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1.
Cir Pediatr ; 37(1): 33-36, 2024 Jan 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38180100

RESUMO

INTRODUCTION: Cutis marmorata telangiectatica congenita (CMTC) is a rare capillary malformation characterized by persistent reticular and violaceous erythema. We present two cases of CMTC. CLINICAL OBSERVATION: The first case involved a 13-month-old male with a reticular violaceous macule on the left gluteal region and a brownish papule with Darier's sign on the inner malleolus of the left foot, which was biopsied, revealing > 15 mast cells per field, leading to a diagnosis of CMTC and solitary cutaneous mastocytoma. The second case involved a newborn with a characteristic CMTC lesion without other malformations at birth, who subsequently developed two cutaneous tumors consistent with infantile hemangiomas during follow-up. DISCUSSION: CMTC is a benign condition. However, approximately 50% of cases exhibit associated anomalies. When CMTC is suspected, musculoskeletal, ophthalmological, and cutaneous malformations should be ruled out. To the best of our knowledge, this is the first report of CMTC associated with mastocytoma and one of the few cases associated with infantile hemangioma.


INTRODUCCION: La cutis marmorata telangiectásica congénita (CMTC) es una rara malformación capilar caracterizada por eritema reticular y violáceo persistente. Presentamos dos casos de CMTC. OBSERVACION CLINICA: Un varón de 13 meses presentaba una mácula violácea reticular en glúteo izquierdo y una pápula parduzca con signo de Darier en el maléolo interno del pie izquierdo, que fue biopsiada identificando > 15 mastocitos/campo, con lo cual se diagnosticó de CMTC y mastocitoma cutáneo solitario. El segundo caso, una recién nacida con una lesión característica de CMTC sin otras malformaciones al nacer, que durante el seguimiento desarrolló dos tumoraciones cutáneas compatibles con hemangiomas infantiles. COMENTARIOS: La CMTC es una condición benigna, sin embargo, aproximadamente el 50% de los casos presentan anomalías asociadas. Ante la sospecha de CMTC se deben descartar malformaciones musculoesqueléticas, oftalmológicas y cutáneas. Hasta donde tenemos conocimiento, este es el primer reporte de CMTC asociada con mastocitoma y uno de los pocos con hemangioma infantil.


Assuntos
Livedo Reticular , Mastocitoma , Recém-Nascido , Masculino , Humanos , Lactente , Biópsia , Livedo Reticular/etiologia
2.
Rev Alerg Mex ; 69(3): 142-145, 2023 Feb 01.
Artigo em Espanhol | MEDLINE | ID: mdl-36869014

RESUMO

BACKGROUND: The solitary cutaneous mastocytoma is a variant of cutaneous mastocytosis which carries a good prognosis. It may develop at a very early age, during the first weeks of life, or even be congenital. Typically, they present as red-brownish lesions that may be asymptomatic or present systemic manifestations associated with histamine release. CASE REPORT: A 19-year-old female patient who attended a medical consultation for a pigmented lesion, slightly raised in the left antecubital fold, asymptomatic, of recent appearance and progressive growth. Dermoscopy reported a fine symmetrical network, yellowish-brown in color and randomly distributed black dots. The pathology report and immunohistochemical findings were consistent with mast cell tumor. CONCLUSIONS: The solitary cutaneous mastocytoma should not be considered as an exclusive entity in the pediatric population. Acknowledgment of its atypical clinical presentation with its dermatoscopic features, is useful for diagnosis.


ANTECEDENTES: El mastocitoma solitario es una variante de mastocitosis cutánea de buen pronóstico, congénita, que aparece durante las primeras semanas de vida. Las manifestaciones clínicas incluyen: lesiones de color rojo-marrón, que pueden ser asintomáticas o generar lesiones sistémicas asociadas con la liberación de histamina. REPORTE DE CASO: Paciente femenina de 19 años, que acudió a consulta médica por una lesión pigmentada, ligeramente sobreelevada en el pliegue antecubital izquierdo, asintomática, de reciente aparición y crecimiento progresivo. La dermatoscopia reportó una fina red simétrica, de color pardo-amarillenta, con puntos negros y distribución al azar. El informe de Anatomía patológica y los hallazgos de inmunohistoquímica fueron compatibles con mastocitoma. CONCLUSIONES: El mastocitoma solitario no es exclusivo de la población pediátrica y su manifestación en la población adulta suele ser atípica. El conocimiento de las características dermatoscópicas es útil para establecer el diagnóstico certero.


