RESUMO
The non-neuronal cholinergic system refers to the presence of acetylcholine, choline acetyltransferase, acetylcholinesterase and cholinergic receptors, nicotinic and muscarinic (mAChRs) expressed in non-neuronal cells. The presence of mAChRs has been detected in different type of tumor cells and they are linked with tumorigenesis. We had previously documented the expression of mAChRs in murine and human mammary adenocarcinomas and the absence of these receptors in normal mammary cells of the same origins. We also demonstrated that mAChRs are involved in breast cancer progression, pointing to a main role for mAChRs as oncogenic proteins. Since the long term treatment of breast cancer cells with the muscarinic agonist carbachol promoted cell death, here we investigated the ability of low doses of this agonist combined with paclitaxel (PX), a taxane usually administered to treat breast cancer, to inhibit the progression of human MCF-7 tumor cells. We demonstrated that PX plus carbachol reduced cell viability and tumor growth in vitro probably due to a down-regulation in cancer stem cells population and in the expression of ATP "binding cassette" G2 drug extrusion pump; also a reduction in malignant-induced angiogenesis was produced by the in vivo administration of the mentioned combination in a metronomic schedule to MCF-7 tumor-bearing NUDE mice. Our results confirm that mAChRs could be considered as therapeutic targets for metronomic therapy in breast cancer as well as the usefulness of a muscarinic agonist as repositioning drug in the treatment of this type of tumors.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Carbacol/administração & dosagem , Agonistas Colinérgicos/administração & dosagem , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Paclitaxel/administração & dosagem , Receptores Muscarínicos/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Administração Metronômica , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Interações Medicamentosas , Feminino , Humanos , Glândulas Mamárias Animais/irrigação sanguínea , Glândulas Mamárias Animais/efeitos dos fármacos , Glândulas Mamárias Animais/metabolismo , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos Nus , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologiaRESUMO
The present study aimed to evaluate the mechanisms modulated by dietary arginine supplementation to sows during lactation regarding antioxidant capacity and vascularization of mammary glands. At 109 days of gestation, animals were transferred to individual farrowing crates equipped with manual feeders and automatic drinker bowls. Environmental temperature and humidity inside the farrowing rooms were registered every 15 min. At farrowing, sows were assigned in a completely randomized design to a control diet (CON) or the CON diet supplemented with 1.0% L-arginine (ARG). A total of three gilts and two sows were fed the CON diet, whereas three gilts and three sows were fed ARG diets. Sows were fed a fixed amount of 6.0 kg/day, subdivided equally in four delivery times (0700, 1000, 1300 and 1600 h) for 21 days. At weaning, sows were slaughtered and mammary tissue samples and blood from the pudendal vein were collected. Data were analyzed considering each sow as an experimental unit. Differences were considered at P<0.05. L-arginine fed sows presented lower messenger RNA (mRNA) expression for prolactin receptor (P=0.002), angiopoietin1 (P=0.03) and receptor tyrosine kinase (P=0.01); higher mRNA expression for prostaglandin synthase 1 (P=0.01); a trend of decrease for glucocorticoid receptor (P=0.06) and IGF receptor 1 (P=0.07); and a trend (P=0.05) for an increased glutathione peroxidase mRNA expression. The angiopoietin2:angiopoietin1 mRNA ratio tended to increase (P=0.07) in ARG fed sows. L-arginine fed sows had greater (P=0.04) volumetric proportion of blood vessels and a trend of enhance (P=0.07) in the number of blood vessels per mm2. These findings show that 1.0% ARG supplementation to sows activates proliferative mechanisms, may improve mammary tissues' angiogenesis and tended to increase mRNA expression of genes that encode antioxidant enzymes in mammary gland of sows.
