RESUMO
In this article we can observe the scanning by the literature for the pretreatment of steam explosion applied to lignocellulose biomass. A comparison of the chemical and physical characterization of potato peel as a lignocellulose biomass. Besides, the innovative design of a continuous reactor for the potato peel steam explosion process is shown, with specific temperature and pressure conditions on a pilot scale, detailing its parts. Finally, a finite element analysis was performed where stress results were obtained from the reactor material, severity factor, structural analysis and thermal analysis, providing a panorama of the reactor's behavior with the conditions specific.
Assuntos
Solanum tuberosum , Vapor , Solanum tuberosum/química , Lignina/química , Desenho de Equipamento , Temperatura , Biomassa , Análise de Elementos Finitos , Pressão , Biotecnologia/métodos , Reatores BiológicosRESUMO
Las patologías y condiciones linguales constituyen una proporción considerable del total de lesiones de la mucosa oral. Los estudios epidemiológicos que describen su frecuencia en la población pediátrica son escasos y variables. El objetivo de este estudio fue establecer la frecuencia de patologías y condiciones de lengua en niños atendidos en la Facultad de Odontología de la Universidad de Chile. Se realizó un estudio observacional, descriptivo y de corte transversal donde se examinaron pacientes pediátricos de 4 a 13 años de ambos sexos. De un total de 179 pacientes, un 53 % presentó al menos una patología o condición lingual. El rango etario de 11 a 13 años presentó un mayor OR de presentar lesiones y/o condiciones linguales al ser comparado con los otros rangos etarios (valor p<0,05). La patología o condición lingual más frecuente fue la lengua saburral (39 %), seguida por la lengua fisurada (15 %), la hipertrofia de papilas linguales (5 %) y la lengua geográfica (3 %). La ubicación más frecuente fue la base lingual con un 59 % del total de ubicaciones registradas. En base a la escasa evidencia que existe y a la alta frecuencia encontrada en esta investigación, se debe destacar la importancia del conocimiento de las patologías y condiciones linguales en niños. A través de este estudio, se sientan bases para futuras investigaciones que ayuden a odontólogos a reconocer, diagnosticar y tratar estas condiciones cuando sea necesario.
Lingual pathologies and conditions constitute a considerable proportion of the total lesions of the oral mucosa.The epidemiological studies that describe its frequency in the pediatric population are limited and variable. The objective of this study was to establish the frequency of pathologies and lingual conditions in children attended at the Faculty of Dentistry of the University of Chile. An observational, descriptive and cross-sectional study was carried out where pediatric patients between 4 and 13 years of both sexes were examined. Of a total of 179 patients, 53 % had at least one pathology or lingual condition. The age range of 11 to 13 years presented a higher OR of presenting lesions and/or lingual conditions when compared with the other age ranges (p value <0.05). The most frequent pathology or lingual condition was coated tongue (39 %), fast due to the fissured tongue (15 %), the hypertrophy of the lingual papillae (5 %) and the geographic tongue (3 %). The most frequent location was the lingual base with 59 % of the total frequency registered. Based on the little evidence that exists and the high frequency found in this research, the importance of knowledge of pathologies and lingual conditions in children should be highlighted. Through this study, foundations are laid for future investigations that help dentists recognize, diagnose, and treat these conditions when necessary.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Neoplasias da Língua/patologia , Neoplasias da Língua/epidemiologia , Doenças da Língua/epidemiologia , Chile/epidemiologia , Epidemiologia Descritiva , Estudos TransversaisRESUMO
PURPOSE: Increasingly epidemiological evidence supports that environmental factors are associated with breast cancer (BC) outcomes after a BC diagnosis. Although evidence suggests that air pollution exposure is associated with higher mortality in women with BC, studies investigating potential mechanisms have been lacking. METHODS: We evaluated women with BC (N = 151) attended at the National Cancer Institute-Mexico from 2012 to 2015. We calculated 1-year average exposures to particulate matter < 2.5 µm (PM2.5) at home address before diagnosis. We used linear and logistic regression models to determine the associations between PM2.5 exposure and BC aggressiveness (tumor size, molecular phenotype). RESULTS: Average annual PM2.5 exposure of this population was 23.0 µg/m3 [standard deviation (SD)]: 1.90 µg/m3]. PM2.5 levels were positively correlated with tumor size at diagnosis (r = 