MIR-203A-3P AND MMP-2 PROTEINS ARE HIGHLY EXPRESSED IN CIRCULATING TUMOR CELLS FROM PATIENTS WITH PANCREATIC CARCINOMA. / PROTEÍNAS MIR-203A-3P E MMP-2 SÃO ALTAMENTE EXPRESSAS EM CÉLULAS TUMORAIS CIRCULANTES DE PACIENTES COM CARCINOMA PANCREÁTICO.

OBJECTIVES: Ductal adenocarcinoma of the pancreas is the fourth most common cancer-associated cause of death in the Western world. The presence of circulating tumor cells (CTCs) can be considered a potential prognostic factor, as these cells represent tumor progression, allowing monitoring of therapeutic efficacy. The objectives of this study were to explore the morphological, molecular, and phenotypic characteristics of CTCs from the blood of patients with pancreatic carcinoma and to correlate the findings with response to treatment, progression-free survival, overall survival (OS), and deep vein thrombosis (DVT). METHODS: Peripheral blood (10 mL) was analyzed before the beginning of treatment after 60 and 120 days. CTCs were detected by using ISET® and characterized by immunocytochemistry. For microRNAs (miRNAs) analysis, peripheral leukocytes from the same patients and healthy individuals (controls) were collected in parallel at baseline. The expression of miRNAs was evaluated (in pool) using TaqMan® Array Human MicroRNA Cards v2.0. RESULTS: Only nine patients were included. The proteins, namely, matrix metalloproteinase-2 (MMP2) and TGFß-RI, were highly expressed (77.7%) in CTCs at baseline; at the first follow-up, MMP2 was predominant (80%) and, at the second follow-up, MMP2 and vimentin were predominant (50%). Circulating tumor microemboli (CTMs) were found in two patients and both presented DVT. The miR-203a-3p was highly expressed in CTCs. The miR-203a-3p is involved in the stimulation of epithelial-to-mesenchymal transition (EMT) and is related to worse OS in pancreatic cancer (TCGA data). CONCLUSION: Due to the low number of patients and short follow-up, we did not observe a correlation between CTCs and response to treatment. However, there was a correlation between CTM and DVT and also miR-203a-3p was highly expressed in CTCs, corroborating the findings of EMT proteins. This study opens the perspectives concerning the dynamic change in the pattern of proteins expressed along with treatment and the use of miRNAs as new targets in pancreatic carcinoma.

OBJETIVOS: O adenocarcinoma ductal do pâncreas é a quarta causa de morte associada ao câncer mais comum no mundo ocidental. A presença de células tumorais circulantes (CTCs) pode ser considerada um potencial fator prognóstico, visto que essas células representam a progressão tumoral, permitindo o monitoramento da eficácia terapêutica. explorar as características morfológicas, moleculares e fenotípicas das células tumorais circulantes (CTCs) do sangue de pacientes com carcinoma pancreático e correlacionar os achados com a resposta ao tratamento, sobrevida livre de progressão, sobrevida global (SG) e trombose venosa profunda (TVP). MÉTODOS: o sangue periférico (10mL) foi analisado antes do início do tratamento e após 60 e 120 dias. As CTCs foram detectadas pelo ISET® e caracterizadas por imunocitoquímica. Para análise de miRNAs, leucócitos periféricos dos mesmos pacientes e indivíduos saudáveis foram coletados em paralelo no início do estudo. A expressão de miRNAs foi avaliada usando TaqMan T Array Human MicroRNA Cards v2.0. RESULTADOS: foram incluídos 9 pacientes. As proteínas MMP2 e TGFß-RI foram altamente expressas (77,7%) nas CTCs no início do estudo. No primeiro acompanhamento, MMP2 era predominante (80%) e no segundo acompanhamento, MMP2 e vimentina eram predominantes (50%). Microêmbolos tumorais circulantes (MTC) foram encontrados em dois pacientes e ambos apresentavam TVP. O miR-203a-3p foi altamente expresso em CTCs. miR-203a-3p está envolvido na estimulação da transição epitelio-mesenquima (TEM) e relacionado a pior SG no câncer pancreático (dados TCGA). CONCLUSÃO: Devido ao baixo número de pacientes e curto seguimento, não observamos correlação entre CTCs e resposta ao tratamento. No entanto, houve uma correlação entre MTC e TVP. Além disso, miR-203a-3p foi altamente expresso em CTCs, corroborando os achados de proteínas EMT. Este estudo abre perspectivas sobre a mudança dinâmica no padrão de proteínas expressas ao longo do tratamento e a utilização de miRNAs como novos alvos no carcinoma pancreático.

