RESUMEN
Canine inflammatory mammary cancer (IMC) has been proposed as a model for the study of human inflammatory breast cancer (IBC). The aims of this study were to compare the immunohistochemical expression of aromatase (Arom) and several hormone receptors [estrogen receptor α (ERα), estrogen receptor ß (ERß), progesterone receptor (PR) and androgen receptor (AR)], in 21 IMC cases vs 19 non-IMC; and to study the possible effect of letrozole on canine IMC and human inflammatory breast cancer (IBC) in vitro using IPC-366 and SUM-149 cell lines. Significant elevations of the means of Arom Total Score (TS), ERß TS and PR TS were found in the IMC group (p = 0.025, p = 0.038 and p = 0.037, respectively). Secondary IMC tumours expressed higher levels of Arom than primary IMC (p = 0.029). Non-IMC PR- tumours contained higher levels of Arom than non-IMC PR+ tumours (p = 0.007). After the addition of letrozole, the number of IMC and IBC cells dropped drastically. The overexpression of Arom found and the results obtained in vitro further support canine IMC as a model for the study of IBC and future approaches to the treatment of dogs with mammary cancer, and especially IMC, using Arom inhibitors.
Asunto(s)
Aromatasa/metabolismo , Enfermedades de los Perros/metabolismo , Regulación Enzimológica de la Expresión Génica/fisiología , Regulación Neoplásica de la Expresión Génica/fisiología , Neoplasias Mamarias Animales/enzimología , Receptores de Esteroides/metabolismo , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Aromatasa/genética , Línea Celular Tumoral , Supervivencia Celular , Perros , Femenino , Letrozol , Neoplasias Mamarias Animales/metabolismo , Nitrilos/administración & dosificación , Nitrilos/farmacología , Receptores de Esteroides/genética , Triazoles/administración & dosificación , Triazoles/farmacologíaRESUMEN
In this prospective study, a canine-adapted histological grading method was compared with histopathological and clinical characteristics and was evaluated as a prognostic indicator in canine mammary carcinomas (CMCs). Recruited dogs with at least 1 malignant mammary tumor (n = 65) were clinically evaluated, surgically treated, and followed up (minimum follow-up 28 months, maximum 38 months). Histopathological diagnoses were performed according to Goldschmidt et al (2011). Tumors were graded as grade I (29/65), grade II (19/65), and grade III (17/65). The tumor size, clinical stage, histological diagnosis, presence/absence of myoepithelial proliferation, and regional lymph node metastases at diagnosis were significantly associated with histological grade. The histological grade, age, clinical stage, tumor subtype group, and lymph node metastases at time of diagnosis were significantly associated with the development of recurrences and/or metastases, cancer-associated death, and survival times (disease-free survival and overall survival) in univariate analyses. A subdivision of clinical stage I (T1N0M0) into stages IA and IB was proposed in terms of prognosis. The clinical stage, histological grade, and spay status were selected as independent prognostic variables (multivariate analyses) with disease-free survival as the dependent variable. When overall survival was evaluated as a dependent variable, clinical stage and histological grade were selected as the independent covariates. This grading system is a useful prognostic tool, facilitates histological interpretation, and offers uniform criteria for veterinary pathologists. Comparative studies on CMCs performed in different countries should take into account possible changes in the prognoses due to different proportions of spayed females among the selected dog population.
Asunto(s)
Enfermedades de los Perros/patología , Glándulas Mamarias Animales/patología , Neoplasias Mamarias Animales/patología , Animales , Estudios de Cohortes , Supervivencia sin Enfermedad , Perros , Femenino , Estudios de Seguimiento , Estimación de Kaplan-Meier , Metástasis Linfática , Análisis Multivariante , Clasificación del Tumor/veterinaria , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , RecurrenciaRESUMEN
Human inflammatory breast cancer (IBC) and canine inflammatory mammary cancer (IMC) are the most aggressive and lethal types of mammary tumors with specific characteristics such as exacerbated angiogenesis, lymphangiogenesis and lymphangiotropism. E-cadherin expression is another specific feature of IBC not previously studied in canine IMC. In this study, the expression of E-cadherin and CADM1 (Cell Adhesion molecule 1) and their possible role as key molecules involved in the pathogenesis of IMC were immunohistochemically analyzed in 19 canine IMC and 15 grade III non-IMC cases. E-cadherin and CADM1 expression was higher in IMC cases (p = 0.002, p = 0.008, respectively). In the IMC group, E-cadherin cytoplasmic immunolabeling was more frequent (p = 0.035) and it was associated to the expression of the angiogenic and lymphangiogenic factors COX-2 (p = 0.009), VEGF-A (p = 0.031) and VEGF-D (p = 0.008). The differential mRNA expression between IMC and non-IMC was studied by microarray analysis in 6 cases. E-cadherin gene (CDH1) was not up-regulated in IMC cases at a transcriptional level; interestingly CADM1 was 7-fold upregulated. The differential expression of E-cadherin protein in IMC suggests a possible role of E-cadherin in the characteristic exacerbated angiogenesis and lymphangiogenesis and further support IMC as a natural model for the study of human IBC. Future studies in IBC and IMC including a broad panel of adhesion molecules are necessary to elucidate their role in the metastatic process and angiogenesis.