Assuntos
Mastocitoma , Neoplasias , Criança , Feminino , Humanos , Adulto Jovem , Adulto , Mastócitos
3.
Int J Dermatol ; 62(5): 616-620, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36807903

RESUMO

BACKGROUND: Mastocytosis is a heterogeneous group of rare disorders characterized by the accumulation of clonal mast cells in organs such as the skin and bone marrow. The diagnosis of cutaneous mastocytosis (CM) is based on clinical findings, positive Darier's sign, and histopathology, if necessary. METHODS: Medical records of 86 children with CM diagnosed during a 35-year long period were reviewed. Most patients (93%) developed CM during the first year of life (median age 3 months). Clinical features at presentation and during the follow-up period were analyzed. Baseline serum tryptase level was measured in 28 patients. RESULTS: A total of 85% of patients had maculopapular cutaneous mastocytosis/urticaria pigmentosa (MPCM/UP), 9% had mastocytoma, and 6% had diffuse cutaneous mastocytosis (DCM). Boy to girl ratio was 1.1:1. Fifty-four of 86 patients (63%) were followed from 2 to 37 years (median 13 years). Complete resolution was registered in 14% of mastocytoma cases, 14% of MCPM/UP, and in 25% of DCM patients. After the age of 18, skin lesion persisted in 14% mastocytoma, 7% MCPM/UP, and 25% children with DCM. Atopic dermatitis was diagnosed in 9.6% of patients with MPCM/UP. Three of 28 patients had elevated serum tryptase. Prognosis in all patients was good, and there were no signs of progression to systemic mastocytosis (SM). CONCLUSION: To the best of our knowledge, our results represent the longest single-center follow-up study of childhood-onset CM. We found no complications of massive mast cell degranulation or progression to SM.


Assuntos
Mastocitoma , Mastocitose Cutânea , Mastocitose Sistêmica , Mastocitose , Urticaria Pigmentosa , Masculino , Feminino , Humanos , Criança , Lactente , Seguimentos , Triptases , Mastocitose/diagnóstico , Mastocitose/epidemiologia , Mastocitose/patologia , Urticaria Pigmentosa/diagnóstico , Urticaria Pigmentosa/patologia , Mastocitose Cutânea/diagnóstico , Mastocitose Cutânea/epidemiologia , Mastocitose Cutânea/patologia , Mastócitos/patologia , Mastocitose Sistêmica/diagnóstico , Mastocitoma/patologia
4.
Mol Biol Rep ; 50(1): 267-277, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36331742

RESUMO

Expression changes for tryptophan hydroxylase 1 (TPH1), the rate-limiting enzyme in serotonin synthesis, by environmental glutamine (GLN) were examined in mouse mastocytoma-derived P815-HTR cells. GLN-treated cells exhibited a robust increase in TPH1 mRNA after a 6 h exposure to GLN. 6-Diazo-5-oxo-L-norleucine (DON), a glutamine-utilizing glutaminase inhibitor, significantly inhibited the GLN-induction of TPH1 mRNA. Nuclear run-on assays and mRNA decay experiments demonstrated that the primary mechanism leading to increased TPH1 mRNA levels was not due to transcriptional changes, but rather due to increased TPH1 RNA stability induced by GLN. Treatment with GLN also led to activation of p38 MAP kinase, but not p42/44 MAPK. In addition, SB203580, a p38 MAP kinase specific inhibitor, completely abolished the GLN-mediated increase of TPH1 mRNA levels, suggesting the pathway stabilizing TPH1 mRNA might be mediated by the activated p38 MAP kinase pathway. Additionally, SB203580 significantly reduced the stability of TPH1 mRNA, and this reduction of the stability was not affected by GLN in the culture medium, implying a sequential signaling from GLN being mediated by p38 MAP kinase, resulting in alteration of TPH1 mRNA stability. TPH1 mRNA stability loss was also dependent on de novo protein synthesis as shown by treatment of cells with a transcriptional/translational blocker. We provide evidence that TPH1 mRNA levels are increased in response to increased exogenous GLN in mouse mastocytoma cells via a stabilization of TPH1 mRNA due to the activity of the p38 MAP kinase.


