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AIM: To determine post-surgical cognitive risk and associated factors according to lesion location in a sample of patients evaluated for epilepsy surgery with Wada test at the Fundacion Instituto Neurologico de Colombia. MATERIALS AND METHODS: An observational, retrospective, analytical study was completed in patients with drug-resistant temporal lobe epilepsy candidates for epilepsy surgery treated from 2001 to 2021, who completed the Wada test as part of the pre-surgical evaluation. A descriptive analysis of sociodemographic, clinical, imaging and neuropsychological variables was completed; a multivariate logistic regression was performed analyzing factors associated with resection risk in patients with left lesions. RESULTS A total of 369 patients were included, 54.74% of the cases were women, with a median age of seizure onset of 11 years. 92.66% of the cases had lesional epilepsy and 68.56% were secondary to hippocampal sclerosis. Left hemisphere was the most frequently affected (65.68%) being dominant for memory and language in most of the patients with a proportion of 42.82% and 81.3%, respectively. The median functional adequacy was 43.75 (IQR 0-75) and the functional reserve was 75 (IQR 25 -93.75). In 104 patients, the Wada test determined a resection risk. In patients with a left lesion, it was found that functional reserve (PRadjusted 0.99, CI 95% 0.9997-0.9998) and having a right hemispheric dominance for memory (PRadjusted 0.92, CI 95% 0.547-0.999) were protective factors for post-surgical resection risk. CONCLUSION: Wada test is a useful tool for surgical decision-making in patients with drug-resistant temporal lobe epilepsy. When considering cognitive risk, components such as memory dominance and functional reserve should be considered as protective factors for postsurgical cognitive function preservation in patients with left lesions.
TITLE: Evaluación de la memoria y el lenguaje mediante el test de Wada en pacientes candidatos a cirugía de epilepsia.Objetivo. Determinar el riesgo cognitivo posquirúrgico y factores asociados según la localización de la lesión en una muestra de pacientes evaluados para cirugía de epilepsia con el test de Wada en la Fundación Instituto Neurológico de Colombia. Materiales y métodos. Se realizó un estudio observacional, retrospectivo y analítico en pacientes con epilepsia farmacorresistente del lóbulo temporal candidatos a cirugía de epilepsia tratados entre 2001 y 2021, que completaron el test de Wada como parte de la evaluación prequirúrgica. Se realizó un análisis descriptivo de variables sociodemográficas, clínicas, imagenológicas y neuropsicológicas. Se realizó una regresión logística multivariada analizando factores asociados al riesgo de resección en pacientes con lesiones izquierdas. Resultados. Se incluyó a 369 pacientes, el 54,74% de los casos fueron mujeres, con una mediana de edad de inicio de las convulsiones de 11 años. El 92,66% de los casos presentó epilepsia lesional; de éstos, el 68,56% fue secundario a esclerosis hipocampal. El hemisferio izquierdo fue el más frecuentemente afectado (65,68%), y éste fue dominante para la memoria y el lenguaje en la mayoría de los pacientes, con una proporción del 42,82 y el 81,3%, respectivamente. La mediana de adecuación funcional fue de 43,75 (rango intercuartílico: 0-75) y la reserva funcional de 75 (rango intercuartílico: 25-93,75). En 104 pacientes, el test de Wada determinó un riesgo de resección. En pacientes con lesiones izquierdas se encontró que la reserva funcional (razón de prevalencia ajustada: 0,99; intervalo de confianza al 95%: 0,9997-0,9998) y tener dominancia del hemisferio derecho para la memoria (razón de prevalencia ajustada: 0,92; intervalo de confianza al 95%: 0,547-0,999) fueron factores asociados para determinar el riesgo de resección posquirúrgico en el test de Wada. Conclusión. El test de Wada es una herramienta útil para la toma de decisiones quirúrgicas en pacientes con epilepsia del lóbulo temporal farmacorresistente. Componentes como la dominancia de la memoria y la reserva funcional en el test de Wada deben considerarse como factores que se deben tener en cuenta en la predicción de la preservación de la función cognitiva posquirúrgica en pacientes con lesiones izquierdas.
Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia do Lobo Temporal , Humanos , Feminino , Masculino , Estudos Retrospectivos , Adulto , Medição de Risco , Epilepsia do Lobo Temporal/cirurgia , Epilepsia Resistente a Medicamentos/cirurgia , Testes Neuropsicológicos , Complicações Pós-Operatórias/etiologia , Adulto Jovem , Adolescente , Criança , IdiomaRESUMO
PURPOSE: The objective of this trial was to evaluate the safety and efficacy of melatonin oral gel mouthwashes in the prevention and treatment of oral mucositis (OM) in patients treated with concurrent radiation and systemic treatment for head and neck cancer. METHODS: Randomized, phase II, double-blind, placebo-controlled trial (1:1 ratio) of 3% melatonin oral gel mouthwashes vs. placebo, during IMRT (total dose ≥ 66 Gy) plus concurrent Q3W cisplatin or cetuximab. Primary endpoint: grade 3-4 OM or Severe Oral Mucositis (SOM) incidence by RTOG, NCI, and a composite RTOG-NCI scales. Secondary endpoints: SOM duration and grade 2-4 OM or Ulcerative Oral Mucositis (UOM) incidence and duration. RESULTS: Eighty-four patients were included in the study. Concurrent systemic treatments were cisplatin (n = 54; 64%) or cetuximab (n = 30; 36%). Compared with the placebo arm, RTOG-defined SOM incidence was numerically lower in the 3% melatonin oral gel arm (53 vs. 64%, P = 0.36). In patients treated with cisplatin, assessed by the RTOG-NCI composite scale, both SOM incidence (44 vs. 78%; P = 0.02) and median SOM duration (0 vs. 22 days; P = 0.022) were significantly reduced in the melatonin arm. Median UOM duration assessed by the RTOG-NCI scale was also significantly shorter in the melatonin arm (49 vs. 73 days; P = 0.014). Rate of adverse events and overall response rate were similar between the two arms. CONCLUSIONS: Treatment with melatonin oral gel showed a consistent trend to lower incidence and shorter SOM duration and shorter duration of UOM. These results warrant further investigation in phase III clinical trial.
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Antineoplásicos/efeitos adversos , Antioxidantes/administração & dosagem , Quimiorradioterapia/efeitos adversos , Melatonina/administração & dosagem , Antissépticos Bucais/administração & dosagem , Estomatite/prevenção & controle , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antioxidantes/efeitos adversos , Cetuximab/administração & dosagem , Cetuximab/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Método Duplo-Cego , Feminino , Géis/administração & dosagem , Neoplasias de Cabeça e Pescoço , Humanos , Incidência , Masculino , Melatonina/efeitos adversos , Pessoa de Meia-Idade , Antissépticos Bucais/efeitos adversos , Placebos/administração & dosagem , Estudo de Prova de Conceito , Estudos Prospectivos , Estomatite/epidemiologia , Estomatite/etiologiaRESUMO
Chronic low-grade inflammation is strongly related to the etiology of diabetes mellitus type 2 (T2DM), and the expression of inflammatory cytokines may be modulated by polymorphisms located in the regulatory regions of the NFκß, IL-1ß, IL-6, TNFα, and LPL genes. We considered it particularly important to investigate the relationship of gene polymorphisms involved in chronic inflammation with the risk of T2DM or uncontrolled biochemical parameters. METHODS: We included 199 individuals with a T2DM diagnosis and 213 individuals without a T2DM diagnosis. Restriction fragment length polymorphism (RFLP) analyses were used to assess polymorphisms. RESULTS: We found a risk association between T2DM and uncontrolled biochemical parameters in a Mexican population for the genotypes del/del of NFκß, -174 and -572 of IL-6, C/C of IL-1ß, -308 and -238 of TNFα, and T/T of LPL. In subjects without diabetes (controls), we found an association between the G/C genotype of the -572 polymorphism and the G/C and C/C genotypes of the -597 polymorphism of IL-6 with the risk of glucose levels > 131 mg/dL. Genotype C/C of polymorphism -174 of the IL-6 gene was associated with high triglyceride levels, and levels > 5.8% of HbA1c were associated with the G/A genotype of TNFα -308. CONCLUSION: Here, we describe for the first time the relationship of T2DM risk and uncontrolled biochemical parameters with polymorphisms in the NFκß, IL-6, TNFα, IL-1ß, and LPL genes in a Mexican population. We also showed that for the population included in this study, there is an additive effect of the polymorphisms of the studied genes that considerably increases the risk of developing T2DM.We also showed that there are interactions between genes related to chronic inflammation that affect the risk of T2DM.
