Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 72
Filtrar
Más filtros

País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Eur J Clin Microbiol Infect Dis ; 43(3): 533-540, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38236366

RESUMEN

PURPOSE: To describe a cohort with a high risk of recurrence who received bezlotoxumab during the first episode of Clostridioides difficile infection (CDI) and to compare this cohort with patients with similar characteristics who did not receive the monoclonal antibody. METHODS: A prospective and multicentre study of patients with a high risk of recurrence (expected recurrence rate>35%) who were treated with bezlotoxumab during their first episode of CDI was conducted. A propensity score-matched model 1:2 was used to compare both cohorts that were weighed according to basal characteristics (hospital-acquisition, creatinine value, and fidaxomicin as a CDI treatment). RESULTS: Sixty patients (mean age:72 years) were prospectively treated with bezlotoxumab plus anti-Clostridioides antibiotic therapy. Vancomycin (48 patients) and fidaxomicin (12 patients) were prescribed for CDI treatment, and bezlotoxumab was administered at a mean of 4.2 (SD:2.1) days from the beginning of therapy. Recurrence occurred in nine out of 54 (16.7%) evaluable patients at 8 weeks. Forty bezlotoxumab-treated patients were matched with 69 non-bezlotoxumab-treated patients. Recurrence rates at 12 weeks were 15.0% (6/40) in bezlotoxumab-treated patients vs. 23.2% (16/69) in non-bezlotoxumab-treated patients (OR:0.58 [0.20-1.65]). No adverse effects were observed related to bezlotoxumab infusion. Only one of 9 patients with previous heart failure developed heart failure. CONCLUSION: We observed that patients treated with bezlotoxumab in a real-world setting during a first episode of CDI having high risk of recurrence, presented low rate of recurrence. However, a significant difference in recurrence could not be proved in comparison to the controls. We did not detect any other safety concerns.


Asunto(s)
Anticuerpos ampliamente neutralizantes , Infecciones por Clostridium , Insuficiencia Cardíaca , Humanos , Anciano , Fidaxomicina/uso terapéutico , Estudios Prospectivos , Recurrencia , Antibacterianos/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Infecciones por Clostridium/microbiología , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/tratamiento farmacológico
2.
Int J Mol Sci ; 24(21)2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-37958993

RESUMEN

Breast cancer (BC) is the most diagnosed cancer in women and the second most common cancer globally. Significant advances in BC research have led to improved early detection and effective therapies. One of the key challenges in BC is the presence of BC stem cells (BCSCs). This small subpopulation within the tumor possesses unique characteristics, including tumor-initiating capabilities, contributes to treatment resistance, and plays a role in cancer recurrence and metastasis. In recent years, microRNAs (miRNAs) have emerged as potential regulators of BCSCs, which can modulate gene expression and influence cellular processes like BCSCs' self-renewal, differentiation, and tumor-promoting pathways. Understanding the miRNA signatures of BCSCs holds great promise for improving BC diagnosis and prognosis. By targeting BCSCs and their associated miRNAs, researchers aim to develop more effective and personalized treatment strategies that may offer better outcomes for BC patients, minimizing tumor recurrence and metastasis. In conclusion, the investigation of miRNAs as regulators of BCSCs opens new directions for advancing BC research through the use of bioinformatics and the development of innovative therapeutic approaches. This review summarizes the most recent and innovative studies and clinical trials on the role of BCSCs miRNAs as potential tools for early diagnosis, prognosis, and resistance.


Asunto(s)
Neoplasias de la Mama , MicroARNs , Humanos , Femenino , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Transducción de Señal , Células Madre Neoplásicas/metabolismo , Diferenciación Celular
3.
Med Res Rev ; 42(5): 1978-2001, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35707911

