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1.
Ars pharm ; 59(3): 121-131, jul.-sept. 2018. graf, ilus
Artigo em Inglês | IBECS | ID: ibc-177728

RESUMO

A series of 4-(2-(4-substituted phenyl)-4-oxoquinazolin-3(4H)-yl)-N-(2-(4-fluorophenyl)-4-oxo-5-(arylidene)thiazolidin-3-yl) benzamides (VIa-n) have been synthesized by condensation of N-(2-(4-fluorophenyl)-4-oxothiazolidin-3-yl)-4-(4-oxo-2-(4-substituted phenyl)quinazolin-3(4H)-yl)benzamides (Va-b) with various aryl/heteroaryl aldehydes using conventional methodology. All compounds were screened for their in vitro anticancer activity against the human breast cancer cell lines (MCF-7), human lung cancer cell lines (A549) using MTT assay method and doxorubicin is used as standard drug. Compound VId, VIk and VIn showed high potency against A549 cell lines with IC50 values 0.035±0.002 µM, 0.031±0.002 µM and 0.030±0.002 µM respectively compared to 0.023±0.002 µM showed by the standard. However, highest activity against MCF-7 cell lines was exhibited by Va, Vb, VIk and VIn with IC50 values between 0.040 - 0.050 µM. All the remaining compounds showed moderate anticancer activity against both the MCF-7 and A549 cell lines. To understand the interactions with active binding site of receptor, molecular docking study was also performed


Una serie de 2- (4-sustituido fenil) -4-oxoquinazolin-3 (4H) -il) -N- (2- (4-fluorofenil) -4-oxo-5- (arilideno) tiazolidin-3-ilo) benzamidas (VIa-n) han sido sintetizadas por condensación de N- (2- (4-fluorofenil) -4-oxotiazolidin-3-il) -4- (4-oxo-2- (4-fenil sustituido) quinazolin-3 (4H) -il) benzamidas (Va-b) con diversos aldehídos de arilo / heteroarilo usando metodología convencional. Todos los compuestos se cribaron para su actividad anticancerosa in vitro contra las líneas celulares de cáncer de mama humano (MCF-7), líneas celulares de cáncer de pulmón humano (A549) usando el método de ensayo MTT y se usa doxorrubicina como fármaco estándar. El compuesto VId, VIk y VIn mostraron alta potencia contra las líneas celulares A549 con valores IC50 de 0.035 ± 0.002 μM, 0.031 ± 0.002 μM y 0.030 ± 0.002 μM, respectivamente, en comparación con 0.023 ± 0.002 μM mostrada por el estándar. Sin embargo, la actividad más alta contra líneas celulares MCF-7 fue exhibida por Va, Vb, VIk y VIn con valores de CI50 entre 0.040 - 0.050 μM. Todos los compuestos restantes mostraron una actividad anticancerígena moderada contra las líneas celulares MCF-7 y A549. Para comprender las interacciones con el sitio de unión activa del receptor, también se realizó el estudio de acoplamiento molecular


Assuntos
Anticarcinógenos/farmacologia , Quinazolinonas/farmacologia , Benzamidas/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Doxorrubicina/uso terapêutico , Condensação/métodos , Técnicas In Vitro/métodos , Mama
2.
J. physiol. biochem ; 74(3): 467-478, ago. 2018. tab, graf, ilus
Artigo em Inglês | IBECS | ID: ibc-179000

