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1.
Foods ; 11(5)2022 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-35267328

RESUMEN

(1) Background: Humic substances are well-known human nutritional supplement materials and they play an important performance-enhancing role as animal feed additives. For decades, ingredients of humic substances have been proven to carry potent antiviral effects against different viruses. (2) Methods: Here, the antiviral activity of a humic substance containing ascorbic acid, Se- and Zn2+ ions intended as a nutritional supplement material was investigated against SARS-CoV-2 virus B1.1.7 Variant of Concern ("Alpha Variant") in a VeroE6 cell line. (3) Results: This combination has a significant in vitro antiviral effect at a very low concentration range of its intended active ingredients. (4) Conclusions: Even picomolar concentration ranges of humic substances, Vitamin C and Zn/Se ions in the given composition, were enough to achieve 50% viral replication inhibition in the applied SARS-CoV-2 virus inhibition test.

3.
J Environ Radioact ; 229-230: 106530, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33482539

RESUMEN

The Acacia auriculiformis is a tree common in tropical Asian countries, capable of growing in many different soil types, so it could be used for biomonitoring for high natural radionuclide areas in tropical and subtropical climates. The transfer factor (TF) of radionuclides from soil to A. auriculiformis in eight uranium and rare earth element (REE) mining areas of North Vietnam was investigated. The activity concentrations 226Ra, 238U, 137Cs, 228Ra, and 40K in both soil and A. auriculiformis showed considerable variation. The TFs of these radionuclides also varied in a wide range. In most of the eight areas, the highest TF was observed for 137Cs and 228Ra. While the TFs for 226Ra and 238U were smallest. In addition, the TFs for radionuclides near REE mines were similar to those observed near uranium mines. The TFs for A. auriculiformis were within the ranges of TF reported for other plants, except for 137Cs.


Asunto(s)
Acacia , Monitoreo de Radiación , Contaminantes Radiactivos del Suelo , Uranio , Suelo , Contaminantes Radiactivos del Suelo/análisis , Árboles , Uranio/análisis , Vietnam
4.
Artículo en Inglés | MEDLINE | ID: mdl-33430080

RESUMEN

The determination of natural radionuclide concentrations plays an important role for assuring public health and in the estimation of the radiological hazards. This is especially true for high level radiation areas. In this study, 226Ra, 228Ra and 238U concentrations were measured in well waters surrounding eight of the high-level natural radiation areas in northern Vietnam. The 226Ra, 228Ra and 238U activity concentrations vary from <1.2 × 10-3-2.7 (0.46), <2.6 × 10-3-0.43 (0.07) and <38 × 10-3-5.32 Bq/L (0.50 of median), respectively. 226Ra and 238U isotopes in most areas are in equilibrium, except for the DT-Thai Nguyen area. The calculated radiological hazard indices are generally higher than WHO (World Health Organization) recommendations. Average annual effective dose and excess lifetime cancer risk values due to drinking well water range from to 130 to 540 µSv/year and 7.4 × 10-6 to 3.1 × 10-5, respectively.


Asunto(s)
Monitoreo de Radiación , Radio (Elemento) , Uranio , Contaminantes Radiactivos del Agua , Radiación de Fondo , Dosis de Radiación , Radio (Elemento)/análisis , Uranio/análisis , Vietnam , Contaminantes Radiactivos del Agua/análisis
5.
Orv Hetil ; 158(49): 1946-1952, 2017 Dec.
Artículo en Húngaro | MEDLINE | ID: mdl-29199436

RESUMEN

IgA nephropathy is an immune-mediated chronic glomerulonephritis with a great variability in clinical presentation and outcome. The disease can progress to end-stage renal failure in 25% of patients. For this reason we should identify patients with potential to progress. Most important risk factors for progression are persistent proteinuria, hypertension, decreased renal function and some histological lesions. The actually suggested treatment is summarized in KDIGO Clinical Practice Guideline from 2012. They suggest to give firstly non-specific supportive treatment (especially renin-angiotensin system blocking agents). Recommendation about steroid/immunosuppression treatment is based on low level of evidence. Recently three studies were organised concerning benefits and risk of steroid/immunosuppressive treatment added together with specific supportive treatment. In the STOP-IgAN study, systemic steroid/immunosuppressive treatment significantly decreased proteinuria but did not stop progression. In the TESTING study, systemic steroid treatment significantly decreased proteinuria and progression. However, the study was recently discontinued due to several severe side effects of steroid treatment. Involvement of intestinal mucosal immunity in the pathogenesis of IgA nephropathy suggested the NEFIGAN study with budesonide treatment. Budesonide releases corticosteroid in distal small intestine and colon. Proteinuria was significantly decreased and renal function remained stabile. High number of withdrawals owing to adverse effects is a major concern implying a substantial systemic effect of budesonide. We need further information on the characteristics of patients who most likely benefit from steroid/immunosuppressive treatment given after or together with specific supportive treatment. Orv Hetil. 2017; 158(49): 1946-1952.