RESUMEN

The complexity of the tumor microenvironment (TME) together with the development of the metastatic process are the main reasons for the failure of conventional anticancer treatment. In recent years, there is an increasing need to advance toward advanced in vitro models of cancer mimicking TME and simulating metastasis to understand the associated mechanisms that are still unknown, and to be able to develop personalized therapy. In this review, the commonly used alternatives and latest advances in biofabrication of tumor-on-chips, which allow the generation of the most sophisticated and optimized models for recapitulating the tumor process, are presented. In addition, the advances that have allowed these new models in the area of metastasis, cancer stem cells, and angiogenesis are summarized, as well as the recent integration of multiorgan-on-a-chip systems to recapitulate natural metastasis and pharmacological screening against it. We also analyze, for the first time in the literature, the normative and regulatory framework in which these models could potentially be found, as well as the requirements and processes that must be fulfilled to be commercially implemented as in vitro study model. Moreover, we are focused on the possible regulatory pathways for their clinical application in precision medicine and decision making through the generation of personalized models with patient samples. In conclusion, this review highlights the synergistic combination of three-dimensional bioprinting systems with the novel tumor/metastasis/multiorgan-on-a-chip systems to generate models for both basic research and clinical applications to have devices useful for personalized oncology.


Asunto(s)
Bioimpresión , Neoplasias , Bioimpresión/métodos , Humanos , Dispositivos Laboratorio en un Chip , Neoplasias/tratamiento farmacológico , Medicina de Precisión/métodos , Microambiente Tumoral
4.
Small ; 17(14): e2006009, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33705602

RESUMEN

For decades, several attempts have been made to obtain a mimetic model for the study of metastasis, the reason of most of deaths caused by cancer, in order to solve the unknown phenomena surrounding this disease. To better understand this cellular dissemination process, more realistic models are needed that are capable of faithfully recreating the entire and essential tumor microenvironment (TME). Thus, new tools known as tumor-on-a-chip and metastasis-on-a-chip have been recently proposed. These tools incorporate microfluidic systems and small culture chambers where TME can be faithfully modeled thanks to 3D bioprinting. In this work, a literature review has been developed about the different phases of metastasis, the remaining unknowns and the use of new models to study this disease. The aim is to provide a global vision of the current panorama and the great potential that these systems have for in vitro translational research on the molecular basis of the pathology. In addition, these models will allow progress toward a personalized medicine, generating chips from patient samples that mimic the original tumor and the metastatic process to perform a precise pharmacological screening by establishing the most appropriate treatment protocol.


Asunto(s)
Bioimpresión , Neoplasias , Humanos , Dispositivos Laboratorio en un Chip , Microfluídica , Microambiente Tumoral
5.
Adv Exp Med Biol ; 1277: 115-126, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33119869

RESUMEN

The importance of the microenvironment in tumor development and their resistance to drugs is increasingly well known. This microenvironment is composed of different cell types, among which cells with stemness properties such as cancer stem cells (CSCs) and mesenchymal stem cells (MSCs) are distinguished for their relevant role in tumor proliferation, angiogenesis, metastasis, and drug resistance. The relationship between these stem cells (SCs) and tumor microenvironment is conducted by the secretome, consisting of several factors, cytokines, chemokines, and hormones released to the surrounding stroma, which plays a deterministic role in tumor hallmarks. Knowing the intrinsic and complex communication network that SCs establish with the microenvironment will allow to address the tumor processes responsible for cancer progression and the generation of new targeted therapeutic approaches useful in the clinic arena.


Asunto(s)
Neoplasias , Células Madre Neoplásicas/metabolismo , Microambiente Tumoral , Quimiocinas , Citocinas , Hormonas , Humanos , Células Madre Mesenquimatosas/metabolismo , Neovascularización Patológica
6.
Adv Exp Med Biol ; 1059: 63-83, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29736569

RESUMEN

Osteoarthritis (OA) is the most prevalent joint disease characterized by pain and degenerative lesions of the cartilage, subchondral bone, and other joint tissues. The causes of OA remain incompletely understood. Over the years, it has become recognized that OA is a multifactorial disease. In particular, aging and trauma are the main risk factors identified for the development of OA; however, other factors such as genetic predisposition, obesity, inflammation, gender and hormones, or metabolic syndrome contribute to OA development and lead to a more severe outcome. While this disease mainly affects people older than 60 years, OA developed after joint trauma affects all range ages and has a particular impact on young individuals and people who have highest levels of physical activity such as athletes. Traumatic injury to the joint often results in joint instability or intra-articular fractures which lead to posttraumatic osteoarthritis (PTOA). In response to injury, several molecular mechanisms are activated, increasing the production and activation of different factors that contribute to the progression of OA.In this chapter, we have focused on the interactions and contribution of the multiple factors involved in joint destruction and progression of OA. In addition, we overview the main changes and molecular mechanisms related to OA pathogenesis.