Asunto(s)
Enfermedades de los Perros , Neoplasias Inflamatorias de la Mama , Neoplasias Mamarias Animales , Animales , Perros , Cadherinas/genética , Cadherinas/metabolismo , Molécula 1 de Adhesión Celular/genética , Enfermedades de los Perros/metabolismo , Neoplasias Inflamatorias de la Mama/metabolismo , Neoplasias Inflamatorias de la Mama/patología , Neoplasias Inflamatorias de la Mama/veterinaria , Neoplasias Mamarias Animales/patología , Neovascularización Patológica/patología , Neovascularización Patológica/veterinariaRESUMEN
Seven of 30 female dogs diagnosed with inflammatory mammary cancer were given chemotherapy and palliative treatment, and the other 23 received only palliative treatment. The median survival time of the seven dogs given chemotherapy was 57 days, compared with 35 days for the 23 given only palliative treatment.
Asunto(s)
Antibacterianos/administración & dosificación , Antiinflamatorios/administración & dosificación , Antineoplásicos/administración & dosificación , Neoplasias de la Mama/veterinaria , Enfermedades de los Perros/terapia , Cuidados Paliativos/métodos , Animales , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Enfermedades de los Perros/mortalidad , Enfermedades de los Perros/patología , Perros , Quimioterapia Combinada , Femenino , Inflamación/veterinaria , Mitoxantrona/administración & dosificación , Análisis Multivariante , Proyectos Piloto , Pronóstico , Estudios Retrospectivos , España , Análisis de Supervivencia , Vincristina/administración & dosificaciónRESUMEN
The aim was to study the effects of flutamide on cell proliferation, in vivo tumour growth and steroid production in canine and human IBC cell lines. IPC-366 and SUM149 cell cultures were exposed to flutamide concentrations for 72 hours. Additionally, IPC-366 and SUM149 xenotransplanted mice were treated subcutaneously with flutamide 3 times a week for 2 weeks. Steroid hormones determination in culture media, serum and tumour homogenates (pregnenolone, progesterone, androstenedione, testosterone, dihydrotestosterone, 17ß-oestradiol and oestrone sulphate) were assayed by EIA. in vitro cell proliferation percentages showed a decrease in all flutamide dosages in IPC-366 and SUM149. in vivo flutamide reduced tumour size by 55% to 65%, and metastasis rates decreased. In treated groups, androgen levels in culture media, serum and tumour homogenates were increased as oestrogen levels decreased. These results suggest that flutamide treatment inhibits cell proliferation and promotes tumour reduction by increasing androgen levels and also support future therapy approaches.
Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Enfermedades de los Perros/tratamiento farmacológico , Flutamida/uso terapéutico , Hormonas Esteroides Gonadales/metabolismo , Neoplasias Mamarias Animales/tratamiento farmacológico , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Androstenodiona/metabolismo , Animales , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Dihidrotestosterona/metabolismo , Perros , Estradiol/metabolismo , Estrona/análogos & derivados , Estrona/metabolismo , Femenino , Humanos , Neoplasias Mamarias Animales/metabolismo , Neoplasias Mamarias Experimentales/metabolismo , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Pregnenolona/metabolismo , Progesterona/metabolismo , Testosterona/metabolismoRESUMEN
Forty-six dogs with pituitary-dependent hyperadrenocorticism were treated with mitotane by the non-selective adrenocorticolysis protocol and 40 were treated twice a day with trilostane. The treatment groups were compared by chi-squared tests, and survival data were analysed using Kaplan-Meier survival plots and a Cox proportional hazard method. The non-selective adrenocorticolysis protocol was very effective (89 per cent), its toxicity was moderate (24 per cent) and there were fewer recurrences (29 per cent) than reported with the classical selective adrenocorticolysis protocol (58 per cent). In a multivariate model, age and bodyweight at diagnosis were significantly negatively correlated with survival time. The median survival time of the dogs treated with trilostane twice a day (900 days) was longer (P=0.05) than that of the dogs treated with mitotane (720 days).
Asunto(s)
Hiperfunción de las Glándulas Suprarrenales/veterinaria , Antineoplásicos Hormonales/uso terapéutico , Dihidrotestosterona/análogos & derivados , Enfermedades de los Perros/tratamiento farmacológico , Mitotano/uso terapéutico , Hiperfunción de las Glándulas Suprarrenales/tratamiento farmacológico , Hiperfunción de las Glándulas Suprarrenales/mortalidad , Factores de Edad , Animales , Antineoplásicos Hormonales/efectos adversos , Peso Corporal/fisiología , Dihidrotestosterona/efectos adversos , Dihidrotestosterona/uso terapéutico , Enfermedades de los Perros/mortalidad , Perros , Femenino , Estimación de Kaplan-Meier , Masculino , Mitotano/efectos adversos , Modelos de Riesgos Proporcionales , Resultado del TratamientoRESUMEN
Inflammatory breast cancer (IBC) is an aggressive type of cancer with poor survival in women. Inflammatory mammary cancer (IMC) in dogs is very similar to human IBC and it has been proposed as a good surrogate model for study the human disease. The aim was to determine if IPC-366 shared characteristics with the IBC cell line SUM149. The comparison was conducted in terms of ability to grow (adherent and nonadherent conditions), stem cell markers expression using flow cytometry, protein production using western blot and tumorigenic capacity. Our results revealed that both are capable of forming long-term mammospheres with a grape-like morphology. Adherent and nonadherent cultures exhibited fast growth in vivo. Stem cell markers expressions showed that IPC-366 and SUM149 in adherent and nonadherent conditions has mesenchymal-like characteristics, E-cadherin and N-cadherin, was higher in adherent than in nonadherent cultures. Therefore, this study determines that both cell lines are similar and IPC-366 is a good model for the human and canine disease.