Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 112
Filtrar
1.
J Hosp Infect ; 139: 33-43, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37331378

RESUMO

BACKGROUND: Antimicrobial resistance (AMR) has become a significant challenge in high-complexity healthcare settings. AIM: To evaluate the prevalence of AMR in bloodstream isolates from high-complexity paediatric units in Spain over a nine-year period. METHODS: A retrospective observational multicentre study was conducted in three tertiary hospitals, analysing bloodstream isolates from patients aged <18 years admitted to the paediatric intensive care, neonatology, and oncology-haematology units between 2013 and 2021. Demographics, antimicrobial susceptibility, and resistance mechanisms were analysed in two periods (2013-2017 and 2017-2021). FINDINGS: In all, 1255 isolates were included. AMR was more prevalent in older patients and those admitted to the oncology-haematology unit. Multidrug resistance was observed in 9.9% of Gram-negative bacteria (GNB); 20.0% of P. aeruginosa vs 8.6% of Entero-bacterales (P < 0.001), with an increase in Enterobacterales from 6.2% to 11.0% between the first and the second period (P = 0.021). Difficult-to-treat resistance was observed in 2.7% of GNB; 7.4% of P. aeruginosa vs 1.6% of Enterobacterales (P < 0.001), with an increasing trend in Enterobacterales from 0.8% to 2.5% (P = 0.076). Carbapenem resistance among Enterobacterales increased from 3.5% to 7.2% (P = 0.029), with 3.3% producing carbapenemases (67.9% VIM). Meticillin resistance was observed in 11.0% of S. aureus and vancomycin resistance in 1.4% of Enterococcus spp., with both rates remaining stable throughout the study period. CONCLUSION: This study reveals a high prevalence of AMR in high-complexity paediatric units. Enterobacterales showed a concerning increasing trend in resistant strains, with higher rates among older patients and those admitted to oncology-haematology units.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Criança , Humanos , Idoso , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Estudos Retrospectivos , Espanha/epidemiologia , Staphylococcus aureus , Testes de Sensibilidade Microbiana , Bactérias Gram-Negativas , Pseudomonas aeruginosa
2.
Radiologia (Engl Ed) ; 65(2): 112-121, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37059577

RESUMO

OBJECTIVES: The primary objective of this study to determine whether infiltrating carcinoma is present in surgical specimens obtained after ultrasound-guided cryoablation from patients with HER2-negative luminal breast cancer without positive axillary lymph nodes at ultrasound. The secondary objective is to demonstrate that placing the presurgical seed-marker immediately before cryoablation does not interfere with the disappearance of tumor cells from freezing or in the surgeon's ability to locate the tumor. METHODS: We treated 20 patients diagnosed with unifocal HR-positive HER2-negative infiltrating ductal carcinoma measuring <2cm by means of ultrasound-guided cryoablation (ICEfx Galil, Boston Scientific) using a triple-phase (freezing‒passive thawing‒freezing; 10min each phase) protocol. All patients later underwent tumorectomy according to the routine operating-room agenda. RESULTS: No infiltrating carcinoma cells were detected in the post-cryoablation surgical specimen in 19 patients; a focus of infiltrating carcinoma cells measuring <1mm was detected in the remaining patient. CONCLUSION: In the near future, if confirmed in larger studies with longer follow-up, cryoablation might constitute a safe and efficacious technique for the treatment of early, low-risk infiltrating ductal carcinoma. In our series, marking with ferromagnetic seeds did not interfere with the efficacy of the procedure or of the subsequent surgical intervention.