Asunto(s)
Glomerulonefritis por IGA/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/prevención & control , Budesonida/efectos adversos , Budesonida/uso terapéutico , Vías Clínicas , Tasa de Filtración Glomerular , Glomerulonefritis por IGA/inmunología , Humanos , Terapia de Inmunosupresión , Fallo Renal Crónico/tratamiento farmacológico , Proteinuria/tratamiento farmacológico , Proteinuria/inmunología , Medición de Riesgo , Esteroides/efectos adversos , Esteroides/uso terapéutico , Resultado del Tratamiento
6.
J Environ Radioact ; 173: 34-43, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27771131

RESUMEN

The raw materials of the phosphate fertilizer industry are the various apatite minerals. Some of these have high levels of natural radionuclides, and thus phosphate fertilizers contain significant amounts of U-238, K-40 and Ra-226. These can leach out of the fertilizers used in large quantities for resupplying essential nutrients in the soil and can then enter the food chain through plants, thereby increasing the internal dose of the affected population. In the current study, the radiological risk of eight commercially available phosphate fertilizers (superphosphate, NPK, PK) and their leaching behaviours were investigated using different techniques (gamma and alpha spectrometry), and the dose contributions of using these fertilizers were estimated. To characterize the leaching behaviour, two leaching procedures were applied and compared -the MSZ 21470-50 (Hungarian standard) and the Tessier five-step sequential extraction method. Based on the evaluation of the gamma-spectra, it is found that the level of Th-232 in the samples was low (max.7 ± 6 Bq kg-1), the average Ra-226 activity concentration was 309 ± 39 Bq kg-1 (min. 10 ± 8 Bq kg-1, max. 570 ± 46 Bq kg-1), while the K-40 concentrations (average 3139 ± 188 Bq kg-1, min. 51 ± 36 Bq kg-1) could be as high as 7057 ± 427 Bq kg-1. The high K-40 can be explained by reference to the composition of the investigated fertilizers (NPK, PK). U concentrations were between 15 and 361 Bq kg-1, with the average of 254 Bq kg-1, measured using alpha spectrometry. The good correlation between P2O5 content and radioactivity reported previously is not found in our data. The leaching studies reveal that the mobility of the fertilizer's uranium content is greatly influenced by the parameters of the leaching methods. The availability of U to water ranged between 3 and 28 m/m%, while the Lakanen-Erviö solution mobilized between 10 and 100% of the U content.


Asunto(s)
Fertilizantes/análisis , Monitoreo de Radiación , Contaminantes Radiactivos del Suelo/análisis , Fosfatos , Radioisótopos/análisis , Suelo/química , Espectrometría gamma , Torio/análisis , Uranio/análisis
8.
Protein Pept Lett ; 22(8): 736-42, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26202368

RESUMEN

Former data of our workgroup indicated that the accumulation of oxidized amino acids (meta- and ortho-tyrosine) due to oxidative stress may play an important role in the impaired insulininduced vasoactive properties of different arterial segments. There are evidences, that incorporation of these amino acids into cellular proteins leads to certain hormonal resistances, which might be restored by supplementation with the physiologic isoform, para-tyrosine. Rats in the control group were kept on a regular diet, rats in the cholesterol-fed group received high-fat diet, while the third group of rats received high-fat diet with para-tyrosine supplementation for 16 weeks. Plasma cholesterol level was significantly higher in the cholesterol-fed group, while the level of cholesterol in the cholesterol+para-tyrosine group did not differ significantly from that of the controls. Plasma level of insulin after glucose stimulation was decreased in the cholesterol-fed group, while that in the para-tyrosine supplemented group did not differ significantly from the controls. Vascular para-, meta- and ortho-tyrosine content was measured with HPLC. Elevated vascular meta-tyrosine/para-tyrosine ratio of cholesterol fed rats could be avoided by para-tyrosine supplementation. Vascular response of the thoracic aorta to insulin and liraglutide was assessed by a DMT multi-myograph. Cholesterol feeding resulted in vascular insulin-and liraglutide resistance, which was restored by para-tyrosine supplementation. Incorporation of the oxidative stress induced pathological tyrosine isoforms leads to vascular-hormone-resistances. We show that the physiological amino acid para-tyrosine is capable of restoring hypercholesterolemia-induced increased meta-tyrosine content of the vascular wall, thus attenuating functional vascular damage.


