RESUMEN
Preventing the infectious disease from breakout and maintaining public health have always been placed at the first place when making public healthy policy. When the epidemic trend of infectious disease arises, compulsory treatment is an efficient pattern to control the rapid spreading. A sliding mode is carried out to evaluate the effect of compulsory treatment in the infectious disease controlling. When the number of infected persons reach a certain level Ic, the policy of compulsory treatment will be carried out at rate f . We analyze the influence of the compulsory treatment rate f and threshold value Ic to commence the control. Finally we investigate the theorems and the existence of the optimality combination.
Asunto(s)
Control de Enfermedades Transmisibles/métodos , Enfermedades Transmisibles/terapia , Infectología/métodos , Algoritmos , Simulación por Computador , Epidemias/prevención & control , Humanos , México , Salud Pública , Reino Unido , Estados UnidosRESUMEN
Non-small-cell lung cancer (NSCLC) is a common malignancy with a poor prognosis. Despite progress targeting oncogenic drivers, there are no therapies targeting tumor-suppressor loss. Smad4 is an established tumor suppressor in pancreatic and colon cancer; however, the consequences of Smad4 loss in lung cancer are largely unknown. We evaluated Smad4 expression in human NSCLC samples and examined Smad4 alterations in large NSCLC data sets and found that reduced Smad4 expression is common in human NSCLC and occurs through a variety of mechanisms, including mutation, homozygous deletion and heterozygous loss. We modeled Smad4 loss in lung cancer by deleting Smad4 in airway epithelial cells and found that Smad4 deletion both initiates and promotes lung tumor development. Interestingly, both Smad4(-/-) mouse tumors and human NSCLC samples with reduced Smad4 expression demonstrated increased DNA damage, whereas Smad4 knockdown in lung cancer cells reduced DNA repair and increased apoptosis after DNA damage. In addition, Smad4-deficient NSCLC cells demonstrated increased sensitivity to both chemotherapeutics that inhibit DNA topoisomerase and drugs that block double-strand DNA break repair by non-homologous end joining. In sum, these studies establish Smad4 as a lung tumor suppressor and suggest that the defective DNA repair phenotype of Smad4-deficient tumors can be exploited by specific therapeutic strategies.