Artículos (Citología e Histología Normal y Patológica)

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Constitutive regulation of mitochondrial morphology by Aurora A kinase depends on a predicted cryptic targeting sequence at the N-terminus
(Royal Society Publishing, 2018-06-13) Grant, Rhys; Abdelbaki, Ahmed; Bertoldi, Alessia; Gavilán Dorronzoro, María de la Paz; Mansfeld, Jörg; Glover, David M.; Lindon, Catherine; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica
Aurora A kinase (AURKA) is a major regulator of mitosis and an important driver of cancer progression. The roles of AURKA outside of mitosis, and how these might contribute to cancer progression, are not well understood. Here, we show that a fraction of cytoplasmic AURKA is associated with mitochondria, co-fractionating in cell extracts and interacting with mitochondrial proteins by reciprocal co-immunoprecipitation. We have also found that the dynamics of the mitochondrial network are sensitive to AURKA inhibition, depletion or overexpression. This can account for the different mitochondrial morphologies observed in RPE-1 and U2OS cell lines, which show very different levels of expression of AURKA. We identify the mitochondrial fraction of AURKA as influencing mitochondrial morphology, because an N-terminally truncated version of the kinase that does not localize to mitochondria does not affect the mitochondrial network. We identify a cryptic mitochondrial targeting sequence in the AURKA N-terminus and discuss how alternative conformations of the protein may influence its cytoplasmic fate.
Calcifilaxis en una paciente sin insuficiencia renal avanzada
(SciELO Espana/Repisalud, 2017-08-27) Sánchez Ruiz-Granados, Elena; Juan Manuel Domínguez Herrera; Macías García, Laura; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica
La calcifilaxis es una enfermedad poco frecuente, aunque presenta una elevada tasa de mortalidad debido sobre todo a complicaciones como sepsis o gangrena. Generalmente se asocia a insuficiencia renal severa y en otras ocasiones a alteraciones del metabolismo calcio-fósforo o al uso de corticoides para enfermedades autoinmunes. Se presenta como lesiones cutáneas que se pueden ulcerar o infectar, debiendo diferenciarlas de las lesiones de causa vascular mediante el estudio histológico de la biopsia de la lesión. La biopsia cutánea muestra alteraciones histológicas características que facilitan el diagnóstico diferencial de esta patología. Para su tratamiento, se deben identificar y corregir los posibles factores implicados en su aparición. El tiosulfato de sodio es útil para el tratamiento. Presentamos el caso de una paciente con insuficiencia renal leve que padeció dicha entidad con buena evolución tras tratamiento.
An Immunohistochemical Profile Predictive of Recurrence and/or Mortality in Patients with Non-Special Type Invasive Mammary Carcinoma
(Sci Printers & Public Inc, 2016) Macías García, Laura; Robles-Frias, A.; García Gutiérrez, Jorge; González Campora, Ricardo; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. Departamento de Lenguajes y Sistemas Informáticos
OBJECTIVE: To identify and deine an immunohistochemical proile predictive of recurrence and/or mortality in patients with non-special type (NST) invasive mammary carcinoma. STUDY DESIGN: We identiied 234 patients diagnosed with NST invasive mammary carcinoma. They were followed up for at least 5 years. Tissue microarrays were constructed for immunohistochemical examination with different antibodies. RESULTS: Signiicant correlations were observed between tumor recurrence and expression of CK 5/6, fascin, FOXA1, Ki67, PR, and TOP2A, and between mortality and CDK-2 expression. Taking both disease outcomes together, signiicant correlations were observed with ER, p53, and the basal-type molecular phenotype (CK5/6). Multivariate analysis highlighted a signiicant correlation between tumor recurrence and coexpression of TOP2A/ER and between mortality and coexpression of C-KIT/ER. CONCLUSION: The present study suggests that expression of ER, PR, FOXA1, C-KIT, and TOPO2A constitutes a favorable immunohistochemical proile, while expression of CK5/6, CDK2, fascin, Ki67, and p53 may be regarded as unfavorable, since individual expression of these markers is associated with a better or worse prognosis, respectively. The immunohistochemical signature proposed here enables the identiication of breast cancer patients with a high or low risk of recurrence