Assuntos
Arginina/farmacologia , Dieta/veterinária , Suplementos Nutricionais , Lactação/fisiologia , Glândulas Mamárias Animais/irrigação sanguínea , Suínos/fisiologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Arginina/administração & dosagem , Feminino , Glândulas Mamárias Animais/efeitos dos fármacos , Distribuição AleatóriaRESUMO
Blood supply of mammary gland is extremely important, since it is a crucial factor in the mammary tissue development. The objective of this study was to describe and assess main mammary artery hemodynamic characteristics of lambs with two growth rates, using Doppler ultrasound. Two experimental groups, A and B, (n=10) of female Brazilian Bergamasca lambs were kept under the same management conditions and facilities. There were two phases: Phase 1, from 90 days of age until onset of puberty; Phase 2, from puberty until 1 year of age. During phase 1, a specific diet was formulated to each experimental group to obtain two different average daily gains: 150g, for treatment A, and 250g, for treatment B. During phase 2, there was no difference on the diet offered to both groups. Every 14 days, all animals were weighed and their body condition score was evaluated. Every 60 days, ultrasound exams (Doppler) of mammary artery were performed to obtain resistance and pulsatility indexes. Treatment B lambs showed higher weight gain and higher body condition score (P<0.05). However, for resistance and pulsatility indexes, there was no difference between treatments (P>0.05). Hemodynamic values remained constant, independent of diet or body development presented by the animals. Obtained data is valuable information on Bergamasca ewe lambs development.(AU)
O suprimento sanguíneo da glândula mamária é extremamente importante, uma vez que é um fator crucial para o desenvolvimento do tecido mamário. Assim, a necessidade de registro dos parâmetros de fluxo sanguíneo arterial é evidente. O objetivo do estudo foi descrever e avaliar as principais características hemodinâmicas da artéria mamária de cordeiras submetidas a diferentes taxas de crescimento, usando o ultrassom Doppler. Dois grupos experimentais, A e B, (n=10) de cordeiras da raça Bergamácia brasileira foram mantidas sob as mesmas condições de manejo e instalações. O estudo foi dividido em diferentes fases, sendo: Fase 1, de 90 dias de idade até o início da puberdade; Fase 2, desde a puberdade até 1 ano de idade. Durante a fase 1, dietas específicas foram formuladas para cada grupo experimental, a fim de obter duas médias diferentes de ganho de peso diário: 150g, para o tratamento A, e 250g, para o tratamento B. Durante a Fase 2, não houve diferença na dieta oferecida para os dois grupos. A cada 14 dias, todos os animais foram pesados e determinado o escore de condição corporal. A cada 60 dias, exames de ultrassom (Doppler) da artéria mamária foram realizados a fim de calcular os índices de resistência e pulsatilidade. As cordeiras do tratamento B registrou maior ganho de peso e escore de condição corporal (P<0,05). No entanto, não houve diferença para os índices de resistência e pulsatilidade entre os tratamentos (P>0,05). Os valores hemodinâmicos permaneceram constantes, independente da dieta ou o desenvolvimento do corpo apresentada pelos animais. Assim, os dados obtidos são informações valiosas sobre o desenvolvimento da raça a que se refere.(AU)
Assuntos
Animais , Feminino , Diagnóstico por Imagem/veterinária , Artéria Torácica Interna , Glândulas Mamárias Animais/irrigação sanguínea , Ovinos , Aumento de Peso , Ultrassonografia Doppler/veterináriaRESUMO
Blood supply of mammary gland is extremely important, since it is a crucial factor in the mammary tissue development. The objective of this study was to describe and assess main mammary artery hemodynamic characteristics of lambs with two growth rates, using Doppler ultrasound. Two experimental groups, A and B, (n=10) of female Brazilian Bergamasca lambs were kept under the same management conditions and facilities. There were two phases: Phase 1, from 90 days of age until onset of puberty; Phase 2, from puberty until 1 year of age. During phase 1, a specific diet was formulated to each experimental group to obtain two different average daily gains: 150g, for treatment A, and 250g, for treatment B. During phase 2, there was no difference on the diet offered to both groups. Every 14 days, all animals were weighed and their body condition score was evaluated. Every 60 days, ultrasound exams (Doppler) of mammary artery were performed to obtain resistance and pulsatility indexes. Treatment B lambs showed higher weight gain and higher body condition score (P<0.05). However, for resistance and pulsatility indexes, there was no difference between treatments (P>0.05). Hemodynamic values remained constant, independent of diet or body development presented by the animals. Obtained data is valuable information on Bergamasca ewe lambs development.(AU)