Assuntos
Mastocitoma , Mitógenos , Camundongos , Animais , Glutamina , RNA Mensageiro/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Inibidores Enzimáticos/farmacologia , Triptofano Hidroxilase/genética
5.
Int J Mol Sci ; 23(4)2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35216060

RESUMO

A new combination of Toceranib (Toc; 5-[(5Z)-(5-Fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[2-(pyrrolidin-1-yl)ethyl]-1H-pyrrole-3-carboxamide) with nanohydroxyapatite (nHAp) was proposed as an antineoplastic drug delivery system. Its physicochemical properties were determined as crystallinity, grain size, morphology, zeta potential and hydrodynamic diameter as well as Toceranib release. The crystalline nanorods of nHAp were synthesised by the co-precipitation method, while the amorphous Toceranib was obtained by its conversion from the crystalline form during nHAp-Toc preparation. The surface interaction between both compounds was confirmed using Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-Vis) and scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS). The nHAp-Toc showed a slower and prolonged release of Toceranib. The release behaviour was affected by hydrodynamic size, surface interaction and the medium used (pH). The effectiveness of the proposed platform was tested by comparing the cytotoxicity of the drug combined with nHAp against the drug itself. The compounds were tested on NI-1 mastocytoma cells using the Alamar blue colorimetric technique. The obtained results suggest that the proposed platform shows high efficiency (the calculated IC50 is 4.29 nM), while maintaining the specificity of the drug alone. Performed analyses confirmed that nanohydroxyapatite is a prospective drug carrier and, when Toceranib-loaded, may be an idea worth developing with further research into therapeutic application in the treatment of canine mast cell tumour.


Assuntos
Doenças do Cão/tratamento farmacológico , Durapatita/farmacologia , Indóis/farmacologia , Mastocitoma/tratamento farmacológico , Nanopartículas/administração & dosagem , Pirróis/farmacologia , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cães , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Sinergismo Farmacológico , Inibidores de Proteínas Quinases/farmacologia
6.
BMC Vet Res ; 17(1): 331, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34649575

RESUMO

BACKGROUND: While lymphadenectomy of metastatic lymph nodes (LNs) has been associated with improved outcome, the clinical utility of prophylactic lymphadenectomy in dogs with stage I cutaneous mast cell tumors (cMCTs) remains a controversial topic. To assess the therapeutic role of lymphadenectomy of uninvolved regional LNs, the long-term outcome of cMCT-bearing dogs with cytologically negative and surgically unresected regional LNs (observation only, OO) was compared with that of dogs with surgically resected and histologically negative regional LNs (prophylactic regional lymphadenectomy, PRL). RESULTS: A retrospective analysis of 64 dogs with a low-grade, completely resected stage I cMCT was performed: 35 (54.7%) dogs were subjected to OO and 29 (45.3%) underwent PRL. Dogs were monitored for a median of 813 and 763 days in the OO group and PRL group, respectively. The number of dogs undergoing MCT progression was significantly higher in the OO group (P = 0.028) and curve comparison revealed a tendency to a better time to progression in the PRL group (P = 0.058). No significant difference in survival time (P = 0.294) was observed between dogs in the OO and PRL groups. CONCLUSIONS: Our results showed that lack of immediate lymphadenectomy was associated with a higher risk for tumor progression. This preliminary judgement, reinforced by the findings that lymphadenectomy was well tolerated in all cases, and that histopathology provides the definitive assessment of the nodal pathological status, may suggest that prophylactic lymphadenectomy is indicated in the management of stage I MCTs. Larger prospective studies are warranted for generating clinical evidence of this latter hypothesis.