Assuntos
Neoplasias da Mama , Carcinoma Ductal , Carcinoma , Criocirurgia , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Criocirurgia/métodos , Carcinoma/cirurgia , Ultrassonografia de Intervenção
3.
J Endocrinol Invest ; 46(11): 2275-2286, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37002436

RESUMO

INTRODUCTION: Pituitary neuroendocrine tumors (PitNETs) represent 15-18.2% of all intracranial tumors. Their clinical presentation can range from chronic headache, visual defects, hypopituitarism to hormone excess syndromes. PitNETS are commonly classified as functioning neuroendocrine tumors (F-PitNETs) and non-functioning neuroendocrine tumors (NF-PitNETs). At the moment, new classification has emerged based on cell lineages. Almost 50% of all patients with PitNETs require surgical intervention, and about 25% of these have residual and persistent disease that may require additional management. SUBJECTS AND METHODS: A retrospective cohort of medical records of patients with PitNETs, aiming to describe the incidence of recurrence of patients who received surgical treatment over a 12 month follow up period at San Jose Hospital (SJH) in Bogotá, Colombia, over an observation period of 10 years. Furthermore, clinical presentation, biochemical characteristics and immunohistochemistry, postoperative complications are detailed. RESULTS: Eight hundred and eighty-seven patients with pituitary tumors were included in the cohort; 83% (737/887) had a diagnosis of PitNET. Of these, 18.9% (140) received surgical management. The majority 58% (98/140) had nonfunctional-PitNETs (NF-PitNETs), followed by growth-hormone-secreting pituitary adenoma (22.1%; 33/140), adrenocorticotropic- hormone-secreting pituitary adenoma (9.3%; 13/140), and prolactinomas (9.3%; 13/140). A recurrence was found in 45.71% (64/140), subclassified as biochemical in 15.71% (22/140), controlled with medications in 20% (28/140), and remission occurred in 18.57% (26/140). CONCLUSION: Clinical presentation and incidence of recurrence in patients with PitNETs in a referral center in Colombia are similar to other surgical cohorts with low cure rates and high recurrence.


Assuntos
Adenoma Hipofisário Secretor de ACT , Adenoma , Tumores Neuroendócrinos , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/terapia , Colômbia/epidemiologia , Estudos Retrospectivos , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/cirurgia , Adenoma Hipofisário Secretor de ACT/cirurgia , Adenoma/diagnóstico , Adenoma/epidemiologia , Adenoma/terapia , Hormônios
4.
Rev Esp Cir Ortop Traumatol ; 66(1): 68-73, 2022.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33663991

RESUMO

INTRODUCTION: One of the most frequently treated pathologies in our department are tendon lesions that affect the rotator cuff of the shoulder. There are different types of treatment for massive or irreparable tears. For a few years, a low-invasive technique was introduced based on the placement of a biodegradable subacromial spacer. The objective of the work is to analyse the results of our experience with the use of this device (InSpaceTM). MATERIAL AND METHOD: The study collects the results obtained in 25 patients with irreparable ruptures of rotator cuff defined by RM, in which they were implanted a balloon subacromial in our centre in the period from January 2015 - until December 2017. All patients were evaluated preoperatively and one year after surgery including the visual analogue scale (VAS), the Constant test (CS) and the QuickDASH (QD). RESULTS: Of the 25 patients, 5 patients (20%) were operated by arthroscopy and 20 (80%) By open approach (mini-open). A total of 22 patients completed the follow-up year. At 12 months, 64% of the patients obtained an improvement of at least 10 points in the CS. Patients departed from an initial average CS of 32 points that improved to 54.9 points of average in the postoperative evaluation at 12 months (average improvement 22.9 points; Value-p < 0.05). In terms of pain assessment, in our study, 87% of patients obtained an improvement of at least 2 points in the EVA at 12 months of follow-up (P-value < 0.05). Patients departed from an initial average EVA of 8.7 that improved to 3.7 points average at 12 months. 73% of the patients responded to be satisfied with the intervention and would return to the surgery. CONCLUSIóN: The results obtained in our series to one year of follow-up speak in favour of the use of the Subacromial Balloon (InSpaceTM), as a therapeutic option available for patients with irreparable ruptures of the rotator cuff. It can be used as an interim procedure, delaying the need for more invasive surgery, or as a definitive procedure in patients medically non-candidates for reverse arthroplasty. It is important to have clear indications of this procedure in order not to make mistakes.

