Human mutations that confer paclitaxel resistance.

The involvement of tubulin mutations as a cause of clinical drug resistance has been intensely debated in recent years. In the studies described here, we used transfection to test whether beta1-tubulin mutations and polymorphisms found in cancer patients are able to confer resistance to drugs that target microtubules. Three of four mutations (A185T, A248V, R306C, but not G437S) that we tested caused paclitaxel resistance, as indicated by the following observations: (a) essentially 100% of cells selected in paclitaxel contained transfected mutant tubulin; (b) paclitaxel resistance could be turned off using tetracycline to turn off transgene expression; (c) paclitaxel resistance increased as mutant tubulin production increased. All the paclitaxel resistance mutations disrupted microtubule assembly, conferred increased sensitivity to microtubule-disruptive drugs, and produced defects in mitosis. The results are consistent with a mechanism in which tubulin mutations alter microtubule stability in a way that counteracts drug action. These studies show that human tumor cells can acquire spontaneous mutations in beta1-tubulin that cause resistance to paclitaxel, and suggest that patients with some polymorphisms in beta1-tubulin may require higher drug concentrations for effective therapy.

Childhood obesity prevention in the 80th Texas legislative session

The increased number of obese children in the United States has prompted many efforts to reduce obesity by predominantly focusing resources to develop better education, awareness, nutrition and physical activity. There has been increased interest within communities and governments to turn to policy makers for help in taking action. The possibility for various health policies geared toward preventing childhood obesity is diverse in nature. In order to understand strategies taken by Texas legislatures to address childhood obesity, this study examines childhood obesity prevention policy recommendations and subsequently uses them to identify relevant legislation. This study follows identified legislation during the 80th Texas legislative session to gain an understanding of the steps that the Texas legislatures are currently taking to prevent childhood obesity. This study concludes that the Texas legislative process was successful at effecting changes in education policy. However, during this legislative session Texas legislators did not follow many strategies and recommendations which may be more effective at reducing childhood obesity. ^