78 research outputs found
Glucocorticoids Inhibit Apoptosis during Fibrosarcoma Development by Transcriptionally Activating Bcl-xL
No full textGlucocorticoids influence many physiological processes, and in particular apoptosis, often with opposite effects depending on the cell type examined. We found that during fibrosarcoma development there is a strong increase in apoptosis at the tumor stage, which is repressed by dexamethasone to levels observed in normal fibroblasts. The anti-apoptotic Bcl-2 family protein Bcl-x(L) is induced by dexamethasone at the transcriptional level at all stages of fibrosarcoma development. The ligand-activated glucocorticoid receptor (GR) activates the Bcl-x promoter in transient transfection experiments, and GR binds to specific Bcl-x promoter sequences in vitro and in vivo. Furthermore, a GR antagonist abolishes this effect, indicating that Bcl-x(L) induction is mediated by GR. Importantly, exogenous Bcl-x(L) inhibits apoptosis and caspase-3 activity in fibrosarcoma cells to levels found in dexamethasone-treated fibrosarcoma cells. We conclude that Bcl-x(L) is a key target mediating the anti-apoptotic effects of glucocorticoids during fibrosarcoma development. These observations provide further understanding of the molecular basis of glucocorticoid regulation of cell death during tumorigenesis
Multidimensional Fluorescence Imaging of Embryonic and Postnatal Mammary Gland Development
No full textMultidimensional fluorescence imaging represents a powerful approach for studying the dynamic cellular processes underpinning the development, function, and maintenance of the mammary gland. Here, we describe key multidimensional imaging strategies that enable visualization of mammary branching morphogenesis and epithelial cell fate dynamics during postnatal and embryonic mammary gland development. These include 4-dimensional intravital microscopy and ex vivo imaging of embryonic mammary cultures, in addition to methods that facilitate 3-dimensional imaging of the ductal epithelium at single-cell resolution within its native stroma. Collectively, these approaches provide a window into mammary developmental dynamics, and the perturbations underlying tissue dysfunction and disease
MiR-24 induces chemotherapy resistance and hypoxic advantage in breast cancer
No full textBreast cancer remains one of the leading causes of cancer mortality among women. It has been proved that the onset of cancer depends on a very small pool of tumor cells with a phenotype similar to that of normal adult stem cells. Cancer stem cells (CSC) possess self-renewal and multilineage differentiation potential as well as a robust ability to sustain tumorigenesis. Evidence suggests that CSCs contribute to chemotherapy resistance and to survival under hypoxic conditions. Interestingly, hypoxia in turn regulates self-renewal in CSCs and these effects may be primarily mediated by hypoxic inducible factors (HIFs). Recently, microRNAs (miRNAs) have emerged as critical players in the maintenance of pluripotency and self-renewal in normal and cancer stem cells. Here, we demonstrate that miR-24 is upregulated in breast CSCs and that its overexpression increases the number of mammospheres and the expression of stem cell markers. MiR-24 also induces apoptosis resistance through the regulation of BimL expression. Moreover, we identify a new miR-24 target, FIH1, which promotes HIFα degradation: miR-24 increases under hypoxic conditions, causing downregulation of FIH1 and upregulation of HIF1α. In conclusion, miR-24 hampers chemotherapy-induced apoptosis in breast CSCs and increases cell resistance to hypoxic conditions through an FIH1−HIFα pathway
Técnicas endoscópicas bariátricas primarias en personas adultas con o sin diabetes mellitus tipo 2
No full textTècniques endoscòpiques bariàtriques; Adults; Diabetis mellitus tipus 2Técnicas endoscópicas bariátricas; Adultos; Diabetes mellitus tipo 2Bariatric endoscopic techniques; Adults; Diabetes mellitus type 2L'objectiu d’aquest informe és identificar i avaluar l’evidència disponible sobre l’eficàcia, efectivitat i seguretat de les tècniques endoscòpiques en el tractament primari de persones adultes amb obesitat, amb DM tipus 2 o sense, i formular recomanacions sobre la seva inclusió o no a la Cartera Comú de Serveis del Sistema Nacional de Salut espanyol.El objetivo de este informe es identificar y evaluar la evidencia disponible sobre la eficacia, efectividad y seguridad de las técnicas endoscópicas en el tratamiento primario de personas adultas con obesidad con o sin DM tipo 2 y formular recomendaciones sobre su inclusión o no en la cartera de servicios comunes del Sistema Nacional de Salud español.The aim of this report is to identify and evaluate all available evidence on efficacy, effectiveness and security of endoscopic techniques in primary treatment of adults with obesity with or without type 2 DM and to draw up recommendations on including them or not in the Health Portfolio of the Spanish National Health System
Cancer stem cells in the human mammary gland and regulation of their differentiation by estrogen
