Person: Cáceres Ramos, Sara Cristina
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First Name
Sara Cristina
Last Name
Cáceres Ramos
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Veterinaria
Department
Fisiología
Area
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16 results
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Now showing 1 - 10 of 16
Item Establishment and Characterization of a New Cell Line of Canine Inflammatory Mammary Cancer: IPC-366(PLoS ONE, 2015) Cáceres Ramos, Sara Cristina; Peña Fernández, Laura Luisa; Andrés Gamazo, Paloma Jimena De; Illera Del Portal, Josefina María; Lopez, Mirtha S.; Woodward, Wendy A.; Reuben, James M.; Illera Del Portal, Juan CarlosCanine inflammatory mammary cancer (IMC) shares epidemiologic, histopathological and clinical characteristics with the disease in humans and has been proposed as a natural model for human inflammatory breast cancer (IBC). The aim of this study was to characterize a new cell line from IMC (IPC-366) for the comparative study of both IMC and IBC. Tumors cells from a female dog with clinical IMC were collected. The cells were grown under adherent conditions. The growth, cytological, ultrastructural and immunohistochemical (IHC) characteristics of IPC-366 were evaluated. Ten female Balb/SCID mice were inoculated with IPC-366 cells to assess their tumorigenicity and metastatic potential. Chromosome aberration test and Karyotype revealed the presence of structural aberration, numerical and neutral rearrangements, demonstrating a chromosomal instability. Microscopic examination of tumor revealed an epithelial morphology with marked anysocytosis. Cytological and histological examination of smears and ultrathin sections by electron microscopy revealed that IPC-366 is formed by highly malignant large round or polygonal cells characterized by marked atypia and prominent nucleoli and frequent multinucleated cells. Some cells had cytoplasmic empty spaces covered by cytoplasmic membrane resembling capillary endothelial cells, a phenomenon that has been related to s vasculogenic mimicry. IHC characterization of IPC-366 was basal-like: epithelial cells (AE1/AE3+, CK14+, vimentin+, actin-, p63-, ER-, PR-, HER-2, E-cadherin, overexpressed COX-2 and high Ki-67 proliferation index (87.15 %). At 2 weeks after inoculating the IPC-366 cells, a tumor mass was found in 100 % of mice. At 4 weeks metastases in lung and lymph nodes were found. Xenograph tumors maintained the original IHC characteristics of the female dog tumor. In summary, the cell line IPC-366 is a fast growing malignant triple negative cell line model of inflammatory mammary carcinoma that can be used for the comparative study of both IMC and IBC.Item Long‐Term Exposure to Isoflavones Alters the Hormonal Steroid Homeostasis‐Impairing Reproductive Function in Adult Male Wistar Rats(Nutrients, 2023) Cáceres Ramos, Sara Cristina; Crespo, Belen; Alonso Diez, Angela; Andrés Gamazo, Paloma Jimena De; Millán Pastor, María Pilar; Silván Granado, Gema; Illera Del Portal, Josefina María; Illera Del Portal, Juan CarlosThe consumption of isoflavones is gaining popularity worldwide due to their beneficial effects on health. However, isoflavones are considered to be endocrine disruptors and cause deleterious effects on hormone‐sensitive organs, especially in males. Therefore, this study aimed to deter‐ mine if a continuous and prolonged exposure to isoflavones in adult males altered the endocrine axis effect of testicular function. For this purpose, seventy‐five adult male rats were administered with low and high mixtures of isoflavones (genistein and daidzein) for 5 months. The determination of steroid hormones (progesterone, androstenedione, dehydroepiandrosterone, testosterone, dihydrotestosterone, 17β‐estradiol, and estrone sulphate) was carried out in serum and testicular homogenate samples. Sperm quality parameters and testicular histology were also determined. The results revealed that low and high doses of isoflavones promote a hormonal imbalance in androgen and estrogen production, resulting in a