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This paper deals with the fabrication, modeling and experimental characterization of a monitorable and renewable graphene-based pollution filter. The main goal is to demonstrate a method to monitor the status of such a filter in real time during its operating phases: pollutant adsorption, saturation, and regeneration. The filter is realized by a disk of pressed graphene nanoplatelets. This is a low-cost type of graphene which has recently drawn great interest due to its potential use in large scale industrial production. Here the nanomaterial is obtained through the exfoliation method assisted by microwave irradiation, by exploiting the thermal expansion of commercial intercalated graphite, according to a low-cost and ecologically friendly procedure. The filter is used here to adsorb acetonitrile, a toxic water-soluble organic compound that is present in some industrial solvents and paints. The monitoring method is based on the interpretation of the time variation of the electrical impedance measured during filter operation. There are two main results of the paper: Firstly, the graphene filter is shown to be effective in adsorbing the above pollutant, with the additional feature of being fully renewable: all the pollutant can be removed from the filter without the need of costly physical or chemical processes. Secondly, monitoring of the time-evolution of the electrical impedance allows efficient detection of the different phases of the filter life cycle: clean, polluted, saturated and regenerated. This feature is of potential interest since it enables the predictive maintenance of such filters.
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Despite laparoscopy in children is considered safe and is routinely used for several procedures, even in neonates and in pediatric oncology, its role in the treatment of pediatric renal tumors is still controversial. This study analyzes the results of laparoscopic nephrectomy for Wilms Tumor (WT) in pediatric age compared with open nephrectomy after 10 years of experience in a single centre. From 1993 in our center of reference for pediatric oncology, 30 patients with WT have been treated. We performed 21 open nephrectomy and in the last 10 years 9 laparoscopic nephrectomy. In all patients treated laparoscopically, the same technique made by the same equip was used. Compared with patients treated by open surgery, we did not find a significant difference in terms of outcome and survival. In the open surgery group, two patients had lung relapse while in the other group there was one local relapse. These three children obtained and maintained a second complete remission with chemotherapy. Open surgery complications were a tumor rupture in two cases, and an episode of pancreatitis 10 days after surgery. In the laparoscopic group, there were two conversions to open surgery not considered as complications but a surgical choice for cystic areas present in the tumor. As far as complications and oncologic outcomes are concerned, both techniques showed similar results. In experienced hands, laparoscopy proves to be an attractive alternative to open surgery for pediatric renal tumors.
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Neoplasias Renales/cirugía , Laparoscopía , Nefrectomía , Tumor de Wilms/cirugía , Niño , Humanos , Recurrencia Local de Neoplasia , Resultado del TratamientoRESUMEN
Schwannoma is a rare tumor that develops from the Schwann cells in the nerve sheath. A 42 years old woman was found incidentally to have a bulky mass in epigastric region. Abdominal ultrasonography CT and MRI have been of aid to know the position and size of the tumor. A massive capsulated retroperitoneal lesion was identified. It moved forward the hepatoduodenal ligament, inferior vena cava laterally and aorta medially. The mass is exte-riorized and detached from adhesions. There were no complications after the operation and the patient was discharged on the fourth post-operative day. The microscopically examina-tion showed features suggestive of Cellular Schwannoma. After 8 months during follow-up, the patient did not report any neurological deficit and control CT did not suggest the presence of recurrent disease.
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Neurilemoma/diagnóstico por imagen , Neoplasias Retroperitoneales/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto , Femenino , Humanos , Neurilemoma/cirugía , Neoplasias Retroperitoneales/cirugíaRESUMEN
Thyroid hemiagenesis is a rare congenital abnormality in which one of the thyroid lobes is not developed. It can be associated with various thyroid diseases, such as Grave's disease, nodular goiter and thyroid neoplasm, rarely with hyperparathyroidism. We report a case of a 50-year old woman with left thyroid lobe agenesis diagnosed by ultrasonography and scintigraphy. Right thyroidectomy was performed and the histopathological examination showed diffuse hyperplasia, multinodular goiter and Hashimoto's thyroiditis. To our knowledge, this is the first description of multinodular goiter and Hashimoto's thyroiditis in a patient with thyroid hemiagenesis.