No full textThe identification and characterization of normal and breast cancer stem cells have provided a new vision of breast tumorigenesis. Cancer stem cells may be responsible for breast tumor initiation, progression and development of resistance to therapy. Most breast cancers express the estrogen receptor, and several studies have linked long-term estrogen exposure to enhanced breast cancer risk; however, estrogen receptor-positive tumors usually present a better prognosis than estrogen receptor-negative ones. The finding that estrogen reduces the pool of human breast stem cells may explain the more differentiated phenotype observed in estrogen receptor-positive tumors. In this article, our current understanding of the complex role of estrogen in human breast stem cells is discussed in the context of breast malignancy. © 2011 Future Medicine Ltd
Alternative HER/PTEN/Akt Pathway Activation in HPV Positive and Negative Penile Carcinomas
No full textThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Multimodal fusion strategies for survival prediction in breast cancer: A comparative deep learning study
No full text[EN] Accurate survival prediction in breast cancer remains a key challenge in oncology, requiring models that can integrate diverse clinical, molecular, and imaging data sources to guide breast cancer management. While recent deep learning models have explored multimodal integration for cancer survival prediction, their generalizability to unseen data remains limited. In this study, we developed and optimized unimodal and multimodal models for breast cancer survival prediction, systematically assessing our optimized early and late integration strategies and their impact on out-of-sample generalization performance. We integrated clinical variables, somatic mutations, RNA expression, copy number variation, miRNA expression, and histopathology images from The Cancer Genome Atlas breast cancer dataset. Across all modality combinations, late fusion models consistently outperformed early fusion approaches and late and intermediate benchmark methods, with the combination of omics and clinical data yielding the highest test-set concordance indices. Explainability analyses showed that our models captured biologically relevant features associated with patient survival. These findings highlight the value of late-fusion multimodal deep learning frameworks for robust and explainable survival prediction in breast cancer.This work has been partially funded by the Basque Government ELKARTEK Program, within the BG24 Project (KK-2024/00019) , granted to AS, XCS, LVP, MdMV, MJG, KL and AG. This project focuses on the exploration and characterization of molecular factors in breast cancer and its innovative applications in precision oncology. B. Calvo acknowledges partial support by the Research Groups 2022-2025 (IT1504-22) from the Basque Government, and the PID2022-137442NB-I00 research project from the Spanish Ministry of Science. The Funding sources were not involved in the design of this study.Sucre, A.;Calle Sánchez, X.;Perez-Herrera, LV.;Vivanco, MD.;Garcia-González, MJ.;Karen Lopez-Linares Roman;Calvo, B.... (2025). Multimodal fusion strategies for survival prediction in breast cancer: A comparative deep learning study. Computational and Structural Biotechnology Journal. 27:4505-4516. https://doi.org/10.1016/j.csbj.2025.10.038S450545162
Interaction of Sex and Diabetes on Outcome After Ischemic Stroke
No full textBackgroundThe relationship between ischemic stroke (IS), diabetes mellitus (DM), and sex is intriguing. The aim of this study was to assess the effect modification of sex in the association between DM and short- and long-term disability and mortality in first-ever IS patients.MethodsIn a retrospective, observational, hospital-based study of a prospective series including first-ever IS patients from January 2006 until July 2011, differences in 3-month and 5-year mortality, and disability between diabetic and non-diabetic patients [modified Rankin Scale (mRS) from 3 to 5] were analyzed by sex.ResultsIn total, 933 patients (36.3% with DM, 50.5% women) were included. Overall 3-month and 5-year mortality were 150 (16.1%) and 407 (44.1%), respectively. Adjusted for age, previous mRS, and stroke severity, patients with DM had significantly higher 3-month disability [hazard ratio (HR): 1.49 (95% confidence interval (CI): 1.39–1.70), p < 0.0001], 5-year disability [HR: 1.41 (95% CI: 1.07–1.86), p = 0.015], and 5-year mortality [HR: 1.48 (95% CI: 1.20–1.81), p < 0.0001], compared with the non-DM group. Compared with non-DM women, women with diabetes had worse 3-month disability [HR: 1.81 (95% CI: 1.33–2.46), p < 0.0001] and 5-year mortality [HR: 1.72 (95% CI: 1.30–2.20), p < 0.0001], and a trend for 5-year disability [HR: 1.40 (95% CI: 0.99–2.09), p = 0.057]. In men, DM had an effect on 3-month disability [HR: 1.45 (95% CI: 1.07–1.96), p = 0.018], a trend for 5-year disability [HR: 1.43 (95% CI: 0.94–2.19), p = 0.096], but no clear effect on 5-year mortality [HR: 1.22 (95% CI: 0.91–1.65), p = 0.186].ConclusionSex has a modifier effect on mortality in first-ever IS diabetic patients. Long-term mortality is increased in diabetic women compared with non-diabetic women, a difference not observed in men
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