Next-generation sequencing of uveal melanoma with clinical and histological correlations: Prognostic value of new mutations in the PI3K/AKT/mTOR pathway
(Wiley, 2023-10) Pérez Pérez, Manuel; Agostino, Alessandro; García de Sola Llamas, Carmen; Ruvolo, Michael; Vilches Arenas, Ángel; Relimpio López, Isabel; Macías García, Laura; Miguel Rodríguez, Manuel de; Idoate Gastearena, Miguel Ángel; Ríos Martín, Juan José; Universidad de Sevilla. Departamento de Medicina Preventiva y Salud Pública; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. CTS312: Análisis de la Demanda Sanitaria; Universidad de Sevilla. CTS949: Biopatología y Estrés Oxidativo
Background: Uveal melanoma (UM) is the eye's most common primary malignancy and there are no effective therapies for disseminated disease. It is important to try to know the patient's prognosis. The aim of this study was to reflect genetic variants, studied using NGS, of a series of 69 cases of UM and its correlation with histopathology and clinical progression. Methods: We performed targeted NGS using a 519-gene panel. Results: There were selected 28 different mutated genes, showing a total of 231 genetic variants that affected the function of the protein. The most common secondary mutations occurred in SF3B1 (in 26%), followed by BAP1 (in 23%), LRP1B (22%) and FGFR4 (20%). BAP1 mutation was associated with a greater likelihood of metastases and with greater presence of epithelioid cells. LRP1B was also associated with presence of epithelioid cells SF3B1 mutation was significantly associated with a spindle morphology. We found variants in the RAD51B, TOP2A, PTPRD, TSC2, DHX9, PDK1 and MTOR that have not been previously reported in consulted databases. The presence of a mutation in: CHEK2, DHX9 and PDK1 was associated with metastases. Conclusions: BAP1 is the most solid biomarker of a poor prognosis in UM and mutations can be detected using NGS. SF3B1 is associated with the spindle cell subtype of UM, which gives it probably a favourable prognostic value. Our study suggests that mutations in DHX9 and PDK1 can have prognostic value. These potential biomarkers are related to the PI3K/AKT/mTOR pathway and makes them candidates for developing new directed therapies.
Characterization of primary cilia in different epithelial cells of thyroid gland
(Springer, 2025) Pérez-Fernández, B.; Vázquez Román, María Victoria; Fernández-Santos, José María; Martín Lacave, Inés María; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Junta de Andalucía; Universidad de Sevilla; Universidad de Sevilla. CTS439: Sistema Neuroendocrino Difuso
The primary cilium (PC) is a biosensor with diverse functions, depending on cellular type. In the thyroid, where it was first described, PCs are located at the apical pole of the follicular epithelium, sensing the lumen's environment. They probably contribute to follicular homeostasis, although their presence in other thyroid epithelial cells remains unclear. Thyroglobulin, stored in the lumen as colloid, is the primary regulator of thyroid-specific gene expression under constant TSH levels. The mechanism by which thyroglobulin signal is transduced remains unresolved. This study investigates the evolution of PCs in different types of thyroid follicles, based on their functional activity, using both normal human thyroids and functional thyroid pathologies as models. It also compares PC morphology between human and rat thyrocytes and explores their presence in other thyroid epithelial components such as C cells and ultimobranchial remnants. Human and Wistar rat thyroid tissues were analyzed using histological, immunohistochemical, immunofluorescence, and electron microscopy techniques. Morphometric analyses quantified PC changes (frequency and length) in various follicular patterns, and statistical analyses were performed. Four types of thyroid follicles were identified: active, hyperactive, hypoactive, and empty follicles. PCs were most abundant and longest in active and significantly reduced in empty follicles. PCs were more prominent in human than in rat thyrocytes, present in both normal and neoplastic C cells, but sporadic in ultimobranchial remnants. PCs vary according to follicular activity and likely act as mechanosensors in thyroid hormone regulation, detecting colloid density and contributing to the regulation of thyroid hormone biosynthesis.
