide (TMZ) on UC cells so as to identify a potential method to overcome therapeutic resistance. TMZ is an alkylating agent with a target different from that of other anticancer drugs used to treat UC, such as cisplatin. TMZ enhanced the autophagic response and senescence, which was mediated via the p53 and p21 pathways. Inhibiting the autophagic response using chloroquine synergistically augmented the cytotoxic effect of TMZ on UC cells. TMZ significantly reduced the invasiveness of UC cells. Notably, the abundance of side population fraction was also significantly reduced following TMZ treatment. Considering that side population fraction is known to confer therapeutic resistance, it is noteworthy that the TMZ treatment markedly decreased side population fraction. Altogether, TMZ may have the potential to be applied as a part of an alternative treatment strategy to reduce the malignancy of UC cells.

13.
J Biomed Res ; 35(6): 448-458, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34497158

RESUMO

Atopic dermatitis (AD) is a common skin disorder difficult to be treated with medication. This study investigated the potential of ovalicin extracted from Cordyceps militaris for the treatment of AD using in vitro and in vivo models. We found that, in canine macrophage cell line DH82, lipopolysaccharide (LPS) upregulated the expression of genes associated with inflammation and pruritic responses through activating calcium and interleukin-31 (IL-31) signaling, and the upregulation could be suppressed by ovalicin, with an effect significantly stronger than dexamethasone. Ovalicin also reduced the expression of IL-31 downstream genes, including JAK2 (Janus kinase 2), TRPV1 (transient receptor potential vanilloid receptor-1), and HRH2 (histamine receptor H2). Ovalicin significantly alleviated the allergic symptoms in the AD mouse model. Histologically, the number of macrophages and mast cells infiltrated in the dermis was significantly reduced by ovalicin treatment. In the skin tissue of AD mice, reduction of IL-31 receptor was observed in the ovalicin treated group compared to the group without ovalicin treatment. To our knowledge, this is the first study to elucidate the anti-atopic mechanism of ovalicin, which could be an alternative to steroidal drugs commonly used for AD treatment.

14.
Exp Cell Res ; 406(2): 112778, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34384778

RESUMO

Cancer-associated fibroblasts (CAFs) are an abundant component of the tumor microenvironment and have distinct features from normal fibroblasts (NFs). However, the discriminative nature of heterogeneous CAFs under glucose starvation remains unknown. In this study, we investigated the changes in the mitochondrial calcium concentration and relevant intracellular machinery in CAFs under glucose-deficient conditions. Xenografted tumor masses were dissected into multiple pieces and subjected to the CAF isolation using magnetically activated cell sorting (MACS). NFs were separated from the normal lung and skin. Under glucose starvation, CAFs from the tumor mass exhibited heterogeneity in cell proliferation, ATP production and calcium concentration. Compared to NFs, mitochondrial calcium concentration was significantly higher in glucose-starved CAFs with upregulation of mitochondrial calcium uniporter (MCU) that led to enhancement of ATP production and cell growth. Intriguingly, treatment of glucose-starved CAFs with oligomycin increased apoptosis by disrupted calcium homeostasis following overactivation of the mPTP. Moreover, oligomycin-induced apoptosis was mitigated by calcium chelation. This study demonstrated that the discriminative calcium influx to mitochondria through MCU coordinated cell growth and apoptosis in glucose-starved CAFs but not in NFs.


Assuntos
Biomarcadores Tumorais/metabolismo , Canais de Cálcio/metabolismo , Fibroblastos Associados a Câncer/patologia , Regulação Neoplásica da Expressão Gênica , Glucose/deficiência , Neoplasias/patologia , Trifosfato de Adenosina/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Fibroblastos Associados a Câncer/metabolismo , Ciclo Celular , Movimento Celular , Proliferação de Células , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitocôndrias , Neoplasias/metabolismo , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Neoplasia ; 23(7): 653-662, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34134082

RESUMO

Tumor hypoxia is known to promote the acquisition of more aggressive phenotypes in human transitional cell carcinoma (TCC), including drug resistance. Accumulating evidence suggests that mitochondria play a central role in the chemoresistance of TCC. However, the role of mitochondria in the hypoxia-induced drug resistance in TCC remains elusive. The present study investigated the function of mitochondria in the drug resistance using a TCC cell line under hypoxic conditions. In vitro hypoxia (0.1% O2, 48 h) was achieved by incubating TCC cells in air chamber. Mitochondrial events involving hypoxia-induced drug resistance were assessed. Hypoxia significantly reduced the cisplatin-induced apoptosis of TCC cells. Additionally, hypoxia substantially decreased the level of mitochondrial reactive oxygen species (ROS) generated by cisplatin treatment. Analogously, elimination of mitochondrial ROS significantly rescued cells from cisplatin-induced apoptosis. Hypoxia enhanced mitochondrial hyperpolarization, which was not related to ATP production or the reversal of ATP synthase activity. The mitochondrial DNA (mtDNA) amplification efficiency data illustrated that hypoxia significantly prevented oxidative damage to the mitogenome. Moreover, transmission electron microscopy revealed that cisplatin-induced disruption of the mitochondrial ultrastructure was abated under hypoxic conditions. Notably, depletion of mtDNA by ethidium bromide abrogated hypoxia-induced resistance to cisplatin. Taken together, the present study demonstrated that TCC cells exposed to hypoxic conditions rendered mitochondria less sensitive to oxidative stress induced by cisplatin treatment, leading to enhanced drug resistance.