0.22; p = 0.007). Multivariable linear models had a similar inference [risk ratio (RR): 1.32; 95% confidence interval (95% CI): 1.04, 1.674]. We did not observe differences in this association by age or menopause status. Further, women with triple-negative BC (TNBC) had significantly higher PM2.5 levels compared with other phenotypes (p = 0.015). Multivariable-adjusted logistic regression models assessing the association between PM2.5 and tumor size had a similar inference (RR 1.41; 95% CI 1.05, 1.89) overall for all ages and also for women who were ≤ 50 years old at diagnosis (RR 1.63; 95% CI 1.036, 2.57). CONCLUSIONS: Our findings suggest a significant association between long-term PM2.5 exposure and BC aggressiveness based on tumor size and phenotype, as well as a worse outcome.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Neoplasias da Mama , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Feminino , Humanos , México , Pessoa de Meia-Idade , Material Particulado/efeitos adversos , Material Particulado/análiseRESUMO
BACKGROUND: In the last decade, efforts have been made in Latin America and the Caribbean to advance in the methodological development of evidence based clinical practice guidelines, among other strategies to improve the health provision of services and indicators. OBJECTIVES: To build an evidence map to show the regional GRADE impact in developing clinical practice guidelines and contrast the results with current needs. METHODS: A systematic literature search was conducted in databases, developer's websites, health ministries, repositories and grey literature. Documents were included when they were evidence based clinical practice guidelines developed in Latin American and Caribbean countries in the last decade. Data from the Global Burden of Disease was used to highlight relevant health conditions. RESULTS: Nine thousand seven hundred seventy-six documents were retrieved. 98 guidelines, with specific mention of the use of GRADE methodology were identified. 81% of the guidelines were developed within the last 4 years. 68% are from Colombia, 13% from Peru, 9% from Chile, 3% from Argentina and Costa Rica and Brazil, Honduras and Dominican Republic account 1%. 67% were developed for non-communicable diseases, 10% for communicable diseases, 9% for neonatal pathologies and 5% for maternal problems, 1% injuries and 7% other topics (nutrition, oral health). DISCUSSION: Our findings show a slow and increasing incorporation of the GRADE methodology in the region. GRADE guidelines have been adopted mainly by Colombia and slowly by other countries. Topics for guidelines continue to be comparable to the high-income countries and they don't address communicable diseases or other relevant health issues in the region, such as violence or malnutrition; thus, the evidence based guidelines for clinical practice are only a tool within a complex multimodal strategy to tackle the challenges of the health determinants. CONCLUSIONS: A prioritizing strategy for relevant regional health topics and the use of robust methodological approaches must be in the political agenda in the region. GRADE methods could help to improve the quality and validity of recommendations not only for chronic pathologies but also for ancient and challenging maladies prevalent in the region, as part of a multimodalintersectoral strategy.
Assuntos
Pesquisa Biomédica/normas , Medicina Baseada em Evidências , Guias de Prática Clínica como Assunto , Região do Caribe , Humanos , América LatinaRESUMO
OBJECTIVE: To evaluate the prognostic factors (clinicalpathological characteristics and treatments) in patients with breast cancer and metastasis to central nervous system (CNS) as the first site of the disease. MATERIAL AND METHODS: Kaplan-Meier method and life tables were used to estimate overall survival time over a retrospective cohort of 125 breast cancer patients treated at the Instituto Nacional de Cancerología (INCan) during 2007-2015, who presented metastasis to the CNS as the first site of extension of the disease. The cox proportional hazards model was used to determine the prognosis factors. RESULTS: The median overall survival time was 14.2 months (IC95%: 11.83-26.93). Patients with triple negative (TN), according to inmunohistochemistry analysis classification, had lower survival times (p=0.0004) and had a risk of dying two times (p=0.037) higher than patients with a different immunophenotype (HR: 2.77. 95%CI: 1.10-6.99). The degree of intermediate SBR increases the risk of dying in patients with metastasis (HR 2.76, 95% CI: 1.17-6.51). CONCLUSIONS: CNS metastasis continues to be a poor prognostic factor that reduces survival and affects quality of life. It is recommended to monitor the early presence of clinical neurological manifestations during follow-up for prompt treatment. TN patients have worse prognosis and HER2+ a better control.
