Cáceres Ramos, Sara Cristina

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Sara Cristina
Last Name
Cáceres Ramos
Universidad Complutense de Madrid
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Now showing 1 - 9 of 9
  • Publication
    Blocking Estrogen Synthesis Leads to Different Hormonal Responses in Canine and Human Triple Negative Inflammatory Breast Cancer
    (MDPI, 2021-10-02) Cáceres Ramos, Sara Cristina; Beatriz Monsalve; Angela Alonso-Diez; Belén Crespo; Illera Del Portal, Josefina María; Andrés Gamazo, Paloma Jimena De; Silván Granado, Gema; Illera Del Portal, Juan Carlos
    Blocking estrogen synthesis by inhibitors of estrogen synthesis is a widely used therapy against estrogen receptor-positive tumors. However, these therapies are less effective in negative expression tumors. Therefore, this study determined the effectiveness of anti-aromatase and anti-sulfatase therapies in canine and human inflammatory breast cancer. Cell cultures and xenografts from IPC-366 and SUM149 were treated with different doses of letrozole (anti-aromatase) and STX-64 (anti-sulfatase), in order to observe their effectiveness in terms of cell proliferation, tumor progression, and the appearance of metastases and hormonal profiles. The results revealed that both treatments are effective in vitro since they reduce cell proliferation and decrease the secreted estrogen levels. In xenograft mice, while treatment with letrozole reduces tumor progression by 30-40%, STX-64 increases tumor progression by 20%. The hormonal results obtained determined that STX-64 produced an increase in circulating and intratumoral levels of estradiol, which led to an increase in tumor progression. However, letrozole was able to block estrogen synthesis by decreasing the levels of circulating and intratumoral estrogen and thus slowing down tumor progression. In conclusion, letrozole can be an effective treatment for canine and human inflammatory breast cancer. The knowledge of the hormonal profile of breast tumors reflects useful information on the effectiveness of different endocrine treatments.
  • Publication
    Tumor Growth Progression in Ectopic and Orthotopic Xenografts from Inflammatory Breast Cancer Cell Lines
    (MDPI, 2021-09-13) 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 Carlos
    Xenografts 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.
  • Publication
    The inhibition of steroid hormones determines the fate of IPC-366 tumor cells, highlighting the crucial role of androgen production in tumor processes
    (Elsevier, 2023-06-01) Crespo, Belen; Cáceres Ramos, Sara Cristina; Silván Granado, Gema; Illera Del Portal, Josefina María; Illera Del Portal, Juan Carlos
    Inflammatory mammary cancer (IMC) is a disease that affects female dogs. It is characterized by poor treatment options and no efficient targets. However, anti-androgenic and anti-estrogenic therapies could be effective because IMC has a great endocrine influence, affecting tumor progression. IPC-366 is a triple negative IMC cell line that has been postulated as a useful model to study this disease. Therefore, the aim of this study was to inhibit steroid hormones production at different points of the steroid pathway in order to determine its effect in cell viability and migration in vitro and tumor growth in vivo. For this purpose, Dutasteride (anti-5αReductase), Anastrozole (anti-aromatase) and ASP9521 (anti-17βHSD) and their combinations have been used. Results revealed that this cell line is positive to estrogen receptor β (ERβ) and androgen receptor (AR) and endocrine therapies reduce cell viability. Our results enforced the hypothesis that estrogens promote cell viability and migration in vitro due to the function of E1SO4 as an estrogen reservoir for E2 production that promotes the IMC cells proliferation. Also, an increase in androgen secretion was associated with a reduction in cell viability. Finally, in vivo assays showed large tumor reduction. Hormone assays determined that high estrogen levels and the reduction of androgen levels promote tumor growth in Balb/SCID IMC mice. In conclusion, estrogen levels reduction may be associated with a good prognosis. Also, activation of AR by increasing androgen production could result in effective therapy for IMC because their anti-proliferative effect.
  • Publication
    Long‐Term Exposure to Isoflavones Alters the Hormonal Steroid Homeostasis‐Impairing Reproductive Function in Adult Male Wistar Rats
    (MDPI, 2023-03-02) 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 Carlos
    The 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.
  • Publication
    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
    (MDPI, 2021-09-17) Andrés Gamazo, Paloma Jimena De; Cáceres Ramos, Sara Cristina; Belén Crespo; Silván Granado, Gema; Illera Del Portal, Juan Carlos
    The 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.
