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In 2013, a screening survey including fish (European perch, Perca fluviatilis) from 20 locations in the Stockholm region of Sweden indicated exceptionally high levels of PCBs (>450 ng ΣPCB7/g ww) in Lake Oxundasjön. An extensive sampling program was launched to define the magnitude and area of impact of PCBs. Moreover, a dynamic mass balance model approach was applied to identify and quantify key transport processes and predict the long-term turnover of PCBs given various remediation scenarios. Based on the dating of sediment profiles, primary emissions of PCBs to Lake Oxundasjön have likely occurred from the end of the 1940s until 1980, reaching the lake via one of its tributaries. Presently, the main source of PCBs is diffusion from the lake sediments. From the lake outlet, >400 g ΣPCB7/yr are transported to Lake Mälaren (the third largest lake in Sweden), supplying drinking water for parts of the Stockholm area. Remediation actions are necessary to reduce the PCB levels in fish below today's marketing limits and environmental quality standards. With natural recovery, our results indicate that the PCB levels in non-migratory fish from Lake Oxundasjön will be elevated for decades to come. The mass of PCBs stored in the lake sediments was estimated, and to our knowledge, Lake Oxundasjön is the most heavily PCB contaminated lake in Sweden. The system constitutes a unique opportunity to test and develop a mathematical mass balance model for PCBs, with substantial data acquired from different aquatic matrices. The model presented in the paper is applicable for risk assessments of PCBs, and the results contribute to the general understanding of the transport and turnover dynamics of PCBs in aquatic ecosystems.
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Agua Potable , Bifenilos Policlorados , Contaminantes Químicos del Agua , Animales , Bifenilos Policlorados/análisis , Lagos , Sedimentos Geológicos , Ecosistema , Suecia , Contaminantes Químicos del Agua/análisis , Peces , Monitoreo del AmbienteRESUMEN
BACKGROUND: This study aimed to describe the clinical and cost-effectiveness evidence supporting reimbursement decisions of new cancer drugs and analyze the influence of trial characteristics and the cost per quality-adjusted life years (QALYs) on the likelihood of reimbursement in Sweden. PATIENTS AND METHODS: Data were extracted from all appraisal dossiers for new cancer drugs seeking reimbursement in Sweden and claiming added therapeutical value between the years 2010 and 2020. The data were analyzed using descriptive statistics, and logistic regression models were also used with the cost per QALY, study design, comparator, and evidence on final outcomes in the clinical trials as predictors of reimbursement. RESULTS: All 60 included appraisals were based on trial evidence that assessed at least one final outcome (overall survival [OS] or quality of life [QoL]), although rarely as a primary outcome. Of the appraisals with a final decision (n = 58), 79% were approved for reimbursement. Among the reimbursed drugs, only half had trial evidence demonstrating improved OS or QoL. Only one drug had trial evidence supporting improvements in both OS and QoL. The average cost per QALY for reimbursed cancer drugs was estimated to be 748 560 SEK (73 583). A higher cost per QALY was found to decrease the likelihood of reimbursement by 9.4% for every 100 000 SEK (9830) higher cost per QALY (P = 0.03). For cost-effectiveness models without direct evidence of improvements in final outcomes, a larger QALY gain was observed compared with those with evidence mainly relying on intermediate and surrogate outcomes. CONCLUSIONS: There are substantial uncertainties in the clinical and cost-effectiveness evidence underlying reimbursement decisions of new cancer drugs. Decision makers should be cautious of the limited evidence on patient-centered outcomes and the implications of allocating resources to expensive treatments with uncertain value for money.