O suprimento sanguíneo da glândula mamária é extremamente importante, uma vez que é um fator crucial para o desenvolvimento do tecido mamário. Assim, a necessidade de registro dos parâmetros de fluxo sanguíneo arterial é evidente. O objetivo do estudo foi descrever e avaliar as principais características hemodinâmicas da artéria mamária de cordeiras submetidas a diferentes taxas de crescimento, usando o ultrassom Doppler. Dois grupos experimentais, A e B, (n=10) de cordeiras da raça Bergamácia brasileira foram mantidas sob as mesmas condições de manejo e instalações. O estudo foi dividido em diferentes fases, sendo: Fase 1, de 90 dias de idade até o início da puberdade; Fase 2, desde a puberdade até 1 ano de idade. Durante a fase 1, dietas específicas foram formuladas para cada grupo experimental, a fim de obter duas médias diferentes de ganho de peso diário: 150g, para o tratamento A, e 250g, para o tratamento B. Durante a Fase 2, não houve diferença na dieta oferecida para os dois grupos. A cada 14 dias, todos os animais foram pesados e determinado o escore de condição corporal. A cada 60 dias, exames de ultrassom (Doppler) da artéria mamária foram realizados a fim de calcular os índices de resistência e pulsatilidade. As cordeiras do tratamento B registrou maior ganho de peso e escore de condição corporal (P<0,05). No entanto, não houve diferença para os índices de resistência e pulsatilidade entre os tratamentos (P>0,05). Os valores hemodinâmicos permaneceram constantes, independente da dieta ou o desenvolvimento do corpo apresentada pelos animais. Assim, os dados obtidos são informações valiosas sobre o desenvolvimento da raça a que se refere.(AU)
Assuntos
Animais , Feminino , Glândulas Mamárias Animais/irrigação sanguínea , Glândulas Mamárias Animais , Ovinos , Artéria Torácica Interna , Aumento de Peso , Ultrassonografia Doppler/veterináriaRESUMO
This study aimed to evaluate the sonographic characteristics of the udder and teats and to determine the Doppler indexes of mammary artery in healthy and undergoing subclinical and clinical mastitis goats. Thirty animals among Saanen and Alpine Brown goats were arranged in three groups, healthy goats (HG), goats with subclinical mastitis (SMG) and goats with clinical mastitis (CMG). Using the B-mode, the sonographic characteristics (echotexture and echogenicity) and biometry (diameter and area of the udder cistern, diameter and area of the teat cistern and thickness of the teat wall) were evaluated. Using Doppler ultrasonography, the vascular indexes of the mammary artery were obtained. It was observed hyperechogenicity with solid component in the gland cistern when comparing animals with clinical mastitis and healthy mammary tissue. Regarding the echotexture of the breast tissue, there was heterogeneity in the mammary parenchyma on the three groups, for the milk, it was observed homogeneity for animals on HG and SMG and heterogeneity for animals on CMG. Grey-scale quantitative assessment revealed increase in echogenicity (mean value) for all the structures when comparing the three groups. Biometry did not reveal statistical difference between groups, for none of the evaluated structures. Doppler examination of the mammary artery showed the decrease of end diastolic velocity and raise of pulsatility index between groups. The association of B-mode and Doppler ultrasonography is useful for the evaluation of the udder of dairy goats with mastitis. It is a sensitive and specific method for the study of this disease. Doppler mode was unable to establish reliable criteria for diagnosis of subclinical mastitis. Moreover, the quantification of echogenicity is a useful technique for the evaluation of the milk in animals with mastitis; therefore, it is suggested that it can be used as complementary technique for the diagnosis of mastitis in goats.