Myeloperoxidase in Health and Disease
(Mdpi, 2023-04-23) Ortiz Cerda, Tamara Andrea; Xie, Kangzhe; Mojadadi, Albaraa; Witting, Paul K.; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica
Anti-obesogenic effect of lupin-derived protein hydrolysate through modulation of adiposopathy, insulin resistance and gut dysbiosis in a diet-induced obese mouse
(Elsevier, 2024) Ponce España, Eduardo; Cruz Chamorro, Iván; Santos Sánchez, Guillermo; Alvarez-Lopez, Ana Isabel; Fernández-Santos, José María; Pedroche, Justo; Millán-Linares, MC; Bejarano Hernando, Ignacio; Lardone, Patricia Judith; Carrillo Vico, Antonio; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica
The prevalence of obesity is increasingly widespread, resembling a global epidemic. Lifestyle changes, such as consumption of high-energy-dense diets and physical inactivity, are major contributors to obesity. Common features of this metabolic pathology involve an imbalance in lipid and glucose homeostasis including dyslipidemia, insulin resistance and adipose tissue dysfunction. Moreover, the importance of the gut microbiota in the development and susceptibility to obesity has recently been highlighted. In recent years, new strategies based on the use of functional foods, in particular bioactive peptides, have been proposed to counteract obesity outcomes. In this context, the present study examines the effects of a lupin protein hydrolysate (LPH) on obesity, dyslipidemia and gut dysbiosis in mice fed a high-fat diet (HFD). After 12 weeks of LPH treatment, mice gained less weight and showed decreased adipose dysfunction compared to the HFD-fed group. HFD-induced dyslipidemia (increased triglycerides, cholesterol and LDL concentration) and insulin resistance were both counteracted by LPH consumption. Discriminant analysis differentially distributed LPH-treated mice compared to non-treated mice. HFD reduced gut ecological parameters, promoted the blooming of deleterious taxa and reduced the abundance of commensal members. Some of these changes were corrected in the LPH group. Finally, correlation analysis suggested that changes in this microbial population could be responsible for the improvement in obesity outcomes. In conclusion, this is the first study to show the effect of LPH on improving weight gain, adiposopathy and gut dysbiosis in the context of diet-induced obesity, pointing to the therapeutic potential of bioactive peptides in metabolic diseases.
Biological Response of the Peri-Implant Mucosa to Different Definitive Implant Rehabilitation Materials
(MDPI, 2024-05-29) Baus Domínguez, María; Oliva-Ferrusola, Elena; Maza-Solano, Serafín; Ruiz-de-León, Gonzalo; Serrera Figallo, María de los Ángeles; Gutiérrez Pérez, José Luis; Torres-Lagares, Daniel; Macías García, Laura; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. Departamento de Estomatología
Background: Sealing the peri-implant tissue is a determining factor for long-term implant survival. In the transmucosal region, the cervical fraction of the prosthetic crown is in contact with these tissues, so mucointegration will also be influenced by the biomaterial used for the prosthetic restoration. This study aims to compare the tissue response generated by definitive restorative materials and polymeric materials from a histological point of view. Methods: This study performed an observational prospective cohort study in which biopsies of the peri-implant mucosa were taken after placement of implant-supported prosthetic restorations made of different materials (zirconium oxide, lithium disilicate, and PMMA). Results: A statistically significant difference was observed in the increase in the thickness of the non-keratinized epithelium when comparing the definitive materials (zirconium oxide/lithium disilicate) vs. the provisional material (PMMA) and in the number of collagen fibers when comparing zirconium oxide and lithium disilicate. Conclusions: This study found that zirconia is the material that presents the most adequate biological response of peri-implant tissues. It shows a lower intensity of inflammatory cellular content, a total normality in the number of collagen fibers (the arrangement of the fibers is normal in 90% of the cases), and vascular proliferation of connective tissue in 83% of the cases. These parameters make it a material with a predictable response. Similarly, only the following slight statistically significant differences between the definitive and provisional materials are observed, indicating that the biological response generated by the provisional material (PMMA) is not very different from that obtained with the placement of the definitive restoration.