Assuntos
Doenças do Cão/patologia , Excisão de Linfonodo/veterinária , Mastocitoma/veterinária , Neoplasias Cutâneas/veterinária , Animais , Estudos de Casos e Controles , Doenças do Cão/cirurgia , Cães , Linfonodos/patologia , Metástase Linfática/patologia , Metástase Linfática/prevenção & controle , Mastocitoma/cirurgia , Estudos Retrospectivos , Neoplasias Cutâneas/cirurgia
7.
Can J Vet Res ; 85(4): 302-308, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34602735

RESUMO

Although glucocorticoid administration has produced impressive results in treating canine mast cell tumors (MCTs), in some cases, glucocorticoids fail to reduce the tumor volume, leading to tumor relapse even after treatment. To date, mechanisms involved in glucocorticoid resistance in canine MCTs remain poorly defined. The objective of this study was to establish glucocorticoid-resistant canine MCT cell lines derived from glucocorticoid-sensitive cell lines after prolonged treatment with dexamethasone (Dex). Real-time polymerase chain reaction (RT-PCR) revealed that elevation of glucocorticoid receptor (GR)-regulated gene expression was suppressed in Dex-resistant cell lines after Dex stimulation compared with parent Dex-sensitive cell lines. This indicated that GR-regulated transcription was suppressed in Dex-resistant cell lines. Insufficient expression of GRs was not detected in Dex-resistant cell lines. Possible inhibitors of GR-regulated transcription were increased in mRNA expression in Dex-resistant cell lines. In addition, it was determined that mRNA expression of drug efflux pumps and anti-apoptosis factors was higher in Dex-resistant cell lines. In conclusion, glucocorticoid-resistant canine MCT cell lines have been established that are derived from glucocorticoid-sensitive cell lines. These cell lines suggest that multiple mechanisms contribute to glucocorticoid resistance in canine MCT cells. The mechanisms of glucocorticoid resistance after long-term treatment can be further investigated using these cell lines and a novel therapeutic strategy for glucocorticoid-resistant canine MCT cells can be developed.


Bien que l'administration de glucocorticoïdes ait produit des résultats impressionnants dans le traitement des mastocytomes (MCT) canins, dans certains cas, les glucocorticoïdes ne parviennent pas à réduire le volume tumoral, entraînant une rechute de la tumeur même après le traitement. À ce jour, les mécanismes impliqués dans la résistance aux glucocorticoïdes dans les MCT canins restent mal définis. L'objectif de cette étude était d'établir des lignées cellulaires MCT canines résistantes aux glucocorticoïdes dérivées de lignées cellulaires sensibles aux glucocorticoïdes après un traitement prolongé avec de la dexaméthasone (Dex). La réaction d'amplification en chaîne par polymérase en temps réel (RT-PCR) a révélé que l'élévation de l'expression génique régulée par le récepteur des glucocorticoïdes (GR) était supprimée dans les lignées cellulaires résistantes à Dex après stimulation par Dex par rapport aux lignées cellulaires parentales sensibles à Dex. Cela indiquait que la transcription régulée par GR était supprimée dans les lignées cellulaires résistantes à Dex. Une expression insuffisante des GR n'a pas été détectée dans les lignées cellulaires résistantes à Dex. Les inhibiteurs possibles de la transcription régulée par GR étaient augmentés dans l'expression de l'ARNm dans les lignées cellulaires résistantes à Dex. De plus, il a été déterminé que l'expression de l'ARNm des pompes d'efflux de médicaments et des facteurs anti-apoptose était plus élevée dans les lignées cellulaires résistantes au Dex. En conclusion, des lignées cellulaires canines MCT résistantes aux glucocorticoïdes ont été établies qui sont dérivées de lignées cellulaires sensibles aux glucocorticoïdes. Ces lignées cellulaires suggèrent que de multiples mécanismes contribuent à la résistance aux glucocorticoïdes dans les cellules MCT canines. Les mécanismes de résistance aux glucocorticoïdes après un traitement à long terme peuvent être étudiés plus en détail à l'aide de ces lignées cellulaires et une nouvelle stratégie thérapeutique pour les cellules MCT canines résistantes aux glucocorticoïdes peut être développée.(Traduit par Docteur Serge Messier).