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Antineoplásicos , Neoplasias , Humanos , Antineoplásicos/uso terapéutico , Análisis Costo-Beneficio , Neoplasias/tratamiento farmacológico , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Ensayos Clínicos como AsuntoRESUMEN
We report a series of 22 experiments in which the implicit associations test (IAT) was used to investigate cross-modal correspondences between visual (luminance, hue [R-G, B-Y], saturation) and acoustic (loudness, pitch, formants [F1, F2], spectral centroid, trill) dimensions. Colors were sampled from the perceptually accurate CIE-Lab space, and the complex, vowel-like sounds were created with a formant synthesizer capable of separately manipulating individual acoustic properties. In line with previous reports, the loudness and pitch of acoustic stimuli were associated with both luminance and saturation of the presented colors. However, pitch was associated specifically with color lightness, whereas loudness mapped onto greater visual saliency. Manipulating the spectrum of sounds without modifying their pitch showed that an upward shift of spectral energy was associated with the same visual features (higher luminance and saturation) as higher pitch. In contrast, changing formant frequencies of synthetic vowels while minimizing the accompanying shifts in spectral centroid failed to reveal cross-modal correspondences with color. This may indicate that the commonly reported associations between vowels and colors are mediated by differences in the overall balance of low- and high-frequency energy in the spectrum rather than by vowel identity as such. Surprisingly, the hue of colors with the same luminance and saturation was not associated with any of the tested acoustic features, except for a weak preference to match higher pitch with blue (vs. yellow). We discuss these findings in the context of previous research and consider their implications for sound symbolism in world languages.
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Percepción Auditiva , Percepción de Color , Estimulación Acústica , Humanos , Estimulación LuminosaRESUMEN
In an attempt to bridge the pressure gap, APXPS was used to follow the surface development of an aluminum brazing sheet during heating in an ambient oxygen-pressure mimicking the environment of an industrial brazing furnace. The studied aluminum alloy brazing sheet is a composite material consisting of two aluminum alloy standards whose surface is covered with a native aluminum oxide film. To emphasize the necessity of studies of this system in ambient sample environments it is compared to measurements in UHV. Changes in thickness and composition of the surface oxide were followed after heating to 300 °C, 400 °C, and 500 °C. The two sets presented in this paper show that the surface development strongly depends on the environment the sample is heated in.
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AIM: Sigmoid volvulus is a condition with a tendency to recur if treated conservatively. Little is known about the best type of treatment or when to perform definitive surgery. The aim of this study was to review treatment, and assess the outcome, of sigmoid volvulus in adult patients treated at a Swedish university hospital. METHOD: The medical records of patients treated for sigmoid volvulus at Sahlgrenska University Hospital, Sweden from January 2000 to September 2016 were reviewed retrospectively. Median follow-up time was 8.3 years. RESULTS: One hundred and sixty-eight patients were included with a total of 453 admissions for sigmoid volvulus. Nonoperative decompression was attempted as the initial treatment in 438/453 (97%), with a success rate of 92% (403/438), which was not influenced by whether it was the first episode or a recurrence. Without planned surgery, recurrence occurred after 84% of successful nonoperative decompressions with a median of two recurrences (1-16). Recurrence was less common after the first episode compared with subsequent episodes. Median time until recurrence was 58 days. Mortality after planned surgery following successful decompression was 3.3% (2/61) compared with 13% (6/46) following emergency surgery. CONCLUSION: In our cohort, the recurrence rate of sigmoid volvulus following successful nonoperative decompression was high. Still, more than 20% of patients did not experience a recurrence after their first episode. Nonoperative decompression could thus be suggested as the sole treatment for the first episode of volvulus. However, after the second episode it is probable that early planned surgery would improve outcome and reduce health-care consumption.