Asunto(s)
Osteoartritis/etiología , Heridas y Lesiones/complicaciones , Envejecimiento/fisiología , Cartílago Articular/lesiones , Cartílago Articular/metabolismo , Cartílago Articular/fisiopatología , Causalidad , Condrocitos/patología , Progresión de la Enfermedad , Fracturas Óseas/complicaciones , Fracturas Óseas/fisiopatología , Predisposición Genética a la Enfermedad , Humanos , Inflamación/complicaciones , Inflamación/fisiopatología , Síndrome Metabólico/complicaciones , Síndrome Metabólico/fisiopatología , Modelos Biológicos , Obesidad/complicaciones , Obesidad/fisiopatología , Procedimientos Ortopédicos , Osteoartritis/genética , Osteoartritis/fisiopatología , Osteoartritis/terapia , Factores Sexuales , Ingeniería de Tejidos , Heridas y Lesiones/fisiopatología
7.
Adv Exp Med Biol ; 1059: 331-350, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29736581

RESUMEN

Osteochondral (OC) lesions are a major cause of chronic musculoskeletal pain and functional disability, which reduces the quality of life of the patients and entails high costs to the society. Currently, there are no effective treatments, so in vitro and in vivo disease models are critically important to obtain knowledge about the causes and to develop effective treatments for OC injuries. In vitro models are essential to clarify the causes of the disease and the subsequent design of the first barrier to test potential therapeutics. On the other hand, in vivo models are anatomically more similar to humans allowing to reproduce the pattern and progression of the lesion in a controlled scene and offering the opportunity to study the symptoms and responses to new treatments. Moreover, in vivo models are the most suitable preclinical model, being a fundamental and a mandatory step to ensure the successful transfer to clinical trials. Both in vitro and in vitro models have a number of advantages and limitation, and the choice of the most appropriate model for each study depends on many factors, such as the purpose of the study, handling or the ease to obtain, and cost, among others. In this chapter, we present the main in vitro and in vivo OC disease models that have been used over the years in the study of origin, progress, and treatment approaches of OC defects.


Asunto(s)
Enfermedades Óseas , Enfermedades de los Cartílagos , Modelos Animales , Animales , Animales Modificados Genéticamente , Enfermedades Óseas/etiología , Enfermedades Óseas/genética , Enfermedades Óseas/terapia , Enfermedades de los Cartílagos/inducido químicamente , Enfermedades de los Cartílagos/etiología , Enfermedades de los Cartílagos/genética , Enfermedades de los Cartílagos/terapia , Técnicas de Cultivo de Célula , Condrocitos/citología , Condrogénesis , Técnicas de Cocultivo , Modelos Animales de Enfermedad , Humanos , Traumatismos de la Rodilla/etiología , Mamíferos , Técnicas de Cultivo de Órganos , Osteoartritis/etiología , Osteoartritis/genética , Osteoartritis/patología , Osteoartritis/terapia , Osteogénesis , Ingeniería de Tejidos/métodos , Andamios del Tejido
8.
Biofabrication ; 16(4)2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-38862006