Assuntos
Proliferação de Células/efeitos dos fármacos , Dexametasona/administração & dosagem , Doenças do Cão/tratamento farmacológico , Glucocorticoides/administração & dosagem , Mastocitoma/veterinária , Animais , Dexametasona/farmacologia , Cães , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/farmacologia , Mastocitoma/tratamento farmacológico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
8.
Eur J Immunol ; 51(6): 1482-1493, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33788263

RESUMO

The dimeric cytokine IL-12 is important in the control of various infections but also contributes to the pathology of certain diseases making it a potential target for therapy. However, its specific inhibition with antibodies is complicated by the fact that its two subunits are present in other cytokines: p40 in IL-23 and p35 in IL-35. This has led to erroneous conclusions like the alleged implication of IL-12 in experimental autoimmune encephalomyelitis (EAE). Here, we report the development of a mouse anti-mouse IL-12 vaccine and the production of monoclonal antibodies (mAbs) that do not react with p40 or p35 (in IL-35) but specifically recognize and functionally inhibit the IL-12 heterodimer. Using one of these mAbs, MM12A1.6, that strongly inhibited IFN-γ production and LPS-induced septic shock after viral infection, we demonstrate the critical role played by IL-12 in the rejection of male skin graft by female C57BL/6 syngeneic recipients and in the clearance of an immunogenic mastocytoma tumor variant by DBA/2 mice, but not in a parent to F1 immune aggression model nor in MOG-induced EAE, which was clearly prevented by anti-p40 mAb C17.8. Given this selective inhibition of IL-12, these mAbs provide new options for reassessing IL-12 function in vivo.


Assuntos
Anticorpos Monoclonais/metabolismo , Encefalomielite Autoimune Experimental/imunologia , Rejeição de Enxerto/imunologia , Interleucina-12/metabolismo , Mastocitoma/imunologia , Esclerose Múltipla/imunologia , Infecções por Nidovirales/imunologia , Nidovirales/fisiologia , Subunidades Proteicas/metabolismo , Sepse/imunologia , Transplante de Pele , Animais , Anticorpos Monoclonais/isolamento & purificação , Modelos Animais de Doenças , Epitopos , Humanos , Hibridomas , Interleucina-12/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Neoplasias Experimentais , Subunidades Proteicas/imunologia
9.
Cell Rep Med ; 2(3): 100209, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33763654

RESUMO

Therapeutic vaccination regimens inducing clinically effective tumor-specific CD8+ T lymphocyte (CTL) responses are an unmet medical need. We engineer two distantly related arenaviruses, Pichinde virus and lymphocytic choriomeningitis virus, for therapeutic cancer vaccination. In mice, life-replicating vector formats of these two viruses delivering a self-antigen in a heterologous prime-boost regimen induce tumor-specific CTL responses up to 50% of the circulating CD8 T cell pool. This CTL attack eliminates established solid tumors in a significant proportion of animals, accompanied by protection against tumor rechallenge. The magnitude of CTL responses is alarmin driven and requires combining two genealogically distantly related arenaviruses. Vector-neutralizing antibodies do not inhibit booster immunizations by the same vector or by closely related vectors. Rather, CTL immunodominance hierarchies favor vector backbone-targeted responses at the expense of self-reactive CTLs. These findings establish an arenavirus-based immunotherapy regimen that allows reshuffling of immunodominance hierarchies and breaking self-directed tolerance for efficient tumor control.


Assuntos
Vacinas Anticâncer/administração & dosagem , Imunoterapia/métodos , Vírus da Coriomeningite Linfocítica/imunologia , Mastocitoma/terapia , Vírus Pichinde/imunologia , Linfócitos T Citotóxicos/imunologia , Alarminas/genética , Alarminas/imunologia , Animais , Anticorpos Neutralizantes/farmacologia , Vacinas Anticâncer/genética , Vacinas Anticâncer/imunologia , Feminino , Expressão Gênica , Engenharia Genética/métodos , Vetores Genéticos/classificação , Vetores Genéticos/imunologia , Cobaias , Imunização Secundária , Vírus da Coriomeningite Linfocítica/classificação , Vírus da Coriomeningite Linfocítica/genética , Mastocitoma/genética , Mastocitoma/imunologia , Mastocitoma/mortalidade , Camundongos , Camundongos Endogâmicos C57BL , Filogenia , Vírus Pichinde/classificação , Vírus Pichinde/genética , Tolerância a Antígenos Próprios , Análise de Sobrevida , Vacinação/métodos
11.
J Zoo Wildl Med ; 51(4): 1025-1034, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33480586