OBJETIVO: Evaluar los factores pronósticos (características clínico-patológicas y tratamientos) en las pacientes con cáncer de mama y metástasis al sistema nervioso central (SNC) como primer sitio de afección. MATERIAL Y MÉTODOS: Cohorte retrospectiva, formada por 125 pacientes con cáncer de mama atendidas en el Instituto Nacional de Cancerología durante 2007-2015, quienes presentaron afección en el SNC como primer sitio de metástasis. A través del método Kaplan-Meier y tablas de vida se estimó la supervivencia global. El modelo de riesgos proporcionales de Cox fue utilizado para determinar los factores pronósticos. RESULTADOS: La mediana de supervivencia global fue de 14.2 meses (IC95% 11.8-26.9). Pacientes clasificadas por inmunohistoquímica como triple negativo (TN) presentaron tiempos de supervivencia más cortos (p<0.004) y con dos veces más riesgo de fallecer, en comparación con los otros inmunofenotipos (HR= 2.77; IC95% 1.10-6.99); asimismo, se identificó que un grado intermedio en la escala Scarff-Bloom-Richardson incrementa el riesgo de morir en pacientes con metástasis (HR=2.76; IC95% 1.17-6.51). CONCLUSIONES: La metástasis al SNC continúa siendo un factor de mal pronóstico que reduce la supervivencia y afecta la calidad de vida. Se recomienda vigilar puntualmente la presencia de manifestaciones clínicas neurológicas durante el seguimiento, para una rápida intervención. Las pacientes TN tienen peor pronóstico, y las HER2+ (es decir, con resultado positivo para el receptor 2 del factor de crecimiento humano epidérmico), mejor control a mediano plazo.
Assuntos
Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
Resumen: Objetivo: Evaluar los factores pronósticos (características clínico-patológicas y tratamientos) en las pacientes con cáncer de mama y metástasis al sistema nervioso central (SNC) como primer sitio de afección. Material y métodos: Cohorte retrospectiva, formada por 125 pacientes con cáncer de mama atendidas en el Instituto Nacional de Cancerología durante 2007-2015, quienes presentaron afección en el SNC como primer sitio de metástasis. A través del método Kaplan-Meier y tablas de vida se estimó la supervivencia global. El modelo de riesgos proporcionales de Cox fue utilizado para determinar los factores pronósticos. Resultados: La mediana de supervivencia global fue de 14.2 meses (IC95% 11.8-26.9). Pacientes clasificadas por inmunohistoquímica como triple negativo (TN) presentaron tiempos de supervivencia más cortos (p<0.004) y con dos veces más riesgo de fallecer, en comparación con los otros inmunofenotipos (HR= 2.77; IC95% 1.10-6.99); asimismo, se identificó que un grado intermedio en la escala Scarff-Bloom-Richardson incrementa el riesgo de morir en pacientes con metástasis (HR=2.76; IC95% 1.17-6.51). Conclusiones: La metástasis al SNC continúa siendo un factor de mal pronóstico que reduce la supervivencia y afecta la calidad de vida. Se recomienda vigilar puntualmente la presencia de manifestaciones clínicas neurológicas durante el seguimiento, para una rápida intervención. Las pacientes TN tienen peor pronóstico, y las HER2+ (es decir, con resultado positivo para el receptor 2 del factor de crecimiento humano epidérmico), mejor control a mediano plazo.
Abstract: Objective: To evaluate the prognostic factors (clinical-pathological characteristics and treatments) in patients with breast cancer and metastasis to central nervous system (CNS) as the first site of the disease. Materials and methods: Kaplan-Meier method and life tables were used to estimate overall survival time over a retrospective cohort of 125 breast cancer patients treated at the Instituto Nacional de Cancerología (INCan) during 2007-2015, who presented metastasis to the CNS as the first site of extension of the disease. The cox proportional hazards model was used to determine the prognosis factors. Result: The median overall survival time was 14.2 months (IC95%: 11.83-26.93). Patients with triple negative (TN), according to inmunohistochemistry analysis classification, had lower survival times (p=0.0004) and had a risk of dying two times (p=0.037) higher than patients with a different immunophenotype (HR: 2.77. 95%CI: 1.10-6.99). The degree of intermediate SBR increases the risk of dying in patients with metastasis (HR 2.76, 95% CI: 1.17-6.51). Conclusion: CNS metastasis continues to be a poor prognostic factor that reduces survival and affects quality of life. It is recommended to monitor the early presence of clinical neurological manifestations during follow-up for prompt treatment. TN patients have worse prognosis and HER2+ a better control.