RESUMEN

There is increasing evidence that cancer progression is linked to tissue viscoelasticity, which challenges the commonly accepted notion that stiffness is the main mechanical hallmark of cancer. However, this new insight has not reached widespread clinical use, as most clinical trials focus on the application of tissue elasticity and stiffness in diagnostic, therapeutic, and surgical planning. Therefore, there is a need to advance the fundamental understanding of the effect of viscoelasticity on cancer progression, to develop novel mechanical biomarkers of clinical significance. Tissue viscoelasticity is largely determined by the extracellular matrix (ECM), which can be simulatedin vitrousing hydrogel-based platforms. Since the mechanical properties of hydrogels can be easily adjusted by changing parameters such as molecular weight and crosslinking type, they provide a platform to systematically study the relationship between ECM viscoelasticity and cancer progression. This review begins with an overview of cancer viscoelasticity, describing how tumor cells interact with biophysical signals in their environment, how they contribute to tumor viscoelasticity, and how this translates into cancer progression. Next, an overview of clinical trials focused on measuring biomechanical properties of tumors is presented, highlighting the biomechanical properties utilized for cancer diagnosis and monitoring. Finally, this review examines the use of biofabricated tumor models for studying the impact of ECM viscoelasticity on cancer behavior and progression and it explores potential avenues for future research on the production of more sophisticated and biomimetic tumor models, as well as their mechanical evaluation.


Asunto(s)
Elasticidad , Matriz Extracelular , Neoplasias , Humanos , Neoplasias/patología , Neoplasias/tratamiento farmacológico , Viscosidad , Matriz Extracelular/metabolismo , Animales , Hidrogeles/química , Fenómenos Biomecánicos
9.
Biofabrication ; 15(3)2023 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-36041423

RESUMEN

Conventionalin vitrocancer models do not accurately reproduce the tumor microenvironment (TME), so three-dimensional (3D)-bioprinting represents an excellent tool to overcome their limitations. Here, two multicellular tri-layered malignant melanoma (MM) models composed by cancer stem cells (CSCs) isolated from a MM established cell line or a primary-patient derived cell line, fibroblasts, mesenchymal stem cells, and endothelial cells, embedded within an agarose-collagen type I hydrogel were bioprinted. Embedded-cells showed high proliferation and metabolic activity, and actively remodeled their TME. MM hydrogels displayed similar rheological properties that skin and were able to support an early onset of vascularization. Besides, MM hydrogels displayed different response to vemurafenib compared with cell cultures, and supported tumorigenesis in murine xenotransplant achieving more mimeticin vivomodels. For the first time a tri-layered 3D-bioprinted CSC-based human MM model is developed recreating TMEin vitroandin vivoand response to treatment, being useful for precision treatment regimens against MM.


Asunto(s)
Bioimpresión , Melanoma , Células Madre Mesenquimatosas , Humanos , Animales , Ratones , Células Endoteliales , Hidrogeles/farmacología , Colágeno Tipo I/metabolismo , Melanoma/tratamiento farmacológico , Melanoma/metabolismo , Bioimpresión/métodos , Impresión Tridimensional , Ingeniería de Tejidos/métodos , Microambiente Tumoral
10.
PLoS One ; 18(9): e0277388, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37682843

RESUMEN

BACKGROUND: Vitamin D may have immunomodulatory functions, and might therefore play a role in the pathogenesis of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, no conclusive evidence exists regarding its impact on the prevalence of this infection, the associated course of disease, or prognosis. OBJECTIVE: To study the association between SARS-CoV-2 infection and vitamin D deficiency in patients attending a tertiary university hospital, and to examine the clinical course of infection and prognosis for these patients. METHODS: This non-interventional, retrospective study, which involved big-data analysis and employed artificial intelligence to capture data from free text in the electronic health records of patients diagnosed with SARS-CoV-2, was undertaken at a tertiary university hospital in Madrid, Spain, between March 2020 and March 2021. The variables recorded were vitamin D deficiency, sociodemographic and clinical characteristics, course of disease, and prognosis. RESULTS: Of the 143,157 patients analysed, 36,261 had SARS-CoV-2 infection (25.33%) during the study period, among whom 2,588 (7.14%) had a vitamin D deficiency. Among these latter patients, women (OR 1.45 [95%CI 1.33-1.57]), adults over 80 years of age (OR 2.63 [95%CI 2.38-2.91]), people living in nursing homes (OR 2.88 [95%CI 2.95-3.45]), and patients with walking dependence (OR 3.45 [95%CI 2.85-4.26]) appeared in higher proportion. After adjusting for confounding factors, a higher proportion of subjects with SARS-CoV-2 plus vitamin D deficiency required hospitalisation (OR 1.38 [95%CI 1.26-1.51]), and had a longer mean hospital stay (3.94 compared to 2.19 days in those with normal levels; P = 0.02). CONCLUSION: A low serum 25(OH) vitamin D concentration in patients with SARS-CoV-2 infection is significantly associated with a greater risk of hospitalisation and a longer hospital stay. Among such patients, higher proportions of institutionalised and dependent people over 80 years of age were detected.