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Tratamiento Conservador/métodos , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Vólvulo Intestinal/terapia , Enfermedades del Sigmoide/terapia , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Procedimientos Quirúrgicos Electivos , Urgencias Médicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mortalidad , Recurrencia , Estudios Retrospectivos , Suecia , Adulto JovenRESUMEN
In this study we report on the adsorbate structures on an Ir(1 1 1) surface during the phase transition from the inactive to the active state during CO oxidation. The CO oxidation over Pt(1 1 1) is used as a reference case. Where Pt(1 1 1) either is inactive and CO covered or active and O covered, Ir(1 1 1) exhibits a transition state with co-existing chemisorbed O and CO. The observed structural differences are explained in terms of DFT-calculated adsorption energies. For Pt(1 1 1) the repulsive CO-O interaction makes co-existing chemisorbed CO and O unfavourable, while for Ir(1 1 1) the stronger O and CO adsorption allows for overcoming the repulsive interaction. At the onset of CO oxidation over Ir(1 1 1), a CO structure containing defects forms, which enables O2 to dissociatively adsorb on the Ir(1 1 1) surface, thus enabling the CO oxidation reaction. At the mass transfer limit, the Ir(1 1 1) surface is covered by a chemisorbed O structure with defects; hence, the active surface is predominately chemisorbed O covered at a total pressure of 0.5 mbar and no oxide formation is observed.
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We have studied the reaction of phenylacetylene (PA) with chloro-, bromo-, and iodobenzene on the Au(1 1 1) surface as a model system for the gold-catalysed Sonogashira cross-coupling. Both ultrahigh vacuum-based and ambient pressure x-ray photoelectron spectroscopy show that iodo- and chlorobenzene (IB and CB) undergo the cross-coupling reaction towards diphenylacetylene. Bromobenzene (BB), in contrast, does not react in the UHV experiments. Further, at ambient pressure signs are found for poisoning of the Au(1 1 1) surface by a carbon species formed in the reaction. The understanding obtained in the reaction experiments are based on a thorough investigation of the adsorption of PA, IB, CB, and BB on the Au(1 1 1) surface by soft x-ray absorption spectroscopy and temperature-dependent x-ray photoelectron spectroscopy. In particular, the experiments provide the orientation of the intact adsorbates with respect to the surfaces at liquid nitrogen temperature. Dissociation in the temperature regime between -80 and -15 °C is observed for iodo- and chlorobenzene, but not for BB, in agreement with that only IB and CB, but not BB, react with PA to form diphenylacetylene. The difference is tentatively attributed to a difference in surface orientation of the different halobenzenes.
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This paper examines the market potential of disposed shredder waste, a resource that is increasingly emphasized as a future mine. A framework with gate requirements of various outlets was developed and contrasted with a pilot project focusing on excavated waste from a shredder landfill, sorted in an advanced recycling facility. Only the smallest fraction by percentage had an outlet, the metals (8%), which were sold according to a lower quality class. The other fractions (92%) were not accepted for incineration, as construction materials or even for re-deposition. Previous studies have shown similar lack of marketability. This means that even if one fraction can be recovered, the outlet of the other material is often unpredictable, resulting in a waste disposal problem, which easily prevents a landfill mining project altogether. This calls for marketability and usability of deposited waste to become a central issue for landfill mining research. The paper concludes by discussing how concerned actors can enhance the marketability, for example by pre-treating the disposed waste to acclimatize it to existing sorting methods. However, for concerned actors to become interested in approaching unconventional resources such as deposited waste, greater regulatory flexibility is needed in which, for example, re-deposition could be allowed as long as the environmental benefits of the projects outweigh the disadvantages.
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Minería/métodos , Eliminación de Residuos/métodos , Instalaciones de Eliminación de Residuos , Materiales de Construcción , Incineración , Mercadotecnía , Metales , Eliminación de Residuos/economía , SueciaRESUMEN
The binding of double-stranded (ds) DNA to mica can be controlled through ion-exchanging the mica with divalent cations. Measurements of the end-to-end distance of linear DNA molecules discriminate whether the binding mechanism occurs through 2D surface equilibration or kinetic trapping. A range of linear dsDNA fragments have been used to investigate length dependences of binding. Mica, ion-exchanged with Ni(II) usually gives rise to kinetically trapped DNA molecules, however, short linear fragments (<800 bp) are seen to deviate from the expected behaviour. This indicates that ion-exchanged mica is heterogeneous, and contains patches or domains, separating different ionic species. These results correlate with imaging of dsDNA under aqueous buffer on Ni(II)-mica and indicate that binding domains are of the order of 100 nm in diameter. Shorter DNA fragments behave intermediate to the two extreme cases of 2D equilibration and kinetic trapping. Increasing the incubation time of Ni(II) on mica, from minutes to hours, brings the conformations of the shorter DNA fragments closer to the theoretical value for kinetic trapping, indicating that long timescale kinetics play a role in ion-exchange. X-ray photoelectron spectroscopy (XPS) was used to confirm that the relative abundance of Ni(II) ions on the mica surface increases with time. These findings can be used to enhance spatial control of binding of DNA to inorganic surfaces with a view to patterning high densities arrays.