Assuntos
Humanos , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Prognóstico , Taxa de Sobrevida , Estudos Retrospectivos , Estudos de CoortesRESUMO
INTRODUCTION: Young age represents an adverse prognostic factor in breast cancer (BC), and young women present with more advanced and aggressive disease. In Latin America, BC is increasing in young women, and there is a lack of information regarding the characteristics and outcomes of this patient population. PATIENTS AND METHODS: We retrospectively analyzed a database of 4315 women treated for BC at a single institution. We compared clinical characteristics, treatment, and survival between women ≤ 40 and > 40 years of age. Survival analyses were performed for each molecular subtype. RESULTS: A total of 662 women (15.3%) were ≤ 40 years old. Younger women had more advanced disease, higher grade, and a larger proportion of luminal B and triple-negative tumors (P < .001). At 5 years, both disease-free and overall survival (OS) were lower in younger women, although there were no differences after adjusting for stage. Five-year OS was worse for young women with hormone receptor-positive, human epidermal growth factor receptor 2-negative subtype (82% vs. 87.1%; P = .03), but not for those with human epidermal growth factor receptor 2-positive or triple-negative disease. This difference can be attributed to luminal B tumors, which showed a worse 5-year OS in younger women (79.1% vs. 85.2%; P = .03). CONCLUSION: Although young Mexican patients with BC have more aggressive disease at presentation than older women, only those with luminal B tumors have a worse survival after adjusting for stage. Strategies aimed at downstaging the disease and at improving the treatment of luminal B tumors in this population are needed.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Neoplasias da Mama/classificação , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , México , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Breast cancer in young women has been shown to have an aggressive behavior and worse prognosis. Studies evaluating young women enrolled in clinical trials of neoadjuvant chemotherapy have shown that age is a determinant factor in the achievement of a pathological complete response (pCR). In this study, we sought to analyze the outcomes of young patients treated with neoadjuvant chemotherapy at a single institution. 1639 patients treated with neoadjuvant chemotherapy were included. 316 patients ≤40 years were compared with 1323 patients aged >40 years regarding the achievement of a pCR (defined as no invasive residual tumor in the breast or lymph nodes). Disease-free survival (DFS) and overall survival were compared between groups according to pCR status and subtype, defined by hormone receptor (HR) and HER2 status. Young women were more likely to have a pCR than their older counterparts (37.4 vs. 26.3 %, P < 0.001). This difference was significant both for HR+/HER2- and triple-negative (TN) tumors. Young age and achieving less than pCR were associated with a greater chance of recurrence for the entire population. Age was not an independent factor for recurrence in TN and HER2+ disease. However, being younger than 40 increased recurrence risk in HR+/HER2- tumors. The achievement of a pCR was not associated with improved DFS in young women with HR+/HER2- tumors. Although young women have a high rate of pCR, they also have a worse prognosis. In a real-world clinical setting, the achievement of a pCR was an independently significant protective factor for recurrence across all subtypes and ages, except for HR+, HER2- disease in young women.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Tratamento Farmacológico/métodos , Terapia Neoadjuvante/métodos , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Cephalic pancreaticoduodenectomy (CPD) is the surgical procedure of choice for curative resection of pancreatic head and periampullary tumors. Preoperative nutritional intervention is crucial for reducing postoperative complications since malnutrition can be found in patients with these tumors. This malnutrition can get even worse during the postoperative period due to fasting and subsequent treatments. Besides, the surgical procedure entails surgical resections that alter the digestive process and can have long-term negative effects on the nutritional status. An aspect infrequently assessed is the alteration of exocrine and endocrine functions after surgery, that noticeably affects both the metabolic and general status of these patients. As regards long-term nutrition, there is no consensus on how to evaluate patients who have undergone a pancreatic resection. Consequently, early nutritional intervention since diagnosis may prevent or lessen the deterioration of nutritional status resulting from the disease itself as well as from the surgery and from the long term. The alimentary and nutritional education that would help the patient gain an adequate control of his metabolism and nutrition becomes vital.