  • Publication
    Physiological Stress Responses in Cattle Used in the Spanish Rodeo
    (MDPI, 2023-08-17) Cáceres Ramos, Sara Cristina; Moreno, Julia; Crespo, Belen; Silván Granado, Gema; Illera Del Portal, Juan Carlos
    Certain 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 animals
  • Publication
    Anti-Angiogenic Treatments Interact with Steroid Secretion in Inflammatory Breast Cancer Triple Negative Cell Lines
    (MDPI, 2021-07-21) Alonso Diez, Angela; Cáceres Ramos, Sara Cristina; Peña Fernández, Laura Luisa; Crespo, Belen; Illera Del Portal, Juan Carlos
    Human inflammatory breast cancer (IBC) is a highly angiogenic disease for which an-tiangiogenic therapy has demonstrated only a modest response, and the reason for this remains unknown. Thus, the purpose of this study was to determine the influence of different antiangiogenic therapies on in vitro and in vivo steroid hormone and angiogenic growth factor production using canine and human inflammatory breast carcinoma cell lines as well as the possible involvement of sex steroid hormones in angiogenesis. IPC-366 and SUM149 cell lines and xenotransplanted mice were treated with different concentrations of VEGF, SU5416, bevacizumab and celecoxib. Steroid hormone (progesterone, dehydroepiandrostenedione, androstenedione, testosterone, dihydrotestos-terone, estrone sulphate and 17β-oestradiol), angiogenic growth factors (VEGF-A, VEGF-C and VEGF-D) and IL-8 determinations in culture media, tumour homogenate and serum samples were assayed by EIA. In vitro, progesterone-and 17β-oestradiol-induced VEGF production promoting cell proliferation and androgens are involved in the formation of vascular-like structures. In vivo, intratumoural testosterone concentrations were augmented and possibly associated with decreased metastatic rates, whereas elevated E1SO4 concentrations could promote tumour progression after antiangiogenic therapies. In conclusion, sex steroid hormones could regulate the production of angiogenic factors. The intratumoural measurement of sex steroids and growth factors may be useful to develop preventive and individualized therapeutic strategies.
  • Publication
    Prácticas virtuales de fisiología
    (2022) García García, Rosa María; Lorenzo González, Pedro Luis; Revuelta Rueda, Luis; Costa Buitrago, Gonzalo Antonio; Triguero Robles, Domingo; García Pascual, Mª de los Ángeles; Picazo González, Rosa Ana; González Gil, Alfredo; Arias Álvarez, María; Silván Granado, Gema; Illera Del Portal, Josefina María; Illera Del Portal, Juan Carlos; Cáceres Ramos, Sara Cristina; Fernández-Pacheco Martorell, Carlota Almudena; Quiroga del Río, Carmen Alejandra; Cascón Hernández, Ignacio; Liceras de Bernardo, Oiane; Sánchez Arévalo, Patricia; Albertos Encinas, Carla; Camargo Plaza, Lucía Candela; Jerónimo Sánchez, Benedicto; García Velasco, Carmen; Moya Ortega, Jesús Modesto; Millán Pastor, María Pilar
    El presente proyecto de innovación educativa ha servido para generar material audiovisual compatible con dispositivos electrónicos para el aprendizaje de fisiología de una manera sencilla y accesible. Es la continuación de un proyecto del curso 2020-21, en el que se generó un material con las prácticas que se realizan con un programa de registros fisiológicos. En esta ocasión, se procedió a la grabación de los procedimientos experimentales de las asignaturas de Fisiología del Grado en Veterinaria y del Grado en CyTA y se han incluido en un formato presentación, en el que se exponen los conocimientos básicos de la práctica, los objetivos, el material y métodos, el procedimiento experimental en vídeo con explicaciones y finalmente la recogida de datos y la interpretación de los resultados. Así, se reduce el número de animales a utilizar en las prácticas porque no es necesario volver a hacer el procedimiento en el animal y el estudiante puede aprender a su ritmo y visualizar la presentación tantas veces como necesite para su aprendizaje, antes, durante y después de la práctica. Se ha contado con un amplio equipo en el que han participado PDI del departamento de Fisiología y de Producción Animal, PAS y estudiantes de grado y posgrado, de modo que la experiencia de todos ellos ha aportado un enfoque multidisciplinar, muy adecuado para la viabilidad del proyecto. El producto generado es un material duradero en el tiempo, que seguirá poniéndose a disposición de los estudiantes en cursos venideros.
  • Publication
    El perro en investigación animal: Enseñanzas en manejo y procesos para incrementar el bienestar animal(II)
    (2020-05-05) 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 Cristina
    El 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. 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.