Person:
Pérez Alenza, María De Los Dolores

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First Name
María De Los Dolores
Last Name
Pérez Alenza
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Veterinaria
Department
Medicina y Cirugía Animal
Area
Medicina y Cirugía Animal
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Now showing 1 - 10 of 13
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    Histopathological and immunohistochemical findings in lymphoid tissues of the endangered Iberian lynx (Lynx pardinus)
    (Comparative Immunology, Microbiology and Infectious Diseases, 2006) Peña Fernández, Laura Luisa; García Palencia, María Del Pilar; Jiménez Martínez, María De Los Ángeles; Benito, Alberto; Pérez Alenza, María De Los Dolores; Sánchez Maldonado, María Belén
    The Iberian lynx (Lynx pardinus) is the most threatened wild feline in the world. Little is known about the diseases and pathology that affect this animal. The aim of this study was to evaluate the histopathological status of the peripheral lymphoid tissues and thymus of Iberian lynxes necropsied between 1998 and 2003. Seventeen animals including females (n=8) and males (n=9), age range of 10 months to 16 years, with different causes of death were histopathologically and immunohistochemically (anti-CD3, CD79, MAC387, CD68) studied. Feline immunosuppressive virus laboratorial tests were negative. Five individuals presented neoplasia and/or tuberculosis. All animals presented some degree of both B and T cells depletion in peripheral lymphoid tissues and follicular hyalinosis in the center of depleted follicles. A viral origin of the lymphoid depletion is postulated although other causes (inbreeding, stress, toxic) are not ruled out. The loss of the effectiveness of the immune system increases the vulnerability of the critically endangered Iberian lynx to pathogens
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    Steroids and receptors in canine mammary cancer
    (Steroids, 2006) Illera Del Portal, Juan Carlos; Pérez Alenza, María De Los Dolores; Nieto Ruiz De Zárate, Ana Isabel; Jiménez, María; Silván Granado, Gema; Dunner Boxberger, Helene Susana; Peña Fernández, Laura Luisa
    The aims of this study were to investigate the serum and tissue content of androgens and estrogens in canine inflammatory mammary carcinomas (IMC) as well as in non-inflammatory malignant mammary tumors (MMT), and assessed the immunoexpression of estrogen and androgen receptors using immunohistochemistry. Profiles for the androgens dehydroepiandrosterone (DHEA), androstenedione (A4), and testosterone (T), and for the estrogens 17β estradiol (E2) and estrone-sulphate (SO4E1) were measured both in tissue homogenates and in serum of MMT and IMC by EIA techniques in 42 non-inflammatory malignant mammary tumors (MMT) and in 14 inflammatory mammary carcinomas (IMC), prospectively collected from 56 female dogs. Androgen receptor (AR) and estrogen receptor alpha (ERα) and beta (ERβ) expression was studied using immunohistochemistry (strepavidin–biotin-peroxidase method) in samples of 32 MMT and 14 IMC, and counted by a computer image analyzer. IMC serum and tissue levels of androgens were significantly higher than MMT levels. Tissue content of estrogens was also significantly higher in IMC than in MMT. Serum values of SO4E1 were significantly higher in IMC, but serum levels of E2 were significantly lower in IMC compared to MMT cases. Medium-high androgen receptor intensity was observed in 64.28% of IMC and 40.62% of MMT. No important differences were found between ERα expression in IMC (100% negative) and MMT (90% negative). ERβ and AR were intensely expressed in highly malignant inflammatory mammary carcinoma cells. To our knowledge, this is the first report relative to AR immunohistochemistry in canine mammary cancer and to estrogens or androgens in serum of dogs with benign or malignant mammary tumors.