5.
Nanoscale Adv ; 3(12): 3491-3496, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-36133728

RESUMO

Scientific interest in iron-oxides and in particular magnetite has been renewed due to the broad scope of their fascinating properties, which are finding applications in electronics and biomedicine. Specifically, iron oxide nanoparticles (IONPs) are gathering attraction in biomedicine. Their cores are usually constituted by a mixture of maghemite and magnetite phases. In view of this, to fine-tune the properties of an ensemble of IONPs towards their applications, it is essential to enhance mass fabrication processes towards the production of monodisperse IONPs with controlled size, shape, and stoichiometry. We exploit the vacancy sensitivity of the Verwey transition to detect the presence of magnetite. Here we provide direct evidence for the Verwey transition in an ensemble of IONPs through neutron diffraction. This transition is observed as a variation in the Fe magnetic moment at octahedral sites and, in turn, gives rise to a change of the net magnetic moment. Finally, we show this variation as the microscopic ingredient driving the characteristic kink that hallmarks the Verwey transition in thermal variation of magnetization.

6.
Rev Neurol ; 71(8): 292-297, 2020 Oct 16.
Artigo em Espanhol | MEDLINE | ID: mdl-33034367

RESUMO

INTRODUCTION: Idiopathic intracranial hypertension is an entity with an incidence of approximately 1.2: 100,000 inhabitants/year. It affects in a greater proportion obese women and women of childbearing age. Headache is the most characteristic symptom, followed by visual disturbances. In recent years, the diagnosis of dural sinus stenosis has increased in cases of intracranial hypertension resistant to conventional treatment. For this reason, the development of endovascular therapy as a therapeutic option in selected patients is booming. CASE REPORTS: We present three cases of intracranial hypertension secondary to dural sinus stenosis, diagnosed and treated in our hospital. Despite the establishment of adequate diuretic treatment and the performance of invasive procedures to bypass the cerebrospinal fluid, they persisted with neurological symptoms and visual deficits. After verifying that they fulfilled the requirements described in the literature, they underwent intracranial stenting, with satisfactory results in all of them, achieving the disappearance of the headache and recovery of visual acuity. CONCLUSION: Stenting of dural sinus stenosis as a cause of intracranial hypertension is an increasingly used technique, which has presented favorable results. Studies are necessary to know its long-term impact.


TITLE: Tratamiento endovascular de la estenosis de los senos venosos intracraneales en la hipertensión intracraneal: descripción de tres casos y discusión de la bibliografía.Introducción. La hipertensión intracraneal idiopática es una entidad con una incidencia anual aproximada de 1,2 por cada 100.000 habitantes. Afecta en mayor proporción a mujeres obesas y en edad fértil. La cefalea es el síntoma más característico, seguido de las alteraciones visuales. En los últimos años, se ha incrementado el diagnóstico de la estenosis de los senos durales en los casos de hipertensión intracraneal resistentes al tratamiento convencional. Por ello, se encuentra en auge el desarrollo de la terapia endovascular como opción terapéutica en pacientes seleccionados. Casos clínicos. Se presentan tres casos de hipertensión intracraneal secundaria a estenosis de los senos durales, diagnosticados y tratados en nuestro hospital. A pesar de la instauración del adecuado tratamiento diurético y de la realización de procedimientos invasivos de derivación del líquido cefalorraquídeo, persistían la clínica neurológica y el déficit visual. Tras comprobar que cumplían los requisitos descritos en la bibliografía, se sometieron a la implantación de stent intracraneal (stenting), con resultado satisfactorio en todos ellos, logrando la desaparición de la cefalea y la recuperación de la agudeza visual. Conclusión. El stenting de la estenosis de los senos durales como causa de hipertensión intracraneal es una técnica cada vez más utilizada que ha presentado resultados favorables. Es necesaria la realización de estudios para conocer su impacto a largo plazo.