Assuntos
Desnutrição/etiologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Humanos , Desnutrição/terapia , Estado Nutricional , Apoio Nutricional/métodos , Neoplasias Pancreáticas/complicações , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-OperatóriasRESUMO
Cephalic pancreaticoduodenectomy (CPD) is the surgical procedure of choice for curative resection of pancreatic head and periampullary tumors. Preoperative nutritional intervention is crucial for reducing postoperative complications since malnutrition can be found in patients with these tumors. This malnutrition can get even worse during the postoperative period due to fasting and subsequent treatments. Besides, the surgical procedure entails surgical resections that alter the digestive process and can have long-term negative effects on the nutritional status. An aspect infrequently assessed is the alteration of exocrine and endocrine functions after surgery, that noticeably affects both the metabolic and general status of these patients. As regards long-term nutrition, there is no consensus on how to evaluate patients who have undergone a pancreatic resection. Consequently, early nutritional intervention since diagnosis may prevent or lessen the deterioration of nutritional status resulting from the disease itself as well as from the surgery and from the long term. The alimentary and nutritional education that would help the patient gain an adequate control of his metabolism and nutrition becomes vital.
Assuntos
Desnutrição/etiologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Humanos , Desnutrição/terapia , Estado Nutricional , Apoio Nutricional/métodos , Neoplasias Pancreáticas/complicações , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-OperatóriasRESUMO
Cephalic pancreaticoduodenectomy (CPD) is the surgical procedure of choice for curative resection of pancreatic head and periampullary tumors. Preoperative nutritional intervention is crucial for reducing postoperative complications since malnutrition can be found in patients with these tumors. This malnutrition can get even worse during the postoperative period due to fasting and subsequent treatments. Besides, the surgical procedure entails surgical resections that alter the digestive process and can have long-term negative effects on the nutritional status. An aspect infrequently assessed is the alteration of exocrine and endocrine functions after surgery, that noticeably affects both the metabolic and general status of these patients. As regards long-term nutrition, there is no consensus on how to evaluate patients who have undergone a pancreatic resection. Consequently, early nutritional intervention since diagnosis may prevent or lessen the deterioration of nutritional status resulting from the disease itself as well as from the surgery and from the long term. The alimentary and nutritional education that would help the patient gain an adequate control of his metabolism and nutrition becomes vital.
Assuntos
Desnutrição/etiologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Apoio Nutricional/métodos , Complicações Pós-Operatórias , Desnutrição/terapia , Estado Nutricional , Humanos , Neoplasias Pancreáticas/complicações , Pancreaticoduodenectomia/efeitos adversosRESUMO
Expression and activity of matrix metalloproteinase-9 (MMP-9) as well as its relationship with hyaluronan (HA) and NF-kappaB activity were analyzed in two murine lymphoma cell lines with dissimilar migration and invasive behavior. MMP activity was evaluated by zymograms in supernatants, membrane extracts of tumor cells, and in the organs invaded by these cells. The more aggressive LBLa cell line showed MMP-9 activity in vitro, which increased after HA treatment and was blocked by anti-CD44 mAb. Such activity was not found in the less aggressive LBLc. MMP-9 and MMP-2 activity was found in organs invaded by both cell lines, although differential MMP-9 activity was observed in lung infiltrated only by LBLa cell line. NF-kappaB activation was evaluated to determine whether differential activity of MMP-9 was dependent on downstream signaling pathway, showing higher NF-kappaB activity in the more aggressive LBLa cell line. Our results showed that MMP-9 activity modulated by HA through NF-kappaB signaling pathway may be involved in the aggressive behavior of LBLa.