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    Transcriptomics of Canine Inflammatory Mammary Cancer Treated with Empty Cowpea Mosaic Virus Implicates Neutrophils in Anti-Tumor Immunity
    (International Journal of Molecular Sciences, 2023) Barreno San Antolín, Lucía; Sevane Fernández, Natalia; Valdivia Lara, Edgar Guillermo; Alonso Miguel, Daniel; Suárez Redondo, María; Alonso Díez, Ángela; Fiering, Steven; Beiss, Veronique; Steinmetz, Nicole F.; Pérez Alenza, María De Los Dolores; Peña Fernández, Laura Luisa
    Canine inflammatory mammary cancer (IMC) is a highly aggressive and lethal cancer in dogs serving as a valuable animal model for its human counterpart, inflammatory breast cancer (IBC), both lacking effective therapies. Intratumoral immunotherapy (IT-IT) with empty cowpea mosaic virus (eCPMV) nanoparticles has shown promising results, demonstrating a reduction in tumor size, longer survival rates, and improved quality of life. This study compares the transcriptomic profiles of tumor samples from female dogs with IMC receiving eCPMV IT-IT and medical therapy (MT) versus MT alone. Transcriptomic analyses, gene expression profiles, signaling pathways, and cell type profiling of immune cell populations in samples from four eCPMV-treated dogs with IMC and four dogs with IMC treated with MT were evaluated using NanoString Technologies using a canine immune-oncology panel. Comparative analyses revealed 34 differentially expressed genes between treated and untreated samples. Five genes (CXCL8, S100A9, CCL20, IL6, and PTGS2) involved in neutrophil recruitment and activation were upregulated in the treated samples, linked to the IL17-signaling pathway. Cell type profiling showed a significant increase in neutrophil populations in the tumor microenvironment after eCPMV treatment. These findings highlight the role of neutrophils in the anti-tumor response mediated by eCPMV IT-IT and suggest eCPMV as a novel therapeutic approach for IBC/IMC.
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    Prevalence of Systemic Hypertension and Control of Systolic Blood Pressure in a Cohort of 14 Dogs with Adrenal-Dependent Hypercortisolism during the First Year of Trilostane Treatment or after Adrenalectomy
    (Animals, 2024) García San José, Paula; Pérez Alenza, María De Los Dolores; Alonso Miguel, Daniel; González Sanz, Sandra; Arenas Bermejo, Carolina
    Hypercortisolism in dogs is frequently associated with systemic hypertension (SH). However, there are no studies evaluating the changes in systolic blood pressure (SBP) in dogs with adrenal-dependent hypercortisolism (ADH) during trilostane treatment or after adrenalectomy and their response to antihypertensive treatments. For this reason, the objectives of this study were to evaluate the changes in SBP in dogs with ADH during the first year of trilostane treatment or after adrenalectomy, the relation with clinical control of hypercortisolism and certain laboratory parameters, and the response to antihypertensive drugs. Fourteen dogs newly diagnosed with ADH were prospectively included and evaluated at diagnosis (T0) and 1, 3, 6, and 12 months after (T1, T3, T6, and T12, respectively). Dogs were classified as hypertensive (HT; SBP ≥ 160 mmHg) and non-hypertensive. In HT dogs, benazepril was considered as the first-line drug, and, if necessary, amlodipine was prescribed. The prevalence of SH at T0 was 79%, and it was reduced to 25% at T12. Blood pressure (BP) was not associated with disease control or selected laboratory parameters at any endpoint. Only 22% of dogs with SH needed more than one drug to normalize their SBP. In all dogs surgically treated that were HT at T0, BP normalized at T3.
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    No Evidence of SARS-CoV-2 Infection in Wild Mink (Mustela lutreola and Neogale vison) from Northern Spain during the First Two Years of Pandemic
    (Animals, 2022) Villanueva-Saz, Sergio; Giner, Jacobo; Palomar, Ana María; Gómez, María Asunción ; Põdra, Madis ; Aranda, María del Carmen ; Jiménez Martínez, María De Los Ángeles; Lizarraga, Patricia; Hernández, Raquel ; Portillo, Aránzazu ; Oteo, José Antonio ; Ruíz-Arrondo, Ignacio ; Pérez Alenza, María De Los Dolores; Tobajas, Ana Pilar ; Verde, Maite ; Lacasta, Delia ; Marteles, Diana ; Hurtado-Guerrero, Ramón ; Santiago, Llipsy ; Ruíz, Héctor ; Fernández, Antonio
    The impact of the SARS-CoV-2 pandemic on wildlife is largely unevaluated, and extended surveillance of animal species is needed to reach a consensus on the role of animals in the emergence and maintenance of SARS-CoV-2. This infection has been detected in farmed and domestic animals and wild animals, mainly in captivity. The interactions or shared resources with wildlife could represent a potential transmission pathway for the SARS-CoV-2 spill over to other wild species and could lead to health consequences or the establishment of new reservoirs in susceptible hosts. This study evaluated the presence of SARS-CoV-2 in European mink (Mustela lutreola) and American mink (Neogale vison) in Spain by enzyme-linked immunosorbent assay (ELISA) using the receptor binding domain (RBD) of Spike antigen in serum samples and/or by RT-qPCR assays in oropharyngeal and rectal swabs. From January 2020 to February 2022, a total of 162 animals (127 European mink and 35 American mink) with no evidence of SARS-CoV-2 infection were included in the study. Antibodies against the SARS-CoV-2 were not found in the serum samples analysed (n = 126), nor was the virus amplified by RT-qPCR (n = 160 swabs). Our results suggest that the potential role of wild mink and the European mink bred in captivity and released to the wild as dispersers of SARS-CoV-2 is so far low. However, wildlife surveillance for early detection of human and animal risks should be continued. In this sense, epidemiological monitoring measures, including serology and molecular analysis, are necessary.