Assuntos
Pseudotumor Cerebral , Stents , Constrição Patológica , Feminino , Humanos , Pseudotumor Cerebral/complicações , Pseudotumor Cerebral/terapia , Transtornos da Visão/etiologia
7.
Exp Oncol ; 42(2): 101-108, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32602283

RESUMO

BACKGROUND: Blueberries are among the fruits with the highest antioxidant activity and have been recognized by their health promoting properties. AIM: In vitro study of the anti-proliferative effects of a blueberry extract on a panel of cancer cells from different origin. MATERIALS AND METHODS: A blueberry extract was produced using ethanol as extracting solvent. The anti-proliferative activity of the extract was evaluated against seven tumor cell lines. The properties of blueberry extract to decrease cell adhesion and migration were also investigated. RESULTS: Blueberry extract showed a dose-dependent inhibitory effect on cell proliferation for all cell lines. Non-cytotoxic concentrations of the extract decreased cell adhesion in five of seven cell lines studied and inhibited the migration of MDA-MB-231 and PC-3 tumor cells. CONCLUSION: This work provides additional evidence regarding the ability of blueberry extract to inhibit the growth and decrease cell adhesion and migration of different cancer cell lines in vitro.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Mirtilos Azuis (Planta)/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Antocianinas/análise , Antineoplásicos Fitogênicos/química , Antioxidantes/química , Antioxidantes/farmacologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Masculino , Polifenóis/análise
8.
Nanotechnology ; 29(42): 425705, 2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30052525

RESUMO

Clustering of magnetic nanoparticles can drastically change their collective magnetic properties, which in turn may influence their performance in technological or biomedical applications. Here, we investigate a commercial colloidal dispersion (FeraSpinTMR), which contains dense clusters of iron oxide cores (mean size around 9 nm according to neutron diffraction) with varying cluster size (about 18-56 nm according to small angle x-ray diffraction), and its individual size fractions (FeraSpinTMXS, S, M, L, XL, XXL). The magnetic properties of the colloids were characterized by isothermal magnetization, as well as frequency-dependent optomagnetic and AC susceptibility measurements. From these measurements we derive the underlying moment and relaxation frequency distributions, respectively. Analysis of the distributions shows that the clustering of the initially superparamagnetic cores leads to remanent magnetic moments within the large clusters. At frequencies below 105 rad s-1, the relaxation of the clusters is dominated by Brownian (rotation) relaxation. At higher frequencies, where Brownian relaxation is inhibited due to viscous friction, the clusters still show an appreciable magnetic relaxation due to internal moment relaxation within the clusters. As a result of the internal moment relaxation, the colloids with the large clusters (FS-L, XL, XXL) excel in magnetic hyperthermia experiments.

9.
Crit Rev Oncol Hematol ; 124: 29-36, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29548483

RESUMO

Rac1 GTPase signaling pathway has a critical role in the regulation of a plethora of cellular functions governing cancer cell behavior. Recently, it has been shown a critical role of Rac1 in the emergence of resistance mechanisms to cancer therapy. This review describes the current knowledge regarding Rac1 pathway deregulation and its association with chemoresistance, radioresistance, resistance to targeted therapies and immune evasion. This supports the idea that interfering Rac1 signaling pathway could be an interesting approach to tackle cancer resistance.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Tolerância a Radiação/genética , Proteínas rac1 de Ligação ao GTP/fisiologia , Animais , Humanos , Terapia de Alvo Molecular , Neoplasias/genética , Transdução de Sinais/genética , Evasão Tumoral/genética
10.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29217349

RESUMO

OBJECTIVE: To assess the radiological and functional outcome of arthrodesis of the 4th and 5th finger using the APEX™ (Extremity Medical, Parsippany,NJ)intermedullary interlocking screw system in patients with severe recurrence of Dupuytren's disease. MATERIAL AND METHOD: The DASH questionnaire and the VAS scale were used to assess the clinical outcomes. The angle of arthrodesis, fusion time and implant fixation were evaluated on x-rays. The patients were monitored for complications during surgery and the follow-up period. RESULTS: The sample comprised 6 patients. Mean follow up was 19.6 months. All of the patients presented clinical and radiological evidence of fusion at 8 weeks, with fusion angles of 30° (3) and 45° (3). There were no complications and none of the implants had to be removed. The functional outcomes in these patients were poor. CONCLUSION: The system offers a reliable method for IPJ arthrodesis at a precise angle. It promotes stable fixation that does not require prolonged immobilisation. It can be used together with other procedures on the hand with severe recurrence of DD. The functional outcomes for this group of patients using this device were poor.