decrease in circulating and testicular androgen levels and an increase in estrogen levels. These results are associated with a reduction in the sperm quality parameters and a reduction in the testicular weight, both in the diameter of the seminiferous tubules and the height of the germinal epithelium. Altogether, these results suggest that a continuous ex‐ posure to isoflavones in adult male rats causes a hormonal imbalance in the testes that disrupts the endocrine axis, causing defects in testicular function.Item Androgen and Estrogen β Receptor Expression Enhances Efficacy of Antihormonal Treatments in Triple-Negative Breast Cancer Cell Lines(International Journal of Molecular Sciences, 2024) Crespo, Belén; Illera Del Portal, Juan Carlos; Silván Granado, Gema; Lopez-Plaza, Paula; Herrera de la Muela, María; De La-Puente Yagüe, Miriam; Díaz Del Arco, Cristina; Illera, María José; Cáceres Ramos, Sara CristinaThe triple-negative breast cancer (TNBC) subtype is characterized by the lack of expression of ERα (estrogen receptor α), PR (progesterone receptor) and no overexpression of HER-2. However, TNBC can express the androgen receptor (AR) or estrogen receptor β (ERβ). Also, TNBC secretes steroid hormones and is influenced by hormonal fluctuations, so the steroid inhibition could exert a beneficial effect in TNBC treatment. The aim of this study was to evaluate the effect of dutasteride, anastrozole and ASP9521 in in vitro processes using human TNBC cell lines. For this, immunofluorescence, sensitivity, proliferation and wound healing assays were performed, and hormone concentrations were studied. Results revealed that all TNBC cell lines expressed AR and ERβ; the ones that expressed them most intensely were more sensitive to antihormonal treatments. All treatments reduced cell viability, highlighting MDA-MB-453 and SUM-159. Indeed, a decrease in androgen levels was observed in these cell lines, which could relate to a reduction in cell viability. In addition, MCF-7 and SUM-159 increased cell migration under treatments, increasing estrogen levels, which could favor cell migration. Thus, antihormonal treatments could be beneficial for TNBC therapies. This study clarifies the importance of steroid hormones in AR and ERβ-positive cell lines of TNBC.Item Canine cell line, IPC‐366, as a good model for the study of inflammatory breast cancer(Veterinary and Comparative Oncology, 2016) Cáceres Ramos, Sara Cristina; Peña Fernández, Laura Luisa; Lacerda, Lara; Illera Del Portal, Josefina María; Andrés Gamazo, Paloma Jimena De; Larson, Richard; Gao, Hui; Debeb, Bisrat; Woodward, Wendy; Reuben, James; Illera Del Portal, Juan CarlosInflammatory 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.Item Predicting Sex in White Rhinoceroses: A Statistical Model for Conservation Management(Animals, 2023) Martínez, Leticia; Andrés Gamazo, Paloma Jimena De; Caperos, José Manuel; Silván Granado, Gema; Fernández-Morán, Jesús; Casares, Miguel; Crespo, Belén; Vélez Serrano, Daniel; Sanz San Miguel, Luis; Cáceres Ramos, Sara Cristina; Illera Del Portal, Juan CarlosEnsuring the effective management of every rhinoceros population is crucial for securing a future for the species, especially considering the escalating global threat of poaching and the challenges faced in captive breeding programs for this endangered species. Steroid hormones play pivotal roles in regulating diverse biological processes, making fecal hormonal determinations a valuable non-invasive tool for monitoring adrenal and gonadal endocrinologies and assessing reproductive status, particularly in endangered species. The purpose of this study was to develop a statistical model for predicting the sex of white rhinoceroses using hormonal determinations obtained from a single fecal sample. To achieve this, 562 fecal samples from 15 individuals of the Ceratotherium simum species were collected, and enzyme immunoassays were conducted to determine the concentrations of fecal cortisol, progesterone, estrone, and testosterone metabolites. The biological validation of the method provided an impressive