Amitriptyline induces mitophagy that precedes apoptosis in human HepG2 cells
(2016-08-07) Villanueva-Paz, Marina; Cordero, Mario D.; Pavón, Ana Delgado; Castejón Vega, Beatriz; Cotán, David; De la Mata, Mario; Oropesa-Ávila, Manuel; Alcocer-Gómez, Elísabet; Muntané Relat, Jordi; Miguel Rodríguez, Manuel de; Sánchez-Alcázar, José Antonio; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica; Universidad de Sevilla. Departamento de Psicología Experimental
Systemic treatments for hepatocellular carcinoma (HCC) have been largely unsuccessful. This study investigated the antitumoral activity of Amitriptyline, a tricyclic antidepressant, in hepatoma cells. Amitriptyline-induced toxicity involved early mitophagy activation that subsequently switched to apoptosis. Amitriptyline induced mitochondria dysfunction and oxidative stress in HepG2 cells. Amitriptyline specifically inhibited mitochondrial complex III activity that is associated with decreased mitochondrial membrane potential (∆Ψm) and increased reactive oxygen species (ROS) production. Transmission electron microscopy (TEM) studies revealed structurally abnormal mitochondria that were engulfed by double-membrane structures resembling autophagosomes. Consistent with mitophagy activation, fluorescence microscopy analysis showed mitochondrial Parkin recruitment and colocalization of mitochondria with autophagosome protein markers. Pharmacological or genetic inhibition of autophagy exacerbated the deleterious effects of Amitriptyline on hepatoma cells and led to increased apoptosis. These results suggest that mitophagy acts as an initial adaptive mechanism of cell survival. However persistent mitochondrial damage induced extensive and lethal mitophagy, autophagy stress and autophagolysome permeabilization leading eventually to cell death by apoptosis. Amitriptyline also induced cell death in hepatoma cells lines with mutated p53 and non-sense p53 mutation. Our results support the hypothesis that Amitriptyline-induced mitochondrial dysfunction can be a useful therapeutic strategy for HCC treatment, especially in tumors showing p53 mutations and/or resistant to genotoxic treatments.
Effects of polyphenolic maqui ( Aristotelia chilensis ) extract on the inhibition of NLRP3 inflammasome and activation of mast cells in a mouse model of Crohn's disease-like colitis
(Frontiers Media S.A., 2024-01-12) Ortiz Cerda, Tamara Andrea; Argüelles Arias, Federico; Macías García, Laura; Vázquez Román, María Victoria; Tapia, Gladys; Xie, Kangzhe; García-García, María Desirée; Merinero de los Santos, Manuel; García Montes, Josefa María; Alcudia Cruz, Ana; Witting, Paul K.; Miguel Rodríguez, Manuel de; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. Departamento de Medicina; Junta de Andalucía
Introduction: Crohn’s disease (CD) involves activation of mast cells (MC) and NFкB in parallel with the PPAR-a/NLRP3 inflammasome/IL-1b pathway in the inflamed colon. Whether polyphenols from maqui (Aristotelia chilensis) represent a natural alternative treatment for CD is unclear. Therefore, we used an animal model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD-like colitis to investigate protective effects of maqui extract through monitoring NLRP3 inflammasome and MC activation in colon tissue. Methods: Maqui extract was administered via orogastric route to mice after (post-Treatment group) or prior (pre-Treatment group) to TNBS-induction. Colon pathology was characterized by histoarchitectural imaging, disease activity index (DAI), and assessing NF-кB, p-NF-кB, PPAR-a/NLRP3 expression and IL-1b levels. Results: Compared to mice treated with TNBS alone administration of anthocyanin-rich maqui extract improved the DAI, colon histoarchitecture and reduced both colon wet-weight and transmural inflammation. Induction with TNBS significantly increased colonic NLPR3 inflammasome activation, while cotreatment with maqui extract (either post- or pre-Treatment) significantly downregulated NLRP3, ASC and caspase-1 levels, which manifested as reduced colonic IL-1b levels. Supplemented maqui extract marginally diminished NF-кB activity in epithelial cells but reached statistical significance in immune cells (as judged by decreased NF-кB phosphorylation). PPAR-a signaling was largely unaffected by Maqui whereas MC infiltration into the colon mucosa and submucosa decreased and their level of degranulation was suppressed. Conclusion: These outcomes show the post- and pre- Treatment effect of a polyphenolic extract rich in anthocyanins from maqui the acute phase of TNBSinduced CD-like colitis is linked to suppression of the NLRP3 inflammasome and reduced MC responses. These data indicate that maqui extract represents a potential nutraceutical for the treatment of inflammatory bowel disease (IBD).