A higher platelet-to-lymphocyte ratio is prevalent in the presence of circulating tumor microemboli and is a potential prognostic factor for non-metastatic colon cancer.

Colorectal cancer is a common and often deadly cancer. Circulating tumor cells (CTCs) have been implicated as a potentially valuable prognosis factor. The detection of circulating tumor microemboli (CTM) and of simple blood component parameters that reflect inflammatory status, such as the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR), may provide information about tumor progression. The aim of this study was to explore the importance of CTCs, CTM, PLR, and NLR prospectively in non-metastatic colon cancer progression. CTCs were enriched using ISETⓇ (Isolation by SizE of Tumor cells) and identified by immunocytochemical exclusion of leukocytes. We evaluated CTCs and blood cell parameters in a cohort of 69 stage I-III colon cancer patients (52.2% men; median age, 61 years; age range, 19-87 years) at a baseline timepoint prior to resection surgery. The median of CTC levels at baseline was 20 cells/8 mL (0-94) and higher levels were associated with CTM presence (p = 0.02). CTM were found in 18 (26.1%) patients. Of 18 stage I patients, 33.3% had CTM and of 51 stages II or III patients, 13.7% had CTM (p = 0.08). Patients with a high PLR (>124) were mostly (75.6%) diagnosed with high-risk stages II/III cancer (stages I/low-risk II, 24.4%; p = 0.014). All 8 patients that had disease recurrence during follow-up had a high PLR (p = 0.02 vs. low PLR). NLR was not significantly associated with disease stage or recurrence. The present results indicate that CTCs and PLR analyses may be clinically useful for colon cancer management and risk stratification.

Proteínas mir-203a-3p e mmp-2 são altamente expressas em células tumorais circulantes de pacientes com carcinoma pancreático / Mir-203a-3p and mmp-2 proteins are highly expressed in circulating tumor cells from patients with pancreatic carcinoma

RESUMO -RACIONAL: O adenocarcinoma ductal do pâncreas é a quarta causa de morte associada ao câncer mais comum no mundo ocidental. A presença de células tumorais circulantes (CTCs) pode ser considerada um potencial fator prognóstico, visto que essas células representam a progressão tumoral, permitindo o monitoramento da eficácia terapêutica. OBJETIVOS: explorar as características morfológicas, moleculares e fenotípicas das células tumorais circulantes (CTCs) do sangue de pacientes com carcinoma pancreático e correlacionar os achados com a resposta ao tratamento, sobrevida livre de progressão, sobrevida global (SG) e trombose venosa profunda (TVP). MÉTODOS: o sangue periférico (10mL) foi analisado antes do início do tratamento e após 60 e 120 dias. As CTCs foram detectadas pelo ISET® e caracterizadas por imunocitoquímica. Para análise de miRNAs, leucócitos periféricos dos mesmos pacientes e indivíduos saudáveis foram coletados em paralelo no início do estudo. A expressão de miRNAs foi avaliada usando TaqMan T Array Human MicroRNA Cards v2.0. RESULTADOS: foram incluídos 9 pacientes. As proteínas MMP2 e TGFß-RI foram altamente expressas (77,7%) nas CTCs no início do estudo. No primeiro acompanhamento, MMP2 era predominante (80%) e no segundo acompanhamento, MMP2 e vimentina eram predominantes (50%). Microêmbolos tumorais circulantes (MTC) foram encontrados em dois pacientes e ambos apresentavam TVP. O miR-203a-3p foi altamente expresso em CTCs. miR-203a-3p está envolvido na estimulação da transição epitelio-mesenquima (TEM) e relacionado a pior SG no câncer pancreático (dados TCGA). CONCLUSÃO: Devido ao baixo número de pacientes e curto seguimento, não observamos correlação entre CTCs e resposta ao tratamento. No entanto, houve uma correlação entre MTC e TVP. Além disso, miR-203a-3p foi altamente expresso em CTCs, corroborando os achados de proteínas EMT. Este estudo abre perspectivas sobre a mudança dinâmica no padrão de proteínas expressas ao longo do tratamento e a utilização de miRNAs como novos alvos no carcinoma pancreático.