accuracy rate of nearly 80% in predicting the sex of hypothetically unknown white rhinoceroses. Implementing this statistical model for sex identification in white rhinoceroses would yield significant benefits, including a better understanding of the structure and dynamics of wild populations. Additionally, it would enhance conservation management efforts aimed at protecting this endangered species. By utilizing this innovative approach, we can contribute to the preservation and long-term survival of white rhinoceros populations.Item Physiological Stress Responses in Cattle Used in the Spanish Rodeo(Animals, 2023) Cáceres Ramos, Sara Cristina; Moreno, Julia; Crespo, Belen; Silván Granado, Gema; Illera Del Portal, Juan CarlosCertain events can cause distress in cattle. In Spain, there is a sport similar to rodeo called persecution and takedown, in which calves are harassed and knocked down by riders. In this study, the physiological stress response of calves (n = 260) is assessed by measuring hormonal physiological parameters. Salivary samples were collected from Salers (n = 110) and Lidia (n = 150) calves before, during, and after the persecution and takedown event. The hormones epinephrine, cortisol, serotonin, and dopamine were determined in saliva samples using enzyme-immunoassay techniques. The results obtained revealed that epinephrine and cortisol levels increased during the event in Salers calves, with a significant increase (p < 0.05) in the case of epinephrine, although after the event, these values returned to their initial state. Therefore, this sport supposes an assumable punctual stressor stimulus for the animal. In contrast, in Lidia calves, cortisol and epinephrine levels decreased, with a significant decrease (p < 0.05) in the case of cortisol, which may be related to the temperament of this breed and facing a stressful situation in a different manner. This is confirmed by serotonin and dopamine levels that were altered in Lidia calves with respect to the other group studied. In conclusion, the sport of persecution and takedown produces a physiological response of adaptive stress assumable for the animalsItem In vitro and in vivo effect of flutamide on steroid hormone secretion in canine and human inflammatory breast cancer cell lines(Veterinary and Comparative Oncology, 2017) Cáceres Ramos, Sara Cristina; Monsalve, Beatriz; Peña Fernández, Laura Luisa; Andrés Gamazo, Paloma Jimena De; Alonso‐Diez, Ángela; Illera Del Portal, Josefina María; Woodward, Wendy; Reuben, James; Silván Granado, Gema; Illera Del Portal, Juan CarlosThe aim was to study the effects of flutamide on cell proliferation, in vivo tumour growth andsteroid production in canine and human IBC cell lines. IPC-366 and SUM149 cell cultures wereexposed to flutamide concentrations for 72 hours. Additionally, IPC-366 and SUM149 xeno-transplanted mice were treated subcutaneously with flutamide 3 times a week for 2 weeks.Steroid hormones determination in culture media, serum and tumour homogenates (pregneno-lone, progesterone, androstenedione, testosterone, dihydrotestosterone, 17β-oestradiol andoestrone sulphate) were assayed by EIA. in vitro cell proliferation percentages showed adecrease in all flutamide dosages in IPC-366 and SUM149. in vivo flutamide reduced tumoursize by 55% to 65%, and metastasis rates decreased. In treated groups, androgen levels in cul-ture media, serum and tumour homogenates were increased as oestrogen levels decreased. These results suggest that flutamide treatment inhibits cell proliferation and promotes tumourreduction by increasing androgen levels and also support future therapy approachesItem Non-Invasive Determination of Annual Fecal Cortisol, Androstenedione, and Testosterone Variations in a Herd of Male Asian Elephants (Elephas maximus) and Their Relation to Some Climatic Variables(Animals, 2021) Andrés Gamazo, Paloma Jimena De; Cáceres Ramos, Sara Cristina; Belén Crespo; Silván Granado, Gema; Illera Del Portal, Juan CarlosThe measurement of stress and reproductive hormones in wild animal species by non-invasive methods is