C-cell differentiation in the wall of an aberrant ultimobranchial sinus in the thyroid gland of an old rat
(Wiley, 2022) Vázquez Román, María Victoria; Fernández-Santos, José María; Martín Lacave, Inés María; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Consejeria de Economia, Innovacion, Ciencia y Empleo, Junta de Andalucia; VII PPIT, CITIUS, Universidad de sevilla
Background In mammals, the thyroid gland possesses two types of endocrine cells, follicular cells and C cells, which have different functions but share a similar endodermal origin (although from different regions of the primitive pharynx). Specifically, follicular cells derive from the ventral pharyngeal floor, while C cells derive from the fourth pair of pharyngeal pouches through the ultimobranchial bodies (UBBs). Disruptions to human midline thyroid morphogenesis are relatively frequent and known as thyroid dysgenesis, which is the leading cause of congenital hypothyroidism. In contrast, fourth branchial apparatus anomalies are very rare clinical entities. Objectives The aim of this study was to analyze the morphological features and the immunohistochemical pattern of an aberrant ultimobranchial remnant, align with its persistent contribution to the formation of new C cells. Methods The thyroid gland of an old rat was serially sectioned and immunostained for the following markers: calcitonin, thyroglobulin, cytokeratins, PCNA, P63, E-cadherin, beta-tubulin and CD3. Results We detected a spontaneous congenital defect in the organogenesis of the UBB in an old rat, giving rise to an ‘ultimobranchial sinus’, which was accompanied by thymic tissue and an abscess. The epithelium contained basal/stem cells and contributed to the formation of abundant C cells and scarce follicular cells. Conclusions The ultimobranchial sinus is an exceptional finding for representing the first spontaneous abnormality in the development of UBB reported in rats, and the opportunity to observe sustained C-cell differentiation from stem cells in an old rat. These findings are consistent with a common origin of both C cells and follicular cells from UBB.
Cancer nano-immunotherapy: the novel and promising weapon to fight cancer
(Mdpi Ag, 2024) García-Domínguez, Daniel J.; López Enriquez, Soledad; Alba Jiménez, Gonzalo; Garnacho Montero, Carmen; Jiménez Cortegana, Carlos; Flores-Campos, Rocío; Cruz Merino, Luis de la; Hajji, Nabil; Sánchez Margalet, Víctor; Hontecillas-Prieto, Lourdes; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. Departamento de Medicina
Cancer is a complex disease that, despite advances in treatment and the greater understanding of the tumor biology until today, continues to be a prevalent and lethal disease. Chemotherapy, radiotherapy, and surgery are the conventional treatments, which have increased the survival for cancer patients. However, the complexity of this disease together with the persistent problems due to tumor progression and recurrence, drug resistance, or side effects of therapy make it necessary to explore new strategies that address the challenges to obtain a positive response. One important point is that tumor cells can interact with the microenvironment, promoting proliferation, dissemination, and immune evasion. Therefore, immunotherapy has emerged as a novel therapy based on the modulation of the immune system for combating cancer, as reflected in the promising results both in preclinical studies and clinical trials obtained. In order to enhance the immune response, the combination of immunotherapy with nanoparticles has been conducted, improving the access of immune cells to the tumor, antigen presentation, as well as the induction of persistent immune responses. Therefore, nanomedicine holds an enormous potential to enhance the efficacy of cancer immunotherapy. Here, we review the most recent advances in specific molecular and cellular immunotherapy and in nano immunotherapy against cancer in the light of the latest published preclinical studies and clinical trials.
