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1.
Biofactors ; 10(2-3): 263-70, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10609892

RESUMEN

Electron transfer reactions for the reduction of glycine in Eubacterium acidaminophilum involve many selenocysteine (U)- and thiol-containing proteins, as shown by biochemical and molecular analysis. These include an unusual thioredoxin system (-CXXC-), protein A (-CXXU-) and the substrate-specific protein B of glycine reductase (-UXXCXXC-). Most probably a selenoether is formed at protein B by splitting the C-N-bond after binding of the substrate. The carboxymethyl group is then transferred to the selenocysteine of protein A containing a conserved motif. The latter protein acts as a carbon and electron donor by giving rise to a protein C-bound acetyl-thioester and a mixed selenide-sulfide bond at protein A that will be reduced by the thioredoxin system. The dithiothreitol-dependent D-proline reductase of Clostridium sticklandii exhibits many similarities to protein B of glycine reductase including the motif containing selenocysteine. In both cases proprotein processing at a cysteine residue gives rise to a blocked N-terminus, most probably a pyruvoyl group. Formate dehydrogenase and some other proteins from E. acidaminophilum contain selenocysteine, e.g., a 22 kDa protein showing an extensive homology to peroxiredoxins involved in the detoxification of peroxides.


Asunto(s)
Aminoácidos/metabolismo , Bacterias Anaerobias/metabolismo , Bacterias Grampositivas/metabolismo , Compuestos de Organoselenio/metabolismo , Proteínas/metabolismo , Selenio/metabolismo , Compuestos de Sulfhidrilo/metabolismo , Proteínas Bacterianas/metabolismo , Oxidorreductasas/metabolismo , Selenocisteína/metabolismo , Selenoproteínas , Tiorredoxinas/metabolismo
2.
Ann Oncol ; 7(7): 677-85, 1996 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8905025

RESUMEN

BACKGROUND: In the Netherlands, 45% of all cancer cases occur in men and women aged 70 years and older. Since the population is ageing and cancer incidence rises with age, the number of new malignancies in the elderly is increasing. It has become apparent that there is a relationship between age at diagnosis and the treatment received. Therefore, age-specific variations in patterns of care for six common forms of cancer in the elderly, are examined. PATIENTS AND METHODS: Patients aged 50 years and older, diagnosed in the period 1988-1992 in Middle and South Limburg with breast, colorectal, lung, ovarian, head and neck cancer and non-Hodgkin lymphoma were included (n = 6911). Data were obtained from the population-based Regional Cancer Registry of the Comprehensive Cancer Centre Limburg. Age-specific differences in diagnostics and treatment were analysed using chi-square analysis (age categories: 50-59, 60-69, 70+). Logistic regression analyses were used to examine the extent to which age increased the chance of not being treated or of receiving less intensive treatment, while controlling for the stage of the disease and the sex of the patient. RESULTS: For all malignancies the stage was unknown in a larger proportion of the patients aged 70 years and older than in the younger patient groups. Compared to their younger counterparts, the diagnosis of elderly breast, colorectal and lung cancer patients was more often based solely on clinical grounds. In the total study population, 16% were not treated. Per age category 50-59 years, 60-69 years and 70+ these percentages were 7%, 12% and 22%, respectively, (P-trend = 0.001). For all malignancies the chance of not receiving treatment increased with increasing age. However, the size and nature of the differences varied with the localisation of the tumour. The proportion of untreated patients was particularly high in the patients with lung cancer and metastatic colorectal and ovarian cancer, and there was an increase with increasing age (P-trend = 0.001). The vast majority of patients with NHL, breast, head and neck and non-metastatic colorectal cancer received treatment, 90%, 94%, 91%, and 99%, respectively. However, elderly patients less often received a combination of treatment modalities. CONCLUSIONS: The diagnostics and choice of treatment for several common types of cancer were dependent on age. This study could not take into account the major problem of co-morbidity which can be a reason to choose for lesser therapy in the elderly. More research is necessary to determine which factors determine the diagnostics and choice of treatment and whether these factors differ between young and elderly patients.