Assuntos
Artrodese/instrumentação , Parafusos Ósseos , Contratura de Dupuytren/cirurgia , Articulações dos Dedos/cirurgia , Idoso , Artrodese/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
11.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28882464

RESUMO

The study objective was to assess the results of a thumb metacarpophalangeal joint (MCPJ) arthrodesis using intramedullary interlocking screws at 25°, XMCP ™ (Extremity Medical, Parsippany, NJ). Radiographs evaluated the angle of arthrodesis, time of fusion and fixation of the implant. Clinical and functional outcomes were assessed using the DASH questionnaire and the VAS scale. Any complications found during surgery or the follow-up period were noted. We studied 9 patients. The mean follow-up was 27.6 months. Patients showed clinical and radiological evidence of fusion in an average of 8 weeks, the angle of fusion was 25°. There were no complications and no implant had to be removed. The XMCP™ system provides a reliable method for MCPJ arthrodesis for several indications and can be used with other procedures in the complex hand.


Assuntos
Artrodese/instrumentação , Parafusos Ósseos , Artropatias/cirurgia , Articulação Metacarpofalângica/cirurgia , Polegar/cirurgia , Idoso , Artrite Reumatoide/cirurgia , Artrodese/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
12.
Andrology ; 5(6): 1089-1099, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28950428

RESUMO

Numerous health consequences of tobacco smoke exposure have been characterized, and the effects of smoking on traditional measures of male fertility are well described. However, a growing body of data indicates that pre-conception paternal smoking also confers increased risk for a number of morbidities on offspring. The mechanism for this increased risk has not been elucidated, but it is likely mediated, at least in part, through epigenetic modifications transmitted through spermatozoa. In this study, we investigated the impact of cigarette smoke exposure on sperm DNA methylation patterns in 78 men who smoke and 78 never-smokers using the Infinium Human Methylation 450 beadchip. We investigated two models of DNA methylation alterations: (i) consistently altered methylation at specific CpGs or within specific genomic regions and (ii) stochastic DNA methylation alterations manifest as increased variability in genome-wide methylation patterns in men who smoke. We identified 141 significantly differentially methylated CpGs associated with smoking. In addition, we identified a trend toward increased variance in methylation patterns genome-wide in sperm DNA from men who smoke compared with never-smokers. These findings of widespread DNA methylation alterations are consistent with the broad range of offspring heath disparities associated with pre-conception paternal smoke exposure and warrant further investigation to identify the specific mechanism by which sperm DNA methylation perturbation confers risk to offspring health and whether these changes can be transmitted to offspring and transgenerationally.


Assuntos
Fumar Cigarros/efeitos adversos , Metilação de DNA , Espermatozoides , Adulto , Ilhas de CpG , Humanos , Masculino
13.
Phys Med ; 37: 37-42, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28535913

RESUMO

PURPOSE: This study aimed to characterize the radiation exposure to patients and workers in a new vascular hybrid operating room during X-ray-guided procedures. METHODS: During one year, data from 260 interventions performed in a hybrid operating room equipped with a Siemens Artis Zeego angiography system were monitored. The patient doses were analysed using the following parameters: radiation time, kerma-area product, patient entrance reference point dose and peak skin dose. Staff radiation exposure and ambient dose equivalent were also measured using direct reading dosimeters and thermoluminescent dosimeters. RESULTS: The radiation time, kerma-area product, patient entrance reference point dose and peak skin dose were, on average, 19:15min, 67Gy·cm2, 0.41Gy and 0.23Gy, respectively. Although the contribution of the acquisition mode was smaller than 5% in terms of the radiation time, this mode accounted for more than 60% of the effective dose per patient. All of the worker dose measurements remained below the limits established by law. CONCLUSIONS: The working conditions in the hybrid operating room HOR are safe in terms of patient and staff radiation protection. Nevertheless, doses are highly dependent on the workload; thus, further research is necessary to evaluate any possible radiological deviation of the daily working conditions in the HOR.