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Bocio Nodular/complicaciones , Enfermedad de Hashimoto/complicaciones , Glándula Tiroides/anomalías , Femenino , Bocio Nodular/cirugía , Enfermedad de Hashimoto/cirugía , Humanos , Hallazgos Incidentales , Persona de Mediana Edad , Glándula Tiroides/cirugíaRESUMEN
We propose a bottom-up procedure to fabricate an easy-to-engineer graphene-based device, consisting of a microstrip-like circuit where few-layer graphene nanoplatelets are used to contact two copper electrodes. The graphene nanoplatelets are obtained by the microwave irradiation of intercalated graphite, i.e., an environmentally friendly, fast and low-cost procedure. The contact is created by a bottom-up process, driven by the application of a DC electrical field in the gap between the electrodes, yielding the formation of a graphene carpet. The electrical resistance of the device has been measured as a function of the gap length and device temperature. The possible use of this device as a gas sensor is demonstrated by measuring the sensitivity of its electrical resistance to the presence of gas. The measured results demonstrate a good degree of reproducibility in the fabrication process, and the competitive performance of devices, thus making the proposed technique potentially attractive for industrial applications.
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A set of epoxy resin composites filled with 0.25-2.0 wt.% of commercially available ENSACO carbon black (CB) of high and low surface area (CBH and CBL respectively) has been produced. The results of broadband dielectric spectroscopy of manufactured CB/epoxy below the percolation threshold in broad temperature (200 K to 450 K) and frequency (20 Hz to 1 MHz) ranges are reported. The dielectric properties of composites below the percolation threshold are mostly determined by alpha relaxation in pure polymer matrix. The glass transition temperature for CB/epoxy decreases in comparison with neat epoxy resin due to the extra free volume at the polymer-filler interface. At room temperature, the dielectric permittivity is higher for epoxy loaded with CBH additives. In contrast, at high temperature, the electrical conductivity was found to be higher for composites with CBL embedded. The established influence of the CB surface area on the broadband dielectric characteristics can be exploited for the production of effective low-cost antistatic paints and coatings working at different temperatures.
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BACKGROUND: In neuroblastoma (NB), the presence of segmental chromosome alterations (SCAs) is associated with a higher risk of relapse. METHODS: In order to analyse the role of SCAs in infants with localised unresectable/disseminated NB without MYCN amplification, we have performed an array CGH analysis of tumours from infants enrolled in the prospective European INES trials. RESULTS: Tumour samples from 218 out of 300 enroled patients could be analysed. Segmental chromosome alterations were observed in 11%, 20% and 59% of infants enroled in trials INES99.1 (localised unresectable NB), INES99.2 (stage 4s) and INES99.3 (stage 4) (P<0.0001). Progression-free survival was poorer in patients whose tumours harboured SCA, in the whole population and in trials INES99.1 and INES99.2, in the absence of clinical symptoms (log-rank test, P=0.0001, P=0.04 and P=0.0003, respectively). In multivariate analysis, a SCA genomic profile was the strongest predictor of poorer progression-free survival. CONCLUSION: In infants with stage 4s MYCN-non-amplified NB, a SCA genomic profile identifies patients who will require upfront treatment even in the absence of other clinical indication for therapy, whereas in infants with localised unresectable NB, a genomic profile characterised by the absence of SCA identifies patients in whom treatment reduction might be possible. These findings will be implemented in a future international trial.
