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1.
Mult Scler Relat Disord ; 56: 103266, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34555758

RESUMO

BACKGROUND: Patients with Multiple Sclerosis (MS) undergoing treatment with natalizumab (NTZ) are at risk of developing progressive multifocal leukoencephalopathy (PML) due to the reactivation of John Cunningham (JC) virus. A relevant characteristic among PML cases is the development of single nucleotide mutations in the VP1 gene of the causal JC virus. The identification of such mutations in timely manner can provide valuable information for MS management. OBJECTIVE: To identify mutations along the JC virus VP1 gene in MS patients undergoing treatment with NTZ, and correlate them with anti-JC virus antibody index. METHODS: Eighty-eight MS patients, one hundred twenty controls, and six patients with diagnosis of Human Immunodeficiency Virus (HIV) with and without secondary PML were included. JC virus was identified in peripheral blood mononuclear cells and cerebrospinal fluid by PCR. Amplification and sequencing of the entire length of the VP1 gene were performed in all positive clinical samples. RESULTS: In MS cases no mutations were observed in the JC virus VP1 gene, but it was positive in HIV controls with PML. Interestingly, the JC virus VP1 gene sequence derived from the HIV patients exhibited a non-silent substitution in position 186 (G â†’ C), leading to an amino acid change (Lys â†’ Asp). We did not find correlation between anti-JC virus antibody index and DNA viral detection. CONCLUSIONS: . The identification of single nucleotide mutants in the JC virus VP1 gene might be an early predictive marker to PML for efficient patient treatment and follow-up.


Assuntos
Vírus JC , Leucoencefalopatia Multifocal Progressiva , Esclerose Múltipla , Infecções por HIV , Humanos , Vírus JC/genética , Leucócitos Mononucleares , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/genética , Mutação , Natalizumab/uso terapêutico
2.
Clin Transl Oncol ; 23(10): 2099-2108, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33864619

RESUMO

PURPOSE: We aimed to evaluate the current situation of electronic health records (EHRs) and patient registries in the oncology departments of hospitals in Spain. METHODS: This was a cross-sectional study conducted from December 2018 to September 2019. The survey was designed ad hoc by the Outcomes Evaluation and Clinical Practice Section of the Spanish Society of Medical Oncology (SEOM) and was distributed to all head of medical oncology department members of SEOM. RESULTS: We invited 148 heads of oncology departments, and 81 (54.7%) questionnaires were completed, with representation from all 17 Spanish autonomous communities. Seventy-seven (95%) of the respondents had EHRs implemented at their hospitals; of them, over 80% considered EHRs to have a positive impact on work organization and clinical practice, and 73% considered that EHRs improve the quality of patient care. In contrast, 27 (35.1%) of these respondents felt that EHRs worsened the physician-patient relationship and conveyed an additional workload (n = 29; 37.6%). Several drawbacks in the implementation of EHRs were identified, including the limited inclusion of information on both outpatients and inpatients, information recorded in free text data fields, and the availability of specific informed consent. Forty-six (56.7%) respondents had patient registries where they recorded information from all patients seen in the department. CONCLUSION: Our study indicates that EHRs are almost universally implemented in the hospitals surveyed and are considered to have a positive impact on work organization and clinical practice. However, EHRs currently have several drawbacks that limit their use for investigational purposes. CLINICAL TRIAL REGISTRATION: Not applicable.


Assuntos
Registros Eletrônicos de Saúde/estatística & dados numéricos , Oncologia/estatística & dados numéricos , Serviço Hospitalar de Oncologia/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Atitude do Pessoal de Saúde , Estudos Transversais , Prescrição Eletrônica/estatística & dados numéricos , Humanos , Relações Médico-Paciente , Qualidade da Assistência à Saúde , Espanha , Inquéritos e Questionários/estatística & dados numéricos , Carga de Trabalho
3.
Ann Oncol ; 32(4): 488-499, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33385521

RESUMO

BACKGROUND: Palbociclib plus endocrine therapy (ET) is the standard treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative, metastatic breast cancer (MBC). However, its efficacy has not been compared with that of chemotherapy in a phase III trial. PATIENTS AND METHODS: PEARL is a multicentre, phase III randomised study in which patients with aromatase inhibitor (AI)-resistant MBC were included in two consecutive cohorts. In cohort 1, patients were randomised 1 : 1 to palbociclib plus exemestane or capecitabine. On discovering new evidence about estrogen receptor-1 (ESR1) mutations inducing resistance to AIs, the trial was amended to include cohort 2, in which patients were randomised 1 : 1 between palbociclib plus fulvestrant and capecitabine. The stratification criteria were disease site, prior sensitivity to ET, prior chemotherapy for MBC, and country of origin. Co-primary endpoints were progression-free survival (PFS) in cohort 2 and in wild-type ESR1 patients (cohort 1 + cohort 2). ESR1 hotspot mutations were analysed in baseline circulating tumour DNA. RESULTS: From March 2014 to July 2018, 296 and 305 patients were included in cohort 1 and cohort 2, respectively. Palbociclib plus ET was not superior to capecitabine in both cohort 2 [median PFS: 7.5 versus 10.0 months; adjusted hazard ratio (aHR): 1.13; 95% confidence interval (CI): 0.85-1.50] and wild-type ESR1 patients (median PFS: 8.0 versus 10.6 months; aHR: 1.11; 95% CI: 0.87-1.41). The most frequent grade 3-4 toxicities with palbociclib plus exemestane, palbociclib plus fulvestrant and capecitabine, respectively, were neutropenia (57.4%, 55.7% and 5.5%), hand/foot syndrome (0%, 0% and 23.5%), and diarrhoea (1.3%, 1.3% and 7.6%). Palbociclib plus ET offered better quality of life (aHR for time to deterioration of global health status: 0.67; 95% CI: 0.53-0.85). CONCLUSIONS: There was no statistical superiority of palbociclib plus ET over capecitabine with respect to PFS in MBC patients resistant to AIs. Palbociclib plus ET showed a better safety profile and improved quality of life.


Assuntos
Inibidores da Aromatase , Neoplasias da Mama , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Capecitabina/uso terapêutico , Família de Proteínas EGF/uso terapêutico , Humanos , Piperazinas , Piridinas , Qualidade de Vida , Receptor ErbB-2/genética , Receptores de Estrogênio
5.
Clin Transl Oncol ; 20(7): 862-869, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29178019

RESUMO

INTRODUCTION: This study aimed to describe the efficacy of fulvestrant 500 mg in postmenopausal women with estrogen receptor (ER)-positive advanced/metastatic breast cancer who had disease progression after receiving anti-estrogen therapy in clinical practice, getting real-world data. MATERIALS AND METHODS: Multicenter, retrospective, observational study conducted in Spain. Postmenopausal women with locally advanced/metastatic ER-positive breast cancer who received treatment with fulvestrant 500 mg after progression with a previous anti-estrogen therapy were eligible. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), clinical benefit rate (CBR), duration of clinical benefit (DoCB), and safety profile. RESULTS: A total of 263 women were evaluated (median age, 65.8 years). At a median follow-up of 21.5 months, median PFS and OS were 10.6 and 43.2 months, respectively. PFS according to 1st, 2nd, 3rd, and ≥ 4th lines were 11.5, 10.6, 9.9, and 8.5 months, respectively (p = 0.0245). PFS in patients with visceral involvement was 10 months vs 10.6 months in patients without visceral involvement (p = 0.6604), 9.6 months in patients with high Ki67 vs 10 months in patients with low Ki67 (p = 0.7224), and 10.2 months in HER2+ patients vs 10.3 months in HER2- patients (p = 0.6809). The CBR was 56.5% and the DoCB was 18.4 months. The most frequently adverse events were injection site pain (10.3%) and musculoskeletal disorders (7.6%). CONCLUSIONS: Fulvestrant 500 mg administered in clinical practice was shown to be effective (PFS, 10.6 months; CBR, 56.5%) and well tolerated, in accordance with previous trials.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Lobular/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Estradiol/análogos & derivados , Pós-Menopausa , Idoso , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/metabolismo , Carcinoma Lobular/secundário , Estradiol/uso terapêutico , Feminino , Seguimentos , Fulvestranto , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos
6.
Gastric Cancer ; 21(1): 96-105, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28393278

RESUMO

BACKGROUND: Although anthracycline-based triplets are one of the most widely used schedules to treat advanced gastric cancer (AGC), the benefit of including epirubicin in these therapeutic combinations remains unknown. This study aims to evaluate both the efficacy and tolerance of triplets with epirubicin vs. doublets with platinum-fluoropyrimidine in a national AGC registry. METHODS: Patients with AGC treated with polychemotherapy without trastuzumab at 28 hospitals in Spain between 2008 and 2016 were included. The effect of anthracycline-based triplets against doublets was evaluated by propensity score matching (PSM) and Cox proportional hazards (PH) regression. RESULT: A total of 1002 patients were included (doublets, n = 653; anthracycline-based triplets, n = 349). The multivariable Cox PH regression failed to detect significantly increased OS in favor of triplets with anthracyclines: HR 0.90 (95% CI, 0.78-1.05), p = 0.20035. After PSM, the sample contained 325 pairs with similar baseline characteristics. This method was also unable to reveal an increase in OS: 10.5 (95% CI, 9.7-12.3) vs. 9.9 (95% CI, 9.2-11.4) months, HR 0.91 (CI 95%, 0.76-1.083), and (log-rank test, p = 0.226). Response rates (42.1 vs. 33.1%, p = 0.12) and PFS (HR 0.95, CI 95%, 0.80-1.13, log-rank test, p = 0.873) were not significantly higher with epirubicin-based regimens. The triplets were associated with greater grade 3-4 hematological toxicity, and increased hospitalization due to toxicity by 68%. The addition of epirubicin is viable, but 23.7% discontinued treatment because of adverse effects or patient decision. CONCLUSION: Anthracyclines added to platinum-fluoropyrimidine doublets did not improve the response rate or survival outcomes in patients with AGC but entailed greater toxicity.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Antraciclinas/administração & dosagem , Antraciclinas/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Sistema de Registros
7.
Br J Cancer ; 116(12): 1526-1535, 2017 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-28463962

RESUMO

BACKGROUND: To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination chemotherapy. METHODS: Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrell's c-index was used to evaluate discrimination. RESULTS: The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5-6.6), 9.4 (95% CI, 8.5-10.6), and 14 months (95% CI, 11.8-16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3-8.1), 12.7 (95% CI, 11.3-14.3), and 18.3 months (95% CI, 14.6-24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591-0.631) and 0.673 (95% CI, 0.636-0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351). CONCLUSIONS: We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/secundário , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica , Nomogramas , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/química , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Ascite/etiologia , Neoplasias Esofágicas/química , Neoplasias Esofágicas/patologia , Nível de Saúde , Humanos , Contagem de Linfócitos , Pessoa de Meia-Idade , Gradação de Tumores , Neutrófilos , Receptor ErbB-2/análise , Neoplasias Gástricas/química , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Trastuzumab/administração & dosagem , Carga Tumoral , População Branca , Adulto Jovem
8.
Clin Transl Oncol ; 19(2): 149-161, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27314861

RESUMO

Metastatic breast cancer is a heterogeneous disease that presents in varying forms, and a growing number of therapeutic options makes it difficult to determine the best choice in each particular situation. When selecting a systemic treatment, it is important to consider the medication administered in the previous stages, such as acquired resistance, type of progression, time to relapse, tumor aggressiveness, age, comorbidities, pre- and post-menopausal status, and patient preferences. Moreover, tumor genomic signatures can identify different subtypes, which can be used to create patient profiles and design specific therapies. However, there is no consensus regarding the best treatment sequence for each subgroup of patients. During the SABCC Congress of 2014, specialized breast cancer oncologists from referral hospitals in Europe met to define patient profiles and to determine specific treatment sequences for each one. Conclusions were then debated in a final meeting in which a relative degree of consensus for each treatment sequence was established. Four patient profiles were defined according to established breast cancer phenotypes: pre-menopausal patients with luminal subtype, post-menopausal patients with luminal subtype, patients with triple-negative subtype, and patients with HER2-positive subtype. A treatment sequence was then defined, consisting of hormonal therapy with tamoxifen, aromatase inhibitors, fulvestrant, and mTOR inhibitors for pre- and post-menopausal patien ts; a chemotherapy sequence for the first, second, and further lines for luminal and triple-negative patients; and an optimal sequence for treatment with new antiHER2 therapies. Finally, a document detailing all treatment sequences, that had the agreement of all the oncologists, was drawn up as a guideline and advocacy tool for professionals treating patients with this disease.


Assuntos
Antineoplásicos/normas , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo
9.
J Mater Chem B ; 4(24): 4356-4365, 2016 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-32263418

RESUMO

Large and critical bone defect reconstruction is still a hard challenge in tumor resections, non-unions, some traumatisms and articular prosthesis revisions. The application of electron beam melting technology (EBM) to implant manufacturing constitutes a promising alternative, which provides better biomechanics and customized solutions. Implant infections are one of the most serious complications associated with surgical treatments, which require immediate solutions for achieving better clinical results. Herein, to confer antimicrobial properties, a simple and cost-effective approach based on a bifunctionalization process to create a zwitterionic surface on Ti6Al4V EBM implants is proposed. The obtained results show a notable reduction of bacterial adhesion (more than 97%) and total inhibition of biofilm formation, combined with demonstrated biocompatibility and bioactivity, permitting cell adhesion on the entire surface of these 3D zwitterionic scaffolds. This surface zwitterionization provides new perspectives for custom-made Ti6Al4V EBM implants for bone tissue regeneration with antimicrobial properties.

10.
Clin Transl Oncol ; 17(12): 939-45, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26497356

RESUMO

Breast cancer is a major public health problem. Despite remarkable advances in early diagnosis and treatment, one in three women may have metastases since diagnosis. Better understanding of prognostic and predictive factors allows us to select the most appropriate adjuvant therapy in each patient. In these guidelines, we summarize current evidence for the medical management of early-stage breast cancer.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/prevenção & controle , Oncologia , Guias de Prática Clínica como Assunto/normas , Sociedades Médicas , Feminino , Humanos , Estadiamento de Neoplasias
11.
Clin Transl Oncol ; 16(12): 1091-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25392080

RESUMO

Cancer of unknown primary site is a histologically confirmed cancer which is manifested in advanced stage, with no identifiable primary site after the use of standard diagnostic procedures. Patients are initially placed into one of categories based upon the examination of the initial biopsy: adenocarcinoma, squamous cell carcinoma, neuroendocrine carcinoma and poorly differentiated carcinoma. Appropriate patient management requires an understanding of several clinicopathologic features that help to identify several subsets of patients with more responsive tumors.


Assuntos
Carcinoma/diagnóstico , Carcinoma/terapia , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Primárias Desconhecidas/terapia , Humanos
12.
Curr Med Chem ; 21(10): 1231-46, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24372208

RESUMO

Human forkhead box class O (FoxO) transcription factors, activated in response to a wide range of external stimuli, like growth factors, insulin, nutrient levels and oxidative stress, are able to control several specific geneexpression programs. Besides their clear implication in metabolic processes, they appear to play a relevant role in tumour suppression by upregulation of genes involved in cell cycle arrest or apoptosis. Recent research efforts provide new insights into the molecular modulation of FoxO in liver cancer and disclose potential opportunities for developing new antitumor drugs. Through an intricate regulatory model, achieved via several post-translational modifications, including phosphorylation, acetylation, and ubiquitination, which control their subcellular localization and DNA binding activity, FoxO factors act as tumour suppressors. Low levels of FoxOs are associated with poor prognosis in cancer patients, and seem to confer chemotherapy resistance. Within FoxO members, FoxO3a appears to present anti-tumour properties in hepatocellular carcinoma, inducing the expression of pro-apoptotic genes, or interfering with signaling cascades commonly altered in this disease such as Wnt/ß-catenin, PI3K/AKT/mTOR or MAPKs pathways. Here, we describe the main mechanisms of FoxO proteins regulation, and their cross-link with altered pathways in liver cancer. Moreover, based on the current knowledge of FoxO modulation, emphasis is placed on the development of novel agents which specifically activate FoxO family members and could be useful in the treatment of hepatocarcinoma.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Fatores de Transcrição Forkhead/agonistas , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/tratamento farmacológico , Proteínas Supressoras de Tumor/agonistas , Acetilação , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Terapia de Alvo Molecular , Fosforilação , Processamento de Proteína Pós-Traducional , Transdução de Sinais , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitinação
13.
Clin Transl Oncol ; 16(4): 351-61, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24085574

RESUMO

The increase in life expectancy in the western world means that we are faced with patients diagnosed with breast cancer in old age with increasing frequency. The management of these cases is a challenge for the oncologist, who must take into account the conditions associated with advanced age and the lack of trials in this population. In this review, we addressed the incorporation of geriatric assessment methods that may be useful in making decisions, the particular biological characteristics of breast cancer in elderly patients and their treatment in both localized and advanced disease. Finally, we collected recommendations based on scientific evidence regarding the monitoring and life-style after finishing treatment.


Assuntos
Neoplasias da Mama/terapia , Avaliação Geriátrica/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos
14.
Br J Cancer ; 109(1): 83-91, 2013 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-23756865

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) growth relies on angiogenesis via vascular endothelial growth factor (VEGF) release. Hypoxia within tumour environment leads to intracellular stabilisation of hypoxia inducible factor 1 alpha (Hif1α) and signal transducer and activator of transcription (STAT3). Melatonin induces apoptosis in HCC, and shows anti-angiogenic features in several tumours. In this study, we used human HepG2 liver cancer cells as an in vitro model to investigate the anti-angiogenic effects of melatonin. METHODS: HepG2 cells were treated with melatonin under normoxic or CoCl2-induced hypoxia. Gene expression was analysed by RT-qPCR and western blot. Melatonin-induced anti-angiogenic activity was confirmed by in vivo human umbilical vein endothelial cells (HUVECs) tube formation assay. Secreted VEGF was measured by ELISA. Immunofluorescence was performed to analyse Hif1α cellular localisation. Physical interaction between Hif1α and its co-activators was analysed by immunoprecipitation and chromatin immunoprecipitation (ChIP). RESULTS: Melatonin at a pharmacological concentration (1 mM) decreases cellular and secreted VEGF levels, and prevents HUVECs tube formation under hypoxia, associated with a reduction in Hif1α protein expression, nuclear localisation, and transcriptional activity. While hypoxia increases phospho-STAT3, Hif1α, and CBP/p300 recruitment as a transcriptional complex within the VEGF promoter, melatonin 1 mM decreases their physical interaction. Melatonin and the selective STAT3 inhibitor Stattic show a synergic effect on Hif1α, STAT3, and VEGF expression. CONCLUSION: Melatonin exerts an anti-angiogenic activity in HepG2 cells by interfering with the transcriptional activation of VEGF, via Hif1α and STAT3. Our results provide evidence to consider this indole as a powerful anti-angiogenic agent for HCC treatment.


Assuntos
Inibidores da Angiogênese/farmacologia , Carcinoma Hepatocelular/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas/metabolismo , Melatonina/farmacologia , Fator de Transcrição STAT3/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Apoptose/efeitos dos fármacos , Hipóxia Celular , Cobalto , Óxidos S-Cíclicos/farmacologia , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Células Endoteliais da Veia Umbilical Humana , Humanos , Neovascularização Patológica/tratamento farmacológico , Regiões Promotoras Genéticas , Transdução de Sinais , Transcrição Gênica , Ativação Transcricional , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genética , Fatores de Transcrição de p300-CBP/metabolismo
15.
Cir Pediatr ; 25(1): 28-34, 2012 Jan.
Artigo em Espanhol | MEDLINE | ID: mdl-23113410

RESUMO

OBJECTIVES: One stop surgery (CAR: Cirugía Alta Resolución) is a step forward in outpatient surgery. The new scheme simplifies ambulatory conventional surgery, achieves more satisfaction between patients and optimizes health resources. METHODS: By One stop surgery we mean the performance in the same day of both pre-surgery assessment and surgical procedure. This new working way allows performing a surgical procedure in only one visit to the hospital, instead of the average four visits used before for surgical outpatients. Diagnosis, presurgery assessment and post surgery progress are made by the primary care paediatricians at theirs NHS offices. It is essential to maintain a close relationship between the Paediatric surgeons, the primary care paediatricians as well as with paediatric anaesthesiologists and nurses. An autoevaluation is made once a year in which quality survey results are made public and possible areas for improvement are identified, following the model proposed by the European Foundation for Quality Management (EFQM). RESULTS: We present 416 children treated following this scheme since 2008. Surgery is performed on the abdominal wall, genitals, skin and soft tissues. Families are satisfied with the quality of the whole medical and nursery received care as they qualified it with a 99% satisfaction index. Complications developed in less than 3%. CONCLUSIONS: One stop surgery is a progress in the outpatient surgery and, for us, it is a consolidated, continuously growing and constantly improving scheme of providing medical care.


Assuntos
Procedimentos Cirúrgicos Ambulatórios/normas , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Satisfação do Paciente , Qualidade da Assistência à Saúde , Inquéritos e Questionários
16.
Purinergic Signal ; 8(2): 199-206, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21969137

RESUMO

Ionotropic purinergic receptors (P2X) are expressed in endothelial and smooth muscle cells of blood vessels. ATP acting on smooth muscle P2X receptors is able to induce vasoconstriction in different kind of vessels. However, to our knowledge, there are no reports that directly show the activity of these purinergic receptors in native human vascular smooth muscle cells. In this work, we describe for the first time an ATP-induced current in freshly isolated human umbilical artery (HUA) smooth muscle cells. The current was measured by patch-clamp technique in whole-cell condition on cells clamped at -50 mV. At 100 µM of ATP the current showed a rapid activation and desensitization, and was carried by both Na(+) and Ca(2+). The current was completely blocked by suramin (300 µM) and partially blocked by 100 µM of Zn(2+) without affecting the kinetic of desensitization. All these properties suggest that the ATP-induced ionic currents are mediated through P2X(1)-like receptors. Moreover, we show that ATP transiently increased cytosolic Ca(2+) in "in situ" smooth muscle cells of intact HUA segments and that this response is dependent of extracellular and intracellular Ca(2+). These data expand the knowledge of purinergic receptors properties in vascular smooth muscle cells and the probable role of ATP as a paracrine modulator of contractile tone in a human artery which is fundamental for feto-placental blood flow.


Assuntos
Trifosfato de Adenosina/fisiologia , Cálcio/metabolismo , Citosol/metabolismo , Líquido Extracelular/fisiologia , Miócitos de Músculo Liso/metabolismo , Artérias Umbilicais/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Citosol/efeitos dos fármacos , Líquido Extracelular/efeitos dos fármacos , Feminino , Humanos , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Gravidez , Suramina/farmacologia , Fatores de Tempo , Artérias Umbilicais/efeitos dos fármacos
17.
Adv Ther ; 28 Suppl 6: 50-65, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21922395

RESUMO

Hormone treatment is one of the key strategies in the management of metastatic breast cancer. Hormone treatment is one of the key strategies in the management of metastatic breast cancer. Aromatase inhibitors (AI) have been extensively studied in this setting. This section summarizes the key data regarding the use of AI in advanced breast cancer. In postmenopausal women, AI are the first line of treatment for untreated patients, or those who had prior AI treatment and progress after 12 months of adjuvant therapy. A longer disease-free interval and absence of visceral disease is associated with a better response. If tumors recur in less than 12 months, it is recommended that tamoxifen (TAM) or the estrogen-receptor antagonist fulvestrant (FUL) treatment be initiated. In the second-line setting, the best option after progression is the administration of either FUL or TAM. In the third-line setting, reintroduction of AI is considered an acceptable option. In premenopausal women who have not received prior treatment or who have progressed after 12 months following adjuvant treatment, it is recommended to initiate therapy with a combination of TAM and a luteinizing hormone-releasing hormone (LHRH) analog. If there is treatment failure with the use of this combination, megestrol acetate or an LHRH agonist plus an AI may be reasonable alternatives. Intensive research is ongoing to understand the mechanisms of resistance to hormone therapy. In human epidermal growth factor receptor 2 positive-patients, combinations with HER2 antagonists are associated with significant clinical activity.


Assuntos
Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Adulto , Fatores Etários , Idoso , Anastrozol , Androstadienos/administração & dosagem , Androstadienos/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/mortalidade , Gerenciamento Clínico , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Sistemas de Liberação de Medicamentos , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Estradiol/análogos & derivados , Feminino , Fulvestranto , Humanos , Letrozol , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Metástase Neoplásica , Nitrilas/administração & dosagem , Nitrilas/efeitos adversos , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento , Triazóis/administração & dosagem , Triazóis/efeitos adversos
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