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Silicatos de Aluminio/química , Silicatos de Aluminio/metabolismo , ADN/química , ADN/metabolismo , Níquel/metabolismo , Sitios de Unión , Intercambio Iónico , Cinética , Modelos Químicos , Conformación de Ácido Nucleico , Espectroscopía de Fotoelectrones , Factores de TiempoRESUMEN
Polybrominated diphenyl ethers (PBDEs), used as additive flame-retardants, are increasing in the environment and are present in human mother's milk, newborns and toddlers. We reported earlier that several PBDEs, highly brominated PBDEs, caused developmental neurotoxic effects in mice, manifested as persistent aberrations in spontaneous behaviour, habituation capability, learning and memory, and changes in the cholinergic system. The present study was undertaken to explore the dose-response effects of PBDE 209 on spontaneous behaviour, habituation and its effects on the murine cholinergic system. Neonatal male NMRI mice were given 1.4, 2.3, 14 or 21micromol PBDE 209/kg body weight, when 3 days old. The agent was administered as a single oral dose via a metal gastric tube. Spontaneous behaviour and response to the cholinergic agonist nicotine were observed in adult mice at 2 and 4 months of age. Mice were also observed for anxiety-like behaviour in an elevated plus-maze. Adult mice, 2 and 4 months old, showed a dose-response related change in spontaneous behaviour, viz. were hyperactive and showed reduced or lack of habituation, effects that worsen with age. At the adult age of 4 months the susceptibility of the cholinergic system was also affected in a dose-response related manner, viz. reduced and/or hypoactive response to nicotine. This shows that PBDE 209 can be as potent as the lower brominated PBDEs in causing developmental neurotoxic defects.
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Acetilcolina/metabolismo , Conducta Exploratoria/efectos de los fármacos , Habituación Psicofisiológica/efectos de los fármacos , Éteres Difenilos Halogenados/toxicidad , Acetilcolina/farmacología , Factores de Edad , Análisis de Varianza , Animales , Animales Recién Nacidos , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Locomoción/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Nicotina/farmacología , Agonistas Nicotínicos/farmacología , EmbarazoRESUMEN
Perfluorinated compounds (PFCs) are found in applications such oil/water repellents for clothing fabrics, carpets, food packaging, lubricants, surfactants and fire extinguishers. PFCs are persistent in the environment. They have been found in humans and in wildlife. We reported earlier that persistent organic pollutants (POPs), such as DDT, PCBs and BFRs, caused developmental neurotoxic defects in mice, manifested as persistent aberrations in spontaneous behaviour, habituation capability, learning and memory, and changes in the cholinergic system in adults, when mice were exposed during a critical period of neonatal brain development. The present study was conducted to see whether PFCs can cause similar developmental neurotoxic effects as earlier observed for POPs as PCBs and PBDEs. NMRI male mice were exposed to a single-oral dose, either 1.4 or 21 micromol/kg body weight of PFOS (0.75 or 11.3 mg), PFOA (0.58 or 8.70 mg), or PFDA (0.72 or 10.8 mg), via a metal gastric-tube at the age of 10 days. The control animals received in the same manner 10 ml/kg body weight of the 20% fat emulsion vehicle. Spontaneous behaviour (locomotion, rearing, and total activity), and habituation were observed in 2- and 4-month-old mice. The susceptibility of the cholinergic system was explored in a nicotine-induced spontaneous behaviour test in 4-month-old mice. Deranged spontaneous behaviour was observed in mice exposed to PFOS and PFOA, manifested as reduced and/or lack of habituation and hyperactivity in adult mice. These effects were also seen to worse with age. Neonatal exposure to PFOS and PFOA affected the cholinergic system, manifested as a hypoactive response to nicotine, compared to a hyperactive response to nicotine in controls. These developmental neurotoxic effects are similar to those we reported earlier for PCBs and PBDEs. This suggests that PFOS and PFOA be included in the group of POPs known to be developmental neurotoxicants.