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Aberraciones Cromosómicas , Neuroblastoma/patología , Proteínas Nucleares/genética , Proteínas Oncogénicas/genética , Humanos , Lactante , Proteína Proto-Oncogénica N-Myc , Neuroblastoma/genética , Pronóstico , Estudios Prospectivos , Recurrencia , Análisis de SupervivenciaRESUMEN
The early diagnosis and treatment of individuals harboring M. tuberculosis is key to ensuring the effectiveness of health programs aimed at the elimination of tuberculosis (TB). Monitoring for TB also has other important health care implications for the related immune pathology caused by the chronic inflammatory response to M. tuberculosis. Moreover, the recent introduction of biologic therapies for the treatment of several immune-mediated inflammatory diseases has shown unexpected high frequencies of reactivation of latent TB. The present cross-sectional study is aimed at estimating the prevalence of latent tuberculosis infection (LTBI) in different groups of subjects, either undergoing a routine program of screening for TB or a clinical monitoring of autoimmune or lung disorders, by analyzing their immune response in vitro to a pool of different M. tuberculosis antigens through an IFN-gamma-release assay (IGRA). We consecutively tested 1,644 subjects including health care workers (931), healthy immigrants from different countries (93), patients with a diagnosis of psoriasis (405), patients with lung inflammatory disease (60) or lung neoplasia (32) and a group of HIV-1 infected Italian subjects (120). The prevalence of IGRAs positive responses among health care workers was 8.9 percent. In comparison, significantly higher frequencies were found in healthy immigrant subjects (33.3%), similar to those found in inflammatory broncho-pneumopathies (34.5%) or lung cancer (29.6%). Interestingly, an unexpected high prevalence was also found in patients affected by psoriasis (18.0%), while HIV-infected subjects had values comparable to those of health care workers (10.8%). An age cut-off was determined and applied for each group by receiver operating characteristic (ROC) curves in order to perform the statistical analysis among age-comparable groups. Multivariate analysis showed that the age and clinical conditions such as having a diagnosis of psoriasis or a lung inflammatory disease were independent risk factors for developing an IGRA positive response. This study highlights an unprecedented high prevalence of IGRA positive responses among patients affected by psoriasis and emphasizes the need for a preliminary assessment of LTBI before the administration of any biologic therapy based on cytokine antagonists such as anti-TNF-alpha. Moreover, screening for LTBI should be routinely performed in the presence of a chronic pulmonary disease.
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Adenocarcinoma/inmunología , Enfermedades Autoinmunes/inmunología , Infecciones por VIH/inmunología , Interferón gamma , Tuberculosis Latente/inmunología , Neoplasias Pulmonares/inmunología , Psoriasis/inmunología , Adenocarcinoma/complicaciones , Adenocarcinoma/epidemiología , Adenocarcinoma/microbiología , Adenocarcinoma del Pulmón , Adulto , Anticuerpos/efectos adversos , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/microbiología , Estudios Transversales , Diagnóstico Precoz , Emigrantes e Inmigrantes , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Infecciones por VIH/microbiología , VIH-1/fisiología , Personal de Salud , Humanos , Interferón gamma/biosíntesis , Interferón gamma/metabolismo , Italia , Tuberculosis Latente/complicaciones , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Tuberculosis Latente/microbiología , Pulmón , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/microbiología , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/crecimiento & desarrollo , Prevalencia , Psoriasis/complicaciones , Psoriasis/epidemiología , Psoriasis/microbiología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/inmunología , Adulto JovenRESUMEN
With the maturation of antibody production technologies, both economic optimization and ecological aspects have become important. Continuous downstream processing is a way to reduce the environmental footprint and improve process economics. We compared different primary recovery, capture, and fermentation methods for two output-based antibody production scales: 50 kg/year and 1000 kg/year. In addition, a fixed fermentation volume case of 1000 L was analysed in terms of total cost of goods and process mass intensity as a measure of the environmental footprint. In our scenario, a significant amount of water can be saved in downstream processing when single use equipment is utilized. The overall economic and ecological impact is governed by the product titre in our perfusion (1 g/L) and fed-batch (4 g/L). A low titre in fermentation with similar downstream purification leads to higher process mass intensity and cost of goods due to the higher media demand upstream. The economic perspective for continuous integrated biomanufacturing is very attractive, but environmental consequences should not be neglected. Here, we have shown that perfusion has a higher environmental footprint in the form of water consumption compared to fed-batch. As general guidance to improve process economics, we recommend reducing water consumption.
