RESUMO
Chemotherapeutic agents and also radiotherapy trigger a series of signalling pathways in the cells that activate not only the apoptotic machinery but also cell survival pathways. Some of these pathways are also altered by genetic changes in specific type of tumours, and are different even between patients with the same tumour. Among these pathways, the majority of survival signals involve the ERK, AKT and nuclear factor-kappaB pathways and those related to cell death, which are driven mainly either by inhibition of such survival networks or by upregulation of the JNK/p38 MAP-kinases. Thus, the efficacy of a given chemotherapy appears as a result of the balance between cell death and survival pathways elicited in each individual tumour. Modulation of such survival pathways would help to increase the efficacy of chemotherapy. Different strategies based on conventional chemotherapy have been used in the past with modest success. The availability of new molecules such as inhibitors of survival pathways and the use of new technologies for the study of individual tumours would have a positive impact on patient survival.
Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Transdução de Sinais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Humanos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Fator de Transcrição RelB/metabolismoRESUMO
SETTING: An aboriginal community of 653 persons. OBJECTIVE: To determine the prevalence of pulmonary tuberculosis (PTB) and to analyse related factors. DESIGN: The total population was surveyed; those with chronic productive cough were asked to provide sputum specimens. PTB was diagnosed by bacilloscopy (acid-fast bacilli [AFB]). An analysis of socio-economic factors and clinical history associated with chronic cough or positive smear for PTB was carried out using multiple correspondence analysis and logistic regression models. RESULTS: Two hundred and two patients were identified with chronic cough and 173 with chronic productive cough. Chronic cough was associated with having a history of PTB (adjusted OR=4.89, 95%CI 2.6-9.4) and with work-related migratory movements (adjusted OR=2.05, 95%CI 1.3-3.3). Of 92 coughers with sputum samples analysed, 44 (47.8%) were PTB-positive, giving a prevalence of 6.7% in the whole population. In the groups aged 15-34 and >or=45 years, women had higher positivity rates than men, whereas in the group aged 35-44 years rates were higher in men. Twenty-seven per cent of families had one to four smear-positive members. CONCLUSION: The Tuberculosis Control Programme in the area studied needs to be strengthened, taking into account the ethnic context, work-related migration and the socio-economic and geographic context.