Behaviour of the Peri-Implant Soft Tissue with Different Rehabilitation Materials on Implants
(MDPI, 2023-08) Baus Domínguez, María; Maza Solano, Serafín; Vazquez-Pachon, Celia; Flores-Cerero, Marta; Torres-Lagares, Daniel; Serrera Figallo, María de los Ángeles; Macías García, Laura; Universidad de Sevilla. Departamento de Estomatología; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. CTS-949: Biopatología y Estrés Oxidativo; Universidad de Sevilla. CTS-523: Innovación y Desarrollo en Técnicas y fundamentos de Cirugía Bucal y Craneofacial
Background: Mucointegration seems to gain interest when talking about success in the maintenance of dental implants. As we well know, collagen fibres cannot be inserted due to the lack of root structure on the implant surface, so the structural integration of peri-implant tissues that provide a firm seal around implants seems to be of interest when it comes to ensuring the survival of dental implants. To achieve a good epithelial barrier, the physicochemical characteristics of the surfaces of the restorative materials are of vital importance; therefore, the objective of this study is to analyse the histological behaviour of the peri-implant soft tissues in three different restorative materials. Methods: Histological analysis of biopsied peri-implant keratinised mucosa, inflammatory epithelium and connective tissue in contact with a reinforced composite (BRILLIANT Crios), a cross-linked polymethylmethacrylate (TELIO CAD), and a hybrid ceramic (Vita Enamic), restored on a customised Atlantis-type abutment (Dentsply Sirona) between 60 and 180 days after restoration. Results: A greater number of cells per mm2 of keratinised epithelium is observed in the reinforced composite, which could indicate greater surface roughness with greater inflammatory response. In this way, the greater number of lymphocytes and the lateral cellular composition of the inflammatory cells confirm the greater inflammatory activity towards that material. The best material to rehabilitate was hybrid ceramic, as it shows a better cellular response. Conclusions: Knowing the limitations of the proposed study, despite the fact that greater inflammation is observed in the reinforced composite relative to the other materials studied, no statistically significant differences were found.
VE-Cadherin modulates β-catenin/TCF-4 to enhance vasculogenic mimicry
(Nature Publishing Group, 2023) Delgado-Bellido, Daniel; Zamudio-Martínez, Esteban; Fernández-Cortés, Mónica; Herrera-Campos, Ana Belén; Olmedo Pelayo, Joaquín; Jordán Pérez, Carmen; Álava Casado, Enrique de; Oliver, F. J.; Universidad de Sevilla. Instituto de Biomedicina de Sevilla (IBIS); Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica
Vasculogenic Mimicry (VM) refers to the capacity to form a blood network from aggressive cancer cells in an independent way of endothelial cells, to provide nutrients and oxygen leading to enhanced microenvironment complexity and treatment failure. In a previous study, we demonstrated that VE-Cadherin and its phosphorylation at Y658 modulated kaiso-dependent gene expression (CCND1 and Wnt 11) through a pathway involving Focal Adhesion kinase (FAK). In the present research, using a proteomic approach, we have found that β-catenin/TCF-4 is associated with nuclear VE-cadherin and enhances the capacity of malignant melanoma cells to undergo VM in cooperation with VE-Cadherin; in addition, preventing the phosphorylation of Y658 of VEcadherin upon FAK disabling resulted in VE-Cadherin/β-catenin complex dissociation, increased β-catenin degradation while reducing TCF-4-dependent genes transcription (C-Myc and Twist-1). Uveal melanoma cells knockout for VE-Cadherin loses β-catenin expression while the rescue of VE-Cadherin (but not of the phosphorylation defective VE-Cadherin Y658F mutant) permits stabilization of β-catenin and tumor growth reduction in vivo experiments. In vivo, the concomitant treatment with the FAK inhibitor PF-271 and the anti-angiogenic agent bevacizumab leads to a strong reduction in tumor growth concerning the single treatment. In conclusion, the anomalous expression of VE-Cadherin in metastatic melanoma cells (from both uveal and cutaneous origins), together with its permanent phosphorylation at Y658, favors the induction of the aggressive VM phenotype through the cooperation of β-catenin with VE-Cadherin and by enhancing TCF-4 genes-dependent transcription.