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Ácidos Alcanesulfónicos , Encefalopatías/inducido químicamente , Caprilatos , Fluorocarburos , Trastornos Mentales/inducido químicamente , Análisis de Varianza , Animales , Animales Recién Nacidos , Conducta Animal/efectos de los fármacos , Encefalopatías/fisiopatología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Conducta Exploratoria/efectos de los fármacos , Femenino , Locomoción/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos Mentales/fisiopatología , Ratones , Nicotina/farmacología , Agonistas Nicotínicos/farmacología , Embarazo , Factores de TiempoRESUMEN
This study investigates collaborative memory performance in very old married couples working in two types of participant constellations, and with two types of memory tasks, i.e. working as couples, or as individuals in episodic or semantic memory tasks. Sixty-two old married couples were a priori classified as high or low on two dimensions suggested to be important for successful collaboration, i.e. responsibility (how division of responsibility was organized) and agreement (how they mutually agreed on each other's view). The episodic memory task was immediate recall of short stories. The semantic memory tasks were to answer questions about names, places, and concepts. The results suggested that: (1) groups outperformed a single individual, but (2) groups in general suffered from collaboration relative to the predicted potential in episodic tasks only, thus replicating earlier results. Nevertheless, (3) the couples scoring high on division of responsibility achieved the same productivity as nominal pairs (i.e. the predicted potential); (4) the couples scoring high on the agreement dimension showed that they were not as affected by collaboration, but then performed less well in "absolute" performance. Finally, the results were discussed in terms of optimal compensation strategies, especially for elderly couples.
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Anciano/psicología , Conducta Cooperativa , Matrimonio/psicología , Recuerdo Mental , Esposos/psicología , Comprensión , Femenino , Humanos , Masculino , Persona de Mediana Edad , Solución de Problemas , Retención en Psicología , Semántica , Aprendizaje VerbalRESUMEN
Although pre-fabricated carbon fibre posts have been used during the past decade clinical evaluations of the technique are still few. Using dental records and radiographs the clinical performance of 65 pre-fabricated carbon fibre posts (Composipost and Endopost) placed in 48 patients who regularly visited a general practice were evaluated in the present study. After an average time of 2.3 +/- 0.8 years (median 2.1 years, range 1-4.9 years) of clinical service the failure rate was 3%. Failure occurred in one tooth with a single crown restoration and in one tooth that was part of a cantilever fixed partial denture. Although the failure rate is lower than those mostly reported for metallic posts and cores more clinical studies are necessary to assess the suitability of pre-fabricated carbon fibre posts for routine use as an alternative to individually cast posts.