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    Neoadjuvant Intratumoral Immunotherapy with Cowpea Mosaic Virus Induces Local and Systemic Antitumor Efficacy in Canine Mammary Cancer Patients
    (Cells, 2023) Valdivia Lara, Edgar Guillermo; Alonso Miguel, Daniel; Pérez Alenza, María De Los Dolores; Zimmermann, Anna Barbara Emilia; Schaafsma, Evelien; Kolling IV, Fred W.; Barreno San Antolín, Lucía; Alonso Díez, Ángela; Beiss, Veronique; Affonso de Oliveira, Jessica Fernanda; Suárez Redondo, María; Fiering, Steven; Steinmetz, Nicole F.; Vom Berg, Johannes; Peña Fernández, Laura Luisa; Arias Pulido, Hugo
    The lack of optimal models to evaluate novel agents is delaying the development of effective immunotherapies against human breast cancer (BC). In this prospective open label study, we applied neoadjuvant intratumoral immunotherapy with empty cowpea mosaic virus-like particles (eCPMV) to 11 companion dogs diagnosed with canine mammary cancer (CMC), a spontaneous tumor resembling human BC. We found that two neoadjuvant intratumoral eCPMV injections resulted in tumor reduction in injected tumors in all patients and in noninjected tumors located in the ipsilateral and contralateral mammary chains of injected dogs. Tumor reduction was independent of clinical stage, tumor size, histopathologic grade, and tumor molecular subtype. RNA-seq-based analysis of injected tumors indicated a decrease in DNA replication activity and an increase in activated dendritic cell infiltration in the tumor microenvironment. Immunohistochemistry analysis demonstrated significant intratumoral increases in neutrophils, T and B lymphocytes, and plasma cells. eCPMV intratumoral immunotherapy demonstrated antitumor efficacy without any adverse effects. This novel immunotherapy has the potential for improving outcomes for human BC patients.
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    Survival of dogs with pituitary‐dependent hyperadrenocorticism treated twice daily with low doses of trilostane
    (Veterinary Record, 2022) García San José, Paula; Arenas Bermejo, Carolina; Alonso Miguel, Daniel; González Sanz, Sandra; Clares Moral, Irene; Portero Fuentes, Miriam; Pérez Alenza, María De Los Dolores
    Background Twice daily low trilostane doses have proven to be effective to manage canine Cushing's syndrome. However, survival and prognostic factors in dogs treated with this protocol have not been evaluated. The aim of the study was to evaluate survival and prognostic factors, including systolic blood pressure (SBP) at diagnosis, in dogs with pituitary-dependent hypercortisolism (PDH) treated with low trilostane doses. Methods Medical records of 91 dogs newly diagnosed with PDH initially treated with 0.2–1.1 mg/kg of trilostane twice daily were retrospectively included. Survival times were calculated using the Kaplan–Meier estimator. Univariable and multivariable analysis were performed using the Cox proportional hazard regression analysis. Results Overall, median survival was 998 days (range 26–1832 days, 95% confidence interval = 755–1241 days). In the multivariable analysis, age (hazard ratio [HR] = 1.337, p < 0.001), presence of calcinosis cutis (HR = 5.271, p < 0.001), body condition score (BCS) ≤3/9 (HR = 8.100, p < 0.001) and higher platelet count (HR = 1.002, p = 0.022) were negatively correlated with survival. SBP was not associated with survival. Conclusions Low-dose trilostane treatment twice daily provides slightly longer survival than previously reported for dogs with PDH treated once or twice daily at higher doses. Older age, presence of calcinosis cutis, low BCS and higher platelet count, but not systemic hypertension, are predictive of poorer prognosis in dogs with PDH.
