Person: Andrés Gamazo, Paloma Jimena De
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First Name
Paloma Jimena De
Last Name
Andrés Gamazo
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Veterinaria
Department
Medicina y Cirugía Animal
Area
Medicina y Cirugía Animal
Identifiers
6 results
Search Results
Now showing 1 - 6 of 6
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 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 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 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.Item 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 CarlosBlocking 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.