Asunto(s)
Factores de Edad , Manejo de la Enfermedad , Neoplasias/diagnóstico , Neoplasias/terapia , Edad de Inicio , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Terapia Combinada , Intervalos de Confianza , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Neoplasias/patología , Neoplasias/fisiopatología , Países Bajos , Sistema de Registros
4.
Ann Oncol ; 4(4): 295-301, 1993 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-8518219

RESUMEN

BACKGROUND: The Comprehensive Cancer Center trial 82-01 is a prospective randomized study to investigate the value of the addition of high-dose medroxyprogesterone acetate (MPA) to chemotherapy in patients with node-positive operable breast cancer. MPA may be of advantage in this setting because of its activity in estrogen receptor ER-positive as well as ER-negative tumors and since it may protect against chemotherapy-induced myelosuppression and thus enable maintenance of the appropriate chemotherapeutic scheduling. PATIENTS AND METHODS: Four hundred eight evaluable patients with node-positive (N+) operable breast cancer (T1-3, N1) were entered in a multicenter randomized trial. Two hundred nine patients were randomized in the MPA- arm and 199 in the MPA+ arm. CAF chemotherapy was given as a short i.v. bolus infusion: cyclophosphamide 500 mg/m2 i.v. day 1, doxorubicin 40 mg/m2 i.v. day 1, and 5-fluorouracil 500 mg/m2 i.v. day 1, q 4 wks x 6. MPA was given intramuscularly (i.m.) 500 mg q d x 28 days, followed by 500 mg i.m. twice weekly during 5 months. RESULTS: The main side effects of MPA were weight gain with a mean of 5.5 kg as opposed to 1.8 kg in the control group (p = 0.01) and vaginal bleeding in 30/199 in the MPA+ group and 0 in the MPA- group. MPA ameliorated vomiting grade III, IV (45% vs. 28%, p < 0.001), nausea grade III, IV (50% vs. 34%, p < 0.001) and leucocyte nadir grade III, IV (20% vs. 11%, p = 0.003). Disease-free survival (DFS) after 5 years was 59% in the MPA+ and 49% in the MPA- group (p = 0.12). Patients > or = 60 years benefitted most from MPA treatment, in particular if freedom from distant metastases was taken as the endpoint (p = 0.02). Overall survival (OS) was not significantly different between the two treatment groups (p = 0.18), but within subgroups analysed there was an advantage for MPA+ in patients > or = 55 years (p = 0.002) and in pT1 patients (p = 0.045). CONCLUSIONS: High-dose MPA ameliorates CAF side effects and reduces the risk of metastatic disease, especially in elderly breast cancer patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Metástasis Linfática , Acetato de Medroxiprogesterona/administración & dosificación , Persona de Mediana Edad , Estudios Prospectivos , Tasa de Supervivencia
5.
Ned Tijdschr Geneeskd ; 136(19): 927-31, 1992 May 09.
Artículo en Holandés | MEDLINE | ID: mdl-1594067

RESUMEN

To estimate the cancer incidence in the middle and southern part of the province of Limburg and to compare these rates with results of the Eindhoven Cancer Registry (IKZ/SOOZ), we carried out a descriptive investigation in the regional cancer registry Comprehensive Cancer Centre Limburg (IKL). The IKL has started a cancer registry in the province of Limburg in the framework of the national cancer registry. Since 1986 all hospitals and pathological laboratories in the area make their data available to the IKL cancer registry. Age-standardized incidence rates were calculated using the European Standard Population. The incidence rate for all malignancies combined over 1986-1988 was 406.3 per 100,000 per year in males and 273.0 per 100,000 per year in females. These incidence rates are very similar to the rates calculated by the Eindhoven Cancer Registry for the years 1983-86. However, the incidence rates are lower in the IKL area for malignancies of the stomach (males, females), bladder (males, females) and ovary. The incidence rates are higher for malignancies of the lung (females), pleura (males) and for 'primary tumor unknown' (males). The incidence rates of the IKL cancer registry correspond very closely to the rates of the Eindhoven cancer registry. However, differences in published mortality rates of both regions compared with the remaining part of the Netherlands suggest that the incidence rates in males differ from the Netherlands as a whole.


Asunto(s)
Neoplasias/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Sistema de Registros , Factores Sexuales
7.
Artículo en Inglés | MEDLINE | ID: mdl-6249866

RESUMEN

The interaction of gaseous NO2 with solid carrier-adsorbed polycyclic aromatic hydrocarbons was studied under laboratory conditions with a specific attention to factors that might possibly influence this reaction, such as type of carrier lighting conditions, NO2 concentration, exposure time, and temperature. At the NO2 concentration of 1.33 ppm there were detected the following nitro derivatives: nitroanthracene, nitropyrene, nitrochrysene, two mononitro derivatives of benzo/a/pyrene, and dinitrobenzo/a/pyrene. The experimental data suggest that the formation of nitroaromates in atmospheric environment is to be expected, provided that there are present, besides polycyclic aromatic hydrocarbons and nitrogen oxides, also suitable types of sorbents, such as silica gel or fly ash.


Asunto(s)
Contaminantes Atmosféricos , Antracenos , Crisenos , Dióxido de Nitrógeno , Fenantrenos , Pirenos , Óxido de Aluminio , Benzopirenos , Carbono , Fenómenos Químicos , Química , Luz , Dióxido de Silicio , Temperatura
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