Asunto(s)
Colesterol/metabolismo , Dieta Alta en Grasa , Insulina/farmacología , Liraglutida/farmacología , Tirosina/farmacología , Vasodilatación/efectos de los fármacos , Animales , Glucemia/efectos de los fármacos , Insulina/sangre , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Tirosina/administración & dosificación
9.
J Environ Radioact ; 148: 27-32, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26093854

RESUMEN

The reuse of industrial by-products is important for members of numerous industrial sectors. However, though the benefits of reuse are evident from an economical point of view, some compounds in these materials can have a negative effect on users' health. In this study, the radon emanation and exhalation features of red mud were surveyed using heat-treatment (100-1200 °C). As a result of the 1200°C-treated samples, massic radon exhalation capacity reduced from 75 ± 10 mBq kg(-1) h(-1) to 7 ± 4 mBq kg(-1) h(-1), approximately 10% of the initial exhalation rate. To find an explanation for internal structural changes, the porosity features of the heat-treated samples were also investigated. It was found that the cumulative pore volume reduced significantly in less than 100 nm, which can explain the reduced massic exhalation capacity in the high temperature treated range mentioned above. SEM snapshots were taken of the surfaces of the samples as visual evidence for superficial morphological changes. It was found that the surface of the high temperature treated samples had changed, proving the decrement of open pores on the surface.


Asunto(s)
Contaminantes Radiactivos del Aire/análisis , Materiales de Construcción/análisis , Monitoreo de Radiación , Radón/análisis , Calor
10.
Orv Hetil ; 155(8): 304-12, 2014 Feb 23.
Artículo en Húngaro | MEDLINE | ID: mdl-24534878

RESUMEN

The gastrointestinal tract is not only regarded as a system where nutrient absorption takes place, but also as a vital barrier against intraluminal pathogens entering the circulation and the maintenance of immune homeostasis. Bacterial translocation is defined as the penetration of viable bacteria or bacterial compounds from the gastrointestinal tract to extraintestinal sites. This disorder has been described in several clinical conditions. The main promoting factors for bacterial translocation have been proposed to be changes in the intestinal microflora, mucosal barrier failure and defects in host immunity. The presence of bacterial translocation has been associated with higher complications and mortality rates; therefore it should be taken into account in the therapeutic strategies of patients with predisposing factors.


Asunto(s)
Bacteriemia/inmunología , Traslocación Bacteriana , Tracto Gastrointestinal/microbiología , Mucosa Intestinal/microbiología , Síndrome de Respuesta Inflamatoria Sistémica/prevención & control , Arginina/administración & dosificación , Bacteriemia/microbiología , Bacteriemia/terapia , Traslocación Bacteriana/inmunología , Suplementos Dietéticos , Nutrición Enteral , Tracto Gastrointestinal/inmunología , Glutamina/administración & dosificación , Humanos , Mucosa Intestinal/inmunología , Prebióticos , Probióticos/administración & dosificación , Sepsis/inmunología , Síndrome de Respuesta Inflamatoria Sistémica/inmunología , Síndrome de Respuesta Inflamatoria Sistémica/microbiología
11.
Radiat Prot Dosimetry ; 146(1-3): 27-30, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21486832

RESUMEN

Theoretically, the human body absorbs radon through the lungs and the skin and excretes it through the lungs and the excretory organs during radon bath therapy. To check this theory, the radon concentrations in urine samples were compared before and after radon bath therapy. During the therapy, the geometric mean (GM) and the geometric standard deviation of the radon concentration in air and in the bath water were 979 Bq m(-3), 1.58 and 73.6 Bq dm(-3), 1.1, respectively. Since radon was detected in each urine sample (GM around 3.0 Bq dm(-3)), urinary excretion of radon was confirmed. The results of this study can neither reject nor confirm the hypothesis of radon absorption through the skin. A 15 times higher increment of inhaled radon level did not cause significant changes in radon of urine samples.