Assuntos
Exposição Ocupacional , Salas Cirúrgicas , Doses de Radiação , Angiografia/instrumentação , Feminino , Pessoal de Saúde , Humanos , Masculino , Monitoramento de Radiação , Proteção Radiológica , Radiografia Intervencionista , Raios X
14.
Actas Urol Esp ; 41(8): 516-521, 2017 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28389028

RESUMO

INTRODUCTION: Microperc is the upgraded form of percutaneous nephrolithotomy miniaturization. The aim of this study is to compare prospectively microperc and retrograde intrarenal surgery for the treatment of renal stones smaller than 2 cm. MATERIAL AND METHODS: A comparative prospective study of both techniques was carried out between January 2014 and June 2015. Thirty-five patients were divided in two groups: Group A, 17 patients treated by retrograde intrarenal surgery and Group B, 18 patients treated by microperc. Stone clearance was assessed using CT scan 3 months after surgery. RESULTS: Both groups were statistically comparable as demographic variables and stone size was similar (16.76 mm Group A vs 15.72 mm Group B). Success rate, hospital stay and JJ stenting were similar for both groups. There was no statistically significant difference regarding post-operatory complications: 17.64% Group A vs 5.56% Group B (p=0,062), all of them Clavien I and II. Surgical time was statistically different (63.82 min Group A vs 103.24 min Group B) as well as hemoglobin drop (0.62 g/dl Group A and 1.89 g/dl Group B). CONCLUSION: Microperc is an effective and safe procedure for the treatment of renal lithiasis smaller than 2 cm, which makes it a good alternative to retrograde intrarenal surgery for this stone size. However, more prospective studies that include a larger cohort are necessary to confirm our results.


Assuntos
Cálculos Renais/cirurgia , Nefrolitotomia Percutânea/métodos , Ureteroscopia/métodos , Adulto , Perda Sanguínea Cirúrgica , Feminino , Tecnologia de Fibra Óptica , Humanos , Cálculos Renais/patologia , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias , Estudos Prospectivos , Resultado do Tratamento
16.
Cell Signal ; 30: 154-161, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27939839

RESUMO

Tamoxifen is a standard endocrine therapy for estrogen receptor positive breast cancer patients. Despite its success, development of resistance mechanisms is still a serious clinical problem. Deregulation of survival signaling pathways play a key role in tamoxifen resistance, being upregulation of Rac1-PAK1 signaling pathway one of the most important. Here, we report the development of the breast cancer cell model MCF7::C1199 having Rac1 enhanced activity with the aim of evaluating the role of Rac1 in acquired endocrine resistance. These cells not only showed distinctive features of Rac1-regulated process as increased migration and proliferation rates, but also showed that upregulation of Rac1 activity triggered a hormonal-independent and tamoxifen resistant phenotype. We also demonstrated that PAK1 activity increases in response to Tamoxifen, increasing phosphorylation levels of estrogen receptor at Ser305, a key phosphorylation site involved in tamoxifen resistance. Finally, we evaluated the effect of 1A-116, a specific Rac1 inhibitor developed by our group, in tamoxifen-resistant cells. 1A-116 effectively restored tamoxifen anti-proliferative effects, switched off PAK1 activity and decreased estrogen receptor phospho-Ser305 levels. Since combination schemes of novel targeted agents with endocrine therapy could be potential new strategies to restore tamoxifen sensibility, these results show that inhibition of Rac1-PAK1 signaling pathway may provides benefits to revert resistance mechanisms in endocrine therapies.


Assuntos
Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacos , Tamoxifeno/farmacologia , Quinases Ativadas por p21/antagonistas & inibidores , Proteínas rac1 de Ligação ao GTP/antagonistas & inibidores , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Estrogênios/farmacologia , Feminino , Humanos , Células MCF-7 , Modelos Biológicos , Fenótipo , Fosforilação/efeitos dos fármacos , Fosfosserina/metabolismo , Regulação para Cima/efeitos dos fármacos , Quinases Ativadas por p21/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo
18.
Cell Death Dis ; 6: e1902, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26469953