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    Steroid pathway and oestrone sulphate production in canine inflammatory mammary carcinoma
    (The Journal of Steroid Biochemistry and Molecular Biology, 2007) Sánchez-Archidona, Ana R.; Jiménez Martínez, María De Los Ángeles; Pérez Alenza, María De Los Dolores; Silván Granado, Gema; Illera Del Portal, Juan Carlos; Peña Fernández, Laura Luisa; Dunner Boxberger, Helene Susana
    Spontaneous canine mammary inflammatory carcinoma (IMC) shares epidemiologic, histopathologic and clinical characteristics with the inflammatory breast carcinoma (IBC) disease in humans. We have analysed the steroids levels in serum and in tissue homogenates of IMC, the expression of two of their receptors (androgen and β-estrogen) and of three enzymes included in the steroidogenesis pathway (aromatase (CYP19A1), steroid sulphatase (STS) and estrogen sulfotransferase (EST)) trying to explain the specific accumulation of steroids in IMC tissues generating deposits in the form of lipid droplets whose presence can be attributed to steroids secreted by IMC cells. According to our working hypothesis, oestrone sulphate would be the main component of these lipid droplets. The presence of these steroid deposits would contribute to the intense proliferation and invasive behaviour of IMC and IBC, although their involvement in angiogenesis is yet to be demonstrated.
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    Comparison of non-selective adrenocorticolysis with mitotane or trilostane for the treatment of dogs with pituitary-dependent hyperadrenocorticism
    (Veterinary Record, 2007) Clemente, Mónica; Andrés Gamazo, Paloma Jimena De; Arenas, Carolina; Melián, Carlos; Morales, Manuel; Pérez Alenza, María De Los Dolores
    Forty-six dogs with pituitary-dependent hyperadrenocorticism were treated with mitotane by the non-selective adrenocorticolysis protocol and 40 were treated twice a day with trilostane. The treatment groups were compared by chi-squared tests, and survival data were analysed using Kaplan-Meier survival plots and a Cox proportional hazard method. The non-selective adrenocorticolysis protocol was very effective (89 per cent), its toxicity was moderate (24 per cent) and there were fewer recurrences (29 per cent) than reported with the classical selective adrenocorticolysis protocol (58 per cent). In a multivariate model, age and bodyweight at diagnosis were significantly negatively correlated with survival time. The median survival time of the dogs treated with trilostane twice a day (900 days) was longer (P=0·05) than that of the dogs treated with mitotane (720 days).
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    Membranous glomerulonephritis in the Iberian lynx (Lynx pardinus)
    (Veterinary Immunology and Immunopathology, 2008) Jiménez Martínez, María De Los Ángeles; Sánchez Maldonado, María Belén; Pérez Alenza, María De Los Dolores; García, Pilar; López, Jose Vicente; Rodriguez, Alejandro; Muñoz, Álvaro; Martínez, Fernando; Vargas, Astrid; Peña Fernández, Laura Luisa
    The Iberian lynx is the most endangered felid species in the world, confined nowadays to two isolated metapopulations in the southwest of Spain, where less than 200 individuals survive. Little is known about the diseases that affect these animals in the wild or in captivity. Kidney samples from necropsies of 27 Iberian lynxes, wild and captive, were examined by histopathology, immunohistochemistry (IgG, IgM, IgA, laminin, type IV collagen, and fibronectin), electron microscopy (n = 8) and immunogold labelling for IgM, IgG and IgA in one case, in order to characterize the glomerulopathy prevalent in this species. Urinalyses from records were available for 9 of the necropsied animals and blood and urine samples from 23 free ranging and captive Iberian lynxes were prospectively obtained in order to evaluate the renal function of the living population. A focal, diffuse membranous glomerulonephritis (MGN) that progressed with age was diagnosed in all but one of the animals in different stages not associated to concurrently known infectious diseases. Positive immunoexpression of IgM and IgG was observed in the glomerular capillary basement membranes and intramembranous electron-dense deposits, compatible with immune complexes (ICs) were seen with electron microscopy. The immunogold labelling was also positive for IgM and IgG in the electron-dense areas. The serum biochemistry and urinalyses also revealed signs of mild chronic kidney disease in 16 of the 23 animals evaluated. In conclusion, the membranous glomerulopathy affecting the Iberian lynx is a progressive disease of immune origin. We postulate a possible genetic predisposition towards the disease, enhanced by inbreeding and a possible connection to an immune-mediated systemic disease.