RESUMO

Mast cell tumors in nondomestic felids are rarely reported and their biological characteristics are not well described. A retrospective review of the pathology records of 52 zoo-housed cheetahs (Acinonyx jubatus) identified five cases of mast cell tumor, involving four closely related individuals. The age at initial presentation varied from 14 mo to 6 yr. Four cases presented as solitary or multiple cutaneous masses that were mostly slow growing, up to 20 mm diameter, and predominantly nonulcerated. The diagnosis was made by fine needle aspiration cytology of a lesion in one case and by excisional biopsy in the others. Histopathologically, the lesions resembled low- to intermediate-grade canine mast cell tumors, with variations in the degree of anisocytosis and anisokaryosis. Surgical excision was incomplete for 80% of the cutaneous lesions, but local recurrence was not observed in any case. One animal with cutaneous lesions subsequently developed fatal visceral mastocytosis involving the spleen, liver, and adrenal gland. There was no evidence of lymph node invasion or paraneoplastic gastrointestinal signs in any of the cases.


Assuntos
Acinonyx , Mastocitoma/veterinária , Neoplasias Cutâneas/veterinária , Animais , Feminino , Masculino , Mastocitoma/patologia , Mastocitoma/cirurgia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia
12.
Vet Comp Oncol ; 19(4): 616-623, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32951309

RESUMO

Histopathologic surgical margin assessment in veterinary patients is an imprecise science with assessment limited to a small proportion of the surgical margin due to time and finances. Incomplete excision of canine mast cell tumours (MCTs) alters treatment recommendations and prognosis. Optical coherence tomography (OCT) is a novel imaging modality that has been reported in a single veterinary study for surgical margin assessment. Twenty-five dogs with 34 MCTs were enrolled in a prospective pilot-study to assess the imaging characteristics of canine MCTs with OCT and to evaluate the feasibility and utility of OCT-guided histopathology. All dogs underwent routine surgical excision of MCTs. OCT imaging was used to assess the entire surgical margin prior to placement in formalin. Either normal areas or areas suspected of incomplete MCT excision were inked. Standard histopathologic sectioning and tangential sectioning of inked areas were performed and compared to OCT results. OCT identified MCT near the surgical margin in 10 of 26 specimens (38.4%). Four specimens suspicious for incomplete margins on OCT had incomplete MCT excision that was missed on standard histopathologic sectioning. Six specimens had OCT-guided sections taken as suspicious, which did not show MCT on histopathology. OCT-guided pathology sections were able to detect incompletely excised MCT near the surgical margin with a sensitivity of 90% and specificity of 56.2% in this preliminary study. OCT imaging shows promise for guiding pathologists to areas of interest to improve the diagnostic accuracy of surgical margin assessment in excised canine MCTs.


Assuntos
Doenças do Cão , Margens de Excisão , Mastocitoma/veterinária , Tomografia de Coerência Óptica , Animais , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/cirurgia , Cães , Estudos de Viabilidade , Mastocitoma/diagnóstico por imagem , Mastocitoma/cirurgia , Projetos Piloto , Estudos Prospectivos , Tomografia de Coerência Óptica/veterinária
13.
Vet Comp Oncol ; 19(1): 132-139, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32926564

RESUMO

Cutaneous mast cell tumours (MCTs) are the most frequent malignant skin tumours in dogs. Mutations in the c-KIT proto-oncogene are correlated with the pathogenesis and aggressiveness of MCTs. To date, studies have focused on c-KIT mutations and KIT protein localization, with a general lack of mRNA-level analyses. In this study, c-KIT mRNA expression was investigated in canine MCTs by RNA in situ hybridization (RNA-ISH). Furthermore, we evaluated associations between c-KIT mRNA expression and the histological grade, KIT immunohistochemical staining pattern and other clinicopathological parameters. c-KIT mRNA expression was observed in all MCT samples, appearing as clusters of dots in the cytoplasm of neoplastic cells. A significant correlation was detected between c-KIT mRNA expression (quantified according to the H-score and the percentage of positive cells) and the histological grade (determined using two-and three-tier grading systems; P < .05). We also found a significant positive correlation (all P < .05) between c-KIT mRNA expression and the proliferation indices (mitotic index, Ki-67, and Ag67). However, no significant associations with c-KIT expression from RNA-ISH were found with respect to different KIT staining patterns. Overall, these results demonstrate that c-KIT mRNA expression might be an additional tool for measuring the c-KIT status in canine cutaneous MCTs and could serve as a potential prognostic factor. Further studies should evaluate the prognostic significance of c-KIT mRNA expression in a large and uniform cohort of canine MCTs.