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Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Interleucina-1beta/genética , Interleucina-6/genética , Lipase Lipoproteica/genética , Masculino , México , Pessoa de Meia-Idade , NF-kappa B/genética , Fator de Necrose Tumoral alfa/genéticaRESUMO
Prolonged exposure to estrogens is the main factor associated with the risk and prognosis of breast cancer (BC). The genes involved in the biotransformation of estrogens and xenobiotics have allelic variants with modified enzymatic activities. We investigated the association of nine polymorphisms of some genes from the classical estrogen pathway with the risk of breast cancer and their role in the clinicopathological characteristics of poor clinical prognosis in a sample of Mexican women with BC. METHODS: We included 150 controls and 150 cases matched by age. To analyze the selected polymorphisms, TaqMan assays and high-resolution melting (HRM) analysis were used. RESULTS: The polymorphisms of the genes ERα, CYP1A1, CYP1B1, COMT, MGMT, and XRCC1 were positively associated with the BC risk. We found negative associations between CYP1B1G/G genotype and tumor size, and status of lymph node, estrogen receptor, triple negative, and survival. CONCLUSIONS: The polymorphisms included in this study are associated not only with the risk of BC, but also with some clinicopathological characteristics for poor prognosis of patients with breast cancer, highlighting the important role of CYP1B1 Leu432Val polymorphism.
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Neoplasias da Mama , Adulto , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Estrogênios/metabolismo , Feminino , Genótipo , Humanos , México , Polimorfismo Genético , Prognóstico , Risco , Carga Tumoral , Xenobióticos/metabolismoRESUMO
Engineered nanoparticles of TiO2 (TiO2-NPs) are used in the industry for a great number of applications. After their usage, the particles end up in aquatic environments, contaminating supply waters and watercourses. Bench-scale studies report removal of TiO2-NPs (450â nm, the mean volumetric diameter) by flocculation followed by settling or by dissolved air flotation (4 bar saturation pressure and 30% recycling ratio). Floc formation was conducted after heterocoagulation with iron hydroxide (30-40â mgâ L-1â Fe3+) and gelatinized corn starch (10-20â mgâ L-1) as flocculant, at pH 7. Particle size distribution and zeta potential, removal efficiencies as a function of time and microphotography of flocs were analyzed. Mechanisms involve ferric hydroxide precipitation, heterocoagulation with the nanoparticles and flocculation of the loaded carrier precipitates with gelatinized starch. Best results showed removals between 95-100% of TiO2-NPs, either by settling or flotation after 5â min. Clear treated waters with low turbidity < 3 nephelometric turbidity units (NTU) and TiO2-NPs concentrations <1â mgâ L-1 were obtained. A practical advantage in DAF was the higher solids content (1.9% w/w) of the sludge, when compared to settling (0.7% w/w). This would facilitate the sludge dewatering and disposal, but DAF has the disadvantage of the poor efficiency at high concentration of the nanoparticles of titanium oxide (>100â mgâ L-1). Conversely, the removal by settling of the flocs increased at high dosages. It is believed that both processes are sustainable in terms of reagents and the removal efficiencies of TiO2 nanoparticles from water.
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Nanopartículas , Titânio , Floculação , EsgotosAssuntos
COVID-19 , Pandemias , Países em Desenvolvimento , Humanos , Peru/epidemiologia , SARS-CoV-2Assuntos
Sintomas Comportamentais/epidemiologia , COVID-19/epidemiologia , Centros Comunitários de Saúde Mental/estatística & dados numéricos , Transtornos Mentais/epidemiologia , Saúde Mental/estatística & dados numéricos , Psiquiatria/estatística & dados numéricos , Saúde Pública/estatística & dados numéricos , Adolescente , Adulto , COVID-19/economia , Criança , Centros Comunitários de Saúde Mental/economia , Humanos , Transtornos Mentais/economia , Saúde Mental/economia , Peru/epidemiologia , Psiquiatria/economia , Saúde Pública/economiaRESUMO
INTRODUCTION: Primary objective of the study was to assess the relative weighting between benefit in survival time (SV), benefit in quality of life (QoL) and willingness to experience adverse events (AEs), in patient preferences for chemotherapy treatment. MATERIALS AND METHODS: We included cancer patients with current or past systemic treatment of cancer (STC) as well as physicians placed as hypothetical patients. Participants filled a choice-based conjoint analysis questionnaire with 19 choices among three STC scenarios with variable amounts of benefit in SV or QoL and different types AEs. RESULTS: One hundred patients (50 on curative and 50 on palliative intention treatment) and 114 physicians (61 oncologists and 53 non-oncologists) were included and asked about their preferred chemotherapy treatment. The relative weighting (sum 100%) of SV-QoL-AEs for making the choice in the 100 patients was SV35%-CV33%-AEs31% what was not significantly different from a random distribution (Goodness of fit Chi square P = 0.91) just as it was not for both subgroups, palliative (SV37%-QoL29%-AEs34%; GoF Chi square P = 0.55) and curative (SV34%-QoL36%-AEs30%; GoF Chi square P = 0.73) treatment. The observed distribution in the group of 114 physicians (SV46%-QoL31%-AEs23%) was significantly different from a random distribution (GoF Chi square P = 0.018) just as it was for both subgroups, medical oncologists (SV48%-QoL29%-AEs23%; GoF Chi square P = 0.006) and non-medical oncologists (SV44%-QoL33%-AEs23%; GoF Chi square P = 0.04). CONCLUSIONS: The three attributes (SV, QoL, and AEs) are considered in the same way by cancer patients to make choices on their STC. On the contrary, when placed as hypothetical patients, physicians prefer for themselves those treatments that provide more SV.
Assuntos
Neoplasias/psicologia , Neoplasias/terapia , Qualidade de Vida/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Atitude do Pessoal de Saúde , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Neoplasias/patologia , Preferência do Paciente , Médicos , Inquéritos e Questionários , Taxa de SobrevidaRESUMO
RESUMEN El aumento del tamaño del timo asociado a hiperplasia tímica (HT) es frecuente en los pacientes con enfermedad de Graves-Basedow (EGB), si bien es poco habitual detectarla en la práctica clínica diaria. Presentamos el caso de una mujer de 38 años con EGB, a quien se le detectó de manera incidental un aumento del timo. La paciente no tenía síntomas compresivos locales y la tomografía computarizada demostró engrosamiento homogéneo de mediastino anterior sugestivo de HT. Durante la evolución, se evidenció reducción del tamaño tras el control de la función tiroidea con fármacos antitiroideos. La presencia de algunas características radiológicas como aumento difuso y homogéneo de la glándula, ausencia de invasión de estructuras vecinas, calcificaciones o imágenes quísticas, sugiere la presencia de una HT. En estos casos, el tratamiento del hipertiroidismo y un control expectante son actitudes razonables. Conocer esta evolución puede evitar intervenciones diagnósticas o terapéuticas innecesarias.
ABSTRACT Thymic enlargement associated with thymic hyperplasia (TH), in patients with Graves-Basedow disease (GBD) is common, although it remains largely unrecognized in routine clinical practice. We present the case of a 38 year-old woman with GBD, to whom an incidental thymic enlargement was detected. The patient did not have local compressive symptoms and the computerized tomography showed homogenous thickening of the anterior mediastinum suggestive of TH. During evolution, a reduction in size was observed after thyroid function was controlled by anti-thyroid drugs. The presence of some radiological features such as diffuse and homogeneous gland enlargement, absence of invasion of neighboring structures, calcifications or cystic images suggests the presence of TH. In these cases treatment of hyperthyroidism and expectant management are reasonable responses. Recognizing this evolution can avoid unnecessary diagnostic or therapeutic interventions.
Assuntos
Humanos , Feminino , Adulto , Hiperplasia do Timo/complicações , Doença de Graves/complicações , Hiperplasia do Timo/diagnóstico , Doença de Graves/diagnóstico , Diagnóstico DiferencialRESUMO
PURPOSE: The aim of this phase II study was to evaluate the activity and safety of the combination of cisplatin and vinorelbine with thoracic radiotherapy in unresectable locally advanced stage III non-small cell lung cancer (NSCLC). The primary endpoint was the objective response rate (ORR). Secondary objectives included toxicity profile, progression-free survival (PFS), and overall survival (OS). MATERIALS AND METHODS: A total of 48 NSCLC patients were enrolled (median age 60 years, 52% stage IIIA and 48% stage IIIB, 52% adenocarcinoma). Patients received three cycles of chemotherapy every 21 days [intravenous cisplatin 80 mg/m2 and intravenous vinorelbine 25 mg/m2 on day 1 and oral vinorelbine on day 8 (60 mg/m2)] concurrent with radiotherapy (66 Gy, administered at 1.8 Gy per day, five consecutive days per week). RESULTS: ORR was 79.2% (72.9% showing partial response and 6.3% showing complete response). With a median follow-up of 20.7 months, median PFS was 12 months and median OS was 36 months. Grade 3/4 toxicities were: neutropenia (14.5%), anaemia (6.2%), vomiting (2%), and oesophagitis (4.2%). No toxic deaths were reported. CONCLUSION: This combined regimen shows efficacy and a manageable safety profile. PFS and OS outcomes are encouraging and warrant further research.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Neoplasias Pulmonares/terapia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Caixa Torácica/efeitos da radiação , Espanha/epidemiologia , Análise de Sobrevida , Vinorelbina/administração & dosagem , Vinorelbina/efeitos adversosRESUMO
BACKGROUND: The abdominal wall may be severely compromised in the vast majority of intestinal and multiorgan transplant candidates, and sometimes as a consequence of complex liver transplantation. Multiple options have been described to overcome this problem, varying from component separation to the extreme need of performing an abdominal wall transplantation. The aim of the present paper is to report the largest and longest-term results of patients that received an abdominal rectus fascia (ARF) after liver, intestinal, or multiorgan transplantation at a single transplant center. METHODS: This is a retrospective report of a prospectively collected dataset of all the patients that received ARF during liver, isolated intestine, combined, or multiorgan transplantation at Fundación Favaloro from May 2006 to June 2016. RESULTS: A total of 19 out of 528 patients (3.5%) that underwent abdominal organ transplant received an ARF graft: 17 patients after receiving an intestine-containing graft, and 2 after liver retransplantations. Three patients required changing the ARF, 2 with a synthetic mesh and 1 with another ARF. Five patients required late reoperations: A relaparotomy was performed by transecting the ARF without encountering adhesions on the inner ARF surface. None of the 2 patients who received liver retransplantations and ARF developed acute or chronic ventral defects. CONCLUSIONS: The use of ARF is a simple and reliable surgical option to close abdominal wall defects during transplantation, the fascia adequately incorporates to the abdominal wall, allowing it to be transected and resutured in the long term and preserving the integrity of the peritoneal layer.
Assuntos
Técnicas de Fechamento de Ferimentos Abdominais , Fáscia/transplante , Intestino Delgado/transplante , Transplante de Fígado , Reto do Abdome/transplante , Adulto , Criança , Seguimentos , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Raw water clarification by flotation was studied by injecting air into a centrifugal multiphase pump to generate microbubbles (MBs) and nanobubbles (NBs). Measurements of gas dispersion parameters were performed and optimal conditions were obtained using a pump pressure of 4 bar. Values showed a bubble Sauter diameter of 75 µm, an air holdup of 1.2%, a bubble surface area flux of 34 s-1 and an NB concentration of 1 × 108 NBs mL-1 (measuring 220 nm). Then, a study compared flotation with bubbles formed with the multiphase pump (F-MP) to lamellar settling at the clarification stage of a water treatment plant (WTP), in Brazil. The F-MP showed a higher separation efficiency at high hydraulic loads (9-15 m h-1), even without the use of a polymer, reaching 2 NTU (10-25 NTU raw water feed), which was much lower than the technical goal of the WTP (5 NTU). The results and the technical aspects are discussed, and it is concluded that the employment of MBs and NBs with pumps widens new research lines and applications in modern flotation.
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Microbolhas , Purificação da Água/métodos , Brasil , ÁguaRESUMO
BACKGROUND AND AIMS: The concern over the weight gain problem continues to grow among both the international scientific community and public health authorities, since overweight and obesity prevalence rates continue to increase worldwide. In Chile, two out of three people are overweight, whereas 25% of the adult population is obese. Abdominal fat, has been linked to the development of a number of metabolic disorders. Waist circumference (WC) and the waist:height ratio (WHtR) have recently been evidenced as good predictors of metabolic risk for both adults and children. Thus, the present work aims at establishing smoothed centile charts and LMS tables for WC and WHtR for Chilean adults based on data from the National Health Survey-ENS, in order to have reliable information for identifying groups at risk. METHODS AND RESULTS: A sample of 4788 subjects aged 15-75 years old (mean age 46 ± 18 years old) was considered. Body weight, height, and WC were measured and Body Mass Index (BMI) and WHtR were also determined. Percentiles were calculated using the L (curve Box-Cox), M (curve median), S (curve coefficient of variation) method. In the obese group the WC cutoff values were 99.75 cm and 92.35 cm for men and women, respectively. The cutoff point for WHtR was 0.59 for both obese men and women. CONCLUSION: The study shows, for the first time, reference values for WC and WHtR for Chilean adults.
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Estatura , Obesidade/diagnóstico , Circunferência da Cintura , Razão Cintura-Estatura , Adolescente , Adulto , Distribuição por Idade , Idoso , Área Sob a Curva , Chile/epidemiologia , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/fisiopatologia , Valor Preditivo dos Testes , Curva ROC , Valores de Referência , Medição de Risco , Fatores de Risco , Distribuição por Sexo , Adulto JovemRESUMO
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract, and this disease has served as a paradigmatic model for successful rational development of targeted therapies. The introduction of tyrosine kinase inhibitors with activity against KIT/PDGFRA in both localized and advanced stages has remarkably improved the survival in a disease formerly deemed resistant to all systemic therapies. The Spanish Society of Medical Oncology (SEOM) guidelines provide a multidisciplinary and updated consensus for the diagnosis and treatment of GIST patients. We strongly encourage that the managing of these patients should be performed within multidisciplinary teams in reference centers.
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Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/terapia , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/terapia , Guias de Prática Clínica como Assunto , Humanos , EspanhaRESUMO
Internal dosimetry intercomparisons are essential for the verification of applied models and the consistency of results'. To that aim, the First Regional Intercomparison was organised in 2005, and that results led to the Second Regional Intercomparison Exercise in 2013, which was organised in the frame of the RLA 9/066 and coordinated by Autoridad Regulatoria Nuclear of Argentina. Four simulated cases covering intakes of (131)I, (137)Cs and Tritium were proposed. Ninteen centres from thirteen different countries participated in this exercise. This paper analyses the participants' results in this second exercise in order to test their skills and acquired knowledge, particularly in the application of the IDEAS Guidelines. It is important to highlight the increased number of countries that participated in this exercise compared with the first one and, furthermore, the improvement in the overall performance. The impact of the International Atomic Energy Agency (IAEA) Projects since 2003 has led to a significant enhancement of internal dosimetry capabilities that strengthen the radiation protection of workers.
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Doses de Radiação , Monitoramento de Radiação/métodos , Proteção Radiológica/métodos , Poluentes Radioativos do Ar , Carga Corporal (Radioterapia) , Radioisótopos de Césio/análise , Guias como Assunto , Humanos , Agências Internacionais , Cooperação Internacional , Radioisótopos do Iodo/análise , América Latina , Exposição Ocupacional/análise , Exposição Ocupacional/prevenção & controle , Monitoramento de Radiação/normas , Proteção Radiológica/normas , Radioisótopos , Reprodutibilidade dos Testes , Medição de Risco/normas , Sensibilidade e Especificidade , Software , TrítioRESUMO
Exposure to estrogen and its metabolites, including catechol estrogens (CEs) and catechol estrogen quinones (CE-Qs) is closely related to breast cancer. Polymorphisms of the genes involved in the catechol estrogens metabolism pathway (CEMP) have been shown to affect the production of CEs and CE-Qs. In this study, we measured the induction of CYP1A1, CYP1B1, COMT, and GSTP1 by 17ß-estradiol (17ß-E2) in leukocytes with CYP1A1(∗)2C, CYP1B1(∗)3, COMT Val158Met and GSTP1 Ile105Val polymorphisms by semi quantitative RT-PCR and compared the values to those of leukocytes with wild type alleles; we also compared the differences in formation of 4- hydroxyestradiol (4-OHE2) and DNA-adducts. The data show that in the leukocytes with mutant alleles treatment with 17ß-E2 up-regulates CYP1A1 and CYP1B1 and down-regulates COMT mRNA levels, resulting in major increments in 4-OHE2 levels compared to leukocytes with wild-type alleles. Therefore, we propose induction levels of gene expression and intracellular 4-OHE2 concentrations associated with allelic variants in response to exposure of 17ß-E2 as a noninvasive biomarker that can help determine the risk of developing non-hereditary breast cancer in women.
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Alelos , Catecol O-Metiltransferase , Citocromo P-450 CYP1A1 , Citocromo P-450 CYP1B1 , Estrogênios de Catecol/metabolismo , Leucócitos/metabolismo , Polimorfismo Genético , Catecol O-Metiltransferase/biossíntese , Catecol O-Metiltransferase/genética , Citocromo P-450 CYP1A1/biossíntese , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1B1/biossíntese , Citocromo P-450 CYP1B1/genética , Estradiol/farmacologia , Estrogênios de Catecol/genética , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/fisiologia , Humanos , Leucócitos/citologiaRESUMO
BACKGROUND: Treatment of metastatic colorectal cancer (mCRC) is generally based on genetic testing performed in primary tumor biopsies, but whether the genomic status of primary tumors is identical to that of metastases is not well known. We compared the gene expression profiles of formalin-fixed paraffin-embedded (FFPE) biopsies of colorectal primary tumors and matched liver metastases. PATIENTS AND METHODS: We compared the expression of 18 genes in FFPE CRC tumors and their matched liver metastases from 32 patients. The expression of each gene in CRC primary tumors and their matched liver metastases was tested using Student's t test for paired samples. Pairwise correlations of each gene in the primary tumors and matched liver metastases were evaluated by Pearson's correlation coefficient. RESULTS: The expression of six genes was significantly different in primary tumors compared with their matched liver metastases [CXCR4 (p < 0.001), THBS1 (p = 0.007), MMP 9 (p = 0.048), GST Pi (p = 0.050), TYMP (p = 0.042) and DPYD (p < 0.001)]. For the remaining genes, where no significant differences were observed, only SMAD4 (r s = 0.447, p = 0.010), ERCC1 (r s = 0.423, p = 0.016) and VEGF A (r s = 0.453, p = 0.009) showed significant correlation in expression between the two tissues. Therefore, we only detected similar gene expression levels between the tumor and the metastases in these three markers. CONCLUSIONS: We only found similar gene expression levels between the tumor and the metastases in three genes (SMAD4, ERCC1, and VEGF A). However, our study could not assess whether the differences in gene expression were secondary to tumoral heterogeneity or to molecular changes induced by previous chemotherapy.
Assuntos
Neoplasias Colorretais/genética , Perfilação da Expressão Gênica , Neoplasias Hepáticas/genética , Proteínas de Neoplasias/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Proteína Smad4/genética , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
PURPOSE: Colorectal liver metastases (CLM) have significant molecular heterogeneity, which contributes to the risk of recurrence following surgery. Most of the traditional scores intended to predict recurrence is based on clinicopathological variables and it is unclear whether incorporating molecular biomarkers might improve our assessment of the risk of recurrence. Our aim was to determine if molecular biomarkers might be associated with the risk of recurrence after surgery of CLM. PATIENTS AND METHODS: A total of 121 patients diagnosed with colorectal cancer (CRC) with resected liver metastases were included. The role of several clinicopathological variables to predict patient's outcome after resection of liver metastases was analyzed. Eighteen genes related to CRC pathogenesis were also included in the analyses. Univariate and multivariate stepwise Cox regression analyses were performed to identify factors associated with recurrence and the risk of death. RESULTS: Eight prognostic factors for progression-free survival and nine factors for overall survival were identified in the univariate analyses. After adjusting for other risk factors, only the expression of two molecular factors was associated with the risk of recurrence: TS (HR 0.631, 95 % CI 0.422-0.944) and SMAD4 (HR 1.680, 95 % CI 1.047-2.695). None of the variables was significantly associated with the risk of death in the multivariate analyses. CONCLUSIONS: The prognostic significance of most traditional clinicopathological variables might be insufficient to define patients at risk for recurrence after liver metastases resection. Molecular biomarkers might improve the identification of patients with higher risk of recurrence.