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Anticuerpos Monoclonales/metabolismo , Ingeniería de Proteínas/instrumentación , Anticuerpos Monoclonales/economía , Anticuerpos Monoclonales/aislamiento & purificación , Técnicas de Cultivo Celular por Lotes , Biotecnología/economía , Biotecnología/instrumentación , Monitoreo del Ambiente , Fermentación , Modelos Económicos , Ingeniería de Proteínas/economía , Proteínas Recombinantes/economía , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismoRESUMEN
INTRODUCTION: Transverse colon cancer (TCC) is poorly studied, and TCC cases are often excluded from large prospective randomized trials because of their complexity and their potentially high complication rate. The best surgical approach for TCC has yet to be established. The aim of this large retrospective multicenter Italian series is to investigate the advantages and disadvantages of both hemicolectomy and transverse colectomy in order to identify the best surgical approach. MATERIALS AND METHODS: This was a retrospective cohort study of patients with mid-transverse colon cancer treated with a segmental colon resection or an extended hemicolectomy (right or left) between 2006 and 2016 in 28 high-volume (more than 70 procedures/year) Italian referral centers for colorectal surgery. RESULTS: The study included 1529 patients, 388 of whom underwent a segmental resection while 1141 underwent an extended resection. A higher number of complications has been reported in the segmental group than in the extended group (30.1% versus 23.6%; p 0.010). In 42 cases the main complication was the anastomotic leak (4.4% versus 2.2%; p 0.020). Recovery outcomes also showed statistical differences: time to first flatus (p 0.014), time to first mobilization (p 0.040), and overall hospital stay (p < 0.001) were significantly shorter in the extended group. Even if overall survival were similar between the groups (95.1% versus 97%; p 0.384), 3-year disease-free survival worsened after segmental resection (78.1% versus 86.2%; p 0.001). CONCLUSIONS: According to our results, an extended right colon resection for TCC seems to be surgically safer and more oncologically valid.
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Fuga Anastomótica/epidemiología , Colectomía/métodos , Colon Transverso/cirugía , Neoplasias del Colon/cirugía , Tiempo de Internación/estadística & datos numéricos , Infección de la Herida Quirúrgica/epidemiología , Anciano , Anciano de 80 o más Años , Colon Transverso/patología , Neoplasias del Colon/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Tasa de Supervivencia , Factores de TiempoRESUMEN
INTRODUCTION: Intraductal papillary mucinous neoplasms (IPMN) are a rare group of pancreatic neoplasms. Often are asymptomatic and, when are symptomatic, patients complain sensation of weight in the abdomen or compression at the neighboring structures. In many cases the diagnosis is incidental, during a CT or MR performed for other raisons. CASE REPORT: We report a case of a 59-year-old woman with diagnosis of post-pancreatitis pseudocyst who, instead, was affected by an intraductal papillary mucinous neoplasm (IPMN), treated by us with pancreatoduodenectomy. DISCUSSION: The diagnosis of IPMN has increased in recent years thanks to an improvement in radiological investigation. The study of pancreatic lesions must be very careful and it is absolutely necessary that diagnostic imaging be accompanied by a correct clinical evaluation of the patient. CONCLUSION: A thorough anamnesis is required in patient with history of acute pancreatitis to avoid the mistake of exchanging an IPMN for a pseudocyst.
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Adenocarcinoma Mucinoso/diagnóstico por imagen , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Papilar/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Seudoquiste Pancreático/diagnóstico por imagen , Adenocarcinoma Mucinoso/cirugía , Carcinoma Ductal Pancreático/cirugía , Carcinoma Papilar/cirugía , Errores Diagnósticos , Femenino , Humanos , Hallazgos Incidentales , Imagen por Resonancia Magnética , Persona de Mediana Edad , Neoplasias Pancreáticas/cirugía , Seudoquiste Pancreático/etiología , Pancreaticoduodenectomía , Pancreatitis/complicaciones , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
In Alzheimer's disease brains, more than 90% of pyramidal neurons in lamina V and 70% in lamina III displayed 2- to 5-fold elevated levels of cathepsin D (Cat D) mRNA by in situ hybridization compared with neurologically normal controls. Most of these cells appeared histologically normal. The less vulnerable nonpyramidal neuron population in lamina IV had relatively normal message levels. Neuronal populations expressing more Cat D mRNA also displayed quantitatively increased Cat D immunoreactive protein. Cat D mRNA expression was only moderately increased in astrocytes. Degenerating neurons exhibited intense immunoreactivity but lowered Cat D mRNA levels. The upregulation of Cat D synthesis and accumulation of hydrolase-laden lysosomes indicate an early activation of the endosomal-lysosomal system in vulnerable neuronal populations, possibly reflecting early regenerative or repair processes. These abnormalities also represent a basis for altered regulation of amyloid precursor protein processing.