Asunto(s)
Balneología , Pulmón/efectos de la radiación , Radón/uso terapéutico , Radón/orina , Piel/efectos de la radiación , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo de Radiación , Adulto Joven
12.
Radiat Environ Biophys ; 48(3): 311-5, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19308439

RESUMEN

Radon bath is a well-established modality of balneotherapy for the management of degenerative musculoskeletal disorders. The present study was conducted to ascertain whether baths of relatively low (80 Bq/l) radon concentration have any influence on the functioning of the endocrine system. In the study, a non-randomized pilot study, 27 patients with degenerative musculoskeletal disorders received 30-min radon baths (of 31-32 degrees C temperature and 80 Bq/l average radon concentration) daily, for 15 days. Twenty-five patients with matching pathologies were subjected to balneotherapy according to the same protocol, using thermal water with negligible radon content (6 Bq/l). Serum thyroid stimulating hormone, prolactin, cortisol, adrenocorticotropic hormone, and dehydroepiandrosterone levels were measured before and after a balneotherapy course of 15 sessions. Comparison of the accumulated data using the Wilcoxon test did not reveal any significant difference between pre- and post-treatment values or between the two patient groups. It is noted that while the beneficial effects of balneotherapy with radon-containing water on degenerative disorders is widely known, only few data have been published in the literature on its effect on endocrine functions. The present study failed to demonstrate any substantial effect of thermal water with relatively low radon content on the functioning of the endocrine system.


Asunto(s)
Balneología , Sistema Endocrino/efectos de la radiación , Radón/efectos adversos , Agua/química , Baños , Relación Dosis-Respuesta en la Radiación , Sistema Endocrino/metabolismo , Femenino , Hormonas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Radón/uso terapéutico , Factores de Tiempo
13.
Int J Radiat Biol ; 85(3): 281-90, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19296342

RESUMEN

BACKGROUND: Radon, as a radioactive noble gas of natural origin, is generally present in the atmosphere of caves during the speleotherapeutic treatment of different diseases. However, the role of radon in the therapeutic effect is not fully clarified yet. Endocrine parameter levels may be influenced by radon-like endocrine levels in balneotherapeutic treatments (bath treatment). For this reason changes of these parameters were examined in this study. PATIENTS AND METHOD: A total of 81 speleotherapy patients were involved in the survey. They spent four hours daily in Tapolca Cave, five days a week, for two weeks. In this study, the thyreoiedea stimulating hormone, free triiodine-tironin, free thyroxine, prolactine, cortisol, dehydroepiandrosterone sulphate, adrenocorticotropic hormone, and beta endorphine levels of the body were examined before and after the treatment. RESULTS: After statistical analysis of the data a significant decrease of cortisol levels of patients was found, which was not directly correlated with radon concentration. In the case of thyroid hormones, there were no significantly detectable changes of the hormone levels except for low radon concentration levels a significant decrease in the free thyroxine and the thyreoiedea stimulating hormone level of male patients was observed. CONCLUSION: Speleotherapy has an effect on the level of endocrine hormones; however, no direct correlation with differences in radon level was found. For patients whose endocrine levels fell outside the normal endocrine parameter values, more striking changes in endocrine hormone levels were seen, but changes of these parameters could not be statistically analyzed due to the small number of cases.


Asunto(s)
Sistema Endocrino/efectos de la radiación , Radón/uso terapéutico , Trastornos Respiratorios/terapia , Espeleoterapia , Hormona Adrenocorticotrópica/sangre , Adulto , Anciano , Anciano de 80 o más Años , Sulfato de Deshidroepiandrosterona/sangre , Endorfinas/sangre , Femenino , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana Edad , Hormonas Tiroideas/sangre , Tiroxina/sangre , Triyodotironina/sangre
14.
J Hazard Mater ; 150(3): 541-5, 2008 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-17566642

RESUMEN

Several researchers have examined and achieved favourable results in connection with the building industry's use of red mud extracted in large quantities from the processing of bauxite. These days more and more precedence is being given to limiting the radiological dose to the population. In this study carried out in Hungary, the use of red mud, bauxite, and clay additives recommended for the production of special cements, were examined from a radiological aspect. (226)Ra and (232)Th activity concentrations measured in Hungarian bauxite, red mud and clay samples were significantly similar with the levels for such raw materials mentioned in international literature. Taking radiation protection aspects into consideration, none of these products can be directly used for building construction. Taking Hungarian and international values into consideration, a small amount of red mud, not exceeding 15% could be used for brick production, for example as a colouring material. However, beyond this amount the standards for building materials would not be met. For the production of cements an even stricter limit needs to be determined when both bauxite and red mud are used.