Asunto(s)
COVID-19 , Deficiencia de Vitamina D , Adulto , Humanos , Femenino , Anciano de 80 o más Años , Estudios Retrospectivos , Estudios de Casos y Controles , COVID-19/epidemiología , Inteligencia Artificial , SARS-CoV-2 , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiología , Vitamina D , Análisis de Datos
11.
Cancers (Basel) ; 15(14)2023 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-37509327

RESUMEN

Malignant melanoma (MM) can spread to other organs and is resistant in part due to the presence of cancer stem cell subpopulations (CSCs). While a controversial high dose of interferon-alpha (IFN-α) has been used to treat non-metastatic high-risk melanoma, it comes with undesirable side effects. In this study, we evaluated the effect of low and high doses of IFN-α on CSCs by analyzing ALDH activity, side population and specific surface markers in established and patient-derived primary cell lines. We also assessed the clonogenicity, migration and tumor initiation capacities of IFN-α treated CSCs. Additionally, we investigated genomic modulations related to stemness properties using microRNA sequencing and microarrays. The effect of IFN-α on CSCs-derived exosomes was also analyzed using NanoSight and liquid chromatography (LC-HRMS)-based metabolomic analysis, among others. Our results showed that even low doses of IFN-α reduced CSC formation and stemness properties, and led to a significant decrease in the ability to form tumors in mice xenotransplants. IFN-α also modulated the expression of genes and microRNAs involved in several cancer processes and metabolomics of released exosomes. Our work suggests the utility of low doses of interferon, combined with the analysis of metabolic biomarkers, as a potential clinical approach against the aggressiveness of CSCs in melanoma.

12.
World Psychiatry ; 22(3): 352-365, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37713566

RESUMEN

We provide here the first bottom-up review of the lived experience of depression, co-written by experts by experience and academics. First-person accounts within and outside the medical field were screened and discussed in collaborative workshops involving numerous individuals with lived experience of depression, family members and carers, representing a global network of organizations. The material was enriched by phenomenologically informed perspectives and shared with all collaborators in a cloud-based system. The subjective world of depression was characterized by an altered experience of emotions and body (feeling overwhelmed by negative emotions, unable to experience positive emotions, stuck in a heavy aching body drained of energy, detached from the mind, the body and the world); an altered experience of the self (losing sense of purpose and existential hope, mismatch between the past and the depressed self, feeling painfully incarcerated, losing control over one's thoughts, losing the capacity to act on the world; feeling numb, empty, non-existent, dead, and dreaming of death as a possible escape route); and an altered experience of time (experiencing an alteration of vital biorhythms, an overwhelming past, a stagnation of the present, and the impossibility of the future). The experience of depression in the social and cultural context was characterized by altered interpersonal experiences (struggling with communication, feeling loneliness and estrangement, perceiving stigma and stereotypes), and varied across different cultures, ethnic or racial minorities, and genders. The subjective perception of recovery varied (feeling contrasting attitudes towards recovery, recognizing recovery as a journey, recognizing one's vulnerability and the need for professional help), as did the experience of receiving pharmacotherapy, psychotherapy, and social as well as physical health interventions. These findings can inform clinical practice, research and education. This journey in the lived experience of depression can also help us to understand the nature of our own emotions and feelings, what is to believe in something, what is to hope, and what is to be a living human being.