Assuntos
Doenças das Cabras/diagnóstico , Glândulas Mamárias Animais/diagnóstico por imagem , Mastite/veterinária , Ultrassonografia/veterinária , Animais , Feminino , Doenças das Cabras/diagnóstico por imagem , Doenças das Cabras/patologia , Cabras , Glândulas Mamárias Animais/irrigação sanguínea , Glândulas Mamárias Animais/patologia , Mastite/diagnóstico , Mastite/diagnóstico por imagem , Ultrassonografia/métodosRESUMO
Prenatal exposure to BPA disturbs mammary gland histoarchitecture and increases the carcinogenic susceptibility to chemical challenges administered long after BPA exposure. Our aim was to assess the effect of prenatal BPA exposure on mammary gland angiogenesis and steroid hormone pathways in virgin cycling rats. Pregnant Wistar rats were exposed to either 25 or 250 g/kg/day (25 and 250 BPA, respectively) or to vehicle. Female offspring were autopsied on postnatal day (PND) 50 or 110. Ovarian steroid serum levels, the expression of steroid receptors and their co-regulators SRC-3 and SMRT in the mammary gland, and angiogenesis were evaluated. At PND 50, all BPA-treated animals had lower serum levels of progesterone, while estradiol levels remained unchanged. The higher dose of BPA increased mammary ERα and decreased SRC-3 expression at PND 50 and PND 110. SMRT protein levels were similar among groups at PND 50, whereas at PND 110, animals exposed to 250 BPA showed a lower SMRT expression. Interestingly, in the control and 25 BPA groups, SMRT increased from PND 50 to PND 110. At PND 50, an increased vascular area associated with higher VEGF expression was observed in the 250 BPA-treated rats. At PND 110, the vascular area was still increased, but VEGF expression was similar to that of control rats. The present results demonstrate that prenatal exposure to BPA alters the endocrine environment of the mammary gland and its angiogenic process. Increased angiogenesis and altered steroid hormone signals could explain the higher frequency of pre-neoplastic lesions found later in life. This article is part of a Special Issue entitled 'Endocrine disruptors'.
Assuntos
Disruptores Endócrinos/efeitos adversos , Glândulas Mamárias Animais/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Fenóis/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Animais , Compostos Benzidrílicos , Estradiol/sangue , Receptor alfa de Estrogênio/biossíntese , Feminino , Glândulas Mamárias Animais/irrigação sanguínea , Glândulas Mamárias Animais/patologia , Gravidez , Progesterona/sangue , Ratos , Ratos Wistar , Proteínas Adaptadoras da Sinalização Shc/biossíntese , Proteína 3 de Transformação que Contém Domínio 2 de Homologia de SrcRESUMO
Analisamos a distribuição e arranjo vascular das artérias da papila mamária (PM) em 45 cães adultos, de diferentes idades, sem raça definida, 15 cadelas multíparas, 15 nulíparas e 15 machos. Objetivamos comparar a irrigação das papilas mamárias nestes grupos para aplicações em morfologia, reprodução, clínica, cirurgia (segmentectomia) e áreas correlacionadas. Os espécimes foram colhidos no Centro de Zoonoses de Goiânia, injetamos látex, fixamos e analisamos o complexo mamário de cada um por dissecação e radiografia. A irrigação da papila mamária foi classificada em: direta terminal (DT), direta contínua (DC) e indireta (I). O modelo de irrigação direta terminal predominou nos pares de mamas 1 e 3 nos três grupos estudados, apresentando maior freqüência, porém pouco significativa, no par de mamas 2 em nulíparas, e certa equivalência com o tipo de irrigação indireta em multíparas e machos neste mesmo par de mamas. A irrigação do tipo indireta predominou no par de mamas 4 e, no par 5 este modelo de irrigação foi descrito em 100 por cento dos casos analisados.