of special interest. To assess whether the adrenal and gonadal hormones show annual variations in male Asian elephants (Elephas maximus) and to evaluate whether there is any influence of climatic variables on hormonal secretion, fecal samples were taken from a herd of 7 Asian elephants over a 14-month period to subsequently determine the concentrations of testosterone (T), androstenedione (A4), and cortisol (C) by a validated immunoassay technique. Data referring to three climatic variables in the place and period of study were collected, namely monthly mean values of temperature, humidity and rainfall. Levels of T and A4 showed two major increases in July (T: 1088.35 ± 131.04 ng/g; A4: 480.40 ± 50.86 ng/g) and October (T: 825.09 ± 31.60 ng/g; A4: 319.96 ± 32.69 ng/g) (p < 0.05). Our results show a secretion of fecal androgens dependent on temperature (T and A4), and humidity (T). Male musth was detected during the initial increases of T and A4 levels. The highest concentrations of C were observed in September (156.67 ± 60.89 ng/g) (p < 0.05), probably due to the stressful fights that occurred during the musth period. The observed results of the fecal levels of T, A4 and C were similar to those obtained by invasive methods. In conclusion, fecal secretion of the three hormones in these captive male Asian elephants showed variations related in some cases to different weather factors.- Project number: 240
Item El perro en investigación animal: Enseñanzas en manejo y procesos para incrementar el bienestar animal(II)(2020) Millán Pastor, María Pilar; González Gil, Alfredo; Mayenco Aguirre, Ana María; Fernández-Pacheco Martorell, Carlota Almudena; García-Velasco Fernández, Carmen; Jerónimo Sánchez, Benedicto; Feyjoo Vico, Pablo; Silván Granado, Gema; Illera Del Portal, Josefina María; Fernández-Pacheco Martorell, Jacobo; Cáceres Ramos, Sara CristinaEl perro es un animal utilizado en investigación en diversos campos como son los estudios fisiológicos farmacológicos u otros de carácter quirúrgico. El bienestar animal es un punto fundamental para el éxito de la experimentación. Por ello, la enseñanza en buenas prácticas en el cuidado y manejo de perros, conduce a mejorar el bienestar de los mismos y a incrementar el conocimiento sobre la biología y el comportamiento de los animales por parte del alumno. La utilización de nuevas tecnologías que incluyen videos, imágenes o esquemas donde se puedan explicar las mejores condiciones de alojamiento, cuidados, técnicas de manejo del animal para la administración de sustancias o la toma de muestras, permite ver y aprender detenidamente todos los procesos. Todos los métodos deben seguir la Guía sobre el Cuidado y Utilización del Animal de Laboratorio y la Directiva 2010/63/UE del Parlamento Europeo y del Consejo de 22 de septiembre de 2010 y a Real Decreto 53/2013, de 1 de febrero, por el que se establecen las normas básicas aplicables para la protección de los animales utilizados en experimentación y otros fines científicos, incluyendo la docencia. http://www.boe.es/boe/dias/2013/02/08/pdfs/BOE-A-2013-1337.pdf. Endicho R.D. se regula fundamentalmente lo siguiente: Artículo 4. Principio de reemplazo, reducción y refinamiento. En este proyecto se podrán explicar con vídeos, imágenes y textos de apoyo los diferentes puntos a desarrollar utilizando adecuadamente muy pocos animales pero sin embargo dando una gran e importante información sobre la utilización de perros en investigación, ética y bienestar animal. Dado que este proyecto es continuación de un proyecto anterior (PIMCD nº380,2014) En el proyecto se hará un pequeño recordatorio en algunos puntos ya realizado y poniendo especial hincapié en los capítulos no abarcados en el primer proyecto. Se apoyará en los siguientes capítulos ya desarrollados: 1.- Bases biológicas, fisiológicas y etológicas de la especie canina. En este punto se desarrollarán aspectos específicos de esta especie como es la fisiología reproductiva o las diferentes características de las distintas razas y cuáles son las más adecuadas para experimentación. 2.