Asunto(s)
Óxido de Aluminio/análisis , Materiales de Construcción/análisis , Residuos Industriales/análisis , Radioisótopos de Potasio/análisis , Contaminantes Radiactivos/análisis , Radio (Elemento)/análisis , Torio/análisis , Silicatos de Aluminio/análisis , Arcilla , Materiales de Construcción/normas , Hungría , Radioisótopos de Potasio/normas , Monitoreo de Radiación , Contaminantes Radiactivos/normas , Radio (Elemento)/normas , Torio/normas
15.
Orv Hetil ; 148(9): 421-4, 2007 Mar 04.
Artículo en Húngaro | MEDLINE | ID: mdl-17344170

RESUMEN

The authors review the case of a 30 years old female patient presenting with a 48 hours-standing anuria, who permanently used products of grist of a virtuous plant, Guarana and occasionally used a parenteral non-steroid painkiller. The clinical history and laboratory results showed acute renal and hepatic failure. The histological picture of the renal biopsy specimen verified an acute tubular necrosis. After temporary dialysis treatment, her renal function recovered progressively with compensatory polyuria. The authors would like to draw the attention to the risks of the use of over-the-counter marketed paramedicinal products, per se or in combination with pharmaceutically registered products, sold in pharmacies and nutrition supplement stores.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/diagnóstico , Antiinflamatorios no Esteroideos/efectos adversos , Túbulos Renales/efectos de los fármacos , Túbulos Renales/patología , Paullinia/efectos adversos , Lesión Renal Aguda/terapia , Adulto , Antiinflamatorios no Esteroideos/administración & dosificación , Femenino , Humanos , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/diagnóstico , Necrosis/inducido químicamente , Extractos Vegetales/efectos adversos , Diálisis Renal
16.
Sci Total Environ ; 367(2-3): 653-65, 2006 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-16725181

RESUMEN

High radon concentration (average 410 kBq m-3) has been measured in a tunnel of a uranium mine, located 15-55 m below the village of Kovágószolos, Hungary. The mine was closed in 1997; the artificial ventilation of the tunnel was then terminated and recultivation works begun. In this paper, a study has been made as to whether the tunnel has an influence on the radon concentration of surface dwellings over the mining tunnel. At different distances from the surface projection of the mining tunnel, radon concentration, the gamma dose, radon exhalation and radon concentration of soil gas were measured. The average radon concentration in the dwellings was 483 Bq m-3. Significantly higher radon concentrations (average 667 Bq m-3) were measured in houses within +/-150 m from the surface projection of the mining tunnel +50 m, compared with the houses further than the 300-m belt (average 291 Bq m-3). The average radon concentration of the soil gas was 88.8 kBq m-3, the average radon exhalation was 71.4 Bq m-2 s-1 and higher values were measured over the passage as well. Frequent fissures crossing the passage and running up to the surface and the high radon concentration generated in the passage (average 410 kBq m-3) may influence the radon concentration of the houses over the mining tunnel.


Asunto(s)
Monitoreo del Ambiente/estadística & datos numéricos , Contaminantes Ambientales/análisis , Minería , Radón/análisis , Hungría , Temperatura , Uranio/análisis
17.
Orv Hetil ; 147(4): 147-58, 2006 Jan 29.
Artículo en Húngaro | MEDLINE | ID: mdl-16515023

RESUMEN

Peritoneal carcinomatosis is a fatal diagnosis, associated with poor prognosis and quality of life. Survival is usually estimated in month. Traditionally surgery for peritoneal carcinomatosis was indicated only for palliative effort. Advances in tumour biology, cytoreductive surgery and pharmacology have improved the approach for this condition. An aggressive combined approach to peritoneal surface malignancy involves peritonectomy and intraperitoneal perioperative hyperthermic chemotherapy. Cytoreductive surgery reduces carcinomatosis to microscopic residual disease so that intraperitoneal hyperthermic chemotherapy is able to eradicate cancer. Hyperthermic chemotherapy enhances the cytotoxicity of the drugs and increases their penetration into the cancerous tissue. Careful patient selection is crucial for this multimodality approach. Quantitative prognostic indicators are useful in the assessment of outcome, like peritoneal cancer index and completeness of cytoreduction score. Cytoreductive surgery combined with intraperitoneal hyperthermic chemotherapy improves survival but is associated with significant morbidity and mortality. This review is based on a case report of a 22-year-old female patient who had peritoneal carcinomatosis of inflammatory myofibroblastic sarcoma and was treated by cytoreductive surgery and intraperitoneal hyperthermic chemotherapy at our department.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Quimioterapia del Cáncer por Perfusión Regional , Hipertermia Inducida , Cuidados Intraoperatorios/métodos , Miosarcoma/secundario , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia del Cáncer por Perfusión Regional/efectos adversos , Quimioterapia del Cáncer por Perfusión Regional/métodos , Femenino , Humanos , Hipertermia Inducida/efectos adversos , Inflamación , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/cirugía , Pronóstico
18.
Pharmacogenet Genomics ; 15(10): 723-30, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16141798