Assuntos
Animais , Masculino , Feminino , Cães , Cães , Glândulas Mamárias Animais/irrigação sanguínea , Anatomia ComparadaRESUMO
Analisamos a distribuição e arranjo vascular das artérias da papila mamária (PM) em 45 cães adultos, de diferentes idades, sem raça definida, 15 cadelas multíparas, 15 nulíparas e 15 machos. Objetivamos comparar a irrigação das papilas mamárias nestes grupos para aplicações em morfologia, reprodução, clínica, cirurgia (segmentectomia) e áreas correlacionadas. Os espécimes foram colhidos no Centro de Zoonoses de Goiânia, injetamos látex, fixamos e analisamos o complexo mamário de cada um por dissecação e radiografia. A irrigação da papila mamária foi classificada em: direta terminal (DT), direta contínua (DC) e indireta (I). O modelo de irrigação direta terminal predominou nos pares de mamas 1 e 3 nos três grupos estudados, apresentando maior freqüência, porém pouco significativa, no par de mamas 2 em nulíparas, e certa equivalência com o tipo de irrigação indireta em multíparas e machos neste mesmo par de mamas. A irrigação do tipo indireta predominou no par de mamas 4 e, no par 5 este modelo de irrigação foi descrito em 100 por cento dos casos analisados. (AU)
We analyzed the distribution and the arterial vascular arrangement of the mammary papilla (MP) in 45 adult mongrel dogs: 15 multiparous females, 15 nulliparous and 15 males. Our ai consists of comparing the irrigation of mammary papillas in these groups for applications in morphology, reproduction, clinic, surgery (anatomicosurgical segmentation) and correlated areas. The specimens were collected in the Center of Zoonosis of Goiânia, they were injected with latex substance, fixed, and then their mammary complexes were analyzed by dissection and also by radiograph. The irrigation of the mammary papilla was classified in direct terminal (DT), direct continuous (DC) and indirect (I). The irrigation of the terminal direct type predominated in the pairs of antimerous 1 and 3 in the three studied groups, showing higher frequency, and not significant in the pair of mamma 2 in nulíparas, and equivalence in comparison to the type of indirect irrigation in multíparas and males in this exactly pair of mama. The type of indirect irrigation prevailed in the pair of mamma 4 and, in the pair of mamma 5, this model of irrigation was described in 100% of the analyzed cases. (AU)
Assuntos
Animais , Cães , Cães , Glândulas Mamárias Animais/irrigação sanguínea , Anatomia ComparadaRESUMO
In order to clearly visualize blood vessels, the monoclonal antibody (mAb) MEC 13.3 was used for an immunohistochemical staining on frozen sections of different mice mammary tumors. MEC 13.3 mAb is specific for endothelial cells (ECs) of mouse blood vessels and recognizes a molecule related to the murine form of CD31/PECAM. This mAb with immunoenzymatic technique or immunofluorescent labelling, was found to be a useful tool to quantify tumor neovascularization. Specifically, membrane reinforcement could be observed in vessel ECs, indicating the expression of CD31/ PECAM in their surface. The staining of ECs from tumors and from normal tissues was also compared. In this work, the use of MEC13.3 mAb is reported to recognize mice mammary tumor ECs as a useful tool to identify neovascularization. It would also be helpful for research on the origin and function of vascular endothelium in murine tumor experimental models.
Assuntos
Adenocarcinoma , Anticorpos Monoclonais , Endotélio Vascular/imunologia , Neoplasias Mamárias Experimentais , Animais , Especificidade de Anticorpos , Reações Antígeno-Anticorpo , Endotélio Vascular/química , Endotélio Vascular/citologia , Feminino , Imuno-Histoquímica , Glândulas Mamárias Animais/irrigação sanguínea , Glândulas Mamárias Animais/citologia , Camundongos , Camundongos Endogâmicos BALB C , Microcirculação , Células Tumorais CultivadasRESUMO
In order to clearly visualize blood vessels, the monoclonal antibody (mAb) MEC 13.3 was used for an immunohistochemical staining on frozen sections of different mice mammary tumors. MEC 13.3 mAb is specific for endothelial cells (ECs) of mouse blood vessels and recognizes a molecule related to the murine form of CD31/PECAM. This mAb with immunoenzymatic technique or immunofluorescent labelling, was found to be a useful tool to quantify tumor neovascularization. Specifically, membrane reinforcement could be observed in vessel ECs, indicating the expression of CD31/ PECAM in their surface. The staining of ECs from tumors and from normal tissues was also compared. In this work, the use of MEC13.3 mAb is reported to recognize mice mammary tumor ECs as a useful tool to identify neovascularization. It would also be helpful for research on the origin and function of vascular endothelium in murine tumor experimental models.(AU)