Person:
Illera Del Portal, Josefina María

First Name

Josefina María

Last Name

Illera Del Portal

URI

https://hdl.handle.net/20.500.14352/80382

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Veterinaria

Department

Fisiología

Area

Fisiología

Identifiers

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Search Results

Now showing 1 - 9 of 9

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 Carlos
Canine 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.
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 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.
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 Carlos
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.
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 Carlos
The 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 approaches
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 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.
Blocking Estrogen Synthesis Leads to Different Hormonal Responses in Canine and Human Triple Negative Inflammatory Breast Cancer
(Cancers, 2021) 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.
The inhibition of steroid hormones determines the fate of IPC-366 tumor cells, highlighting the crucial role of androgen production in tumor processes
(Research in Veterinary Sciences, 2023) 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.
Project number: 105
Desarrollo de material audiovisual aplicable a distintas prácticas de Fisiología para su utilización en un entorno virtual
(2021) González Gil, Alfredo; García Pascual, Mª de los Ángeles; Triguero Robles, Domingo; Millán Pastor, María Pilar; Silván Granado, Gema; Revuelta Rueda, Luis; Picazo González, Rosa Ana; García García, Rosa María; Lorenzo González, Pedro Luis; Illera Del Portal, Juan Carlos; Illera Del Portal, Josefina María; Costa Buitrago, Gonzalo Antonio; Jerónimo Sánchez, Benedicto; García-Velasco Fernández, Carmen Pilar; Modesto Moya, Jesús; Ramírez Gómez, Esther; Martínez Millán, Alejandro
Los nuevos retos a los que se enfrenta la universidad en la última década, hacen necesaria la elaboración de un material audiovisual apropiado que permita la impartición eficaz de unas prácticas innovadoras y que faciliten su replicabilidad a través de vías online. Este trabajo supone el desarrollo de material audiovisual de 6 prácticas seleccionadas de Fisiología, perfectamente aplicables a distintas disciplinas dentro del área de Ciencias de la Salud. Las prácticas seleccionadas (Ejercicio aeróbico, Electroencefalografía, Electrooculografía, Espirometría, Metabolismo basal y Reflejos medulares) sonrealizadas con un sistema de laboratorio virtual (Biopac Student Lab), basado en la obtención de una serie de datos fisiológicos a lo largo de un registro para su posterior análisis y discusión. Cada video ha sido dividido en tres partes: Introducción (explicación de forma atractiva de los fundamentos y objetivos de la práctica, junto con videos/imágenes procedentes de webs que permiten su descarga gratuita); Desarrollo (explicación detallada del procedimiento de la práctica y su ejecución); y Análisis del registro (análisis y discusión de los distintos resultados obtenidos durante el desarrollo de la práctica). Este material puede ser aprovechado por el alumno en distintas situaciones: a) antes de la impartición de las prácticas, adquiriendo una serie de conocimientos previos y que permitan entender la práctica y su desarrollo (parte 1 y 2 del vídeo), destinando el tiempo de la práctica para la interpretación y discusión de los resultados (parte 3); b) después de la impartición de la práctica, ya que el alumno puede disponer en todo momento de dicho material audiovisual, revisarlo las veces que sea necesario y fomentar también el autoaprendizaje; c) en situaciones en las que la impartición de clases presenciales no sea posible, como por ejemplo, las derivadas de la pandemia por COVID-19. La elaboración del material audiovisual garantiza un material docente de calidad, persistente en el tiempo (innovación pedagógica); permite la transferencia de conocimientos al ser un recurso en abierto (Open Educational Resources); posibilita la gestión del ritmo de trabajo por parte del alumno/docente (e-learning); estimula la autonomía en el estudio por el alumno (autoaprendizaje); posibilita que el tiempo empleado para la clase presencial se dedique para resolución de dudas o explicación de mecanismos más complejos (Flipped classroom).
Project number: 120
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.