Recurrent growth factor starvation promotes drug resistance in human leukaemic cells

Multi-drug resistance can be induced by various environmental stresses including an exposure to chemical drugs and X-ray irradiation. In addition, hypo-nutritive conditions are known to promote multi-drug resistance in solid tumours. To understand the importance of nutritive conditions in the development of drug resistance in non-solid tumours and to know whether a transient malnutrition could induce a permanent reduction in drug sensitivity, leukaemic cells were transiently cultured under growth factor-starved conditions. Granulocyte-macrophage colony-stimulating factor-dependent human leukaemic MO7e cells were cultured in the absence of granulocyte-macrophage colon-stimulating factor for 2 weeks, during which the majority of the cells died, and the minor viable cells were expanded in the presence of granulocyte-macrophage colon-stimulating factor for following 1 week. This procedure was repeated three times, and the surviving cells were cloned by limiting dilution. These clones underwent G1 arrest in the absence of granulocyte-macrophage colon-stimulating factor, while parental cells underwent apoptosis. Interestingly, activities of the downstream targets of granulocyte-macrophage colon-stimulating factor receptor were regulated in a granulocyte-macrophage colon-stimulating factor-independent manner, indicating that the ligand-independent activation of granulocyte-macrophage colon-stimulating factor receptor had not taken place. Moreover, the 4–7-fold increases in IC50 for etoposide and the 2–6-fold increase in IC90 for doxorubicin was observed. Furthermore, Bcl-2 protein expression was significantly up-regulated in the clones while no significant changes in Bax, Bcl-xL, P-glycoprotein and Hsp70 protein expression and no consistent changes in p53 expression were detected. We propose that recurrent growth factor starvation, which may occur in vivo when stromal function is damaged after intensive chemotherapy or bone marrow occupation by malignant cells, causes selection of drug resistant leukaemia cells that will expand when the growth factor supply recovers

Processionary Moths and Associated Urtication Risk: Global Change–Driven Effects

Processionary moths carry urticating setae, which cause health problems in humans and other warm-blooded animals. The pine processionary moth Thaumetopoea pityocampa has responded to global change (climate warming and increased global trade) by extending its distribution range. The subfamily Thaumetopoeinae consists of approximately 100 species. An important question is whether other processionary moth species will similarly respond to these specific dimensions of global change and thus introduce health hazards into new areas. We describe, for the first time, how setae are distributed on different life stages (adult, larva) of major groups within the subfamily. Using the available data, we conclude that there is little evidence that processionary moths as a group will behave like T. pityocampa and expand their distributional range. The health problems caused by setae strongly relate to population density, which may, or may not, be connected to global change