Hepatocyte growth factor (HGF) protects c-met-expressing Burkitt''s lymphoma cell lines from apoptotic death induced by DNA damaging agents

The relative sensitivity of neoplastic cells to DNA damaging agents is a key factor in cancer therapy. In this paper, we show that pretreatment of Burkitt's lymphoma cell lines expressing the c-met protooncogene with hepatocyte growth factor (HGF) protects them from death induced by DNA damaging agents commonly used in tumour therapy. This protection was observed in assays based on morphological assessment of apoptotic cells and DNA fragmentation assays. The protection was dose- and time-dependent — maximal protection requiring pre-incubation with 100 ng/ml HGF for 48 h. Western blotting analysis and flow cytometric studies revealed that HGF inhibited doxorubicin- and etoposide-induced decreases in the levels of the anti-apoptotic proteins Bcl-XL, and to a lesser extent Bcl-2, without inducing changes in the pro-apoptotic Bax protein. Overall, these studies suggest that the accumulation of HGF within the microenvironment of neoplastic cells may contribute to the development of a chemoresistant phenotype.

An Investigation of the Flow Field through a Variable Geometry Turbine Stator with Vane Endwall Clearance

Variable geometry turbines provide an extra degree of flexibility in air management in turbocharged engines. The pivoting stator vanes used to achieve the variable turbine geometry necessitate the inclusion of stator vane endwall clearances. The consequent leakage flow through the endwall clearances impacts the flow in the stator vane passages and an understanding of the impact of the leakage flow on stator loss is required. A numerical model of a typical variable geometry turbine was developed using the commercial CFX-10 computational fluid dynamics software, and validated using laser doppler velocimetry and static pressure measurements from a variable geometry turbine with stator vane endwall clearance. Two different stator vane positions were investigated, each at three different operating conditions representing different vane loadings. The vane endwall leakage was found to have a significant impact on the stator loss and on the uniformity of flow entering the turbine rotor. The leakage flow changed considerably at different vane positions and flow incidence at vane inlet was found to have a significant impact.