RESUMO

Receptor-associated coactivator 3 (RAC3) is a nuclear receptor coactivator usually overexpressed in tumors that exerts oncogenic functions in the cytoplasm and the nucleus. Although as part of its oncogenic actions it was previously identified as an inhibitor of apoptosis and autophagy, its expression is required in order to preserve the pluripotency and embryonic stem cell self-renewal. In this work we investigated its role in cellular senescence. We found that RAC3 overexpression in the nontumoral HEK293 cells inhibits the premature senescence induced by hydrogen peroxide or rapamycin. The mechanism involves not only the inhibition of autophagy early induced by these stimuli in the pathway to senescence, but also the increase in levels and nuclear localization of both the cell cycle suppressors p53/p21 and the longevity promoters FOXO1A, FOXO3A and SIRT1. Furthermore, we found that RAC3 overexpression is required in order to maintain the telomerase activity. In tumoral HeLa cells its activity was inhibited by depletion of RAC3 inducing replicative senescence. Moreover, we demonstrated that in vivo, levels of RAC3 are downregulated in the liver from aged as compared with young rats, whereas the levels of p21 are increased, correlating with the expected senescent cell contents in aged tissues. A similar downregulation of RAC3 was observed in the premature and replicative senescence of human fetal WI-38 cells and premature senescence of hepatocyte HepG2 cell line. Taken together, all these results demonstrate that RAC3 is an inhibitor of senescence whose downregulation in aged individuals could be probably a tumor suppressor mechanism, avoiding the clonal expansion of risky old cells having damaged DNA.


Assuntos
Proteínas rac de Ligação ao GTP/fisiologia , Envelhecimento , Animais , Proliferação de Células , Senescência Celular , Regulação para Baixo , Feminino , Expressão Gênica , Técnicas de Silenciamento de Genes , Células HEK293 , Células HeLa , Humanos , Peróxido de Hidrogênio/farmacologia , Ratos Wistar , Sirolimo/farmacologia
19.
Br J Cancer ; 112(10): 1636-43, 2015 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-25880012

RESUMO

BACKGROUND: We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose. METHODS: Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using (99)Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry. RESULTS: Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1 ± 8.9 vs 31.3 ± 12.9 mg (P = 0.01). Both, AUC24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P < 0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P = 0.03) in tumour specimens. CONCLUSION: Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.


Assuntos
Peptídeos Cíclicos/administração & dosagem , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Área Sob a Curva , Método Duplo-Cego , Regulação para Baixo/efeitos dos fármacos , Feminino , Meia-Vida , Humanos , Injeções Intralesionais/métodos , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , Nucleofosmina , Neoplasias do Colo do Útero/metabolismo
20.
Actas Urol Esp ; 38(9): 571-5, 2014 Nov.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-24881777

RESUMO

OBJECTIVES: The objectives of this prospective study are to present our experience with retrograde intrarenal surgery (RIRS), and to analyze its results and complications. MATERIAL AND METHODS: 150 patients with renal stones were treated with RIRS. 111 cases showed single stones whilst multiple stones were observed in 39 cases. The mean size was 19.12mm (r: 5-74). Success rate was defined as the absence of residual stones or the presence of fragments ≤2mm. RESULTS: in 21 (14%) patients RIRS could not be performed on first attempt because it was impossible to place the ureteral access sheath. The immediate success rate was 85.7%, and 91.6% at three months later. The average operating time was 85min (r: 25-220). Postoperative complications were observed in 22 cases (14.6%), although most of them were classified as Clavien 1 and 2 (19 cases), and only 2% (3 cases) showed Clavien 4 complications (sepsis requiring admission in the intensive care unit). 10 patients underwent a second procedure in order to complete the treatment. Thus, the number of procedures per patient was 1.06. There were no late complications. CONCLUSIONS: the treatment of renal stones with flexible ureteroscopy using the ureteral access sheath shows a high successful rate with a low complication rate. In order to define its indication more precisely, randomized studies comparing RIRS with minimally invasive percutaneous nephrolithotomy procedures (miniperc and microperc) would be necessary.


Assuntos
Cálculos Renais/cirurgia , Ureteroscopia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA