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Altered cell metabolism is a hallmark of cancer and critical for its development. Particularly, activation of one-carbon metabolism in tumor cells can sustain oncogenesis while contributing to epigenetic changes and metabolic adaptation during tumor progression. We assessed whether increased one-carbon metabolism activity is a metabolic feature of invasive ductal carcinoma (IDC). Differences in the metabolic profile between biopsies from IDC (n = 47) and its adjacent tissue (n = 43) and between biopsies from different breast cancer subtypes were assessed by gas spectrometry in targeted (Biocrates Life Science ® ) and untargeted approaches, respectively. The metabolomics data were statistically treated using MetaboAnalyst 4.0, SIMCA P+ (version 12.01), Statistica 10 software and t test with p < 0.05. The Cancer Genome Atlas breast cancer dataset was also assessed to validate the metabolomic profile of IDC. Our targeted metabolomics analysis showed distinct metabolomics profiles between IDC and adjacent tissue, where IDC displayed a comparative enrichment of metabolites involved in one-carbon metabolism (serine, glycine, threonine, and methionine) and a predicted increase in the activity of pathways that receive and donate carbon units (i.e., folate, methionine, and homocysteine). In addition, the targeted and untargeted metabolomics analyses showed similar metabolomics profiles between breast cancer subtypes. The gene set enrichment analysis identified different transcription-related functions between IDC and non-tumor tissues that involved one-carbon metabolism. Our data suggest that one-carbon metabolism may be a central pathway in IDC and even in general breast tumors, representing a potential target for its treatment and prevention.
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We evaluated whether the excluded stomach (ES) after Roux-en-Y gastric bypass (RYGB) can represent a premalignant environment. Twenty obese women were prospectively submitted to double-balloon enteroscopy (DBE) with gastric juice and biopsy collection, before and 3 months after RYGB. We then evaluated morphological and molecular changes by combining endoscopic and histopathological analyses with an integrated untargeted metabolomics and transcriptomics multiplatform. Preoperatively, 16 women already presented with gastric histopathological alterations and an increased pH (≥4.0). These gastric abnormalities worsened after RYGB. A 90-fold increase in the concentration of bile acids was found in ES fluid, which also contained other metabolites commonly found in the intestinal environment, urine, and faeces. In addition, 135 genes were differentially expressed in ES tissue. Combined analysis of metabolic and gene expression data suggested that RYGB promoted activation of biological processes involved in local inflammation, bacteria overgrowth, and cell proliferation sustained by genes involved in carcinogenesis. Accumulated fluid in the ES appears to behave as a potential premalignant environment due to worsening inflammation and changing gene expression patterns that are favorable to the development of cancer. Considering that ES may remain for the rest of the patient's life, long-term ES monitoring is therefore recommended for patients undergoing RYGB.
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Obesidad/patología , Estómago/patología , Adolescente , Adulto , Femenino , Derivación Gástrica/métodos , Jugo Gástrico/fisiología , Expresión Génica/fisiología , Humanos , Inflamación/patología , Inflamación/cirugía , Metabolómica/métodos , Persona de Mediana Edad , Obesidad/cirugía , Estómago/cirugía , Transcriptoma/fisiología , Pérdida de Peso/fisiología , Adulto JovenRESUMEN
OBJECTIVES: The assessment of nutritional intake before and after bariatric surgery assists in identifying eating disorders, nutritional deficiencies and weight loss/maintenance. The 7-day record is the gold standard for such an assessment and is interpreted using specialized software. This study sought to compare the Virtual Nutri Plus® and Dietpro 5i® software systems in assessing nutrient intake in obese patients with type 2 diabetes mellitus who underwent a Roux-en-Y gastric bypass. METHODS: Nutritional intake was assessed in 10 obese women with type 2 diabetes mellitus before and 3 months after Roux-en-Y gastric bypass. The 7-day record was used to assess food intake and then, the Virtual Nutri Plus® and Dietpro 5i® software systems were used to calculate calorie, macronutrient and micronutrient intake based on validated food chemical composition databases. Clinicaltrials.gov: NCT01251016. RESULTS: During the preoperative period, deficits in the ingestion of total fiber and 15 out of 22 estimated micronutrients were observed when using the Virtual Nutri Plus®, compared to deficiencies in total fiber and 4 micronutrients when using the Dietpro 5i®. During the postoperative period, both the Virtual Nutri Plus® and Dietpro 5i® systems detected deficits in the ingestion of total fiber, carbohydrates and 19 micronutrients, but only the Virtual Nutri Plus® detected deficits in complex B vitamins (except B12) and minerals. CONCLUSION: Virtual Nutri Plus® was more sensitive than Dietpro 5i® for the identification of deficits in nutrient intake in obese, type 2 diabetes mellitus patients undergoing Roux-en-Y gastric bypass.