Assuntos
Doenças do Cão/metabolismo , Mastocitoma/veterinária , Proteínas Proto-Oncogênicas c-kit/metabolismo , RNA Mensageiro/metabolismo , Neoplasias Cutâneas/veterinária , Animais , Biomarcadores Tumorais , Doenças do Cão/patologia , Cães , Feminino , Regulação Neoplásica da Expressão Gênica , Masculino , Mastocitoma/metabolismo , Mastocitoma/patologia , Prognóstico , RNA Mensageiro/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia
15.
Vet Comp Oncol ; 19(3): 451-462, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32840038

RESUMO

Canine mast cell tumours (MCTs) typically spread to lymph nodes (LNs) before reaching distant sites, and LN assessment is an important part of MCT staging. Sentinel LN (SLN) mapping techniques to identify draining LNs are being developed and could improve the accuracy of MCT staging. The primary objective of this feasibility study was to determine the safety and effectiveness of contrast-enhanced ultrasound (CEUS) to identify SLNs. Secondary objectives were to determine if the SLNs identified by CEUS coincided with the regional LN predicted by the anatomical lymphosomes, if previous MCT excision altered CEUS SLN findings, and if CEUS could identify MCT nodal metastases. Between June 2017 and March 2019, 59 dogs with 62 MCTs were enrolled. No adverse events related to CEUS were reported. CEUS detected at least 1 SLN in 59/62 MCTs (95.2%, 95% CI: 86.5-99.0%). In only 32/59 (54.2%) MCTs, clinicians would have correctly predicted the SLN(s) identified by CEUS. Among the 35 MCTs that had histological examination of the SLN(s), the prevalence of metastasis was 60% (95% CI: 42.1-76.1%). Additional staging procedures did not reveal any metastases in dogs with histologically non-metastatic SLNs. Integration of CEUS SLN mapping into the routine staging of MCTs is promising, but future studies are required to refine this procedure and to investigate if it would translate into a clinical benefit.


Assuntos
Doenças do Cão , Mastocitoma , Linfonodo Sentinela , Ultrassonografia/veterinária , Animais , Meios de Contraste , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/patologia , Cães , Estudos de Viabilidade , Metástase Linfática/diagnóstico por imagem , Mastocitoma/diagnóstico por imagem , Mastocitoma/veterinária , Estadiamento de Neoplasias/veterinária , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/veterinária
16.
Sci Rep ; 10(1): 18918, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33144602

RESUMO

Cutaneous mast cell tumours (MCTs) are common skin neoplasms in dogs. MicroRNAs (miRNAs) are post-transcriptional regulators involved in several cellular processes, and they can function as tumour promoters or suppressors. However, the role of miRNAs in canine MCTs has not yet been elucidated. Thus, the current study aimed to characterize miRNA profiles and to assess their value as biomarkers for MCTs. miRNA expression profiles were assessed in formalin-fixed, paraffin-embedded samples by next-generation sequencing. Ten samples were MCT tissues, and 7 were healthy adjacent tissues. Nine dysregulated miRNAs (DE-miRNAs) were then validated using RT-qPCR in a larger group of MCT samples, allowing the calculation of ROC curves and performance of multiple factor analysis (MFA). Pathway enrichment analysis was performed to investigate miRNA biological functions. The results showed that the expression of 63 miRNAs (18 up- and 45 downregulated) was significantly affected in MCTs. Five DE-miRNAs, namely, miR-21-5p, miR-92a-3p, miR-338, miR-379 and miR-885, were validated by RT-qPCR. The diagnostic accuracy of a panel of 3 DE-miRNAs-miR-21, miR-379 and miR-885-exhibited increased efficiency in discriminating animals with MCTs (AUC = 0.9854) and animals with lymph node metastasis (AUC = 0.8923). Multiple factor analysis revealed clusters based on nodal metastasis. Gene Ontology and KEGG analyses confirmed that the DE-miRNAs were involved in cell proliferation, survival and metastasis pathways. In conclusion, the present study demonstrated that the miRNA expression profile is changed in the MCT microenvironment, suggesting the involvement of the altered miRNAs in the epigenetic regulation of MCTs and identifying miR-21, miR-379 and miR-885 as promising biomarkers.