Qué es la epigenética
(Universidad de Sevilla, 2018) Rivero Canalejo, Sabrina; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica
El término epigenética hace referencia al estudio de los mecanismos por medio de los cuales el genotipo, o la información genética de una célula u organismo, da origen al fenotipo, el conjunto de características observables de una célula u organismo. Hoy sabemos que los mecanismos epigenéticos actúan generando huellas sobre el ADN que van a determinar la forma en la que se expresan nuestros genes. Estos mecanismos son esenciales para el establecimiento y el mantenimiento del patrón específico de expresión génica de cada tipo celular concreto. Así, como guardianes de la identidad celular, estos mecanismos actúan en respuesta a un complejo proceso de regulación. No obstante, al igual que ocurre en el caso del genoma, el epigenoma, o información epigenética de una célula u organismo, es también vulnerable a la influencia de factores externos que podrían generar huellas epigenéticas accidentales asociadas en muchos casos a la aparición de patologías. Ahora sabemos que, en cada nueva generación, las huellas epigenéticas son borradas y reiniciadas de nuevo, lo que deja pocas posibilidades de heredar marcas epigenéticas, ya sean programadas, accidentales o inducidas por el medioambiente. No obstante, estudios recientes en animales han demostrado que existe una aparente resistencia al borrado completo de las huellas epigenéticas, lo que permitiría una verdadera herencia epigenética transgeneracional. Aunque en los últimos años se han producido grandes avances en esta área, son numerosas las cuestiones que permanecen por responder. Este trabajo pretende clarificar determinados conceptos esenciales que nos ayuden a entender qué es la epigenética, y que sabemos acerca de la herencia de estas huellas que marcan nuestro ADN.
Cost-effectiveness analysis of molecular diagnosis by next-generation sequencing versus sequential single testing in metastatic non-small cell lung cancer patients from a south Spanish hospital perspective
(Taylor and Francis LTD, 2022) Álava Casado, Enrique de; Pareja, María Jesús; Carcedo, David; Arrabal, Natalia; García, José-Francisco; Bernabé-Caro, Reyes; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. Departamento de Medicina
Background: To assess the cost-effectiveness of using next-generation sequencing (NGS) compared to sequential single-testing (SST) for molecular diagnostic and treatment of patients with advanced non- small cell lung cancer (NSCLC) from a Spanish single-center perspective, the Hospital Universitario Virgen del Rocio (HUVR). Research design and methods: A decision-tree model was developed to assess the alterations detection alterations and diagnostic cost in patients with advanced NSCLC, comparing NGS versus SST. Model inputs such as testing, positivity rates, or treatment allocation were obtained from the literature and the clinical practice of HUVR experts through consultation. Several sensitivity analyses were performed to test the robustness of the model. Results: Using NGS for molecular diagnosis of a 100-patients hypothetical cohort, 30 more alterations could be detected and 3 more patients could be enrolled in clinical-trials than using SST. On the other hand, diagnostic costs were increased up to €20,072 using NGS instead of SST. Using NGS time-to- results would be reduced from 16.7 to 9 days. Conclusions: The implementation of NGS at HUVR for the diagnostic of patients with advanced NSCLC provides significant clinical benefits compared to SST in terms of alterations detected, treatment with targeted-therapies and clinical-trial enrollment, and could be considered a cost-effective strategy.
Collision tumour involving a rectal gastrointestinal stromal tumour with invasion of the prostate and a prostatic adenocarcinoma
(BMC, 2012-10-30) Macías García, Laura; Hoz-Herazo, Haydee de la; Robles Frías, Antonio; Pareja Megía, María Jesús; López-Garrido, Juan; López, José Ignacio; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. CTS-949: Biopatología y Estrés Oxidativo
Background: Gastrointestinal stromal tumours (GISTs) are the most common primary mesenchymal neoplasia in the gastrointestinal tract, although they represent only a small fraction of total gastrointestinal malignancies in adults (<2%). GISTs can be located at any level of the gastrointestinal tract; the stomach is the most common location (60-70%), in contrast to the rectum, which is most rare (4%). When a GIST invades into the adjacent prostate tissue, it can simulate prostate cancer. In this study, we report on a case comprising the unexpected collision between a rectal GIST tumour and a prostatic adenocarcinoma. Findings: We describe the complexity of the clinical, endoscopic and radiological diagnosis, of the differential diagnosis based on tumour biopsy, and of the role of neoadjuvant therapy using imatinib prior to surgical treatment. Conclusions: Although isolated cases of coexisting GISTs and prostatic adenocarcinomas have previously been described, this is the first reported case in the medical literature of a collision tumour involving a rectal GIST and prostatic adenocarcinoma components.