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Ingestión de Alimentos , Derivación Gástrica/métodos , Evaluación Nutricional , Programas Informáticos , Adulto , Diabetes Mellitus Tipo 2 , Ingestión de Energía , Femenino , Humanos , Desnutrición/diagnóstico , Persona de Mediana Edad , Obesidad/cirugía , Periodo Posoperatorio , Periodo Preoperatorio , Reproducibilidad de los Resultados , Estadísticas no Paramétricas , Factores de TiempoRESUMEN
OBJECTIVES: The assessment of nutritional intake before and after bariatric surgery assists in identifying eating disorders, nutritional deficiencies and weight loss/maintenance. The 7-day record is the gold standard for such an assessment and is interpreted using specialized software. This study sought to compare the Virtual Nutri Plus® and Dietpro 5i® software systems in assessing nutrient intake in obese patients with type 2 diabetes mellitus who underwent a Roux-en-Y gastric bypass. METHODS: Nutritional intake was assessed in 10 obese women with type 2 diabetes mellitus before and 3 months after Roux-en-Y gastric bypass. The 7-day record was used to assess food intake and then, the Virtual Nutri Plus® and Dietpro 5i® software systems were used to calculate calorie, macronutrient and micronutrient intake based on validated food chemical composition databases. Clinicaltrials.gov: NCT01251016. RESULTS: During the preoperative period, deficits in the ingestion of total fiber and 15 out of 22 estimated micronutrients were observed when using the Virtual Nutri Plus®, compared to deficiencies in total fiber and 4 micronutrients when using the Dietpro 5i®. During the postoperative period, both the Virtual Nutri Plus® and Dietpro 5i® systems detected deficits in the ingestion of total fiber, carbohydrates and 19 micronutrients, but only the Virtual Nutri Plus® detected deficits in complex B vitamins (except B12) and minerals. CONCLUSION: Virtual Nutri Plus® was more sensitive than Dietpro 5i® for the identification of deficits in nutrient intake in obese, type 2 diabetes mellitus patients undergoing Roux-en-Y gastric bypass. .
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Adulto , Femenino , Humanos , Persona de Mediana Edad , Ingestión de Alimentos , Derivación Gástrica/métodos , Evaluación Nutricional , Programas Informáticos , Ingestión de Energía , Desnutrición/diagnóstico , Obesidad/cirugía , Periodo Posoperatorio , Periodo Preoperatorio , Reproducibilidad de los Resultados , Estadísticas no Paramétricas , Factores de TiempoRESUMEN
In HER-2-overexpressing breast cells, HER-2 receptors exist on the cell surface as monomers, homodimers and heterodimers. For signal activation and transduction to occur, HER-2 must be localized to lipid rafts. Therefore, we hypothesized that the amount of lipid rafts on the cell membrane would be a factor in HER-2 signaling. To test this, we used HB4a (an untransformed human mammary epithelial cell line) and HB4aC5.2 cells. HB4aC5.2 cells are HB4a derivatives that have been transfected with five copies of pJ5E.c-ErbB-2 and express approximately 900 times more HER-2 than HB4a cells. In these cells, HER-2 overexpression was accompanied by increased lipid rafts in cell membranes, a hyperactivation of downstream Akt and ERK1/2 proteins, and an increased rate of cell growth compared to HB4a. In addition, HER-2 overexpression was associated with an increased activation of FASN, a key enzyme involved in cellular lipogenesis. Its final product, palmitate, is frequently used to synthesize lipid rafts. We further hypothesized that treatment with docosahexaenoic acid (DHA), an omega-3 fatty acid, would disrupt the lipid rafts and lead to a growth arrest. In HB4aC5.2 cells, but not HB4a cells, we found that DHA treatment disrupted lipid raft; inhibited HER-2 signaling by decreasing activation of Akt, ERK1/2 and FASN proteins; and induced apoptosis. Although little is known about lipid rafts, our data support the idea that disturbances in these microdomains induced by DHA may represent a useful tool for controlling the signaling initiated by HER-2 receptors and its therapeutic potential in the treatment of HER-2 positive breast cancer.
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Apoptosis/efectos de los fármacos , Ácidos Docosahexaenoicos/farmacología , Células Epiteliales/efectos de los fármacos , Microdominios de Membrana/efectos de los fármacos , Receptor ErbB-2/genética , Western Blotting , Mama/citología , Mama/metabolismo , Línea Celular Transformada , Proliferación Celular/efectos de los fármacos , Células Epiteliales/metabolismo , Femenino , Humanos , Lipogénesis , Glándulas Mamarias Humanas/citología , Microdominios de Membrana/metabolismo , Microscopía Confocal , Proteína Quinasa 3 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor ErbB-2/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND & AIMS: We evaluated the ability of Nutritional Risk Screening 2002 (NRS 2002) and Subjective Global Assessment (SGA) to predict malnutrition related to poor clinical outcomes. METHODS: We assessed 705 patients at a public university hospital within 48 h of admission. Logistic regression and number needed to screen (NNS) were calculated to test the complementarity between the tools and their ability to predict very long length of hospital stay (VLLOS), complications, and death. RESULTS: Of the patients screened, 27.9% were at nutritional risk (NRS+) and 38.9% were malnourished (SGA B or C). Compared to those patients not at nutritional risk, NRS+, SGA B or C patients were at increased risk for complications (p=0.03, 0.02, and 0.003, respectively). NRS+ patients had an increased risk of death (p=0.03), and SGA B and C patients had an increased likelihood of VLLOS (p=0.008 and p<0.0001, respectively). Patients who were both NRS+ and SGA C had lower estimates of NNS than patients who were NRS+ or SGA C only, though their confidence intervals did overlap. CONCLUSIONS: The concurrent application of SGA in NRS+ patients might enhance the ability to predict poor clinical outcomes in hospitalized patients in Brazil.