ABSTRACT - BACKGROUND: Ductal adenocarcinoma of the pancreas is the fourth most common cancer-associated cause of death in the Western world. The presence of circulating tumor cells (CTCs) can be considered a potential prognostic factor, as these cells represent tumor progression, allowing monitoring of therapeutic efficacy. OBJECTIVES: The objectives of this study were to explore the morphological, molecular, and phenotypic characteristics of CTCs from the blood of patients with pancreatic carcinoma and to correlate the findings with response to treatment, progression-free survival, overall survival (OS), and deep vein thrombosis (DVT). METHODS: Peripheral blood (10 mL) was analyzed before the beginning of treatment after 60 and 120 days. CTCs were detected by using ISET® and characterized by immunocytochemistry. For microRNAs (miRNAs) analysis, peripheral leukocytes from the same patients and healthy individuals (controls) were collected in parallel at baseline. The expression of miRNAs was evaluated (in pool) using TaqMan® Array Human MicroRNA Cards v2.0. RESULTS: Only nine patients were included. The proteins, namely, matrix metalloproteinase-2 (MMP2) and TGFβ-RI, were highly expressed (77.7%) in CTCs at baseline; at the first follow-up, MMP2 was predominant (80%) and, at the second follow-up, MMP2 and vimentin were predominant (50%). Circulating tumor microemboli (CTMs) were found in two patients and both presented DVT. The miR-203a-3p was highly expressed in CTCs. The miR-203a-3p is involved in the stimulation of epithelial-to-mesenchymal transition (EMT) and is related to worse OS in pancreatic cancer (TCGA data). CONCLUSION: Due to the low number of patients and short follow-up, we did not observe a correlation between CTCs and response to treatment. However, there was a correlation between CTM and DVT and also miR-203a-3p was highly expressed in CTCs, corroborating the findings of EMT proteins. This study opens the perspectives concerning the dynamic change in the pattern of proteins expressed along with treatment and the use of miRNAs as new targets in pancreatic carcinoma.

Avaliação da expressão de proteínas e microRNAs relacionados à transição epitélio-mesênquima em células tumorais circulantes provenientes de pacientes com carcinoma de pâncreas / Evaluation of the expression of proteins and microRNAs related to the epithelial-mesenchymal transition in circulating tumor cells from patients with pancreatic carcinoma