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Enfermedad de Alzheimer/enzimología , Catepsina D/metabolismo , Endosomas/enzimología , Regulación Enzimológica de la Expresión Génica , Expresión Génica , Lisosomas/enzimología , Neuronas/enzimología , Corteza Prefrontal/enzimología , Anciano , Northern Blotting , Catepsina D/biosíntesis , Humanos , Hidrolasas/metabolismo , Hibridación in Situ , Persona de Mediana Edad , Degeneración Nerviosa , Neuronas/patología , Corteza Prefrontal/patología , Procesamiento Proteico-Postraduccional , ARN Mensajero/análisis , ARN Mensajero/biosíntesis , Valores de ReferenciaRESUMEN
Survivors of retinoblastoma (Rb) are at high risk of dying from second malignant tumour. The occurrence of second malignant neoplasm (SMN) and related mortality in a cohort of 1111 cases from the Italian Retinoblastoma Registry was analysed, considering the possible role of both genetic and iatrogenic causes. Rb patients had a greater than 10-fold excess in overall mortality compared with the general population (standardized mortality ratio (SMR) 10.73, 95% CI 9.00-12.80). Their excess risk attributable to cancers other than Rb was 14.93 95% CI 10.38-21.49). Survivors of hereditary Rb had an SMR for all causes of 16.25 (95% CI 13.20-20.00), whereas their SMR for all cancers was 25.72 (95% CI 17.38-38.07). Survivors of unilateral sporadic Rb had an SMR of 4.12 from all cancers (95% CI 1.55-10.98) and a much higher excess for overall mortality (SMR 13.34, 95% CI 10.74-16.56). As expected, survivors of hereditary Rb had higher mortality from cancers of the bone (SMR 391.90, 95% CI 203.90-753.20) and soft tissue (SMR 453.00, 95% CI 203.50-1008.40), small intestine (SMR 1375.50, 95% CI 344.00-5499.70), nasal cavity (SMR 13.71, 95% CI 1.93-97.35) and cancers of the brain and central nervous system (SMR 41.14, 95% CI 13.2-127.55).
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Neoplasias Primarias Secundarias/mortalidad , Neoplasias de la Retina/patología , Retinoblastoma/patología , Estudios de Cohortes , Lateralidad Funcional , Mutación de Línea Germinal , Humanos , Italia , Sistema de Registros , Neoplasias de la Retina/genética , Retinoblastoma/genética , Análisis de Supervivencia , SobrevivientesRESUMEN
INTRODUCTION: SIOPEN INES protocol yielded excellent 5-year survival rates for MYCN-non-amplified metastatic neuroblastoma. Patients deemed ineligible due to lack or delay of MYCN status or late registration were treated, but not included in the study. Our goal was to analyse survival at 10 years among the whole population. MATERIALS AND METHODS: Italian and Spanish metastatic INES patients' data are reported. SPSS 20.0 was used for statistical analysis. RESULTS: Among 98 infants, 27 had events and 19 died, while 79 were disease free. Five- and 10-year event-free survival (EFS) were 73 and 70 %, and overall survival (OS) was 81 and 74 %, respectively. MYCN status was significant for EFS, but not for OS in multivariate analysis. CONCLUSIONS: The survival rates of patients who complied with all the inclusion criteria for INES trials are higher compared to those that included also not registered patients. Five-year EFS and OS for INES 99.2 were 87.8 and 95.7 %, while our stage 4s population obtained 78 and 87 %. Concerning 99.3, 5-year EFS and OS were 86.7 and 95.6 %, while for stage 4 we registered 61 and 68 %. MYCN amplification had a strong impact on prognosis and therefore we consider it unacceptable that many patients were not studied for MYCN and probably inadequately treated. Ten-year survival rates were shown to decrease: EFS from 73 to 70 % and OS from 81 to 74 %, indicating a risk of late events, particularly in stage 4s. Population-based registries like European ENCCA WP 11-task 11 will possibly clarify these data.