- Alojamiento, medioambiente y condiciones sanitarias. Se expondrán las condiciones de alojamiento en cuanto al tipo de perreras, sus características en tamaño y construcción. También se proporcionará información sobre las condiciones de luz, temperatura y humedad recomendadas por la legislatura. Un punto importante será tratar los aspectos higiénico-sanitarios del espacio y del animal. 3.- Necesidades sociales, nutricionales y de ejercicio. Aspecto fundamental para que los animales se encuentren en un entorno favorable, incluyendo programas de enriquecimiento ambiental que cubra sus necesidades psicológicas que colaboren en el bienestar animal. 4.- Técnicas de manejo y sujeción. Medidas necesarias para realizar los procesos experimentales en las mejores condiciones posibles, evitando factores estresantes y disconfort del animal. En los capítulos que a continuación se relatan, se hará un estudio en profundidad de los mismos 1- Procedimientos menores comunes en experimentación. En este capítulo se abordarán técnicas básicas de administración de sustancias o de recogida de muestras. Se explicaran las diferentes metodologías para la administración y dosificación de sustancias distintas vías. Vía oral de sustancias líquidas y sólidas; vía subcutánea; vía intramuscular y vía intravenosa. 2.- También se pondrá especial dedicación a la recogida de semen y el análisis de sus características así como a las procedimientos para realizar una inseminación artificial. 3.- Técnicas de recogida de muestras sanguíneas, de orina y dermatológicas. 4.-- Bases sobre anestesia y analgesia. En este punto se orientará sobre las bases de la anestesia y analgesia del perro, los productos que se utilizan, la adecuación del proceso y las diferentes técnicas anestésicas. 7.- Protección del personal. Tan importante como todo lo anterior, el conocer el comportamiento de los animales y las diferentes técnicas de manejo, conlleva el saber cómo actuar con los perros para evitar y prevenir accidentes. Para el desarrollo del proyecto se utilizarán 6-8 perros Beagle machos y hembras, pertenecientes al Departamento de Fisiología Animal de la Facultad de Veterinaria UCM, alojados en el animalario adscrito al mismo Departamento con nº de registro Ex 011 U. Dichos animales y dependencias del Departamento serán generosamente cedidos para la realización del proyecto. Item Tumor Growth Progression in Ectopic and Orthotopic Xenografts from Inflammatory Breast Cancer Cell Lines(Veterinary Sciences, 2021) Cáceres Ramos, Sara Cristina; Alonso-Diez, Angela; Crespo, Belén; Peña Fernández, Laura Luisa; Illera Del Portal, Josefina María; Silván Granado, Gema; Andrés Gamazo, Paloma Jimena De; Illera Del Portal, Juan CarlosXenografts can grow in immunosuppressed hosts, such as SCID mice, and tumor material can be injected into hosts either ectopically or orthotopically. Choosing the correct model to use is a crucial step in animal research. The aim of this study was to report the differences between ectopic and orthotopic xenografts in tumor progression, metastasis capacity, histological features, and steroid hormone profiles in xenografts from the cIMC (canine inflammatory mammary cancer) cell line IPC-366 and hIBC (human inflammatory breast cancer) cell line SUM149. To achieve this purpose, 40 female mice 6–8 weeks old were inoculated with IPC-366 and SUM149 cells subcutaneously (ectopic models) or into mammary fat pad (orthotopic models). Mice were monitored for tumor progression and appearance of metastases, and generated tumors were analyzed in terms of histological examination and steroid hormone production. The results revealed differences in tumor appearance and percentage of metastasis between ectopic and orthotopic models, which were higher in the ectopic xenografts from both cell lines. However, both models had similar characteristics of tumor progression, histological features, and steroid hormone secretion profiles. We show that the ectopic model can be validated as a good and useful model of tumor development in addition to, not contrary to, the orthotopic model in breast cancer research.