O adenocarcinoma ductal do pâncreas é a quarta causa associada a câncer mais comum de morte no mundo ocidental. A presença de células tumorais circulantes (CTCs) no sangue pode ser considerada como um potencial fator prognóstico. Assim, o estudo de componentes que contribuem para sua formação de metástases tem se mostrado promissor. CTCs representam, em tempo real, a progressão tumoral, permitindo o monitoramento da eficácia terapêutica. O presente projeto teve por objetivo detectar CTCs presentes no sangue periférico de pacientes com adenocarcinoma ductal de pâncreas, avaliar a expressão de proteínas relacionadas à transição epitélio-mesênquima (TEM) tais como a mesotelina, vimentina, Metaloproteinase de Matriz 2 (MMP2) e o Receptor Beta do Fator de Crescimento Transformador I (TGFß-RI) e correlacionar com a resposta ao tratamento e sobrevida livre de progressão. Ainda, tentamos correlacionar os níveis de CTCs e expressão dos miRNAs destas células com sobrevidas livre de progressão (SLP) e global (SG). Foram analisadas amostras de sangue de 9 pacientes com adenocarcinoma de pâncreas (10 ml de sangue periférico) antes do início do tratamento e após 60 e 120 dias. As CTCs foram detectadas pelo sistema ISET (Rarecells, France) e depois caracterizadas por imunocitoquímica . Para análise de miRNAS das CTCs, foram colhidos em paralelo, leucócitos periféricos dos mesmos pacientes e de indivíduos saudáveis, como controle. Para essa análise, utilizamos apenas o material da coleta baseline. A extração do material foi realizada com um kit comercial (Qiagen) e a avaliação da expressão dos microRNAs com TaqMan Low Density Array (TLDA) em pool. As análises das proteínas envolvidas na TEM na coleta baseline, indicam que as CTCs expressavam predominantemente MMP2 (77,77%), seguida de TGFß-RI (44,44%), vimentina (33,33%) e mesotelina (22,22%). No primeiro grupo de acompanhamento de 5 pacientes, as CTCs expressaram MMP2 e vimentina (80%), TGFß-RI (60%) e mesotelina (20%). Comparadas ao grupo de 8 pacientes do segundo seguimento, as CTCs expressaram MMP2 (50%), vimentina (25%) e TGF-RI (12,5%). Constatamos que 3/9 pacientes no presente estudo progrediram (33,33%). Em dois pacientes, foram encontrados microêmbolos tumorais circulantes (MTC) e ambos apresentaram Trombose Venosa Periférica (TVP), mostrando que talvez haja uma correlação entre MTC e TVP. Encontramos dois microRNAs altamente expressos nas CTCs dos pacientes aqui avaliados, ambos envolvidos na estimulação do processo de TEM: hsa-miR-203a-3p e hsa-324-5p. Não houve diferença estatisticamente significante no número de casos com presença de proteína ou correlação com outros fatores, embora a MMP2 tenha sido altamente expressa nas três coletas, seguida por TGFß-RI e vimentina. Também não encontramos qualquer correlação entre as variáveis analisadas e SLP e SG. Neste trabalho foi possível encontrar CTCs em todos os 9 pacientes com câncer de pâncreas. Devido ao baixo número de pacientes incluídos e curto tempo de follow-up, não conseguimos ver correlação entre níveis de CTCs e expressão de proteínas e SLPe SG, mas continuaremos acompanhando o pacientes. Encontramos correlação entre presença de MTC e TEP. E conforme esperávamos, encontramos microRNAs relacionados à TEM altamente expressos em CTCs de pacientes com câncer de pâncreas (AU)

Ductal adenocarcinoma of the pancreas is the fourth most common cancer-associated cause of death in the Western world. The presence of circulating tumor cells (CTCs) in the blood can be considered as a potential prognostic factor. Thus, the study of components that contribute to metastases formation has shown to be promising. CTCs represent, in real time, tumor progression, allowing monitoring of therapeutic efficacy. The aim of this project was to detect CTCs present in the peripheral blood of patients with pancreatic ductal adenocarcinoma, to evaluate the expression of proteins related to the epithelial-mesenchymal transition (TEM) such as mesothelin, vimentin, Matrix Metalloproteinase 2 (MMP2) and Transforming Growth Factor Beta Receptor I (TGFß-RI) and correlate with response to treatment, progression-free survival (PFS) and overall survival (OS). Still, we tried to correlate the levels of CTCs and expression of miRNAs of these cells with progression-free and global survival. Blood samples from 9 patients with pancreatic adenocarcinoma (10 ml of peripheral blood) were analyzed before the start of treatment and after 60 and 120 days. CTCs were detected by the ISET system (Rarecells, France) and then characterized by immunocytochemistry. For analysis of the CTCs miRNAs, peripheral leukocytes from the same patients and healthy individuals were collected in parallel as a control. For this analysis, we used only the material from the baseline collection. The extraction of the material was made with a commercial kit (Qiagen) and the evaluation of the expression of the microRNAs with TaqMan Low Density Array (TLDA) in pool. The analysis of proteins involved in TEM in the baseline collection, indicates that CTCs expressed predominantly MMP2 (77.77%), TGFß-RI (44.44%), vimentin (33.33%) and mesothelin (22.22%). In the first follow-up group of 5 patients, CTCs expressed MMP2 in (80%), vimentin and TGFß-RI in (60%) and mesothelin (20%). Compared to the group of 8 patients in the second follow-up, CTCs expressed MMP2 in (50%), vimentin (25%) and TGF-RI in (12.5%). We found that 3/9 patients in the present study progressed (33.33%). In two patients, circulating tumor microemboli (CTM) were found and both had Peripheral Venous Thrombosis (PVT), showing that there may be a correlation between CTM and PVT. We found two microRNAs highly expressed in the CTCs of the patients evaluated here, both involved in the stimulation of the TEM process: hsa-miR-203a-3p and hsa-324-5p. There was no statistically significant difference in the number of cases with protein or correlation with other factors, although MMP2 was highly expressed in the three collections, followed by TGFß-R1 and vimentin. We also found no correlation between the variables analyzed and PFS and OS. In this work, it was possible to find CTCs in all 9 pancreatic cancer patients. Due to the low number of patients included and short follow-up time, we were unable to see a correlation between CTC levels and protein expression and PFS and OS, but we will continue to monitor the patients. Here, we found a correlation between the presence of CTM and PVT. As we expected, we found TEM-related microRNAs highly expressed in CTCs of patients with pancreatic cancer (AU)

Construction of a predictive model for concentration of nickel and vanadium in vacuum residues of crude oils using artificial neural networks and LIBS.

A predictive model to determine the concentration of nickel and vanadium in vacuum residues of Colombian crude oils using laser-induced breakdown spectroscopy (LIBS) and artificial neural networks (ANNs) with nodes distributed in multiple layers (multilayer perceptron) is presented. ANN inputs are intensity values in the vicinity of the emission lines 300.248, 301.200 and 305.081 nm of the Ni(I), and 309.310, 310.229, and 311.070 nm of the V(II). The effects of varying number of nodes and the initial weights and biases in the ANNs were systematically explored. Average relative error of calibration/prediction (REC/REP) and average relative standard deviation (RSD) metrics were used to evaluate the performance of the ANN in the prediction of concentrations of two elements studied here.

Reflexiones acerca del aprendizaje basado en problemas (ABP). Una alternativa en la educación médica / Some reflections on problem-based learning (PBL): an alternative in medical education

El presente estudio es un ensayo reflexivo, argumentativo, cuya tesis de discusión es que el Aprendizaje Basado en Problemas (ABP) puede ser una mejor alternativa a las necesidades actuales de la formación médica. Para la argumentación, el autor se basó en las recomendaciones que sobre educación médica han emitido organismos tales como la AAMC (American Association of Medical College) y la Academia Nacional de Medicina de Colombia, entre otros. Se hizo una revisión de teorías de la psicología cognitiva (constructivismo y andragogía), que son el fundamento conceptual del ABP, y se revisaron artículos descriptivos, prospectivos y metanálisis sobre los resultados de las investigaciones realizadas a la fecha en escuelas de medicina de diferentes culturas, con la más larga experiencia en la aplicación de ABP. El autor concluye que vale la pena incursionar en la aplicación de la ABP en las escuelas de medicina, ya que se obtiene como mínimo una mejoría significativa en la satisfacción de profesores y alumnos, así como una mejoría en el caudal de conocimiento de los estudiantes dentro del proceso de enseñanza-aprendizaje.

Nutrición parental total durante el embarazo

Presentamos un caso de hiperemesis gravídica severa que requirió soporte nutricional por via parental durante la segunda mitad del embarazo hasta la culminación del mismo. Se revisan las indicaciones, alternativas y la necesidad de mantener un estado nutricional óptimo durante el embarazo.