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Biomarcadores de Tumor/genética , Ensayos Clínicos como Asunto , Amplificación de Genes , Proteína Proto-Oncogénica N-Myc/genética , Neuroblastoma/mortalidad , Niño , Preescolar , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Estadificación de Neoplasias , Neuroblastoma/genética , Neuroblastoma/secundario , Neuroblastoma/terapia , Pronóstico , Tasa de SupervivenciaRESUMEN
The repertoire of the lysosomal system extends beyond its function in degrading biologic macromolecules for energy and recycling purposes. Controlled shifts in lysosomal activity help neurons to regulate their cytoplasmic volume and to remodel local cellular domains. Newly identified regulatory controls over targeting to lysosomes and the limited proteolytic actions of 'lysosomal' hydrolases, together with other recent findings, are suggesting potential roles for the endosomal-lysosomal system in modifying functions of specific proteins, acquiring nutrients essential for growth and repair, influencing the output of secretory products, and helping neurons to modulate trophic signals. The prominent involvement of the endosomal-lysosomal system in Alzheimer's disease and other major pathologies has redoubled interest in how this system serves neurons.
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Endosomas/fisiología , Lisosomas/fisiología , Neuronas/fisiología , Animales , Citoplasma/fisiología , Espacio Extracelular/fisiología , Humanos , Hidrolasas/fisiología , Lisosomas/enzimología , Enfermedades del Sistema Nervioso/fisiopatologíaRESUMEN
Experimental and clinical data have proved that anticholinesterase drugs are responsible for vigorous peristaltic contractions and for an increase of the intraluminal pressure, because they determine muscarinic effects on the smooth muscle of the intestine both in small and large intestine. Therefore, a greater incidence of intestinal anastomotic disruption has been supposed when anticholinesterases are used both in the early postoperative period, to reverse curarization, and in myasthenic patients. The authors report a case of a patient with myasthenia gravis who received maximal doses of pyridostigmine and underwent left hemicolectomy and small intestine resection and afterwards total colectomy in order to treat a sigmoid perforated diverticulitis. In the postoperative course an anastomotic leak developed after both surgical operations. The authors believe that pyridostigmine could have had an important role in the pathogenesis of the leak and assert that, when an intestinal resection has to be performed in a myasthenic patient, it could be useful to reduce in the preoperative period the administration of anticholinesterase drugs and always perform a protective ileostomy.
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Anastomosis Quirúrgica/efectos adversos , Colectomía , Diverticulitis/cirugía , Divertículo del Colon/cirugía , Enfermedades del Íleon/cirugía , Fístula Intestinal/cirugía , Perforación Intestinal/cirugía , Miastenia Gravis/complicaciones , Enfermedades del Sigmoide/cirugía , Dehiscencia de la Herida Operatoria/etiología , Anciano , Inhibidores de la Colinesterasa/administración & dosificación , Inhibidores de la Colinesterasa/uso terapéutico , Humanos , Ileostomía , Masculino , Miastenia Gravis/tratamiento farmacológico , Cuidados Preoperatorios , Bromuro de Piridostigmina/administración & dosificación , Bromuro de Piridostigmina/uso terapéuticoRESUMEN
It is established that the interaction between microenvironment and cancer cells has a critical role in tumor development, given the dependence of neoplastic cells on stromal support. However, how this communication promotes the activation of normal (NFs) into cancer-associated fibroblasts (CAFs) is still not well understood. Most microRNA (miRNA) studies focused on tumor cell, but there is increasing evidence of their involvement in reprogramming NFs into CAFs. Here we show that miR-9, upregulated in various breast cancer cell lines and identified as pro-metastatic miRNA, affects the properties of human breast fibroblasts, enhancing the switch to CAF phenotype, thus contributing to tumor growth. Expressed at higher levels in primary triple-negative breast CAFs versus NFs isolated from patients, miR-9 improves indeed migration and invasion capabilities when transfected in immortalized NFs; viceversa, these properties are strongly impaired in CAFs upon miR-9 inhibition. We also demonstrate that tumor-secreted miR-9 can be transferred via exosomes to recipient NFs and this uptake results in enhanced cell motility. Moreover, we observed that this miRNA is also secreted by fibroblasts and in turn able to alter tumor cell behavior, by modulating its direct target E-cadherin, and NFs themselves. Consistently with the biological effects observed, gene expression profiles of NFs upon transient transfection with miR-9 show the modulation of genes mainly involved in cell motility and extracellular matrix remodeling pathways. Finally, we were able to confirm the capability of NFs transiently transfected with miR-9 to promote in vivo tumor growth. Taken together, these data provide new insights into the role of miR-9 as an important player in the cross-talk between cancer cells and stroma.