Assuntos
Carcinoma de Células de Transição/metabolismo , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Hipóxia/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Hipóxia Tumoral/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Carcinoma de Células de Transição/tratamento farmacológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Modelos Biológicos , Espécies Reativas de Oxigênio/metabolismo , Hipóxia Tumoral/genética
16.
Mol Carcinog ; 60(7): 455-468, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34003526

RESUMO

Canine mammary gland tumors (CMTs) are the most common tumor type in female dogs. This study evaluated the expression pattern and role of thyroglobulin (Tg) in CMT and in human breast cancer (HBC). CMT samples were subjected to fine-needle aspiration, primary cell culture, and histopathology. The expression level of Tg was higher in benign CMT than in malignant CMT (mCMT) primary cells, particularly in the epithelial lineage. Moreover, treatment with Tg enhanced the sensitivity of doxorubicin in mCMT epithelial cells and mitigated proinflammatory response by increasing nuclear factor erythroid 2-related factor 2 (Nrf2). The proximal region of the Tg promoter was hypermethylated in mCMT epithelial cells, silencing Tg expression with concurrent downregulation of Nrf2-mediated antioxidant signaling. An identical pattern of Tg expression was observed in cytological and tissue samples. Tissue microarray analysis showed that Tg was highly expressed in normal and benign tissues when compared with their malignant counterparts, which was diminished along with higher histological grades. The survival rate was significantly higher in HBC patients with high Tg expression than those with low Tg expression. This study also showed that the progression of HBC is accompanied by the reduction of Tg expression along with augmentation of proinflammatory signaling. Our data suggested that Tg could be a negative indicator of malignancy in canine and human breast neoplasia.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Doenças do Cão/patologia , Neoplasias Mamárias Animais/patologia , Tireoglobulina/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Linhagem Celular Tumoral , Doenças do Cão/metabolismo , Cães , Doxorrubicina/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Mamárias Animais/tratamento farmacológico , Neoplasias Mamárias Animais/metabolismo , Metilação , Fator 2 Relacionado a NF-E2/metabolismo , Regiões Promotoras Genéticas , Taxa de Sobrevida , Tireoglobulina/genética , Tireoglobulina/farmacologia
17.
J Vet Sci ; 22(1): e14, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33522166

RESUMO

BACKGROUND: Quantitation of urine protein is important in dogs with chronic kidney disease. Various analyzers are used to measure urine protein-to-creatinine ratios (UPCR). OBJECTIVES: This study aimed to compare the UPCR obtained by three types of analyzers (automated wet chemistry analyzer, in-house dry chemistry analyzer, and dipstick reading device) and investigate whether the differences could affect clinical decision process. METHODS: Urine samples were collected from 115 dogs. UPCR values were obtained using three analyzers. Bland-Altman and Passing Bablok tests were used to analyze agreement between the UPCR values. Urine samples were classified as normal or proteinuria based on the UPCR values obtained by each analyzer and concordance in the classification evaluated with Cohen's kappa coefficient. RESULTS: Passing and Bablok regression showed that there were proportional as well as constant difference between UPCR values obtained by a dipstick reading device and those obtained by the other analyzers. The concordance in the classification of proteinuria was very high (κ = 0.82) between the automated wet chemistry analyzer and in-house dry chemistry analyzer, while the dipstick reading device showed moderate concordance with the automated wet chemistry analyzer (κ = 0.52) and in-house dry chemistry analyzer (κ = 0.53). CONCLUSIONS: Although the urine dipstick test is simple and a widely used point-of-care test, our results indicate that UPCR values obtained by the dipstick test are not appropriate for clinical use. Inter-instrumental variability may affect clinical decision process based on UPCR values and should be emphasized in veterinary practice.


Assuntos
Creatinina/urina , Testes Diagnósticos de Rotina/veterinária , Doenças do Cão/urina , Proteinúria/veterinária , Urinálise/veterinária , Animais , Testes Diagnósticos de Rotina/instrumentação , Cães , Feminino , Masculino , Proteinúria/urina , Urinálise/instrumentação , Urinálise/métodos
18.
Autoimmunity ; 52(5-6): 199-207, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468991