Assuntos
Biomarcadores Tumorais/genética , Doenças do Cão/genética , Perfilação da Expressão Gênica/veterinária , Mastocitoma/veterinária , MicroRNAs/genética , Neoplasias Cutâneas/veterinária , Animais , Cães , Análise Fatorial , Feminino , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Metástase Linfática , Masculino , Mastocitoma/genética , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Cutâneas/genética , Microambiente Tumoral
17.
BMC Vet Res ; 16(1): 415, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33129329

RESUMO

BACKGROUND: The WW domain-containing oxidoreductase (WWOX) tumor suppressor gene is frequently lost in a variety of solid and hematopoietic malignancies in humans. Dysregulation of WWOX has been implicated as playing a key role in tumor cell survival, DNA damage repair, and genomic stability. The purpose of this study was to characterize WWOX expression in spontaneous canine mast cell tumors (MCTs) and malignant cell lines and investigate the potential contribution of WWOX loss on malignant mast cell behavior. METHODS/RESULTS: WWOX expression is decreased in primary canine MCTs and malignant mast cell lines compared to normal canine bone marrow-cultured mast cells. In transformed canine mastocytoma cell lines, overexpression of WWOX or WWOX knockdown had no effect on mast cell viability. Inhibition of WWOX enhanced clonogenic survival following treatment with ionizing radiation in the C2 mast cell line. Lastly, immunohistochemistry for WWOX was performed using a canine MCT tissue microarray, demonstrating that WWOX staining intensity and percent of cells staining for WWOX is decreased in high-grade MCTs compared to low-grade MCTs. CONCLUSIONS: These data suggest that WWOX expression is attenuated or lost in primary canine MCTs and malignant mast cell lines. Given the observed increase in clonogenic survival in WWOX-deficient C2 mast cells treated with ionizing radiation, further investigation of WWOX and its role in mediating the DNA damage response in malignant mast cells is warranted.


Assuntos
Mastócitos/patologia , Mastocitoma/veterinária , Neoplasias Cutâneas/veterinária , Oxidorredutase com Domínios WW/genética , Animais , Linhagem Celular Tumoral , Cães , Regulação Neoplásica da Expressão Gênica , Mastócitos/metabolismo , Mastócitos/efeitos da radiação , Mastocitoma/metabolismo , Neoplasias Cutâneas/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Oxidorredutase com Domínios WW/metabolismo
19.
Top Companion Anim Med ; 41: 100472, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32891740

RESUMO

Mast cell tumor (MCT) or mastocytoma is one of the most frequent malignant cutaneous tumors in the dog, and the second most frequent in the cat. Several mast cell tumor therapeutic approaches have been proposed in the past years for dogs and cats, resulting in very distinct outcomes. The current comprehensive literature review presents a critical approach to the scientific information published about the MCTs treatments and the subsequent prognosis and survival times, in dogs and in cats diagnosed with MCTs. A systematic review of the literature following the Cochrane principles and methodology was performed. The authors resorted to MEDLINE, Scopus, Google Scholar and Web of Science databases to select the 133 publications with evidence-based treatments for MCTs in companion animals. Results of the review suggest that the recommended treatment, prognosis and survival times for dogs and cats with MCTs depends at all times on the clinical staging, histological grade and location of the tumor.


Assuntos
Doenças do Gato/terapia , Doenças do Cão/terapia , Mastocitoma/veterinária , Neoplasias Cutâneas/veterinária , Animais , Gatos , Cães , Mastocitoma/terapia , Neoplasias Cutâneas/terapia , Resultado do Tratamento
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