13.
Int J Mol Sci ; 13(3): 3847-3886, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22489186

RESUMEN

In the last decade, both regenerative medicine and nanotechnology have been broadly developed leading important advances in biomedical research as well as in clinical practice. The manipulation on the molecular level and the use of several functionalized nanoscaled materials has application in various fields of regenerative medicine including tissue engineering, cell therapy, diagnosis and drug and gene delivery. The themes covered in this review include nanoparticle systems for tracking transplanted stem cells, self-assembling peptides, nanoparticles for gene delivery into stem cells and biomimetic scaffolds useful for 2D and 3D tissue cell cultures, transplantation and clinical application.


Asunto(s)
Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Sistemas de Liberación de Medicamentos/métodos , Nanoestructuras/uso terapéutico , Ingeniería de Tejidos/métodos , Materiales Biocompatibles/uso terapéutico , Regeneración Ósea , Cartílago/metabolismo , Técnicas de Transferencia de Gen , Humanos , Nanotecnología , Medicina Regenerativa , Trasplante de Células Madre , Andamios del Tejido
14.
Arch Esp Urol ; 65(1): 158-65, 2012.
Artículo en Español | MEDLINE | ID: mdl-22318186

RESUMEN

UNLABELLED: To evaluate the pathological variables predictive of biochemical recurrence after radical prostatectomy and their implications for decision making in the adjuvant setting. METHODS: 684 patients with localized prostate cancer who were treated with radical prostatectomy between 1996 and 2007. Before surgery they were classified according to D'Amico risk groups for recurrence. Following prostatectomy the following variables were collected: Gleason score, pathological stage, capsular invasion, surgical margins, perineural invasion and percentage of involvement in the piece. Univariate analysis was performed and subsequently adjusted using a Cox proportional hazards model (method enter). RESULTS: The median follow up of the series was 61 months. 29.1% of patients had biochemical recurrence. Overall mortality of the series was 4.9% and cancer-specific mortality 1.2%. In univariate analysis the Gleason score of surgical specimens, capsular invasion, perineural invasion, involvement of surgical margins, pathological stage and percentage of involvement of the piece had statistically significant (p <0.001) relation with biochemical recurrence. In multivariate analysis, a Gleason score ≥ 8 in the surgical specimen (HR = 3.08), existence of affected surgical margins (HR = 2.98), pT3 stage (HR = 1.61) and involvement of more than 50% of the piece by cancer (HR = 3.39) were identified as independent predictors of biochemical recurrence. Stratifying by independent predictors of biochemical recurrence (pT, Gleason score and margin), patients with at least 2 of these factors had an incidence of biochemical recurrence at 5 years exceeding 50%. CONCLUSIONS: Patients who have a Gleason score ≥ 8, positive margins, pT3 tumour or a percentage of >50% after prostatectomy have an increased risk of biochemical recurrence. Patients with at least 2 predictors of relapse have a probability of recurrence over 50% in the first 5 years of recurrence and should therefore be candidates for adjuvant radiotherapy.


Asunto(s)
Terapia Neoadyuvante , Recurrencia Local de Neoplasia/epidemiología , Prostatectomía , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/cirugía , Humanos , Masculino , Recurrencia Local de Neoplasia/sangre , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Factores de Riesgo
15.
Transl Res ; 247: 117-136, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-34844003

RESUMEN

BACKGROUND: A deeper knowledge of the functional versatility and dynamic nature of the ECM has improved the understanding of cancer biology. Translational Significance: This work provides an in-depth view of the importance of the ECM to develop more mimetic breast cancer models, which aim to recreate the components and architecture of tumor microenvironment. Special focus is placed on decellularized matrices derived from tissue and cell culture, both in procurement and applications, as they have achieved great success in cancer research and pharmaceutical sector. The extracellular matrix (ECM) is increasingly recognized as a master regulator of cell behavior and response to breast cancer (BC) treatment. During BC progression, the mammary gland ECM is remodeled and altered in the composition and organization. Accumulated evidence suggests that changes in the composition and mechanics of ECM, orchestrated by tumor-stromal interactions along with ECM remodeling enzymes, are actively involved in BC progression and metastasis. Understanding how specific ECM components modulate the tumorigenic process has led to an increased interest in the development of biomaterial-based biomimetic ECM models to recapitulate key tumor characteristics. The decellularized ECMs (dECMs) have emerged as a promising in vitro 3D tumor model, whose recent advances in the processing and application could become the biomaterial by excellence for BC research and the pharmaceutical industry. This review offers a detailed view of the contribution of ECM in BC progression, and highlights the application of dECM-based biomaterials as promising personalized tumor models that more accurately mimic the tumorigenic mechanisms of BC and the response to treatment. This will allow the design of targeted therapeutic approaches adapted to the specific characteristics of each tumor that will have a great impact on the precision medicine applied to BC patients.