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Mama/metabolismo , Mama/patología , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Exosomas/metabolismo , MicroARNs/metabolismo , Animales , Cadherinas/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones SCID , Fenotipo , Transcriptoma , Transfección , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Microambiente TumoralRESUMEN
Two genes encoding conglutin gamma have been isolated from a Lupinus albus genomic library and sequenced. The expression of conglutin gamma was studied by partial amino acid sequencing of the mature seed protein and by nucleotide sequencing of reverse transcriptase-polymerase chain reaction products from various tissues during the plant life cycle.
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Genes de Plantas , Proteínas de Plantas/genética , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , Regulación de la Expresión Génica de las Plantas , Biblioteca Genómica , Germinación , Datos de Secuencia Molecular , Proteínas de Plantas/química , Raíces de Plantas/metabolismo , Semillas/metabolismo , Alineación de SecuenciaRESUMEN
PURPOSE: As part of a study on the pharmacokinetics associated with the administration of asparaginase (ASNase) from Erwinia to the CNS, we determined the levels of asparagine in the CSF of children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Twenty children received eight standard doses of intramuscular ASNase (10,000 IU/m2) every 3 days as part of induction therapy. In the postremission phase of therapy, the children were randomized to receive either 20 courses of high-dose intramuscular ASNase (25,000 IU/m2) weekly (n = 8) or four courses of standard-dose intramuscular ASNase (10,000 IU/m2) every 3 days (n = 12). RESULTS: All patients had detectable levels of L-asparagine in the CSF at the time of diagnosis. The levels of L-asparagine in CSF were undetectable in 15 of 20 (75%) and in seven of 19 (36.8%) children 3 and 5 days, respectively, after administration of standard-dose ASNase. After administration of high-dose ASNase, the levels of L-asparagine in the CSF were undetectable in five (62.5%) and two (25%) of eight children after 3 and 5 days, respectively. CONCLUSION: In this study 60% to 70% and 25% to 35% of children had complete depletion of L-asparagine from the CSF after 3 and 5 days, respectively, after administration of both schedules of ASNase from Erwinia. In the remaining patients, administration of ASNase may have resulted in a suboptimal antileukemic effect at the CNS level.
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Asparaginasa/administración & dosificación , Asparagina/líquido cefalorraquídeo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Administración Oral , Adolescente , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Niño , Preescolar , Erwinia , Humanos , Lactante , Recién Nacido , Inyecciones Intramusculares , Inducción de Remisión , Factores de TiempoRESUMEN
PURPOSE: To define factors that influence outcome in children with localized but unresectable neuroblastoma by retrospective investigation of response to therapy and outcome in 21 Italian institutions. PATIENTS AND METHODS: Of 145 assessable children diagnosed between 1979 and 1990, 77 were treated between 1979 and 1984 with three consecutive standard-dose (SD) protocols, and 68 between 1985 and 1990 with a high-dose (HD) protocol. All protocols included chemotherapy, followed by resection of primary tumor if feasible. If at least partial resection was achieved, consolidation therapy followed, except that from 1985 onward, patients considered disease-free following surgery received no further treatment. RESULTS: Ninety-four of 145 patients (65%) achieved a complete response (CR) or partial response (PR) with chemotherapy and 75 (52%) subsequently underwent complete resection of the primary tumor. Eighty-one patients are alive (73 without disease, eight with disease), 63 have died, and one is lost to follow-up. The 5-year overall survival (OS) rate is 55% and progression-free survival (PFS) rate 50%. Both OS and PFS correlated with response to chemotherapy, removal of primary tumor, HD therapy, and serum lactate dehydrogenase (LDH) levels. Infants (< 1 year), independent of primary tumor site, and children aged 1 to 15 years with a nonabdominal primary tumor, did better compared with children aged 1 to 15 years with an abdominal primary tumor (PFS, 72% and 64% v 30%; P < .001 and < .01, respectively). Outcome of this last group improved with the HD protocol (PFS, 40% v 23%; P = .01). CONCLUSION: In children with unresectable neuroblastoma, risk categories can be defined by age and primary tumor site. HD chemotherapy should be investigated for the poor-risk category age 1 to 15 years with an abdominal primary tumor.