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Carbono/uso terapéutico , Materiales Dentales/uso terapéutico , Técnica de Perno Muñón , Tratamiento del Conducto Radicular/métodos , Adulto , Anciano , Anciano de 80 o más Años , Diente Premolar/diagnóstico por imagen , Fibra de Carbono , Diente Canino/diagnóstico por imagen , Cavidad Pulpar/diagnóstico por imagen , Femenino , Humanos , Incisivo/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Diente Molar/diagnóstico por imagen , Radiografía , Estudios Retrospectivos , Insuficiencia del TratamientoRESUMEN
OBJECTIVES: The aim of the study was to evaluate the retention of prefabricated root canal posts made of a variety of materials that have recently been introduced into dentistry. MATERIALS AND METHODS: The posts studied were CosmoPost, Composipost carbon fibres, Composipost Aestheti-Plus, Composipost Light-Post and Para Post Fiber White. The posts were luted in extracted human premolars and the cores were built up with the resin composites recommended by the manufacturers. The retention of individually cast gold alloy posts luted with zinc-phosphate cement were used as reference. A universal testing machine was used to determine the retention of each cemented post Data were compared using ANOVA supplemented with Fisher's PLSD at a significance level of p < 0.05. RESULTS: Only the CosmoPost system exhibited retention values that were significantly lower than for the conventionally cast gold alloy posts luted with zinc-phosphate cement The force necessary to loosen the CosmoPost specimens was significantly less than that needed to loosen the Composipost. Estheti-Plus (p < 0.05) and the Composipost Ught-Post systems (p < 0.001]. The force necessary to loosen the ParaPost Fiber White specimens was significantly less than for the Composipost Light-Post system (p < 0.01). Other combinations did not differ significantly (p > 0.05). CONCLUSIONS: When zirconium oxide ceramic posts are luted with resin composites the bonding between the ceramic and resin composite seems to be weak. Further studies are thus necessary to achieve improved retention of all-ceramic root canal posts.
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Materiales Dentales/química , Diseño de Prótesis Dental , Retención de Prótesis Dentales , Técnica de Perno Muñón/instrumentación , Análisis de Varianza , Diente Premolar , Carbono/química , Fibra de Carbono , Cementación , Cerámica/química , Resinas Compuestas/química , Aleaciones de Oro/química , Humanos , Cuarzo/química , Cementos de Resina/química , Estrés Mecánico , Propiedades de Superficie , Cemento de Fosfato de Zinc/química , Circonio/químicaRESUMEN
Blood levels of ochratoxin A were determined in 406 Scandinavian blood donors (206 from Oslo, Norway, and 200 from Visby on the island of Gotland, Sweden), using an HPLC method. In connection with the blood collection, the subjects were asked to fill in a food questionnaire to obtain individual dietary information relevant to ochratoxin A exposure. The mean plasma level of ochratoxin A was 0.18 ng/ml in Oslo and slightly higher, 0.21 ng/ml (P=0.046) in Visby. There was no correlation between plasma levels of ochratoxin A and the estimated total dietary intake of ochratoxin A based on consumption data and levels in food (retrieved from the literature), neither was the plasma level of ochratoxin A correlated with the total amount of food consumed. However, consumption of several foods, including cereal products, wine, beer and pork, were to some minor degree related to high plasma levels of ochratoxin A. The strongest correlations (correlation coefficient r>0.4; P<0.001) were observed for women in relation to the consumption of beer or medium brown bread. Correlation analysis of combinations of two or more food categories did not result in any statistically significant correlation.
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Carcinógenos/análisis , Contaminación de Alimentos/análisis , Ocratoxinas/sangre , Adulto , Animales , Cerveza/análisis , Donantes de Sangre , Cromatografía Líquida de Alta Presión , Grano Comestible/química , Femenino , Análisis de los Alimentos , Humanos , Masculino , Carne/análisis , Noruega/epidemiología , Estadística como Asunto , Encuestas y Cuestionarios , Suecia/epidemiología , Porcinos , Vino/análisisRESUMEN
The aim of the present study was to characterise the ability of malignant chondrosarcomas to invade normal bone by analysing their production of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). For this purpose 12 chondrosarcomas were investigated for the expression of mRNAs for several MMPs and all 4 TIMPs by Northern hybridisation, and for immunohistochemical localisation of the proteins. A characteristic finding of these analyses was increased expression of MMP-13, MMP-14 and TIMP-2 mRNAs in chondrosarcomas when compared with nonmalignant control samples. Individual chondrosarcomas also exhibited elevated levels of MMP-1, MMP-7 and MMP-9 mRNAs. The results of Northern hybridisations were supported by immunohistochemical stainings of the corresponding tumour areas for MMP-2, MMP-14 and TIMP-2, further suggesting that these may have prognostic value for determining whether individual chondrosarcomas are locally aggressive or have a probability of recurrence. Another finding of the present study was a marked heterogeneity in histologic appearance and gene expression of the chondrosarcomas, emphasising the importance of analysing several areas of these tumours to get representative results. These findings suggest that analysis of MMPs could be a useful diagnostic indicator in patients with cartilaginous tumours and could help in differentiating between a low-grade malignant chondrosarcoma and a benign growing enchondroma.