RESUMEN

The present study aimed to prospectively investigate the influence of thymidylate synthase (TS) polymorphisms (5'-TSER, 3'-TSUTR) on the disease-free survival (DFS) and overall survival (OS) of patients with colorectal cancer (CRC) who were treated with adjuvant 5-fluorouracil (5-FU) therapy. Patients were followed up for 19+/-14 months (median+/-SD). TS genotypes were determined from the peripheral blood mononuclear cells of 166 patients by polymerase chain reaction-polyacrylamide gel electrophoresis and restriction fragment length polymorphism methods. 5'-TSER 3R homozygotes showed significantly longer DFS (P = 0.048) and OS (P = 0.009). The 5'-TSER and 3'-TSUTR genotype combination groups showed a significant difference for DFS (P = 0.039) and OS (P = 0.029). Significantly better DFS (P = 0.049) and OS (P = 0.043) were observed for 6 bp/6 bp genotypes in 5'-TSER heterozygotes (n = 80). Based on this, and on hazard ratios obtained by Cox regression analysis of the DFS of genotype-combinations, the patients were classified as belonging to prognostic groups A and B. The DFS and OS of these two groups showed a highly significant difference (P = 0.002 and 0.001). In the multivariate Cox regression model, beside tumour location, the prognostic classification (groups A and B) proved to be an independent prognostic factor. Our data suggest that those TS genotypes and their combinations (group A: 3R/3R with any 3'-TSUTR genotype and 2R/3R with 6 bp/6 bp), which have been reported earlier as having high TS expression, predict significantly longer DFS and OS. We found that a combination of germline TS polymorphisms is an independent prognostic marker in selecting CRC patients with worse prognosis, and it may be worthwhile to examine whether these patients would benefit from an alternative therapy.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Fluorouracilo/uso terapéutico , Polimorfismo Genético , Regiones Promotoras Genéticas , Timidilato Sintasa/genética , Regiones no Traducidas 3'/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Quimioterapia Adyuvante , Neoplasias Colorrectales/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/tratamiento farmacológico , Metástasis de la Neoplasia/genética , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/enzimología , Recurrencia Local de Neoplasia/genética , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Resultado del Tratamiento
19.
Oncology ; 62(2): 167-74, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-11914603

RESUMEN

The aim of the present study was to determine the relative intratumoral activity of two pyrimidine biosynthetic enzymes, i.e. thymidylate synthase (TS) and thymidine kinase (TK), in human colorectal cancers to compare their possible relationship with demographic and pathologic characteristics of the patients and their tumors, and moreover to evaluate their predictive significance regarding 5-fluorouracil (5-FU) sensitivity and the overall survival of patients, respectively. TS and TK levels were significantly increased in the tumor compared to peritumoral tissue. However, no significant relationship between TS/TK activity and demographic features of the patients or pathologic characteristics of their tumors could be demonstrated. Kaplan-Meier analysis showed that the overall survival of patients with low TS activity was significantly longer (p < 0.012) compared to those with high TS activity. Such a difference could not be demonstrated between patients with high or low TK activity; however, combined evaluation of the two parameters proved that TK may contribute to the more precise assessment of disease prognosis, and it may further influence treatment decisions, i.e. the selection of patients for adjuvant therapy with 5-FU and folinic acid. Multivariate analysis showed that among the variables tested, beside Dukes' stage, TS and TK activities were significant prognostic factors for the overall survival of colorectal cancer patients.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/enzimología , Timidina Quinasa/metabolismo , Timidilato Sintasa/metabolismo , Adulto , Anciano , Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Femenino , Fluorouracilo/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Resultado del Tratamiento
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