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Tiempo de Internación , Desnutrición/complicaciones , Desnutrición/diagnóstico , Evaluación Nutricional , Brasil , Hospitalización , Humanos , Modelos Logísticos , Desnutrición/mortalidad , Enfermedades Metabólicas/complicaciones , Enfermedades Metabólicas/diagnóstico , Enfermedades Metabólicas/mortalidad , Estado Nutricional , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
Emulsões lipídicas parenterais (EL) podem modular funções leucocitárias, influenciando a resposta imune. O processo de apresentação de antígenos por leucócitos ocorre pela expressão de moléculas de superfície específicas e constitui o ponto-chave para o desencadeamento de resposta imune eficiente / Parenteral lipid emulsion (LE) can modulate leukocytes function and modify immune response. The antigen presenting process by leucocytes occurs through the expression of specific surface molecules and constitutes the key point for the start of an efficient immune response...
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Masculino , Adulto , Persona de Mediana Edad , Humanos , Emulsiones Grasas Intravenosas , Técnicas In Vitro , Leucocitos Mononucleares , Peróxidos , Citometría de FlujoRESUMEN
O uso de emulsöes lipídicas em nutriçäo parenteral total tem sido associado a alteraçöes do sistema mononuclear fagocitário. O objetivo do presente estudo foi avaliar a influência da nutriçäo parenteral contendo diferentes emulsöes lipídicassobre a fagocitose de macrófagos (Mf). Setenta ratos Wistar com a veia jugular externa cateterizada receberam, por via intrravenosa, diferentes regimes de nutriçäo parenteral total, isocalóricos, isonitrogenados e isogordurosos ou dieta oral e foram separados em sete grupos: 1) Grupo OS: dieta oral com infusäo intravenosa de soro fisiológico a 9 porcento; 2) Grupo GLU: NPT sem lípides; 3) GrupoLCT: NPT contendo emulsäo lipídica a 10 porcento de trtiglicérides de cadeia longa (TCL); 4) Grupo LCTFO1: NPT contendo TCL e emulsäo lipídica de óleo de peixe(FO) a 10 por cento; 5) Grupo LCTFO2: contendo TCL e FO; 6) Grupo MCT: NPT contendo emulsäo lipídicaa 10 porcento com 50 porcento de triglicérides de cadeia média (TCM) e 50 porcento de TCL; 7) Grupo MCTFO1: NPT contendo TCM, TCL e FO. Após 96 horas de ministraçäo de NPT ou SF, foi injetado, pela veia caudal do rato, 1,0 Ml/kg de peso corpóreo de carväo coloidal. Após três horas os animais foram sacrificados. Fígado, baço e pulmöes forampesados e estudados por imuno-histoquímica, com o método avidina-biotina utilizando o anticorpo anti-MfHAM-56. Verificou-se microscopicamente o número total de Mf (MT) e Mf que haviam fagocitado (MF) o carväo coloidal e estabeleceu-se o índice de fagocitose. O grupo que recebeu dieta oral foi o único a ganhar peso. Em nenhum grupo observou-se diferença no peso dos órgäos. A NPT em regime glicídico e lipídico com TCL inibiu a fagocitose de Mf no fígado,baço e pulmöes. A adiçäo de emulsäo lipidica de óleo de peixe às fórmulas de NPT contendo emulsöes lipídicas de TCM e TCL aumentou o número e a fagocitose de Mf no fígado e pulmöes. Perspectivas apontam a necessidade de estudos com diferentes concentraçöes de lípides em NPT valorizando outras funçöes dos macrófagos.(au)
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Animales , Ratas , Lípidos/deficiencia , Macrófagos/inmunología , Nutrición Parenteral TotalRESUMEN
O uso de nutricao parenteral total (NPT) tem sido associado a alteracoes anatomicas e funcionais do sistema mononuclear fagocitario. Os efeitos das emulsoes lipidicas parenterais sobre a fagocitose do sistema mononuclear fagocitario ainda sao controversos. O objetivo do presente estudo foi avaliar a influencia da nutricao parenteral total sem lipides e contendo diferentes emulsoes lipidicas sobre a fagocitose de macrofagos. Setenta ratos Wistar com a veia jugular externa cateterizada receberam, por via intravenosa central, diferentes regimes de nutricao parenteral total, isocaloricos (1,16 kcal/mL), isonitrogenados (1,5 g/mL), e isogordurosos (30 a 32 por cento do valor calorico nao proteico) ou dieta oral e foram separados em sete grupos...