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Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Condrosarcoma/genética , Condrosarcoma/metabolismo , Metaloproteinasas de la Matriz/genética , Metaloproteinasas de la Matriz/metabolismo , Inhibidores Tisulares de Metaloproteinasas/genética , Inhibidores Tisulares de Metaloproteinasas/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Northern Blotting , Neoplasias Óseas/enzimología , Estudios de Casos y Controles , Condrosarcoma/enzimología , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismoAsunto(s)
Citocromo P-450 CYP1A1/metabolismo , Modelos Biológicos , Bifenilos Policlorados/toxicidad , Animales , Citocromo P-450 CYP1A1/biosíntesis , Relación Dosis-Respuesta a Droga , Contaminantes Ambientales/toxicidad , Inducción Enzimática/efectos de los fármacos , Neoplasias Hepáticas Experimentales , Análisis Multivariante , Bifenilos Policlorados/química , Relación Estructura-Actividad Cuantitativa , Ratas , Estándares de Referencia , Células Tumorales CultivadasRESUMEN
Controlled degradation of extracellular matrix (ECM) is essential for the growth, invasion, and metastasis of malignant tumors, and for tumor-induced angiogenesis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases collectively capable of degrading essentially all ECM components and they apparently play an important role in all these aspects of tumor development. Furthermore, recent evidence suggests that MMPs also play a role in tumor cell survival. In this review, we discuss the current concept concerning the role of MMPs and their inhibitors in tumor invasion, as a basis for prognosis and targeted therapeutic intervention in cancer.
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Movimiento Celular , Metaloproteinasas de la Matriz/metabolismo , Invasividad Neoplásica/patología , Neoplasias/enzimología , Neoplasias/patología , Animales , Colagenasas/genética , Colagenasas/metabolismo , Matriz Extracelular/metabolismo , Gelatinasas/antagonistas & inhibidores , Gelatinasas/genética , Gelatinasas/metabolismo , Regulación Enzimológica de la Expresión Génica , Humanos , Metaloproteinasa 3 de la Matriz/genética , Metaloproteinasa 3 de la Matriz/metabolismo , Inhibidores de la Metaloproteinasa de la Matriz , Metaloproteinasas de la Matriz/genética , Invasividad Neoplásica/genética , Neoplasias/genética , Inhibidores Tisulares de Metaloproteinasas/metabolismoRESUMEN
Controlled degradation of extracellular matrix (ECM) is essential in many physiological situations including developmental tissue remodeling, angiogenesis, tissue repair, and normal turnover of ECM. In addition, degradation of matrix components is an important feature of tumor growth, invasion, metastasis, and tumor-induced angiogenesis. Matrix metallo-proteinases (MMPs) are a family of zinc-dependent neutral endopeptidases, which are collectively capable of degrading essentially all ECM components. MMPs apparently play an important role in all the above mentioned aspects of tumor development. In addition, there is recent evidence that MMP activity is required for tumor cell survival. At present, several MMP inhibitors are in clinical trials of malignant tumors of different histogenetic origin. In this review we discuss the current view on the role of MMPs and their inhibitors in development and invasion of squamous cell carcinomas, as a basis for prognostication and therapeutic intervention in these tumors.