RESUMO

FoxP3 reporter mice expressing green fluorescence protein (GFP) have been used as a very convenient tool to investigate the impact of regulatory T (Treg) cells on pathogenesis in autoimmune diseases. Here, we found that GFP-FoxP3+ knock-in (KI) mice showed alterations in the production of anti-nuclear autoantibodies (ANAs) and nephritis with different extent, depending on the presence or absence of lupus susceptibility gene locus 1 (Sle1) and KI method: contrasting with B6.Sle1.fGFP-FoxP3 mice, expressing GFP via N-terminal insertion, B6.Sle1.iGFP-FoxP3, expressing GFP via bicistronic internal ribosome entry site-driven promotion, exhibited significantly lower penetrance of serum ANA, comparing to control B6.Sle1 mice. Moreover, B6.Sle1.GFP-FoxP3+ mice reduced the Sle1-induced splenomegaly and B-cell expansion independently of the KI method employed, mainly by reducing the numbers of transitional 1 (T1) B cells and CD21-CD23- B cells, including plasmablasts and plasma cells. The absolute numbers of both splenic CD4+ T cells and Treg cells from B6.Sle1.GFP-FoxP3 KI mice were significantly reduced but their proportion was not changed, compared to B6.Sle1 mice. Although the glomerular basement membranes were thickened in both B6.Sle1 and B6.Sle1.iGFP-FoxP3 mice, they were thinner in B6.Sle1.fGFP-FoxP3 mice. The latter mice expressed more nephrophilic autoantibodies and deposited more complement component 3 in glomeruli compared to B6.iGFP-FoxP3 mice. FoxP3+ Treg cells may modulate B-cell tolerance in lupus-prone B6.Sle1 mice, presumably by modulating pathogenic, nephrophilic autoantibody production and nephritis.


Assuntos
Técnicas de Introdução de Genes , Proteínas de Fluorescência Verde , Lúpus Eritematoso Sistêmico , Penetrância , Linfócitos T Reguladores , Animais , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Linfócitos B/imunologia , Linfócitos B/patologia , Modelos Animais de Doenças , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/imunologia , Tolerância Imunológica , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Camundongos , Camundongos Transgênicos , Especificidade da Espécie , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia
19.
Vet Dermatol ; 30(4): 359-e105, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31090152

RESUMO

BACKGROUND: Reports of canine pyoderma gangrenosum (PG) are uncommon in the veterinary literature. Rarer still are cases describing dogs with both skin lesions and internal organ involvement. OBJECTIVE: To describe a case of canine PG with skin and internal organ involvement. ANIMALS: A client-owned dog. METHODS AND MATERIALS: Complete blood count, serum chemistry, C-reactive protein and SNAP cPL tests, and abdominal ultrasonography and fine-needle aspiration of the spleen were performed. RESULTS: The dog was treated with oral prednisolone and ciclosporin. After three months of therapy, ultrasonography revealed normalization of the spleen and resolution of skin lesions. CONCLUSION AND CLINICAL IMPORTANCE: Dogs with skin lesions compatible with PG should be screened carefully for internal organ involvement. Ciclosporin may be a useful treatment for the immediate and long-term management of canine PG.


Assuntos
Doenças do Cão/diagnóstico , Pancreatite/veterinária , Pioderma Gangrenoso/veterinária , Dermatopatias/veterinária , Pele/patologia , Baço/patologia , Animais , Ciclosporina/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Doenças do Cão/tratamento farmacológico , Cães , Feminino , Pancreatite/diagnóstico , Pancreatite/tratamento farmacológico , Prednisolona/uso terapêutico , Pioderma Gangrenoso/complicações , Pioderma Gangrenoso/tratamento farmacológico , Dermatopatias/tratamento farmacológico , Dermatopatias/etiologia , Baço/diagnóstico por imagem , Resultado do Tratamento , Ultrassonografia
20.
J Vet Diagn Invest ; 31(3): 408-414, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30776981

RESUMO

Glycated hemoglobin A1c (HbA1c) is widely used for monitoring and diagnosing human diabetes mellitus, but is rarely used in veterinary clinics. The goal of our study was to validate the commercial HbA1c testing system SD A1cCare analyzer (Bionote, Gyeoggi-do, South Korea) for use in dogs. Dogs were recruited with owner's consent. Diabetic status was determined based on clinical signs, fasting hyperglycemia, and glycosuria. Intra-assay precision and linearity were evaluated with EDTA, heparin, or citrate as anticoagulants, and had excellent precision with mean coefficients of variation (CVs) of 2.47%, 2.26%, and 1.92%, respectively. Diluted anticoagulated blood samples showed excellent linear relationships with R2 of 0.991, 0.996, and 0.994, respectively. Inter-assay precision revealed that the mean CV of the normal control was 2.18% and that of the high control was 2.01% (30 repeats). Observed total error of a normal control was 7.81%, and 6.12% for the high control. HbA1c level measured before and after removal of plasma and replacement by saline showed minimal interference by lipid contents ( p = 0.929). The HbA1c concentrations of diabetic dogs were significantly higher than those of non-diabetic dogs ( p < 0.001). HbA1c value >6.2% indicated canine diabetes through a classification and regression tree model. In most cases, fructosamine and HbA1c were highly correlated ( r = 0.674, p < 0.001). The HbA1c testing system could be a valuable testing system to evaluate canine diabetes mellitus, providing an alternative in-house option for use by veterinary clinicians.


Assuntos
Diabetes Mellitus/veterinária , Doenças do Cão/diagnóstico , Hemoglobinas Glicadas/metabolismo , Animais , Glicemia , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Doenças do Cão/sangue , Cães , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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