Infiltration of abdominal striae distensae by Hodgkin's lymphoma
(Wiley, 2018-10) Macías García, Laura; Vallejo Benítez, Ana; Márquez-García, Ana; Marcos Domínguez, Ángel José; Ríos Martín, Juan José; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. CTS-949: Biopatología y Estrés Oxidativo
Cutaneous Hodgkin’s lymphoma (HL) is generally secondary to dissemination from a nodal HL; it tends to occur late in thecourse of the disease, and is associated with a poor progno-sis. It often manifests first as painless erythematous nodules and papules in the chest area. Primary cutaneous HL is extremely uncommon.
Mature Cystic Teratoma of the Lung With a Somatic-Like Malignant Component in a Patient With Testicular Germ-Cell Tumor
(Sociedad Española de Neumología y Cirugía Torácica SEPAR, 2018-12) Vallejo Benítez, Ana; Rodríguez-Zarco, Enrique; Pereira Gallardo, Sofía; Macías García, Laura; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. CTS-949: Biopatología y Estrés Oxidativo
In urological oncology, the diagnosis of teratoma with a somatic-like malignant component refers to the presence of a malignant neoplasm, e.g. carcinoma or sarcoma, either within a teratoma of the genital tract (usually the testis) or, more commonly, in a metastasis, following initial cisplatin therapy. The somatic-type malignancy (STM) most widely observed in germ cell tumors (GCT) is rhabdomyosarcoma; neuroendocrine carcinoma is extremely rare.
Postnatal Fate of the Ultimobranchial Remnants in the Rat Thyroid Gland
(Wiley Periodicals, Inc., 2013-07) Vázquez Román, María Victoria; Utrilla Alcolea, José Carmelo; Fernández-Santos, José María; Conde Amiano, Esperanza; Bernabé-Caro, Reyes; Sampedro, Consuelo; Martín Lacave, Inés María; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. CTS-629: Oncología Molecular y Nuevas Terapias
The ultimobranchial follicles (UBFs) areconsidered embryonic remnants from the ultimobran-chial body (UBB). They are follicular structures thatvary in size and appearance depending on the age of therat. The main objective of this article was to study theprogressive changes in shape, size, and frequency of theUBFs in the postnatal rat, from birth to old-age. Toaccomplish that objective, a systematic morphometricand incidental study of the UBF has been carried out in110 Wistar rats of different ages and both sexes, dividedinto three groups: 1) young rats (5–90-day-old); 2) adultrats (6–15-month-old), and 3) old rats (18–24-month-old).The glands were serially sectioned and immunostainedfor calcitonin at five equidistant levels. According to ourresults, UBFs were observed in all thyroid glands but amore exhaustive sampling was occasionally necessary inmale rats. In young rats, immature UBFs predominantlyappeared whereas in adult rats, mature UBFs withcystic appearance and variable luminal content pre-vailed. We frequently found spontaneous anomalousUBFs in old rats, which we have termed as ‘‘ultimobran-chial cystadenomata.’’ Additionally, in young rats, UBFareas significantly increased with age and they werelarger when compared to that of normal thyroid follicles.Likewise, in adult rats, UBFs were significantly largerthan normal thyroid follicles but only in female rats. Ingeneral, UBFs in females were also significantly largerthan those found in male rats. Finally, all these differen-ces related to UBFs together with a higher incidence infemales of UB cystadenomata suggest a sexual dimor-phism in regard to the destiny of these embryonic rem-nants during postnatal thyroid development.

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