Asunto(s)
Neoplasias de la Mama , Materiales Biocompatibles , Biomimética , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Matriz Extracelular , Femenino , Humanos , Microambiente Tumoral
16.
Adv Healthc Mater ; 11(19): e2200251, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35857383

RESUMEN

Osteoarthritis is a disease with a great socioeconomic impact and mainly affects articular cartilage, a tissue with reduced self-healing capacity. In this work, 3D printed 1,4 butanediol thermoplastic polyurethane (b-TPUe) scaffolds are functionalized and infrapatellar mesenchymal stem cells are used as the cellular source. Since b-TPUe is a biomaterial with mechanical properties similar to cartilage, but it does not provide the desired environment for cell adhesion, scaffolds are functionalized with two methods, one based on collagen type I and the other in 1-pyrenebutiric acid (PBA) as principal components. Alamar Blue and confocal assays display that PBA functionalized scaffolds support higher cell adhesion and proliferation for the first 21 days. However, collagen type I functionalization induces higher proliferation rates and similar cell viability than the PBA method. Further, both functionalization methods induce extracellular matrix synthesis, and the presence of chondrogenic markers (Sox9, Col2a, and Acan). Finally, SEM images probe that functionalized 3D printed scaffolds present much better cell/biomaterial interactions than controls and confirm early chondrogenesis. These results indicate that the two methods of functionalization in the highly hydrophobic b-TPUe enhance the cell-biomaterial interactions and the improvement in the chondro-inductive properties, which have great potential for application in cartilage tissue engineering.


Asunto(s)
Cartílago Articular , Ingeniería de Tejidos , Materiales Biocompatibles/farmacología , Butileno Glicoles , Diferenciación Celular , Condrogénesis , Colágeno Tipo I , Poliuretanos , Ingeniería de Tejidos/métodos , Andamios del Tejido/química
17.
Artículo en Inglés | MEDLINE | ID: mdl-35490091

RESUMEN

OBJECTIVE: To describe the clinical experience with dalbavancin in the treatment of diabetic foot infection in a multidisciplinary unit of a second level hospital. METHODS: A retrospective, descriptive study was made with all patients with diabetic foot infection treated with dalbavancin in the Diabetic Foot Unit of Hospital Universitario Fundación Alcorcón, covering the period from September 2016 to December 2019. Demographic parameters and comorbidities, characteristics of the infection and treatment with dalbavancin were recorded. The cure rate is estimated at 90 days after finishing the treatment. RESULTS: A total of 23 patients with diabetic foot infection (osteomyelitis) started treatment with dalbavancin, 19 were men and the mean age was 65 years. The microorganisms most frequently isolated for the indication of treatment with dalbavancin were Staphylococcus aureus (11) and Corynebacterium striatum (7). Dalbavancin was used as a second choice therapy in 22 cases, in 11 due to toxicity from other antibiotics. The median duration of treatment was 5 (4-7) weeks; the most frequent dose of dalbavancin (8 patients) was 1000 mg followed by 500 mg weekly for 5 weeks. 3 patients presented mild side effects (nausea and gastrointestinal discomfort). At 90 days after completion of dalbavancin therapy, 87% (20) of the patients were cured (95% CI: 65.2%-94.52%). CONCLUSION: Patients with osteomyelitis due to gram-positive microorganisms who received as part of the multidisciplinary antibiotic treatment with dalbavancin, had a high rate of cure with adequate tolerance and few side effects. Dalbavancin offers a safe alternative in treating deep diabetic foot infection.