Assuntos
Ácido Hialurônico/farmacologia , Linfoma/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , NF-kappa B/metabolismo , Animais , Western Blotting , Linhagem Celular , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Núcleo Celular/metabolismo , DNA Complementar/metabolismo , Receptores de Hialuronatos/biossíntese , Receptores de Hialuronatos/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Reação em Cadeia da Polimerase , Proteínas Recombinantes/química , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de SinaisRESUMO
En las últimas décadas la medicina evolucionó hacia un enfoque molecular en la búsqueda de blancos específicos que permitan seguir adecuadamente la progresión de las patologías neoplásicas y desarrollar terapias exitosas. El conocimiento y comprensión de que la matriz extracelular (MEC) que rodea a un tumor influye sobre el comportamiento del mismo, reveló la importancia que cumplen las metaloproteinasas (MMPs) en la regulación de los componentes de la MEC, y por lo tanto en el desarrollo tumoral. Es por ello que actualmente se está evaluando la eficacia de inhibidores sintéticos de estas enzimas en ensayos clínicos, algunos ya en fase clínica III de investigación. También se propone que estas MMPs podrían ser utilizadas como marcadores bioquímicos, permitiendo evaluar la progresión de la enfermedad en pacientes que sufren patologías neoplásicas, e incluso dar un valor pronóstico. Es en este punto en que el laboratorio de análisis clínicos cumplirá un papel fundamental y deberá contar con los conocimientos y las herramientas necesarias para evaluar la presencia y actividad de estas enzimas. En este trabajo se expone el conocimiento actual de la estructura y funciones biológicas de las MMPs así como los antecedentes que muestran el papel que cumplen en las enfermedades neoplásicas, en especial en leucemias y linfomas
Assuntos
Humanos , Fatores de Crescimento Endotelial , Leucemia , Linfoma , Biomarcadores Tumorais , Neoplasias , Neoplasias Experimentais , Neovascularização Patológica/etiologia , Regulação Neoplásica da Expressão Gênica , Invasividade Neoplásica/fisiopatologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Leucemia , Leucemia Mieloide Aguda , Linfoma , Transtornos Linfoproliferativos , Metástase Neoplásica , Neoplasias , Neoplasias Experimentais , Neovascularização Patológica/fisiopatologia , Progressão da DoençaRESUMO
En las últimas décadas la medicina evolucionó hacia un enfoque molecular en la búsqueda de blancos específicos que permitan seguir adecuadamente la progresión de las patologías neoplásicas y desarrollar terapias exitosas. El conocimiento y comprensión de que la matriz extracelular (MEC) que rodea a un tumor influye sobre el comportamiento del mismo, reveló la importancia que cumplen las metaloproteinasas (MMPs) en la regulación de los componentes de la MEC, y por lo tanto en el desarrollo tumoral. Es por ello que actualmente se está evaluando la eficacia de inhibidores sintéticos de estas enzimas en ensayos clínicos, algunos ya en fase clínica III de investigación. También se propone que estas MMPs podrían ser utilizadas como marcadores bioquímicos, permitiendo evaluar la progresión de la enfermedad en pacientes que sufren patologías neoplásicas, e incluso dar un valor pronóstico. Es en este punto en que el laboratorio de análisis clínicos cumplirá un papel fundamental y deberá contar con los conocimientos y las herramientas necesarias para evaluar la presencia y actividad de estas enzimas. En este trabajo se expone el conocimiento actual de la estructura y funciones biológicas de las MMPs así como los antecedentes que muestran el papel que cumplen en las enfermedades neoplásicas, en especial en leucemias y linfomas (AU)
Assuntos
Humanos , Biomarcadores Tumorais , Neoplasias/fisiopatologia , Neoplasias Experimentais/fisiopatologia , Leucemia/fisiopatologia , Linfoma/fisiopatologia , Neovascularização Patológica/etiologia , Fatores de Crescimento Endotelial/sangue , Neoplasias/enzimologia , Neoplasias/irrigação sanguínea , Neoplasias Experimentais/enzimologia , Leucemia/enzimologia , Linfoma/enzimologia , Progressão da Doença , Neovascularização Patológica/fisiopatologia , Regulação Neoplásica da Expressão Gênica , Invasividade Neoplásica/fisiopatologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Leucemia Mieloide Aguda/enzimologia , Leucemia Mieloide Aguda/fisiopatologia , Transtornos Linfoproliferativos , Metástase Neoplásica/fisiopatologiaRESUMO
The combination of platinum and paclitaxel is the standard treatment of advanced ovarian carcinoma; however, recent studies have questioned the actual role of the combination as compared to either of the two agents alone. We report an open-label, two-center, phase II study of upfront paclitaxel for patients with histological diagnosis of stage III ovarian carcinoma. Treatment consisted of paclitaxel at 175 mg/m2 administered in a 3-h infusion every 21 days. Response was evaluated after the third course by either laparoscopy or exploratory laparotomy. Patients with stable or progressive disease discontinued treatment, whereas responding patients continued treatment until a maximum of six courses. Response, toxicity, time to progression (TTP) and survival were evaluated. From November 1993 to December 1995, 30 patients were accrued. All patients underwent primary cytoreduction; 17 (57%) and 13 (43%) patients had residual tumors <2 and >2 cm, respectively. Of 27 patients evaluable, objective responses were seen in 18 (66.4%) (95% CI 49.5-83.2)--12 complete (45%) and six partial (22%). Four patients had stable disease (15%) and five (18%) patients progressed. A total of 149 courses were administered to 30 patients, median 4 (range 1-6). Grade 3/4 neutropenia was seen in 13% of courses, peripheral neuropathy, myalgia and arthralgia were frequent, but transitory and relieved with analgesics. At a median follow-up time of 44.5 months (0-99) the TTP and median survival were 16.6 and 43.1 months, respectively. We conclude that single-agent paclitaxel is an effective and well-tolerated first-line treatment for advanced ovarian carcinoma.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/uso terapêutico , Adulto , Idoso , Antineoplásicos Fitogênicos/efeitos adversos , Progressão da Doença , Feminino , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Ovário/patologia , Paclitaxel/efeitos adversos , Análise de SobrevidaRESUMO
Cell migration is a key event in the invertebrate immuno-defense system. Microbial products like lipopolysacharide (LPS) and formyl-methyl-leucyl-phenylalanine (fMLP) promote cell recruitment to sites of infection. In mammals, complement activation by factors such as zymosan induces C5a production, which influences leukocyte migration. The endogenous factor hyaluronic acid (HA), an extracellular matrix component, also promotes cell migration through its receptor CD44. We evaluated whether coelomocytes from the sipunculan worm T. petricola migrated towards LPS, fMLP, or zymosan treated plasma (ZTP) and if HA was involved in coelomocyte migration and adhesion. We also evaluated if antibodies specific for mouse HA receptor CD44 inhibited any of the effects induced by HA. Using microchemotaxis chambers we found that coelomocytes migrated towards exogenously and endogenously derived chemoattractants. We also observed that HA was a potent chemotactic signal and that coelomocytes adhered strongly to plates coated with LMW-HA but not with HMW-HA. In addition we found that these HA mediated effects were blocked by the monoclonal antibody IM7 directed to mouse CD44, suggesting that a CD44-like cross-reactive antigen might play a role in HA mediated coelomocyte locomotion.
Assuntos
Fatores Quimiotáticos/farmacologia , Fatores Quimiotáticos/fisiologia , Nematoides/citologia , Nematoides/efeitos dos fármacos , Animais , Movimento Celular , Interações Medicamentosas , Receptores de Hialuronatos/fisiologia , Ácido Hialurônico/fisiologia , Nematoides/fisiologiaRESUMO
Interaction between hyaluronic acid (HA) and CD44 has been considered a key event in tumor invasion and metastasis. HA is a linear, high molecular weight glycosaminoglycan in its native state, but fragmented low molecular forms are found at sites ofneoplastic or inflammatory infiltrates. Both high and low molecular weights HA are involved in diverse biological functions. In this study, we used two clonal variants of a T cell murine lymphoma designated LBLa and LBLc. These cell lines were found to differ in their in vivo and in vitro growth rates. LBLa grew faster and exhibited an enhanced invasive capacity as compared to LBLc. In contrast, cell lines did not differ in the expression of surface markers (CD8, CD24, CD25, CD44, and CD18), or in their capacity to bind HA. However, LBLa cells exhibited higher capacity to migrate to low molecular weight HA than did LBLc. Migration was mediated by CD44 since it was abrogated by anti-CD44 monoclonal antibody as well as by hyaluronidase. We suggest that interaction between CD44 and low molecular weight HA may trigger migration mechanisms in LBLa cells, thus contributing to enhanced invasive cell capacity.
Assuntos
Adesão Celular/fisiologia , Movimento Celular/fisiologia , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/metabolismo , Linfoma de Células T/metabolismo , Animais , Feminino , Citometria de Fluxo , Humanos , Linfoma de Células T/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Contraste de Fase , Peso Molecular , Invasividade Neoplásica , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
Gut ischemia-reperfusion (G-IR) induces a systemic inflammatory response, in which leukocyte contribution to this injury in distant organs is important. ICAM-1 as well as CD11/CD18 have been involved in leukocyte infiltration in liver and lungs. CD44 adhesion molecule plays an essential role in other inflammatory processes such as rheumatoid arthritis and allergic contact dermatitis, however its implication in G-IR has not been described. In order to establish a possible role of CD44 in the development of systemic inflammation by G-IR, we have studied CD44 mRNA expression by RT-PCR in a murine model of gut ischemia reperfusion. Animals subjected to G-IR showed an increased number of CD44 variable isoforms expressed in liver and spleen compared to non-treated animals or animals subjected to laparotomy. This finding indicates that G-IR specifically induces the expression of different CD44 variable isoforms. Liver CD44 upregulation in animals subjected to G-IR suggests a contribution of this molecule to lymphocyte activation and migration to this injured organ. Moreover, increased isoform expression in spleen may be induced by the proinflammatory environment resulting from a systemic depuration activity.(Au)
Assuntos
Animais , Camundongos , RESEARCH SUPPORT, NON-U.S. GOVT , Receptores de Hialuronatos/metabolismo , Enteropatias/imunologia , Traumatismo por Reperfusão/imunologia , Adjuvantes Imunológicos/metabolismo , Receptores de Hialuronatos/genética , Modelos Animais de Doenças , Enteropatias/metabolismo , Isquemia/imunologia , Isquemia/metabolismo , Fígado/imunologia , Fígado/metabolismo , Camundongos Endogâmicos BALB C , Isoformas de Proteínas/imunologia , Isoformas de Proteínas/metabolismo , Traumatismo por Reperfusão/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
We have established and characterized a cell line (LBL) from a spontaneous murine T lymphoma LB. Histopathological analysis has demonstrated LB primary tumor infiltration in spleen, lymph nodes, liver, thymus, bone marrow and lung. However LBL cells infiltrated all these organs except lung. Two sublines with different growth behavior were derived from LBL cell line. One of them grew in suspension as clusters (LBLc) while the other one grew as adherent monolayers (LBLa). Growth rate, response to mitogenic stimuli and apoptosis induction were different among the parental cell line and the derived sublines. CD44 was expressed constitutively in LBL and LBLa cells. In contrast LBLc cells only expressed similar levels of this molecule when stimulated with PMA. LBLa cells showed hyaluronic acid (HA) binding properties, while LBL and LBLc cells were not able to bind HA even when activated with PMA. We postulate that differences in HA binding could be related with different infiltration behaviors.(Au)
Assuntos
Animais , Camundongos , Adjuvantes Imunológicos/metabolismo , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/metabolismo , Leucemia de Células T/patologia , Células Tumorais Cultivadas/patologia , Divisão Celular , Intervalos de Confiança , Citometria de Fluxo , Leucemia de Células T/metabolismo , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Ligação Proteica , Células Tumorais Cultivadas/metabolismoRESUMO
We have established and characterized a cell line (LBL) from a spontaneous murine T lymphoma LB. Histopathological analysis has demonstrated LB primary tumor infiltration in spleen, lymph nodes, liver, thymus, bone marrow and lung. However LBL cells infiltrated all these organs except lung. Two sublines with different growth behavior were derived from LBL cell line. One of them grew in suspension as clusters (LBLc) while the other one grew as adherent monolayers (LBLa). Growth rate, response to mitogenic stimuli and apoptosis induction were different among the parental cell line and the derived sublines. CD44 was expressed constitutively in LBL and LBLa cells. In contrast LBLc cells only expressed similar levels of this molecule when stimulated with PMA. LBLa cells showed hyaluronic acid (HA) binding properties, while LBL and LBLc cells were not able to bind HA even when activated with PMA. We postulate that differences in HA binding could be related with different infiltration behaviors.