RESUMO

Despite the effectiveness of renin-angiotensin blockade in retarding diabetic nephropathy progression, a considerable number of patients still develop end-stage renal disease. The present investigation aims to evaluate the protective potential of FPS-ZM1, a selective inhibitor of receptor for advanced glycation end products (RAGE), alone and in combination with valsartan, an angiotensin receptor blocker, against glomerular injury parameters in streptozotocin-induced diabetic rats. FPS-ZM1 at 1 mg/kg (i.p.), valsartan at 100 mg/kg (p.o.), and their combination were administered for 4 weeks, starting 2 months after diabetes induction in rats. Tests for kidney function, glomerular filtration barrier, and podocyte slit diaphragm integrities were performed. Combined FPS-ZM1/valsartan attenuated diabetes-induced elevations in renal levels of RAGE and phosphorylated NF-κB p65 subunit. It ameliorated glomerular injury due to diabetes by increasing glomerular nephrin and synaptopodin expressions, mitigating renal integrin-linked kinase (ILK) levels, and lowering urinary albumin, collagen type IV, and podocin excretions. FPS-ZM1 also improved renal function as demonstrated by decreasing levels of serum cystatin C. Additionally, the combination also alleviated indices of renal inflammation as revealed by decreased renal monocyte chemoattractant protein 1 (MCP-1) and chemokine (C-X-C motif) ligand 12 (CXCL12) expressions, F4/80-positive macrophages, glomerular TUNEL-positive cells, and urinary alpha-1-acid glycoprotein (AGP) levels. These findings underline the benefits of FPS-ZM1 added to valsartan in alleviating renal glomerular injury evoked by diabetes in streptozotocin rats and suggest FPS-ZM1 as a new potential adjunct to the conventional renin-angiotensin blockade


No disponible


Assuntos
Humanos , Masculino , Ratos , Benzamidas/uso terapêutico , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/prevenção & controle , Barreira de Filtração Glomerular , Valsartana/uso terapêutico , Insuficiência Renal/prevenção & controle , Administração Oral , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Biomarcadores , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/fisiopatologia , Barreira de Filtração Glomerular/metabolismo , Barreira de Filtração Glomerular/patologia , Valsartana/administração & dosagem
3.
J. physiol. biochem ; 74(1): 35-45, feb. 2018. tab, graf
Artigo em Inglês | IBECS | ID: ibc-178916

RESUMO

Caffeine has been shown to stimulate multiple major regulators of cell energetics including AMP-activated protein kinase (AMPK) and Ca2+/calmodulin-dependent protein kinase II (CaMKII). Additionally, caffeine induces peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alfa) and mitochondrial biogenesis. While caffeine enhances oxidative metabolism, experimental concentrations often exceed physiologically attainable concentrations through diet. This work measured the effects of low-level caffeine on cellular metabolism and gene expression in myotubes, as well as the dependence of caffeine's effects on the nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPAR Beta/Delta). C2C12 myotubes were treated with various doses of caffeine for up to 24 h. Gene and protein expression were measured via qRT-PCR and Western blot, respectively. Cellular metabolism was determined via oxygen consumption and extracellular acidification rate. Caffeine significantly induced regulators of mitochondrial biogenesis and oxidative metabolism. Mitochondrial staining was suppressed in PPARBeta/Delta -inhibited cells which was rescued by concurrent caffeine treatment. Caffeine-treated cells also displayed elevated peak oxidative metabolism which was partially abolished following PPARβ/δ inhibition. Similar to past observations, glucose uptake and GLUT4 content were elevated in caffeine-treated cells, however, glycolytic metabolism was unaltered following caffeine treatment. Physiological levels of caffeine appear to enhance cell metabolism through mechanisms partially dependent on PPARBeta/Delta


No disponible


Assuntos
Animais , Camundongos , Cafeína/metabolismo , Regulação da Expressão Gênica , Mitocôndrias Musculares/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Proteínas Musculares/metabolismo , PPAR beta/agonistas , PPAR delta/agonistas , Benzamidas/farmacologia , Bioensaio , Linhagem Celular , Técnicas de Cocultura , Concentração de Íons de Hidrogênio , Metabolismo dos Lipídeos , Mitocôndrias Musculares , Dinâmica Mitocondrial , Fibras Musculares Esqueléticas , Biogênese de Organelas
4.
Clin. transl. oncol. (Print) ; 15(8): 608-618, ago. 2013. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-127476

RESUMO

PURPOSE: To explore the expression of tumoral Gal-1 in association with clinical parameters and outcome in a large population with laryngeal squamous cell carcinomas (LSCCs). METHODS: A total of 187 patients with LSCC were retrospectively enrolled. Immunohistochemistry was performed to evaluate the tumoral expression of Gal-1, apoptosis-related proteins and the density of tumor infiltrating lymphocytes (TILs) in tumor tissues before any intervene. Survival curves were estimated by the Kaplan-Meier method, and differences in survival between groups were determined using the log-rank test. Prognostic effects were evaluated by Cox regression analysis. RESULTS: A total of 102 carcinomas (54.5 %) were identified as high Gal-1 expression, and 85 carcinomas (45.5 %) as low expression. Tumoral Gal-1 expression was not significantly related with clinical stage and histology differentiation. No correlation of Gal-1 expression with apoptosis-related protein was identified. Instead, Gal-1 status was correlated positively with the ratio of FOXP3(+)/CD8(+) TILs (P = 0.024). In multivariate regression analysis, advanced clinical stage and the presence of metastases were identified as the independent predictors for poor survival in entire cohort. Especially, the statistical correlation between the Gal-1 expression and prognosis was particularly due to the late-stage tumors (P < 0.05). CONCLUSION: Current results represent valuable advancements in Gal-1 research and provided further support for using Gal-1 as a diagnostic biomarker and immunotherapeutic target for LSCC (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Benzamidas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias Laríngeas/patologia , Tirosina/análogos & derivados , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Imuno-Histoquímica , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/metabolismo , Prognóstico , Estudos Retrospectivos , Tirosina/metabolismo
5.
Med. clín (Ed. impr.) ; 139(supl.2): 41-45, oct. 2012. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-141309

RESUMO

El síndrome coronario agudo (SCA) aparece tras la ruptura de una placa aterosclerótica y la consiguiente activación plaquetaria y de la coagulación que conducen a la formación de trombo y la obstrucción coronaria. La trombina y el factor X activado son elementos clave en la cascada de la coagulación. La utilización de anticoagulantes en el síndrome coronario agudo durante la fase aguda y a largo plazo ha mejorado su pronóstico debido a la reducción de episodios trombóticos, pero asociándose a mayor riesgo de sangrado. En los últimos años se han desarrollado nuevos anticoagulantes orales que no requieren monitorización y presentan menor riesgo de sangrado. Rivaroxaban es el único que presenta un perfil de riesgo-beneficio favorable en pacientes con síndrome coronario agudo. El estudio ATLAS ACS 2-TIMI 51 es el primer ensayo de fase III que demuestra que la adición de rivaroxaban a dosis bajas a la terapia antiagregante óptima reduce la mortalidad, la mortalidad cardiovascular, el infarto o el ictus sin un aumento significativo en los sangrados fatales (AU)


Acute coronary syndrome (ACS) occurs as a result of atherosclerotic plaque rupture and subsequent platelet activation and coagulation leading to thrombus formation and coronary occlusion. Thrombin and activated factor X (FXa) are key elements in the coagulation cascade. The use of anticoagulants in ACS, both in the acute phase and in the long term, has improved prognosis by reducing thrombotic events, but is associated with an increased risk of bleeding. In recent years, new oral anticoagulants have been developed that do not require monitoring and produce a lower risk of bleeding. Rivaroxaban is the only drug with a favorable risk-benefit profile in patients with ACS. The ATLAS ACS TIMI 2-51 is the first phase III trial demonstrating that the addition of low-dose rivaroxaban to optimal antiplatelet therapy reduces mortality, cardiovascular mortality, infarct or stroke without significantly increasing fatal bleeding (AU)


Assuntos
Humanos , Síndrome Coronariana Aguda/tratamento farmacológico , Anticoagulantes/uso terapêutico , Benzilaminas/uso terapêutico , Morfolinas/uso terapêutico , Pirazóis/uso terapêutico , Administração Oral , Azepinas/uso terapêutico , Azetidinas/uso terapêutico , Benzamidas/uso terapêutico , Benzimidazóis/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Esquema de Medicação , Piridonas/uso terapêutico , Tiofenos/uso terapêutico , beta-Alanina/análogos & derivados , beta-Alanina/uso terapêutico
6.
Clin. transl. oncol. (Print) ; 14(8): 619-629, ago. 2012.
Artigo em Inglês | IBECS | ID: ibc-126959

RESUMO

BACKGROUND: The identification of activating mutations in either c-KIT cell surface growth factor receptor or platelet-derived growth factor receptor alpha (PDGFRA) has lead the way for the development of novel agents that selectively inhibit key molecular events in gastrointestinal stromal tumour (GIST) pathogenesis. The aim of this study was to investigate the role of c-KIT and PDGFRA gene mutations in primary resectable, imatinib naïve GISTs located in the stomach and small intestine. METHODS: All adult patients with GIST located in either stomach or small intestine who underwent surgical resection without prior imatinib (Glivec) treatment were included. DNA extraction and mutational analysis were performed. Mutational analyses were performed for c-KIT (exons 9, 11, 13, and 17) and the PDGFRA genes (exons 12, 14 and 18). Clinical and pathological parameters were analyzed in relation to the mutations in c-KIT and PDGFRA. RESULTS: A total of 38 patients who underwent surgery for GIST located in either the stomach (n = 24) or in the small intestines (n = 14) were included. Mutations were found in 31 of 38 (81.6 %) patients, with 24 (63.2 %) located in c-KIT and 7 (18.4 %) in the PDGRFA exons, respectively. Seven patients (18.4 %) were wildtype (WT). The most common mutation was in c-KIT exon 11. Incidentally found GISTs were significantly smaller (size >5 cm in 15 % for incidental vs. 71 % for symptomatic; OR of 13.4, 95 % CI 2.3-76.5; P = 0.001) and had lower mitotic rate (0 % for incidental vs. 44 % of the symptomatic; OR 0.52, 95 % CI 0.36-0.75; P = 0.005). Accordingly, the Fletcher grade was significantly better for incidental cases, with most having very low or low risk (85 %) in contrast to 19 of 25 (76 %) symptomatic cases showing moderate to high-risk features (OR 17.4, 95 % CI 2.98-101.7; P < 0.001). However, the distribution of c-KIT, PDGFRA and WT was not differently distributed between incidental and symptomatic GISTs. Long-term survival up to 25 years (median: 8 years) was best determined by Fletcher risk-score in the multivariate model (HR 14.1, 95 % CI 1.7-114.5; p = 0.013). CONCLUSIONS: Long-term survival in resected GISTs of the stomach and small intestine is best determined by Fletcher risk-score. Mitotic activity appears related to tumour size and young age at onset. Mutational status did not influence the clinical or tumour-specific features in this cohort (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Tumores do Estroma Gastrointestinal/genética , Neoplasias Intestinais/genética , Piperazinas/uso terapêutico , Proteínas Proto-Oncogênicas c-kit/genética , Pirimidinas/uso terapêutico , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Neoplasias Gástricas/genética , Análise Mutacional de DNA , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/cirurgia , Éxons , Neoplasias Intestinais/patologia , Neoplasias Intestinais/cirurgia , Intestino Delgado , Intestino Delgado/patologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
9.
Rev. clín. esp. (Ed. impr.) ; 211(supl.2): 22-30, mar. 2011. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-148576

RESUMO

La enfermedad pulmonar obstructiva crónica (EPOC) es un término que engloba un grupo de trastornos caracterizados por la presencia de obstrucción crónica de las vías aéreas. Este amplio paraguas diagnóstico incluye varios fenotipos clínicos que se solapan y que responden de forma diferente a cada tipo de intervención terapéutica. Roflumilast es un fármaco perteneciente a la nueva clase terapéutica de los inhibidores de la fosfodiesterasa 4 (PDE4). Se puede considerar el primer fármaco desarrollado para el tratamiento de un fenotipo específico de la EPOC (EPOC asociada a bronquitis crónica). En modelos preclínicos, roflumilast ha mostrado una potente acción antiinflamatoria sobre una amplia variedad de células y mediadores inflamatorios, así como sobre otros mecanismos etiopatogénicos propios de la EPOC. El presente documento revisa la evidencia generada durante el desarrollo clínico de roflumilast , con un énfasis especial en los estudios que valoran el fármaco en el contexto similar a nuestra práctica clínica habitual (AU)


Chronic obstructive pulmonary disease (COPD) encompasses a group of diseases characterized by chronic airway obstruction. This broad diagnostic umbrella includes several clinical phenotypes that overlap and respond differently to each type of therapeutic intervent ion. Roflumilast is a drug belonging to the new therapeutic class of phosphyldiesterase-4 (PDE4) inhibitors and can be considered the first drug to be developed for a specific COPD phenotype (COPD associated with chronic bronchit is). In preclinical models, roflumilast has shown potent ant iinflammatory action against a wide variety of cells and inflammatory mediators, as well as against the etiopathogenic mechanisms of COPD. The present article reviews the evidence generated during the clinical development of roflumilast , with special emphasis on studies evaluating the drug in a context similar to that of routine clinical pract ice (AU)


Assuntos
Humanos , Aminopiridinas/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Benzamidas/uso terapêutico , Inibidores da Fosfodiesterase 4/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Broncodilatadores/uso terapêutico , Ciclopropanos/uso terapêutico , Quimioterapia Combinada , Derivados da Escopolamina/uso terapêutico
11.
Clin. transl. oncol. (Print) ; 12(10): 670-676, oct. 2010. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-124356

RESUMO

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs are characterised by the expression of KIT, a type III tyrosine kinase receptor, and the presence of mutations in KIT or PDGFRA in about 80-85% of cases. The primary treatment for GIST is surgery, which cures most patients with low- or intermediate-risk tumours. The introduction of the kinase inhibitor imatinib mesylate, and sunitinib in second line, against KIT and PDGFRA has provided the first evidence of directed therapy in GIST. The aim of this review is to highlight the growing evidence that KIT and PDGFRA genotyping provides valuable information for the clinical management of GIST patients. We show that KIT and PDGFRA genotyping has emerged as one of the principal factors in the evaluation of GISTs, particularly in those tumours that are clearly malignant or have a high risk of recurrence. In addition to helping establish the diagnosis of GIST in unusual cases, genotyping can be very useful to physicians and patients in deciding on imatinib dose, in estimating the likelihood and duration of benefit, and potentially in selecting second-line therapies (AU)


Assuntos
Humanos , Masculino , Feminino , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/genética , Proteínas Proto-Oncogênicas c-kit/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/efeitos dos fármacos , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Antineoplásicos/uso terapêutico , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Genótipo , Mutação , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico
12.
Actas esp. psiquiatr ; 37(6): 330-342, nov.-dic. 2009. graf
Artigo em Espanhol | IBECS | ID: ibc-78791

RESUMO

El tratamiento de la esquizofrenia ha evolucionado a lo largo de la segunda mitad del siglo pasado, principalmente gracias al desarrollo de los fármacos antipsicóticos. A pesar del gran avance realizado, que ha permitido la disponibilidad y uso de nuevos y diferentes fármacos, éstos continuan constituyendo tres grupos básicos (atipsicóticos típicos, atípicos y agonistas parciales dopaminérgicos), y todos ellos tienen como principal mecanismo de acción, la actuación sobre los sistemas dopaminérgicos. Se cree que una gran parte de los antipsicóticos de segunda generación (antipsicóticos atípicos y agonistas parciales dopaminérgicos) ofrecen ventajas añadidas a los de primera generación en el tratamiento de la esquizofrenia. No obstante, las propiedades farmacológicas y terapéuticas que confieren respecto a los de primera generación no están claras, y ciertos efectos colaterales pueden todavía, afectar a la salud y calidad de vida del paciente. Además, la eficacia de los antipsicóticos es limitada, lo que ha llevado a la utilización de medicaciones adyuvantes para potenciar los efectos del tratamiento. Por otro lado, se ha trabajado en el desarrollo de nuevas líneas de investigación para el desarrollo de nuevos fármacos antipsicóticos no dopaminérgicos, siendo los resultados poco exitosos. Este artículo realiza una breve revisión crítica sobre el actual arsenal terapéutico para la esquizofrenia, estrategias de desarrollo de fármacos, y teorías sobre los mecanismos de acción de los antipsicóticos, centrándose en las nuevas dianas terapéuticas para el desarrollo de futuros tratamientos (AU)


Schizophrenic treatment was developed during the second half of the last century, mainly within the context of the development of antipsychotic drugs. Even though there has been significant progress due to the availability and use of multiple drugs, these can still be classified into three basic groups of antipsychotic drugs (atypical antipsychotics, typical antipsychotics and dopamine partial agonist antipsychotics). Their primary antipsychotic mechanism is still the action on the dopamine systems. Many of the second-generation antipsychotics are believed to offer advantages over first-generation agents in the treatment for schizophrenia. However, the drug properties that provide the different therapeutic effects from those of the first generation are not clear and some adverse effects may still affect the patient’s health and quality of life. Furthermore, the efficacy of the antipsychotics is limited. This has led to the use of adjuvant medications to strengthen the treatment effects. On the other hand, work is being done on the development of new research lines to develop new nondopaminergic antipsychotic drugs, with not very successful results. The aim of this paper is to make a brief review on the current therapeutic armamentarium for schizophrenia, the strategies to develop drugs, and theories of mechanisms of action of antipsychotics. Emphasis is placed on the new therapeutic targets for the development of future treatments (AU)


Assuntos
Humanos , Esquizofrenia/tratamento farmacológico , Antipsicóticos/farmacologia , Antipsicóticos/efeitos adversos , Benzamidas/farmacologia , Colinérgicos/farmacologia , Receptores Dopaminérgicos/uso terapêutico
13.
Clin. transl. oncol. (Print) ; 10(12): 831-839, dic. 2008.
Artigo em Inglês | IBECS | ID: ibc-123563

RESUMO

INTRODUCTION: Sunitinib is a multiselective oral inhibitor of several tyrosine-kinase receptors that has demonstrated its efficacy in patients with metastatic and/or unresectable gastrointestinal stroma tumours (GIST) who were resistant to or intolerant to previous treatment with imatinib. The purpose of this study is to assess the cost-effectiveness of sunitinib vs. best supportive care (BSC) in GIST as a second- line treatment, from the perspective of the Spanish National Health System. MATERIALS AND METHODS: A Markov model was used to assess the cost effectiveness of sunitinib (50 mg/day, 4 weeks "on" and 2 weeks "off") vs. BSC in GIST as a second-line treatment. Transition probabilities between the three health states considered in the model (progression-free survival (PFS), progression and death) were obtained from a clinical trial [Demetri et al. (2006) Lancet 368:1329-1338]. Health resource data (drugs, medical visits, laboratory and radiology tests, palliative care and adverse events) were obtained from an expert panel. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Projected PFS years, life years (LY) and quality of life adjusted years (QALYs) were higher for sunitinib compared with BSC: 0.50 vs. 0.24, 1.59 vs. 0.88 and 1.00 vs. 0.55. Mean costs per patient were 23,259 euros with sunitinib and 1,622 euros with BSC. The incremental cost-effectiveness ratios (ICERs) obtained were: 4,090 euros/month PFS, 30,242 euros/LY and 49,090 euros/QALY gained. The most influential variables for the results were the efficacy and unit cost of sunitinib. CONCLUSIONS: According to the efficiency thresholds for oncology patients in developed countries, sunitinib is considered cost-effective vs. BSC with acceptable costs per LY and QALY gained (AU)


No disponible


Assuntos
Humanos , Masculino , Feminino , Quimioterapia Adjuvante/economia , Antineoplásicos/economia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/economia , Indóis/economia , Indóis/uso terapêutico , Cadeias de Markov , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Algoritmos , Benzamidas , Análise Custo-Benefício , Progressão da Doença , Método Duplo-Cego , Resistencia a Medicamentos Antineoplásicos , Tumores do Estroma Gastrointestinal/mortalidade , Tumores do Estroma Gastrointestinal/patologia , Recursos em Saúde
14.
Rev. esp. med. nucl. (Ed. impr.) ; 27(3): 168-175, mayo 2008. ilus
Artigo em Espanhol | IBECS | ID: ibc-147868

RESUMO

Objetivo. Diferentes trabajos han demostrado la efectividad del tratamiento adyuvante con mesilato de imatinib en el tumor del estroma gastrointestinal (GIST) irresecable, metastásico o recidivado. Hemos estudiado, retrospectivamente, el papel de la PET/TAC con 18F-FDG en la valoración de la respuesta del GIST al tratamiento con imatinib. Material y métodos. El estudio incluyó 8 pacientes consecutivos con GIST confirmado por cirugía (4 estómago, 2 intestino delgado, 1 intestino delgado y peritoneo y 1 recto) a los cuales se les realizaron 18 PET/TAC con 18F-FDG después de iniciar el tratamiento con mesilato de imatinib (400 mg/día o dosis mayores si se detectó progresión). La PET/TAC se adquirió a los 60-90 minutos después de la administración intravenosa de 333-707 MBq de 18F-FDG. Se realizó un análisis visual y semicuantitativo (standardized uptake value [SUV]) de las imágenes. La respuesta a la terapia se valoró siguiendo las recomendaciones de la EORTC para la PET. Los resultados se confirmaron por seguimiento clínico, hallazgos radiológicos o histología. Resultados. La respuesta al imatinib fue completa en 5 pacientes. Cuatro de ellos tuvieron adenopatías abdominales, asociadas a metástasis hepáticas en dos; el otro paciente tuvo una masa tumoral residual. La respuesta fue parcial (disminución del SUV y de la extensión de la captación de FDG) en un paciente con nódulos pulmonares. Se observó progresión de la enfermedad en un paciente por la aparición de nuevas metástasis hepáticas en la PET/TAC. Una paciente no respondió a la terapia y tuvo múltiples implantes peritoneales y una masa abdominal, falleciendo a los 2 meses de la PET/TAC. Conclusión. La PET/TAC con 18F-FDG identificó el grado de respuesta del GIST a la terapia con imatinib. En los pacientes que respondieron al tratamiento se observó la normalización de la captación de FDG o un descenso en el SUV de las lesiones (AU)


Objective. Several studies have demonstrated the effective use of adjuvant treatment with Imatinib mesylate for unresectable, metastatic or recurrent gastrointestinal stromal tumours (GIST). We retrospectively evaluated the role of 18F-FDG PET/CT scanning in assessing the response of GIST patients to imatinib mesylate therapy. Materials and methods. Eight consecutive patients with GIST confirmed by surgery (4 stomach, 2 small bowel, 1 small bowel and peritoneum, and 1 rectum) underwent eighteen 18F-FDG PET/CT imaging after beginning imatinib mesylate therapy (400 mg/day or greater if disease progression). PET/CT scan was acquired 60-90 minutes after the intravenous injection of 333-707 MBq of 18F-FDG. Visual and semiquantitative (standardized uptake value [SUV]) analysis of images was performed. Response to therapy was assessed according to EORTC recommendations for PET. Results were confirmed by clinical follow-up, radiographic findings or histological analysis. Results. Complete response to imatinib mesylate was observed in 5 patients. Four had abdominal lymph nodes, associated with liver metastases in 2, and the other had a residual tumour mass. Partial response (reduction in SUV and in the extent of FDG uptake) was demonstrated in a patient with lung nodules. Disease progression was observed in one patient who had developed new liver metastases on the PET/CT scan. One patient with multiple peritoneal implants and abdominal mass was a non-responder and died 2 months after the 18F-FDG PET/CT. Conclusion. 18F-FDG PET/CT scan identified the degree of GIST response to imatinib therapy. Patients who responded to therapy showed normalisation of FDG uptake or a decrease in the SUV of lesions (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Piperazinas/uso terapêutico , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Pirimidinas/uso terapêutico , Compostos Radiofarmacêuticos , Indução de Remissão , Antineoplásicos/uso terapêutico , Benzamidas , Monitoramento de Medicamentos/métodos , Fluordesoxiglucose F18 , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas , Neoplasias Hepáticas , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares , Neoplasias Pulmonares , Neoplasias Pulmonares/secundário
15.
Gastroenterol. hepatol. (Ed. impr.) ; 29(5): 291-294, may. 2006. ilus
Artigo em Espanhol | IBECS | ID: ibc-048353

RESUMO

El tratamiento del bezoar es empírico. Las diferentes opciones terapéuticas incluyen modificaciones de la dieta, fármacos procinéticos, lavado gástrico, disolución enzimática, terapéutica endoscópica y cirugía. Presentamos dos casos de fitobezoar resueltos con éxito tras la administración de Coca-Cola®


The treatment of phytobezoar is empiric. The various therapeutic choices include dietary modifications, prokinetic drugs, gastric lavage, enzymatic dissolution, endoscopic treatment, and surgery. We present two cases of phytobezoar with successful outcome after Coca-Cola® administration


Assuntos
Masculino , Idoso , Humanos , Bezoares/terapia , Bebidas Gaseificadas , Estômago , Antiulcerosos/uso terapêutico , Benzamidas/uso terapêutico , Bezoares/complicações , Duodeno/cirurgia , Esofagite/terapia , Esofagite/complicações , Gastroenterostomia , Gastroscopia , Jejuno/cirurgia , Plantas Comestíveis , Complicações Pós-Operatórias/terapia , Antro Pilórico , Solubilidade , Úlcera Gástrica/complicações , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/terapia
16.
Neurología (Barc., Ed. impr.) ; 19(6): 292-300, jul. 2004.
Artigo em Espanhol | IBECS | ID: ibc-33926

RESUMO

Introducción. Existen pacientes con parkinsonismo o temblor de presentación o evolución atípica. En los parkinsonismos neurodegenerativos las alteraciones estructurales de la tomografía computarizada (TC) o de la resonancia magnética (RM) aparecen en estadios avanzados de la enfermedad y no ayudan en el diagnóstico diferencial precoz. Por otro lado, en los pacientes con parkinsonismo vascular puede coexistir enfermedad de Parkinson (EP). El diagnóstico clínico diferencial entre enfermedad de Alzheimer (EA) y demencia con cuerpos de Lewy (DCL) puede ser difícil. Objetivo. Definir la utilidad de las pruebas de neuroimagen funcional para establecer el diagnóstico diferencial entre EP, temblor esencial (TE), parkinsonismo inducido por drogas, enfermedades multisistema y parkinsonismo vascular, y entre EA y DCL, cuando la presentación clínica, evolución o respuesta al tratamiento plantean dudas diagnósticas. Pacientes y métodos. La serie comprende 75 pacientes con parkinsonismo consecutivamente atendidos en una consulta de neurología y clínicamente catalogados siguiendo criterios ad hoc. La vía nigroestriada se estudió mediante DaTSCAN (123I-FP-CTI, marcador de la proteína transportadora de dopamina). IBZM SPECT (marcador de los receptores D2) se utilizó para el estudio postsináptico. Resultados. La correlación entre el diagnóstico clínico inicial y el resultado del DaTSCAN o el IBZM en nuestros pacientes no llega a la descrita (más del 90 por ciento) para estas técnicas en los estudios previos publicados. Conclusiones. Dada la sensibilidad y especificidad atribuidas a estas técnicas funcionales en los estudios realizados con pacientes en los que no hay dudas diagnósticas, publicados en estudios previos, la utilización del (DaTSCAN) SPECT, completado en algunos casos con el estudio con IBZM, en pacientes con síntomas acineticorrígidos o temblor es útil para el diagnóstico diferencial entre los diversos síndromes que se asocian a este tipo de síntomas cuando los criterios clínicos o la respuesta al tratamiento plantean dudas diagnósticas (AU)


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Idoso de 80 Anos ou mais , Adulto , Tomografia Computadorizada de Emissão de Fóton Único , Radioisótopos do Iodo , Pirrolidinas , Terminações Pré-Sinápticas , Dopamina , Diagnóstico Diferencial , Corpo Estriado , Benzamidas , Transtornos Parkinsonianos , Potenciais Pós-Sinápticos Excitadores , Telencéfalo
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