Asunto(s)
Enfermedades Transmisibles , Diabetes Mellitus , Pie Diabético , Osteomielitis , Anciano , Antibacterianos , Diabetes Mellitus/inducido químicamente , Diabetes Mellitus/tratamiento farmacológico , Pie Diabético/inducido químicamente , Pie Diabético/complicaciones , Pie Diabético/tratamiento farmacológico , Femenino , Humanos , Masculino , Osteomielitis/tratamiento farmacológico , Osteomielitis/microbiología , Estudios Retrospectivos , Teicoplanina/análogos & derivados
18.
J Clin Med ; 11(4)2022 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-35207411

RESUMEN

We evaluated in this randomised, double-blind clinical trial the efficacy of melatonin as a prophylactic treatment for prevention of SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Healthcare workers fulfilling inclusion criteria were recruited in five hospitals in Spain and were randomised 1:1 to receive melatonin 2 mg administered orally for 12 weeks or placebo. The main outcome was the number of SARS-CoV-2 infections. A total of 344 volunteers were screened, and 314 were randomised: 151 to placebo and 163 to melatonin; 308 received the study treatment (148 placebo; 160 melatonin). We detected 13 SARS-CoV-2 infections, 2.6% in the placebo arm and 5.5% in the melatonin arm (p = 0.200). A total of 294 adverse events were detected in 127 participants (139 in placebo; 155 in melatonin). We found a statistically significant difference in the incidence of adverse events related to treatment: 43 in the placebo arm and 67 in the melatonin arm (p = 0.040), and in the number of participants suffering from somnolence related to treatment: 8.8% (n = 14) in the melatonin versus 1.4% (n = 2) in the placebo arm (p = 0.008). No severe adverse events related to treatment were reported. We cannot confirm our hypothesis that administration of melatonin prevents the development of SARS-CoV-2 infection in healthcare workers.

19.
Rev Enferm ; 34(10): 42-4, 2011 Oct.
Artículo en Español | MEDLINE | ID: mdl-22135936

RESUMEN

Reflections on the UN decree of June 15 as International Day of No Abuse of the Elderly which have been enhanced by the celebration in Madrid, Hospital Clinico San Carlos, a day devoted to this topic with the aim of raising awareness among professionals working in health centers and other interest groups, groups of retirees and social services, health problems and abuse in the elderly


Asunto(s)
Abuso de Ancianos , Anciano , Abuso de Ancianos/diagnóstico , Abuso de Ancianos/prevención & control , Humanos
20.
Bioeng Transl Med ; 6(1): e10192, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33532591

RESUMEN

Tissue engineering (TE) seeks to fabricate implants that mimic the mechanical strength, structure, and composition of native tissues. Cartilage TE requires the development of functional personalized implants with cartilage-like mechanical properties capable of sustaining high load-bearing environments to integrate into the surrounding tissue of the cartilage defect. In this study, we evaluated the novel 1,4-butanediol thermoplastic polyurethane elastomer (b-TPUe) derivative filament as a 3D bioprinting material with application in cartilage TE. The mechanical behavior of b-TPUe in terms of friction and elasticity were examined and compared with human articular cartilage, PCL, and PLA. Moreover, infrapatellar fat pad-derived human mesenchymal stem cells (MSCs) were bioprinted together with scaffolds. in vitro cytotoxicity, proliferative potential, cell viability, and chondrogenic differentiation were analyzed by Alamar blue assay, SEM, confocal microscopy, and RT-qPCR. Moreover, in vivo biocompatibility and host integration were analyzed. b-TPUe demonstrated a much closer compression and shear behavior to native cartilage than PCL and PLA, as well as closer tribological properties to cartilage. Moreover, b-TPUe bioprinted scaffolds were able to maintain proper proliferative potential, cell viability, and supported MSCs chondrogenesis. Finally, in vivo studies revealed no toxic effects 21 days after scaffolds implantation, extracellular matrix deposition and integration within the surrounding tissue. This is the first study that validates the biocompatibility of b-TPUe for 3D bioprinting. Our findings indicate that this biomaterial can be exploited for the automated biofabrication of artificial tissues with tailorable mechanical properties including the great potential for cartilage TE applications.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA